FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Pogge, A Slikker, W AF Pogge, A Slikker, W TI Neuroimaging: New approaches for neurotoxicology SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 20th International Neurotoxicology Conference CY NOV 18-21, 2002 CL LITTLE ROCK, AR DE neuroimaging; neurotoxicology; in vitro NMR; magnetic resonance imaging (MRI); magnetic resonance imaging microscopy (MRM); positron emission tomography (PET); apoptosis; risk assessment ID NMDA RECEPTOR ANTAGONISTS; NONHUMAN-PRIMATES; PET; BRAIN; PERFORMANCE; MICROSCOPY AB Over the last 20 years, the impact of imaging on the clinical sciences is unquestionable. It has revolutionized the diagnosis and treatment of disease. Interestingly, the use of imaging in preclinical neurotoxicology has been relatively negligible. This has been in part due to the lack of knowledge or understanding of the capabilities of these powerful technologies. However some of the more immediately applicable imaging approaches could impact the present approach to neurotoxicology. In addition, the recent advent of the development of imagers specifically for application to small animals will provide the opportunity of obtaining information for neurotoxicological risk assessment in a more timely and relevant manner. The ability to visualize changes in structure and function due to neurotoxic insult in a noninvasive manner is a promising direction. Changes in anatomy of soft and hard tissue, metabolism, function and gene expression can now be done in both a preclinical and a clinical setting using such technologies as magnetic resonance imaging (MRI), magnetic resonance imaging microscopy (MRM), and positron emission tomography (PET). This type of information is not readily accessible using conventional preclinical neurotoxicological procedures and usually requires total destruction of the intrinsic structure of the sample of interest. Imaging provides an opportunity to produce much of these data in a nondestructive manner and presents the data in a three-dimensional format. This permits longitudinal studies of the same subject subsequently reducing the number of animals required for studies while providing more information. In addition, as these technologies have been primarily developed for clinical purposes, they provide an outstanding opportunity for cross-species and animal-to-human extrapolation and testing. (C) 2003 Elsevier Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Pogge, A (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM apogge@nctr.fda.gov NR 19 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD JUN PY 2004 VL 25 IS 4 BP 525 EP 531 DI 10.1016/j.neuro.2003.10.007 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 830KW UT WOS:000222121900008 PM 15183007 ER PT J AU Bowyer, JF Harris, AJ Delongchamp, RR Jakab, RL Miller, DB Little, AR O'Callaghan, JP AF Bowyer, JF Harris, AJ Delongchamp, RR Jakab, RL Miller, DB Little, AR O'Callaghan, JP TI Selective changes in gene expression in cortical regions sensitive to amphetamine during the Neurodegenerative process SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 20th International Neurotoxicology Conference CY NOV 18-21, 2002 CL LITTLE ROCK, AR DE amphetamine; gene expression; neurodegeneration ID METHAMPHETAMINE-INDUCED NEUROTOXICITY; MESSENGER-RNA EXPRESSION; IMMEDIATE-EARLY GENE; DOPAMINE TRANSPORTER; NEURONAL DEGENERATION; RAT STRIATUM; MOUSE-BRAIN; SUBSTITUTED AMPHETAMINES; DIFFERENTIAL REGULATION; INDUCED HYPERTHERMIA AB Gene expression profiles in several brain regions of adult male rats were evaluated following a D-amphetamine (AMPH) exposure paradigm previously established to produce AMPH neurotoxicity. Escalating doses of AMPH (530 mg/kg) were given over the course of 16 h per day in an 18 degreesC environment for 2 days. This paradigm produces neurotoxicity but eliminates or minimizes the hyperthermia and seizure activity that might influence gene expression in a manner unrelated to the neurotoxic effects of AMPH. The expression of 1185 genes was monitored in the striatum, parietal cortex, piriform cortex and posteriolateral cortical amygdaloid nucleus (PLCo) using cDNA array technology, and potentially significant changes were verified by RT-PCR. Gene expression was determined at time points after AMPH when neurodegeneration was beginning to appear (16 h) or maximal (64 h). Expression was also determined 14 days after AMPH to find long-term changes in gene expression that might be biomarkers of a neurotoxic event. In the parietal cortex there was a two-fold increase in neuropeptide Y precursor protein mRNA whereas nerve growth factor-induced receptor protein I-A and I-B mRNA decreased 50% at 16 h after the end of AMPH exposure. Although these changes in expression were not observed in the PLCo, insulin-like growth factor binding protein I mRNA was increased two-fold in the PLCo at 16 and 64 h after AMPH. Changes in gene expression in the cortical regions were all between 1.2- and 1.5-fold 14 days after AMPH but some of these changes, such as annexin V increases, may be relevant to neurotoxicity. Gene expression was not affected by more than 1.5-fold at the time points in the striatum, although 65% dopamine depletions occurred, but the plasma membrane-associated dopamine transporter and dopamine D2 receptor were decreased about 40% in the substantia nigra at 64 h and 14 days post-AMPH. Thus, the 2-day AMPH treatment produced a few changes in gene expression in the two-fold range at time points 16 h or more after exposure but the majority of expression changes were less than 1.5-fold of control. Nonetheless, some of these lesser fold-changes appeared to be relevant to the neurotoxic process. (C) 2003 Elsevier Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biometry, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Risk Assessment & Genet Toxicol, Jefferson, AR 72079 USA. NIOSH, Ctr Dis Control & Prevent, Morgantown, WV 26505 USA. RP Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. EM jbowyer@nctr.fda.gov RI O'Callaghan, James/O-2958-2013; Little, Roger/O-6191-2014 OI Little, Roger/0000-0001-6831-0177 NR 70 TC 18 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X EI 1872-9711 J9 NEUROTOXICOLOGY JI Neurotoxicology PD JUN PY 2004 VL 25 IS 4 BP 555 EP 572 DI 10.1016/j.neuro.2003.08.005 PG 18 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 830KW UT WOS:000222121900011 PM 15183010 ER PT J AU Slikker, W AF Slikker, W TI The fetal programming hypothesis: Possible role in childhood obesity. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 20th International Neurotoxicology Conference CY NOV 18-21, 2002 CL LITTLE ROCK, AR C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD JUN PY 2004 VL 25 IS 4 BP 681 EP 681 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 830KW UT WOS:000222121900062 ER PT J AU Xu, ZJ McCastlain, K Cawthon, D Slikker, W Ali, S AF Xu, ZJ McCastlain, K Cawthon, D Slikker, W Ali, S TI Selective alterations in gene expression using real-time PCR in MPTP-induced neurtoxicity in mice. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 20th International Neurotoxicology Conference CY NOV 18-21, 2002 CL LITTLE ROCK, AR C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD JUN PY 2004 VL 25 IS 4 BP 702 EP 702 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 830KW UT WOS:000222121900114 ER PT J AU James, SJ Slikker, W Melnyk, S New, E Jernigan, S AF James, SJ Slikker, W Melnyk, S New, E Jernigan, S TI Prevention of thimerosal-induced neurotoxicity by glutathione and cysteine, but not methionine. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 20th International Neurotoxicology Conference CY NOV 18-21, 2002 CL LITTLE ROCK, AR DE thimerosal; neurotoxicity; glutathione C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Arkansas Childrens Hosp, Res Inst, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD JUN PY 2004 VL 25 IS 4 BP 711 EP 711 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 830KW UT WOS:000222121900135 ER PT J AU Yetley, EA Rader, JI AF Yetley, EA Rader, JI TI Modeling the level of fortification and post-fortification assessments: US experience SO NUTRITION REVIEWS LA English DT Article; Proceedings Paper CT Technical Consultations on Recommeded Levels of Folic Acid and Vitamin B12 Fortification CY JAN 23-24, 2003 CL Washington, DC SP Pan Amer Hlth Assoc (PAHO), March Dimes (MOD), Ctr Dis Control Prevention (CDC) DE fortification; folic acid; post-fortification; assessments; vitamin B-12 ID FOLIC-ACID FORTIFICATION; NEURAL-TUBE DEFECTS; CEREAL-GRAIN PRODUCTS; FOOD FORTIFICATION; UNITED-STATES; FOLATE FORTIFICATION; PLASMA HOMOCYSTEINE; SERUM FOLATE AB Mandatory fortification of enriched cereal-grain products became effective in the United States on January 1, 1998. This fortification was undertaken to assist women of child-bearing age in increasing their intake of folic acid to reduce their risk of having a pregnancy affected by a neural tube birth defect. The process by which the Food and Drug Administration modeled the level of fortification with folic acid illustrates the complex issues and general principles that emerge when fortification of a nation's food supply is evaluated as a means of addressing a public health concern. The effectiveness of fortification for a target population and safety for the much larger general population impose conflicting challenges that must be considered concurrently when making decisions regarding fortification. Recent data show improved folate status and apparent decreases in risk of neural tube birth defects in the U.S. Much about the long-term effects of the fortification program remains unknown and careful monitoring over time will be necessary to ensure that the program functions as intended. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Yetley, EA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 35 TC 29 Z9 29 U1 1 U2 6 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 JUN PY 2004 VL 62 IS 6 SU S BP S50 EP S59 DI 10.1301/nr.2004.jun.S50-S59 PN 2 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 906AD UT WOS:000227612000014 PM 15298449 ER PT J AU Hutter, JC Luu, HM Kim, CS AF Hutter, JC Luu, HM Kim, CS TI A dynamic simulation of bisphenol A dosimetry in neuroendocrine organs SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE bisphenol A; neuroendocrine organs; pharmacokinetic modelling ID TISSUE DISTRIBUTION; RATS; BINDING; DISPOSITION; METABOLISM; ESTROGENS; EXPOSURE; MCF-7 AB Bisphenol A (BPA) is a known xenoestrogen with similar properties to 17beta-estradiol. BPA and estrogen are hydrophobic compounds, and this affects the pharmacokinetics of both compounds in mammals. In a previous study we measured the distribution of BPA in female F344 rats exposed to oral doses of 0.1, 10 and 100 mg/kg. The results showed distribution to target neuroendocrine organs at all doses tested. Using these results, we developed a pharmacokinetic model to predict the dynamic uptake and excretion of BPA by various routes of exposure (po, iv, sc, ip). The model was able to simulate the entire time course (48 h) following various routes of exposure in rats over the dose ranges tested. The model indicated that the ultimate tissue uptake of BPA was established by the rapid initial transfer of free BPA into tissues. After free BPA enters the systemic circulation, metabolism and excretion reactions cause a relatively short duration and rapid decline. This period is followed by a slower long-term decline characteristic of BPXs biphasic pharmacokinetics. Plasma protein and tissue binding reactions established the long-term half-life of BPA in the body. Route differences in tissue uptake were directly related to the competition between transfer and binding reactions during the absorption phase. C1 US FDA, Off Sci, Ctr Device & Radiol Hlth, Rockville, MD 20852 USA. US FDA, Engn Labs, Ctr Device & Radiol Hlth, Rockville, MD 20852 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Saftey Assessment, Laurel, MD USA. RP Hutter, JC (reprint author), US FDA, Off Sci, Ctr Device & Radiol Hlth, 12725 Twinbrook Pkwy HFZ-150, Rockville, MD 20852 USA. EM jch@cdrh.fda.gov NR 32 TC 4 Z9 4 U1 1 U2 1 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD JUN PY 2004 VL 20 IS 1-5 BP 29 EP 40 DI 10.1191/0748233704th187oa PG 12 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 904KK UT WOS:000227496500004 PM 15807406 ER PT J AU Kim, CS Sapienza, PP Ross, IA Johnson, W Luu, HMD Hutter, JC AF Kim, CS Sapienza, PP Ross, IA Johnson, W Luu, HMD Hutter, JC TI Distribution of bisphenol A in the neuroendocrine organs of female rats SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE bisphenol A; neuroendocrine organs; pharmacokinetics ID TISSUE DISTRIBUTION; DISPOSITION; METABOLISM; FLORIDA; BRAIN AB The distribution of C-14-bisphenol A (BPA) in plasma and neuroendocrine organs was determined in Fischer 344 female rats following three oral doses (0.1, 10 or 100 mg/kg). Plasma and tissue maximum concentrations (C-max) were reached within 15-30 min of dosing. Plasma areas-under-the-curve (AUC) ranged from 0.06 to 53.9 mug-h/mL. The AUCs of the pituitary gland and uterus/gonads were 16-21% higher than that of plasma. The AUCs of hypothalamus and the rest of the brain were 43.7% and 77% of the plasma AUCs, respectively. In the brain tissue, the exposure increased linearly with the oral dose, as the dose was increased from 0.1 to 10 and 100 mg/kg; the exposure in the brain relative to the plasma increased by factors of 1, 1.19 and 1.24. This indicates that the brain barrier systems do not limit the access of the lipophilic BPA to the brain. The increases of the uterus/gonads relative to the plasma were 1, 1.07 and 1.04. Tissue partitioning was also examined in vitro by the uptake of C-14-BPA. The BPA tissue/blood partition coefficients were as follows: heart, 7.5; liver, 6.1; kidney, 6.4; fat, 3.6; muscle, 2.6; breast, 3.6; ovaries, 9.1; uterus, 5.9; stomach, 5.1; and small intestine, 6.7. The tissue/cerebrospinal fluid partition coefficients were as follows: pituitary gland, 12.8; brain stem, 6.1; cerebellum, 6.4; hippocampus, 7.1; hypothalamus, 6.1; frontal cortex, 4.9; and caudate nucleus, 6.8. C1 US FDA, Off Appl Res & Saftey Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. US FDA, Ctr Devices & Radiol Hlth, Off Sci, Rockville, MD 20857 USA. US FDA, Ctr Devices & Radiol Hlth, Engn Labs, Rockville, MD 20857 USA. RP Kim, CS (reprint author), US FDA, Off Appl Res & Saftey Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. EM csk@cfsan.fda.gov NR 18 TC 14 Z9 15 U1 3 U2 6 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD JUN PY 2004 VL 20 IS 1-5 BP 41 EP 50 DI 10.1191/0748233704th186oa PG 10 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 904KK UT WOS:000227496500005 PM 15807407 ER PT J AU Phelps, R Robbins, K Liberti, T Machuca, A Leparc, G Chamberland, M Kalish, M Hewlett, I Folks, T Lee, LM McKenna, M AF Phelps, R Robbins, K Liberti, T Machuca, A Leparc, G Chamberland, M Kalish, M Hewlett, I Folks, T Lee, LM McKenna, M TI Window-period human immunodeficiency virus transmission to two recipients by an adolescent blood donor SO TRANSFUSION LA English DT Article ID UNITED-STATES; INFECTIOUS-DISEASES; RISK; TRANSFUSION; HIV-1; DONATIONS; ASSAY; HCV AB BACKGROUND: Pooled NAT and donor screening have reduced the diagnostic window period for HIV in the blood donor population to approximately 10 to 15 days. This report describes two cases of transfusion-acquired HIV infection and verification of transmission from the donor to the recipients, and attempts to identify how the 18-year-old donor acquired her infection. STUDY DESIGN AND METHODS: After a repeat donor had a positive HIV test result, two recipients of the donor's previous donation were identified and tested. The donor and recipients were interviewed and blood samples were obtained for HIV DNA sequencing and phylogenetic analysis. RESULTS: The two recipients had positive HIV test results. Phylogenetic analysis showed a high genetic similarity among the viruses (bootstrap 100%), consistent with transmission from the donor to the recipients. Four of five men with whom the donor had sexual contact during the critical time period when infection most likely occurred were located and tested; results were negative for HIV. CONCLUSIONS: Pooled NAT of blood donations has not eliminated the window period for HIV identification during seroconversion. C1 Natl Ctr HIV STD & TB Prevent, Div HIV AIDS Prevent, Atlanta, GA USA. Natl Ctr HIV STD & TB Prevent, Div AIDS STD & TB Lab Res, Atlanta, GA USA. Ctr Dis Control, Natl Ctr Infect Dis, Div Viral & Rickettsial Dis, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Florida Dept Hlth, Tallahassee, FL USA. US FDA, CBER, Mol Biol Lab,Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, Bethesda, MD USA. Florida Blood Serv, St Petersburg, FL USA. RP Phelps, R (reprint author), Ctr Dis Control & Prevent, Natl Ctr HIV STD & TB Prevent, Off Commun, MS E-07, Atlanta, GA 30333 USA. EM RPhelps@cdc.gov NR 19 TC 40 Z9 44 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 2004 VL 44 IS 6 BP 929 EP 933 DI 10.1111/j.1537-2995.2004.03364.x PG 5 WC Hematology SC Hematology GA 826IU UT WOS:000221823600022 PM 15157262 ER PT J AU Ellenberg, SS George, SL AF Ellenberg, SS George, SL TI Should statisticians reporting to data monitoring committees be independent of the trial sponsor and leadership? SO STATISTICS IN MEDICINE LA English DT Article DE clinical trials; data monitoring; interim analysis; conflict of interest ID CLINICAL-TRIALS; ISSUES AB It has long been a fundamental principle of clinical trials that interim comparative data should be kept confidential, with such data accessible only to a small number of individuals responsible for its analysis and monitoring. The rationale for keeping investigators and sponsors blinded to interim data has been extensively discussed, but the possible conflicts of interest that could arise for the statistician who performs the analysis of the interim data and presents it to a data monitoring committee has received little attention. We describe these potential conflicts, and the advantages and disadvantages of approaches that might be taken to minimize them. We have invited commentary on this issue from several statisticians with substantial experience in clinical trials and interim data monitoring. Published in 2004 by John Wiley Sons, Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27706 USA. RP Ellenberg, SS (reprint author), 1401 Rockville Pike,HFM-210, Rockville, MD 20852 USA. EM ellenberg@eber.fda.gov NR 9 TC 14 Z9 16 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAY 30 PY 2004 VL 23 IS 10 BP 1503 EP 1505 DI 10.1002/sim.1784 PG 3 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 818GP UT WOS:000221233900002 PM 15122727 ER PT J AU Siegel, JP O'Neill, RT Temple, R Campbell, G Foulkes, MA AF Siegel, JP O'Neill, RT Temple, R Campbell, G Foulkes, MA TI Independence of the statistician who analyses unblinded data SO STATISTICS IN MEDICINE LA English DT Article AB This discussion considers arguments for and against separating responsibility for the unblinded interim analysis of a clinical trial from responsibility for trial management and modifications to the ongoing trial. The degree to which one or different statisticians carry out these responsibilities and thus the degree of statistician independence for the two activities can vary, but a sponsor should recognize that giving a single statistician both responsibilities might limit flexibility in managing the trial, particularly with respect to modifying an ongoing trial. Published in 2004 by John Wiley Sons, Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Foulkes, MA (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-210, Rockville, MD 20852 USA. EM foulkes@cber.fda.gov NR 0 TC 9 Z9 9 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAY 30 PY 2004 VL 23 IS 10 BP 1527 EP 1529 DI 10.1002/sim.1789 PG 3 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 818GP UT WOS:000221233900007 PM 15122732 ER PT J AU Hartigan, MD Crompton, LA Reynolds, CK Wray-Cahen, D Lomax, MA France, J AF Hartigan, MD Crompton, LA Reynolds, CK Wray-Cahen, D Lomax, MA France, J TI An integrative model of amino acid metabolism in the liver of the lactating dairy cow SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article DE model; liver; metabolism; amino acid; dairy cow; lactation ID PARTITIONING LEUCINE UPTAKE; PORTAL-DRAINED VISCERA; ISOTOPE-DILUTION MODEL; BOVINE MAMMARY-GLAND; VOLATILE FATTY-ACIDS; MESENTERIC VEIN; SPLANCHNIC METABOLISM; HOLSTEIN COWS; PROTEIN-METABOLISM; HEPATIC-METABOLISM AB The objective of this work was to construct a dynamic model of hepatic amino acid metabolism in the lactating dairy cow that could be parameterized using net flow data from in vivo experiments. The model considers 22 amino acids, ammonia, urea, and 13 energetic metabolites, and was parameterized using a steady-state balance model and two in vivo, net flow experiments conducted with mid-lactation dairy cows. Extracellular flows were derived directly from the observed data. An optimization routine was used to derive nine intracellular flows. The resulting dynamic model was found to be stable across a range of inputs suggesting that it can be perturbed and applied to other physiological states. Although nitrogen was generally in balance, leucine was in slight deficit compared to predicted needs for export protein synthesis, suggesting that an alternative source of leucine (e.g. peptides) was utilized. Simulations of varying glucagon concentrations indicated that an additional 5 mol/d of glucose could be synthesized at the reference substrate concentrations and blood flows. The increased glucose production was supported by increased removal from blood of lactate, glutamate, aspartate, alanine, asparagine, and glutamine. As glucose Output increased, ketone body and acetate release increased while CO2 release declined. The pattern of amino acids appearing in hepatic vein blood was affected by changes in amino acid concentration in portal vein blood, portal blood flow rate and glucagon concentration, with methionine and phenylalanine being the most affected of essential amino acids. Experimental evidence is insufficient to determine whether essential amino acids are affected by varying gluconeogenic demands. (C) 2004 Published by Elsevier Ltd. C1 Univ Guelph, Dept Anim & Poultry Sci, Guelph, ON N1G 2W1, Canada. Univ London Imperial Coll Sci Technol & Med, Dept Agr Sci, Ashford TN25 5AH, Kent, England. US FDA, Ctr Devices & Radiol Hlth, OST, DLS,HSB, Laurel, MD 20708 USA. Ohio State Univ, Ohio Agr Res & Dev Ctr, Dept Anim Sci, Wooster, OH 44691 USA. Univ Reading, Sch Agr Policy & Dev, Reading RG6 6AR, Berks, England. Purina Mills LLC, St Louis, MO 63166 USA. RP France, J (reprint author), Univ Guelph, Dept Anim & Poultry Sci, 50 Gordon St, Guelph, ON N1G 2W1, Canada. EM jfrance@uoguelph.ca NR 63 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD MAY 21 PY 2004 VL 228 IS 2 BP 271 EP 289 DI 10.1016/j.jtbi.2004.01.010 PG 19 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 817VQ UT WOS:000221205400011 PM 15094021 ER PT J AU Shefcheck, KJ Musser, SM AF Shefcheck, KJ Musser, SM TI Confirmation of the allergenic peanut protein, Ara h 1, in a model food matrix using liquid chromatography/tandem mass spectrometry (LC/MS/MS) SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE allergenicity; analysis; confirmation; LC/MS/MS; peanut; proteins ID ARA-H-I; ANAPHYLACTIC REACTIONS; ATOPIC-DERMATITIS; IGE BINDING; PROTEOMICS; CANCER; IDENTIFICATION; BIOMARKERS; DISCOVERY; CHALLENGE AB Enzymatic digestion of total protein along with liquid chromatography/tandem mass spectrometry (LC/MS/MS) was used to confirm the presence of a major peanut allergen in food. Several peptides obtained from the enzymatic digestion of the most abundant peanut allergen, Ara h 1, were identified as specific peptide biomarkers for peanut protein. Using ice cream as a model food matrix, a method was developed for the detection of the allergen peptide biomarkers. A key component of the method was the use of molecular mass cutoff filters to enrich the Ara h 1 in the protein extracts. By applying the method to ice cream samples containing various levels of peanut protein, levels as low as 10 mg/kg of Ara h 1 could routinely be detected. This method provides an unambiguous means of confirming the presence of the peanut allergen, Ara h 1, in foods and can easily be modified to detect other food allergens. C1 US FDA, Ctr Food Safety & Nutr, College Pk, MD 20740 USA. RP Shefcheck, KJ (reprint author), US FDA, Ctr Food Safety & Nutr, College Pk, MD 20740 USA. EM kshefche@cfsan.fda.gov NR 31 TC 46 Z9 53 U1 1 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY 19 PY 2004 VL 52 IS 10 BP 2785 EP 2790 DI 10.1021/jf035129h PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 820WE UT WOS:000221419500007 PM 15137814 ER PT J AU Yu, MYW Bartosch, B Zhang, P Guo, ZP Renzi, PM Shen, LM Granier, C Feinstone, SM Cosset, FL Purcell, RH AF Yu, MYW Bartosch, B Zhang, P Guo, ZP Renzi, PM Shen, LM Granier, C Feinstone, SM Cosset, FL Purcell, RH TI Neutralizing antibodies to hepatitis C virus (HCV) in immune globulins derived from anti-HCV-positive plasma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POST-TRANSFUSION HEPATITIS; HYPERVARIABLE REGION 1; INTRAVENOUS IMMUNOGLOBULIN; HYPERIMMUNE SERUM; GAMMA-GLOBULIN; INFECTION; PREVENTION; CHIMPANZEES; FRACTIONATION; PARTICLES AB The role of humoral immunity in hepatitis C virus (HCV) infections is uncertain. Nevertheless, there is increasing evidence for neutralizing antibodies to HCV in the serum or plasma of chronically infected individuals. Immune globulins prepared by ethanol fractionation of plasma had long been considered safe until a commercial immune globulin product, Gammagard, prepared from plasma from which units containing anti-HCV had been excluded, transmitted HCV to recipients. Studies suggested that the exclusion might have removed neutralizing antibodies from the plasma and hence compromised the safety of the resulting immune globulins. In the present study, by using chimpanzees and a recently validated in vitro system based on neutralization of infectious HCV pseudoparticles, we found broadly reactive neutralizing and protective antibodies in experimental immune globulin preparations made from anti-HCV-positive donations. Neutralizing antibodies were also found in Gammagard lots made from unscreened plasma that did not transmit hepatitis C but not in Gammagard lots, which were prepared from anti-HCV-screened plasma, that did transmit hepatitis C. The results provide an explanation for the mechanism by which the safety of this product was compromised. Immune globulins made from anti-HCV-positive plasma and containing broadly reactive neutralizing antibodies may provide a method of preventing HCV infection. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. Ecole Normale Super Lyon, Lab Vectorol Retrovirale & Therapie Genique, Inst Natl Sante & Rech Med, U412, F-69364 Lyon, France. NIAID, Lab Infect Dis, NIH, Bethesda, MD 20892 USA. RP Purcell, RH (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM rpurcell@niaid.nih.gov NR 35 TC 105 Z9 110 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 18 PY 2004 VL 101 IS 20 BP 7705 EP 7710 DI 10.1073/pnas.0402458101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 822GW UT WOS:000221528100040 PM 15136748 ER PT J AU Casciano, DA Fuscoe, JC AF Casciano, DA Fuscoe, JC TI Preface to mutation research special issue on toxicogenomics SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Editorial Material C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72223 USA. RP Casciano, DA (reprint author), US FDA, Natl Ctr Toxicol Res, HFT-1,3900 NCTR Rd, Jefferson, AR 72223 USA. EM dcasciano@nctr.fda.gov; jfuscoe@nctr.fda.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAY 15 PY 2004 VL 549 IS 1-2 BP 1 EP 3 DI 10.1016/j.mrfmmm.2004.02.008 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 823BB UT WOS:000221583600001 ER PT J AU Akerman, GS Rosenzweig, BA Domon, OE McGarrity, LJ Blankenship, LR Tsai, CA Culp, SJ MacGregor, JT Sistare, FD Chen, JJ Morris, SM AF Akerman, GS Rosenzweig, BA Domon, OE McGarrity, LJ Blankenship, LR Tsai, CA Culp, SJ MacGregor, JT Sistare, FD Chen, JJ Morris, SM TI Gene expression profiles and genetic damage in benzo(a)pyrene diol epoxide-exposed TK6 cells SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE cDNA microarray; benzo(a)pyrene diol epoxide; BPDE; TK6 cells; gene expression profiles ID HUMAN LYMPHOBLASTOID-CELLS; S-ADENOSYLMETHIONINE DECARBOXYLASE; POLYCYCLIC AROMATIC-HYDROCARBONS; KAPPA-B ACTIVATION; HMG-COA REDUCTASE; DNA-ADDUCTS; POLYAMINE METABOLISM; MUTATION-INDUCTION; RECENT DISCOVERIES; OXIDATIVE STRESS AB Microarray analysis is a powerful tool to identify the biological effects of drugs or chemicals on cellular gene expression. In this study, we compare the relationships between traditional measures of genetic toxicology and mutagen-induced alterations in gene expression profiles. TK6 cells were incubated with 0.01, 0.1, or 1.0 muM+/-anti-benzo(a)pyrene-trans-7, 8-dihydrodiol-9,10-epoxide (BPDE) for 4 h and then cultured for an additional 20 h. Aliquots of the exposed cells were removed at 4 and 24 h in order to quantify DNA adduct levels by P-32 post-labeling and measure cell viability by cloning efficiency and flow cytometry. Gene expression profiles were developed by extracting total RNA from the control and exposed cells at 4 and 24 h, labeling with Cy3 or Cy5 and hybridizing to a human 350 gene array. Mutant frequencies in the Thymidine Kinase and Hypoxanthine Phosphoribosyl Transferase genes were also determined. The 10alpha-(deoxyguanosin-N-2-yl)-7alpha,8beta,9beta-trihydroxy-7,8,9, 10-tetrahydrobenzo(a)pyrene (dG-N-2-BPDE) adduct increased as a function of dose and was the only adduct identified. A dose-related decrease in cell viability was evident at 24 h, but not at 4 h. Cell death occurred by apoptosis. At 4 h, analysis of the gene expression profiles revealed that Glutathione Peroxidase and Gadd45 were consistently upregulated (greater than 1.5-fold and significantly (P<0.001) greater than the control in two experiments) in response to 1.0 μM BPDE exposure. Fifteen genes were consistently down-regulated (less than 0.67-fold and significantly (P<0.001) lower than the control in two experiments) at 4 h in cultures exposed to 1.0 muM BPDE. Genes with altered expression at 4 h included genes important in the progression of the cell-cycle and those that inhibit apoptosis. At 24 h post-exposure, 16 genes, involved in cell-cycle control, detoxification, and apoptosis were consistently upregulated; 10 genes were repressed in cultures exposed to the high dose of BPDE. Real-time quantitative PCR confirmed the differential expression of selected genes. These data suggest that changes in gene expression will help to identify effects of drugs and chemicals on molecular pathways in cells, and will provide useful information about the molecular responses associated with DNA damage. Of the endpoints evaluated, DNA adduct formation was the most sensitive indicator of DNA damage. DNA adduct formation was clearly evident at low doses, but the number of genes with significantly altered expression (P<0.001) was minimal. Alterations in gene expression were more robust at doses associated with cellular toxicity and induction of mutations. C1 US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Laurel, MD USA. US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Environm Hlth & Program Assurance Staff, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Washington Operat Off, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. RP Morris, SM (reprint author), US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM smorris@nctr.fda.gov OI Tsai, Chen-An/0000-0002-7490-4331 NR 83 TC 53 Z9 56 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAY 15 PY 2004 VL 549 IS 1-2 BP 43 EP 64 DI 10.1016/j.mrfmmm.2003.11.013 PG 22 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 823BB UT WOS:000221583600004 PM 15120962 ER PT J AU Harris, AJ Dial, SL Casciano, DA AF Harris, AJ Dial, SL Casciano, DA TI Comparison of basal gene expression profiles and effects of hepatocarcinogens on gene expression in cultured primary human hepatocytes and HepG2 cells SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE filter array; gene expression; HepG2; primary human hepatocytes ID GROWTH FACTOR-II; ORGANIC CATION TRANSPORTERS; LOOP-HELIX PROTEINS; RAT HEPATOCYTES; HEPATOMA-CELL; HUMAN-LIVER; CREATINE-TRANSPORTER; MICROARRAY ANALYSIS; IN-VITRO; HUMAN FIBROBLASTS AB Toxicogenomics is a relatively new discipline of toxicology. Microarrays and bioinformatics tools are being used successfully to understand the effects of toxicants on in vivo and in vitro model systems, and to gain a better understanding of the relevance of in vitro models commonly used in toxicological studies. In this study, cDNA filter arrays were used to deter-mine the basal expression patterns of human cultured primary hepatocytes from different male donors; compare the gene expression profile of HepG2 to that of primary hepatocytes; and analyze the effects of three genotoxic hepatocarcinogens; aflatoxin B-1 (AFB(1)), 2-acetylaminofluorene (2AAF), and dimethylnitrosamine (DMN), as well as one non-gentoxic hepatotoxin, acetaminophen (APAP) on gene expression in both in vitro systems. Real-time PCR was used to verify differential gene expression for selected genes. Of the approximately 3 1,000 genes screened, 3-6% were expressed in primary hepatocytes cultured on matrigel for 16 h. Of these genes, 867 were expressed in cultured hepatocytes from all donors. HepG2 cells expressed about 98% of the genes detectable in cultured primary hepatocytes, however, 31% of the HepG2 transcriptome was unique to the cell line. A number of these genes are expressed in human liver but expression is apparently lost during culture. There was considerable variability in the response to chemical carcinogen exposure in primary hepatocytes from different donors. The transcription factors, E2F1 and ID1 mRNA were increased three-fold and six-fold (P<0.05, P<0.01), respectively, in AFB(1) treated primary human hepatocytes but were not altered in HepG2. ID1 expression was also increased by dimethylnitrosamine, acetylaminofluorene and acetaminophen in both primary hepatocytes and HepG2. Identification of Genes that are expressed in primary hepatocytes from most donors, as well as those genes with variable expression, will aid in understanding the variability in human reactions to drugs and chemicals. This study suggests that identification of biomarkers of exposure to some chemicals may be possible in the human through microarray analysis, despite the variability in responses. (C) 2004, Published by Elsevier B.V. C1 US FDA, Ctr Hepatotox, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Off Director, Jefferson, AR 72079 USA. RP Harris, AJ (reprint author), US FDA, Ctr Hepatotox, Natl Ctr Toxicol Res, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM aharris@cteh.com FU NIDDK NIH HHS [N01-DK-9-2310] NR 75 TC 69 Z9 71 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 MAY 15 PY 2004 VL 549 IS 1-2 BP 79 EP 99 DI 10.1016/j.mrfmmm.2003.11.014 PG 21 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 823BB UT WOS:000221583600006 PM 15120964 ER PT J AU Desai, VG Moland, CL Branham, WS Delongchamp, RR Fang, H Duffy, PH Peterson, CA Beggs, ML Fuscoe, JC AF Desai, VG Moland, CL Branham, WS Delongchamp, RR Fang, H Duffy, PH Peterson, CA Beggs, ML Fuscoe, JC TI Changes in expression level of genes as a function of time of day in the liver of rats SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE microarray analysis; circadian rhythm; liver ID PERIPHERAL CIRCADIAN OSCILLATORS; SUPRACHIASMATIC NUCLEUS; TISSUE TRANSGLUTAMINASE; CLINICAL IMPLICATIONS; CROSS-LINKING; RECEPTOR; MOUSE; CELLS; PHARMACOLOGY; TOXICOLOGY AB Daily, rhythmic variation in various biochemical, physiological, and behavioral events is a fundamental property of biological organization. Here, we report analysis of relative levels of gene expression in the liver of 16 Fischer 344 rats as a function of time of day. Expression levels were determined for 3906 genes using high-density oligonucleotide microarrays. Of the 3906 genes, 1171 (30%) were clearly expressed while 2735 (70%) were not expressed or the expression was too low to distinguish from background levels. The maximum estimated changes observed for most genes (1029, 88%) were less than 1.5-fold. Analysis of variance and the Kruskal-Wallis tests were used to identify 67 genes whose expression was significantly altered as a function of time of day. These significantly altered genes were classified according to their functions and fall into key cellular pathways including drug metabolism, ion transport, signal transduction, DNA binding and regulation of transcription, and immune response. (C) 2004, Elsevier B.V All rights reserved. C1 US FDA, Ctr Funct Genom, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Cent Arkansas Vet Hlth Care Syst, Little Rock, AR 72205 USA. RP Desai, VG (reprint author), US FDA, Ctr Funct Genom, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM vdesai@nctr.fda.gov NR 52 TC 28 Z9 31 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAY 15 PY 2004 VL 549 IS 1-2 BP 115 EP 129 DI 10.1016/j.mrfmmm.2003.11.016 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 823BB UT WOS:000221583600008 PM 15120966 ER PT J AU Tong, WD Harris, S Cao, XX Fang, H Shi, LM Sun, HM Fuscoe, J Harris, A Hong, HX Xie, Q Perkins, R Casciano, D AF Tong, WD Harris, S Cao, XX Fang, H Shi, LM Sun, HM Fuscoe, J Harris, A Hong, HX Xie, Q Perkins, R Casciano, D TI Development of public toxicogenomics software for microarray data management and analysis SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE toxicogenomics software; DNA microarray; database ID NORMALIZATION; TOXICOLOGY; BIOLOGY AB A robust bioinformatics capability is widely acknowledged as central to realizing the promises of toxicogenomics. Successful application of toxicogenomic approaches, such as DNA microarray, inextricably relies on appropriate data management, the ability to extract knowledge from massive amounts of data and the availability of functional information for data interpretation. At the FDA's National Center for Toxicological Research (NCTR), we are developing a public microarray data management and analysis software, called ArrayTrack. ArrayTrack is Minimum Information About a Microarray Experiment (MIAME) supportive for storing both microarray data and experiment parameters associated with a toxicogenomics study. A quality control mechanism is implemented to assure the fidelity of entered expression data. ArrayTrack also provides a rich collection Of functional information about genes, proteins and pathways drawn from various public biological databases for facilitating data interpretation. In addition, several data analysis and visualization tools are available with ArrayTrack, and more tools will be available in the next released version. Importantly, gene expression data, functional information and analysis methods are fully integrated so that the data analysis and interpretation process is simplified and enhanced. ArrayTrack is publicly available online and the prospective user can also request a local installation version by contacting the authors. (C) 2004 Elsevier B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Ctr Toxicoinformat, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Northrop Grumman Informat Technol, Jefferson, AR 72079 USA. US FDA, Ctr Funct Genom, Div Reprod & Genet Toxicol, NCTR, Jefferson, AR 72079 USA. US FDA, Ctr Hepatotox, NCTR, Jefferson, AR 72079 USA. US FDA, Off Director, NCTR, Jefferson, AR 72079 USA. RP Tong, WD (reprint author), Natl Ctr Toxicol Res, Ctr Toxicoinformat, Div Biometry & Risk Assessment, 3900 NCTR Rd,HFT-020, Jefferson, AR 72079 USA. EM wtong@nctr.fda.gov NR 22 TC 73 Z9 77 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAY 15 PY 2004 VL 549 IS 1-2 BP 241 EP 253 DI 10.1016/j.mrfmmm.2003.12.024 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 823BB UT WOS:000221583600016 PM 15120974 ER PT J AU Garcia, G Hicks, R Skanchy, D Moorad-Doctor, D AF Garcia, G Hicks, R Skanchy, D Moorad-Doctor, D TI The Huperzine A (Hup A) metabolite from the rat SO FASEB JOURNAL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Biochemistry-and-Molecular-Biology/8th Congress of the International-Union-for-Biochemistry-and-Molecular-Biology CY JUN 12-16, 2004 CL Boston, MA SP Amer Soc BioChem & Mol Biol, Int Union Biochem & Mol Biol C1 WRAIR, Div Biochem, Dept Biochem Pharmacol, Silver Spring, MD 20910 USA. WRAIR, Div Expt Therapeut, Dept Med Chem, Rockville, MD USA. US FDA, Rockville, MD 20857 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 MAY 14 PY 2004 VL 18 IS 8 SU S BP C45 EP C45 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 823UP UT WOS:000221639100205 ER PT J AU Cordoba-Rodriguez, R Fang, H Lankford, CSR Frucht, DM AF Cordoba-Rodriguez, R Fang, H Lankford, CSR Frucht, DM TI Anthrax lethal toxin rapidly activates caspase-1/ICE and induces extracellular release of interleukin (IL)-1 beta and IL-18 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BACILLUS-ANTHRACIS; CONVERTING-ENZYME; MICE DEFICIENT; FACTOR CLEAVES; TNF-ALPHA; MACROPHAGES; APOPTOSIS; KINASE; PHOSPHORYLATION; INACTIVATION AB Anthrax lethal toxin (LT), a critical virulence factor for Bacillus anthracis, has been demonstrated to cleave and to inactivate mitogen-activated protein kinase kinases (MAPKKs) that propagate prosurvival signals in macrophages (1-5). Whether this action of anthrax LT leads to the production of proinflammatory cytokines by macrophages has been more controversial (6, 7). We now report that anthrax LT treatment leads to the specific extracellular release of interleukin (IL)-1beta and IL-18 by the murine macrophage cell lines, RAW264.7 and J774A.1. Studies of the processing of IL-1beta reveal that the levels of activated/cleaved IL-1beta in RAW264.7 and J774.A1 cells are increased following treatment with anthrax LT. Enhanced processing of IL-1beta directly correlates with increased levels in the activation of its upstream regulator, IL-1beta-converting enzyme/Caspase-1 (ICE). The extracellular release of IL-1beta and IL-18 in response to anthrax LT is ICE-dependent, as an ICE-specific inhibitor blocks this process. These data indicate that ICE, IL-1beta, and IL-18 are downstream effectors of anthrax LT in macrophages, providing the basis for new bioassays for anthrax LT activity and representing potential therapeutic targets. C1 US FDA, Div Monoclonal Antibodies, Off Biotechnol, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Frucht, DM (reprint author), US FDA, Div Monoclonal Antibodies, Off Biotechnol, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bldg 29B,Rm 3NN22, Bethesda, MD 20892 USA. EM frucht@cber.fda.gov NR 23 TC 50 Z9 54 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 14 PY 2004 VL 279 IS 20 BP 20563 EP 20566 DI 10.1074/jbc.C300539200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 818VY UT WOS:000221273800003 PM 15010463 ER PT J AU Kleinman, S Busch, M Caglioti, S Stramer, SL Dodd, R Strong, DM Dickey, W Salvidar, B Gilchrist, M Brend, S Nakhasi, H Epstein, J Goodman, J Chamberland, M Kuehnert, M Petersen, L Crall, N Marfin, A Boo, T Montgomery, S AF Kleinman, S Busch, M Caglioti, S Stramer, SL Dodd, R Strong, DM Dickey, W Salvidar, B Gilchrist, M Brend, S Nakhasi, H Epstein, J Goodman, J Chamberland, M Kuehnert, M Petersen, L Crall, N Marfin, A Boo, T Montgomery, S TI Update: West Nile virus screening of blood donations and transfusion-associated transmission - United States, 2003 (Reprinted from MMWR, vol 53, pg 281-284, 2004) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Amer Assoc Blood Banks, Victoria, BC, Canada. Blood Syst Res Inst, San Francisco, CA USA. Blood Syst Labs, Tempe, AZ USA. Amer Red Cross, Gaithersburg, MD USA. Puget Sound Blood Ctr, Seattle, WA 98104 USA. Belle Bonfils Mem Blood Ctr, Denver, CO USA. Univ Iowa, Hyg Lab, Iowa City, IA USA. Iowa Dept Publ Hlth, Des Moines, IA 50319 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. CDC, Div Viral & Rickettsial Dis, Atlanta, GA 30333 USA. CDC, Div Vector Borne Infect Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. RP Kleinman, S (reprint author), Amer Assoc Blood Banks, Victoria, BC, Canada. NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 12 PY 2004 VL 291 IS 18 BP 2184 EP + PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 819GR UT WOS:000221303500008 ER PT J AU Shames, DA AF Shames, DA TI Risks of testosterone replacement SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Shames, DA (reprint author), US FDA, Rockville, MD 20857 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 6 PY 2004 VL 350 IS 19 BP 2004 EP 2004 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 818AU UT WOS:000221218800023 PM 15128905 ER PT J AU Racoosin, JA Knudsen, JF AF Racoosin, JA Knudsen, JF TI Safety of newer antiepileptic drugs SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Div Neuropharmacol Drug Prod, Rockville, MD 20857 USA. RP Racoosin, JA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Neuropharmacol Drug Prod, Rockville, MD 20857 USA. EM racoosinj@cder.fda.gov NR 5 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 5 PY 2004 VL 291 IS 17 BP 2074 EP 2074 DI 10.1001/jama.291.17.2074-a PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 817JR UT WOS:000221174300012 PM 15126428 ER PT J AU Machuca, A Ding, L Taffs, R Lee, SW Wood, O Hu, JJ Hewlett, I AF Machuca, A Ding, L Taffs, R Lee, SW Wood, O Hu, JJ Hewlett, I TI HIV type 2 primary isolates induce a lower degree of apoptosis "in vitro" compared with HIV type 1 primary isolates SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELLS; IMMUNE ACTIVATION; DISEASE PROGRESSION; VIRAL LOAD; INFECTION; SUBTYPES; TAT; PATHOGENICITY; PATHOGENESIS AB To determine whether subtypes of HIV-1 and HIV-2 vary in their ability to induce T cell apoptosis in vitro, human peripheral blood mononuclear cells (PBMC) from healthy donors and CEM.NKR-CCR5 cells were infected with a variety of HIV-1 and HIV-2 isolates in vitro. Apoptotic cell levels and chemokine and cytokine production were analyzed. Significant variations in cytopathic effects following in vitro infection with primary isolates of HIV-1 or HIV-2 subtypes were observed in PBMCs. The percent of apoptotic cells from each individual ranged from 2 to 78% after HIV-1 infection and from 0 to 28% after HIV-2 infection (p < 0.01). We did not observe significant differences in the degree of apoptosis induced among cells infected with different HIV-1 group M subtypes or group 0 virus, nor among cells infected with different HIV-2 isolates. However, HIV-2 induced significantly lower degree of apoptosis overall in PBMC and CEM.NKR-CC5 cells when compared with HIV-1 subtypes (p < 0.0001). No significant differences were observed in the production of chemokines, such as RANTES, MIP-1alpha, and MIP-1beta, and cytokines, such as TNF-alpha and TNF-beta when PBMC cultures were infected with different HIV-1 subtype viruses, or HIV-2 isolates. In conclusion, HIV-2 isolates induced significantly lower levels of T cell apoptosis in both PBMC and CEM.NKR-CCR5 cells than HIV-1 isolates. No differences in T cell apoptosis levels were seen between different subtypes of HIV-1 group M or group O isolates. This is consistent with the mild clinical course of infection with HIV-2 that has been reported relative to that observed with HIV-1. C1 US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Off Blood Review & Res,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Lab Bacterial Parasit & Unconvent Agents, Div Emerging & Transfus Transmitted Dis, Off Blood Review & Res,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Hewlett, I (reprint author), US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, HFM 315,1401 Rockville Pike, Rockville, MD 20852 USA. EM Hewlett@cber.fda.gov NR 39 TC 9 Z9 10 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2004 VL 20 IS 5 BP 507 EP 512 DI 10.1089/088922204323087750 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 825MV UT WOS:000221763500007 PM 15186525 ER PT J AU Roy, S Caillouette, JC Roy, T Faden, JS AF Roy, S Caillouette, JC Roy, T Faden, JS TI Vaginal pH is similar to follicle-stimulating hormone for menopause diagnosis SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE vaginal pH value; follicle-stimulating hormone; menopause; estrogen therapy ID URINARY-TRACT-INFECTIONS; POSTMENOPAUSAL WOMEN; UROGENITAL SYMPTOMS; ESTROGEN THERAPY; ESTRIOL; RING; CYTOLOGY; EFFICACY; ATROPHY; HEALTH AB Objective: This paper is intended to demonstrate whether vaginal pH value is associated with menopausal status and symptoms, to review the sensitivity of follicle-stimulating hormone or vaginal pH to diagnose menopause, to compare these findings to a group of practice patients, and to determine whether vaginal pH could be used in place of follicle-stimulating hormone as an initial screen to determine menopause. Study design: Sixteen studies regarding vaginal pH and menopausal symptoms before and after estrogen administration were analyzed. Two epidemiologic studies that reported follicle-stimulating hormone or vaginal pH with menopause were reviewed. These findings were compared with similar data from the practice of one of the authors (J.C.C.). Results: Menopausal women who do not receive estrogen therapy have a weighted average vaginal pH of 6.0, which is reduced significantly to 4.5 with estrogen therapy. To diagnose menopause, follicle-stimulating hormone greater than or equal to 15 or greater than or equal to 20 mIU/mL in the Third National Health and Nutrition Examination Survey had a sensitivity of 65% to 68%. In a study in Costa Rica, where 3 definitions of menopause were used, a pH of > 5.0 had a sensitivity of 64% to 67%. From the practice patients, the 95% confidence interval sensitivities and positive predictive values of vaginal pH and follicle-stimulating hormone to diagnose menopause overlapped, while a pH less than or equal to 4.5 indicated mid follicular phase estradiol levels. Conclusion: In women without vaginitis and no estrogen therapy, a vaginal pH of > 4.5 indicates menopause, because it demonstrates a similar sensitivity as follicle-stimulating hormone in epidemiologic studies. In the practice patients, the sensitivity of follicle-stimulating hormone was no different than vaginal pH in the diagnosis of menopause. Furthermore, with estrogen therapy, a vaginal pH of less than or equal to 4.5 indicates a mid follicular phase estradiol. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ So Calif, Keck Sch Med, Womens & Childrens Hosp, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA. US FDA, Washington, DC 20204 USA. RP Roy, S (reprint author), Univ So Calif, Keck Sch Med, Womens & Childrens Hosp, Dept Obstet & Gynecol, 1240 N Mission Rd,Rm L1022, Los Angeles, CA 90033 USA. EM subirro@usc.edu NR 37 TC 25 Z9 27 U1 0 U2 2 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 MAY PY 2004 VL 190 IS 5 BP 1272 EP 1277 DI 10.1016/j.ajog.2003.12.015 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 826JJ UT WOS:000221825100018 PM 15167829 ER PT J AU Kanal, E Borgstede, JP Barkovich, AJ Bell, C Bradley, WG Etheridge, S Felmlee, JP Froelich, JW Hayden, J Kaminski, EM Lester, JW Scoumis, EA Zaremba, LA Zinninger, MD AF Kanal, E Borgstede, JP Barkovich, AJ Bell, C Bradley, WG Etheridge, S Felmlee, JP Froelich, JW Hayden, J Kaminski, EM Lester, JW Scoumis, EA Zaremba, LA Zinninger, MD TI American college of radiology white paper on MR safety: 2004 update and revisions SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Amer Coll Radiol, Reston, VA USA. Univ Pittsburgh, Dept Radiol, Magnet Resonance Serv, Pittsburgh, PA 15213 USA. Penrose St Francis Hlth Syst, Colorado Springs, CO 80907 USA. Univ Calif San Francisco, Dept Neuroradiol, San Francisco, CA 94143 USA. NYU, Dept Anesthesiol, Sch Med, New York, NY 10016 USA. Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. Hitachi Med Syst Amer Inc, Natl Elect Manufacturers Assoc, Twinsburg, OH 44087 USA. Mayo Clin, Dept Radiol, Rochester, MN 55902 USA. Hennepin Cty Med Ctr, Dept Radiol, Minneapolis, MN 55415 USA. Univ Minnesota, Minneapolis, MN 55415 USA. Durham Radiol Associates, Durham, NC 27704 USA. US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Kanal, E (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA USA. NR 6 TC 83 Z9 86 U1 2 U2 2 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 MAY PY 2004 VL 182 IS 5 BP 1111 EP 1114 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 815DF UT WOS:000221022300004 PM 15100103 ER PT J AU Weininger, S Shang, AB Kopotic, RJ Goldman, JM Pennello, GA AF Weininger, S Shang, AB Kopotic, RJ Goldman, JM Pennello, GA TI Using the infrared (IR) plethysmogram to assess the effects of motion on the performance of pulse oximeters SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT International Meeting on Medical Simulation CY JAN 16-18, 2004 CL Albuquerque, NM C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Duke Univ, Dept Anesthesia, Durham, NC 27706 USA. Imagyn, Irvine, CA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2004 VL 98 IS 5 SU S MA A35 BP S16 EP S16 PG 1 WC Anesthesiology SC Anesthesiology GA 816PI UT WOS:000221121400036 ER PT J AU Brown, SL Morrison, AE AF Brown, SL Morrison, AE TI Local anesthetic infusion pump systems adverse events reported to the Food and Drug Administration SO ANESTHESIOLOGY LA English DT Article ID WOUND PERFUSION; PAIN-CONTROL; BUPIVACAINE C1 US FDA, Div Postmarket Surveillance, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Brown, SL (reprint author), US FDA, Div Postmarket Surveillance, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, 1350 Piccard Dr,HFZ-541, Rockville, MD 20850 USA. EM syb@cdrh.fda.gov NR 8 TC 31 Z9 33 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2004 VL 100 IS 5 BP 1305 EP 1306 DI 10.1097/00000542-200405000-00036 PG 2 WC Anesthesiology SC Anesthesiology GA 815VS UT WOS:000221070400034 PM 15114230 ER PT J AU Krieg, RC Fogt, F Braunschweig, T Herrmann, PC Wollscheidt, V Wellmann, A AF Krieg, RC Fogt, F Braunschweig, T Herrmann, PC Wollscheidt, V Wellmann, A TI ProteinChip((R)) array analysis of microdissected colorectal carcinoma and associated tumor stroma shows specific protein bands in the 3.4 to 3.6 kDa range SO ANTICANCER RESEARCH LA English DT Article DE SELDI; ProteinChip; proteome; protein; array; colorectal cancer; carcinoma ID AFFINITY MASS-SPECTROMETRY; PROTEOMIC ANALYSIS; PROSTATE-CANCER; IDENTIFICATION; BIOCHIP AB Multiple pathways of carcinogenesis have been associated with colorectal carcinomas, including the adenoma-carcinoma sequence. The non polyposis coli gene has also been implicated in the pathogenesis of these tumors. Identification of the epithelial- mesenchymal interaction may help in understanding the pathways of invasion and may lead to the development of new, non-invasive tools for the diagnosis and prognosis of colon carcinomas. A ProteinChip(R) Array technology (SELDI=Surface Enhanced Laser Desoiption Ionization) has been developed enabling analysis and profiling of complex protein mixtures from a few cells. This study describes the protein analysis of approximately 500-1000 freshly obtained cells from normal and malignant colonic epithelium and its associated stroma by SELDI-TOF-MS (Surface Enhanced Laser Desorption Ionization Time-of-Flight Mass Spectrometry). Pure cell populations of normal and malignant epithelium as well as stroma (without tumor cells) were selected by microdissection from 9 patients. A pattern of 3 peptides of 3.48, 3.55 and 3.6 kDa, which were increased in the colon tumor epithelium and stroma compared to associated normal colon and stroma in all 9 patients, was observed. Coupling microdissection with SELDI represents a powetful tool to identify cell and tumor specific proteins and to understand molecular events underlying the invasive event in colorectal carcinomas. The presence of certain proteins in invasive carcinomas may lead to the development of non invasive biomarkers for the identification or detection of recurrence of colorectal malignancies. C1 Univ Bonn, Inst Pathol, D-53127 Bonn, Germany. Rhein Westfal TH Aachen, UK Aachen, D-52074 Aachen, Germany. Univ Penn, Presbyterian Med Ctr, Philadelphia, PA 19104 USA. PALM Microlaser Technol AG, D-82347 Bernried, Germany. NCI, US FDA, Clin Proteom Program, Bethesda, MD 20892 USA. RP Wellmann, A (reprint author), Univ Bonn, Inst Pathol, Siegmund Freud Str 25, D-53127 Bonn, Germany. EM axel_wellmann@yahoo.com NR 14 TC 23 Z9 25 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAY-JUN PY 2004 VL 24 IS 3A BP 1791 EP 1796 PG 6 WC Oncology SC Oncology GA 839AW UT WOS:000222756700066 PM 15274357 ER PT J AU Huber, AM Feldman, BM Rennebohm, RM Hicks, JE Lindsley, CB Perez, MD Zemel, LS Wallace, CA Ballinger, SH Passo, MH Reed, AM Summers, RM White, PH Katona, IM Miller, FW Lachenbruch, PA Rider, LG AF Huber, AM Feldman, BM Rennebohm, RM Hicks, JE Lindsley, CB Perez, MD Zemel, LS Wallace, CA Ballinger, SH Passo, MH Reed, AM Summers, RM White, PH Katona, IM Miller, FW Lachenbruch, PA Rider, LG TI Validation and clinical significance of the childhood myositis assessment scale for assessment of muscle function in the juvenile idiopathic inflammatory myopathies SO ARTHRITIS AND RHEUMATISM LA English DT Article ID DISEASE-ACTIVITY; DAMAGE INDEXES; HEALTH-STATUS; CHILDREN; DERMATOMYOSITIS; RESPONSIVENESS; RELIABILITY AB Objective. To examine the measurement characteristics of the Childhood Myositis Assessment Scale (CMAS) in children with juvenile idiopathic inflammatory myopathy (juvenile IIM), and to obtain preliminary data on the clinical significance of CMAS scores. Methods. One hundred eight children with juvenile IIM were evaluated on 2 occasions, 7-9 months apart, using various measures of physical function, strength, and disease activity. Interrater reliability, construct validity, and responsiveness of the CMAS were examined. The minimum clinically important difference (MID) and CMAS scores corresponding to various degrees of physical disability were estimated. Results. The intraclass correlation coefficient for 26 patients assessed by 2 examiners was 0.89, indicating very good interrater reliability. The CMAS score correlated highly with the Childhood Health Assessment Questionnaire (C-HAQ) score and with findings on manual muscle testing (MMT) (r(s) = -0.73 and 0.73, respectively) and moderately with physician-assessed global disease activity and skin activity, parent-assessed global disease severity, and muscle magnetic resonance imaging (rs = -0.44 to -0.61), thereby demonstrating good construct validity. The standardized response mean was 0.81 (95% confidence interval 0.53, 1.09) in patients with at least 0.8 cm improvement on a 10-cm visual analog scale for physician-assessed global disease activity, indicating strong responsiveness. In bivariate regression models predicting physician-assessed global disease activity, MMT remained significant in models containing the CMAS (P = 0.03) while the C-HAQ did not (P = 0.4). Estimates of the MID ranged from 1.5 to 3.0 points on a 0-52-point scale. CMAS scores corresponding to no, mild, mild-to-moderate, and moderate physical disability, respectively, were 48, 45, 39, and 30. Conclusion. The CMAS exhibits good reliability, construct validity, and responsiveness, and is therefore a valid instrument for the assessment of physical function, muscle strength, and endurance in children with juvenile IIM. Preliminary data on MID and corresponding levels of disability should aid in the clinical interpretation of CMAS scores when assessing patients with juvenile IIM. C1 IWK Hlth Ctr, Halifax, NS B3J 3G9, Canada. Dalhousie Univ, Halifax, NS, Canada. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Univ Toronto, Toronto, ON, Canada. Ohio State Univ, Columbus, OH 43210 USA. Columbus Childrens Hosp, Columbus, OH USA. NIH, Ctr Clin, Bethesda, MD USA. Univ Kansas, Kansas City, KS USA. Baylor Coll Med, Houston, TX 77030 USA. Texas Childrens Hosp, Houston, TX 77030 USA. Univ Connecticut, Hartford, CT 06112 USA. Connecticut Childrens Med Ctr, Hartford, CT USA. Childrens Hosp, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. James Whitcomb Riley Hosp Children, Indianapolis, IN 46202 USA. Indiana Univ, Indianapolis, IN 46204 USA. Childrens Hosp, Cincinnati, OH 45229 USA. Univ Cincinnati, Cincinnati, OH USA. Mayo Clin, Rochester, MN USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Natl Inst Environm Hlth Sci, NIH, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD USA. RP Huber, AM (reprint author), IWK Hlth Ctr, 5850 Univ Ave, Halifax, NS B3J 3G9, Canada. EM adam.huber@iwk.nshealth.ca RI Feldman, Brian/A-8586-2011; OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 NR 21 TC 83 Z9 86 U1 2 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 2004 VL 50 IS 5 BP 1595 EP 1603 DI 10.1002/art.20179 PG 9 WC Rheumatology SC Rheumatology GA 819UI UT WOS:000221340900028 PM 15146430 ER PT J AU Dong, L Ito, SI Ishii, KJ Klinman, DM AF Dong, L Ito, SI Ishii, KJ Klinman, DM TI Suppressive oligonucleotides protect against collagen-induced arthritis in mice SO ARTHRITIS AND RHEUMATISM LA English DT Article ID INDUCED IMMUNE ACTIVATION; DNA; AUTOIMMUNITY; OLIGODEOXYNUCLEOTIDES; INHIBITION; MOTIFS; MODEL AB Objective. To examine whether systemic administration of oligonucleotides (ODNs), known to inhibit the production of proinflammatory cytokines, alters host susceptibility to collagen-induced arthritis (CIA), a murine model of rheumatoid arthritis (RA). Methods. CIA was induced by injecting DBA/1 mice with type II collagen (CII) in Freund's complete adjuvant, followed 3 weeks later by CH in Freund's incomplete adjuvant. The effect of suppressive ODNs on the incidence and severity of disease was monitored, as were immune correlates of CIA. Results. Suppressive ODNs administered during the inductive phase of CIA significantly reduced the incidence and severity of arthritis. Treatment with suppressive ODNs significantly decreased serum titers of pathogenic IgG anti-CII autoantibodies and interferon-gamma production by collagen-reactive T cells. Conclusion. Suppressive ODNs may be of therapeutic value in the treatment of RA, and potentially other autoimmune diseases. C1 US FDA, CBER, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, CBER, Bldg 29A,Room 3D10, Bethesda, MD 20892 USA. EM klinman@cber.fda.gov RI Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 14 TC 50 Z9 60 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 2004 VL 50 IS 5 BP 1686 EP 1689 DI 10.1002/art.20263 PG 4 WC Rheumatology SC Rheumatology GA 819UI UT WOS:000221340900038 PM 15146440 ER PT J AU Hendry, WJ Branham, WS Sheehan, DM AF Hendry, WJ Branham, WS Sheehan, DM TI Diethylstilbestrol versus estradiol as neonatal disruptors of the hamster (Mesocricetus auratus) cervix SO BIOLOGY OF REPRODUCTION LA English DT Article DE cervix; developmental; biology; estradiol; female reproductive tract; toxicology ID RECEPTOR NULL MICE; ESTROGEN-RECEPTOR; GENITAL-TRACT; REPRODUCTIVE-TRACT; ALPHA-FETOPROTEIN; VAGINAL ADENOSIS; SERUM-ALBUMIN; GUINEA-PIG; EXPOSURE; BINDING AB The synthetic estrogen diethylstilbestrol (DES) is an established, estrogenic endocrine disruptor (ED). The Syrian golden hamster (Mesocricetus auratus) offers some unique advantages as an experimental system to investigate the perinatal ED action of DES and other estrogenic EDs. Previous analyses regarding the consequences of neonatal administration (100 mug) of DES versus estradiol-17beta (E-2) showed that DES had a more potent disruptive effect on morphogenesis and gene expression in the uterus, oviduct, and ovary as well as in the testis and male accessory organs. The objectives of the present study were to describe the histopathological consequences of the two neonatal treatment regimens in the hamster cervix and to compare them with our previous observations in the hamster uterus. As previously found in the hamster uterus, DES was more potent than E-2 as a neonatal disruptor of the hamster cervix in prepubertal animals and in ovarian-intact adult animals. However, the cervix-versus-uterus scenario diverged in animals that were ovari-ectomized prepubertally and then chronically stimulated with natural estrogen (E-2). We confirmed previous observations that neonatal exposure to DES, but not to E-2 permanently alters estrogen responsiveness in the adult hamster uterus, but neither neonatal treatment regimen affected estrogen responsiveness in the adult hamster cervix. These results suggest that an unidentified ovarian factor influences the extent of neonatal DES-induced disruption of the cervix, but not of the uterus, in hamsters. C1 Wichita State Univ, Dept Biol Sci, Wichita, KS 67260 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Daniel M Sheehan & Associates, Little Rock, AR 72202 USA. RP Hendry, WJ (reprint author), Wichita State Univ, Dept Biol Sci, 1845 Fairmount, Wichita, KS 67260 USA. EM william.hendry@wichita.edu FU NCI NIH HHS [CA60250]; NCRR NIH HHS [P20 RR16475] NR 44 TC 7 Z9 7 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD MAY PY 2004 VL 70 IS 5 BP 1306 EP 1316 DI 10.1095/biolreprod.103.024992 PG 11 WC Reproductive Biology SC Reproductive Biology GA 815ME UT WOS:000221045600012 PM 14711791 ER PT J AU Chera, H Schaecher, KE Rocchini, A Imam, SZ Sribnick, EA Ray, SK Ali, SF Banik, NL AF Chera, H Schaecher, KE Rocchini, A Imam, SZ Sribnick, EA Ray, SK Ali, SF Banik, NL TI Immunofluorescent labeling of increased calpain expression and neuronal death in the spinal cord of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice SO BRAIN RESEARCH LA English DT Article DE calpain; double immunofluorescent labeling; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neuronal death; Parkinson's disease; spinal cord ID PARKINSONS-DISEASE; DOPAMINERGIC-NEURONS; SUBSTANTIA-NIGRA; CELL-DEATH; APOPTOTIC DEATH; UP-REGULATION; HUMAN BRAIN; DEGENERATION; VULNERABILITY; DEMYELINATION AB Parkinson's disease (PD) is a movement disorder characterized by rigidity, tremor, and bradykinesia, originating from degeneration of dopaminergic neurons in the substantia nigra (SN), retrorubral area, and locus ceoruleus (LC). Calpain has been implicated in the pathophysiology of neurodegenerative diseases. Since the spinal cord (SC) and brain are integrally connected and calpain is involved in cell death and mitochondrial dysfunction, we hypothesized that SC neurons are also affected in PD. In order to examine this hypothesis, we examined both brain and SC from mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). To identify cells expressing calpain, double immunofluorescent labeling was performed with antibodies specific for calpain and a cell type (OX-42, GFAP, or NeuN). Combined terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and double immunofluorescent labeling were used to identify death of specific cells in the central nervous system (CNS). There was an increase in calpain expression in microglia, astrocytes, and neurons in the SC of MPTP-treated mice at 1 and 7 days, as compared to controls. TUNEL-positive neurons in the SC and SN showed apoptotic characteristics. These results demonstrated that neuronal death occurred not only in SN but also in the SC of MPTP-treated mice and has provided evidence for a possible calpain-mediated SC neuronal death in MPTP-induced parkinsonism in mice. (C) 2004 Elsevier B.V. All rights reserved. C1 Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Uniformed Serv Univ Hlth Sci, Walter Reed Mem Inst, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Banik, NL (reprint author), Med Univ S Carolina, Dept Neurol, 96 Jonathan Lucas St,POB 250606, Charleston, SC 29425 USA. EM baniknl@musc.edu NR 28 TC 16 Z9 16 U1 1 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 MAY 1 PY 2004 VL 1006 IS 2 BP 150 EP 156 DI 10.1016/j.brainres.2004.01.065 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 812EK UT WOS:000220822600002 ER PT J AU Massirer, KB Hirata, MH Silva, AEB Ferraz, MLG Nguyen, NY Hirata, RDC AF Massirer, KB Hirata, MH Silva, AEB Ferraz, MLG Nguyen, NY Hirata, RDC TI Interferon-alpha receptor 1 mRNA expression in peripheral blood mononuclear cells is associated with response to interferon-alpha therapy of patients with chronic hepatitis C SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article DE IFNAR1-mRNA expression; interferon-alpha therapy; chronic hepatitis C; interferon-alpha receptor; peripheral blood mononuclear cells; reverse transcription-polymerase chain reaction ID CHRONIC LIVER-DISEASES; VIRUS AB Interferon (IFN)-alpha receptor mRNA expression in liver of patients with chronic hepatitis C has been shown to be a response to IFN-alpha therapy. The objective of the present study was to determine whether the expression of mRNA for subunit 1 of the IFN-alpha receptor (IFNAR1) in peripheral blood mononuclear cells (PBMC) is associated with the response to IFN-alpha in patients with chronic hepatitis C. Thirty patients with positive anti-HCV and HCV-RNA, and abnormal levels of alanine aminotransferase in serum were selected and treated with IFN-alpha2b for one year. Those with HBV or HIV infection, or using alcohol. were not included. Thirteen discontinued the treatment and were not evaluated. The IFN-alpha response was monitored on the basis of alanine aminotransferase level and positivity for HCV-RNA in serum. IFNAR1-mRNA expression in PBMC was measured by reverse transcription-polymerase chain reaction before and during the first three months of therapy. The results are reported as IFNAR1-mRNA/beta-actin-mRNA ratio (mean +/- SD). Before treatment, responder patients had significantly higher IFNAR1-mRNA expression in PBMC (0.67 +/- 0.15; N = 5; P < 0.05) compared to non-responders (0.35 +/- 0.17; N = 12) and controls (0.30 +/- 0.16; N = 9). Moreover, IFNAR1-mRNA levels were significantly reduced after 3 months of treatment in responders, whereas there were no differences in IFNAR1 expression in nonresponders during IFN-alpha therapy. Basal IFNAR1-mRNA expression was not correlated with the serum level of alanine and aspartate aminotransferases or the presence of cirrhosis. The present results suggest that IFNAR1-mRNA expression in PBMC is associated with IFN-alpha, response to hepatitis C and may be useful for monitoring therapy in patients with chronic hepatitis C. C1 Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, Sao Paulo, Brazil. Univ Fed Sao Paulo, Dept Gastroenterol, Sao Paulo, Brazil. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Hirata, MH (reprint author), Av Prof Lineu Prestes 580, BR-05508900 Sao Paulo, Brazil. EM mdchirta@usp.br RI Hirata, Rosario/A-7284-2011; Hirata, Mario/C-9718-2013 NR 20 TC 13 Z9 18 U1 0 U2 0 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PD MAY PY 2004 VL 37 IS 5 BP 643 EP 647 DI 10.1590/S0100-879X2004000500003 PG 5 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA 820EK UT WOS:000221369800003 PM 15107924 ER PT J AU Kioi, M Kawakami, K Puri, RK AF Kioi, M Kawakami, K Puri, RK TI Mechanism of action of interleukin-13 antagonist (IL-13E13K) in cells expressing various types of IL-4R SO CELLULAR IMMUNOLOGY LA English DT Article DE interleukin-4; interleukin-13; antagonist; receptor; signal transduction ID COMMON GAMMA-CHAIN; RECEPTOR-ALPHA CHAIN; SIGNAL-TRANSDUCTION; FUNCTIONAL COMPONENT; BINDING SUBUNIT; CARCINOMA-CELLS; HUMAN BREAST; T-CELLS; B-CELLS; CLONING AB As interleukin (IL)-13 and IL-4 play a major role in various diseases including asthma, allergy, and malignancies, it is desirable to generate a molecule that blocks the effects of both cytokines. We previously generated a human IL-13 mutant (IL-13E13K), which is a powerful antagonist of IL-13, blocking the biological activities of IL-13. We now show that IL-13E13K also competitively inhibits signaling and biological activities of IL-4 through type 11 and partially through type III IL-4 receptor (R) system. IL-13E13K completely blocked the IL-4-induced phosphorylation of STAT6 and IL-4-dependent protein synthesis in cells expressing type 11 and partially type Ill IL-4R but not type I IL-4R. Consistent with the inhibition of biological activities, IL-13E13K inhibited IL-4 binding to type 11 IL-4R-expressing cells but not to type I IL-4R-expressing cells. The inhibition efficiency of IL-4 binding by IL-13E13K was relatively lower compared to wtIL-13 even though IL-13E13K bound to IL-13Ralpha1 positive cells with a similar affinity to IL-4Ralpha. These results indicate that Glu 13 in IL- 13 associates with IL-4Ralpha, and mutation to lysine decreases its binding ability to IL-4Ralpha chain. IL-13E13K binds to IL-13Ralpha1, which is shared by both IL-13R and IL-4R systems. Consequently, IL-13E13K inhibits IL-4 binding to these cells and prevents heterodimer formation between IL-13Ralpha1 and IL-4Ra chains. This interference by IL-13E13K blocks the biological activities of not only IL-13 but also partially of IL-4. Thus, IL-13E13K may be a useful agent for the treatment of diseases such as asthma, allergic rhinitis, and cancer, which are dependent on signaling through both IL-4 and IL-13 receptors. Published by Elsevier Inc. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM puri@cber.fda.gov OI Kioi, Mitomu/0000-0002-7981-3340 NR 38 TC 17 Z9 17 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD MAY PY 2004 VL 229 IS 1 BP 41 EP 51 DI 10.1016/j.cellimm.2004.06.005 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 851SZ UT WOS:000223707000005 PM 15331327 ER PT J AU Xia, QS Chou, MW Lin, G Fu, PP AF Xia, QS Chou, MW Lin, G Fu, PP TI Metabolic formation of DHP-derived DNA adducts from a representative otonecine type pyrrolizidine alkaloid clivorine and the extract of Ligularia hodgsonnii hook SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; CARCINOGENIC ACTIVITY; MICROSOMAL METABOLITES; PETASITES-JAPONICUS; HEPATIC-TUMORS; ISLET-CELL; IN-VITRO; RATS; LASIOCARPINE; RIDDELLIINE AB Plants that contain pyrrolizidine alkaloids (PAs) are widely distributed, and PAs have been shown to be genotoxic and tumorigenic in experimental animals. Our recent mechanistic studies indicated that riddelhine, a tumorigenic retronecine type PA, induced tumors via a genotoxic mechanism mediated by the formation of a set of eight 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts. However, it is not known if this mechanism is general to PAs of other types. In this study, we report that the metabolism of clivorine, a tumorigenic otonecine type PA, by F344 rat liver microsomes results in DHP formation. When incubations were conducted with clivorine in the presence of calf thymus DNA, eight DHP-derived DNA adducts were formed. The Ligularia hodgsonnii Hook plant, an antitussive traditional Chinese medicine, was found to contain otonecine type PAs with clivorine being predominant. DHP and DHP-derived DNA adducts were also obtained when microsomal incubations were conducted with extracts of L. hodgsonnii Hook. This is the first report that DHP-derived DNA adducts are formed from the metabolic activation of otonecine type PA and that these DHP-derived DNA adducts are potential biomarkers of PA exposure and PA-induced tumorigenicity. These results also provide evidence that the principal metabolic activation pathway of clivorine leading to liver genotoxicity and tumorigenicity is (i) formation of the corresponding dehydropyrrolizidine (pyrrolic) derivative through oxidative N-demethylation of the necine base followed by ring closure and dehydration and (ii) binding of the pyrrolic metabolite to DNA leading to the DNA adduct formation and tumor initiation. C1 Chinese Univ Hong Kong, Dept Pharmacol, Shatin, Hong Kong, Peoples R China. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Fu, PP (reprint author), Chinese Univ Hong Kong, Dept Pharmacol, Shatin, Hong Kong, Peoples R China. EM linge@cuhk.edu.hk; pfu@nctr.fda.gov NR 50 TC 40 Z9 42 U1 1 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 MAY PY 2004 VL 17 IS 5 BP 702 EP 708 DI 10.1021/tx030030q PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 822HF UT WOS:000221529100015 PM 15144228 ER PT J AU Spellberg, B Powers, JH Brass, EP Miller, LG Edwards, JE AF Spellberg, B Powers, JH Brass, EP Miller, LG Edwards, JE TI Trends in antimicrobial drug development: Implications for the future SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 43rd Interscience Convention on Antimicrobial Agents and Chemotherapy CY MAR, 2003 CL San Diego, CA ID RESISTANT PSEUDOMONAS-AERUGINOSA; UNITED-STATES; STREPTOCOCCUS-PNEUMONIAE; STAPHYLOCOCCUS-AUREUS; TUBERCULOSIS; INFECTIONS; PREVALENCE; OUTBREAK AB The need for new antimicrobial agents is greater than ever because of the emergence of multidrug resistance in common pathogens, the rapid emergence of new infections, and the potential for use of multidrug-resistant agents in bioweapons. Paradoxically, some pharmaceutical companies have indicated that they are curtailing anti-infective research programs. We evaluated the United States Food and Drug Administration (FDA) databases of approved drugs and the research and development programs of the world's largest pharmaceutical and biotechnology companies to document trends in the development of new antimicrobial agents. FDA approval of new antibacterial agents decreased by 56% over the past 20 years ( 1998 - 2002 vs. 1983 - 1987). Projecting future development, new antibacterial agents constitute 6 of 506 drugs disclosed in the developmental programs of the largest pharmaceutical and biotechnology companies. Despite the critical need for new antimicrobial agents, the development of these agents is declining. Solutions encouraging and facilitating the development of new antimicrobial agents are needed. C1 Univ Calif Los Angeles, Los Angeles Cty Harbor Med Ctr, Res & Educ Inst, Div Infect Dis, Torrance, CA 90502 USA. Univ Calif Los Angeles, Los Angeles Cty Harbor Med Ctr, Dept Med, Torrance, CA 90509 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. US FDA, Off Drug Evaluat 4, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Edwards, JE (reprint author), Univ Calif Los Angeles, Los Angeles Cty Harbor Med Ctr, Res & Educ Inst, Div Infect Dis, 1124 W Carson St, Torrance, CA 90502 USA. EM edwards@humc.edu RI a, a/M-9467-2013 FU NIAID NIH HHS [P01 AI37194, R01 AI19990] NR 77 TC 409 Z9 433 U1 5 U2 60 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 MAY 1 PY 2004 VL 38 IS 9 BP 1279 EP 1286 DI 10.1086/420937 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 813SG UT WOS:000220926200014 PM 15127341 ER PT J AU Schleinitz, TA Telford, WG Perfetto, SP Caporaso, NE Stetler-Stevenson, M Abbasi, F Zenger, VE Marti, GE AF Schleinitz, TA Telford, WG Perfetto, SP Caporaso, NE Stetler-Stevenson, M Abbasi, F Zenger, VE Marti, GE TI Multicolor flow cytometry (MCFCM) analysis of precursor states in chronic lymphocytic leukemia (CLL) SO CYTOMETRY PART A LA English DT Meeting Abstract CT 22nd Congress of the International-Society-for-Analytical-Cytology CY MAY 22-27, 2004 CL Montpellier, FRANCE SP Ins Soc Analyt Cytol C1 Inst J Paoli I Calmettes, CBER FDA, F-13009 Marseille, France. NCI, Flow Core Facil, Bethesda, MD 20892 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, CBER, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-4763 J9 CYTOM PART A JI Cytom. Part A PD MAY PY 2004 VL 59A IS 1 BP 39 EP 39 PG 1 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 819MV UT WOS:000221319900045 ER PT J AU Holleran, JL Fourcade, J Egorin, MJ Eiseman, JL Parise, RA Musser, SM White, KD Covey, JM Forrest, GL Pan, SS AF Holleran, JL Fourcade, J Egorin, MJ Eiseman, JL Parise, RA Musser, SM White, KD Covey, JM Forrest, GL Pan, SS TI In vitro metabolism of the phosphatidylinositol 3-kinase inhibitor, wortmannin, by carbonyl reductase SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID PHOSPHOINOSITIDE 3-KINASE; ANTICANCER AGENTS; KINASE INHIBITORS; LIQUID-CHROMATOGRAPHY; SIGNAL-TRANSDUCTION; BINDING PROTEIN; CANCER; TARGETS; LIPIDS AB The phosphatidylinositol 3-kinase inhibitor, wortmannin, is extensively used in molecular signaling studies and has been proposed as a potential antineoplastic agent. The failure to detect wortmannin in mouse plasma after i.v. administration prompted in vitro studies of wortmannin metabolism. Wortmannin was incubated with mouse tissue homogenates, homogenate fractions, or purified, recombinant human carbonyl reductase in the presence of specified cofactors and inhibitors. Reaction products were characterized and quantified with liquid chromatography (LC)/mass spectrometry. Reaction rates were characterized using Michaelis-Menten kinetics. Wortmannin was metabolized to a material 2 atomic mass units greater than wortmannin. Liver homogenate had the highest metabolic activity. Some metabolism occurred in kidney and lung homogenates. Very little metabolism occurred in brain or red blood cell homogenates. Liver S9 fraction and cytosol metabolized wortmannin in the presence of NADPH and, to a much lesser extent, in the presence of NADH. Microsomal metabolism of wortmannin was minimal. Purified, recombinant human carbonyl reductase metabolized wortmannin. Quercetin, a carbonyl reductase inhibitor, greatly decreased wortmannin metabolism by S9, cytosol, and carbonyl reductase. The K-M for wortmannin metabolism by purified, recombinant human carbonyl reductase was 119+/-9 muM, and the V-max was 58+/-9 nmol/min/mg of protein. LC-tandem mass spectrometry spectra indicated that carbonyl reductase metabolized wortmannin to 17-OH-wortmannin. Wortmannin reduction by carbonyl reductase may partly explain why wortmannin is not detected in plasma after being administered to mice. Metabolism of wortmannin to 17-OH-wortmannin has mechanistic, and possibly toxicologic, implications because 17-OH-wortmannin is 10-fold more potent an inhibitor of phosphatidylinositol 3-kinase than is wortmannin. C1 Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. US FDA, Instrumentat & Biophys Branch, Ctr Food Safety & Appl Nutr, College Pk, MD USA. NCI, Toxicol & Pharmacol Branch, DTP, Bethesda, MD 20892 USA. City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA. RP Egorin, MJ (reprint author), Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Room G27E,Hillman Res Pavil,5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM egorinmj@msx.upmc.edu FU NCI NIH HHS [2P30 CA 47904, N01 CM 07106] NR 38 TC 11 Z9 11 U1 2 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD MAY 1 PY 2004 VL 32 IS 5 BP 490 EP 496 DI 10.1124/dmd.32.5.490 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 814BZ UT WOS:000220951500004 PM 15100170 ER PT J AU Komoroski, BJ Zhang, SM Cai, HB Hutzler, JM Frye, R Tracy, TS Strom, SC Lehmann, T Ang, CYW Cui, YY Venkataramanan, R AF Komoroski, BJ Zhang, SM Cai, HB Hutzler, JM Frye, R Tracy, TS Strom, SC Lehmann, T Ang, CYW Cui, YY Venkataramanan, R TI Induction and inhibition of cytochromes P450 by the St. John's wort constituent hyperforin in human hepatocyte cultures SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID GENE INDUCTION; DEPRESSION; METABOLISM; HYPERICUM; ENZYMES; LIVER AB St. John's wort extract (SJW) (Hypericum perforatum L.) is among the most commonly used herbal medications in the United States. The predominance of clinical reports indicates that SJW increases the activity of cytochrome P450 3A4 (CYP3A4) enzyme and reduces plasma concentrations of certain drugs. Although the inductive effect of SJW on CYP3A4 is clear, other reports indicate that SJW constituents may have, to a small degree, some enzyme inhibitory effects. Therefore, we sought to study the induction and inhibition effects of the constituents of SJW on CYP3A4 in the human hepatocyte model. Moreover, most research has focused on the induction of CYP3A4 by SJW with little attention paid to other prominent drug-metabolizing enzymes such as CYP1A2, CYP2C9, and CYP2D6. To examine the effects of SJW on CYP1A2, CYP2C9, CYP2D6, as well as CYP3A4, hepatocytes were exposed to hyperforin and hypericin, the primary constituents of SJW extract. Hepatocytes treated with hypericin or hyperforin were exposed to probe substrates to determine enzyme activity and protein and RNA harvested. Hyperforin treatment resulted in significant increases in mRNA, protein, and activity of CYP3A4 and CYP2C9, but had no effect on CYP1A2 or CYP2D6. Acute administration of hyperforin at 5 and 10 muM 1 h before and along with probe substrate inhibited CYP3A4 activity. Hypericin had no effect on any of the enzymes tested. These results demonstrate that with chronic exposure, the inductive effect of SJW on drug-metabolizing enzymes predominates, and human hepatocyte cultures are a versatile in vitro tool for screening the effect of herbal products on cytochrome P450 enzymes. C1 Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15261 USA. W Virginia Univ, Sch Pharm, Morgantown, WV 26506 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Venkataramanan, R (reprint author), Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, 718 Salk Hall, Pittsburgh, PA 15261 USA. EM rv@pitt.edu RI Strom, Stephen/A-6501-2008; OI Frye, Reginald/0000-0002-1841-1401 FU NIDDK NIH HHS [N01 DK 92310] NR 25 TC 109 Z9 112 U1 0 U2 8 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD MAY 1 PY 2004 VL 32 IS 5 BP 512 EP 518 DI 10.1124/dmd.32.5.512 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 814BZ UT WOS:000220951500007 PM 15100173 ER PT J AU Zhou, M Lucas, DA Chan, KC Issaq, HJ Petricoin, EF Liotta, LA Veenstra, TD Conrads, TR AF Zhou, M Lucas, DA Chan, KC Issaq, HJ Petricoin, EF Liotta, LA Veenstra, TD Conrads, TR TI An investigation into the human serum "interactome" SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT 14th Annual Frederick Conference on Capillary Electrophoresis/Proteomics CY NOV 03-04, 2003 CL NCI, Frederick, MD HO NCI DE albumin; biomarker; human serum; proteome; surface-enhanced laser desorption/ionization ID PROSTATE-SPECIFIC ANTIGEN; HUMAN PLASMA PROTEOME; PANCREATIC-CANCER; OVARIAN-CANCER; DOWN-SYNDROME; EXPRESSION; IDENTIFICATION; PATTERNS; PROTEINS; BINDING AB The protein content of human serum is composed of a millieu of proteins from almost every type of cell and tissue within the body. The serum proteome has been shown to contain information that directly reflects pathophysiological states and represents an invaluable source of diagnostic information for a variety of different diseases. Unfortunately, the dynamic range of protein abundance, ranging from much greater than mg/mL level to much less than pg/mL level, renders complete characterization of this proteome nearly impossible with current analytical methods. To study low-abundance proteins, which have potential value for clinical diagnosis, the high-abundant species, such as immunoglobulins and albumin, are generally eliminated as the first step in many analytical protocols. This step, however, is hypothesized to concomitantly remove proteins/peptides associated with the high-abundant proteins targeted for depletion. In this study, immunoprecipitation was combined with microcapillary reversed-phase liquid chromatography (muRPLC) coupled on-line with tandem mass spectrometry (MS/MS) to investigate the low-molecular-weight proteins/peptides that associate with the most abundant species in serum. By this targeted isolation of select highly abundant serum proteins, the associated proteins/peptides can be enriched and effectively identified by muRPLC-MS/MS. Among the 210 proteins identified, 73% and 67% were not found in previous studies of the low-molecular-weight or whole-serum proteome, respectively. C1 SAIC Frederick Inc, Natl Canc Inst, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. US FDA, Ctr Biol Evaluat & Res, Natl Canc Inst, Clin Proteom Program, Bethesda, MD 20014 USA. NCI, Ctr Canc Res, Pathol Lab, Bethesda, MD 20892 USA. RP Conrads, TR (reprint author), SAIC Frederick Inc, Natl Canc Inst, Lab Proteom & Analyt Technol, POB B, Frederick, MD 21702 USA. EM Conrads@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 48 TC 222 Z9 229 U1 2 U2 17 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD MAY PY 2004 VL 25 IS 9 SI SI BP 1289 EP 1298 DI 10.1002/elps.200405866 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 825DB UT WOS:000221735100016 PM 15174051 ER PT J AU Rabatsky-Ehr, T Whichard, J Rossiter, S Holland, B Stamey, K Headrick, ML Barrett, TJ Angulo, FJ AF Rabatsky-Ehr, T Whichard, J Rossiter, S Holland, B Stamey, K Headrick, ML Barrett, TJ Angulo, FJ CA NARMS Working Grp TI Multidrug-resistant strains of Salmonella enterica typhimurium, United States, 1997-1998 SO EMERGING INFECTIOUS DISEASES LA English DT Article ID SEROTYPE TYPHIMURIUM; DT104; INFECTIONS; EMERGENCE; SPECTRUM; HUMANS; GENES AB To evaluate multidrug-resistant strains of Salmonella enterica serotype Typhimurium, including definitive type 104 (DT104) in the United States, we reviewed data from the National Antimicrobial Resistance Monitoring System (NARMS). In 1997 to 1998, 703 (25%) of 2,767 serotyped Salmonella isolates received at NARMS were S. Typhimurium; antimicrobial susceptibility testing and phage typing were completed for 697. Fifty-eight percent (402) were resistant to greater than or equal to1 antimicrobial agent. Three multidrug-resistant (greater than or equal to5 drugs) strains accounted for (74%) 296 of all resistant isolates. Ceftriaxone resistance was present in 8 (3%), and nalidixic acid resistance in 4 (1%), of these multidrug-resistant strains. By phage typing, 259 (37%) of S. Typhimurium isolates were DT104, 209 (30%) were of undefined type and 103 (15%) were untypable. Fifty percent (202) of resistant (greater than or equal to1 drug) isolates were DT104. Multidrug-resistant S. Typhimurium isolates, particularly DT104, account for a substantial proportion of S. Typhimurium isolates; ceftriaxone resistance is exhibited by some of these strains. C1 Yale Univ, Sch Med, New Haven, CT USA. Ctr Dis Control & Prevent, Atlanta, GA USA. US FDA, Bethesda, MD 20014 USA. RP Rabatsky-Ehr, T (reprint author), Dept Publ Hlth Epidemiol & Emerging Infect, 401 Capital Ave,MS Epi 11,POB 340308, Hartford, CT USA. EM Therese.Rabatsky-Ehr@po.state.ct.us FU ODCDC CDC HHS [U50/CCU111188-07] NR 21 TC 25 Z9 28 U1 0 U2 1 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD MAY PY 2004 VL 10 IS 5 BP 795 EP 801 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 818GL UT WOS:000221233500005 PM 15200811 ER PT J AU Olsen, SJ Ying, M Davis, MF Deasy, M Holland, B Iampietro, L Baysinger, CM Sassano, F Polk, LD Gormley, B Hung, MJ Pilot, K Orsini, M Van Duyne, S Rankin, S Genese, C Bresnitz, EA Smucker, J Moll, M Sobel, J AF Olsen, SJ Ying, M Davis, MF Deasy, M Holland, B Iampietro, L Baysinger, CM Sassano, F Polk, LD Gormley, B Hung, MJ Pilot, K Orsini, M Van Duyne, S Rankin, S Genese, C Bresnitz, EA Smucker, J Moll, M Sobel, J TI Multidrug-resistant Salmonella Typhimurium infection from milk contaminated after pasteurization SO EMERGING INFECTIOUS DISEASES LA English DT Article ID OUTBREAK AB An outbreak of multidrug-resistant Salmonella enterica serotype Typhimurium infections occurred in Pennsylvania and New Jersey. A case-control study implicated pasteurized milk from a dairy, and an inspection indicated the potential for contamination after pasteurization. Dairy cattle are the likely reservoir, and milk may be an important vehicle of Salmonella transmission to humans. C1 Ctr Dis Control & Prevent, Atlanta, GA USA. Penn Dept Hlth, Harrisburg, PA 17108 USA. Montgomery Cty Dept Hlth, Norristown, PA USA. Bucks Cty Dept Hlth, Doylestown, PA USA. Gloucester Cty Hlth Dept, Turnersville, NJ USA. New Jersey State Dept Hlth & Senior Serv, Trenton, NJ USA. Univ Penn, Philadelphia, PA 19104 USA. US FDA, Washington, DC 20204 USA. RP Olsen, SJ (reprint author), Ctr Dis Control & Prod, Int Emerging Infect Program, Amer Embassy, APO, AP 96546 USA. EM sco2@cdc.gov OI Davis, Meghan/0000-0002-3475-4578 NR 15 TC 45 Z9 47 U1 0 U2 4 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD MAY PY 2004 VL 10 IS 5 BP 932 EP 935 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 818GL UT WOS:000221233500029 PM 15200835 ER PT J AU Kim, YH Pak, K Pothuluri, JV Cerniglia, CE AF Kim, YH Pak, K Pothuluri, JV Cerniglia, CE TI Mineralization of erythromycin A in aquaculture sediments SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE desorption; erythromycin A; erythromycin esterase; microcosm; mineralization ID AROMATIC-COMPOUNDS; BIODEGRADATION; DEGRADATION; DECOMPOSITION; ADSORPTION; KINETICS; CLAY AB Mineralization of erythromycin A was studied using two differently C-14-labeled erythromycins A, which were added to aqua-culture sediment samples obtained from the two salmon hatchery sites in Washington state. The added erythromycin A did not significantly alter the numbers of the total viable colonies and erythromycin-resistant bacteria. Erythromycin-resistant Pseudomonas species contained a constitutive erythromycin esterase activity contributing to the inactivation of biologically active erythromycin A in aquatic and sediment environments. The initial rate of mineralization of erythromycin A appeared to be governed by the rate of release of soil-sorbed erythromycin A. After a prolonged lag time, the S-curves of erythromycin A mineralization were observed probably because of the increase in the Population density metabolizing it. This study suggests that erythromycin A is partially or completely mineralized by the sediment microbial populations. (C) 2004 Federation of European Microbiological Societies. Published by Elsevier B.V.. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM ccerniglia@uctr.fda.gov NR 26 TC 19 Z9 20 U1 3 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD MAY 1 PY 2004 VL 234 IS 1 BP 169 EP 175 DI 10.1016/j.femsle.2004.03.027 PG 7 WC Microbiology SC Microbiology GA 818AP UT WOS:000221218300024 PM 15109736 ER PT J AU Il Kim, P Chung, KC AF Il Kim, P Chung, KC TI Production of an antifungal protein for control of Colletotrichum lagenarium by Bacillus amyloliquefaciens MET0908 SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE Colletotrichum lagenarium; watermelon anthracnose; Bacillus amyloliquefaciens; antifungal agent; beta-glucanase ID BIOLOGICAL-CONTROL; TRICHODERMA-HARZIANUM; FUSARIUM-SOLANI; BIOCONTROL; MECHANISM; AGENT; MOLD AB A plant pathogenic fungus, Colletotrichum lagenarium, causing watermelon anthracnose, was isolated from naturally infected leaves, stems, and fruits of watermelon. A bacterial strain, MET0908, showing a potent antifungal activity against C lagenarium, was isolated from soil. An antifungal protein was purified by 30% ammonium sulfate saturation and concentrated using Centricon 10, DEAE-Sepharose(TM) Fast Flow column and Sephacryl S-100 gel filtration chromatography. The molecular weight of the purified protein was estimated as 40 kDa by SIDS-PAGE. The purified protein was stable at 80degreesC for 20 min and exhibited a broad spectrum of antifungal activity against various plant pathogenic fungi. Confocal microscopy image analysis and scanning electron microscopy showed that the protein acted on the cell wall of C. lagenarium. The purified antifungal protein exhibited beta-1,3-glucanase activity. The N-terminal amino acid sequence of the purified protein was determined as Ser-Lys-Ile-x-Ile-Asn-Ile-Asn-Ile-x-Gln-Ala-Pro-Ala-Pro-x-Ala. A search of the sequence with NCBI BLAST showed no significant homology with any known proteins, suggesting that the purified protein may be novel. (C) 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved. C1 Chonnam Natl Univ, Dept Genet Engn, Kwangju, South Korea. Chonnam Natl Univ, Biotechnol Res Inst, Kwangju, South Korea. Food & Drug Adm, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR USA. RP Chonnam Natl Univ, Dept Genet Engn, Kwangju, South Korea. EM pkim@nctr.fda.gov; chungkc@chon-nam.ac.kr NR 30 TC 2 Z9 3 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0378-1097 EI 1574-6968 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD MAY 1 PY 2004 VL 234 IS 1 BP 177 EP 183 DI 10.1016/j.femsle.2004.03.032 PG 7 WC Microbiology SC Microbiology GA 818AP UT WOS:000221218300025 ER PT J AU Cisneros, FJ AF Cisneros, FJ TI DNA methylation and male infertility SO FRONTIERS IN BIOSCIENCE LA English DT Review DE infertility; epigenetics; DNA methylation; gene expression; spermatogenesis; male reproductive organ development; review ID FEMALE SEX REVERSAL; X-CHROMOSOME INACTIVATION; TESTIS-DETERMINING REGION; EMBRYONIC STEM-CELLS; DE-NOVO METHYLATION; ACID-DEFINED DIETS; MALE GERM-CELLS; Y-CHROMOSOME; MAMMALIAN DEVELOPMENT; GONADAL DEVELOPMENT AB Male infertility is one of the biggest concerns of today's health care community. In the US and other developed countries, approximately 70% of infertility among couples is attributed to male reproductive failure. Alterations in reproductive organ development and sperm production have been listed as the major causes of this phenomenon. Sex determination and differentiation, X chromosome inactivation, gene imprinting and normal germ cell development are important biological processes that, in turn, control mammalian reproduction. Specific patterns of gene expression and repression are important in such processes. The strong correlation between DNA methylation, a major epigenetic modification of the genome, and gene expression patterns is well documented. The effects of DNA methylation on the expression of genes affecting male reproductive organ development, spermatogenesis, and male sexual behavior have been reported, suggesting that alterations in DNA methylation could induce abnormal male sexual development and reproductive performance. Inheritance of epigenetic processes and changes in DNA methylation patterns induced by certain diets have been demonstrated in recent years. However, the effects of DNA methylation on male fertility have not been well studied. Since inherited altered DNA methylation patterns could be a cause of increased susceptibility to xenobiotics or abnormal phenotype in future generations, multigenerational studies oriented to determine the effects of xenobiotics affecting DNA methylation in male fertility are recommended. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Cisneros, FJ (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM fcisneros@nctr.fda.gov NR 184 TC 23 Z9 26 U1 0 U2 6 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY PY 2004 VL 9 BP 1189 EP 1200 DI 10.2741/1332 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 779ZA UT WOS:000189333700012 PM 14977536 ER PT J AU Pitts, P AF Pitts, P TI FDA decision making SO HEALTH AFFAIRS LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Pitts, P (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD MAY-JUN PY 2004 VL 23 IS 3 BP 287 EP 287 DI 10.1377/hlthaff.23.3.287 PG 1 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 818HX UT WOS:000221237300038 PM 15160828 ER PT J AU Rochon, G Caron, A Toussaint-Hacquard, M Alayash, AI Gentils, M Labrude, P Stoltz, JF Menu, P AF Rochon, G Caron, A Toussaint-Hacquard, M Alayash, AI Gentils, M Labrude, P Stoltz, JF Menu, P TI Hemodilution with stoma-free hemoglobin at physiologically maintained viscosity delays the onset of vasoconstriction SO HYPERTENSION LA English DT Article DE hemoglobin; vascular resistance; viscosity ID NITRIC-OXIDE; BLOOD-VISCOSITY; RENAL HEMODYNAMICS; RAT; SUBSTITUTES; VOLUME; OXYGENATION; CONSUMPTION; HEMORRHAGE; RABBITS AB Solutions of modified cell-free hemoglobin, prepared from outdated red blood cells, have been developed during the past decade to circumvent the increasing need for allogeneic blood. Despite improvements in the safety and efficacy of these solutions, undesirable effects such as an increase in vascular tone leading to hypertension have not been fully resolved, which might hinder their clinical usefulness. To discriminate between the pharmacological and rheological effects of cell-free hemoglobin, we compared the effects of blood/cell-free hemoglobin mixtures of high versus low viscosity on hemodynamics and vascular hindrance, an index of vascular tone, which was normalized for blood viscosity. Anesthetized rats were subjected to 50% exchange transfusion with ( 1) high-viscosity solutions: whole blood (n = 5) or red blood cells mixed with cell-free hemoglobin (Hb-Hv group, n = 5); ( 2) low-viscosity solutions: cell-free hemoglobin (Hb-Lv group, n = 5) or human albumin ( n = 5). Two hours after hemodilution, vascular hindrance remained unchanged in animals transfused with whole blood and albumin. Hb-Lv induced an immediate and sustained increase in vascular hindrance (208%). Conversely, in Hb-Hv animals, the vascular hindrance increase was delayed and smaller (27% to 147%), whereas peripheral resistance increased gradually (94% after 2 hours). Our results demonstrate the beneficial effects of cell-free hemoglobin in the presence of the animals' own red blood cells in maintaining physiological viscosity and limiting vasoconstriction because of the pharmacological properties of cell-free hemoglobin. C1 Univ Henri Poincare, Sch Pharm, Dept Hematol & Physiol, Nancy, France. US FDA, Lab Biochem & Vasc Biol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Fac Med, Lab Mech Engn Cells & Tissue, Nancy, France. RP Menu, P (reprint author), Fac Pharm Nancy, Lab Hematol & Physiol, 5 Rue Albert Lebrun, F-54001 Nancy, France. EM menu@pharma.uhp-nancy.fr NR 28 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 2004 VL 43 IS 5 BP 1110 EP 1115 DI 10.1161/01.HYP.0000123075.48420.e8 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 816ME UT WOS:000221113200037 PM 15051666 ER PT J AU Pickering, AK Merkel, TJ AF Pickering, AK Merkel, TJ TI Macrophages release tumor necrosis factor alpha and interleukin-12 in response to intracellular Bacillus anthracis spores SO INFECTION AND IMMUNITY LA English DT Article ID EXPERIMENTAL INHALATION ANTHRAX; LETHAL TOXIN; ALVEOLAR MACROPHAGES; TNF-ALPHA; GERMINATION; PATHOGENESIS; PATHOLOGY; CELLS; MICE AB Herein we report that infection of a murine macrophage cell line with Bacillus anthracis results in the production of tumor necrosis factor alpha and interleukin-12 (IL-12). When infected with B. anthracis spores in combination with lipopolysaccharide, macrophages release increased amounts of IL-12. We found no evidence of inhibition of cytokine responses in macrophages infected with B. anthracis spores. C1 US FDA, CBE, DBPAP, Lab Resp & Special Pathogens, Bethesda, MD 20892 USA. RP Merkel, TJ (reprint author), US FDA, CBE, DBPAP, Lab Resp & Special Pathogens, Bldg 29, Room 418,29 Lincoln Dr, Bethesda, MD 20892 USA. EM merkel@cber.fda.gov NR 27 TC 34 Z9 35 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 MAY PY 2004 VL 72 IS 5 BP 3069 EP 3072 DI 10.1128/IAI.72.5.3069-3072.2004 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 816OV UT WOS:000221120100074 PM 15102824 ER PT J AU Gallagher, G Eskdale, J Jordan, W Peat, J Campbell, J Boniotto, M Lennon, GP Dickensheets, H Donnelly, RP AF Gallagher, G Eskdale, J Jordan, W Peat, J Campbell, J Boniotto, M Lennon, GP Dickensheets, H Donnelly, RP TI Human interleukin-19 and its receptor: a potential role in the induction of Th2 responses SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Review DE interleukin-19; Th-2 response; induction ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; EARLY-ONSET PERIODONTITIS; T-REGULATORY-CELLS; GENE-EXPRESSION; IL-10 LOCUS; IN-VIVO; TRANSCRIPTION FACTOR; INDUCIBLE FACTOR; DENDRITIC CELLS; IL-TIF AB Interleukin-19 (IL-19) is a newly discovered member of the IL-10 family of ligands whose function is presently undefined. We recently described its cloning and initial characterization and in so doing, noted that the induction of IL-19 by LPS in human monocytes was down-regulated by interferon-gamma (IFN-gamma) and up-regulated by IL-4. This preliminary observation led us to speculate that IL-19 may play a role in the Th1/Th2 system and we examined this hypothesis further. Our results suggested that IL-19 is able to influence the maturation of human T-cells. CD4+ T-cells resulting from SEB stimulation in the presence of IL-19 contained a higher proportion of IL-4 producing cells than those developing in the absence of IL-19. This observation was complimented by the observation that fewer IFN-gamma cells accrued in the presence of IL-19, thereby suggesting that IL-19 altered the balance of Th1/Th2 cells in favour of Th2. Furthermore, in whole PBMC cultures, IL-19 up-regulated IL-4 and down-regulated IFNgamma in a dose-dependent manner. These results are presented here in review format, in the context of an overall discussion of IL-19 and its receptor. (C) 2004 Published by Elsevier B.V. C1 Univ Med & Dent New Jersey, Dept Oral Biol, Newark, NJ 07103 USA. Univ Glasgow, Dept Med, Glasgow, Lanark, Scotland. US FDA, Div Therapeut Prot, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Glasgow, Dept Surg, Glasgow, Lanark, Scotland. RP Gallagher, G (reprint author), Univ Med & Dent New Jersey, Dept Oral Biol, Room C-636,MSB,185 S Orange Ave, Newark, NJ 07103 USA. EM gallaggr@umdnj.edu RI Boniotto, Michele/F-1857-2010 OI Boniotto, Michele/0000-0002-9548-2254 NR 64 TC 80 Z9 84 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 EI 1878-1705 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD MAY PY 2004 VL 4 IS 5 BP 615 EP 626 DI 10.1016/j.intimp.2004.01.005 PG 12 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 820FY UT WOS:000221374000005 PM 15120647 ER PT J AU Lard-Whiteford, SL Matecka, D O'Rear, JJ Yuen, IS Litterst, C Reichelderfer, P AF Lard-Whiteford, SL Matecka, D O'Rear, JJ Yuen, IS Litterst, C Reichelderfer, P CA The International Working Grp on M TI Recommendations for the nonclinical development of topical microbicides for prevention of HIV transmission: An update SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; topical microbicides; antimicrobial activities; toxicological and chemical testing ID IMMUNODEFICIENCY-VIRUS TYPE-1; SODIUM DODECYL-SULFATE; SPERMICIDE BENZALKONIUM CHLORIDE; GENITAL HERPES INFECTION; CELL-ASSOCIATED HIV-1; IN-VITRO; VAGINAL MICROBICIDES; CHLAMYDIA-TRACHOMATIS; LAURYL SULFATE; BACTERIAL VAGINOSIS AB The development of methods to prevent HIV infection is critical to curbing the rising epidemic. Topical microbicides represent a potential new strategy for reduction of HIV transmission. The purpose of this article is to update and expand upon the nonclinical recommendations of a previously published document on the development of microbicides prepared by the International Working Group on Microbicides. The nonclinical studies discussed here represent general concepts and regulatory considerations that are pertinent to the development of topical microbicides for prevention or reduction of HIV transmission. Essential early steps in product development include the determination of antiviral activity, cytotoxicity, mechanism of action, pathways to resistance, and cross-resistance to approved drugs. Other parameters to consider include activity against vaginal microflora and pathogens that cause sexually transmitted diseases. Before and during clinical trials, nonclinical data on toxicology and pharmacokinetics should be obtained. Finally, product quality issues, including microbicide formulation characteristics, interaction with other products, and stability, should be addressed. C1 US FDA, Ctr Drug Evaluat & Res, Div Antiviral Drug Prod, Rockville, MD 20857 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NIAID, NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Yuen, IS (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Antiviral Drug Prod, HFD-530,5600 Fisheries Lane, Rockville, MD 20857 USA. EM yueni@cder.fda.gov NR 80 TC 64 Z9 73 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAY 1 PY 2004 VL 36 IS 1 BP 541 EP 552 DI 10.1097/00126334-200405010-00001 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 817KX UT WOS:000221177500001 PM 15097296 ER PT J AU Howell, MD Tomazic, VJ Leakakos, T Truscott, W Meade, BJ AF Howell, MD Tomazic, VJ Leakakos, T Truscott, W Meade, BJ TI Immunomodulatory effect of endotoxin on the development of latex allergy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE latex; endotoxin; mouse model; IgE; airway hyperreactivity ID CYTOKINE GENE-EXPRESSION; HEALTH-CARE WORKERS; INTERFERON-GAMMA; BRONCHIAL HYPERRESPONSIVENESS; LIPOPOLYSACCHARIDE EXPOSURE; AIRWAY HYPERREACTIVITY; BACTERIAL-ENDOTOXIN; MOUSE LUNG; IFN-GAMMA; MICE AB Background: Although numerous studies have been conducted delineating the clinical manifestations of latex allergy and characterizing the protein allergens, little is known regarding the natural history of the disease. Objective: These studies were undertaken to investigate the immunomodulatory role of inhaled endotoxin on the development of latex-specific IgE-mediated responses to natural rubber latex (NRL) proteins by using a mouse model. Methods: Female BALB/c mice were exposed to 25 mug of NRL proteins with or without increasing concentrations of endotoxin (50-25,000 EU) through the respiratory tract. Serum antibody levels were evaluated biweekly during the study. After sensitization, mice were challenged with methacholine or NRL proteins, and airway hyperreactivity (AHR) was evaluated with whole-body plethysmography. After NRL challenge, lungs were excised for histopathology, and lung-associated lymph nodes were removed for cytokine mRNA evaluation. Results: When compared with mice exposed to latex alone, mice exposed to latex and endotoxin demonstrated up to 50% lower levels of latex-specific IgE and decreased latex-specific AHR and mucin production. Conversely, these same animals demonstrated increased levels of latex-specific serum IgG2a and IgA antibodies and an increase in IFN-gamma and IL-12 mRNA levels in the draining lymph node cells. Concurrent exposure to LPS with nonammoniated latex resulted in increased alveolitis and nonspecific AHR on respiratory challenge with methacholine. Conclusion: Coexposure with LPS and allergen decreased latex-specific IgE but augmented nonspecific AHR. These studies demonstrate that endotoxin associated with NRL gloves can modulate the development of allergic responses to NRL proteins. C1 NIOSH, Agr & Immunotoxicol Grp, Morgantown, WV 26505 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. FeRX Inc, Preclin Dev, San Diego, CA USA. Kimberly Clark Inc, Sci Affairs & Clin Educ, Roswell, GA USA. RP Meade, BJ (reprint author), MS 4020,1095 Willowdale Rd, Morgantown, WV 26505 USA. FU NIEHS NIH HHS [Y1 ES 000102] NR 46 TC 11 Z9 11 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 MAY PY 2004 VL 113 IS 5 BP 916 EP 924 DI 10.1016/j.jaci.2004.02.017 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 818UC UT WOS:000221269000015 PM 15131575 ER PT J AU Ross, IA Sapienza, PP Hanes, DE Johnson, W Kim, CS AF Ross, IA Sapienza, PP Hanes, DE Johnson, W Kim, CS TI Determination of the rat tissue partitioning of endotoxin in vitro for physiologically-based pharmacokinetic (PBPK) modeling SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the Society-of-Toxicology CY MAR 24-29, 2001 CL SAN FRANCISCO, CA SP Soc Toxicol DE partition coefficients; endotoxin; PBPK modeling ID 2,4-DICHLOROPHENOXYACETIC ACID DOSIMETRY; CEREBROSPINAL FLUID; RABBIT BRAIN; TRANSPORT; BACTERIAL; GLYCINE; RISK AB The biosynthetically double-labeled lipopolysaccharide (LPS), containing H-3-labeled on the fatty acyl-chains and C-14-labeled on the glucosamine of Salmonella enterica serotype typhimurium, was isolated from bacteria grown in proteose peptone-beef extract (PPBE) medium in the presence of labeled precursors; 133 muCi/ml of [2-H-3] acetate sodium salt and 0.167 muCi/ml of N-acetyl[D-1-C-14]glucosamine. The LPS was extracted from the bacteria with 90% phenol/chloroform/petroleum ether, purified and stored in 0.1% (v/v) triethylamine/10 mM Tris HCl at -70 degreesC. Tissue slices and portions of the meninges were prepared and incubated in artificial cerebrospinal fluid (CSF) or Krebs phosphate buffer (Krebs) containing 150 ng/ml LPS with [H-3] LPS (0.004 muCi/ml, sp. act. 28 muCi/mg LPS). The tissues were incubated under 95% oxygen/5% carbon dioxide at 37 degreesC with constant agitation until steady-state uptake was reached (60 min). At the end of the incubation period, tissues were processed for radioactivity measurement. The rat tissue partitioning of LPS in artificial CSF for brain and Krebs for other organs was measured by using the ratio of tissue to medium at the steady state in vitro. The following results were obtained from the study: Heart, 0.15; liver, 0.19; spleen, 0.12; kidney, 0.18; stomach, 0.17; small intestine, 0.18; brain stem, 0.10; cerebellum, 0.11; meninges, 0.77; hippocampus, 0.12; hypothalamus, 0.12; frontal cortex, 0.09 and caudate nucleus, 0.10. This information, along with plasma or blood/buffer partition coefficients, is a requisite for constructing a physiologically-based pharmacokinetic (PBPK) model of endotoxins for quantitative risk assessment. Copyright (C) 2004 John Wiley Sons, Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Laurel, MD 20708 USA. RP Kim, CS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, HFS25, Laurel, MD 20708 USA. NR 19 TC 5 Z9 5 U1 2 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD MAY-JUN PY 2004 VL 24 IS 3 BP 177 EP 181 DI 10.1002/jat.956 PG 5 WC Toxicology SC Toxicology GA 826DL UT WOS:000221809400002 PM 15211610 ER PT J AU Hilbert, SL Boerboom, LE Livesey, SA Ferrans, VJ AF Hilbert, SL Boerboom, LE Livesey, SA Ferrans, VJ TI Explant pathology study of decellularized carotid artery vascular grafts SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE pathology; decellularized; small-diameter vascular graft ID VEIN BYPASS GRAFTS; SAPHENOUS-VEIN; GASTROEPIPLOIC ARTERY; REVASCULARIZATION; POLYTETRAFLUOROETHYLENE; ASSIST AB The purpose of this study was to evaluate the morphologic findings in small-diameter freeze-dried decellularized carotid artery grafts implanted in goats as carotid artery interposition grafts for 6-7 months. Unimplanted decellularized carotid artery grafts did not contain intact cells; however, remnants of smooth muscle cells were present in the media. The extracellular matrix was well preserved. All decellularized grafts were patent at explant, without significant dimensional changes or aneurysm formation. Their luminal surfaces were lined by a thin neointima, consisting of myofibroblasts, collagen, and a discontinuous layer of endothelial cells. Histologic evidence of calcification within the explants was not observed; however, electron microscopy showed calcification of minute remnants of cell membranes. Inflammatory cells were not present in the graft wall. Host cell migration was greatest in the adventitia along the length of the graft. Migration of host cells into the media was more apparent close to the anastomoses, forming cellular nests rich in extracellular proteoglycans, whereas cell migration into areas subjacent to the lumen was minimal. Ingrowth of host blood vessels was not observed. These results demonstrate satisfactory structural and morphologic features of a decellularized carotid artery small-diameter graft implanted for up to 7 months. (C) 2004 Wiley Periodicals, Inc. C1 US FDA, Off Sci & Technol HFZ150, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. LifeCell Corp, Branchburg, NJ USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Hilbert, SL (reprint author), US FDA, Off Sci & Technol HFZ150, Ctr Devices & Radiol Hlth, 9200 Corp Blvd, Rockville, MD 20850 USA. EM sxh@cdrh.fda.gov NR 17 TC 16 Z9 23 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD MAY 1 PY 2004 VL 69A IS 2 BP 197 EP 204 DI 10.1002/jbm.a.10135 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 812ST UT WOS:000220859900001 PM 15057992 ER PT J AU Guan, EN Wang, J Norcross, MA AF Guan, EN Wang, J Norcross, MA TI Amino-terminal processing of MIP-1 beta/CCL4 by CD26/dipeptidyl-peptidase IV SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE mip-1 beta; CD26/DPPIV; HIV-1 Tat ID DIPEPTIDYL-PEPTIDASE-IV; T-CELL-ACTIVATION; CD26 EXPRESSION; RECEPTOR SPECIFICITY; CHEMOKINE RECEPTORS; ADENOSINE-DEAMINASE; HUMAN-LYMPHOCYTES; BETA-CHEMOKINES; FACTOR 1-ALPHA; HIV-1 TAT AB CD26 is a membrane-bound ectopeptidase with dipeptidyl peptidase IV (DPPIV) activity that has diverse functional properties in T cell physiology and in regulation of bioactive peptides. We have previously reported that activated human peripheral lymphocytes (PBL) secrete an amino-terminal truncated form of macrophage inflammatory protein (MIP)-1 beta/(3-69) with novel functional specificity for CCR1, 2, and 5. In this report, we show that the full length MIP-1 beta is processed by CD26/DPPIV to the truncated form and that cleavage can be blocked by DPPIV inhibitory peptides derived from HIV Tat(1-9) or the thromboxane A2 receptor, TAX2-R(1-9). Addition of Tat(] -9) or TAX2-R(l -9) peptides to PBL cultures partially blocks endogenous MIP-1 beta processing. The kinetics of conversion of MIP-1 beta from intact to MIP-1 beta(3-69) in activated PBLs correlates with cell surface expression of CD26. Our results suggest that NH2-terminal processing of MIP-1 beta and possibly other chemokines may depend on the balance between CD26/DPPIV enzymatic activity and cellular and viral proteins that modulate enzyme function. (C) 2004 Wiley-Liss, Inc. C1 US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, NIH, Bethesda, MD 20892 USA. RP Guan, EN (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, NIH, Bldg 29B,Room 4E12,HFM 535,8800 Rockville Pike, Bethesda, MD 20892 USA. EM guan@cber.fda.gov; norcross@cber.fda.gov NR 40 TC 24 Z9 24 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAY 1 PY 2004 VL 92 IS 1 BP 53 EP 64 DI 10.1002/jcb.20041 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 818IT UT WOS:000221239500006 PM 15095403 ER PT J AU Beger, RD Young, JF Fang, H AF Beger, RD Young, JF Fang, H TI Discriminant function analyses of liver-specific carcinogens SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article ID BINDING; RECEPTOR; SPECTRA; MODELS; NMR AB The ability to predict organ-specific carcinogenicity would aid FDA reviewers in evaluating new chemical applications. A NCTR liver cancer database (NCTRlcdb) containing 999 compounds has been developed with three sets of descriptors. The NCTRlcdb has Cerius2, Molconn-Z, and C-13 NMR descriptors for each compound. Each compound in the database was assigned a liver cancer or a nonliver cancer classification. Compounds within the NCTRlcdb were evaluated for liver-specific carcinogenicity using partial least squares principal component discriminant function (PLS-DF) modeling. PLS-DF models based on estimated a priori classification probabilities of 0.29 for liver cancer and 0.71 for noncancer yielded an overall predictability of 70.6% which was comprised of a liver cancer sensitivity of 18.8% and a noncancer specificity of 90.8%. PLS-DF models based on equal a priori classification probabilities, 0.50 for liver cancer and 0.5 for noncancer, yielded an overall predictability of 61.0% which was comprised of a liver cancer sensitivity of 50.5% and a noncancer specificity of 65.3%. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Logicon ROW Sci, Jefferson, AR 72079 USA. RP Beger, RD (reprint author), US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. EM rbeger@nctr.fda.gov NR 11 TC 4 Z9 4 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD MAY-JUN PY 2004 VL 44 IS 3 BP 1107 EP 1110 DI 10.1021/ci0342829 PG 4 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 823JQ UT WOS:000221608000037 PM 15154779 ER PT J AU Sergeev, N Volokhov, D Chizhikov, V Rasooly, A AF Sergeev, N Volokhov, D Chizhikov, V Rasooly, A TI Simultaneous analysis of multiple Staphylococcal enterotoxin genes by an oligonucleotide microarray assay SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SHOCK-SYNDROME TOXIN-1; ATOPIC-DERMATITIS; PATHOGENICITY ISLANDS; RHEUMATOID-ARTHRITIS; EXFOLIATIVE TOXINS; COMMON ANTIBODIES; AUREUS; SUPERANTIGENS; PCR; DETERMINANTS AB Staphylococcal enterotoxins (SEs) are a family of 17 major serological types of heat-stable enterotoxins that are one of the leading causes of gastroenteritis resulting from consumption of contaminated food. SEs are considered potential bioweapons. Many Staphylococcus aureus isolates contain multiple SEs. Because of the large number of SEs, serological typing and PCR typing are laborious and time-consuming. Furthermore, serological typing may not always be practical because of antigenic similarities among enterotoxins. We report on a microarray-based one-tube assay for the simultaneous detection and identification (genetic typing) of multiple enterotoxin (ent) genes. The proposed typing method is based on PCR amplification of the target region of the ent genes with degenerate primers, followed by characterization of the PCR products by microchip hybridization with oligonucleotide probes specific for each ent gene. We verified the performance of this method by using several other techniques, including PCR amplification with gene-specific primers, followed by gel electrophoresis or microarray hybridization, and sequencing of the enterotoxin genes. The assay was evaluated by analysis of previously characterized staphylococcal isolates containing 16 ent genes. The microarray assay revealed that some of these isolates contained additional previously undetected ent genes. The use of degenerate primers allows the simultaneous amplification and identification of as many as nine different ent genes in one S. aureus strain. The results of this study demonstrate the usefulness of the oligonucleotide microarray assay for the analysis of multitoxigenic strains, which are common among S. aureus strains, and for the analysis of microbial pathogens in general. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. US FDA, Ctr Biol Evaluat & Res, College Pk, MD USA. RP Rasooly, A (reprint author), NCI, NIH, EPN, 6130 Execut Blvd,Room 6035A, Rockville, MD 20852 USA. EM rasoolya@mail.nih.gov NR 42 TC 65 Z9 75 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2004 VL 42 IS 5 BP 2134 EP 2143 DI 10.1128/JCM.42.5.2134-2143.2004 PG 10 WC Microbiology SC Microbiology GA 820XU UT WOS:000221424100041 PM 15131181 ER PT J AU Jakubzick, C Choi, ES Kunkel, SL Evanoff, H Martinez, FJ Puri, RK Flaherty, KR Toews, GB Colby, TV Kazerooni, EA Gross, BH Travis, WD Hogaboam, CM AF Jakubzick, C Choi, ES Kunkel, SL Evanoff, H Martinez, FJ Puri, RK Flaherty, KR Toews, GB Colby, TV Kazerooni, EA Gross, BH Travis, WD Hogaboam, CM TI Augmented pulmonary IL-4 and IL-13 receptor subunit expression in idiopathic interstitial pneumonia SO JOURNAL OF CLINICAL PATHOLOGY LA English DT Article ID CRYPTOGENIC FIBROSING ALVEOLITIS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; HUMAN LUNG FIBROBLASTS; GROWTH-FACTOR; SIGNAL-TRANSDUCTION; CYTOKINE PROFILES; CELL-TYPES; INTERLEUKIN-13; DISEASE; CLASSIFICATION AB Background: Some idiopathic interstitial pneumonias (IIPs) are characterised by fibroproliferation and deposition of extracellular matrix. Because efficacious treatment options are limited, research has been directed towards understanding the cytokine networks that may affect fibroblast activation and, hence, the progression of certain IIPs. Aims: To examine the expression of interleukin 4 (IL-4), IL-13, and their corresponding receptor subunits in the various forms of IIP and normal patient groups. Methods: Molecular and immunohistochemical analysis of IL-4, interferon gamma (IFNgamma), IL-13, IL-4 receptor (IL-R), and IL-13 receptor subunits in surgical lung biopsies (SLBs) from 39 patients (21 usual interstitial pneumonia (UIP), six non-specific interstitial pneumonia (NSIP), eight respiratory bronchiolitic interstitial lung disease (RBILD), and five normal controls). Results: Molecular analysis demonstrated that IL-13Ralpha2, IL-13Ralpha1, and IL-4Ralpha were present in a greater proportion of upper and lower lobe biopsies from patients with UIP than patients with NSIP and RBILD. Immunohistochemical analysis of patients with UIP, NSIP, and RBILD revealed interstitial staining for all three receptor subunits, whereas such staining was only seen in mononuclear cells present in normal SLBs. Fibroblastic foci in patients with UIP strongly stained for IL-4Ralpha and IL-13Ralpha2. Localised expression of IL-4Ralpha was also seen in SLBs from patients with NSIP but not in other groups. Conclusion: Some histological subtypes of IIP are associated with increased pulmonary expression of receptor subunits responsive to IL-4 and IL-13. These findings may be of particular importance in understanding the pathogenesis of IIP and, more importantly, may provide important novel therapeutic targets. C1 Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Med, Div Pulm & Crit Care Med, Ann Arbor, MI 48104 USA. Univ Michigan, Sch Med, Dept Radiol, Ann Arbor, MI 48104 USA. US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Mayo Clin, Scottsdale, AZ 85259 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. RP Hogaboam, CM (reprint author), Univ Michigan, Sch Med, Dept Pathol, Room 5214,Med Sci 1,1301 Catherine Rd, Ann Arbor, MI 48109 USA. EM Hogaboam@med.umich.edu RI hogaboam, cory /M-3578-2014 FU NIAID NIH HHS [T32 AI007413] NR 53 TC 33 Z9 35 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0021-9746 J9 J CLIN PATHOL JI J. Clin. Pathol. PD MAY 1 PY 2004 VL 57 IS 5 BP 477 EP 486 DI 10.1136/jcp.2003.012799 PG 10 WC Pathology SC Pathology GA 815WS UT WOS:000221073000006 PM 15113854 ER PT J AU Seo, KH Valentin-Bon, IE Brackett, RE Holt, PS AF Seo, KH Valentin-Bon, IE Brackett, RE Holt, PS TI Rapid, specific detection of Salmonella enteritidis in pooled eggs by real-time PCR SO JOURNAL OF FOOD PROTECTION LA English DT Article ID POLYMERASE-CHAIN-REACTION; ENTERICA SEROTYPE ENTERITIDIS; QUANTIFICATION; PLASMIDS; SHELL; GENE AB An assay was developed for the specific detection of Salmonella Enteritidis in eggs with the use of an application of the fluorogenic 5' nuclease assay (TaqMan). In this assay, a segment of the gene sefA specific to Salmonella group D strains such as Salmonella Enteritidis was used. The amplification of the target gene products was monitored in real-time by incorporating a fluorescent dye-labeled gene-specific probe in the PCR reaction. This method correctly detected and distinguished Salmonella Enteritidis from nearly 50 of non-group D Salmonella and other non-Salmonella strains. Detection of the sefA gene was linear for DNA extracted from approximately 10(2) to 10(9) CFU/ml in phosphate-buffered saline and 10(3) to 10(8) CFU/ml in raw egg. In two trials, when applied to detection of Salmonella Enteritidis in homogenized egg pools and compared with conventional culture methods, the newly developed PCR method yielded a 100% correlation with results obtained by a conventional culture method. However, the PCR method required only 2 days, compared to the 5 days required by the culture method. The sensitivity of this assay was approximately less than 1 CFU/600 g of egg pool. The real-time PCR assay proved to be a rapid, highly sensitive test for detection and quantification of low concentrations of Salmonella Enteritidis in egg samples. C1 US FDA, CFSAN, OPDFB, College Pk, MD 20740 USA. USDA ARS, SE Poultry Res Lab, Athens, GA 30605 USA. RP Seo, KH (reprint author), US FDA, CFSAN, OPDFB, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM kseo@cfsan.fda.gov NR 23 TC 43 Z9 46 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 MAY PY 2004 VL 67 IS 5 BP 864 EP 869 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 820FU UT WOS:000221373600001 PM 15151219 ER PT J AU Hammack, TS Valentin-Bon, IE Jacobson, AP Andrews, WH AF Hammack, TS Valentin-Bon, IE Jacobson, AP Andrews, WH TI Relative effectiveness of the Bacteriological Analytical Manual method for the recovery of Salmonella from whole cantaloupes and cantaloupe rinses with selected preenrichment media and rapid methods SO JOURNAL OF FOOD PROTECTION LA English DT Article ID BOARD SURFACES; MICROORGANISMS; PRODUCE AB Soak and rinse methods were compared for the recovery of Salmonella from whole cantaloupes. Cantaloupes were surface inoculated with Salmonella cell suspensions and stored for 4 days at 2 to 6degreesC. Cantaloupes were placed in sterile plastic bags with a nonselective preenrichment broth at a 1:1.5 cantaloupe weight-to-broth volume ratio. The cantaloupe broths were shaken for 5 min at 100 rpm after which 25-ml aliquots (rinse) were removed from the bags. The 25-ml rinses were preenriched in 225-ml portions of the same uninoculated broth type at 35degreesC for 24 h (rinse method). The remaining cantaloupe broths were incubated at 35degreesC for 24 h (soak method). The preenrichment broths used were buffered peptone water (BPW), modified BPW, lactose (LAC) broth, and Universal Preenrichment (UP) broth. The Bacteriological Analytical Manual Salmonella culture method was compared with the following rapid methods: the TECRA Unique Salmonella method, the VIDAS ICS/SLM method, and the VIDAS SLM method. The soak method detected significantly more Salmonella-positive cantaloupes (P < 0.05) than did the rinse method: 367 Salmonella-positive cantaloupes of 540 test cantaloupes by the soak method and 24 Salmonella-positive cantaloupes of 540 test cantaloupes by the rinse method. Overall, BPW, LAC, and UP broths were equivalent for the recovery of Salmonella from cantaloupes. Both the VIDAS ICS/SLM and TECRA Unique Salmonella methods detected significantly fewer Salmonella-positive cantaloupes than did the culture method: the VIDAS ICS/SLM method detected 23 of 50 Salmonella-positive cantaloupes (60 tested) and the TECRA Unique Salmonella method detected 16 of 29 Salmonella-positive cantaloupes (60 tested). The VIDAS SLM and culture methods were equivalent: both methods detected 37 of 37 Salmonella-positive cantaloupes (60 tested). 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 24 TC 12 Z9 12 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 MAY PY 2004 VL 67 IS 5 BP 870 EP 877 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 820FU UT WOS:000221373600002 PM 15151220 ER PT J AU Lampel, KA Dyer, D Kornegay, L Orlandi, PA AF Lampel, KA Dyer, D Kornegay, L Orlandi, PA TI Detection of Bacillus spores using PCR and FTA filters SO JOURNAL OF FOOD PROTECTION LA English DT Article ID TEMPLATE PREPARATION; ANTHRACIS; SUBTILIS AB Emphasis has been placed on developing and implementing rapid detection systems for microbial pathogens. We have explored the utility of expanding FTA filter technology for the preparation of template DNA for PCR from bacterial spores. Isolated spores from several Bacillus spp., B. subtilis, B. cereus, and B. megaterium, were applied to FIFA filters, and specific DNA products were amplified by PCR. Spore preparations were examined microscopically to ensure that the presence of vegetative cells, if any, did not yield misleading results. PCR primers SRM86 and SRM87 targeted a conserved region of bacterial rRNA genes, whereas primers Bsub5F and Bsub3R amplified a product from a conserved sequence of the B. subtilis rRNA gene. With the use of the latter set of primers for nested PCR, the sensitivity of the PCR-based assay was increased. Overall, 53 spores could be detected after the first round of PCR, and the sensitivity was increased to five spores by nested PCR. FTA filters are an excellent platform to remove PCR inhibitors and have universal applications for environmental, clinical, and food samples. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Lampel, KA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. EM klampel@cfsan.fda.gov NR 13 TC 11 Z9 13 U1 0 U2 4 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD MAY PY 2004 VL 67 IS 5 BP 1036 EP 1038 PG 3 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 820FU UT WOS:000221373600029 PM 15151247 ER PT J AU Stewart, SFC Herman, BA Nell, DM Retta, SM AF Stewart, SFC Herman, BA Nell, DM Retta, SM TI Effects of valve characteristics on the accuracy of the Bernoulli equation: A survey of data submitted to the USFDA SO JOURNAL OF HEART VALVE DISEASE LA English DT Article; Proceedings Paper CT 2nd Biennial Meeting of the Society-for-Heart-Valve-Disease CY JUN 28-JUL 01, 2003 CL PARIS, FRANCE SP Soc Heart Valve Dis ID PRESSURE-GRADIENT MEASUREMENT; DOPPLER ULTRASOUND; PROSTHETIC VALVES; AORTIC-STENOSIS; STARR-EDWARDS; INVITRO; RECOVERY; HANCOCK; ERRORS; SIZE AB Background and aim of the study: In 1988, valve manufacturers petitioned the U. S. Food & Drug Administration (FDA) to replace catheter with Doppler ultrasound measurements of pressure gradient (DeltaP) in clinical studies. Manufacturers agreed to submit bench data validating the Bernoulli equation used to calculate DeltaP: DeltaP = K(V-d(2) - V-p(2)), where K = constant, V-d = distal Doppler velocity, and V-p = proximal Doppler velocity. Previous studies suggest that K may vary from the idealized 4.0, which could lead to incorrect valve assessment and clinical errors. Methods: Variation in K-values in marketing application data submitted to the FDA was assessed. Pulse duplicator data included four bileaflet valves, two stented bioprostheses, and seven stentless bioprostheses, sized from 19 to 33 mm. Effects of valve type, valve size, blood-mimicking fluid used, and distal pressure tap position (DPTP) were evaluated via an analysis of variance. * Results: K-values varied from 2.50 to 7.40 (n = 90). K was found to be dependent on valve type (p <0.0001), blood-mimicking fluid (p <0.0001) and DPTP (p <0.0001), but not valve size. At DPTP 30 mm, K = 3.43 +/- 0.56, 5.15 +/- 0.81, and 4.81 +/- 1.02, for bileaflet, stented and stentless valves, respectively. K averaged 10% less using the 100-mm DPTP, due to pressure recovery. Variations due to blood-mimicking fluid were likely related to the fluid density. Conclusion: Variations due to DPTP and fluid used are consistent with physical mechanisms of pressure recovery and fluid density. Results from previous studies have suggested that effects of valve type on K are also real. The magnitude of these effects appeared to be 25%. Extrapolation to patients is difficult, but clinicians should be aware that Doppler measurements may vary by similar amounts. Doppler pressure gradients should be interpreted qualitatively and moderated by other diagnostic measures of valve performance. C1 US FDA, Off Sci & Engn Labs, Rockville, MD 20850 USA. US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Rockville, MD 20850 USA. RP Stewart, SFC (reprint author), US FDA, Off Sci & Engn Labs, 9200 Corp Blvd,HFZ-132, Rockville, MD 20850 USA. EM sxs@cdrh.fda.gov NR 16 TC 1 Z9 1 U1 0 U2 1 PU I C R PUBLISHERS PI NORTHWOOD PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD HA6 2ET, ENGLAND SN 0966-8519 J9 J HEART VALVE DIS JI J. Heart Valve Dis. PD MAY PY 2004 VL 13 IS 3 BP 461 EP 466 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 824PN UT WOS:000221698600026 PM 15222294 ER PT J AU Tomazic-Jezic, VJ Lucas, AD Sanchez, BA AF Tomazic-Jezic, VJ Lucas, AD Sanchez, BA TI Binding and measuring natural rubber latex proteins on glove powder SO JOURNAL OF IMMUNOASSAY & IMMUNOCHEMISTRY LA English DT Article DE natural rubber latex; latex proteins; glove powder; immunoassay; latex allergy ID AIRBORNE LATEX; CORNSTARCH; ALLERGENS; QUANTIFICATION; AEROALLERGENS; RISK AB Cornstarch used as a donning powder on natural rubber latex (NRL) gloves adsorbs NRL proteins. During glove use, powder-carried proteins can be aerosolized and can cause allergic reactions in NRL sensitized individuals. The amount of NRL proteins bound to glove powder and its relative relationship to the total amount of proteins on the glove has not been studied, due to the difficulty in measuring proteins on powder. Using the ELISA inhibition assay for NRL proteins [Standard test method for the immunological measurement of antigenic protein in natural rubber and its products. In: The Annual Book of ASTM Standards; ASTM: West Conshohocken, PA, 2000; ASTM D 64-0] we have investigated possible protocol modifications in order to include measurement of proteins bound to glove powder, as well as the water-extractable glove proteins. Possible interference of the starch itself was evaluated by adding clean cornstarch to the assay. No significant interference was observed with powder concentrations below 5 mg/mL. We analyzed 19 extracts of powdered surgical and examination gloves before and after removal of the particulate component. Comparison of NRL glove extracts with, and without, the cornstarch powder fraction indicated significant variations in the ratios of powder-bound protein and corresponding water-extractable protein. The ratios did not appear to correlate with either the total protein on the glove, the glove weight, or the total amount of powder on the glove. However, when virgin glove powders were exposed to NRL proteins, binding was proportional to the protein concentration in the suspension. Temperature in the range from 4degreesC to 37degreesC, did not affect binding intensity, while a higher pH resulted in a higher level of protein associated with, or bound to, the starch. The major differences in the propensity for NRL protein binding were observed among different glove powders. The data indicate that the amount of protein that binds to glove powder does not depend only on the initial protein levels in the raw NRL. More likely, other physical or chemical factors introduced during the manufacturing process, as well as the properties of the donning powder itself, may influence protein binding. Moreover, we demonstrated that the ELISA inhibition assay could be successfully modified for quantitation of proteins adsorbed on the glove powder, together with water-extractable proteins. C1 US FDA, Ctr Devices & Radiol Hlth, Div Life Sci, Rockville, MD 20852 USA. RP Tomazic-Jezic, VJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Life Sci, HFZ-112,12709 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 25 TC 2 Z9 2 U1 1 U2 5 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1532-1819 J9 J IMMUNOASS IMMUNOCH JI J. Immunoass. Immunoch. PD MAY PY 2004 VL 25 IS 2 BP 109 EP 123 DI 10.1081/IAS-120030521 PG 15 WC Biochemical Research Methods; Immunology; Medical Laboratory Technology SC Biochemistry & Molecular Biology; Immunology; Medical Laboratory Technology GA 818VG UT WOS:000221272000001 PM 15162915 ER PT J AU Kucuk, O Sarkar, F Sakr, W Wood, D Cher, M Abrams, J Doerge, DD Pollak, MM Djuric, Z Majumdar, A AF Kucuk, O Sarkar, F Sakr, W Wood, D Cher, M Abrams, J Doerge, DD Pollak, MM Djuric, Z Majumdar, A TI Clinical trial of soy isoflavone supplementation before radical prostatectomy in patients with localized prostate cancer. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT 5th International Symposium on the Role of Soy in Preventing and Treating Chronic Disease CY SEP 21-24, 2003 CL Orlando, FL C1 Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Detroit, MI USA. Univ Michigan, Ann Arbor, MI 48109 USA. US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. McGill Univ, Montreal, PQ H3A 2T5, Canada. RI Djuric, Zora/H-5147-2013 OI Djuric, Zora/0000-0002-8886-8853 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 2004 VL 134 IS 5 BP 1258S EP 1258S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 820XK UT WOS:000221423000108 ER PT J AU Vaishampayan, UV Forman, JJ Hussain, M Cher, M Pontes, E Fontana, J Alluri, KC Doerge, D Sarkar, F Kucuk, O AF Vaishampayan, UV Forman, JJ Hussain, M Cher, M Pontes, E Fontana, J Alluri, KC Doerge, D Sarkar, F Kucuk, O TI Soy isoflavones and lycopene in the treatment of hormone-sensitive and hormone-refractory prostate cancer. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT 5th International Symposium on the Role of Soy in Preventing and Treating Chronic Disease CY SEP 21-24, 2003 CL Orlando, FL C1 Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Detroit, MI USA. Univ Michigan, Ann Arbor, MI 48109 USA. US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 2004 VL 134 IS 5 BP 1258S EP 1258S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 820XK UT WOS:000221423000110 ER PT J AU Miller, FR Tait, LR Doerge, D Sarkar, F Kucuk, O AF Miller, FR Tait, LR Doerge, D Sarkar, F Kucuk, O TI Genistein and tamoxifen interaction in MCF10DCIS.corn xenograft model for chemoprevention. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT 5th International Symposium on the Role of Soy in Preventing and Treating Chronic Disease CY SEP 21-24, 2003 CL Orlando, FL C1 US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. Wayne State Univ, Detroit, MI USA. Karmanos Canc Inst, Detroit, MI USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 2004 VL 134 IS 5 BP 1261S EP 1261S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 820XK UT WOS:000221423000117 ER PT J AU Kucuk, O Sarkar, F Adsay, V Newman, L Bouwman, D Djuric, Z Doerge, D Parchment, R Banerjee, M Majumdar, A AF Kucuk, O Sarkar, F Adsay, V Newman, L Bouwman, D Djuric, Z Doerge, D Parchment, R Banerjee, M Majumdar, A TI Clinical trial of soy Isoflavones before breast cancer surgery. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT 5th International Symposium on the Role of Soy in Preventing and Treating Chronic Disease CY SEP 21-24, 2003 CL Orlando, FL C1 Univ Michigan, Ann Arbor, MI 48109 USA. Wayne State Univ, Detroit, MI USA. Karmanos Canc Inst, Detroit, MI USA. US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. RI Djuric, Zora/H-5147-2013 OI Djuric, Zora/0000-0002-8886-8853 NR 0 TC 2 Z9 2 U1 0 U2 4 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 2004 VL 134 IS 5 BP 1262S EP 1262S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 820XK UT WOS:000221423000122 ER PT J AU Kodali, U Kucuk, O Jaszewski, R Levi, E Doerge, D Sarkar, F Majumdar, APN AF Kodali, U Kucuk, O Jaszewski, R Levi, E Doerge, D Sarkar, F Majumdar, APN TI Genistein and EGFR related protein (ERRP) potentiate each other in gastric, colon and prostate cancer cells. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT 5th International Symposium on the Role of Soy in Preventing and Treating Chronic Disease CY SEP 21-24, 2003 CL Orlando, FL C1 US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. Wayne State Univ, Detroit, MI USA. Karmanos Canc Inst, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 2004 VL 134 IS 5 BP 1263S EP 1264S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 820XK UT WOS:000221423000126 ER PT J AU Mohammad, R Al-Katib, A Aboukameel, A Ibrahim, D Doerge, D Sarkar, F Kucuk, O AF Mohammad, R Al-Katib, A Aboukameel, A Ibrahim, D Doerge, D Sarkar, F Kucuk, O TI Genistein sensitizes resistant diffuse large cell lymphoma cells to chemotherapy. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT 5th International Symposium on the Role of Soy in Preventing and Treating Chronic Disease CY SEP 21-24, 2003 CL Orlando, FL C1 Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Detroit, MI USA. US FDA, Natl Ctr Toxicol Res, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 2004 VL 134 IS 5 BP 1264S EP 1264S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 820XK UT WOS:000221423000128 ER PT J AU Parchment, RE Sarkar, F Kassab, J Ellis, KL Doerge, D Kucuk, O AF Parchment, RE Sarkar, F Kassab, J Ellis, KL Doerge, D Kucuk, O TI Genistein does not sensitize human bone marrow to XK469 toxicity at concentrations that sensitize BxPC3 pancreatic cancer to XK469 chemotherapy. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT 5th International Symposium on the Role of Soy in Preventing and Treating Chronic Disease CY SEP 21-24, 2003 CL Orlando, FL C1 Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Detroit, MI USA. US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 2004 VL 134 IS 5 BP 1264S EP 1264S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 820XK UT WOS:000221423000127 ER PT J AU Sahin, K Onderci, M Gursu, MF Sahin, N Doerge, D Sarkar, F Kucuk, O AF Sahin, K Onderci, M Gursu, MF Sahin, N Doerge, D Sarkar, F Kucuk, O TI Genistein supplementation alleviates the deterioration in performance and antioxidant status of Japanese quail associated with heat stress. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT 5th International Symposium on the Role of Soy in Preventing and Treating Chronic Disease CY SEP 21-24, 2003 CL Orlando, FL C1 Firat Univ, Elazig, Turkey. Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Detroit, MI USA. US FDA, Natl Ctr Toxicol Res, Rockville, MD USA. RI Sahin, Kazim/D-5625-2009; Sahin, Nurhan/D-5626-2009 NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 2004 VL 134 IS 5 BP 1266S EP 1267S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 820XK UT WOS:000221423000136 ER PT J AU Thomas, LC Kerr, LN Andersen, PC Carter, EJ McIlvain, LD AF Thomas, LC Kerr, LN Andersen, PC Carter, EJ McIlvain, LD TI Water testing natural rubber latex condoms: A comparison of surveillance test methods SO JOURNAL OF TESTING AND EVALUATION LA English DT Article DE condoms; water test methods; holes; natural rubber latex ID TRANSMISSION AB Manufacturers, consumers, and regulators use various water test methods to test the integrity of the barrier offered by natural rubber latex condoms. The purpose of this study is to analyze three alternative water test methods and determine which is the best method for detecting holes in condoms. Three types of holes (laser, acupuncture, and 28 gage insulin needles), approximating defects that occur in condoms, were placed in condoms and then into equal size test sets for testing by six laboratories for the purpose of evaluating the three alternative methods: the ASTM method, the ISO/FDA method, and the CSI/FHI method. Each method shares a hang portion for 1 min, and then uses a different form of manipulation; either elevate (ASTM), roll (ISO/FDA), or squeeze (CSI/FHI). The interlaboratory study data indicate the CSI/FHI is the most sensitive method for locating holes in condoms, becoming more sensitive as the defect approaches the closed end. C1 Custom Serv Int Inc, Las Vegas, NV 89118 USA. US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. Church & Dwight Co Inc, Princeton, NJ 08543 USA. Family Hlth Int, Prod Qual & Compliance Dept, Res Triangle Pk, NC 27713 USA. Ansell Healthcare Inc, Dothan, AL 36303 USA. RP Thomas, LC (reprint author), Custom Serv Int Inc, 3111 W Post Rd, Las Vegas, NV 89118 USA. NR 13 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0090-3973 J9 J TEST EVAL JI J. Test. Eval. PD MAY PY 2004 VL 32 IS 3 BP 202 EP 216 PG 15 WC Materials Science, Characterization & Testing SC Materials Science GA 839TD UT WOS:000222806900005 ER PT J AU Holm, GH Zhang, CS Gorry, PR Peden, K Schols, D De Clercq, E Gabuzda, D AF Holm, GH Zhang, CS Gorry, PR Peden, K Schols, D De Clercq, E Gabuzda, D TI Apoptosis of bystander T cells induced by human immunodeficiency virus type 1 with increased envelope/receptor affinity and coreceptor binding site exposure SO JOURNAL OF VIROLOGY LA English DT Article ID CHEMOKINE RECEPTOR CXCR4; HUMAN LYMPHOID-TISSUE; EXPRESS FAS LIGAND; CD4 CROSS-LINKING; IN-VIVO; ENVELOPE GLYCOPROTEINS; MEMBRANE-FUSION; INFECTED INDIVIDUALS; CLINICAL PROGRESSION; DEPENDENT APOPTOSIS AB Apoptosis of uninfected bystander CD4(+) T cells contributes to T-cell depletion during human immunodeficiency virus type 1 (HIV-1) pathogenesis. The viral and host mechanisms that lead to bystander apoptosis are not well understood. To investigate properties of the viral envelope glycoproteins (Env proteins) that influence the ability of HIV-1 to induce bystander apoptosis, we used molecularly cloned viruses that differ only in specific amino acids in Env. The ability of these strains to induce bystander apoptosis was tested in herpesvirus saimiri-immortalized primary CD4(+) T cells (CD4/HVS), which resemble activated primary T cells. Changes in Env that increase affinity for CD4 or CCR5 or increase coreceptor binding site exposure enhanced the capacity of HIV-1 to induce bystander apoptosis following viral infection or exposure to nonreplicating virions. Apoptosis induced by HIV-1 virions was inhibited by CD4, CXCR4, and CCR5 antibodies or by the CXCR4 inhibitor AMD3100, but not the fusion inhibitor T20. HIV-1 virions with mutant Envs that bind CXCR4 but are defective for CD4 binding or membrane fusion induced apoptosis, whereas CXCR4 binding-defective mutants did not. These results demonstrate that HIV-1 virions induce apoptosis through a CXCR4- or CCR5-dependent pathway that does not require Env/CD4 signaling or membrane fusion and suggest that HIV-1 variants with increased envelope/receptor affinity or coreceptor binding site exposure may promote T-cell depletion in vivo by accelerating bystander cell death. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. US FDA, Ctr Biol Evaluat & Res, Lab Retrovirus Res, Bethesda, MD 20892 USA. Katholieke Univ Leuven, Rega Inst Med Res, Lab Expt Chemotherapy, Louvain, Belgium. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JFB 816,44 Binney St, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu RI Holm, Geoffrey/C-3188-2009 FU NIAID NIH HHS [P30 AI028691, AI28691]; NINDS NIH HHS [NS35734, R01 NS035734] NR 82 TC 48 Z9 49 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2004 VL 78 IS 9 BP 4541 EP 4551 DI 10.1128/JVI.78.9.4541-4551.2004 PG 11 WC Virology SC Virology GA 813AO UT WOS:000220880200017 PM 15078935 ER PT J AU Mohan, KVK Muller, J Som, I Atreya, CD AF Mohan, KVK Muller, J Som, I Atreya, CD TI The N- and C-terminal regions of rotavirus NSP5 are the critical determinants for the formation of viroplasm-like structures independent of NSP2 (vol 77, pg 12184, 2003) SO JOURNAL OF VIROLOGY LA English DT Correction C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Pediat & Resp Viral Dis,Sect Viral Pathogenes, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Vector Borne Viral Dis, Bethesda, MD 20892 USA. RP Atreya, CD (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Pediat & Resp Viral Dis,Sect Viral Pathogenes, Bethesda, MD 20892 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 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2004 VL 78 IS 9 BP 4951 EP 4951 DI 10.1128/JVI.78.9.4951.2004 PG 1 WC Virology SC Virology GA 813AO UT WOS:000220880200064 ER PT J AU Budge, PJ Li, YQ Beeler, JA Graham, BS AF Budge, PJ Li, YQ Beeler, JA Graham, BS TI RhoA-derived peptide dimers share mechanistic properties with other polyanionic inhibitors of respiratory syncytial virus (RSV), including disruption of viral attachment and dependence on RSV G SO JOURNAL OF VIROLOGY LA English DT Article ID REPLICATION IN-VITRO; DEXTRAN SULFATE; FUSION PROTEIN; ANTIVIRAL ACTIVITY; HEPARAN-SULFATE; F-GLYCOPROTEIN; INFECTION; TYPE-1; CELLS; BINDING AB Large polyanionic molecules, such as sulfated polysaccharides (including soluble heparin and dextran sulfate), synthetic polyanionic polymers, and negatively charged proteins, have been shown to broadly inhibit several enveloped viruses. We recently reported the antiviral activity of a peptide derived from amino acids 77 to 95 of a potential binding partner of respiratory syncytial virus F protein (RSV F), the GTPase RhoA. A subsequent study with a truncated peptide (amino acids 80 to 94) revealed that optimal antiviral activity required dimerization via intermolecular disulfide bonds. We report here that the net negative charge of this peptide is also a determining factor for its antiviral activity and that it, like other polyanions, inhibits virus attachment. In a flow cytometry-based binding assay, peptide 80-94, heparin, and dextran sulfate inhibited the attachment of virus to cells at 4degreesC at the same effective concentrations at which they prevent viral infectivity. Interestingly, time-of-addition experiments revealed that peptide 80-94 and soluble heparin were also able to inhibit the infectivity of a virus that had been prebound to cells at 4degreesC, as had previously been shown for dextran sulfate, suggesting a potential role for postattachment effects of polyanions on RSV entry. Neutralization experiments with recombinant viruses showed that the antiviral activities of peptide 80-94 and dextran sulfate were diminished in the absence of the RSV attachment glycoprotein (G). Taken together, these data indicate that the antiviral activity of RhoA-derived peptides is functionally similar to that of other polyanions, is dependent on RSV G, and does not specifically relate to a protein-protein interaction between F and RhoA. C1 NIAID, Vaccine Res Ctr, NIH, Viral Pathogenesis Lab, Bethesda, MD 20892 USA. Vanderbilt Univ, Med Ctr, Dept Microbiol & Immunol, Nashville, TN 37232 USA. US FDA, Ctr Biol Evaluat & Res, Lab Pediat & Resp Virus Dis, Bethesda, MD 20892 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, Viral Pathogenesis Lab, MSC 3017,Bldg 40,Room 2502,40 Convent Dr, Bethesda, MD 20892 USA. EM bgraham@nih.gov NR 53 TC 12 Z9 14 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2004 VL 78 IS 10 BP 5015 EP 5022 DI 10.1128/JVI.78.10.5015-5022.2004 PG 8 WC Virology SC Virology GA 817YF UT WOS:000221212100008 PM 15113882 ER PT J AU Brown, SL Todd, JF Do Luu, HM AF Brown, SL Todd, JF Do Luu, HM TI Breast implant adverse events during mammography: Reports to the food and drug administration SO JOURNAL OF WOMENS HEALTH LA English DT Article ID AUGMENTATION MAMMAPLASTY; RUPTURE; CANCER; WOMEN; PREVALENCE; DIAGNOSIS AB Objective: To characterize reports of adverse events occurring during mammography to women with breast implants submitted to the Food and Drug Administration (FDA). Methods: We searched the adverse events database for any report on silicone gel breast implants or saline breast implants that included the word "mammography" or "mammogram" in the text. We also searched adverse event reports for mammographic equipment that included the term "breast implant" in the text. Results: We retrieved 714 adverse event reports using this strategy. Sixty-six of these reports detailed an adverse event that occurred during mammography or described breast implant interference with mammography. The majority of these reports, 41 of 66 (62.1%), described breast implant rupture during mammography. Other adverse events reported included mammographic compression crushing implants, pain during mammography attributed to implants, inability to perform mammography because of capsular contracture or fear of implant rupture, and delayed detection of cancer attributed to implants. Conclusions: It is important that women considering breast implants be informed of these potential risks and that clinicians, radiologists, and mammographic technicians keep them in mind when imaging women with implants. C1 US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Div Postmarket Surveillance, Rockville, MD 20850 USA. US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Div Mech & Mat Sci, Rockville, MD 20850 USA. RP Brown, SL (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Div Postmarket Surveillance, 1350 Piccard Dr,HFZ 541, Rockville, MD 20850 USA. EM syb@cdrh.fda.gov NR 32 TC 13 Z9 14 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAY PY 2004 VL 13 IS 4 BP 371 EP 378 DI 10.1089/154099904323087042 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 825NC UT WOS:000221764200003 PM 15195650 ER PT J AU Vila, MR Kaplan, GG Feigelstock, D Nadal, M Morote, J Porta, R Bellmunt, J Meseguer, A AF Vila, MR Kaplan, GG Feigelstock, D Nadal, M Morote, J Porta, R Bellmunt, J Meseguer, A TI Hepatitis A virus receptor blocks cell differentiation and is overexpressed in clear cell renal cell carcinoma SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Symposium on Immunology in Renal Disease CY JUN 02-05, 2003 CL Berlin, GERMANY SP Int Soc Nephrol DE ccRCC; differentiation; hhavcr-1; kidney tumors; proximal tubule cells; RAP-PCR; tumor markers ID POLYMERASE-CHAIN-REACTION; KIDNEY INJURY MOLECULE-1; SCATTER-FACTOR; CANCER-CELLS; RNA; IDENTIFICATION; ADHESION; GENE; CHROMOSOME-3; EXPRESSION AB Background. The molecular mechanisms underlying tumorigenesis and progression of clear cell renal cell carcinoma (ccRCC) are not well understood. We aimed to identify new molecular markers to provide insight into these processes. Methods. This work reports on the identification of human hepatitis A virus cellular receptor 1 (hHAVcr-1) as a differentially expressed gene in ccRCC using RNA-based arbitrarily primed polymerase chain reaction (RAP-PCR). Results were further confirmed by Northern and Western blot assays. Carcinoma 769-P and normal HK-2 cells derived from proximal tubule epithelial cells. grown under different culture conditions, were used to understand the putative role of hHAVcr-1 in renal malignancy hHAVcr-1 stable transfected clones and dipeptidyl peptidase IV (DPPIV) assays allowed assessing its involvement in cell differentiation. Results. The hHAVcr-1 is overexpressed in eight out of 13 ccRCC and its expression neglected in benign oncocytomas. In culture, hhavcr-1 is dramatically overexpressed in normal and tumor cell lines that, having acquired the fully differentiated phenotype, are induced to de-differentiate by means of phorbol ester phorbol 12-myristate-13-acetate (PMA) treatment. Similarly differentiation prevention by addition of PMA to confluent cells also increases hhavcr-1 expression. hHAVcr-1 stable transfected 769-P cells proved that hhavcr-1 itself blocks differentiation. Since hhavcr-1 is expressed at higher levels in tumor cells. we used an African green monkey cell model to show that immunotoxins directed against the monkey homologue of hhavcr-1 could kill kidney cells. Conclusion. Our results showed that hHAVcr-1 blocks differentiation of proximal tubule epithelial cells and that it could be used as a target for therapy of kidney carcinomas. C1 Hosp Univ Vall Hebron, Ctr Invest Bioquim & Biol Mol, Barcelona 08035, Spain. Hosp Univ Vall Hebron, Serv Oncol, Barcelona, Spain. Hosp Univ Vall Hebron, Serv Urol, Barcelona, Spain. Hosp Duran i Reynals, Inst Recerca Oncol, Barcelona, Spain. US FDA, Lab Hepatitis & Related Emerging Agents, CBER, Bethesda, MD 20014 USA. RP Meseguer, A (reprint author), Hosp Univ Vall Hebron, Ctr Invest Bioquim & Biol Mol, Pg Vall Hebron 119-129, Barcelona 08035, Spain. EM ameseguer@vhebron.net RI Meseguer Navarro, Anna/M-2222-2014 OI Meseguer Navarro, Anna/0000-0003-3833-2249 NR 42 TC 21 Z9 22 U1 0 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2004 VL 65 IS 5 BP 1761 EP 1773 DI 10.1111/j.1523-1755.2004.00601.x PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 815CR UT WOS:000221020900035 PM 15086915 ER PT J AU Cieslak, TJ Pavlin, JA Noah, DL Dire, DJ Stanek, SA Kortepeter, MG Jarrett, DG Pastel, RH Darling, RG Jacocks, JM Hurst, CG Richards, BA Eitzen, EM AF Cieslak, TJ Pavlin, JA Noah, DL Dire, DJ Stanek, SA Kortepeter, MG Jarrett, DG Pastel, RH Darling, RG Jacocks, JM Hurst, CG Richards, BA Eitzen, EM TI Military medical education: Nuclear, biological, and chemical medical defense training as a model for planners SO MILITARY MEDICINE LA English DT Article ID STUDENTS C1 San Antonio Mil Pediat Ctr, San Antonio, TX USA. Walter Reed Army Inst Res, Silver Spring, MD USA. Bolling AFB, Off AF Surg Gen, Washington, DC USA. USA, Med Grp 5, Birmingham, AL USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. Armed Forces Radiobiol Res Inst, Bethesda, MD USA. USA, Med Res Inst Chem Def, Aberdeen Proving Ground, MD 21010 USA. US FDA, Ctr Devices & Radiol Hlth, Gaithersburg, MD USA. US Dept HHS, Washington, DC 20201 USA. RP Cieslak, TJ (reprint author), Brooke Army Med Ctr, Dept Pediat, Ft Sam Houston, TX 78234 USA. EM Ted.Cieslak@amedd.army.mil NR 10 TC 1 Z9 2 U1 0 U2 0 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD MAY PY 2004 VL 169 IS 5 BP 337 EP 341 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 019IU UT WOS:000235829600003 PM 15185995 ER PT J AU Ravichandran, V Vasquez, GB Srivastava, S Verma, M Petricoin, E Lubell, J Sriram, RD Barker, PE Gilliland, GL AF Ravichandran, V Vasquez, GB Srivastava, S Verma, M Petricoin, E Lubell, J Sriram, RD Barker, PE Gilliland, GL TI Data standards for proteomics: mitochondrial two-dimensional polyacrylamide gel electrophoresis data as a model system SO MITOCHONDRION LA English DT Article DE 2D gel electrophoresis; data standards; interoperability; proteomics; data uniformity ID PROTEIN IDENTIFICATION AB Proteomics has emerged as a major discipline that led to a re-examination of the need for consensus and a nationally sanctioned set of proteomics technology standards. Such standards for databases and data reporting may be applied to two-dimensional polyacrylamide gel electrophoresis (2D PAGE) technology as a pilot project for assessing global and national needs in proteomics, and the role of the National Institute of Standards and Technology (NIST) and other similar standards and measurement organizations. The experience of harmonizing the heterogeneous data included in the Protein Data Bank (PDB) provides a paradigm for technology in an area where significant heterogeneity in technical detail and data storage has evolved. Here we propose an approach toward standardizing mitochondrial 2D PAGE data in support of a globally relevant proteomics consensus. (C) 2004 Elsevier B.V. and Mitochondria Research Society. All rights reserved. C1 Natl Inst Stand & Technol, Div Biotechnol, Gaithersburg, MD 20899 USA. Natl Inst Stand & Technol, Mfg Syst Integrat Div, Gaithersburg, MD 20899 USA. Natl Canc Inst, Div Canc Prevent, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prod, Off Therapeut Res & Review, Bethesda, MD 20892 USA. RP Ravichandran, V (reprint author), Univ Maryland, Ctr Adv Res Biotechnol, 9600 Gudelsky Dr, Rockville, MD 20850 USA. EM vravi@nist.gov NR 12 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 J9 MITOCHONDRION JI Mitochondrion PD MAY PY 2004 VL 3 IS 6 BP 327 EP 336 DI 10.1016/j.mito.2004.02.006 PG 10 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 823TE UT WOS:000221635300002 PM 16120364 ER PT J AU Bernstein, RM Mills, FC Mitchell, M Max, EE AF Bernstein, RM Mills, FC Mitchell, M Max, EE TI Complex mechanisms for inhibition of immunoglobulin gene expression in a germinal center B cell line SO MOLECULAR IMMUNOLOGY LA English DT Article DE B lymphocytes; human; antibodies; cytokines; gene regulation ID NF-KAPPA-B; DNA-BINDING; TRANSCRIPTION FACTORS; SYNERGISTIC ACTIVATION; PROTEIN COMPLEXES; ENHANCER FUNCTION; CD40 RECEPTOR; CROSS-LINKING; IN-VITRO; OCA-B AB CD40 ligation and IL-4 stimulation are critical Th2 cell-derived signals that act on germinal center B cells to stimulate immunoglobulin isotype switching. In addition to this well-known effect, these same Th2 signals have also been reported to inhibit ongoing immunoglobulin synthesis in germinal center B cells. To study the mechanism of this inhibition, we have investigated which immunoglobulin gene regulatory regions might be affected by IL-4 and CD40 Ligand (CD40L). CL-01 cells, a human B cell line of germinal center phenotype, were transiently transfected with luciferase reporter constructs containing various light and heavy chain enhancers and promoters; the cells were then incubated with or without CD40L and IL-4 and then assayed for luciferase expression. We find that the intronic enhancer of the kappa light chain (but not the heavy chain) is upregulated by CD40 ligation, but that VH and Vkappa promoters and the 3' enhancers of both the kappa and heavy chain loci are inhibited by CD40 ligation and the Th2 cytokines IL-4 and IL-10. The inhibitory response of the 3'alpha enhancer can be observed with a 130 by core fragment of the enhancer, and remains unaffected by mutations in several motifs known or suspected to contribute to enhancer function. The ultimate effects of cytokines and CD40 ligation on immunoglobulin gene transcription therefore represent a complex integration of positive and negative stimuli acting on enhancers and promoters. Published by Elsevier Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Bethesda, MD 20892 USA. RP Max, EE (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Therapeut Res & Review, HFM-541, Bethesda, MD 20892 USA. EM max@cber.fda.gov NR 34 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD MAY PY 2004 VL 41 IS 1 BP 63 EP 72 DI 10.1016/j.molimm.2004.01.005 PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 826EO UT WOS:000221812300007 PM 15140576 ER PT J AU Delogu, G Pusceddu, C Bua, A Fadda, G Brennan, MJ Zanetti, S AF Delogu, G Pusceddu, C Bua, A Fadda, G Brennan, MJ Zanetti, S TI Rv1818c-encoded PE_PGRS protein of Mycobacterium tuberculosis is surface exposed and influences bacterial cell structure SO MOLECULAR MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; COLONY MORPHOLOGY; GENOME SEQUENCE; BOVIS BCG; LOCALIZATION; ANTIGENS; FAMILY; GENE; EXPRESSION; VIRULENCE AB Identification of the novel PE multigene family was an unexpected finding of the genomic sequencing of Mycobacterium tuberculosis. Presently, the biological role of the PE and PE_PGRS proteins encoded by this unique family of mycobacterial genes remains unknown. In this report, a representative PE_PGRS gene (Rv1818c/PE_PGRS33) was selected to investigate the role of these proteins. Cell fractionation studies and fluorescence analysis of recombinant strains of Mycobacterium smegmatis and M. tuberculosis expressing green fluorescent protein (GFP)-tagged proteins indicated that the Rv1818c gene product localized in the mycobacterial cell wall, mostly at the bacterial cell poles, where it is exposed to the extracellular milieu. Further analysis of this PE_PGRS protein showed that the PE domain is necessary for subcellular localization. In addition, the PGRS domain, but not PE, affects bacterial shape and colony morphology when Rv1818c is overexpressed in M. smegmatis and M. tuberculosis. Taken together, the results indicate that PE_PGRS and PE proteins can be associated with the mycobacterial cell wall and influence cellular structure as well as the formation of mycobacterial colonies. Regulated expression of PE genes could have implications for the survival and pathogenesis of mycobacteria within the human host and in other environmental niches. C1 Univ Sassari, Dept Biomed Sci, I-07100 Sassari, Italy. Univ Sacred Heart, Inst Microbiol, I-00168 Rome, Italy. US FDA, Ctr Biol Evaluat & Res, Lab Mycobacteriol Dis & Cellular Immunol, Bethesda, MD USA. RP Delogu, G (reprint author), Univ Cattolica Sacro Cuore, Ist Microbiol, Largo F Vito, I-00168 Rome, Italy. EM gdelogu@rm.unicatt.it RI Delogu, Giovanni/I-3701-2012; Fadda, Giovanni/K-6224-2012 OI Delogu, Giovanni/0000-0003-0182-8267; NR 35 TC 117 Z9 123 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 2004 VL 52 IS 3 BP 725 EP 733 DI 10.1111/j.1365-2958.2004.04007.x PG 9 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 813YC UT WOS:000220941400011 PM 15101979 ER PT J AU Smith, JS Tian, R Lozier, JN Byrnes, AP AF Smith, JS Tian, R Lozier, JN Byrnes, AP TI Severe pulmonary pathology after intravenous administration of adenovirus vectors in cirrhotic rats SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 US FDA, Div Cellular & Gene Therapies, CBER, Bethesda, MD 20014 USA. US FDA, Div Hematol, CBER, Bethesda, MD 20014 USA. RI Byrnes, Andrew/D-2808-2013 OI Byrnes, Andrew/0000-0003-1135-2629 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 464 BP S176 EP S176 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600465 ER PT J AU Chelonis, JJ Flake, RA Baldwin, RL Blake, DJ Paule, MG AF Chelonis, JJ Flake, RA Baldwin, RL Blake, DJ Paule, MG TI Developmental aspects of timing behavior in children SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE timing; time production; temporal response differentiation; age; sex; intelligence; children ID DEFICIT HYPERACTIVITY DISORDER; OPERANT TEST BATTERY; TIME-ESTIMATION; INTERNAL CLOCK; YOUNG-CHILDREN; TEMPORAL DISCRIMINATION; REINFORCEMENT HISTORY; RESPONSE DURATION; DRL PERFORMANCE; SEX DIFFERENCES AB This research examined the association of age, sex, and intelligence on the performance of a time production (temporal response differentiation, TRD) task. Variations of this task have been used extensively with both animals and humans to study factors that affect aspects of timing ability. The participants in this study (720 children, ages 5 to 13 years) were required to hold down a response lever for at least 10 s, but no more than 14 s, to receive a nickel. Older children made more correct lever holds and exhibited less variability in the duration of their lever holds than did the younger children. Boys and girls performed similarly on this task, whereas children with higher IQs made more correct lever holds. Young children with below average IQs exhibited increased variability in lever hold duration compared with young children with average and above average IQs. The results of this study illustrate that both age and intelligence influence timing ability. The use of this timing task in children, which also has been widely used in animal models, provides unique opportunities for interspecies comparisons. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Arkansas, Dept Psychol, Little Rock, AR 72204 USA. Univ Arkansas Med Sci, Arkansas Childrens Hosp, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chelonis, JJ (reprint author), Univ Arkansas, Dept Psychol, 2801 S Univ Ave, Little Rock, AR 72204 USA. EM JJChelonis@UALR.edu NR 85 TC 21 Z9 21 U1 3 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2004 VL 26 IS 3 BP 461 EP 476 DI 10.1016/j.ntt.2004.01.004 PG 16 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 820DH UT WOS:000221366500012 PM 15113607 ER PT J AU Gardner, S Schultz, DG AF Gardner, S Schultz, DG TI Complications associated with global endometrial ablation: The utility of the MAUDE database SO OBSTETRICS AND GYNECOLOGY LA English DT Letter C1 US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD USA. RP Gardner, S (reprint author), US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 1 TC 1 Z9 1 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 MAY PY 2004 VL 103 IS 5 BP 995 EP 996 DI 10.1097/01.AOG.0000125669.32200.be PN 1 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 875IR UT WOS:000225414200026 PM 15121577 ER PT J AU Kovalchuk, I Abramov, V Pogribny, I Kovalchuk, O AF Kovalchuk, I Abramov, V Pogribny, I Kovalchuk, O TI Molecular aspects of plant adaptation to life in the Chernobyl zone SO PLANT PHYSIOLOGY LA English DT Article ID INTRACHROMOSOMAL HOMOLOGOUS RECOMBINATION; RADIOACTIVE CONTAMINATION; TRANSGENIC PLANTS; PINUS-SILVESTRIS; POST-CHERNOBYL; MUTATION-RATE; WHOLE PLANTS; DNA; REPAIR; GERMLINE AB With each passing year since the Chernobyl accident of 1986, more questions arise about the potential for organisms to adapt to radiation exposure. Often this is thought to be attributed to somatic and germline mutation rates in various organisms. We analyzed the adaptability of native Arabidopsis plants collected from areas with different levels of contamination around the Chernobyl nuclear power plant from 1986 to 1992. Notably, progeny of Chernobyl plants resisted higher concentrations of the mutagens Rose Bengal and methyl methane sulfonate. We analyzed the possible molecular mechanisms of their resistance to mutagens and found a more than 10-fold lower frequency of extra chromosomal homologous recombination, significant differences in the expression of radical scavenging (CAT1 and FSD3) and DNA-repair (RAD1 and RAD51-like) genes upon exposure to mutagens (Rose Bengal and x-rays), and a higher level of global genome methylation. This data suggests that adaptation to ionizing radiation is a complex process involving epigenetic regulation of gene expression and genome stabilization that improves plants' resistance to environmental mutagens. C1 Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. Russian Acad Sci, NI Vavilov Gen Genet Res Inst, Moscow 117809, Russia. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Kovalchuk, I (reprint author), Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. EM olga.kovalchuk@uleth.ca NR 35 TC 78 Z9 86 U1 3 U2 36 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD MAY PY 2004 VL 135 IS 1 BP 357 EP 363 DI 10.1104/pp.104.040477 PG 7 WC Plant Sciences SC Plant Sciences GA 820WQ UT WOS:000221420800037 PM 15133154 ER PT J AU Badano, A AF Badano, A TI AAPM/RSNA tutorial on equipment selection: PACS equipment overview - Display systems SO RADIOGRAPHICS LA English DT Article DE cathode ray tubes; computers; images, display; images, quality ID LIQUID-CRYSTAL DISPLAYS; VEILING GLARE; MONOCHROME; LUMINANCE; CROSSTALK; MONITOR; DEVICES AB Display systems are key components of the digital radiology department. Current display systems for medical imaging are based on cathode-ray tubes (CRTs) or active-matrix liquid crystal displays (AMLCDs). The CRT is a cathodoluminescent display: Light is generated by exciting a luminescent material with energetic electrons. AMLCDs are light-modulating devices that form the image in the screen by controlling the transparency of individual display pixels. Many image quality aspects of CRTs are determined by the way the pixel luminance is generated in the cathodoluminescent screen. The resolution properties of AMLCDs are much better than those of CRTs. In CRT devices, phosphor granularity and raster scanning patterns are the main components of spatial noise. In AMLCDs, the most notable feature of the noise characteristic is the subpixel structure of complex pixel designs used in medical displays. The small-spot contrast of CRTs is dominated mainly by veiling glare and reflections of ambient illumination. In addition to display reflectance, the contrast of medical AMLCDs is affected by crosstalk and by variations of the luminance at off-normal viewing angles. C1 Off Sci & Technol, Ctr Devices & Radiol Hlth, US FDA, Rockville, MD 20857 USA. RP Badano, A (reprint author), Off Sci & Technol, Ctr Devices & Radiol Hlth, US FDA, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. EM agb@cdrh.fda.gov OI badano, aldo/0000-0003-3712-6670 NR 37 TC 25 Z9 25 U1 4 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAY-JUN PY 2004 VL 24 IS 3 BP 879 EP 889 DI 10.1148/rg.243035133 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 819CB UT WOS:000221289700020 PM 15143237 ER PT J AU Chang, I Mikityansky, I Wray-Cahen, D Pritchard, W Karanian, JW Wood, BJ AF Chang, I Mikityansky, I Wray-Cahen, D Pritchard, W Karanian, JW Wood, BJ TI Effects of perfusion on radiofrequency ablation in Swine kidneys SO RADIOLOGY LA English DT Article DE animals; experimental study; kidney, interventional procedures; kidney, perfusion; radiofrequency (RF) ablation ID RENAL-CELL CARCINOMA; NEPHRON SPARING SURGERY; PORCINE MODEL; IN-VIVO; VASCULAR OCCLUSION; THERMAL ABLATION; LESION SIZE; BLOOD-FLOW; FOLLOW-UP; EXPERIENCE AB PURPOSE: To evaluate the effect of vascular occlusion on the size of radiofrequency (RF) ablation lesions and to evaluate embolization as an occlusion method. MATERIALS AND METHODS: The kidneys of six swine were surgically exposed. Fifteen RF ablation lesions were created in nine kidneys by using a 2-cm-tip single-needle ablation probe in varying conditions: Seven lesions were created with normal blood flow and eight were created with blood flow obstructed by means of vascular clamping (n = 5) or renal artery embolization (n = 3). The temperature, applied voltage, current, and impedance were recorded during RF ablation. Tissue-cooling curves acquired for 2 minutes immediately after the ablation were compared by using regression analysis. Lesions were bisected, and their maximum diameters were measured and compared by using analysis of variance. RESULTS: The mean diameter of ablation lesions created when blood flow was obstructed was 60% greater than that of lesions created when blood flow was normal (1.38 cm +/- 0.05 [standard error of mean] vs 0.86 cm +/- 0.07, P < .001). The two methods of flow obstruction yielded lesions of similar mean sizes: 1.40 cm 0.06 with vascular clamping and 1.33 cm +/- 0.07 with embolization. The temperature at the probe tip when lesions were ablated with normal blood flow decreased more rapidly than did the temperature when lesions were ablated after flow obstruction (P <.001). but no significant differences in tissue-cooling curves between the two flow obstruction methods were observed. CONCLUSION: Obstruction of renal blood flow before and during RF ablation resulted in larger thermal lesions with potentially less variation in size compared with the lesions created with normal nonobstructed blood flow. Selective arterial embolization of the kidney vessels may be a useful adjunct to RF ablation of kidney tumors. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20852 USA. NIH, Dept Diagnost Radiol, Special Procedures Div, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Chang, I (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, 12725 Twinbrook Pkwy,HFZ-133, Rockville, MD 20852 USA. EM iac@cdrh.fda.gov FU Intramural NIH HHS [Z99 CL999999] NR 34 TC 50 Z9 54 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2004 VL 231 IS 2 BP 500 EP 505 DI 10.1148/radiol.2312021248 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 817CH UT WOS:000221155100029 PM 15128994 ER PT J AU Duncan, R AF Duncan, R TI DNA microarray analysis of protozoan parasite gene expression: outcomes correlate with mechanisms of regulation SO TRENDS IN PARASITOLOGY LA English DT Article ID PLASMODIUM-FALCIPARUM; TOXOPLASMA-GONDII; GENOMIC ORGANIZATION; TRYPANOSOMA-BRUCEI; CDNA MICROARRAY; LEISHMANIA; PATTERNS; TRANSCRIPTION; PROTEINS; MALARIA AB DNA microarray analysis has been successfully applied to most of the protozoan parasites that cause human disease, but has not made equal progress in all cases. The results for kinetoplastid parasites (Leishmania and Trypanosoma) are primarily at the stage of validation and new gene discovery. By contrast, the results for apicomplexan parasites (Plasmodium and Toxoplasma) have advanced to the analysis of coordinate regulation of clusters of genes. This difference in progress relates to the more complete genome sequence identified for the apicomplexans and, more significantly, to the differences in the regulation of gene expression between these two groups. C1 US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Rockville, MD 20852 USA. RP Duncan, R (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, 1401 Rockville Pk, Rockville, MD 20852 USA. EM duncan@cber.fda.gov RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 NR 32 TC 21 Z9 22 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4922 J9 TRENDS PARASITOL JI Trends Parasitol. PD MAY PY 2004 VL 20 IS 5 BP 211 EP 215 DI 10.1016/j.pt.2004.02.008 PG 5 WC Parasitology SC Parasitology GA 820NH UT WOS:000221396000007 PM 15105020 ER PT J AU Mendelsohn, AB Governale, LA AF Mendelsohn, AB Governale, LA TI The impact of the System to Manage Accutane-Related Teratogenicity (TM) (SMART (TM)) risk management program on isotretinoin prescribing trends SO VALUE IN HEALTH LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. CDC, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2004 VL 7 IS 3 BP 263 EP 263 DI 10.1016/S1098-3015(10)62198-5 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 819ZW UT WOS:000221356600137 ER PT J AU Morrato, E Staffa, J AF Morrato, E Staffa, J TI Analysis of longitudinal claims data to examine first and second-line use of pemoline (Cylert (R)) SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2004 VL 7 IS 3 BP 282 EP 282 DI 10.1016/S1098-3015(10)62254-1 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 819ZW UT WOS:000221356600193 ER PT J AU Bright, R Mermel, L Richards, C Yoder, D AF Bright, R Mermel, L Richards, C Yoder, D TI Mechanical and allergic adverse events related to central vascular catheters: Epidemiology in the Medicare hospitalized surgical population, 2002 SO VALUE IN HEALTH LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Brown Med Sch, Providence, RI USA. Rhode Isl Hosp, Providence, RI USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RI Bright, Roselie/D-2240-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2004 VL 7 IS 3 BP 331 EP 332 DI 10.1016/S1098-3015(10)62411-4 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 819ZW UT WOS:000221356600350 ER PT J AU Bright, R Cope, J AF Bright, R Cope, J TI Tampon-related toxic shock syndrome (TSS) continues to peak among adolescent girls: A nationwide hospital study SO VALUE IN HEALTH LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. RI Bright, Roselie/D-2240-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2004 VL 7 IS 3 BP 352 EP 352 DI 10.1016/S1098-3015(10)62474-6 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 819ZW UT WOS:000221356600413 ER PT J AU Drum, B AF Drum, B TI FDA regulation of labeling and promotional claims in therapeutic color vision devices: A tutorial SO VISUAL NEUROSCIENCE LA English DT Article; Proceedings Paper CT 17th Biennial Symposium of the International-Colour-Vision-Society CY JUL, 2003 CL Seattle, WA SP Int Colour Vision Soc DE color-vision aid; color vision deficiency; colored prescription lens; reading discomfort aid; FDA device evaluation AB The Food and Drug Administration (FDA) is responsible for determining whether medical device manufacturers have provided reasonable assurance, based on valid scientific evidence, that new devices are safe and effective for their intended use before they are introduced into the U.S. market. Most existing color vision devices pose so little risk that their manufacturers are not required to submit a premarket notification [510(k)] to FDA prior to market. However, even low-risk devices may not be acceptable if they are marketed on the basis of misleading or excessive claims. Although most color vision devices are diagnostic, two types that are therapeutic rather than diagnostic are colored lenses intended to improve deficient color vision and colored lenses intended to improve reading performance. Both of these devices have presented special regulatory challenges to FDA because the intended uses and effectiveness claims initially proposed by the manufacturers were not Supported by valid scientific evidence. fro each instance. however, FDA worked with the manufacturer to restrict labeling and promotional claims in ways that were consistent with the available device performance data and that allowed for the legal marketing of the device. C1 US FDA, CDRH, ODE, DOED, Rockville, MD 20850 USA. RP Drum, B (reprint author), US FDA, CDRH, ODE, DOED, HFZ-460,9200 Corp Blvd, Rockville, MD 20850 USA. EM bad@cdrh.fda.gov NR 3 TC 2 Z9 2 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0952-5238 J9 VISUAL NEUROSCI JI Visual Neurosci. PD MAY-JUN PY 2004 VL 21 IS 3 BP 461 EP 463 DI 10.1017/S0952523804213256 PG 3 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 863FU UT WOS:000224547200044 PM 15518230 ER PT J AU Verthelyi, D Wang, VW Lifson, JD Klinman, DM AF Verthelyi, D Wang, VW Lifson, JD Klinman, DM TI CpG oligodeoxynucleotides improve the response to hepatitis B immunization in healthy and SIV-infected rhesus macaques SO AIDS LA English DT Article DE CpG oligodeoxynucleotides; hepatitis B vaccine; rhesus macaques; SIV ID PLASMACYTOID DENDRITIC CELLS; VIRUS-INFECTION; HIV-1 INFECTION; BACTERIAL-DNA; VACCINE; MOTIFS; INDIVIDUALS; ACTIVATION; MONOCYTES; ADJUVANTS AB Objective: The development of an immunogenic vaccine against hepatitis B virus (HBV) is particularly important for HIV-infected patients since shared epidemiological risks result in HIV-infected subjects having a high incidence of HBV, and coinfection with HBV increases the occurrence of hepatotoxicity with aritiretroviral therapy. Although HBV vaccination is recommended to all HIV-positive patients, its efficacy in these patients is reduced. Methods: Healthy (n = 15) and SIV-infected (n = 17) rhesus macaques were immunized with Engerix B alone or combined with type D or type K CpG ODN. SIV plasma RNA levels were determined by a real time reverse transcriptase polymerase chain reaction and antibody titers to HBV surface antigen (HbsAg) were measured by enzyme-linked immunosorbent assay every 2 weeks. Results: In healthy macaques, adding D or K ODN to Engerix B accelerated and boosted the titer of the anti-HbsAg response. In SIV-infected macaques, Engerix B alone elicited no detectable antibody response but a significant response was seen when it was combined with K or D ODN. The antibody titer induced by vaccinating HIV-infected macaques was inversely correlated with their initial viral load, with animals having > 10(7) copies/ml being unable to mount a significant response. No adverse events or changes in SIV viral load were evident during the study. Conclusions: These findings support the development of clinical studies to assess the use of CpG ODN as an adjuvant for HBV vaccination in healthy and immunocompromised HIV-infected subjects. (C) 2004 Lippinecott Williams Wilkins. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. NCI, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21701 USA. RP Verthelyi, D (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bldg 29A Rm 3B19,8800 Rockville Pike, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CO-12400] NR 33 TC 35 Z9 39 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR 30 PY 2004 VL 18 IS 7 BP 1003 EP 1008 DI 10.1097/01.aids.0000111474.61782.d1 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 821OG UT WOS:000221470100008 PM 15096802 ER PT J AU Yue, HF Strauss, KI Borenstein, MR Barbe, MF Rossi, LJ Jansen, SA AF Yue, HF Strauss, KI Borenstein, MR Barbe, MF Rossi, LJ Jansen, SA TI Determination of bioactive eicosanoids in brain tissue by a sensitive reversed-phase liquid chromatographic method with fluorescence detection SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE eicosanoids ID ARACHIDONIC-ACID; CARBOXYLIC-ACIDS; P-450 METABOLITES; CYTOCHROME-P-450; EPOXYGENASE; DERIVATIZATION; ULTRAVIOLET; INJURY AB Arachidonic acid (AA) is metabolized to prostaglandins (PGs) via cyclooxygenases (COX) catalysis, and to epoxyeicosatrienoic acids (EETs), dihydroxyeicosatrienoic acids (DiHETrEs), and hydroxyeicosatetraenoic acids (HETEs) via cytochrome P450 (CYP450) enzymes. A reliable and robust fluorescence based HPLC method for these eicosanoids was developed. A new selective reverse-phase solid phase extraction (SPE) procedure was developed for PG, DiHETrEs, HETE, and EETs of interest from rat cortical brain tissue. The eicosanoids were derivatized with 2-(2,3-naphthalimino)ethyl-trifluoromethanesulphonate (NE-OTf), followed by separation and quantification at high sensitivity using reverse-phase HPLC with fluorescent detection, and further identified via LC/MS. The derivatization was studied and optimized to obtain reproducible reactions. Various PGs, DiHETrEs, HETEs, EETs, and AA were sensitively detected and baseline resolved simultaneously. LC/MS under positive electrospray ionization selected ion monitoring (SIM) mode was developed to further identify the peaks of these eicosanoids in cortical brain tissue. The method was applied in the traumatic brain injured rat brain. (C) 2004 Elsevier B.V. All rights reserved. C1 Temple Univ, Dept Chem, Philadelphia, PA 19122 USA. Univ Cincinnati, Coll Med, Dept Neurosurg, Cincinnati, OH 45267 USA. Temple Univ, Sch Pharm, Philadelphia, PA 19140 USA. Temple Univ, Dept Phys Therapy, Philadelphia, PA 19140 USA. Temple Univ, Dept Anat & Cell Biol, Philadelphia, PA 19140 USA. US FDA, Philadelphia, PA 19106 USA. RP Jansen, SA (reprint author), Temple Univ, Dept Chem, 1901 N 13th St, Philadelphia, PA 19122 USA. EM suebee@unix.temple.edu FU NINDS NIH HHS [R01 NS038654-03] NR 26 TC 35 Z9 38 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD APR 25 PY 2004 VL 803 IS 2 BP 267 EP 277 DI 10.1016/j.jchromb.2003.12.027 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 809MG UT WOS:000220640200012 PM 15063335 ER PT J AU Werler, M McCloskey, C Edmonds, LD Olney, R Honein, MA Reefhuis, J AF Werler, M McCloskey, C Edmonds, LD Olney, R Honein, MA Reefhuis, J CA CDCP TI Evaluation of an association between loratadine and hypospadias - United States, 1997-2001 (Reprinted from MMWR, vol 53, pg 219-221, 2004) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint ID BIRTH-DEFECTS PREVENTION; PREGNANCY C1 Boston Univ, Sch Publ Hlth, Slone Epidemiol Ctr, Boston, MA 02215 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NCBDDD, Div Birth Defects & Dev Disabil, Atlanta, GA USA. CDC, Atlanta, GA USA. RP Werler, M (reprint author), Boston Univ, Sch Publ Hlth, Slone Epidemiol Ctr, Boston, MA 02215 USA. RI Reefhuis, Jennita/E-1793-2011 OI Reefhuis, Jennita/0000-0002-4747-4831 NR 10 TC 2 Z9 2 U1 3 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 21 PY 2004 VL 291 IS 15 BP 1828 EP 1830 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 812XC UT WOS:000220871200010 ER PT J AU Xu, B Bhattacharjee, A Roy, B Feldman, GM Cathcart, MK AF Xu, B Bhattacharjee, A Roy, B Feldman, GM Cathcart, MK TI Role of protein kinase C isoforms in the regulation of interleukin-13-induced 15-lipoxygenase gene expression in human monocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN ATHEROSCLEROTIC PLAQUES; STAT1 SERINE PHOSPHORYLATION; CENTRIFUGAL ELUTRIATION CCE; SUPEROXIDE ANION PRODUCTION; MONONUCLEAR CELL SUBSETS; POLAR STEROL ESTERS; TYROSINE PHOSPHORYLATION; ENRICHED FRACTIONS; ENDOTHELIAL-CELLS; HUMAN ATHEROMA AB We reported previously that interleukin-13 (IL-13) induces tyrosine phosphorylation/activation of Jak2 and Tyk2 kinases and Stats 1, 3, 5, and 6 in primary human monocytes. We recently revealed that p38 MAPK-mediated serine phosphorylation of both Stat1 and Stat3 is required for the induction of 15-lipoxygenase (15-LO) expression by IL-13. In this study, we present data indicating that another serine/threonine kinase, PKCdelta, is also required for IL-13-induced 15-LO expression. PKCdelta, a member of the novel protein kinase C (PKC) subclass, was rapidly phosphorylated and activated upon exposure to IL-13. Treatment of cells with rottlerin, a PKCdelta inhibitor, blocked IL-13-induced 15-LO mRNA and protein expression, whereas Go6976, an inhibitor of the conventional PKC subclass, had no inhibitory effects. Down-regulation of cellular PKCdelta protein levels by PKCdelta-specific antisense oligodeoxyribonucleotides also inhibited 15-LO expression markedly. IL-13-induced 15-LO expression resulted in significant inhibition of synthesis of the potent chemotactic factor leukotriene B-4, and that process was reversed by rottlerin, presumably through the blockage of PKCdelta-dependent 15-LO expression. Furthermore, our data demonstrate that IL-13-mediated activation of PKCdelta and p38 MAPK are independent pathways, because inhibition of one kinase activity had no effect on the other, suggesting that the two pathways act in parallel to regulate the downstream targets necessary for 15-LO expression. Inhibition of PKCdelta activation by rottlerin also markedly attenuated IL-13-induced Stat3 DNA binding activity. Our findings indicate that PKCdelta plays an important role in regulating IL-13-induced 15-LO expression in human monocytes and subsequently modulates the inflammatory responses mediated by 15-LO products. C1 Cleveland Clin Fdn, Dept Cell Biol, Lerner Res Inst, Cleveland, OH 44195 USA. US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Off Therapeut Res & Review, Bethesda, MD 20892 USA. RP Cathcart, MK (reprint author), Cleveland Clin Fdn, Dept Cell Biol, Lerner Res Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM cathcam@ccf.org FU NHLBI NIH HHS [HL51068] NR 45 TC 22 Z9 24 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 16 PY 2004 VL 279 IS 16 BP 15954 EP 15960 DI 10.1074/jbc.M400413200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 811BR UT WOS:000220747900032 PM 14757756 ER PT J AU Morel, F Rauch, C Petit, E Piton, A Theret, N Coles, B Guillouzo, A AF Morel, F Rauch, C Petit, E Piton, A Theret, N Coles, B Guillouzo, A TI Gene and protein characterization of the human glutathione S-transferase Kappa and evidence for a peroxisomal localization* SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 2-HYDROXYCHROMENE-2-CARBOXYLATE ISOMERASE; CHROMOSOMAL LOCALIZATION; GENOMIC ORGANIZATION; PEROXIDASE ACTIVITY; METABOLISM; SEQUENCE; CLUSTER; BINDING; ENZYME; ALPHA AB Kappa class glutathione S-transferase (GST) cDNA sequences have been identified in rat, mouse, and human. In the present study, we determined the structure and chromosomal location of the human GST Kappa 1 (hGSTK1) gene, characterized the protein, and demonstrated its subcellular localization. The human gene spans similar to5 kb, has 8 exons, and maps onto chromosome 7q34. The 5'-flanking region lacks TATA or CCAAT boxes, but there is an initiator element overlapping the transcription start site. hGSTK1 amino acid sequence showed homology to bacterial 2-hydroxychromene-2-carboxylate isomerase, an enzyme involved in naphthalene degradation pathway. hGSTK1 mRNA was expressed in all of the organs examined. Subcellular fractionation of HepG2 cells showed that the protein was located in peroxisomes and mitochondria and was not detectable in cytoplasm. The peroxisomal localization was confirmed by transfection of HepG2 cells with a plasmid coding a green fluorescent protein fused in-frame to the N terminus of hGSTK1. The C terminus of hGSTK1 was essential for localization of the protein to peroxisomes, and the C-terminal sequence Ala-Arg-Leu represents a peroxisome targeting signal. This is the first time that a human GST has been found in peroxisomes, suggesting a new function for this family of enzymes. C1 Univ Rennes 1, INSERM, U456, F-35043 Rennes, France. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Morel, F (reprint author), Univ Rennes 1, INSERM, U456, 2 Ave Prof Leon Bernard, F-35043 Rennes, France. EM Fabrice.Morel@rennes.inserm.fr RI Theret, Nathalie/I-2871-2015; OI Piton, Amelie/0000-0003-0408-7468 NR 38 TC 75 Z9 78 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 16 PY 2004 VL 279 IS 16 BP 16246 EP 16253 DI 10.1074/jbc.M313357200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 811BR UT WOS:000220747900068 PM 14742434 ER PT J AU Bhattacharya, B Miura, T Brandenberger, R Mejido, J Luo, YQ Yang, AX Joshi, BH Ginis, I Thies, RS Amit, M Lyons, I Condie, BG Itskovitz-Eldor, J Rao, MS Puri, RK AF Bhattacharya, B Miura, T Brandenberger, R Mejido, J Luo, YQ Yang, AX Joshi, BH Ginis, I Thies, RS Amit, M Lyons, I Condie, BG Itskovitz-Eldor, J Rao, MS Puri, RK TI Gene expression in human embryonic stem cell lines: unique molecular signature SO BLOOD LA English DT Article ID ZINC-FINGER PROTEIN; IN-VITRO; DIFFERENTIATION; MICROARRAY; PLURIPOTENCY; NEURONS; PRECURSORS; PROGRAMS; CLONING; NANOG AB Human embryonic stem (huES) cells have the ability to differentiate into a variety of cell lineages and potentially provide a source of differentiated cells for many therapeutic uses. However, little is known about the mechanism of differentiation of huES cells and factors regulating cell development. We have used high-quality microarrays containing 16 659 seventy-base pair oligonucleotides to examine gene expression in 6 of the 11 available huES cell lines. Expression was compared against pooled RNA from multiple tissues (universal RNA) and genes enriched in huES cells were identified. All 6 cell lines expressed multiple markers of the undifferentiated state and shared significant homology in gene expression (overall similarity coefficient > 0.85). A common subset of 92 genes was identified that included Nanog, GTCM-1, connexin 43 (GJA1), oct-4, and TDGF1 (cripto). Gene expression was confirmed by a variety of techniques including comparison with databases, reverse transcriptase-polymerase chain reaction, focused cDNA microarrays, and immunocytochemistry. Comparison with published "sternness" genes revealed a limited overlap, suggesting little similarity with other stem cell populations. Several novel ES cell-specific expressed sequence tags were identified and mapped to the human genome. These results represent the first detailed characterization of undifferentiated huES cells and provide a unique set of markers to profile and better understand the biology of huES cells. C1 NIH, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,Food & Drug Adm, Bethesda, MD 20892 USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. Geron Corp, Menlo Pk, CA USA. BresaGen Inc, Athens, GA USA. Univ Georgia, Dept Genet, Athens, GA 30602 USA. Rambam Med Ctr, Dept Obstet & Gynecol, IL-31096 Haifa, Israel. Fac Med, Haifa, Israel. RP Puri, RK (reprint author), NIH, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,Food & Drug Adm, Bldg 29B,Rm 2NN22,29 Lincoln Dr, Bethesda, MD 20892 USA. EM raomah@grc.nia.nih.gov FU NIAMS NIH HHS [PAR-02-023] NR 42 TC 284 Z9 304 U1 1 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2004 VL 103 IS 8 BP 2956 EP 2964 DI 10.1182/blood-2003-09-3314 PG 9 WC Hematology SC Hematology GA 830ZU UT WOS:000222163500025 PM 15070671 ER PT J AU Twaddle, NC McDaniel, LP da Costa, GG Churchwell, MI Belanda, FA Doerge, DR AF Twaddle, NC McDaniel, LP da Costa, GG Churchwell, MI Belanda, FA Doerge, DR TI Determination of acrylamide and glycidamide serum toxicokinetics in B6C3F(1) mice using LC-ES/MS/MS SO CANCER LETTERS LA English DT Article DE acrylamide; glycidamide; mass spectrometry; toxicokinetics ID HEMOGLOBIN ADDUCTS; MASS-SPECTROMETRY; MAILLARD REACTION; RAT; METABOLISM; MOUSE; INTRAPERITONEAL; ACRYLONITRILE; EXPOSURE; WORKERS AB Acrylamide (AA) is a well-studied industrial toxicant; however, recent findings of AA at ppm levels in cooked starchy foods have refocused attention on the potential for neurotoxicity, germ cell mutagenicity, and carcinogenicity from AA. Oxidative metabolism of AA to glycidamide (GA) in experimental animals has previously been linked with many toxic effects of AA exposure. We report a new sensitive and selective analytical method, based on LC with electrospray tandem mass spectrometry, for the quantification of AA and GA in serum and its application to a preliminary toxicokinetic evaluation of AA and GA in adult 1360171 mice following oral administration of AA. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-1049001 Lisbon, Portugal. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM ddoerge@nctr.fda.gov NR 30 TC 47 Z9 47 U1 0 U2 7 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 APR 15 PY 2004 VL 207 IS 1 BP 9 EP 17 DI 10.1016/j.canlet.2003.10.017 PG 9 WC Oncology SC Oncology GA 813UI UT WOS:000220931600002 PM 15050729 ER PT J AU Chou, MW Yan, J Nichols, J Xia, QS Beland, FA Chan, PC Fu, PP AF Chou, MW Yan, J Nichols, J Xia, QS Beland, FA Chan, PC Fu, PP TI Correlation of DNA adduct formation and riddelliine-induced liver tumorigenesis in F344 rats and B6C3F(1) mice (vol 193, pg 119, 2003) SO CANCER LETTERS LA English DT Correction ID CARCINOGENIC ACTIVITY; PYRROLIZIDINE ALKALOIDS; CELL SPECIFICITY; HEPATIC-TUMORS; IN-VIVO; 2-ACETYLAMINOFLUORENE; HEPATOCYTES; INDUCTION; REPAIR; HONEY AB The Publisher regrets that in the original printing of the above-mentioned paper, the citations to the references were missing on pages 119, 122 and 123 of the printed paper. The missing references are now included in the following article. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Inst Environm Hlth Res, Res Triangle Pk, NC 22709 USA. RP Chou, MW (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM mchou@nctr.fda.gov NR 24 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD APR 15 PY 2004 VL 207 IS 1 BP 117 EP + DI 10.1016/j.canlet.2003.11.004 PG 8 WC Oncology SC Oncology GA 813UI UT WOS:000220931600014 ER PT J AU Fleischer, R Boxwell, D Sherman, KE AF Fleischer, R Boxwell, D Sherman, KE TI Nucleoside analogues and mitochondrial toxicity SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID RIBAVIRIN AB An evaluation of the US Food and Drug Administration's Adverse Event Reporting System identified that patients coinfected with human immunodeficiency virus and chronic hepatitis C virus who were treated with a regimen of ribavirin and didanosine, with or without stavudine, were at increased risk for events associated with mitochondrial toxicity, including fatal hepatic failure, peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/ lactic acidosis. In response, the US product labels for didanosine and ribavirin have been revised to caution clinicians against coadministration of these drugs. C1 US FDA, Div Antiviral Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Off Drug Safety, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Univ Cincinnati, Coll Med, Dept Internal Med, Div Digest Dis, Cincinnati, OH 45221 USA. RP Fleischer, R (reprint author), US FDA, Div Antiviral Drug Prod, Ctr Drug Evaluat & Res, HFD-530, Rockville, MD 20857 USA. EM fleischerr@cder.fda.gov NR 5 TC 57 Z9 58 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 APR 15 PY 2004 VL 38 IS 8 BP E79 EP E80 DI 10.1086/383151 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 810WU UT WOS:000220735200034 PM 15095236 ER PT J AU Doublet, B Carattoli, A Whichard, JM White, DG Baucheron, S Chaslus-Dancla, E Cloeckaert, A AF Doublet, B Carattoli, A Whichard, JM White, DG Baucheron, S Chaslus-Dancla, E Cloeckaert, A TI Plasmid-mediated florfenicol and ceftriaxone resistance encoded by the floR and bla(CMY-2) genes in Salmonella enterica serovars Typhimurium and Newport isolated in the United States SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE Salmonella; multidrug resistance; phenicols; cephalosporins; plasmid; conjugation ID ESCHERICHIA-COLI; BETA-LACTAMASE; STRAINS; ANIMALS; IDENTIFICATION; SEQUENCE; CMY-2 AB Multidrug resistance plasmids carrying the bla(CMY-2) gene have been identified in Salmonella enterica serovars Typhimurium and Newport from the United States. This gene confers decreased susceptibility to ceftriaxone, and is most often found in strains with concomitant resistance to ampicillin, chloramphenicol, streptomycin, sulfamethoxazole and tetracycline. The bla(CMY-2)-carrying plasmids studied here were shown to also carry the florfenicol resistance gene, floR, on a genetic structure previously identified in Escherichia coli plasmids in Europe. These data indicate that the use of different antimicrobial agents, including phenicols, may serve to maintain multidrug resistance plasmids on which extended-spectrum cephalosporin resistance determinants co-exist with other resistance genes in Salmonella. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Microbiological Societies. C1 INRA, Unite Bioagresseurs, F-37380 Nouzilly, France. Ist Super Sanita, Batteriol & Micol Med Lab, I-00161 Rome, Italy. CDCP, Natl Ctr Infect Dis, Div Bacterial & Mycot Dis, Foodborne & Diarrheal Dis Branch, Atlanta, GA 30333 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Cloeckaert, A (reprint author), INRA, Unite Bioagresseurs, F-37380 Nouzilly, France. EM cloeckae@tours.inra.fr NR 20 TC 27 Z9 30 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD APR 15 PY 2004 VL 233 IS 2 BP 301 EP 305 DI 10.1016/j.femsle.2004.02.023 PG 5 WC Microbiology SC Microbiology GA 812BQ UT WOS:000220815400017 PM 15063500 ER PT J AU Baylor, MS Johann-Liang, R AF Baylor, MS Johann-Liang, R TI Hepatotoxicity associated with nevirapine use SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Letter C1 US FDA, Div Antiviral Drug Prod, Rockville, MD 20857 USA. RP Baylor, MS (reprint author), US FDA, Div Antiviral Drug Prod, Rockville, MD 20857 USA. NR 9 TC 70 Z9 77 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR 15 PY 2004 VL 35 IS 5 BP 538 EP 539 DI 10.1097/00126334-200404150-00014 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 809JC UT WOS:000220632000014 PM 15021321 ER PT J AU Pogribny, IP James, SJ Jernigan, S Pogribna, M AF Pogribny, IP James, SJ Jernigan, S Pogribna, M TI Genomic hypomethylation is specific for preneoplastic liver in folate/methyl deficient rats and does not occur in non-target tissues SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE DNA hypomethylation; DNA methyltransferase; rat folate/methyl deficiency ID PERICENTROMERIC SATELLITE REGIONS; HUMAN HEPATOCELLULAR-CARCINOMA; CPG-BINDING PROTEINS; DNA-METHYLTRANSFERASE; METHYLATION PATTERNS; HUMAN HEPATOCARCINOGENESIS; MESSENGER-RNA; CANCER-CELLS; P53 GENE; EXPRESSION AB Chronic dietary insufficiency of the lipotropic nutrients choline and methionine is hepatocarcinogenic in male rats and certain mouse strains. Despite the fact that DNA hypomethylation is a hallmark of most cancer genomes, the tissue-specific consequences of this alternation with respect to tumorigenesis remain to be determined. In the present study, the folate/methyl deficient model of multistage hepatocarcinogenesis was used to evaluate in vivo alterations in DNA methylation in the liver, the carcinogenesis target tissue, and in non-target tissues, including pancreas, spleen, kidney, and thymus, of male F344 rats. By utilizing the HpaII/MspI-based cytosine extension assay, we demonstrated that the percent of CpG sites that lost methyl groups on both strands progressively increased in liver tissue after 9, 18, and 36 weeks of folate/methyl deficiency. The endogenous activity of DNA methyltransferase in liver of rats fed with folate/methyl deficient diet for the 36-week period Gradually increased with time. In contrast, non-target tissues displayed no changes in DNA methylation level or activity of DNA methyltransferase. The failure of DNA methyltransferase to restore and maintain DNA methylation patterns in preneoplastic liver tissue may lead to the establishment of tumor-specific DNA methylation and DNA methyltransferase profiles that are not expressed in normal liver. These results provide additional information about alterations in DNA methylation during early preneoplastic stages of carcinogenesis. They also demonstrate that DNA hypomethylation is localized to tissue that undergoes carcinogenesis, and is not altered in non-target tissues. (C) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. RP Pogribny, IP (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM ipogribny@nctr.fda.gov NR 31 TC 81 Z9 83 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 APR 14 PY 2004 VL 548 IS 1-2 BP 53 EP 59 DI 10.1016/j.mrfmmm.2003.12.014 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 814BA UT WOS:000220949000007 PM 15063136 ER PT J AU Kovalchuk, O Burke, P Besplug, J Slovack, M Filkowski, J Pogribny, I AF Kovalchuk, O Burke, P Besplug, J Slovack, M Filkowski, J Pogribny, I TI Methylation changes in muscle and liver tissues of male and female mice exposed to acute and chronic low-dose X-ray-irradiation SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE ionizing radiation; low doses; global genome methylation; promoter methylation; gene expression; p16(INK alpha); MGMT ID INDUCED GENOMIC INSTABILITY; IONIZING-RADIATION; DNA METHYLATION; PROMOTER HYPERMETHYLATION; CHERNOBYL ACCIDENT; TUMOR-SUPPRESSOR; MOUSE-TISSUES; MUTATION-RATE; CPG ISLANDS; GENE AB The biological and genetic effects of chronic low-dose radiation (LDR) exposure and its relationship to carcinogenesis have received a lot of attention in the recent years. For example, radiation-induced genome instability, which is thought to be a precursor of tumorogenesis, was shown to have a transgenerational nature. This indicates a possible involvement of epigenetic mechanisms in LDR-induced genome instability. Genomic DNA methylation is one of the most important epigenetic mechanisms. Existing data on radiation effects on DNA methylation patterns is limited, and no one has specifically studied the effects of the LDR. We report the first study of the effects of whole-body LDR exposure on global genome methylation in muscle and liver tissues of male and female mice. In parallel, we evaluated changes in promoter methylation and expression of the tumor suppressor gene p16(INKa) and DNA repair gene O-6-methylguanine-DNA methyltransferase (MGMT). We observed different patterns of radiation-induced global genome DNA methylation in the liver and muscle of exposed males and females. We also found sex and tissue-specific differences in p16(INKa) promoter methylation upon LDR exposure. In male liver tissue, p16(INKa) promoter methylation was more pronounced than in female tissue. In contrast, no significant radiation-induced changes in p16(INKa) promoter methylation were noted in the muscle tissue of exposed males and females. Radiation also did not significantly affect methylation status of MGMT promoter. We also observed substantial sex differences in acute and chronic radiation-induced expression of p16(INKa) and MGMT genes. Another important outcome of our study was the fact that chronic low-dose radiation exposure proved to be a more potent inducer of epigenetic effects than the acute exposure. This supports previous findings that chronic exposure leads to greater genome destabilization than acute exposure. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Kovalchuk, O (reprint author), Univ Lethbridge, Dept Biol Sci, 4401 Univ Dr, Lethbridge, AB T1K 3M4, Canada. EM olga.kovalchuk@uleth.ca NR 40 TC 58 Z9 70 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD APR 14 PY 2004 VL 548 IS 1-2 BP 75 EP 84 DI 10.1016/j.mrfmmm.2003.12.01 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 814BA UT WOS:000220949000009 PM 15063138 ER PT J AU Auch, CJ Saha, RN Sheikh, FG Liu, XJ Jacobs, BL Pahan, K AF Auch, CJ Saha, RN Sheikh, FG Liu, XJ Jacobs, BL Pahan, K TI Role of protein kinase R in double-stranded RNA-induced expression of nitric oxide synthase in human astroglia SO FEBS LETTERS LA English DT Article DE double-stranded RNA; human astroglia; inducible nitric oxide synthase; nuclear factor-kappa B; CCAAT/enhancer-binding protein beta ID CENTRAL-NERVOUS-SYSTEM; HUMAN CORONAVIRUS OC43; NF-KAPPA-B; HUMAN ASTROCYTES; ACTIVATION; INDUCTION; INFECTION; GENE; PKR; INHIBITION AB Environmental factor(s), such as viral infection, has been implicated as one of the triggering events leading to neuro-inflammation in multiple sclerosis. This study underlines the importance of double-stranded RNA (dsRNA), the active component of a viral infection, in inducing the expression of inducible nitric oxide synthase (iNOS) in human astroglia. DsRNA in the form of synthetic polyinosinic-polycytidylic acid (poly IC) induced expression of iNOS and iNOS promoter-driven luciferase activity through activation of nuclear factor (NF)-kappaB and CCAAT/enhancer-binding proteinbeta (C/EBPbeta). In addition, we show that inhibitors of protein kinase R attenuated iNOS by suppressing the activation of NF-kappaB but not C/EBPbeta. In contrast, knock down of p38 mitogen-activated protein kinase (MAPK) attenuated iNOS by suppressing the activation of C/EBPbeta but not NF-kappaB. This study delineates a novel role of dsRNA in inducing the expression of iNOS through dsRNA-activated protein kinase (PKR)-mediated activation of NF-kappaB and p38-mediated activation of C/EBPbeta in human astroglia that may participate in virus-induced neurological abnormalities. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 Univ Nebraska, Med Ctr, Dept Oral Biol, Lincoln, NE 68583 USA. US FDA, Div Therapeut Prot, Bethesda, MD 20892 USA. Arizona State Univ, Dept Microbiol, Tempe, AZ 85287 USA. RP Pahan, K (reprint author), Univ Nebraska, Med Ctr, Dept Oral Biol, 40th & Holdrege, Lincoln, NE 68583 USA. EM kpahan@unmc.edu RI Saha, Ramendra/C-7000-2014 OI Saha, Ramendra/0000-0002-5494-2584 FU NINDS NIH HHS [R01 NS039940-03, NS39940, R01 NS039940] NR 28 TC 33 Z9 33 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 9 PY 2004 VL 563 IS 1-3 BP 223 EP 228 DI 10.1016/S0014-5793(04)00302-3 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 811LK UT WOS:000220773200042 PM 15063753 ER PT J AU Hasan, RK Wulfkuhle, JD Liotta, LA Petricoin, EF AF Hasan, RK Wulfkuhle, JD Liotta, LA Petricoin, EF TI Molecular technologies for personalized cancer management SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PHASE PROTEIN MICROARRAYS; BREAST-CANCER; OVARIAN-CANCER; CHEMOTHERAPY; SURVIVAL; PROGRESSION; MUTATIONS; DNA C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. NCI, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20014 USA. RP Hasan, RK (reprint author), Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. NR 20 TC 3 Z9 3 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 7 PY 2004 VL 291 IS 13 BP 1644 EP 1645 DI 10.1001/jama.291.13.1644 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 809PQ UT WOS:000220649000033 PM 15069056 ER PT J AU Andrzejewski, D Roach, JAG Gay, ML Musser, SM AF Andrzejewski, D Roach, JAG Gay, ML Musser, SM TI Analysis of coffee for the presence of acrylamide by LC-MS/MS SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE acrylamide; LC-MS/MS; coffee; FDA ID MASS-SPECTROMETRY; MAILLARD REACTION; HEATED FOODS; CHROMATOGRAPHY AB A variety of popular instant, ground, and brewed coffees were analyzed using a modified liquid chromatography-tandem mass spectrometry (LC-MS/MS) method specifically developed for the determination of acrylamide in foods. Coffee test portions were spiked with C-13(3)-labeled acrylamide as an internal standard prior to their extraction and cleanup. Ground coffees (1 g) and instant coffees (0.5 g) were extracted by shaking with 9 mL of water for 20 min. Brewed coffee test portions (9 mL) were taken through the cleanup procedure without further dilution with extraction solvent. Coffee test portions were cleaned up by passing 1.5 mL first through an Oasis HLB (hydrophilic/lipophilic copolymer sorbent) solid phase extraction (SPE) cartridge and then a Bond Elut-Accucat (cation and anion exchange sorbent) SPE cartridge. The cleaned up extracts were analyzed by positive ion electrospray LC-MS/MS. The MS/MS data was used to detect, confirm, and quantitate acrylamide. The limit of quantitation of the method was 10 ng/g for ground and instant coffees and 1.0 ng/mL for brewed coffee. The levels of acrylamide ranged from 45 to 374 ng/g in unbrewed coffee grounds, from 172 to 539 ng/g in instant coffee crystals, and from 6 to 16 ng/mL in brewed coffee. C1 US FDA, Ctr Food Safety & Appl Nutr, Instrumentat & Biophys Branch, College Pk, MD 20740 USA. RP Andrzejewski, D (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Instrumentat & Biophys Branch, HFS-717,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM dandrzej@cfsan.fda.gov NR 18 TC 100 Z9 104 U1 1 U2 30 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD APR 7 PY 2004 VL 52 IS 7 BP 1996 EP 2002 DI 10.1021/jf0349634 PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 809KZ UT WOS:000220636900033 PM 15053542 ER PT J AU Padayatty, SJ Sun, H Wang, YH Riordan, HD Hewitt, SM Katz, A Wesley, RA Levine, M AF Padayatty, SJ Sun, H Wang, YH Riordan, HD Hewitt, SM Katz, A Wesley, RA Levine, M TI Vitamin C pharmacokinetics: Implications for oral and intravenous use SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID RECOMMENDED DIETARY ALLOWANCE; ASCORBIC-ACID; DISEASE PREVENTION; ADVANCED CANCER; CYTOTOXICITY; VOLUNTEERS; TRIAL AB Background: Vitamin C at high concentrations is toxic to cancer cells in vitro. Early clinical studies of vitamin C in patients with terminal cancer suggested clinical benefit, but 2 double-blind, placebo-controlled trials showed none. However, these studies used different routes of administration. Objective: To determine whether plasma vitamin C concentrations vary substantially with the route of administration. Design: Dose concentratior. studies and pharmacokinetic modeling. Setting: Academic medical center. Participants: 17 healthy hospitalized volunteers. Measurements: Vitamin C plasma and urine concentrations were measured after administration of oral and intravenous doses at a dose range of 0.015 to 1.25 g, and plasma concentrations were calculated for a dose range of 1 to 100 g. Results: Peak plasma vitamin C concentrations were higher after administration of intravenous doses than after administration of oral doses (P < 0.001), and the difference increased according to dose. Vitamin C at a dose of 1.25 g administered orally produced mean ( +/- SD) peak plasma concentrations of 134.8 +/- 20.6 mumol/L compared with 885 +/- 201.2 mumol/L for intravenous administration. For the maximum tolerated oral dose of 3 g every 4 hours, pharmacokinetic modeling predicted peak plasma vitamin C concentrations of 220 mumol/L and 13 400 mumol/L for a 50-g intravenous dose. Peak predicted urine concentrations of vitamin C from intravenous administration were 140-fold higher than those from maximum oral doses. Limitations: Patient data are not available to confirm pharmacokinetic modeling at high doses and in patients with cancer. Conclusions: oral vitamin C produces plasma concentrations that are tightly controlled. Only intravenous administration of vitamin C produces high plasma and urine concentrations that might have antitumor activity. Because efficacy of vitamin C treatment cannot be judged from clinical trials that use only oral dosing, the role of vitamin C in cancer treatment should be re-evaluated. C1 NIH, Mol & Clin Nutr Sect, Bethesda, MD 20892 USA. NCI, NIDDKD, Bethesda, MD 20892 USA. NIH, Clin Ctr, Bethesda, MD 20892 USA. Food & Drug Adm, Rockville, MD USA. Biocommun Res Inst, Wichita, KS USA. RP Levine, M (reprint author), NIH, Mol & Clin Nutr Sect, Bldg 10,Room 4D52-MSC 1372, Bethesda, MD 20892 USA. RI Padayatty, Sebastian/A-8581-2012; OI Padayatty, Sebastian/0000-0001-8758-3170; Hewitt, Stephen/0000-0001-8283-1788 FU NIDDK NIH HHS [Z01 DK 54506] NR 20 TC 245 Z9 255 U1 4 U2 20 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 6 PY 2004 VL 140 IS 7 BP 533 EP 537 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 808OE UT WOS:000220577600005 PM 15068981 ER PT J AU Powers, JH Higgins, KM AF Powers, JH Higgins, KM TI Itraconazole versus fluconazole for antifungal prophylaxis SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20850 USA. RP Powers, JH (reprint author), US FDA, Rockville, MD 20850 USA. NR 3 TC 4 Z9 4 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 6 PY 2004 VL 140 IS 7 BP 580 EP 580 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 808OE UT WOS:000220577600017 PM 15068992 ER PT J AU Cieslak, J Grajkowski, A Livengood, V Beaucage, SL AF Cieslak, J Grajkowski, A Livengood, V Beaucage, SL TI Thermolytic 4-methylthio-1-butyl group for phosphate/thiophosphate protection in solid-phase synthesis of DNA oligonucleotides SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID SULFUR-TRANSFER REAGENT; 3H-1,2-BENZODITHIOL-3-ONE 1,1-DIOXIDE; OLIGODEOXYRIBONUCLEOTIDE SYNTHESIS; PHOSPHATE PROTECTION; OXIDATION; PHOSPHITES; CHEMISTRY AB The thermolabile 4-methylthio-1-butyl phosphate/thiophosphate protecting group for DNA oligonucleotides has been investigated for its potential application to a "heat-driven" process for either oligonucleotide synthesis on diagnostic microarrays or, oppositely, to the large-scale preparation of therapeutic oligonucleotides. The preparation of phosphoramidites 10a-d is straightforward, and the incorporation of these amidites into oligonucleotides via solid-phase techniques proceeds as efficiently as that achieved with 2-cyanoethyl deoxyribonucleoside phosphoramidites. The versatility of the 4-methylthio-1-butyl phosphate/thiophosphate protecting group is exemplified by its facile removal from oligonucleotides upon heating for 30 min at 55 degreesC in an aqueous buffer under neutral conditions or within 2 h at 55 degreesC in concentrated NH4OH. The deprotection reaction occurs through an intramolecular cyclodeesterification mechanism leading to the formation of sulfonium salt 18. When mixed with deoxyribonucleosides and N-protected 2'-deoxyribonucleosides or with a model phosphorothioate diester under conditions approximating those of large-scale (>50 mmol) oligonucleotide deprotection reactions, the salt 18 did not significantly alter DNA nucleobases or desulfurize the phosphorothioate diester model to an appreciable extent. C1 US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Beaucage, SL (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM beaucage@cber.fda.gov NR 28 TC 16 Z9 16 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD APR 2 PY 2004 VL 69 IS 7 BP 2509 EP 2515 DI 10.1021/jo035861f PG 7 WC Chemistry, Organic SC Chemistry GA 807MS UT WOS:000220506200040 PM 15049652 ER PT J AU Dodd, LE Wagner, RF Armato, SG McNitt-Gray, MF Beiden, S Chan, HP Gur, D McLennan, G Metz, CE Petrick, N Sahiner, B Sayre, J AF Dodd, LE Wagner, RF Armato, SG McNitt-Gray, MF Beiden, S Chan, HP Gur, D McLennan, G Metz, CE Petrick, N Sahiner, B Sayre, J CA Lung Image Database Consortium Res TI Assessment methodologies and statistical issues for computer-aided diagnosis of lung nodules in computed tomography: Contemporary research topics relevant to the lung image database consortium SO ACADEMIC RADIOLOGY LA English DT Article DE computer-aided diagnosis (CAD); database development; lung cancer; lung nodule; MRMC; ROC ID OPERATING CHARACTERISTIC ANALYSIS; OF-VARIANCE MODELS; FINITE-SAMPLE SIZE; OBSERVER-PERFORMANCE; ROC ANALYSIS; CONDITIONAL DEPENDENCE; MULTIPLE-ABNORMALITIES; REGRESSION METHODOLOGY; DISEASE VERIFICATION; SELECTION BIAS AB Cancer of the lung and bronchus is the leading fatal malignancy in the United States. Five-year survival is low, but treatment of early stage disease considerably improves chances of survival. Advances in multidetector-row computed tomography technology provide detection of smaller lung nodules and offer a potentially effective screening tool. The large number of images per exam, however, requires considerable radiologist time for interpretation and is an impediment to clinical throughput. Thus, computer-aided diagnosis (CAD) methods are needed to assist radiologists with their decision making. To promote the development of CAD methods, the National Cancer Institute formed the Lung Image Database Consortium (LIDC). The LIDC is charged with developing the consensus and standards necessary to create an image database of multidetector-row computed tomography lung images as a resource for CAD researchers. To develop such a prospective database, its potential uses must be anticipated. The ultimate applications will influence the information that must be included along with the images, the relevant measures of algorithm performance, and the number of required images. In this article we outline assessment methodologies and statistical issues as they relate to several potential uses of the LIDC database. We review methods for performance assessment and discuss issues of defining "truth" as well as the complications that arise when truth information is not available. We also discuss issues about sizing and populating a database. (C) AUR, 2004. C1 NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. Univ Calif Los Angeles, Dept Radiol, David Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA. Univ Iowa, Dept Med, Iowa City, IA 52242 USA. Univ Calif Los Angeles, Dept Biostat, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Radiol, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Radiol, Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Biostat, Sch Med, Los Angeles, CA 90024 USA. RP NCI, Biometr Res Branch, Div Canc Treatment & Diag, 6130 Execut Blvd,MSC 7434, Bethesda, MD 20892 USA. EM doddl@mail.nih.gov FU NCI NIH HHS [U01CA091103, U01CA091099, U01CA091090, U01CA091100, U01CA091085] NR 85 TC 51 Z9 52 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD APR PY 2004 VL 11 IS 4 BP 462 EP 475 DI 10.1016/S1076-6332(03)00814-6 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 807HC UT WOS:000220491600011 PM 15109018 ER PT J AU Haylock, PJ AF Haylock, PJ TI Nurses against tobacco SO AMERICAN JOURNAL OF NURSING LA English DT Editorial Material C1 Univ Texas, Med Branch, Sch Nursing, Galveston, TX 77550 USA. US FDA, Oncol Drugs Advisory Committee, Rockville, MD 20857 USA. RP Haylock, PJ (reprint author), Univ Texas, Med Branch, Sch Nursing, Galveston, TX 77550 USA. EM pjhaylock@indian-creek.net NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD APR PY 2004 VL 104 IS 4 BP 13 EP 13 PG 1 WC Nursing SC Nursing GA 812ZY UT WOS:000220878600002 PM 15171109 ER PT J AU Cantril, CA Haylock, PJ AF Cantril, CA Haylock, PJ TI Tumor lysis syndrome - Prevention and early defection are crucial in caring for patients with cancer SO AMERICAN JOURNAL OF NURSING LA English DT Article ID LYMPHOMA C1 Montana State Univ, Sch Nursing, Bozeman, MT 59717 USA. Univ Texas, Med Branch, Sch Nursing, Galveston, TX 77550 USA. US FDA, Oncol Drugs Advisory Committee, Rockville, MD 20857 USA. NR 9 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD APR PY 2004 VL 104 IS 4 BP 49 EP 52 PG 4 WC Nursing SC Nursing GA 812ZY UT WOS:000220878600024 PM 15171115 ER PT J AU Lachenbruch, PA Rosenberg, AS Bonvini, E Cavaille-Coll, MW Colvin, RB AF Lachenbruch, PA Rosenberg, AS Bonvini, E Cavaille-Coll, MW Colvin, RB TI Biomarkers and surrogate endpoints in renal transplantation: Present status and considerations for clinical trial design SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Review DE allograft rejection; predictive variables; surrogate endpoints ID CHRONIC ALLOGRAFT-REJECTION; KIDNEY-TRANSPLANTATION; QUANTITATIVE DETECTION; HUMORAL REJECTION; MESSENGER-RNA; EXPRESSION; CLASSIFICATION; BIOPSIES; REPRODUCIBILITY; CAPILLARIES AB Of major importance in clinical trials is the ability to predict individual patient outcome or endpoints using biomarkers, also known as variables or predictors, in as safe, efficient, and accurate a manner as possible. This review addresses the concepts and possible strategies for use of predictor and surrogate biomarkers in the design of clinical trials in renal transplantation. The statistical concepts apply equally well to other organ grafts. C1 US FDA, Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Div Therapeut Prot, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Div Biostat, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Div Special Pathogen & Immunol Drug Prod, Rockville, MD USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Rosenberg, AS (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Div Therapeut Prot, Bethesda, MD 20892 USA. EM rosenberg@cber.fda.gov NR 31 TC 49 Z9 50 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2004 VL 4 IS 4 BP 451 EP 457 DI 10.1111/j.1600-6143.2004.00386.x PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA 810YZ UT WOS:000220740900001 PM 15023136 ER PT J AU Jiang, J Chan, TC Temenak, JJ Dasch, GA Ching, WM Richards, AL AF Jiang, J Chan, TC Temenak, JJ Dasch, GA Ching, WM Richards, AL TI Development of a quantitative real-time polymerase chain reaction assay specific for Orientia tsutsugamushi SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID LINKED IMMUNOSORBENT ASSAYS; PROTEIN ANTIGEN R56; SCRUB TYPHUS; RICKETTSIA-TSUTSUGAMUSHI; FLOW ASSAY; ANTIBODIES; DIAGNOSIS; AMPLIFICATION; EXPRESSION; CHIGGERS AB Two specific and sensitive polymerase chain reaction (PCR) assays were developed to detect and quantitate Orientia tsutsugamushi, the agent of scrub typhus, using a portion of the 47-kD outer membrane protein antigen/ high temperature requirement A gene as the target. A selected 47-kD protein gene primer pair amplified a 118-basepair fragment from all 26 strains of O. tsutsugamushi evaluated, but it did not produce amplicons when 17 Rickettsia and 18 less-related bacterial nucleic acid extracts were tested. Similar agent specificity for the real-time PCR assay, which used the same primers and a 31-basepair fluorescent probe, was demonstrated. This sensitive and quantitative assay determination of the content of O. tsutsugamushi nucleic acid used a plasmid containing the entire 47-kD gene from the Kato strain as a standard. Enumeration of the copies of O. tsutsugamushi DNA extracted from infected tissues from mice and monkeys following experimental infection with Orientia showed 27-5,552 copies/muL of mouse blood, 14,448-86,012 copies/muL of mouse liver/spleen homogenate, and 3-21 copies/muL of monkey blood. C1 USN, Rickettsial Dis Dept, Med Res Ctr, Silver Spring, MD 20910 USA. US FDA, Div Vaccines & Related Prod Applicat, Rockville, MD 20857 USA. Ctr Dis Control & Prevent, Div Viral & Rickettsial Dis, Atlanta, GA USA. Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. RP Jiang, J (reprint author), USN, Rickettsial Dis Dept, Med Res Ctr, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. EM JiangJ@nmrc.navy.mil; ChanC@nmrc.navy.mil NR 44 TC 97 Z9 105 U1 0 U2 6 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 APR PY 2004 VL 70 IS 4 BP 351 EP 356 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 814RI UT WOS:000220991400003 PM 15100446 ER PT J AU Xing, Y He, ZM Warnock, JN Hilbert, SL Yoganathan, AP AF Xing, Y He, ZM Warnock, JN Hilbert, SL Yoganathan, AP TI Effects of constant static pressure on the biological properties of porcine aortic valve leaflets SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE aortic valve leaflets; collagen synthesis; tissue engineering ID EXTRACELLULAR-MATRIX SYNTHESIS; SMOOTH-MUSCLE CELLS; HUMAN HEART-VALVES; INTERSTITIAL-CELLS; HYDROSTATIC-PRESSURE; HYPERTENSIVE RATS; ENDOTHELIAL-CELLS; MESSENGER-RNA; EXPRESSION; METABOLISM AB An understanding of how mechanical forces impact cells within valve leaflets would greatly benefit the development of a tissue-engineered heart valve. In this study, the effect of constant ambient pressure on the biological properties of heart valve leaflets was evaluated using a custom-designed pressure system. Native porcine aortic valve leaflets were exposed to static pressures of 100, 140, or 170 mmHg for 48 h. Collagen synthesis, DNA synthesis, sulfated glycoaminoglycan (sGAG) synthesis, alpha-SMC actin expression, and extracellular matrix (ECM) structure were examined. Results showed that elevated pressure caused an increase in collagen synthesis. This increase was not statistically significant at 100 mmHg, but at 140 mmHg and 170 mmHg collagen synthesis increased by 37.5 and 90%, respectively. No significant difference in DNA or sGAG synthesis was observed at elevated pressures, with the exception that DNA synthesis at 100 mmHg decreased. A notable decline in a-SMC actin was observed over the course of the experiments although no significant difference was observed between the pressure and control groups. It was concluded that elevated pressure caused a proportional increase in collagen synthesis of porcine aortic valve leaflets, but was unable to preserve alpha-SMC actin immunoreactive cells. C1 Georgia Inst Technol, Wallace H Coulter Sch Biomed Engn, Atlanta, GA 30332 USA. Georgia Inst Technol, Bioengn Program, Sch Chem Engn, Atlanta, GA 30332 USA. Georgia Inst Technol, George W Woodruff Sch Mech Engn, Atlanta, GA 30332 USA. CDRH, Rockville, MD USA. RP Yoganathan, AP (reprint author), Georgia Inst Technol, Wallace H Coulter Sch Biomed Engn, 315 Ferst DR,Suite 1121, Atlanta, GA 30332 USA. EM ajit.yoganathan@bme.gatech.edu NR 23 TC 31 Z9 31 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD APR PY 2004 VL 32 IS 4 BP 555 EP 562 DI 10.1023/B:ABME.0000019175.12013.8f PG 8 WC Engineering, Biomedical SC Engineering GA 835FC UT WOS:000222465200006 PM 15117029 ER PT J AU Lu, JH Dveksler, G Kaplan, GG AF Lu, JH Dveksler, G Kaplan, GG TI Rescue of Hepatitis A virus from cDNA-transfected but not virion RNA-transfected mouse Ltk-cells SO ARCHIVES OF VIROLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; CAP-INDEPENDENT TRANSLATION; MONKEY KIDNEY-CELLS; WILD-TYPE VIRUS; CULTURE; ADAPTATION; MUTATIONS; GROWTH; REPLICATION; IDENTIFICATION AB Hepatitis A virus (HAV) has stringent replication requirements and a restricted host-range. Mouse Ltk-cells do not support growth of HAV upon infection or transfection of virion RNA. However, low levels of HAV were rescued from Ltk- cells transiently transfected with its infectious cDNA. Ltk- stable transfectants that expressed HAV antigens and produced infectious HAV were selected and termed Ltk-pJH15 cells. After a few serial passages, HAV became undetectable in the Ltk-pJH15 cells. Multiple rounds of single cell cloning of HAV antigen positive Ltk-pJH15 cells resulted in the isolation of clone E8 that produced higher levels of HAV for at least 5 passages. HAV produced in E8 cells was similar to the parental virus as shown by infectivity assays. Luciferase assays using a bi-cistronic construct containing the HAV 5' noncoding region showed similar levels of HAV IRES-dependent translation in Ltk- and Ltk-pJH15 cells, which suggested that HAV IRES-dependent translation was not a limiting factor for HAV growth in these cells. The availability of the Ltk-pHJ15 cells will allow the identification of cellular factors required for HAV growth, which could lead to the development of a mouse model to study pathogenesis of HAV. C1 US FDA, Ctr Biol Evaluat & Res, Hepatatis Lab, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. RP Kaplan, GG (reprint author), 8800 Rockville Pike,Bldg 29-NIH,Rm 225,HFM-325, Bethesda, MD 20892 USA. EM gk@helix.nih.gov NR 27 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PD APR PY 2004 VL 149 IS 4 BP 759 EP 772 DI 10.1007/s00705-003-0226-2 PG 14 WC Virology SC Virology GA 812NN UT WOS:000220846300007 PM 15045562 ER PT J AU Atreya, CD Kulkarni, S Mohan, KVK AF Atreya, CD Kulkarni, S Mohan, KVK TI Rubella virus P90 associates with the cytokinesis regulatory protein Citron-K kinase and the viral infection and constitutive expression of P90 protein both induce cell cycle arrest following S phase in cell culture SO ARCHIVES OF VIROLOGY LA English DT Article ID VIRUS-INDUCED APOPTOSIS; BINDING PROTEIN; RUBELLA; RHO; IDENTIFICATION; REPLICATION; INTERACTS; TARGET; RB AB In utero infection of developing fetus by Rubella virus (RV) causes cell division inhibition of critical precursor cells in organogenesis, CNS-associated birth defects and induction of apoptosis in cell culture. The underlying mechanisms of RV-induced congenital abnormalities are not known. Here, we identified a novel interaction between RV replicase P90 protein and a cytokinesis-regulatory protein, the Citron-K kinase (CK), in a yeast two-hybrid cDNA library screen. Aberrations in cytokinesis and subsequent apoptosis do occur in specific cell types when the CK gene is knocked out or, its regulatory function is perturbed. Our analysis found that full-length P90 binds CK and in RV-infected cells P90 colocalizes with CK in the cytoplasm. Furthermore, during RN infection as well as cellular expression of P90 alone, we identified a discrete subpopulation of cells containing 4N DNA content, indicating that these cells are arrested in the cell cycle following S phase, suggesting that cellular expression of viral P90 during RV infection perturbs cytokinesis. Previous reports by others established that RV infection leads to apoptosis in cell culture. These observations together taken to the fetal organogenesis level, favor the idea that RV P90, by binding to cellular CK, invokes cell cycle aberrations resulting in the cell-and organ-specific growth inhibition and programmed cell death during RV infection in utero, which commonly is referred to as RV-induced teratogenesis. C1 US FDA, Ctr Biol Evaluat & Res, Sect Viral Pathogenesis & Adverse React, Lab Pediat & Resp Viral Dis, Bethesda, MD 20892 USA. RP Atreya, CD (reprint author), US FDA, Ctr Biol Evaluat & Res, Sect Viral Pathogenesis & Adverse React, Lab Pediat & Resp Viral Dis, HFM-460,Bldg 29A,2C-11,NIH Campus,8800 Rockville, Bethesda, MD 20892 USA. EM Atreya@cber.fda.gov NR 31 TC 11 Z9 11 U1 1 U2 3 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PD APR PY 2004 VL 149 IS 4 BP 779 EP 789 DI 10.1007/s00705-003-0267-6 PG 11 WC Virology SC Virology GA 812NN UT WOS:000220846300009 PM 15045564 ER PT J AU Sung, KD Stern, NJ Hiett, KL AF Sung, KD Stern, NJ Hiett, KL TI Relationship of messenger RNA reverse transcriptase-polymerase chain reaction signal to Campylobacter spp. viability SO AVIAN DISEASES LA English DT Article DE Campylobacter; detection in production; poultry ID NON-CULTURABLE CAMPYLOBACTER; ESCHERICHIA-COLI; VIBRIO-CHOLERAE; SALMONELLA-ENTERITIDIS; UNITED-STATES; JEJUNI CELLS; RT-PCR; RECOVERY; AMPLIFICATION; ENVIRONMENT AB Discriminating viable from dead cells is of importance in the development of bacterial detection methods. A positive reverse transcriptase-polymerase chain reaction (RTPCR) amplification signal was tested as a potential predictor of chick colonization. Some researchers have suggested that the presence of messenger RNA (mRNA) may not correlate with cell viability. Chicken colonization by cells that have positive mRNA signal but that are noncultivable would provide a correlation in cell viability and persistence of mRNA. The role of a viable but noncultivable (VBNC) form of Campylobacter spp. for colonization of poultry could be verified by such an mRNA signal. The levels of four strains of Campylobacter spp., previously isolated from poultry feces, declined progressively over time, and loss of cultivability occurred after 6 to 7 wk incubation in phosphate-buffered saline (PBS) at 4 C. Cold-stored, noncultivable and heat-inactivated (60 C for 10 min) Campylobacter spp. produced inconsistent amplified products from RT-PCR assay, depending on the target transcripts and strains used, although all fresh cultures showed mRNA signals. For the most part, signals of mRNA species from VBNC and heat-killed Campylobacter spp. AH-1, AH-2, and CH-3 persisted. RT-PCR amplification of transcripts originating from the tkt and cmp genes and a 256-base pair amplicon (from a previously described putative haem-copper oxidase) provided consistent signals, whereas transcripts from the M gene did not. Presumed VBNC and heat-inactivated Campylobacter spp., which produced positive mRNA signal but was not cultivable by conventional culture-based methods, did not establish colonization in the intestine of chicks 7 days after challenge. These results lead us to question the correlation between mRNA durability with cell viability as well as the significance of the VBNC cells in environmental transmission of Campylobacter spp. C1 Russell Res Ctr, Poultry Microbiol Safety Res Unit, Athens, GA 30604 USA. Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Univ Georgia, Dept Food Sci & Technol, Athens, GA 30606 USA. RP Stern, NJ (reprint author), Russell Res Ctr, Poultry Microbiol Safety Res Unit, Athens, GA 30604 USA. NR 33 TC 7 Z9 7 U1 2 U2 5 PU AMER ASSOC AVIAN PATHOLOGISTS PI ATHENS PA 953 COLLEGE STATION RD, ATHENS, GA 30602-4875 USA SN 0005-2086 J9 AVIAN DIS JI Avian Dis. PD APR-JUN PY 2004 VL 48 IS 2 BP 254 EP 262 DI 10.1637/7062 PG 9 WC Veterinary Sciences SC Veterinary Sciences GA 937IF UT WOS:000229917100004 PM 15283412 ER PT J AU Acheson, DWK Luccioli, S AF Acheson, DWK Luccioli, S TI Mucosal immune responses SO BEST PRACTICE & RESEARCH IN CLINICAL GASTROENTEROLOGY LA English DT Article DE mucosal immunity; intestinal epithelial cells; food-borne pathogens; gut-associated lymphoid tissue; follicle associated epithelia ID INTESTINAL EPITHELIAL-CELLS; NF-KAPPA-B; HELICOBACTER-PYLORI; BACTERIAL TRANSLOCATION; LYMPHOCYTE-ACTIVATION; T-CELLS; LISTERIA-MONOCYTOGENES; ENTAMOEBA-HISTOLYTICA; GIARDIA-LAMBLIA; BRUGIA-MALAYI AB The host gastrointestinal tract is exposed to countless numbers of foreign antigens and has embedded a unique and complex network of immunological and non-immunological mechanisms, often termed the gastrointestinal 'mucosal barrier', to protect the host from potentially harmful pathogens while at the same time 'tolerating' other resident microbes to allow absorption and utilization of nutrients. Of the many important roles of this barrier, it is the distinct responsibility of the mucosal immune system to sample and discriminate between harmful and beneficial antigens and to prevent entry of food-borne pathogens through the gastrointestinal (GI) tract. This system comprises an immunological network termed the gut-associated lymphoid tissue (GALT) that consists of unique arrangements of B cells, T cells and phagocytes which sample luminal antigens through specialized epithelia termed the follicle associated epithelia (FAE) and orchestrate co-ordinated molecular responses between immune cells and other components of the mucosal barrier. Certain pathogens have developed ways to bypass and/or withstand defence by the mucosal immune system to establish disease in the host. Some 'opportunistic' pathogens (such as Clostridium difficile) take advantage of host or other factors (diet, stress, antibiotic use) which may alter or weaken the response of the immune system. Other pathogens have developed mechanisms for invading gastrointestinal epithelium and evading phagocytosis/destruction by immune system defences. Once cellular invasion occurs, host responses are activated to limit local mucosal damage and repel the foreign influence. Some pathogens (Shigella spp, parasites and viruses) primarily establish localized disease while others (Salmonella, Yersinia, Listeria) use the lymphatic system to enter organs or the bloodstream and cause more systemic illness. In some cases, pathogens (Helicobacter pylori and Salmonella typhi) colonize the GI tract or associated lymphoid structures for extended periods of time and these persistent pathogens may also be potential triggers for other chronic or inflammatory diseases, including inflammatory bowel disease and malignancies. The ability of certain pathogens to avoid or withstand the host's immune assault and/or utilize these host responses to their own advantage (i.e. enhance further colonization) will dictate the pathogen's success in promoting illness and furthering its own survival. C1 US FDA, CFSAN, DHSS, College Pk, MD 20740 USA. RP Acheson, DWK (reprint author), US FDA, CFSAN, DHSS, 5100 Paint Branch Pkwy,Mail Code HFS 6,Room 2B-00, College Pk, MD 20740 USA. EM david.acheson@cfsan.fda.gov NR 90 TC 53 Z9 69 U1 2 U2 7 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-6918 J9 BEST PRACT RES CL GA JI Best Pract. Res. Clin. Gastroenterol. PD APR PY 2004 VL 18 IS 2 BP 387 EP 404 DI 10.1053/ybega.2004.449 PG 18 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 816NR UT WOS:000221117100013 PM 15123077 ER PT J AU Owen, MP Kiernan, JA AF Owen, MP Kiernan, JA TI The M'Fadyean reaction: a stain for anthrax bacilli SO BIOTECHNIC & HISTOCHEMISTRY LA English DT Editorial Material C1 FDA Pacific Reg Lab NW, Bothell, WA 98021 USA. Univ Western Ontario, Dept Anat & Cell Biol, London, ON N6A 5C1, Canada. RP Owen, MP (reprint author), FDA Pacific Reg Lab NW, 22201 23rd Dr SE, Bothell, WA 98021 USA. EM michael.owen@fda.gov; kiernan@uwo.ca OI Kiernan, John/0000-0002-3324-1092 NR 6 TC 2 Z9 2 U1 0 U2 0 PU B I O S SCIENTIFIC PUBLISHERS LTD PI OXFORD PA 9 NEWTEC PLACE, MAGDALEN RD, OXFORD OX4 1RE, ENGLAND SN 1052-0295 J9 BIOTECH HISTOCHEM JI Biotech. Histochem. PD APR PY 2004 VL 79 IS 2 BP 107 EP 108 PG 2 WC Biotechnology & Applied Microbiology; Cell Biology SC Biotechnology & Applied Microbiology; Cell Biology GA 865YR UT WOS:000224740600010 PM 15513713 ER PT J AU Goel, V Shuren, J Sheesley, L Grafman, J AF Goel, V Shuren, J Sheesley, L Grafman, J TI Asymmetrical involvement of frontal lobes in social reasoning SO BRAIN LA English DT Article DE reasoning; frontal lobes; Wason selection task; social knowledge ID WASON SELECTION TASK; HUMAN PREFRONTAL CORTEX; BRAIN; EXPERIENCE; MINDS; LOGIC AB The frontal lobes are widely implicated in logical reasoning. Recent neuroimaging studies suggest that frontal lobe involvement in reasoning is asymmetric (L>R) and increases with the presence of familiar, meaningful content in the reasoning situation. However, neuroimaging data can only provide sufficiency criteria. To determine the necessity of prefrontal involvement in logical reasoning, we tested 19 patients with focal frontal lobe lesions and 19 age- and education-matched normal controls on the Wason Card Selection Task, while manipulating social knowledge. Patients and controls performed equivalently on the arbitrary rule condition. Normal controls showed the expected improvement in the social knowledge conditions, but frontal lobe patients failed to show this facilitation in performance. Furthermore, left hemisphere patients were more affected than right hemisphere patients, suggesting that frontal lobe involvement in reasoning is asymmetric (L>R) and necessary for reasoning about social situations. C1 York Univ, Dept Psychol, Toronto, ON M3J 1P3, Canada. NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. US FDA, Off Policy, Rockville, MD 20857 USA. RP Goel, V (reprint author), York Univ, Dept Psychol, Toronto, ON M3J 1P3, Canada. EM vgoel@yorku.ca OI Grafman, Jordan H./0000-0001-8645-4457 NR 39 TC 28 Z9 32 U1 4 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD APR PY 2004 VL 127 BP 783 EP 790 DI 10.1093/brain/awh086 PN 4 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 807ET UT WOS:000220485500012 PM 14976069 ER PT J AU Kim, DH Kadlubar, FF Teitel, CH Guengerich, FP AF Kim, DH Kadlubar, FF Teitel, CH Guengerich, FP TI Formation and reduction of aryl and heterocyclic nitroso compounds and significance in the flux of hydroxylamines SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID HUMAN CYTOCHROME-P450 1A2; HUMAN LIVER-MICROSOMES; AROMATIC-AMINES; METABOLIC-ACTIVATION; CARCINOGENIC ARYLAMINES; SALMONELLA-TYPHIMURIUM; N-ACETYLTRANSFERASE; ENZYMATIC REDUCTION; HUMAN HEPATOCYTES; ESCHERICHIA-COLI AB Cytochrome P450 (P450) 1A2 and NADPH-P450 reductase (NPR) catalyzed the oxidation of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), with consumption of NADPH. The oxidation rate of NADPH by P450 1A2/NPR increased with time in the presence of IQ until depletion of NADPH. This unusual autocatalytic pattern of NADPH oxidation could be rationalized by formation of a nitroso derivative (IQ-N=O) and the subsequent reduction of the hydroxylamine, (IQ-NHOH) and IQ-N=O, which would consume more NADPH. The formation of IQ-NHOH and IQ-N=O from IQ was confirmed using HPLC/MS. Reduction of IQ-NHOH and IQ-N=O was NPR-dependent but did not require P450. Autocatalytic NADPH oxidation was also observed in the oxidation of other heterocyclic and arylamines. However, the N-hydroxyl and nitroso oxidation products of 2-aminofluorene and 4-aminobiphenyl were reduced nonenzymatically by NADPH, and NPR did not catalyze the reactions. We simulated the enzymatic kinetic model for possible pathways for IQ metabolism, which included the formation of IQ-N=O, using some. kinetic parameters obtained from the experimental results. In the kinetic model, we could reproduce the similar curvature for NADPH oxidation and the formation of IQ-N=O, and the reduction of IQ-NHOH and IQ-N=O is required to explain the observed results for NADPH oxidation. Our results support a role for nitroso derivatives of HAAS in the unusual autocatalytic NADPH oxidation and may have relevance in terms of possible toxicities of the nitroso derivatives. Both IQ-NHOH and IQ-N=O were mutagenic in a bacterial tester system devoid of P450 and NPR; the mutagenicity of both was decreased by expression of NPR, consistent with the reduction of these compounds observed with purified NPR. C1 Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Ctr Mol Toxicol, Nashville, TN 37232 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Guengerich, FP (reprint author), Vanderbilt Univ, Sch Med, Dept Biochem, 221 Kirkland Hall, Nashville, TN 37232 USA. EM f.guengerich@vanderbilt.edu FU NCI NIH HHS [R01 CA90426]; NIEHS NIH HHS [P30 ES00267] NR 62 TC 24 Z9 24 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD APR PY 2004 VL 17 IS 4 BP 529 EP 536 DI 10.1021/tx034267y PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 814JQ UT WOS:000220971400009 PM 15089095 ER PT J AU Brinker, A Johnston, M AF Brinker, A Johnston, M TI Acute pulmonary injury in association with amiodarone SO CHEST LA English DT Letter ID TOXICITY C1 US FDA, CDER, Off Drug Safety, Rockville, MD 20857 USA. RP Brinker, A (reprint author), US FDA, CDER, Off Drug Safety, 15B-08 HFD-430,5600 Fishers Ln, Rockville, MD 20857 USA. EM brinkera@cder.fda.gov NR 5 TC 9 Z9 10 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD APR PY 2004 VL 125 IS 4 BP 1591 EP 1592 DI 10.1378/chest.125.4.1591-a PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 825YB UT WOS:000221793700071 PM 15078784 ER PT J AU Davis, RD Gilman, JW Sutto, TW Callahan, JH Trulove, PC De Long, H AF Davis, RD Gilman, JW Sutto, TW Callahan, JH Trulove, PC De Long, H TI Improved thermal stability of organically modified layered silicates SO CLAYS AND CLAY MINERALS LA English DT Article DE alkyl ammonium; montmorillonite; nanocomposites; organic modifier degradation; organoclay; synthetic mica ID CLAY NANOCOMPOSITES; MONTMORILLONITE; DISPERSION; QUALITY AB Bromide-containing impurities were found to decrease the thermal stability of quaternary alkyl ammonium-modified layered silicates. Improved purification procedures completely removed bromide and led to a 20degreesC to >100degreesC increase in organic modified layered silicate thermal stability. Using mass spectrometry and thermal and electrochemical analysis, N,N-dimethyl-N,N-dioctadecyl quaternary ammonium-modified montmorillonite and fluorinated synthetic mica were found to degrade primarily through elimination and nucleophilic attack by these anions. The nature of residual bromides was identified and quantified, and the efficiency of removing these anions was found to be solvent dependent; sequential extraction, first ethanol then tetrahydrofuran, gave the best results. This exhaustive extraction method represents a viable alternative to the use of expensive, more thermally stable oniumion treatments for layered silicates. C1 Natl Inst Stand & Technol, Bldg & Fire Res Labs, Gaithersburg, MD 20899 USA. USN Acad, Washington, DC 20375 USA. Naval Res Lab, Washington, DC 20375 USA. US FDA, CFSAN, Instrumentat & Biophys Branch, College Pk, MD 20740 USA. USAF, Off Sci Res, Arlington, VA 22203 USA. RP Davis, RD (reprint author), Natl Inst Stand & Technol, Bldg & Fire Res Labs, Gaithersburg, MD 20899 USA. EM rick.davis@nist.gov NR 11 TC 56 Z9 57 U1 2 U2 12 PU CLAY MINERALS SOC PI CHANTILLY PA 3635 CONCORDE PKWY, STE 500, CHANTILLY, VA 20151-1125 USA SN 0009-8604 J9 CLAY CLAY MINER JI Clay Clay Min. PD APR PY 2004 VL 52 IS 2 BP 171 EP 179 DI 10.1346/CCMN.2004.0520203 PG 9 WC Chemistry, Physical; Geosciences, Multidisciplinary; Mineralogy; Soil Science SC Chemistry; Geology; Mineralogy; Agriculture GA 813LZ UT WOS:000220909900003 ER PT J AU Linnet, K Kondratovich, M AF Linnet, K Kondratovich, M TI Partly nonparametric approach for determining the limit of detection SO CLINICAL CHEMISTRY LA English DT Article AB Background: According to recent International Organization for Standardization (ISO) standards, the limit of detection (LoD) of an assay should be estimated taking both type I (alpha) and II (beta) errors into account. The suggested procedure, however, supposes gaussian distributions of both blank and sample measurements and a linear calibration curve. In clinical chemistry, asymmetric, nongaussian blank distributions are common, and the calibration curve may be nonlinear. We present a partly nonparametric procedure that takes these aspects into account. Methods: Using theoretical distribution models and simulation studies, we developed a LoD estimation, procedure suitable for the field of clinical chemistry that is partly based on nonparametric statistics. Results: For sample size n, the nonparametrically determined 95th percentile of the blank measurements {obtained as the value of the [n(95/100) + 0.5]th ordered observation} defines the limit for results significantly exceeding zero [limit of, blank (LoB)]. The LoD is the lowest value that is likely to yield a result exceeding the LoB. LoD is estimated as: LoB + c(beta) x SDS, where SDS is the analytical SD of a sample with a low concentration; C-beta = z(1-beta)/[1 - 1/(4 x f)]; z(1-beta) is the standard normal deviate; and f is the number of degrees of freedom for estimation of SDS. c(beta) is approximately equal to 1.65 for a type II error of 5%. Approaches and needed tabular values for calculation of confidence limits are presented as well as sample size. Worked examples are given to illustrate estimation and verification of the limit of detection. Simulation results are used to document performance. Conclusion: The proposed procedure appears useful for application in the field of clinical chemistry and promotes a standardized approach for estimating LoDs of clinical chemistry assays. (C) 2004 American Association for Clinical Chemistry. C1 Psychiat Univ Hosp, Lab Clin Biochem, DK-8240 Risskov, Denmark. US FDA, Div Biostat, Rockville, MD 20857 USA. RP Linnet, K (reprint author), Psychiat Univ Hosp, Lab Clin Biochem, Skovagervej 2, DK-8240 Risskov, Denmark. EM linnet@post7.tele.dk OI Linnet, Kristian/0000-0001-6974-5535 NR 26 TC 45 Z9 45 U1 0 U2 4 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD APR PY 2004 VL 50 IS 4 BP 732 EP 740 DI 10.1373/clinchem.2003.029983 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 807TS UT WOS:000220524400007 PM 14764644 ER PT J AU Rafii, F Hotchkiss, C Heinze, TM Park, M AF Rafii, F Hotchkiss, C Heinze, TM Park, M TI Metabolism of daidzein by intestinal bacteria from rhesus monkeys (Macaca mulatta) SO COMPARATIVE MEDICINE LA English DT Article ID GUT MICROFLORA; SOY PROTEIN; ISOFLAVONOID DAIDZEIN; SOYBEAN ISOFLAVONES; CYNOMOLGUS MONKEYS; BREAST-CANCER; C-RING; PHYTOESTROGENS; EQUOL; GENISTEIN AB Purpose: To identify the metabolites produced from an isoflavonoid, daidzein, by colonic bacteria of rhesus monkeys. Methods: The metabolism of daidzein by the fecal bacteria of nine monkeys was investigated. Daidzein was incubated anaerobically with fecal bacteria, and the metabolites were analyzed by use of liquid chromatography and mass spectrometry. Results: The fecal bacteria of all of the monkeys metabolized daidzein to various extents. Dihydrodaidzein was found in cultures of fecal bacteria from two monkeys; dihydrodaidzein and equol were found in cultures from four monkeys; dihydrodaidzein, equol, and an unknown metabolite (MW = 244) were found in cultures from one monkey; and dihydrodaidzein and the unknown metabolite were found in cultures from two monkeys. Conclusions: Similar to that in humans, variation was evident in the metabolism of isoflavonoids by fecal bacteria from rhesus monkeys. Some metabolites produced by fecal bacteria from monkeys were the same as those produced by fecal bacteria from humans. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Bionet Corp, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Rafii, F (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 35 TC 12 Z9 13 U1 0 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD APR PY 2004 VL 54 IS 2 BP 165 EP 169 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 817YS UT WOS:000221213400005 PM 15134361 ER PT J AU Turesky, RJ AF Turesky, RJ TI The role of genetic polymorphisms in metabolism of carcinogenic heterocyclic aromatic amines SO CURRENT DRUG METABOLISM LA English DT Review DE heterocyclic aromatic amines; xenobiotic metabolism enzymes; polymorphisms; cancer ID GLUTATHIONE-S-TRANSFERASE; BREAST-CANCER RISK; HUMAN CYTOCHROME-P450 1A2; DONE MEAT INTAKE; HUMAN UDP-GLUCURONOSYLTRANSFERASES; N-ACETYLTRANSFERASE EXPRESSION; MAMMARY EPITHELIAL-CELLS; DNA ADDUCT FORMATION; LOS-ANGELES-COUNTY; COLORECTAL-CANCER AB More than twenty heterocyclic aromatic amines (HAAs) have been identified in grilled meats, Fish, poultry, and tobacco smoke condensate. HAAS are carcinogens and induce tumors at Multiple Sites in experimental laboratory animals. Because of the widespread occurrence of HAAs in foods, these chemicals may contribute to the etiology of several common human cancers that are associated with frequent consumption of grilled meals including colon, rectum, prostate, and breast. HAAs require metabolism in order to exert their genotoxic effects. Metabolic activation occurs by N-hydroxylation, a reaction catalyzed by cytochromes P450 (CYP). Sonic N-hydroxy-HAA metabolites may directly react with DNA. but further metabolism by N-acetyltransferases (NATs) or sulfotransferases (SULTs) may occur to form highly reactive N-acetoxy or N-sulfonyloxy esters that readily react with DNA bases. The N-acetoxy ester of the HAA 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP) is detoxified by glutathione S-transferases (GSTs), which catalyze the reduction of the reactive intermediate back to the parent amine. Sonic HAAs also undergo detoxification through conjugation reactions with the phase II enzymes Such as UDP-glucuronosyltransferases (UGTs) or SULTs to form stable, polar products that are readily eliminated. All of these xenobiotic metabolism enzyme systems (XMEs) display common genetic polymorphisms, which may affect protein expression, protein stability, catalytic activity, and thus, the biological potency of these procarcinogens. In this review, the roles of common genetic polymorphisms of XMEs involved in HAA metabolism and cancer risk are discussed. C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Turesky, RJ (reprint author), Natl Ctr Toxicol Res, Div Chem, Bldg 26 Room A155, Jefferson, AR 72079 USA. EM RTuresky@nctr.fda.gov NR 156 TC 43 Z9 45 U1 0 U2 5 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1389-2002 J9 CURR DRUG METAB JI Curr. Drug Metab. PD APR PY 2004 VL 5 IS 2 BP 169 EP 180 DI 10.2174/1389200043489036 PG 12 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 812QY UT WOS:000220855200004 PM 15078194 ER PT J AU Ishii, KJ Gursel, I Gursel, M Klinman, DM AF Ishii, KJ Gursel, I Gursel, M Klinman, DM TI Immunotherapeutic utility of stimulatory and suppressive oligodeoxynucleotides SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Article DE CpG DNA; immunotherapy; innate immunity; suppressive ODNs; toll-like receptor 9 ID BACTERIAL CPG-DNA; TOLL-LIKE RECEPTOR-9; INDUCED IMMUNE ACTIVATION; IMMUNOSTIMULATORY DNA; MURINE MODEL; PROTEIN-KINASE; IN-VIVO; SYNTHETIC OLIGODEOXYNUCLEOTIDES; DEPENDENT PROTECTION; AIRWAY INFLAMMATION AB Bacterial DNA contains immunostimulatory CpG motifs that interact with toll-like receptor 9 on immune cells to stimulate the production of cytokines, chemokines and immunoglobulins. Synthetic oligodeoxynucleotides (ODNs) containing CpG motifs mimic the activity of bacterial DNA. Recently, several structurally distinct types of CpG ODN were identified that differentially activate human immune cells. These ODNs may be useful as vaccine adjuvants, anti-allergens and in the treatment of infectious diseases and cancer. Yet CpG-driven immune activation can have deleterious consequences, such as increasing the host's susceptibility to autoimmune disease. The immunomodulatory activity of CpG DNA can be blocked by DNA containing G-rich 'suppressive' motifs. The therapeutic potential of these immunostimulatory and immunosuppressive ODNs are discussed in this review. C1 US FDA, Sect Retroviral Immunmol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Osaka Univ, Akira Innate Immun Project, ERATO,Res Inst Microbial Dis, Japan Sci & Technol Agcy,Dept Host Def, Osaka 5650871, Japan. RP Klinman, DM (reprint author), US FDA, Sect Retroviral Immunmol, Ctr Biol Evaluat & Res, Bldg 29A Rm 3D10, Bethesda, MD 20892 USA. EM Klinman@cber.fda.gov RI Gursel, Mayda /H-1812-2012; Ishii, Ken/B-1685-2012; OI Ishii, Ken/0000-0002-6728-3872; Gursel, Ihsan/0000-0003-3761-1166 NR 73 TC 39 Z9 42 U1 0 U2 0 PU CURRENT DRUGS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD APR PY 2004 VL 6 IS 2 BP 166 EP 174 PG 9 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 838UA UT WOS:000222737600009 PM 15195929 ER PT J AU Gendel, SM AF Gendel, SM TI Riboprint analysis of Listeria monocytogenes isolates obtained by FDA from 1999 to 2003 SO FOOD MICROBIOLOGY LA English DT Article DE riboprint; ribotyping; molecular subtyping; Listeria monocytogenes ID SMOKED FISH; POULTRY; MEAT AB Listeria monocytogenes is a widespread human and annual pathogen. Despite the potential value of ribotyping for tracking patterns of strain distribution in Listeria monocytogenes, the application of this technology for this species has been limited to sets of isolates that are linked either by epidemiology, geography, or food type. To broadly characterize the population structure of L. monocytogenes, automated ribotyping was carried out on a large set of unrelated isolates obtained by the US FDA from late 1999 to early 2003. The results showed the widespread occurrence of a few strains, and no indication of geographic or food-related stratification. Published by Elsevier Ltd. C1 US FDA, Biotechnol Studies Branch, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Gendel, SM (reprint author), US FDA, Biotechnol Studies Branch, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM sgendel@cfsan.fda.gov NR 14 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD APR PY 2004 VL 21 IS 2 BP 187 EP 191 DI 10.1016/S0740-0020(03)00054-6 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 779XX UT WOS:000189328500008 ER PT J AU Brooks, BE Zhan, M Cote, T Baquet, CR AF Brooks, BE Zhan, M Cote, T Baquet, CR TI Surveillance, Epidemiology, and End Results analysis of 2677 cases of uterine sarcoma 1989-1999 SO GYNECOLOGIC ONCOLOGY LA English DT Article DE uterine sarcoma; race; survival ID ENDOMETRIAL CARCINOMA; CANCER; TAMOXIFEN; UTERUS AB Objective. To determine the association of race with incidence, histology, treatment, and survival in women with uterine sarcoma during the period 1989-1999. Method. Uterine sarcomas were defined as leiomyosarcoma, carcinosarcoma, high-grade endometrial stromal sarcoma (HGESS), adenosarcoma, and sarcoma not otherwise specified (NOS). We used cases from Surveillance, Epidemiology, and End Results (SEER) program to compare uterine sarcoma among women >35 years of age. Using data from 1989 to 1999, we compared race-specific age-adjusted incidences, histological distributions, extent of disease at diagnosis, and race-specific survival. Results. During the period of 1989-1999, 2677 women were diagnosed with uterine sarcoma, 2098 (78%) of whom were white and 420 (16%) of whom were black, and 159 (6%) of whom were of other races. The overall age-adjusted incidence for blacks was twice that of whites and more than twice that of women of other races (7/10(5) vs. 3.6/10(5) vs. 2.7/10(5), p < 0.0001). Racial differences in the incidence of uterine sarcoma existed for leiomyosarcoma (1.51/10(5) for blacks vs. 0.91/10(5) for whites, and 0.89 for women of other races, P < 0.01) and carcinosarcoma (4.3/10(5) for blacks, vs. 1.7/10(5) for whites, and 0.99 for women of other races, P < 0.001), but not for other histological types. Blacks with stage II disease were less likely to receive radiation in addition to surgery compared to whites (33% vs. 54%, P < 0.05). Five-year relative survival of patients with disease beyond the uterus was significantly longer for those that received radiation and surgery compared to those that received surgery alone. There were no racial differences in survival for women that received similar therapy. Conclusions. Adjuvant therapy improved survival for women with stage II-IV disease. Survival of black and white patients who received comparable treatment was similar. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Maryland, Sch Med, Dept Obstet & Gynecol & Reprod Sci, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. US FDA, Rockville, MD 20857 USA. RP Brooks, BE (reprint author), Univ Maryland, Sch Med, Dept Obstet & Gynecol & Reprod Sci, 3rd Floor,405 W Redwood St, Baltimore, MD 21201 USA. EM sbrooks@umm.edu NR 17 TC 29 Z9 33 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 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2004 VL 93 IS 1 BP 204 EP 208 DI 10.1016/j.ygyno.2003.12.029 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 812PG UT WOS:000220850800032 ER PT J AU Ak, M Babaoglu, A Dagci, H Turk, M Bayram, S Ertabaklar, H Ozcel, MA Uner, A Charoenvit, Y Kumar, S Hoffman, SL AF Ak, M Babaoglu, A Dagci, H Turk, M Bayram, S Ertabaklar, H Ozcel, MA Uner, A Charoenvit, Y Kumar, S Hoffman, SL TI Production of monoclonal antibodies against a 19-kD recombinant Plasmodium vivax MSPI for detection of P-vivax malaria in Turkey SO HYBRIDOMA AND HYBRIDOMICS LA English DT Article ID MEROZOITE SURFACE PROTEIN-1; YOELII SPOROZOITES; VACCINE CANDIDATE; IMMUNOGENICITY; BLOOD; EXPRESSION; ANTIGEN; PROTECT; GROWTH AB Plasmodium vivax malaria, which is transmitted to humans by mosquitoes, is one of the most important parasitic diseases in Turkey. The major protein on the surface of asexual erythrocytic stage merozoites of P. vivax (Pv) is 200 kD and called major merozoite surface protein-1 (PvMSP1). Polyclonal antibodies against the 19-kD C-terminal fragment of PvMSP1 (PvMSP1(19)) are protective in monkey models of P. vivax and associated with protection in field studies. In this research, monoclonal antibodies were produced against PvMSP1(19). A total of 214 IgG(1) antibody-releasing hybridomas were obtained and three monoclonal antibodies were produced (PvMSP1(19).1, PvMSP1(19).2, and PvMSP1(19).3) and selected for further study. They have now been purified from ascitic fluid on a Staphylococcus protein A affinity column. These are the first monoclonal antibodies produced against P. vivax in Turkey and the first monoclonal antibodies produced against this recombinant PvMSP1(19) in the world. The monoclonal antibodies will be used to study the epidemiology of P. vivax in patients with malaria in Turkey, and to develop better strategies for early diagnosis and treatment of the disease in our population. C1 Ege Univ, Fac Med, Dept Parasitol, Izmir, Turkey. Izmir State Hosp, Microbiol Lab, Izmir, Turkey. Eylul Univ 9, Fac Med, Dept Parasitol, Izmir, Turkey. Adnan Menderes Univ, Fac Med, Dept Parasitol, Aydin, Turkey. NMRC, IDD, Malaria Program, Silver Spring, MD USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Sanaria Inc, Rockville, MD USA. RP Ak, M (reprint author), Ege Univ, Fac Med, Dept Parasitol, Izmir, Turkey. EM ak@med.ege.edu.tr RI Dagci, Hande/B-1840-2008 NR 17 TC 0 Z9 0 U1 2 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0272-457X J9 HYBRIDOMA HYBRIDOM JI Hybrid. Hybridomics PD APR PY 2004 VL 23 IS 2 BP 133 EP 136 DI 10.1089/153685904774129748 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA 822AL UT WOS:000221505600007 PM 15165487 ER PT J AU Cheung, AM Farizo, KM Burns, DL AF Cheung, AM Farizo, KM Burns, DL TI Analysis of relative levels of production of pertussis toxin Subunits and Ptl proteins in Bordetella pertussis SO INFECTION AND IMMUNITY LA English DT Article ID AGROBACTERIUM-TUMEFACIENS VIRB; MONOCLONAL-ANTIBODIES; SUBCELLULAR-LOCALIZATION; BARTONELLA-HENSELAE; T-PILUS; GENES; SECRETION; OPERON; PROMOTER; CLONING AB Pertussis toxin is transported across the outer membrane of Bordetella pertussis by the type TV secretion system known as the Ptl transporter, which is composed of nine different proteins. In order to determine the relative levels of production of pertussis toxin subunits and Ptl proteins in B. pertussis, we constructed translational fusions of the gene for alkaline phosphatase, phoA, with various ptx and ptl genes. Comparison of the alkaline phosphatase activity of strains containing ptx'- or ptl'-phoA fusions indicated that pertussis toxin subunits are produced at higher levels than Ptl proteins, which are encoded by genes located toward the 3' end of the ptx-ptl operon. We also engineered strains of B. pertussis by introducing multiple copies of the ptl genes or subsets of these genes and then examined the ability of each of these strains to secrete pertussis toxin. From these studies, we determined that certain Ptl proteins appear to be limiting in the secretion of pertussis toxin from the bacteria. These results represent an important first step in assessing the stoichiometric relationship of pertussis toxin and its transporter within the bacterial cell. C1 US FDA, CBER, HFM 434, Lab Resp & Special Pathogens, Bethesda, MD 20892 USA. RP Burns, DL (reprint author), US FDA, CBER, HFM 434, Lab Resp & Special Pathogens, Bldb 29,Room 130,8800 Rockville Pike, Bethesda, MD 20892 USA. EM burns@cber.fda NR 33 TC 4 Z9 4 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 APR PY 2004 VL 72 IS 4 BP 2057 EP 2066 DI 10.1128/IAI.72.4.2057-2066.2004 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 807DG UT WOS:000220481600025 PM 15039327 ER PT J AU McCutchan, TF Grim, KC Li, J Weiss, W Rathore, D Sullivan, M Graczyk, TK Kumar, S Cranfield, MR AF McCutchan, TF Grim, KC Li, J Weiss, W Rathore, D Sullivan, M Graczyk, TK Kumar, S Cranfield, MR TI Measuring the effects of an ever-changing environment on malaria control SO INFECTION AND IMMUNITY LA English DT Article ID PENGUINS SPHENISCUS-DEMERSUS; COLONY-STIMULATING FACTOR; PLASMODIUM-FALCIPARUM; AVIAN MALARIA; CIRCUMSPOROZOITE PROTEIN; INTERFERON-GAMMA; DNA VACCINES; T-CELL; IMMUNIZATION; PROTECTION AB The effectiveness of malaria control measures depends not only on the potency of the control measures themselves but also upon the influence of variables associated with the environment. Environmental variables have the capacity either to enhance or to impair the desired outcome. An optimal outcome in the field, which is ultimately the real goal of vaccine research, will result from prior knowledge of both the potency of the control measures and the role of environmental variables. Here we describe both the potential effectiveness of control measures and the problems associated with testing in an area of endemicity. We placed canaries with different immunologic backgrounds (e.g., naive to malaria infection, vaccinated naive, and immune) directly into an area where avian malaria, Plasmodium relictum, is endemic. In our study setting, canaries that are naive to malaria infection routinely suffer approximately 50% mortality during their first period of exposure to the disease. In comparison, birds vaccinated and boosted with a DNA vaccine plasmid encoding the circumsporozoite protein of P. relictum exhibited a moderate degree of protection against natural infection (P < 0.01). In the second year we followed the fate of all surviving birds with no further manipulation. The vaccinated birds from the first year were no longer statistically distinguishable for protection against malaria from cages of naive birds. During this period, 36% of vaccinated birds died of malaria. We postulate that the vaccine-induced protective immune responses prevented the acquisition of natural immunity similar to that concurrently acquired by birds in a neighboring cage. These results indicate that dominant environmental parameters associated with malaria deaths can be addressed before their application to a less malleable human system. C1 NIAID, Parasit Dis Lab, Sect Growth & Dev, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Review & Res, Div Emerging Transfus Transmitted Dis, Bethesda, MD 20014 USA. USN, Med Res Ctr, Malaria Program, Silver Spring, MD 20903 USA. Johns Hopkins Univ, Johns Hopkins Sch Med, Baltimore, MD USA. Baltimore Zoo, Dept Med, Baltimore, MD USA. St Clares Hosp, Dept Pathol, Denville, NJ USA. RP McCutchan, TF (reprint author), NIAID, Parasit Dis Lab, Sect Growth & Dev, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM tmccutchan@niaid.nih.gov NR 31 TC 5 Z9 5 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2004 VL 72 IS 4 BP 2248 EP 2253 DI 10.1128/IAI.72.4.2248-2253.2004 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 807DG UT WOS:000220481600047 PM 15039349 ER PT J AU Mahmood, I Tammara, V AF Mahmood, I Tammara, V TI A comparison of two sparse sampling population pharmacokinetic approaches for the estimation of pharmacokinetic parameters in children SO INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE sparse sampling; population pharmacokinetics; Bayesian approach; variable and fixed sampling ID MAXIMUM PLASMA-CONCENTRATION; CONCENTRATION C-MAX; UNDER-THE-CURVE; COMPUTER-SIMULATION; MODEL; AREA; AUC; CARBAMAZEPINE; PERFORMANCE; TIME AB (Background and objective:) under bar The objectives of this study were to assess pharmacokinetic parameters (clearance, volume and half-life) in children using sparse sampling population as well as Bayesian (post hoc) approach. (Methods:) under bar Three drugs were selected for this study. Two sparse sampling methods (variable or fixed) using population and Bayesian approaches were used to assess pharmacokinetic parameters in children following a single oral dose. The initial estimates of the model parameters and inter- and intrasubject variability were obtained from the pharmacokinetic studies conducted in adults. The estimated pharmacokinetic parameters using sparse sampling (3 blood samples) were compared with the pharmacokinetic parameters obtained by extensive sampling (greater than or equal to7 blood samples). (Results and conclusions:) under bar The results indicated that both variable and fixed sampling approaches could be used to estimate mean population as well as individual pharmacokinetic parameters in children with fair degree of accuracy. The methods described here can be used to assess either population or individual pharmacokinetic parameters in children, provided there is a prior knowledge of the pharmacokinetics of a drug in adult population. C1 Wyeth Pharmaceut, Collegeville, PA USA. RP Mahmood, I (reprint author), US FDA, Div Clin Trial Design & Anal, Off Therapeut Res & Review,Ctr Biol Evaluat & Res, Clin Pharmacol & Toxicol Branch HFD 579, Woodmont Off Ctr 1,Suite 200N,1401 Rockville Pike, Rockville, MD 20852 USA. EM Mahmoodi@CBER.FDA.GOV NR 18 TC 5 Z9 5 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI OBERHACHING PA BAJUWARENRING 4, D-82041 OBERHACHING, GERMANY SN 0946-1965 J9 INT J CLIN PHARM TH JI Int. J. Clin. Pharmacol. Ther. PD APR PY 2004 VL 42 IS 4 BP 240 EP 245 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 808LQ UT WOS:000220571000006 PM 15124982 ER PT J AU Monday, SR Minnich, SA Feng, PCH AF Monday, SR Minnich, SA Feng, PCH TI A 12-base-pair deletion in the flagellar master control gene flhC causes nonmotility of the pathogenic German sorbitol-fermenting Escherichia coli O157 : H- strains SO JOURNAL OF BACTERIOLOGY LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; MOLECULAR CHARACTERIZATION; MONOCLONAL-ANTIBODY; EXPRESSION; OPERON; IDENTIFICATION; SEROTYPES; MUTATIONS; SEQUENCE; SHIGELLA AB An atypical, Stx2-producing, pathogenic Escherichia coli O157:H- strain has been isolated with increasing frequency from hemolytic uremic syndrome patients in Germany. The lack of the H7 antigen coupled with the strain's ability to ferment sorbitol and express beta-glucuronidase have complicated its detection and identification. In this study, we have determined that the loss of motility in these German sorbitol-fermenting (SF) O157 strains is due to a 12-bp in-frame deletion in flhC that is required for transcriptional activation of genes involved in flagellum biosynthesis. Either complementation with a functional flhC or repair of this mutation restored H7 antigen expression and motility. PCR analysis of several nonmotile E. coli O157 strains from various geographical sources confirmed that the 12-bp flhC deletion is found only in the cluster of German SF O157 strains, providing a potentially useful marker by which these atypical strains can be identified. The loss of motility via mutations in the flhDC operon that we observed in the German SF O157 strains is consistent with a similar phenomenon currently observed in a significant subset of other important gram-negative pathogens. C1 US FDA, Div Microbiol Studies, College Pk, MD 20740 USA. Univ Idaho, Dept Microbiol Mol Biol & Biochem, Moscow, ID 83843 USA. RP Feng, PCH (reprint author), US FDA, Div Microbiol Studies, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM pfeng@cfsan.fda.gov FU NCRR NIH HHS [P20 RR16454] NR 35 TC 37 Z9 38 U1 0 U2 2 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 2004 VL 186 IS 8 BP 2319 EP 2327 DI 10.1128/JB.186.8.2319-2327.2004 PG 9 WC Microbiology SC Microbiology GA 809ZE UT WOS:000220673800012 PM 15060034 ER PT J AU Van Do, N Mino, L Merriam, GR LeMar, H Case, HS Palinkas, LA Reedy, K Reed, HL AF Van Do, N Mino, L Merriam, GR LeMar, H Case, HS Palinkas, LA Reedy, K Reed, HL TI Elevation in serum thyroglobulin during prolonged antarctic residence: Effect of thyroxine supplement in the polar 3,5,3 '-triiodothyronine syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 83rd Annual Meeting of the Endocrine-Society CY JUN 20-23, 2001 CL DENVER, CO SP Endocrine Soc ID RECOMBINANT HUMAN THYROTROPIN; THYROID-CARCINOMA; CLINICAL-PRACTICE; PITUITARY; KINETICS AB Extended Antarctic residence (AR) is associated with an increase in serum TSH, a decrease in free T(4), and an increase in T(3) production and clearance. It is not clear whether these adaptations reflect changes in clearance alone or whether intrinsic thyroidal synthetic activity also changes. Thyroglobulin (Tg) secretion is an independent marker of intrinsic thyroid activity whose kinetics are independent of those of T(3) and T(4). In this study we examined changes in Tg levels in healthy subjects before and during AR and their responses to thyroid supplementation to help determine whether alterations in thyroid activity, and not just kinetics of clearance, underlie the changes seen with the polar T(3) syndrome. In cohort 1, we compared measurements of TSH and Tg in 12 subjects before deployment and monthly for 11 months during AR. In cohort 2, we compared the same measurements in 12 subjects monthly for 11 months of AR. Subjects were randomized to receive either placebo or levothyroxine in cohort 1 for 7 months and in cohort 2 for 11 months. Tg increased over baseline during the first 4 months of AR by 17.0+/-4.6% and after 7 more months by 31.7+/-4.3% over baseline in the placebo group of both cohorts ( P<0.0002). When L-T(4) was taken, Tg returned to a value not different from baseline (4.5 +/- 3.9%). The percent changes from baseline in serum TSH and Tg during AR were highly correlated (P<0.00003) in the placebo group for both cohorts. The rise in Tg with TSH and the reduction in Tg with L-T(4) provide evidence of target tissue response to TSH and further confirm the TSH rise as physiologically significant. The results also suggest that the adaptive changes in thyroid hormone economy with AR reflect TSH-dependent changes in thyroid synthetic activity, which may help explain a portion of the increases in T(3) production found with AR. C1 Madigan Army Med Ctr, Internal Med Serv, Tacoma, WA 98431 USA. New Mexico Resonance, Albuquerque, NM USA. Vet Affairs Puget Sound Hlth Care Syst, Tacoma, WA 98493 USA. Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. William Beaumont Army Med Ctr, Endocrine Serv, El Paso, TX 79920 USA. McDaniel Coll, Dept Exercise Sci & Phys Educ, Westminster, MD 21157 USA. Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. US FDA, Rockville, MD 20857 USA. Multicare Med Grp, Tacoma, WA 98415 USA. RP Van Do, N (reprint author), Stanford Med Informat, Sch Med, Off Bldg,X-215,251 Campus Dr, Stanford, CA 94305 USA. EM nhan.do@us.army.mil NR 23 TC 2 Z9 3 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2004 VL 89 IS 4 BP 1529 EP 1533 DI 10.1210/jc.2003-031747 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 810OV UT WOS:000220714500004 PM 15070908 ER PT J AU Tsang, RSW Tsai, CM Zhu, PX Ringuette, L Lorange, M Law, DKS AF Tsang, RSW Tsai, CM Zhu, PX Ringuette, L Lorange, M Law, DKS TI Phenotypic and genetic characterization of a unique variant of serogroup C ET-15 meningococci (with the antigenic formula C : 2a : P1.7,1) causing invasive meningococcal disease in Quebec, Canada SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID NEISSERIA-MENINGITIDIS SEROTYPE-2A; MASS IMMUNIZATION CAMPAIGN; OUTER-MEMBRANE PROTEIN; UNITED-STATES; ET-37 COMPLEX; POPULATION-GENETICS; VIRULENT CLONE; EPIDEMIOLOGY; DIVERSITY; EMERGENCE AB Serogroup C Neisseria meningitidis belonging to the electrophoretic type (ET) ET-15, a variant of ET-37, is endemic in Canada. Like other serogroup C ET-37 meningococci, the endemic ET-15 strains are usually found to carry the serotype and serosubtype antigens of 2a:P1.5,2. In 2001, a sudden increase in the number of cases of serogroup C meningococcal disease in Quebec, Canada, was caused by an antigenic variant of the ET-15 strain. This antigenic variant carries the unique serosubtype marker of P1.7,1. Strains of C:2a:P1.7,1 meningococci were not isolated in Canada in large numbers prior to 2001, and the characteristics of these meningococcal strains linked to an outbreak in Quebec, Canada, are described in the present study. C1 CNS, Infect & Vaccine Preventable Bacterial Dis Div, Natl Microbiol Lab, Winnipeg, MB R3E 3R2, Canada. Inst Natl Sante Publ, Lab Sante Publ, Ste Anne De Bellevue, PQ, Canada. US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, Washington, DC USA. RP Tsang, RSW (reprint author), CNS, Infect & Vaccine Preventable Bacterial Dis Div, Natl Microbiol Lab, 1015 Arlington St, Winnipeg, MB R3E 3R2, Canada. EM rtsang@hc-sc.gc.ca NR 39 TC 18 Z9 19 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 2004 VL 42 IS 4 BP 1460 EP 1465 DI 10.1128/JCM.42.4.1460-1465.2004 PG 6 WC Microbiology SC Microbiology GA 814GK UT WOS:000220963000012 PM 15070989 ER PT J AU Williams, TL Musser, SM Nordstrom, JL DePaola, A Monday, SR AF Williams, TL Musser, SM Nordstrom, JL DePaola, A Monday, SR TI Identification of a protein biomarker unique to the pandemic O3 : K6 clone of Vibrio parahaemolyticus SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID FLIGHT MASS-SPECTROMETRY; STRAINS; MICROORGANISMS; EMERGENCE; CHOLERAE; PCR; EXPRESSION; SEQUENCE; BACTERIA; SPREAD AB The present method of characterizing Vibrio parahaemolyticus strains involves serotyping or detection methods based on assessment of the presence or absence of genes thought to be markers of an organism's pathogenicity. It is unclear whether these assays detect all pathogenic V. parahaemolyticus strains since a clear correlation between the presence of a particular gene and the organism's pathogenicity has not yet been observed. We have described a proteomics-based method to distinguish individual V. parahaemolyticus strains on the basis of their protein profiles and identified a specific protein that is characteristic of the pandemic O3:K6 strain and its clonal derivatives. In the pandemic clone of V. parahaemolyticus, a histone-like DNA-binding protein, HU-alpha, has a C-terminal amino acid sequence different from those of other strains of V. parahaemolyticus. Upon further study, it was discovered that the gene encoding this protein has a 16-kbp insert at the 3' terminus of the open reading frame for this protein. By using the protein sequence of the unique biomarker for the pandemic clone of V. parahaemolyticus, it was possible to rationally design specific PCR-based probes and assays that permit the rapid and precise identification of pandemic strains of V. parahaemolyticus. C1 US FDA, Instrumentat & Biophys Branch, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Musser, SM (reprint author), US FDA, Instrumentat & Biophys Branch, Ctr Food Safety & Appl Nutr, HFS 717,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM smusser@cfsan.fda.gov NR 31 TC 36 Z9 39 U1 0 U2 8 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 2004 VL 42 IS 4 BP 1657 EP 1665 DI 10.1128/JCM.42.4.1657-1665.2004 PG 9 WC Microbiology SC Microbiology GA 814GK UT WOS:000220963000045 PM 15071022 ER PT J AU Soares, CC Volotao, EM Albuquerque, MCM Nozawa, CM Linhares, REC Volokhov, D Chizhikov, V Lu, XY Erdman, D Santos, N AF Soares, CC Volotao, EM Albuquerque, MCM Nozawa, CM Linhares, REC Volokhov, D Chizhikov, V Lu, XY Erdman, D Santos, N TI Genotyping of enteric adenoviruses by using single-stranded conformation polymorphism analysis and Heteroduplex mobility assay SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RESTRICTION-ENDONUCLEASE ANALYSIS; PCR; IDENTIFICATION; STRAINS AB Single-stranded conformation polymorphism (SSCP) analysis and heteroduplex mobility assays (HMAs) were used to identify and genotype enteric adenoviruses (EAd). The results were compared to those of restriction endonuclease assays, species-specific PCRs, and direct nucleotide sequence analyses. Of the 31 stool samples tested, 15 isolates were identified as EAd and 7 were identified as nonenteric Ad by all methods. An agreement of 100% was found between the SSCP and HMA results. C1 Univ Fed Rio de Janeiro, Dept Virol, Inst Microbiol, BR-21941590 Rio De Janeiro, Brazil. Univ Estadual Londrina, Dept Microbiol, BR-86061970 Londrina, PR, Brazil. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Ctr Dis Control & Prevent, Div Viral & Rickettsial Dis, Atlanta, GA 30333 USA. RP Santos, N (reprint author), Univ Fed Rio de Janeiro, Dept Virol, Inst Microbiol, Cidade Univ,CCS,Bl I, BR-21941590 Rio De Janeiro, Brazil. EM nsantos@micro.ufrj.br RI Santos, Norma/H-6986-2015 OI Santos, Norma/0000-0002-5123-9172 NR 14 TC 6 Z9 6 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 2004 VL 42 IS 4 BP 1723 EP 1726 DI 10.1128/JCM.42.4.1723-1729.2004 PG 4 WC Microbiology SC Microbiology GA 814GK UT WOS:000220963000055 PM 15071032 ER PT J AU Sreenivas, G Raju, BVS Singh, R Selvapandiyan, A Duncan, R Sarkar, D Nakhasi, HL Salotra, P AF Sreenivas, G Raju, BVS Singh, R Selvapandiyan, A Duncan, R Sarkar, D Nakhasi, HL Salotra, P TI DNA polymorphism assay distinguishes isolates of Leishmania donovani that cause kala-azar from those that cause post-kala-azar dermal leishmaniasis in humans SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID COMPLEX AB Leishmania donovani in India causes visceral infection (kala-azar) and dermal infection (post-kala-azar dermal leishmaniasis). We report here the identification of polymorphism in a well-defined genetic locus among the Leishmania parasites causing the visceral and dermal manifestations, in a comparison of 15 post-kala-azar dermal leishmaniasis and 12 kala-azar patient isolates. C1 ICMR, Inst Pathol, New Delhi 110029, India. Indian Inst Chem Biol, Kolkata, India. US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review, Rockville, MD 20892 USA. RP Salotra, P (reprint author), ICMR, Inst Pathol, Safdarjung Hosp Campus, New Delhi 110029, India. EM salotra@vsnl.com RI Duncan, Robert/I-8168-2015; OI Duncan, Robert/0000-0001-8409-2501; Singh, Ruchi/0000-0001-8094-4703 NR 20 TC 20 Z9 20 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 2004 VL 42 IS 4 BP 1739 EP 1741 DI 10.1128/JCM.42.4.1739-1741.2004 PG 3 WC Microbiology SC Microbiology GA 814GK UT WOS:000220963000059 PM 15071036 ER PT J AU Averbuch, M Katzper, M AF Averbuch, M Katzper, M TI Assessment of visual analog versus categorical scale for measurement of osteoarthritis pain SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE visual analog; categorical; scale; pain ID RATING-SCALES; CLINICAL PAIN; SENSITIVITY; QUESTIONNAIRE; DESCRIPTORS; INTENSITY; PRECISION; EFFICACY; CANCER AB There is disagreement in the literature regarding which scales to use in pain measurement. The difference has usually been between nonverbal scales, such as visual analog scales and verbal ones, which usually provide only a limited number of response categories. A 12-week, randomized, double-blind naproxen sodium (500 mg bid) and placebo-controlled trial using the hip osteoarthritis (OA) flare-up pain mode, in which pain was measured on both visual analog and categorical scales simultaneously, was analyzed. The authors found a good correlation (> 0.995) between the time-series overage of the unconstrained visual analog scale and a 5-point categorical scale pain measurement in the osteoarthritis pain model in both active and placebo treatment arms. However, for individuals, there is a wide range of VAS responses for each categorical score, with overlaps between categories, The visual analog and categorical scales appear as effective in determining average osteoarthritis pain. However, a combined metric scale for pain measurement that provides the subject with multiple cues may improve communication and concordance between scales for individual pain determination. C1 US FDA, Ctr Drug Evaluat & Res, Div Analges Anti Inflammatory & Ophthalm Drug Pro, Rockville, MD 20857 USA. RP Katzper, M (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Analges Anti Inflammatory & Ophthalm Drug Pro, HFD-550,5600 Fishers Lane, Rockville, MD 20857 USA. NR 25 TC 27 Z9 28 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD APR PY 2004 VL 44 IS 4 BP 368 EP 372 DI 10.1177/0091270004263995 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 805UD UT WOS:000220390300005 PM 15051743 ER PT J AU Foley, SL Simjee, S Meng, JH White, DG McDermott, PF Zhao, SH AF Foley, SL Simjee, S Meng, JH White, DG McDermott, PF Zhao, SH TI Evaluation of molecular typing methods for Escherichia coli O157 : H7 isolates from cattle, food, and humans SO JOURNAL OF FOOD PROTECTION LA English DT Article ID FIELD GEL-ELECTROPHORESIS; SEROTYPE O157-H7; EAE GENE; PCR; MICROORGANISMS; IDENTIFICATION; PATHOGENS AB Escherichia coli O157:H7, a Shiga toxin-producing E. coli, has been the causative agent of many cases of severe, often life-threatening foodborne illness. Because of the importance of E. coli O157:H7 to public health, many molecular typing methods have been developed to determine its transmission routes and source of infection during epidemiological investigations. Pulsed-field gel electrophoresis (PFGE) is currently used by public health organizations to track infections of E. coli O157:117 and other foodborne pathogens. In this study, we compared the ability of PFGE, multilocus sequence typing (MLST), and repetitive-element PCR (Rep-PCR) to distinguish among 92 E. coli O157:H7 isolates from cattle, food, and infected humans. Several virulence genes, including the intimin gene (eaeA), the hemolysin gene (hlyA), and the H7 fimbrial gene (fliC), and a housekeeping gene for beta-glucuronidase (uidA) were included in MLST Rep-PCR reactions were performed using a commercially available typing kit (Bacterial Barcodes Inc., Houston, Tex.) with the provided Uprime-RI primer set. Results of the study indicated that PFGE provided the most discrimination among the techniques, identifying 72 distinct PFGE profiles for the isolates; Rep-PCR elucidated 14 different profiles, whereas MLST generated five profiles. Additionally, there did not appear to be any correlation among the typing methods examined in this study. Therefore, to date, PFGE remains the technique of choice for molecular subtyping of E. coli O157:H7. C1 US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. Univ Cent Arkansas, Dept Biol, Conway, AR 72035 USA. Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. RP Zhao, SH (reprint author), US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. EM szhao@cvm.fda.gov NR 31 TC 27 Z9 32 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 APR PY 2004 VL 67 IS 4 BP 651 EP 657 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 810LM UT WOS:000220705800004 PM 15083714 ER PT J AU Mills, JL Schonberger, LB Wysowski, DK Brown, P Durako, SJ Cox, C Kong, FH Fradkin, JE AF Mills, JL Schonberger, LB Wysowski, DK Brown, P Durako, SJ Cox, C Kong, FH Fradkin, JE TI Long-term, mortality in the united states cohort of pituitary-derived growth hormone recipients SO JOURNAL OF PEDIATRICS LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; CHILDREN; THERAPY; DEFICIENCY AB Objective Patients who received pituitary-derived growth hormone (GH) are at excess risk of mortality from Creutzfeldt-Jakob disease. We investigated whether they were at increased risk of death from other conditions, particularly preventable conditions. Study design A cohort (N = 6107) from known US pituitary-derived GH recipients (treated 1963-1985) was studied. Deaths were identified by reports from physicians and parents and the National Death Index. Rates were compared with the expected rates for the US population standardized for race, age, and sex. Results There were 433 deaths versus 114 expected (relative risk [RR], 3.8; 95% confidence interval [CI], 3.4-4.2; P < .0001) from 1963 through 1996. Risk was increased in subjects with GH deficiency caused by any tumor (RR, 10.4; 95% CI, 9.1-12.0; P < .0001). Surprisingly, subjects with hypoglycemia treated within the first 6 months of life were at extremely high risk (RR, 18.3; 95% CI, 9.2-32.8; P < .0001), as were all subjects with adrenal insufficiency (RR, 7.1; 95% CI, 6.2-8.2; P < .0001). A quarter of all deaths were sudden and unexpected. Of the 26 cases of Creutzfeldt-Jakob disease, four cases have died since 2000. Conclusions The death rate in pituitary-derived GH recipients was almost four times the expected rate. Replacing pituitary derived GH with recombinant GH has eliminated only the risk of Creutzfeldt-Jakob disease. Hypoglycemia and adrenal insufficiency accounted for far more mortality than Creutzfeldt-Jakob disease. The large number of potentially preventable deaths in patients with adrenal insufficiency and hypo glycemia underscores the importance of early intervention when infection occurs in patients with adrenal insufficiency, and aggressive treatment of panhypopituitarism. C1 NINDS, NICHHD, Bethesda, MD 20892 USA. NIDDKD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA USA. RP Mills, JL (reprint author), NICHD, Pediat Epidemiol Sect, NIH, DHHS, 6100 Bldg Room 7B03, Bethesda, MD 20892 USA. EM jamesmills@nih.gov NR 14 TC 72 Z9 73 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD APR PY 2004 VL 144 IS 4 BP 430 EP 436 DI 10.1016/j.jpeds.2003.12.036 PG 7 WC Pediatrics SC Pediatrics GA 811GO UT WOS:000220760600015 PM 15069388 ER PT J AU Jasper, JP Westenberger, BJ Spencer, JA Buhse, LF Nasr, M AF Jasper, JP Westenberger, BJ Spencer, JA Buhse, LF Nasr, M TI Stable isotopic characterization of active pharmaceutical ingredients SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE pharmaceutical materials; active pharmaceutical ingredients; stable isotopes; delta(13)C; delta(15)N; delta(18)O; delta D; isotropic fingerprinting ID RATIOS AB Stable isotopic characterization or "fingerprinting" of active pharmaceutical ingredients (APIs) is a highly-specific means of defining the provenance of these pharmaceutical materials. The isotopic analysts in this study were provided with 20 blind samples of four APIs (tropicamide, hydrocortisone, quinine HCL, and tryptophan) from one-to-five production batch(es) from one-to-five manufacturer(s). Only the chemical identity of the APIs was initially provided to the isotopic analysts. Depending on the API chemical composition, isotopic ratios of either three or four elements ((13)C/(12)C, (15)N/(14)N, (18)O/(16)O, and/or D/H) were measured by either elemental analyzer/isotope ratio mass spectrometry (EV/IRMS: carbon (delta(13)C) and nitrogen (delta(15)N)) or by thermal conversion-EV/IRMS (TCEA/IRMS; hydrogen (deltaD) and oxygen (delta(15)N)); in all cases, the isotopic results are reported in the standard delta-notation which represents part-per-thousand (parts per thousand) variations from the isotopic ratios of international standards. The stable isotopic analyses of the four suites of APIs spanned broad ranges in absolute value (A 8) and in estimated specificity (a product of dynamic ranges (DR, unitless)-note that these are upper limits of specificity because some of these isotope values may be partially interdependent). The five samples of tropicamide from one production batch and one manufacturer demonstrated the narrowest ranges (Deltadelta(13)C = 0.13parts per thousand; Deltadelta(15)N = 0.52parts per thousand; Delta(18)O = 0.24parts per thousand; DeltadeltaD = 2.8parts per thousand) and the smallest specificity of 1:30.9. By contrast, the five samples of tryptophan that came from five separate manufacturers had some of the widest isotopic ranges observed (Adelta(13)C = 21.32parts per thousand; Deltadelta(15)N = 5.26parts per thousand; Delta(18)O = 22.07parts per thousand; DeltadeltaD = 55.3parts per thousand) and had the largest specificity of 1:19.6 x 10(6). The isotopic provenance of the four suites of APIs readily emerged from bivariate plots of selected isotope ratios, particularly deltaD versus delta(18)O. (C) 2003 Elsevier B.V. All rights reserved. C1 Mol Isotope Technol LLC, Niantic, CT 06357 USA. US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Jasper, JP (reprint author), Mol Isotope Technol LLC, 8 Old Oak Lane, Niantic, CT 06357 USA. EM jpjasper@molecularisotopes.com NR 14 TC 29 Z9 30 U1 3 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD APR 1 PY 2004 VL 35 IS 1 BP 21 EP 30 DI 10.1016/S0731-7085(03)00581-8 PG 10 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 810JC UT WOS:000220699600003 PM 15030876 ER PT J AU Idowu, OR Peggins, JO AF Idowu, OR Peggins, JO TI Simple, rapid determination of enrofloxacin and ciprofloxacin in bovine milk and plasma by high-performance liquid chromatography with fluorescence detection SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE enrofloxacin; ciprofloxacin; bovine milk; bovine plasma; HPLC ID PRIMARY METABOLITE CIPROFLOXACIN; BIOLOGICAL-FLUIDS; 4 FLUOROQUINOLONES; TISSUES; PHARMACOKINETICS; PEFLOXACIN; RESIDUES; SINGLE; ASSAY; SERUM AB A rapid and simple procedure for determination of enrofloxacin and ciprofloxacin in bovine milk and plasma is described. Protein precipitation from both milk and plasma samples was achieved by addition of acetonitrile and phosphoric acid. Acetonitrile was removed with methylene chloride, leaving enrofloxacin and ciprofloxacin in the acidic aqueous extract. The aqueous extract was analyzed by high-performance liquid chromatography (HPLC) with fluorescence detection. The limit of quantitation (LOQ) for enrofloxacin and ciprofloxacin in milk was found to be 2 ng/ml. LOQ for enrofloxacin and ciprofloxacin in plasma was found to be I ng/ml. Linear calibration curves were obtained with correlation coefficient (r(2)) greater than or equal to0.99. Analysis of quality control (QC) samples gave results within +/-10% of the nominal values. Inter-assay precision for the analysis of milk QC samples were in the ranges: 4.63-12.49% (for enrofloxacin) and 4.67-9.86% (for ciprofloxacin). Inter-assay precision for the analysis of plasma QC samples were in the ranges: 6.60-17.31% (for enrofloxacin) and 6.14-13.87% (for ciprofloxacin). Intra-assay precision for the analysis of milk QC samples were in the following ranges: 3.65-7.21% (for enrofloxacin) and 1.58-14.28% (for ciprofloxacin). Intra-assay precision for the analysis of plasma QC samples were in the following ranges: 2.17-16.95% (for enrofloxacin) and 3.31-16.31% (for ciprofloxacin). The effectiveness of protein precipitants other than phosphoric acid was investigated. The method described has been applied to a study of the pharmacokinetics of enrofloxacin and ciprofloxacin in lactating dairy cows and beef steers. (C) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Idowu, OR (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM oidowu@cvm.fda.gov NR 26 TC 92 Z9 99 U1 0 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD APR 1 PY 2004 VL 35 IS 1 BP 143 EP 153 DI 10.1016/j.jpba.2004.01.006 PG 11 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 810JC UT WOS:000220699600016 PM 15030889 ER PT J AU Spann, KM Tran, KC Chi, B Rabin, RL Collins, PL AF Spann, KM Tran, KC Chi, B Rabin, RL Collins, PL TI Suppression of the induction of alpha, beta, and gamma interferons by the NS1 and NS2 proteins of human respiratory syncytial virus in human epithelial cells and macrophages SO JOURNAL OF VIROLOGY LA English DT Article ID MESSENGER-RNA; VACCINE; IFN; LIVE; CHIMPANZEES; EXPRESSION; RESPONSES; MUTANTS; GENES; RSV AB Wild-type human respiratory syncytial virus (HRSV) is a poor inducer of alpha/beta interferons (IFN-alpha/beta). However, recombinant HRSV lacking the NS1 and NS2 genes (DeltaNSI/2) induced high levels of IFN-alpha and -beta in human pulmonary epithelial cells (A549) as well as in macrophages derived from primary human peripheral blood monocytes. Results with NS1 and NS2 single- and double-gene-deletion viruses indicated that the two proteins function independently as well as coordinately to achieve the full inhibitory effect, with NS1 having a greater independent role. The relative contributions of the individual NS proteins were the converse of that recently described for bovine RSV (J. F. Valarcher, J. Furze, S. Wyld, R. Cook, K. K. Conzelmann, and G. Taylor, J. Virol. 77:8426-8439, 2003). This pattern of inhibition by HRSV NS1 and NS2 also extended to the newly described antiviral cytokines IFN-lambda1, -2 and -3. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Ctr Biol Evaluat & Res, Food & Drug Adm, Lab Immunobiochem, Bethesda, MD 20892 USA. RP Collins, PL (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 50,Room 6507,50 S Dr,MSC 8007, Bethesda, MD 20892 USA. EM pcollins@niaid.nih.gov RI Spann, Kirsten/B-4524-2013 OI Spann, Kirsten/0000-0003-0567-8382 NR 28 TC 249 Z9 264 U1 2 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 APR PY 2004 VL 78 IS 8 BP 4363 EP 4369 DI 10.1128/JVI.78.8.4363-4396.2004 PG 7 WC Virology SC Virology GA 809MU UT WOS:000220641600056 PM 15047850 ER PT J AU Hubbard, WK AF Hubbard, WK TI High prescription drug prices and the influence of the food and drug administration - In reply SO MAYO CLINIC PROCEEDINGS LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Hubbard, WK (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD APR PY 2004 VL 79 IS 4 BP 569 EP 570 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 807MM UT WOS:000220505600018 ER PT J AU Badano, A Gagne, RM Jennings, RJ Drilling, SE Imhoff, BR Muka, E AF Badano, A Gagne, RM Jennings, RJ Drilling, SE Imhoff, BR Muka, E TI Noise in flat-panel displays with subpixel structure SO MEDICAL PHYSICS LA English DT Article DE liquid crystal display; medical display; noise; noise-power spectrum ID RESOLUTION; DEVICES AB Subpixel structures found in medical monochrome active-matrix liquid crystal displays (AMLCDs) affect noise estimates measured with conventional methods. In this work, we discuss methods that identify sources of noise and permit the comparison of luminance noise estimates across technologies independent of pixel design and device technology. We used a three-million pixel AMLCD with a pixel structure consisting of three color stripes, each in a two-domain, in-plane switching mode. Images of uniform fields displayed on the AMLCD were acquired using a low-noise, high-resolution CCD camera. The camera noise and flat-field response were characterized using a uniform light source constructed for this purpose. We show results in terms of spatial luminance noise and noise power spectrum for high-resolution images and for the same images processed with a pixel-aligned aperture. We find that the pixel-aligned aperture eliminates almost all the noise found in the high-resolution images, suggesting that most of the luminance noise in AMLCDs comes from the subpixel structure and less-than-100% aperture ratio, rather than from interpixel variations. (C) 2004 American Association of Physicists in Medicine. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Marquette Univ, Milwaukee, WI 53201 USA. Washington Univ, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. EM agb@cdrh.fda.gov OI badano, aldo/0000-0003-3712-6670 NR 18 TC 26 Z9 26 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 APR PY 2004 VL 31 IS 4 BP 715 EP 723 DI 10.1118/1.1656529 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 813HK UT WOS:000220898000004 PM 15124988 ER PT J AU Haffner, ME AF Haffner, ME TI Developing treatments for inborn errors: incentives available to the clinician SO MOLECULAR GENETICS AND METABOLISM LA English DT Article; Proceedings Paper CT Workshop on New Developments in Urea Cycle Disorders CY AUG 31-SEP 01, 2003 CL Sydney, AUSTRALIA SP Ucyclyd Pharma, Orphan Europe, Swedish Orphan Int AB, Orphan Australia, Abbott Labs, Mead Johnson, Natl Urea Cycle Disorders Fdn DE orphan; Orphan Drug Act; incentives; research grants; rare disease AB Disorders resulting from inborn errors of metabolism (IEM) affect very small numbers of individuals. The entire population, however, of patients suffering the results of inherited metabolic disorders is large, and has been of increasing concern to patient groups and health care professionals in the United States as well as other countries throughout the world. The 1983 US Orphan Drug Act (ODA) serves to facilitate the development of drugs to treat rare diseases by providing several economic incentives. The sponsor of a product designated as an orphan by the Food & Drugs Administration (FDA) Office of Orphan Products Development (OPD) qualifies for tax credits on clinical trial expenses, the award of grant funding by FDA, through the OPD, and 7 years of marketing exclusivity for a designated drug, or biological product that receives FDA market approval. Orphan drug legislation in the US has benefited victims of IEM by encouraging development of drugs for metabolic deficiencies affecting populations that otherwise would be ignored. America's solution to the orphan drug problem has had worldwide impact. The success of this legislation was a factor leading to the 1993 orphan drug law in Japan; the 1997 implementation of a process whereby most FDA-approved orphan drugs and biological products will be similarly approved in Australia; and, in 1999, regulation on orphan medicinal products in the European Union (EU). Today, international support for rare disease research is providing stimulus and motivation to overcome the financial barriers and encourage development of treatment for very rare diseases throughout the world. Published by Elsevier Inc. 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. EM mhaffner@oc.fda.gov NR 0 TC 1 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD APR PY 2004 VL 81 SU 1 BP S63 EP S66 DI 10.1016/j.ymgme.2003.10.015 PG 4 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 816QT UT WOS:000221125100010 PM 15050976 ER PT J AU Klinman, DM AF Klinman, DM TI Immunotherapeutic uses of CpG oligodeoxynucleotides SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID B SURFACE-ANTIGEN; PLASMACYTOID DENDRITIC CELLS; TOLL-LIKE RECEPTORS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; ALLERGIC LUNG INFLAMMATION; INDUCE AUTOIMMUNE-DISEASE; NATURAL-KILLER ACTIVITY; SIMPLEX-VIRUS TYPE-2; BACTERIAL-DNA; IMMUNOSTIMULATORY DNA AB Synthetic oligodeoxynucleotides (ODNs) that contain immunostimulatory CpG motifs trigger an immunomodulatory cascade that involves B and T cells, natural killer cells and professional antigen-presenting cells. The response to CpG ODNs skews the host's immune milieu in favour of T helper 1 (T(H)1)-cell responses and pro-inflammatory cytokine production-an effect that underlies their use as immunoprotective agents, vaccine adjuvants and anti-allergens. Preclinical studies provide evidence that CpG ODNs are effective for each of these uses. Ongoing clinical studies indicate that CpG ODN use is safe in humans, and that they modulate the immune response to co-administered allergens and vaccines. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29A,Room 3D10, Bethesda, MD 20892 USA. EM klinman@cber.FDA.gov NR 145 TC 32 Z9 32 U1 3 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD APR PY 2004 VL 4 IS 4 BP 248 EP 257 DI 10.1038/nri1329 PG 10 WC Immunology SC Immunology GA 808HI UT WOS:000220559800011 ER PT J AU Rudolf, PM Bernstein, IBG AF Rudolf, PM Bernstein, IBG TI Counterfeit drugs SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Rudolf, PM (reprint author), US FDA, Rockville, MD 20857 USA. NR 1 TC 33 Z9 33 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 1 PY 2004 VL 350 IS 14 BP 1384 EP 1386 DI 10.1056/NEJMp038231 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 808IJ UT WOS:000220562500004 PM 15070787 ER PT J AU Karadag, A Riminucci, M Bianco, P Cherman, N Kuznetsov, SA Nguyen, N Collins, MT Robey, PG Fisher, LW AF Karadag, A Riminucci, M Bianco, P Cherman, N Kuznetsov, SA Nguyen, N Collins, MT Robey, PG Fisher, LW TI A novel technique based on a PNA hybridization probe and FRET principle for quantification of mutant genotype in fibrous dysplasia/McCune-Albright syndrome SO NUCLEIC ACIDS RESEARCH LA English DT Article ID POLYMERASE-CHAIN-REACTION; MITOCHONDRIAL-DNA; POINT MUTATIONS; DIABETES-MELLITUS; GENE; BONE; DISEASE; ACCUMULATION; HETEROPLASMY; CARDIOMYOPATHY AB Somatic mutations are present in various proportions in numerous developmental pathologies. Somatic activating missense mutations of the GNAS gene encoding the Gs(alpha) protein have previously been shown to be the cause of fibrous dysplasia of bone (FD)/McCune-Albright syndrome (MAS). Because in MAS patients, tissues as diverse as melanocytes, gonads and bone are affected, it is generally accepted that the GNAS mutation in this disease must have occurred early in development. Interestingly, it has been shown that the development of an active FD lesion may require both normal and mutant cells. Studies of the somatic mosaic states of FD/MAS and many other somatic diseases need an accurate method to determine the ratio of mutant to normal cells in a given tissue. A new method for quantification of the mutant:normal ratio of cells using a PNA hybridization probe-based FRET technique was developed. This novel technique, with a linear sensitivity of 2.5% mutant alleles, was used to detect the percentage mutant cells in a number of tissue and cell culture samples derived from FD/MAS lesions and could easily be adapted for the quantification of mutations in a large spectrum of diseases including cancer. C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, DHHS, Bethesda, MD 20892 USA. Univ Aquila, Dipartimento Med Sperimentale, I-67100 Laquila, Italy. Parco Sci Biomed San Raffaele, Rome, Italy. Univ Roma La Sapienza, Dipartimento Med Sperimentale & Patol, Rome, Italy. US FDA, Ctr Biol Evaluat & Res, Dept Hlth & Human Serv, Bethesda, MD USA. RP Karadag, A (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, DHHS, 30 Convent Dr,Bldg 30,Room 223,MSC 4320, Bethesda, MD 20892 USA. EM akaradag@dir.nidcr.nih.gov RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Telethon [E.1029] NR 40 TC 25 Z9 26 U1 1 U2 2 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. PD APR PY 2004 VL 32 IS 7 AR e63 DI 10.1093/nar/gnh059 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 816YO UT WOS:000221145400029 PM 15096559 ER PT J AU Ornstein, DK Petricoin, EF AF Ornstein, DK Petricoin, EF TI Proteomies to diagnose human tumors and provide prognostic information SO ONCOLOGY-NEW YORK LA English DT Article ID LASER CAPTURE MICRODISSECTION; PROSTATE-SPECIFIC ANTIGEN; CODED AFFINITY TAGS; MASS-SPECTROMETRY; GEL-ELECTROPHORESIS; PROTEIN EXPRESSION; SWISS-2DPAGE DATABASE; OVARIAN-CANCER; CELL-LINES; SELDI-TOF AB Proteomics is a rapidly emerging scientific discipline that holds great promise in identifying novel diagnostic and prognostic biomarkers for human cancer. Technologic improvements have made it possible to profile and compare the protein composition within defined populations of cells. Laser capture microdissection is a tool for procuring pure populations of cells from human tissue sections to be used for downstream proteomic analysis. Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) has been used traditionally to separate complex mixtures of proteins. Improvements in this technology have greatly enhanced resolution and sensitivity providing a more reproducible and comprehensive survey. Image analysis software and robotic instrumentation have been developed to facilitate comparisons of complex protein expression patterns and isolation of differentially expressed proteins spots. Differential in-gel electrophoresis (DIGS) facilitates protein expression by labeling different populations of proteins with fluorescent dyes. Isotope-coded affinity tagging (ICAT) uses mass spectroscopy for protein separation and different isotope tags for distinguishing populations of proteins. Although in the past proteomics has been primarily used for discovery, significant efforts are being made to develop proteomic technologies into clinical tools. Reverse phase protein arrays offer a robust new method of quantitatively assessing expression levels and the activation status of a panel of proteins. Surface-enhanced laser-desorption/ionization time-of-flight (SELDI-TOF) mass spectroscopy rapidly assesses complex protein mixtures in tissue or serum. Combined with artificial intelligence-based pattern recognition algorithms, this emerging technology can generate highly accurate diagnostic in = formation. It is likely that mass spectroscopy-based serum proteomics will evolve into useful clinical tools for the detection and treatment of human cancers. C1 Univ Calif Irvine, Dept Urol, UCI Med Ctr, Orange, CA 92868 USA. US FDA, FDA NCI Clin Proteom Program, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Ornstein, DK (reprint author), Univ Calif Irvine, Dept Urol, UCI Med Ctr, 101 City Dr,Bldg 55,Rm300, Orange, CA 92868 USA. EM dornstei@uci.edu NR 42 TC 24 Z9 28 U1 0 U2 1 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD APR PY 2004 VL 18 IS 4 BP 521 EP 529 PG 9 WC Oncology SC Oncology GA 052DG UT WOS:000238210700021 PM 15134357 ER PT J AU Mohan, AK Braun, MM Ellenberg, S Hedje, J Cote, TR AF Mohan, AK Braun, MM Ellenberg, S Hedje, J Cote, TR TI Deaths among children less than two years of age receiving palivizumab: an analysis of comorbidities SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE synagis; palivizumab; respiratory syncytial virus ID RESPIRATORY SYNCYTIAL VIRUS; REDUCES HOSPITALIZATION; MONOCLONAL-ANTIBODY; INFANT-MORTALITY; PROPHYLAXIS; MEDI-493 AB Background. Palivizumab (Synagis) is used for prophylaxis against respiratory syncytial virus infection among children at high risk for respiratory syncytial virus disease. A number of deaths after palivizumab use among children <2 years have been reported to the Food and Drug Administration. We assessed available information, including the extent to which preexisting medical conditions may have put these children at higher than normal risk of death. Methods. We reviewed reports of deaths to the Food and Drug Administration (June 1998 to December 2001) among children <2 years of age who received palivizumab. Results. There were 133 deaths reported after palivizumab use. Median age at death was 5 months, and 54% of the children were male. At least one congenital anomaly was reported in 85 cases (64%), and 44% of cases had multiple anomalies. Of the 100 cases with reported gestational age at birth, 36% were severely premature (<28 weeks), 48% were moderately premature (28 to 36 weeks) and 16% had normal gestational age. Only 2% of all cases were full term and were born without congenital anomalies; 50% had both conditions, 34% had prematurity alone and 14% had congenital anomalies alone. A cause of death was reported for 88 (66%) cases; most (38%) died from their congenital anomalies or from respiratory infections (23%). Conclusions. Most children dying after palivizumab treatment were at increased risk of death; many had multiple congenital anomalies and/or premature birth. Patterns of outcomes and the reported medical course did not suggest that palivizumab further elevated the risk of death. Current data do not alter the safety and efficacy assessment that led to the licensure of palivizumab. C1 US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Rockville, MD 20852 USA. NIAID, Off Global Affairs, NIH, Bethesda, MD 20892 USA. RP Mohan, AK (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, 1404 Rockville Pike,Suite 200S, Rockville, MD 20852 USA. EM mohan@cber.fda.gov NR 24 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD APR PY 2004 VL 23 IS 4 BP 342 EP 345 DI 10.1097/00006454-200404000-00013 PG 4 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 812YD UT WOS:000220873900012 PM 15071290 ER PT J AU Galvez, MP Vanable, L Forman, JA Landrigan, PJ Akeredolu, E Leighton, J Nagin, D Yip, W Simmonds, K AF Galvez, MP Vanable, L Forman, JA Landrigan, PJ Akeredolu, E Leighton, J Nagin, D Yip, W Simmonds, K TI A case of childhood lead poisoning from commercially manufactured European ceramic dinnerware, New York City, 2003 SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 03-06, 2003 CL SEATTLE, WA SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ C1 CUNY Mt Sinai Sch Med, New York, NY 10029 USA. New York City Dept Hlth & Mental Hyg, Lead Poisoning Prevent Program, New York, NY USA. US FDA, Food Chem Branch, NE Reg Lab, Jamaica, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 1425 BP 251A EP 252A PN 2 PG 2 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591101474 ER PT J AU El-Mohandes, AAE Aly, H Hammad, TA Mohamed, M Janosy, N Urso, P AF El-Mohandes, AAE Aly, H Hammad, TA Mohamed, M Janosy, N Urso, P TI Does pre-pregnancy maternal obesity influence length of gestation and birth weight (BW)?: A multivariate analysis SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 04, 2004 CL San Francisco, CA SP Pediatr Acad Soc C1 George Washington Univ, Med Ctr, Newborn Serv, Washington, DC 20037 USA. US FDA, Rockville, MD 20857 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 3370 BP 594A EP 594A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591103447 ER PT J AU Mone, SM Gillman, MW Miller, TL Herman, EH Lipshultz, SE AF Mone, SM Gillman, MW Miller, TL Herman, EH Lipshultz, SE TI Effects of environmental exposures on the cardiovascular system: Prenatal period through adolescence SO PEDIATRICS LA English DT Review DE environmental exposures; cardiovascular system; pediatric; fetal ID HUMAN-IMMUNODEFICIENCY-VIRUS; CONGENITAL HEART-DEFECTS; PERICONCEPTIONAL MULTIVITAMIN SUPPLEMENTATION; PROSPECTIVE (PCHIV)-C-2-H-2 MULTICENTER; VITAMIN-A INTAKE; PERSISTENT PULMONARY-HYPERTENSION; EARLY ATHEROSCLEROTIC LESIONS; ACUTE LYMPHOBLASTIC-LEUKEMIA; DRINKING-WATER CONTAMINANTS; P(2)C(2) HIV MULTICENTER AB Exposures to drugs, chemical and biological agents, therapeutic radiation, and other factors before and after birth can lead to pediatric or adult cardiovascular anomalies. Furthermore, nutritional deficiencies in the perinatal period can cause cardiovascular anomalies. These anomalies may affect heart structure, the conduction system, the myocardium, blood pressure, or cholesterol metabolism. Developmental periods before and after birth are associated with different types of risks. The embryonic period is the critical window of vulnerability for congenital malformations. The fetal period seems to have lifelong effects on coronary heart disease and its precursors. During the weeks immediately after birth, susceptibility to myocardial damage seems to be high. Exposure to cancer chemotherapy or radiotherapy in childhood raises the risk of long-term progressive left ventricular dysfunction and other cardiovascular problems. In childhood and adolescence, use of recreational drugs such as cocaine and tobacco poses cardiovascular dangers as well. Where evidence about environmental exposures is limited, we have included models of disease and other exposures that are suggestive of the potential impact of environmental exposures. C1 Univ Miami, Sch Med, Holtz Childrens Hosp, Jackson Mem Med Ctr, Miami, FL 33136 USA. Childrens Hosp, Med Ctr, Div Pediat Cardiol, Cincinnati, OH 45229 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Univ Miami, Sch Med, Div Pediat Clin Res, Miami, FL 33136 USA. Univ Miami, Sch Med, Dept Pediat, Miami, FL 33136 USA. Univ Miami, Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. US FDA, Div Appl Pharmacol Res HFD910, Laurel, MD USA. RP Lipshultz, SE (reprint author), Univ Miami, Sch Med, Holtz Childrens Hosp, Jackson Mem Med Ctr, 1601 NW 12th Ave,9th Fl, Miami, FL 33136 USA. EM SLipshultz@med.miami.edu FU NCI NIH HHS [CA 34183, CA 68484, CA 79060]; NCRR NIH HHS [RR02172]; NHLBI NIH HHS [HL 59837, HL 07937, HL 48012, HL 48020, HL 53392, HL 58731, HL 64925, HL 68041, HL 68228, HL 72705, HR 96041]; NICHD NIH HHS [HD 34568] NR 198 TC 50 Z9 58 U1 2 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 APR 1 PY 2004 VL 113 IS 4 SU S BP 1058 EP 1069 PG 12 WC Pediatrics SC Pediatrics GA 808RC UT WOS:000220585200017 PM 15060200 ER PT J AU Solhaug, MJ Bolger, PM Jose, PA AF Solhaug, MJ Bolger, PM Jose, PA TI The developing kidney and environmental toxins SO PEDIATRICS LA English DT Article DE kidney; toxins; development; angiotensin; prostanoids ID RENIN-ANGIOTENSIN SYSTEM; ACUTE-RENAL-FAILURE; FUMONISIN B-1; RAT-KIDNEY; DEVELOPMENTAL TOXICITY; 2ND-TRIMESTER FETUSES; POSTNATAL-DEVELOPMENT; PERINATAL-DEVELOPMENT; ADULT HYPERTENSION; MERCURIC-CHLORIDE AB The effects of environmental chemicals, drugs, and physical agents on the developing kidney are influenced by the state of renal development and maturation. The development of the kidney, the major excretory organ after birth, consists of 3 stages: the pronephros, or cervical kidney; mesonephros, or thoracic kidney; and metanephros, or abdominal kidney, the definitive kidney. In humans, nephrogenesis and organogenesis occur from the 6th to the 36th weeks of gestational age. After 36 weeks, nephrogenesis is complete and each kidney has a full complement of nephrons. The extent of chemical-induced renal toxicity is related, in part, to the efficiency in which the particular compound is transported by renal tubules. Because renal tubular transport capacities vary with maturation, the degree of nephrotoxicity may also vary with maturation. The signs and symptoms of nephrotoxicity can appear acutely or insidiously. Unexplained acute renal failure, chronic mild proteinuria, or even hypertension can be a manifestation of nephrotoxic agents. Species differences occur, thus the need for studies in humans. C1 Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. Eastern Virginia Med Sch, Dept Physiol, Norfolk, VA 23501 USA. US FDA, Washington, DC 20204 USA. Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20007 USA. RP Jose, PA (reprint author), Georgetown Univ, Med Ctr, Dept Pediat, 3800 Reservoir Rd NW, Washington, DC 20007 USA. EM pjose01@georgetown.edu FU NIDDK NIH HHS [DK52612] NR 80 TC 32 Z9 32 U1 1 U2 4 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 1 PY 2004 VL 113 IS 4 SU S BP 1084 EP 1091 PG 8 WC Pediatrics SC Pediatrics GA 808RC UT WOS:000220585200020 PM 15060203 ER PT J AU Haber, P Chen, RT Zanardi, LR Mootrey, GT English, R Braun, MM AF Haber, P Chen, RT Zanardi, LR Mootrey, GT English, R Braun, MM CA VAERS Working Grp TI An analysis of rotavirus vaccine reports to the vaccine adverse event reporting system: More than intussusception alone? SO PEDIATRICS LA English DT Article DE rotavirus vaccine; Vaccine Adverse Event Reporting System; VAERS; vaccine safety; postmarketing surveillance; rotavirus vaccine ID SPONTANEOUS REDUCTION; SURVEILLANCE; VAERS; IMMUNIZATION; ASSOCIATION; PREVENTION; INFECTION; INFANTS; DISEASE; SAFETY AB Background. The rhesus-human rotavirus reassortant-tetravalent vaccine (RRV-TV) was licensed on August, 31, 1998, and subsequently recommended for routine infant immunizations in the United States. After similar to1 million doses had been administered, an increase in acute risk of intussusception in vaccinees led to the suspension of the use of RRV-TV and its withdrawal from the market. These postmarketing safety studies focused on a single adverse event ( intussusception) and, to minimize the risk of a false-positive finding, accepted only cases that met a strict case definition. Safer rotavirus vaccines are needed to prevent the substantial global morbidity and mortality caused by rotavirus infections; their development and future use may benefit from a better understanding of the postmarketing safety profile of RRV-TV beyond intussusception. Objective. To characterize more completely the postmarketing surveillance safety profile of RRV-TV more completely by review and analysis of Vaccine Adverse Event Reporting System (VAERS) case reports to better understand 1) whether severe adverse events other than intussusception may have occurred after RRV-TV and 2) the likely scope of gastrointestinal illnesses, of which the previously identified, highly specific intussusception cases may account for just a fraction. Setting and Participants. Infants vaccinated with RRV-TV and other vaccines in the United States and for whom a report was submitted to VAERS during September 1, 1998, to December 31, 1999. Methodology. To detect adverse events of interest other than intussusception, we used proportional morbidity analysis to compare the adverse event profile of VAERS reports among infants who received routine vaccines including RRV-TV ( after excluding confirmed and suspected intussusception reports) with infants who received identical vaccine combinations but without RRV-TV. Next, to better capture all described diagnoses, signs, and symptoms associated with the suspected adverse events, a set of new codes was developed and assigned to each VAERS report. All 448 nonfatal RRV-TV-associated reports ( including intussusception) were recoded manually from the clinical description on the VAERS report and categorized into clinical groups to better describe a spectrum of reported illnesses after the vaccine. Each report was assigned to one of the following hierarchical and mutually exclusive clinical groups: 1) diagnosed intussusception; 2) suspected intussusception; 3) illness consistent with either gastroenteritis or intussusception; 4) gastroenteritis; 5) other gastrointestinal diagnoses (ie, not consistent with intussusception or rotavirus-like gastroenteritis); and 6) nongastrointestinal diagnoses. Results. Even after excluding intussusception cases, a higher proportion of RRV-TV reports than non-RRV-TV reports included fever and various gastrointestinal symptoms, most notably bloody stool but also vomiting, diarrhea, abdominal pain, gastroenteritis, abnormal stool, and dehydration. Distribution of RRV-TV reports by clinical groups was as follows: diagnosed intussusception (109 [24%], suspected intussusception (36 [8%]), and illness consistent with gastroenteritis or intussusception (33 [7%]), gastroenteritis (101 [22%]), other gastrointestinal diagnoses (10 [2%]), and nongastrointestinal outcomes (159 [35%]). The median time interval between vaccination and illness onset decreased incrementally among the first 4 clinical groups: from 7 days for diagnosed intussusceptions to 3 days for gastroenteritis. Conclusions. Intussusception and gastroenteritis were the most commonly reported outcomes; however, a substantial number of reports indicate signs and symptoms consistent with either illness, possibly suggestive of a spectrum of gastrointestinal illness(es) related to RRV-TV. Although VAERS data have recognized limitations such as underreporting ( that may differ by vaccine) and are nearly always insufficient to prove causality between a vaccine and an adverse event, this safety profile of RRV-TV may aid better understanding of the pathophysiology of intussusception as well as development of future safer rotavirus vaccines. C1 CDCP, Immunizat Safety Branch, Epidemiol & Surveillance Div, Natl Immunizat Program, Atlanta, GA 30333 USA. US FDA, Div Epidemiol, Off Biostat & Epidemiol, Rockville, MD 20857 USA. RP Haber, P (reprint author), CDCP, Immunizat Safety Branch, Epidemiol & Surveillance Div, Natl Immunizat Program, Mail Stop E-61,1600 Clifton Rd, Atlanta, GA 30333 USA. EM phaber@cdc.gov NR 34 TC 25 Z9 26 U1 1 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR 1 PY 2004 VL 113 IS 4 BP E353 EP E359 DI 10.1542/peds.113.4.e353 PG 7 WC Pediatrics SC Pediatrics GA 808RB UT WOS:000220585100054 PM 15060267 ER PT J AU Willy, ME Li, ZL AF Willy, ME Li, ZL TI What is prescription labeling communicating to doctors about hepatotoxic drugs? A study of FDA approved product labeling SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article; Proceedings Paper CT Conference of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR, 2002 CL Atlanta, GA SP Amer Soc Clin Pharmacol Therapeut DE hepatic failure; labeling; FDA AB Purpose The objective of this study was to evaluate the informativeness and consistency of product labeling of hepatotoxic drugs marketed in the United States. Methods We searched the Physicians' Desk Reference-2000 for prescription drugs with hepatic failure and/or hepatic necrosis listed in the labeling. We used a six-item checklist to evaluate the 'informativeness' and consistency of the labeling content. An informativeness score equaled the proportion of checklist items present in each drug's labeling. Results Ninety-five prescription drugs were included in the study. Eleven (12%) of the drugs had information related to hepatic failure in a Black Boxed Warning, 52 (54%) in the Warnings section and 32 (34%) in the Adverse Reactions section of the label. The mean informativeness score was 35%; the score was significantly higher, 61%, when the risk was perceived to be high. The informativeness of labeling was not affected by the time of the labeling, but differed across the Center for Drug Evaluation and Research (CDER) Review Division responsible for the labeling. Conclusions The information provided in labeling is variable and affected by many factors, including the perceived level of risk and review division strategy. Product labeling may benefit from current FDA initiatives to improve the consistency of risk-related labeling. Published in 2003 by John Wiley Sons, Ltd. C1 US FDA, Off Drug Safety, Rockville, MD 20857 USA. RP Willy, ME (reprint author), US FDA, Off Drug Safety, 5600 Fishers Ln,HDF-440,Room 15B-18, Rockville, MD 20857 USA. EM WillyM@cder.fda.gov FU PHS HHS [00-015] NR 2 TC 18 Z9 18 U1 0 U2 1 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 2004 VL 13 IS 4 BP 201 EP 206 DI 10.1002/pds.856 PG 6 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 810VE UT WOS:000220731000001 PM 15255086 ER PT J AU Hanna, GM AF Hanna, GM TI NMR regulatory analysis: determination and characterization of S-adeno-syl-L-methionine in dietary supplements SO PHARMAZIE LA English DT Article ID DOUBLE-BLIND MULTICENTER; KNEE OSTEO-ARTHRITIS; CLINICAL-TRIAL; CEREBROSPINAL-FLUID; THERAPEUTIC AGENT; RENAL-FAILURE; ADENOSYLMETHIONINE; ADENOSYLHOMOCYSTEINE; METHYLATION; OSTEOARTHRITIS AB H-1 NMR methodology is described for the determination and characterization of the dietary supplement S-adenosyl-L-Imethionine (SAM), recently introduced to the US market, utilizing a 400 MHz spectrometer without the need of pure reference standards. The developed methodology is able to assess chemical structure, differentiate between biologically-active (S)-diastereomer and biologically-inactive (R)-diastereomer, and determine the ratio of each in the dietry supplement formulation. The determination of the percentage of declared SAM was based on the integrals for the methyl proton of 2-methyl-2-propanol served as an internal standard at delta 1.24 and the methine proton H-1, of SAM ribose ring at delta 6.06. The percentage of the active diastereomer was calculated from the relative intensities of the sulfonium methyl singlets corresponding to the major component (S)-diastereomer at delta 2.98 and the minor (R)-counterpart at delta 2.93. The accuracy was established by analyzing synthetic mixtures of the analyte and the internal standard. Excellent agreement was verified between the assay results and the quantities of analyte in the mixture. The mean +/- SD recovery values for SAM and its (R)-diastereomer impurity from a set of 10 synthetic mixtures were 99.6 +/- 0.8% and 22.5 +/- 0.1%, respectively. Using 10 lots, the percentage of SAM ranged from 0 to 110.7% of the declared value and the percentage of the active (S)-diastereomer ranged from 0 to 82.3%. C1 US FDA, NE Reg Lab, Dept Hlth & Human Serv, Jamaica, NY 11433 USA. RP Hanna, GM (reprint author), US FDA, NE Reg Lab, Dept Hlth & Human Serv, 158-15 Liberty Ave, Jamaica, NY 11433 USA. EM ghanna@ora.fda.gov NR 51 TC 6 Z9 6 U1 0 U2 2 PU GOVI-VERLAG GMBH PI ESCHBORN PA PHARMAZEUTISCHER VERLAG GINNHEIMER STRASSE 26, D-65760 ESCHBORN, GERMANY SN 0031-7144 J9 PHARMAZIE JI Pharmazie PD APR PY 2004 VL 59 IS 4 BP 251 EP 256 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 811IN UT WOS:000220765700002 PM 15125566 ER PT J AU Chen, HZ Wang, RF Cerniglia, CE AF Chen, HZ Wang, RF Cerniglia, CE TI Molecular cloning, overexpression, purification, and characterization of an aerobic FMN-dependent azoreductase from Enterococcus faecalis SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE Enterococcus faecalis; aerobic azoreductase; azo dye; human intestinal microflora ID HUMAN INTESTINAL MICROFLORA; AZO DYES; ESCHERICHIA-COLI; BACTERIA; BENZIDINE; METABOLISM; REDUCTION; DRUG; NITROREDUCTASE; DEGRADATION AB Azo dyes represent a major class of synthetic colorants that are ubiquitous in foods and consumer products. Enterococcus faecalis is a predominant member of the human gastrointestinal microflora. Strain ATCC 19433 grew in the presence of azo dyes and metabolized them to colorless products. A gene encoding a putative FMN-dependent aerobic azoreductase that shares 34% identity with azoreductase (AcpD) of Escherichia coli has been identified in this strain. The gene in E faecalis, designated as azoA, encoded a protein of 208 amino acids with a calculated isoelectric point of 4.8. AzoA was heterologously overexpressed in E. coli with a strong band of 23 kDa on SDS-PAGE. The purified recombinant enzyme was a homodimer with a molecular weight of 43 kDa, probably containing one molecule of FMN per dimer. AzoA required FMN and NADH, but not NADPH, as a preferred electron donor for its activity. The apparent K-m values for both NADH and 2-[4-(dimethylamino)phenylazo]benzoic acid (Methyl red) substrates were 0.14 and 0.024 mM, respectively. The apparent V-max was 86.2 muM/min/mg protein. The enzyme was not only able to decolorize Methyl red, but was also able to convert sulfonated azo dyes Orange II, Amaranth, Ponceau BS, and Ponceau S. AzoA is the first aerobic azoreductase to be identified and characterized from human intestinal gram-positive bacteria. (C) 2004 Elsevier Inc. All rights reserved. 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 36 TC 94 Z9 107 U1 3 U2 21 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD APR PY 2004 VL 34 IS 2 BP 302 EP 310 DI 10.1016/j.pep.2003.12.016 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 803LU UT WOS:000220233400019 PM 15003265 ER PT J AU Thomas, K Aalbers, M Bannon, GA Bartels, M Dearman, RJ Esdaile, DJ Fu, TJ Glatt, CM Hadfield, N Hatzos, C Hefle, SL Heylings, JR Goodman, RE Henry, B Herouet, C Holsapple, M Ladics, GS Landry, TD MacIntosh, SC Rice, EA Privalle, LS Steiner, HY Teshima, R van Ree, R Woolhiser, M Zawodny, J AF Thomas, K Aalbers, M Bannon, GA Bartels, M Dearman, RJ Esdaile, DJ Fu, TJ Glatt, CM Hadfield, N Hatzos, C Hefle, SL Heylings, JR Goodman, RE Henry, B Herouet, C Holsapple, M Ladics, GS Landry, TD MacIntosh, SC Rice, EA Privalle, LS Steiner, HY Teshima, R van Ree, R Woolhiser, M Zawodny, J TI A multi-laboratory evaluation of a common in vitro pepsin digestion assay protocol used in assessing the safety of novel proteins SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE digestive stability; protein allergenicity; biotechnology; genetically modified foods; pepsinolysis ID POLYACRYLAMIDE-GEL ELECTROPHORESIS; IGE-BINDING EPITOPES; FOOD ALLERGENS; GASTROINTESTINAL PH; STABILITY; DIGESTIBILITY; PRODUCTS; MILK; EGG; HYPERSENSITIVITY AB Rationale. Evaluation of the potential allergenicity of proteins derived from genetically modified foods has involved a weight of evidenced approach that incorporates an evaluation,of protein digestibility in pepsin. Currently, there is no standardized protocol to assess the digestibility of proteins using simulated gastric fluid. Potentia I I variations in assay parameters include: pH, pepsin purity, pepsin to target protein ratio, target protein purity, and method of detection. The objective was to assess the digestibility of a common set of proteins in nine independent laboratories to determine the reproducibility of the assay when performed using a common protocol. Methods. A single lot of each test protein and pepsin was obtained and distributed to each laboratory. The test proteins consisted of Ara h 2 (a peanut conglutin-like protein), beta-lactoglobulin, bovine serum albumin, concanavalin A, horseradish peroxidase, ovalbumin, ovomucoid, phosphinothricin acetyltransferase, ribulose diphosphate carboxylase, and soybean trypsin inhibitor. A ratio of 10 U of pepsin activity/mug test protein was selected for all tests (3: 1 pepsin to protein, w:w). Digestions were performed at pH 1.2 and 2.0, with sampling at 0.5, 2 5, 10, 20, 30, and 60 min. Protein digestibility was assessed from stained gels following SDS-PAGE of digestion samples and controls. Results. Results were relatively consistent across laboratories for the full-length proteins. The identification of proteolytic fragments was less consistent, being affected by different fixation and staining methods. Overall, assay pH did not influence the time to disappearance of the full-length protein or protein fragments, however, results across laboratories were more consistent at pH 1.2 (91% agreement) than pH 2.0 (77%). Conclusions. These data demonstrate that this common protocol for evaluating the in vitro digestibility of proteins is reproducible and yields consistent results when performed using the same proteins at different laboratories. (C) 2003 Elsevier Inc. All rights reserved. C1 ILSI Hlth & Environm Sci Inst, Washington, DC USA. Sanquin Res, Amsterdam, Netherlands. Monsanto Co, St Louis, MO USA. Dow Chem Co USA, Midland, MI 48674 USA. Syngenta Cent Toxicol Lab, Alderley Pk, England. Bayer CropSci, Sophia Antipolis, France. US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL USA. DuPont Co Inc, Newark, DE 19714 USA. Univ Nebraska, Lincoln, NE 68583 USA. Bayer CropSci, Res Triangle Pk, NC USA. Syngenta Biotechnol Inc, Res Triangle Pk, NC USA. Natl Inst Hlth Sci, Tokyo 158, Japan. RP Thomas, K (reprint author), ILSI Hlth & Environm Sci Inst, Washington, DC USA. EM kthomas@ilsi.org NR 47 TC 140 Z9 150 U1 5 U2 37 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 APR PY 2004 VL 39 IS 2 BP 87 EP 98 DI 10.1016/j.yrtph.2003.11.003 PG 12 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 809IY UT WOS:000220631600003 PM 15041142 ER PT J AU Harris, GR Gammell, PM Lewin, PA Radulescu, EG AF Harris, GR Gammell, PM Lewin, PA Radulescu, EG TI Interlaboratory evaluation of hydrophone sensitivity calibration from 0.1 to 2 MHz via time delay spectrometry SO ULTRASONICS LA English DT Article; Proceedings Paper CT Ultrasonics International 2003 Meetng CY JUN 30-JUL 03, 2003 CL Granada, SPAIN DE hydrophone; calibration; time delay spectrometry; 1-3 piezocomposite transducer AB Knowing the low-frequency response of hydrophones, down to 100 kHz at least, is important for accurate biomedical ultrasound measurements. However, current international standards do not extend below 500 kHz. Furthermore, commercial hydrophone sources typically do not supply sensitivity data below 1-2 MHz. Therefore, to help identify and validate practical calibration methods below 2 MHz, the authors have extended their previous individual efforts in an interlaboratory evaluation of sensitivity calibration using the swept-frequency technique, time delay spectrometry (TDS). Calibrations were performed for needle and membrane PVDF hydrophones using each laboratory's TDS system. Each site employed the same purpose-built broadband source transducers, comprising both plano-concave and biconcave 1-3 piezocomposite elements 4 cm in diameter, with maximum and minimum thicknesses of approximately 1.5 and 0.1 cm. Agreement between laboratories was within the estimated measurement precision of +/-0.6 dB. The results demonstrated that a TDS system employing such transducers constitutes a viable method for hydrophone calibrations in this frequency range. (C) 2003 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. Gammell Appl Technol, Exmore, VA USA. Drexel Univ, Dept Elect & Comp Engn, Sch Biomed Engn Sci & Hlth Syst, Philadelphia, PA 19104 USA. RP Harris, GR (reprint author), FDA, CDRH, 12725 Twinbrook Pkwy,Room 293,HFZ-132, Rockville, MD 20852 USA. EM grh@cdrh.fda.gov NR 11 TC 20 Z9 20 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0041-624X J9 ULTRASONICS JI Ultrasonics PD APR PY 2004 VL 42 IS 1-9 BP 349 EP 353 DI 10.1016/j.ultras.2003.12.008 PG 5 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 812DP UT WOS:000220820500058 PM 15047310 ER PT J AU Hunyady, L Gaborik, Z Shah, BH Jagadeesh, G Clark, AJL Catt, KJ AF Hunyady, L Gaborik, Z Shah, BH Jagadeesh, G Clark, AJL Catt, KJ TI Structural determinants of agonist-induced signaling and regulation of the angiotensin AT(1) receptor SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Aldosterone CY APR 28-30, 2003 CL London, ENGLAND SP Wellcome Trust, Pharmacia Inc, NIH, Astra Zeneca DE angiotensin II; Ca2+signaling; inositol phosphate responses; receptor internalization; site-directed mutagenesis ID II TYPE-1 RECEPTOR; PROTEIN-COUPLED RECEPTORS; 3RD INTRACELLULAR LOOP; CARBOXYL-TERMINAL TAIL; GROWTH-FACTOR RECEPTOR; INDUCED INTERNALIZATION; CYTOPLASMIC LOOP; RAT AT(1A); INDUCED PHOSPHORYLATION; TRANSMEMBRANE HELIX AB Angiotensin II (Ang II) regulates aldosterone secretion by stimulating inositol phosphate production and Ca2+ signaling in adrenal glomerulosa cells via the G(q)-coupled AT(1) receptor, which is rapidly internalized upon agonist binding. AngII also binds to the heptahelical AT(2) receptor, which neither activates inositol phosphate signaling nor undergoes receptor internalization. The differential behaviors of the AT, and AT2 receptors were analyzed in chimeric angiotensin receptors created by swapping the second (IL2), the third (IL3) intracellular loops and/or the cytoplasmic tail (CT) between these receptors. When transiently expressed in COS-7 cells, the chimeric receptors showed only minor alterations in their ligand binding properties. Measurements of the internalization kinetics and inositol phosphate responses of chimeric AT(1A) receptors indicated that the CT is required for normal receptor internalization, and IL2 is a determinant of G protein activation. In addition, the amino-terminal portion of IL3 is required for both receptor functions. However, only substitution of IL2 impaired Ang II-induced ERK activation, suggesting that alternative mechanisms are responsible for ERK activation in signaling-deficient mutant AT, receptors. Substitution of 1L2, 1L3, or CT of the AT(1A) receptor into the AT, receptor sequence did not endow the latter with the ability to internalize or to mediate inositol phosphate signaling responses. These data suggest that the lack of receptor internalization and inositol phosphate signal generation by the AT, receptor is a consequence of its different activation mechanism, rather than the inability of its cytoplasmic domains to couple to intracellular effectors. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Semmelweis Univ, Fac Med, Dept Physiol, H-1088 Budapest, Hungary. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. US FDA, Div Cardio Renal Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Barts & London Queen Marys Sch Med & Dent, Dept Endocrinol, London EC1A 7BE, England. RP Hunyady, L (reprint author), Semmelweis Univ, Fac Med, Dept Physiol, H-1088 Budapest, Hungary. EM hunyady@puskin.sote.hu RI Jagadeesh, Gowraganahalli/G-6408-2010 NR 71 TC 9 Z9 10 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD MAR 31 PY 2004 VL 217 IS 1-2 BP 89 EP 100 DI 10.1016/j.mce.2003.10.014 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 823TG UT WOS:000221635500013 PM 15134806 ER PT J AU Berkower, I Raymond, M Muller, J Spadaccini, A Aberdeen, A AF Berkower, I Raymond, M Muller, J Spadaccini, A Aberdeen, A TI Assembly, structure, and antigenic properties of virus-like particles rich in HIV-1 envelope gp120 SO VIROLOGY LA English DT Article DE virus-like particles; HIV-1; envelope glycoprotein gp120 ID HUMAN-IMMUNODEFICIENCY-VIRUS; B SURFACE-ANTIGEN; HUMAN MONOCLONAL-ANTIBODY; NEUTRALIZING ANTIBODIES; TYPE-1 PARTICLES; GLYCOPROTEIN; EPITOPE; PROTEIN; VACCINE; BINDING AB In order to improve the immunogenicity of HIV-1 envelope glycoproteins, we have fused gp120 to a carrier protein, hepatitis B surface antigen (HBsAg), which is capable of spontaneous assembly into virus-like particles. The HBsAg-gp120 hybrid proteins assembled efficiently into 20-30 nm particles. The particles resemble native HBsAg particles in size and density, consistent with a lipid composition of about 25% and a gp120 content of about 100 per particle. Particulate gp120 folds in its native conformation and is biologically active, as shown by high affinity binding of CD4. The particles express conformational determinants targeted by a panel of broadly cross-reactive neutralizing antibodies, and they show tight packing of gp120. Because the particles are lipoprotein micelles, an array of gp120 on their surface closely mimics gp120 on the surface of HIV-1 virions. These gp120-rich particles can enhance the quality, as well as quantity, of antibodies elicited by a gp120 vaccine. Published by Elsevier Inc. C1 Off Vaccine Res & Review, Ctr Biol, Div Viral Prod, Lab Immunoregulat, Bethesda, MD 20892 USA. RP Berkower, I (reprint author), Off Vaccine Res & Review, Ctr Biol, Div Viral Prod, Lab Immunoregulat, FDA,Bldg 29,Room 523,NIH Campus, Bethesda, MD 20892 USA. EM Berkower@cber.fda.gov NR 63 TC 23 Z9 24 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAR 30 PY 2004 VL 321 IS 1 BP 75 EP 86 DI 10.1016/j.virol.2003.12.017 PG 12 WC Virology SC Virology GA 807KB UT WOS:000220499300009 PM 15033567 ER PT J AU Li, ZQ Rubin, SA Taffs, RE Merchlinsky, M Ye, ZP Carbone, KM AF Li, ZQ Rubin, SA Taffs, RE Merchlinsky, M Ye, ZP Carbone, KM TI Mouse neurotoxicity test for vaccinia-based smallpox vaccines SO VACCINE LA English DT Article DE smallpox vaccine; vaccinia virus; neurotoxicity ID CENTRAL NERVOUS-SYSTEM; VIRUS-INFECTION; HERPES-SIMPLEX; MICE; PATHOGENESIS; NEUROVIRULENCE; ENCEPHALITIS; MATURATION; MENINGITIS; VIRULENCE AB The only US FDA licensed smallpox vaccine, Dryvax, was associated with rare but serious neurological adverse events. After smallpox was eradicated in the United States, mass vaccination ceased in 1971. As counter-bioterrorism/biowarfare measures, new smallpox vaccines are now being investigated. However, there are no established pre-clinical neurotoxicity assays with which to evaluate these new vaccines prior to licensure. Here we report the development and initial characterization of a small animal neurotoxicity assay for vaccinia-based smallpox vaccines using Dryvax virus as a reference vaccine strain and the neuroadapted Western Reserve (WR) strain as a neurotoxic positive control. In neonatally inoculated mice, the WR strain produced significantly greater and more rapid onset of mortality than the Dryvax vaccine reference. Expression of virus antigen in neural cells and infectious virus replication in the brain was also significantly different between the two strains. In addition, the appearance of high titer virus antibody correlated with the clearance of virus from brain. With further validation, this assay incorporating a licensed vaccine reference standard and positive control strain may provide important pre-clinical neurotoxicity data on new vaccinia-based smallpox vaccine strains. Published by Elsevier Ltd. C1 US FDA, CBER, OD, Lab Pediat & Resp Viral Dis, Bethesda, MD 20892 USA. US FDA, CBER, OVRR,DVP, Lab DNA Viruses, Bethesda, MD 20892 USA. US FDA, CBER, OBRR,DETTD, Lab Bacterial Parasit & Unconvent Agents, Bethesda, MD 20892 USA. RP Carbone, KM (reprint author), US FDA, CBER, OD, Lab Pediat & Resp Viral Dis, HFM-460,Bldg 29B,Room 5NN22,8800 Rockville Pike, Bethesda, MD 20892 USA. EM zli@smtp.salk.edu; rubins@cber.fda.gov; taffs@cber.fda.gov; merchlinsky@cber.fda.gov; carbonek@cber.fda.gov NR 31 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAR 29 PY 2004 VL 22 IS 11-12 BP 1486 EP 1493 DI 10.1016/vaccine.2003.10.022 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 812EB UT WOS:000220821700019 PM 15063573 ER PT J AU Isaguliants, MG Iakimtchouk, K Petrakova, NV Yermalovich, MA Zuber, AK Kashuba, VI Belikov, SV Andersson, S Kochetkov, SN Klinman, DM Wahren, B AF Isaguliants, MG Iakimtchouk, K Petrakova, NV Yermalovich, MA Zuber, AK Kashuba, VI Belikov, SV Andersson, S Kochetkov, SN Klinman, DM Wahren, B TI Gene immunization may induce secondary antibodies reacting with DNA SO VACCINE LA English DT Article DE DNA immunization; anti-DNA antibodies; HIV-1 reverse transcriptase; nef; HCV core ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; IMMUNODEFICIENCY-VIRUS TYPE-1; HIV-1 REVERSE-TRANSCRIPTASE; DOUBLE-STRANDED DNA; CORE PROTEIN; ANTI-DSDNA; AUTOIMMUNE-DISEASE; BACTERIAL-DNA; MAMMALIAN DNA; IN-VIVO AB The fear of autoimmunity in DNA-vaccine recipients initiated screening for anti-DNA antibodies in rabbits immunized with genes of viral nucleic acid-binding and adapter proteins. Of 11 DNA/protein-immunized rabbits, seven had developed secondary antibodies against DNA detected at weeks 11-50 from the on-start of immunization. Two rabbits immunized with HIV-1 reverse transcriptase gene developed transient anti-double-stranded DNA antibodies of high avidity that recognized DNA in the kinetoplasts of Crithidia luciliae. Others developed antibodies reacting with DNA in ELISA and targeting nuclear-associated antigens in the immunolluoresence test. No anti-DNA antibodies were detected at these time-points in any of the controls (P = 0.036). Induction of anti-DNA antibodies by epitope spreading from protein domains involved in nucleic acid-binding versus maturation of anti-protein antibodies to dual protein-DNA specificity is discussed. (126 words). (C) 2003 Published by Elsevier Ltd. C1 Karolinska Inst, Ctr Microbiol & Tumor Biol, SE-17182 Solna, Sweden. DI Ivanovskii Inst Virol, Moscow 123098, Russia. Karolinska Inst, Dept Mol Cell Biol, SE-17177 Stockholm, Sweden. Reg Sjukhuset, Dept Clin Microbiol & Immunol, SE-70185 Orebro, Sweden. VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. US FDA, CBER, Div Viral Prod, Rockville, MD 20902 USA. Karolinska Inst, Swedish Inst Infect Dis Control, SE-17182 Solna, Sweden. RP Isaguliants, MG (reprint author), Karolinska Inst, Ctr Microbiol & Tumor Biol, SE-17182 Solna, Sweden. EM isaguliats@hotmail.com NR 51 TC 7 Z9 9 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAR 29 PY 2004 VL 22 IS 11-12 BP 1576 EP 1585 DI 10.1016/j.vaccine.2003.09.033 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 812EB UT WOS:000220821700030 PM 15063584 ER PT J AU Ang, CYW AF Ang, CYW TI Challenges in assessing bioactive botanical ingredients in functional beverages. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 227th National Meeting of the American-Chemical Society CY MAR 28-APR 01, 2004 CL Anaheim, CA SP Amer Chem Soc C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. EM cang@nctr.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 28 PY 2004 VL 227 MA 119-AGFD BP U47 EP U47 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851AJ UT WOS:000223655600127 ER PT J AU Brorson, K AF Brorson, K TI Impact of multiple re-use of chromatography media on virus removal. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 227th National Meeting of the American-Chemical Society CY MAR 28-APR 01, 2004 CL Anaheim, CA SP Amer Chem Soc C1 Food & Drug Adm, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. EM brorson@cber.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 28 PY 2004 VL 227 MA 037-BIOT BP U128 EP U128 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851AJ UT WOS:000223655600584 ER PT J AU Freedberg, SO Ano, SO Norris, SE Venable, RM AF Freedberg, SO Ano, SO Norris, SE Venable, RM TI Is there a correlation between lactose's anomeric configuration and its three-dimensional structure? SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 227th National Meeting of the American-Chemical Society CY MAR 28-APR 01, 2004 CL Anaheim, CA SP Amer Chem Soc C1 US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, 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 28 PY 2004 VL 227 MA 011-CARB BP U263 EP U264 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 851AJ UT WOS:000223655600986 ER PT J AU Hanson, M Brorson, K Moreira, A AF Hanson, M Brorson, K Moreira, A TI Gene arrays, cell culture process changes and comparability. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 227th National Meeting of the American-Chemical Society CY MAR 28-APR 01, 2004 CL Anaheim, CA SP Amer Chem Soc C1 Univ Maryland Baltimore Cty, CDER, FDA, Bethesda, MD 20892 USA. EM mhanson1@umbc.edu 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 28 PY 2004 VL 227 MA 286-BIOT BP U234 EP U234 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851AJ UT WOS:000223655600839 ER PT J AU Jackson, LS Al-Taher, F Jablonski, JE Fleischman, G AF Jackson, LS Al-Taher, F Jablonski, JE Fleischman, G TI Effects of consumer food preparation on acrylamide formation. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 227th National Meeting of the American-Chemical Society CY MAR 28-APR 01, 2004 CL Anaheim, CA SP Amer Chem Soc C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. IIT, Natl Ctr Food Safety & Technol, Chicago, IL USA. EM Lauren.Jackson@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 28 PY 2004 VL 227 MA 125-AGFD BP U48 EP U48 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851AJ UT WOS:000223655600133 ER PT J AU Jackson, LS Al-Taher, F Jablonski, JE Fleischman, G AF Jackson, LS Al-Taher, F Jablonski, JE Fleischman, G TI Surface browning as an indicator of acrylamide levels in food. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 227th National Meeting of the American-Chemical Society CY MAR 28-APR 01, 2004 CL Anaheim, CA SP Amer Chem Soc C1 US FDA, Natl Ctr Food Safety & Technol, Rockville, MD 20857 USA. IIT, Natl Ctr Food Safety & Technol, Chicago, IL 60616 USA. EM Lauren.Jackson@cfsan.fda.gov; altaher@iit.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 28 PY 2004 VL 227 MA 085-AGFD BP U41 EP U41 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851AJ UT WOS:000223655600093 ER PT J AU Jia, YP Alayash, AI AF Jia, YP Alayash, AI TI Cross-linking with 0-raffinose lowers oxygen affinity and stabilizes hemoglobin in a non-cooperative T-STATE conformation. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 227th National Meeting of the American-Chemical Society CY MAR 28-APR 01, 2004 CL Anaheim, CA SP Amer Chem Soc C1 FDA, CBER, DH, LBVB,Div Hematol, Rockville, MD 20852 USA. EM jia@cber.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 28 PY 2004 VL 227 MA 035-BIOT BP U127 EP U127 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851AJ UT WOS:000223655600582 ER PT J AU Kozlowski, S AF Kozlowski, S TI Role of mechanism of action in drug development and regulation. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 227th National Meeting of the American-Chemical Society CY MAR 28-APR 01, 2004 CL Anaheim, CA SP Amer Chem Soc C1 US FDA, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. EM kozlowski@cber.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 28 PY 2004 VL 227 MA 030-BIOT BP U127 EP U127 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851AJ UT WOS:000223655600577 ER PT J AU Lee, CHR Frasch, CE AF Lee, CHR Frasch, CE TI A method with increased yield for production of polysaccharide-protein conjugate vaccines using hydrazide chemistry. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 227th National Meeting of the American-Chemical Society CY MAR 28-APR 01, 2004 CL Anaheim, CA SP Amer Chem Soc C1 Ctr Biol Evaluat & Res, Div Bacterial Prod, Rockville, MD 20852 USA. US FDA, Div Bacterial Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM lee_r@cber.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 28 PY 2004 VL 227 MA 082-BIOT BP U137 EP U137 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851AJ UT WOS:000223655600637 ER PT J AU Lee, CHR AF Lee, CHR TI A method with increased yield for production of polysaccharide-protein conjugate vaccines using hydrazide chemistry. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 227th National Meeting of the American-Chemical Society CY MAR 28-APR 01, 2004 CL Anaheim, CA SP Amer Chem Soc C1 Ctr Biol Evaluat & Res, Div Bacterial Prod, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, Rockville, MD 20852 USA. EM lee_r@cber.fda.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 28 PY 2004 VL 227 MA 082-BIOT BP U135 EP U135 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851AJ UT WOS:000223655600627 ER PT J AU Swann, PG AF Swann, PG TI Regulatory considerations when using model systems in process validation for biotechnological products. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 227th National Meeting of the American-Chemical Society CY MAR 28-APR 01, 2004 CL Anaheim, CA SP Amer Chem Soc C1 Ctr Drug Evaluat & Res Food & Drug Adm, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. EM swannp@cber.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 28 PY 2004 VL 227 MA 032-BIOT BP U127 EP U127 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851AJ UT WOS:000223655600579 ER PT J AU Nomaguchi, M Teramoto, T Yu, L Markoff, L Padmanabhan, R AF Nomaguchi, M Teramoto, T Yu, L Markoff, L Padmanabhan, R TI Requirements for West Nile virus (-)- and (+)-strand subgenomic RNA synthesis in vitro by the viral RNA-dependent RNA polymerase expressed in Escherichia coli SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEPATITIS-C VIRUS; PUTATIVE METHYLTRANSFERASE DOMAIN; FLAVIVIRUS GENOMIC RNA; 3' UNTRANSLATED REGION; NEGATIVE-STRAND RNA; DE-NOVO SYNTHESIS; DENGUE VIRUS; SECONDARY STRUCTURE; NS3 PROTEIN; NTPASE ACTIVITY AB RNA-dependent RNA polymerases (RdRPs) of the Flaviviridae family catalyze replication of positive (+)strand viral RNA through synthesis of minus (-)- and progeny (+)- strand RNAs. West Nile virus (WNV), a mosquito-borne member, is a rapidly re-emerging human pathogen in the United States since its first outbreak in 1999. To study the replication of the WNV RNA in vitro, an assay is described here that utilizes the WNV RdRP and subgenomic (-)- and (+)- strand template RNAs containing 5'- and 3'-terminal regions (TR) with the conserved sequence elements. Our results show that both 5'- and 3'-TRs of the (+)- strand RNA template including the wild type cyclization (CYC) motifs are important for RNA synthesis. However, the 3'-TR of the (-)- strand RNA template alone is sufficient for RNA synthesis. Mutational analysis of the CYC motifs revealed that the (+)- strand 5'- CYC motif is critical for (+)- strand RNA synthesis but neither the (-)- strand 5'- nor 3'-CYC motif is important for the (+)- strand RNA synthesis. Moreover, the 5'- cap inhibits the (+)- strand RNA synthesis from the 3' fold-back structure of (+)- strand RNA template without affecting the de novo synthesis of RNA. These results support a model that "cyclization" of the viral RNA play a role for (-)- strand RNA synthesis but not for (+)- strand RNA synthesis. C1 Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20057 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Padmanabhan, R (reprint author), Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, SW309 Med Dent Bldg,3900 Reservoir Rd, Washington, DC 20057 USA. EM rp55@georgetown.edu FU NIAID NIH HHS [AI 32078] NR 60 TC 38 Z9 40 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 26 PY 2004 VL 279 IS 13 BP 12141 EP 12151 DI 10.1074/jbc.M310839200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 804YV UT WOS:000220334900020 PM 14699096 ER PT J AU Turesky, RJ Vouros, P AF Turesky, RJ Vouros, P TI Formation and analysis of heterocyclic aromatic amine-DNA adducts in vitro and in vivo SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Review DE reviews; heterocyclic aromatic amine-DNA adducts; DNA ID CHROMATOGRAPHY/MICROELECTROSPRAY MASS-SPECTROMETRY; MAMMARY EPITHELIAL-CELLS; FOOD-BORNE CARCINOGEN; P-32 POSTLABELING METHOD; POST-LABELING ANALYSIS; N-ACETOXY DERIVATIVES; MEA-ALPHA-C; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; ELECTROSPRAY-IONIZATION; METABOLIC-ACTIVATION AB The detection and quantification of heterocyclic aromatic amine (HAA)-DNA adducts, critical biomarkers in interspecies extrapolation of toxicity data for human risk assessment, remains a challenging analytical problem. The two main analytical methods currently in use to screen for HAA-DNA adducts are the P-32-postlabeling assay and mass spectrometry, using either accelerated mass spectrometry (AMS) or liquid chromatography and electrospray ionization mass spectrometry (LC-ESI-MS). In this review, the principal methods to synthesize and characterize DNA adducts, and the methods applied to measure HAA-DNA adduct in vitro and vivo are discussed. (C) 2003 Elsevier B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. Northeastern Univ, Dept Chem, Boston, MA 02115 USA. Northeastern Univ, Barnett Inst, Boston, MA 02115 USA. RP Turesky, RJ (reprint author), Natl Ctr Toxicol Res, Div Chem, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM rturesky@nctr.fda.gov FU NCI NIH HHS [1R01CA69390] NR 102 TC 67 Z9 68 U1 1 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 MAR 25 PY 2004 VL 802 IS 1 BP 155 EP 166 DI 10.1016/j.jchromb.2003.10.053 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 778NY UT WOS:000189248700018 PM 15036007 ER PT J AU Wysowski, DK Farinas, E AF Wysowski, DK Farinas, E TI Finasteride in benign prostatic hyperplasia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID THERAPY C1 US FDA, Rockville, MD 20857 USA. RP Wysowski, DK (reprint author), US FDA, Rockville, MD 20857 USA. NR 4 TC 5 Z9 5 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 25 PY 2004 VL 350 IS 13 BP 1359 EP 1359 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 805VN UT WOS:000220393900023 PM 15044649 ER PT J AU Arcidiacono, JA Bloom, E AF Arcidiacono, JA Bloom, E TI The role of adhesion molecules in determining the susceptibility of porcine endothelial cells to lysis by human NK cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 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 24 PY 2004 VL 18 IS 5 SU S BP A1181 EP A1181 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470702017 ER PT J AU Belyakov, IM Klinman, D Kuznetsov, VA Moniuszko, M Ahlers, JD Kelsall, B Strober, W Franchini, G Berzofsky, JA AF Belyakov, IM Klinman, D Kuznetsov, VA Moniuszko, M Ahlers, JD Kelsall, B Strober, W Franchini, G Berzofsky, JA TI Progress on new mucosal vaccine strategies for HIV SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI, Metab Branch, Bethesda, MD 20892 USA. NICHD, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. NCI, Basic Res Lab, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 3 Z9 3 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 24 PY 2004 VL 18 IS 5 SU S BP A821 EP A821 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470700302 ER PT J AU Berkower, I Ni, YS Lynch, R Paul, S Spadaccini, A AF Berkower, I Ni, YS Lynch, R Paul, S Spadaccini, A TI Assembled particles rich in HIV gp120 for improved vaccine potency SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 US FDA, Ctr Biol, Off Vaccines, Div Viral Prod, 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 24 PY 2004 VL 18 IS 5 SU S BP A822 EP A823 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470700308 ER PT J AU Epstein, SL AF Epstein, SL TI Reexamination of archival records from the 1957 influenza pandemic: Heterosubtypic immunity in humans? SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 24 PY 2004 VL 18 IS 5 SU S BP A802 EP A802 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470700206 ER PT J AU Fernandez, E Elkins, K AF Fernandez, E Elkins, K TI The role of B cells in immunity to Francisella tularensis LVS SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 US FDA, CBER, Rockville, MD 20852 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 24 PY 2004 VL 18 IS 5 SU S BP A805 EP A805 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470700220 ER PT J AU Huang, LYC Ishii, KJ Bafica, A Akira, S Sher, A Aliberti, J Golding, B AF Huang, LYC Ishii, KJ Bafica, A Akira, S Sher, A Aliberti, J Golding, B TI Toll-like receptor 9 is required for IL-12 induction in response to bacterial stimulation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 CBER FDA, Div Hematol, Rockville, MD 20852 USA. Osaka Univ, RIMD, Suita, Osaka 565, Japan. NIAID, LPD, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27706 USA. RI Aliberti, Julio/I-7354-2013; Ishii, Ken/B-1685-2012 OI Aliberti, Julio/0000-0003-3420-8478; Ishii, Ken/0000-0002-6728-3872 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 24 PY 2004 VL 18 IS 5 SU S BP A1157 EP A1157 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470701903 ER PT J AU Inoue, S Golding, B Golding, H Scott, D AF Inoue, S Golding, B Golding, H Scott, D TI CD4 T cells are required not for primary but for secondary CTL responses against protein plus adjuvant SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 US FDA, Ctr Biol Evaluat & Res, 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 24 PY 2004 VL 18 IS 5 SU S BP A824 EP A824 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470700313 ER PT J AU Lumsden, J Shen, RN Petiniot, L McCarty, T Barlow, C Wynn, T Morse, H Wynshaw-Boris, A Max, E Hodes, R AF Lumsden, J Shen, RN Petiniot, L McCarty, T Barlow, C Wynn, T Morse, H Wynshaw-Boris, A Max, E Hodes, R TI Immunoglobulin class switch recombination is impaired in Atm-deficient mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIH, Expt Immunol Branch, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NCHGR, NIH, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RI Lumsden, Joanne/B-6475-2009 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 24 PY 2004 VL 18 IS 5 SU S BP A1132 EP A1132 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470701782 ER PT J AU Max, EE Bernstein, RM Mills, FC AF Max, EE Bernstein, RM Mills, FC TI Chromatin features suggest a boundary downstream of the murine IgH locus SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 US FDA, OBP, CBER, 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 24 PY 2004 VL 18 IS 5 SU S BP A812 EP A813 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470700258 ER PT J AU Mills, FC Bernstein, RM Max, EE AF Mills, FC Bernstein, RM Max, EE TI Examination of the human 3 ' IgH region for insulator function SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 US FDA, CDER, DTP, OTRR, Bethesda, MD 20892 USA. US FDA, CDER, OBP, 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 24 PY 2004 VL 18 IS 5 SU S BP A816 EP A816 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470700274 ER PT J AU Porter, CM Bloom, E AF Porter, CM Bloom, E TI CD4+CD25+ regulatory T cells suppress human anti-porcine responses SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 US FDA, Div Cellular & Gene Therapy, 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 24 PY 2004 VL 18 IS 5 SU S BP A1178 EP A1179 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470702007 ER PT J AU Puri, RK Bhattacharya, B Miura, T Mejido, J Luo, YQ Yang, AX Joshi, BH Irene, G Rao, M AF Puri, RK Bhattacharya, B Miura, T Mejido, J Luo, YQ Yang, AX Joshi, BH Irene, G Rao, M TI Microrray analysis of gene expression identities unique molecular signature in human embryonic stem cell lines SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 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 24 PY 2004 VL 18 IS 5 SU S BP A1121 EP A1121 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470701726 ER PT J AU Smith, GW Haschek, WM Fredrickson, RL Tumbleson, ME James, SJ Eppley, RM Constable, PD AF Smith, GW Haschek, WM Fredrickson, RL Tumbleson, ME James, SJ Eppley, RM Constable, PD TI Effect of chronic fumonisin B-1 ingestion on serum folate, homocysteine, and methionine concentrations in Sinclair minipigs SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 N Carolina State Univ, Dept Farm Anim Hlth, Raleigh, NC 27606 USA. Univ Illinois, Dept Vet Pathobiol, Urbana, IL 61801 USA. Univ Illinois, Dept Vet Biosci, Urbana, IL 61801 USA. Univ Illinois, Dept Vet Clin Med, Urbana, IL 61801 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, CFSAN, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 24 PY 2004 VL 18 IS 5 SU S BP A1209 EP A1210 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470702155 ER PT J AU Wang, W Merchlinsky, M Inman, J Golding, B AF Wang, W Merchlinsky, M Inman, J Golding, B TI Identification of a novel immunodominant CTL epitope derived from human factor VIII in a murine model of hemophilia A SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 US FDA, Ctr Biol Evaluat & Res, OBRR, DH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, OVRR, Bethesda, MD 20892 USA. NIAID, 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 24 PY 2004 VL 18 IS 5 SU S BP A826 EP A826 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470700324 ER PT J AU Zhao, ZS McElroy, M Lo, CY Misplon, JA Tompkins, SM Ye, ZP Benton, K Epstein, SL AF Zhao, ZS McElroy, M Lo, CY Misplon, JA Tompkins, SM Ye, ZP Benton, K Epstein, SL TI Protection against influenza A virus challenge by vaccination with acidic polymerase (PA) expressed by DNA and recombinant vaccinia virus SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Bethesda, MD 20817 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 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 24 PY 2004 VL 18 IS 5 SU S BP A822 EP A822 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470700305 ER PT J AU Zubkova, I Golding, H Zaitseva, M AF Zubkova, I Golding, H Zaitseva, M TI The role of intrathymic IL-7 in restoration of thymopoiesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 US FDA, Ctr Biol Evaluat & Res, 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 24 PY 2004 VL 18 IS 5 SU S BP A794 EP A794 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470700164 ER PT J AU Collazo, CM Sher, A Elkins, K AF Collazo, CM Sher, A Elkins, K TI The function of myeloid differentiation factor-88 (MyD88) and Toll-like receptors in Francisella tularensis LVS infection in mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 US FDA, CBER, Rockville, MD 20852 USA. NIAID, LPD, NIH, 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 23 PY 2004 VL 18 IS 4 SU S BP A454 EP A454 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602188 ER PT J AU Cook, KK White, KD Rader, JI AF Cook, KK White, KD Rader, JI TI Use of pyrrolizidine alkaloid profiles to distinguish Symphytum officinale (common comfrey) from S. x uplandicum (Russian Comfrey) in comfirey products sold in the United States SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A128 EP A129 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600624 ER PT J AU Cowley, S Elkins, K AF Cowley, S Elkins, K TI Membrane TNF contributes to resistance against Francisella tularensis infection SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 US FDA, CBER, Rockville, MD 20852 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 23 PY 2004 VL 18 IS 4 SU S BP A92 EP A92 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600451 ER PT J AU Dalloul, RA Lillehoj, H Babu, US Raybourne, RB Heckert, RA AF Dalloul, RA Lillehoj, H Babu, US Raybourne, RB Heckert, RA TI CpG-containing oligodeoxynucleotides protect chickens against Eimeria infections SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Univ Maryland, College Pk, MD 20742 USA. USDA, Anim Parasit Dis Lab, Beltsville, MD 20705 USA. US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 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 23 PY 2004 VL 18 IS 4 SU S BP A418 EP A418 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602016 ER PT J AU Delmonte, P Perry, J Rader, JI AF Delmonte, P Perry, J Rader, JI TI Analysis of isoflavones in soy- and red clover-containing foods or dietary supplements SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 US FDA, College Pk, MD USA. US FDA, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A128 EP A128 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600622 ER PT J AU Hansen, CM Shultz, TD James, SJ Melnyk, S Leklem, JE Hardin, K Ames, BN AF Hansen, CM Shultz, TD James, SJ Melnyk, S Leklem, JE Hardin, K Ames, BN TI Effects of smoking and vitamin B-6 intake on plasma thiol concentrations SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Iowa State Univ Sci & Technol, Ames, IA 50011 USA. Washington State Univ, Pullman, WA 99164 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Oregon State Univ, Corvallis, OR 97331 USA. Childrens Hosp, Oakland Res Inst, Nutr Genom Ctr, Oakland, CA 94609 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 23 PY 2004 VL 18 IS 4 SU S BP A176 EP A176 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600850 ER PT J AU Harris, DN Besselink, E Tolleson, WH Roberts, DW Heber, D AF Harris, DN Besselink, E Tolleson, WH Roberts, DW Heber, D TI Estrogenic activity of biochanin A and formononetin compared to O-demethylated metabolites produced by hepatic microsomes in vitro SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Human Nutr, Los Angeles, CA 90095 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 23 PY 2004 VL 18 IS 4 SU S BP A127 EP A127 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600617 ER PT J AU Leak, LV Liotta, LA Calvert, VS Petricoin, EF AF Leak, LV Liotta, LA Calvert, VS Petricoin, EF TI Proteomic analysis of lymphangiogenesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Howard Univ, Washington, DC 20059 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20014 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 23 PY 2004 VL 18 IS 4 SU S BP A259 EP A259 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470601247 ER PT J AU Manigold, T Piccirillo, CA Shin, EC Mihalik, K Rice, CM Feinstone, SM Rehermann, B AF Manigold, T Piccirillo, CA Shin, EC Mihalik, K Rice, CM Feinstone, SM Rehermann, B TI CD4+ CD25+ regulatory T cells control effector functions of HCV-specific memory CD8+ T cells in HCV-recovered chimpanzees SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIDDK, LDS, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Immunol Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis Viruses, Bethesda, MD USA. Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 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 23 PY 2004 VL 18 IS 4 SU S BP A85 EP A85 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600417 ER PT J AU Miyaji, M Okazaki, T Bloom, ET Amakawa, R Fukuhara, S Umehara, H AF Miyaji, M Okazaki, T Bloom, ET Amakawa, R Fukuhara, S Umehara, H TI Functional roles of sphingomyelin in Fas-mediated apoptosis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Kansai Med Sch, Dept Med 1, Moriguchi, Osaka 5708506, Japan. Kyoto Univ, Grad Sch Med, Dept Hematol & Oncol, Kyoto, Japan. US FDA, CBER, DCGT, LIV, Bethesda, MD USA. Kyoto Univ, Dept Rheum Clin Immunol, Grad Sch Med, Kyoto, Japan. 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 23 PY 2004 VL 18 IS 4 SU S BP A41 EP A41 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600200 ER PT J AU Mueller, CL McCue, J Ouyang, Y Portas, M Lazis, S Quintana, N Freed, BM AF Mueller, CL McCue, J Ouyang, Y Portas, M Lazis, S Quintana, N Freed, BM TI Acrolein in cigarette smoke inhibits NF-[kappa]B p50 DNA binding SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Univ Colorado, Denver, CO 80262 USA. US FDA, CDER 2, Rockville, MD 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 23 PY 2004 VL 18 IS 4 SU S BP A433 EP A433 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602088 ER PT J AU Shin, EC Protzer, U Untergasser, A Hasselschwert, D Rice, CM Feinstone, SM Rehermann, B AF Shin, EC Protzer, U Untergasser, A Hasselschwert, D Rice, CM Feinstone, SM Rehermann, B TI Effect of liver-directed IFN-gamma gene delivery in chronic hepatitis C virus infection SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. Univ Cologne, Ctr Mol Med, Cologne, Germany. Univ Louisiana, New Iberia Res Ctr, Lafayette, LA USA. Rockefeller Univ, Ctr Study Hepatitis C, New York, NY USA. US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis Viruses, Bethesda, MD 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 23 PY 2004 VL 18 IS 4 SU S BP A91 EP A92 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600450 ER PT J AU Song, K Rabin, RL Hill, BJ De Rosa, S Perfetto, SP Reiner, JS Zhang, HWH Foley, JF Marmol, J Douek, DC Roederer, M Farber, JM AF Song, K Rabin, RL Hill, BJ De Rosa, S Perfetto, SP Reiner, JS Zhang, HWH Foley, JF Marmol, J Douek, DC Roederer, M Farber, JM TI CXCR3 and CCR4 reveal polarized early central memory CD4+T cells in humans SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAID, LCI, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NIAID, VRC, NIH, 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 23 PY 2004 VL 18 IS 4 SU S BP A467 EP A467 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602251 ER PT J AU Stolzenberg-Solomon, RZ Mason, JB Poirier, LA Choi, SW Selhub, J Crott, J Rothman, N Sinha, R AF Stolzenberg-Solomon, RZ Mason, JB Poirier, LA Choi, SW Selhub, J Crott, J Rothman, N Sinha, R TI Evaluation of integrative biochemical and molecular biomarkers of one-carbon metabolism in healthy SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI, DCEG, Rockville, MD 20852 USA. Tufts Univ, HNRC, Boston, MA 02111 USA. US FDA, NCTR, Jefferson, AR 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 23 PY 2004 VL 18 IS 4 SU S BP A110 EP A111 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600539 ER PT J AU Stratton, SL Sealey, WM Hansen, DK Mock, DM AF Stratton, SL Sealey, WM Hansen, DK Mock, DM TI Marginal maternal biotin deficiency in CD-1 mice decreases the abundance of the biotin-dependent carboxylases in fetal liver SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Univ Arkansas Med Sci, Little Rock, AR 72205 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 23 PY 2004 VL 18 IS 4 SU S BP A176 EP A176 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600847 ER PT J AU Tompkins, SM Lo, CY Tumpey, TM Epstein, SL AF Tompkins, SM Lo, CY Tumpey, TM Epstein, SL TI Protection against lethal influenza virus challenge by RNA interference in vivo SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Div Viral & Rickettsial Dis, Influenza Branch, Atlanta, GA USA. RI Tompkins, Stephen/A-3317-2008 OI Tompkins, Stephen/0000-0002-1523-5588 NR 0 TC 0 Z9 0 U1 0 U2 4 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 23 PY 2004 VL 18 IS 4 SU S BP A460 EP A460 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602214 ER PT J AU Umehara, H Miyaji, M Mimori, T Bloom, ET Imai, T AF Umehara, H Miyaji, M Mimori, T Bloom, ET Imai, T TI A role of fractalkine as the vascular gateway for cytotoxic lymphocytes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Kyoto Univ, Grad Sch Med, Dept Rheumatol & Clin Immunol, Kyoto 6068507, Japan. Kansai Med Sch, Dept Med 21, Osaka, Japan. US FDA, Ctr Biol Evaluat & Res, LIV, Bethesda, MD 20014 USA. Kan Res Inst, Project 2, Kyoto, Japan. 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 23 PY 2004 VL 18 IS 4 SU S BP A449 EP A449 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602163 ER PT J AU White, KD Delmonte, P Rader, JI AF White, KD Delmonte, P Rader, JI TI Identification of active components in Cimicifuga racemosa satchithanandam subramaniam SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 US FDA, College Pk, MD 20740 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 23 PY 2004 VL 18 IS 4 SU S BP A128 EP A128 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600623 ER PT J AU Zhao, CWL Andrews, KW Holden, JM Brandt, MM Spease, C Dwyer, J Picciano, MF AF Zhao, CWL Andrews, KW Holden, JM Brandt, MM Spease, C Dwyer, J Picciano, MF TI Caffeine containing dietary supplements SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. ARS, Nutrient Data Lab, USDA, Beltsville, MD 20705 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 23 PY 2004 VL 18 IS 4 SU S BP A128 EP A128 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600620 ER PT J AU Baric, I Fumic, K Glenn, B Cuk, M Schulze, A Finkelstein, JD James, SJ Mejaski-Bosnjak, V Pazanin, L Pogribny, IP Rados, M Sarnavka, V Scukanec-Spoljar, M Allen, RH Stabler, S Uzelac, L Vugrek, O Wagner, C Zeisel, S Mudd, SH AF Baric, I Fumic, K Glenn, B Cuk, M Schulze, A Finkelstein, JD James, SJ Mejaski-Bosnjak, V Pazanin, L Pogribny, IP Rados, M Sarnavka, V Scukanec-Spoljar, M Allen, RH Stabler, S Uzelac, L Vugrek, O Wagner, C Zeisel, S Mudd, SH TI S-adenosylhomocysteine hydrolase deficiency in a human: A genetic disorder of methionine metabolism SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GLYCINE N-METHYLTRANSFERASE; TOTAL HOMOCYSTEINE; DNA METHYLATION; PLASMA HOMOCYSTEINE; CREATINE DEFICIENCY; MASS-SPECTROMETRY; FOLATE-DEFICIENCY; COPPER-BINDING; INBORN ERROR; SERUM AB We report studies of a Croatian boy, a proven case of human S-adenosylhomocysteine (AdoHcy) hydrolase deficiency. Psychomotor development was slow until his fifth month; thereafter, virtually absent until treatment was started. He had marked hypotonia with elevated serum creatine kinase and transaminases, prolonged prothrombin time and low albumin. Electron microscopy of muscle showed numerous abnormal myelin figures; liver biopsy showed mild hepatitis with sparse rough endoplasmic reticulum. Brain MRI at 12.7 months revealed white matter atrophy and abnormally slow myelination. Hypermethioninemia was present in the initial metabolic study at age 8 months, and persisted (up to 784 muM) without tyrosine elevation. Plasma total homocysteine was very slightly elevated for an infant to 14.5-15.9 muM. In plasma, S-adenosylmethionine was 30-fold and AdoHcy 150-fold elevated. Activity of AdoHcy hydrolase was approximate to3% of control in liver and was 5-10% of the control values in red blood cells and cultured fibroblasts. We found no evidence of a soluble inhibitor of the enzyme in extracts of the patient's cultured fibroblasts. Additional pretreatment abnormalities in plasma included low concentrations of phosphatidylcholine and choline, with elevations of guanidinoacetate, betaine, dimethylglycine, and cystathionine. Leukocyte DNA was hypermethylated. Gene analysis revealed two mutations in exon 4: a maternally derived stop codon, and a paternally derived missense mutation. We discuss reasons for biochemical abnormalities and pathophysiological aspects of AdoHcy hydrolase deficiency. C1 Univ Zagreb, Hosp Ctr, Dept Pediat, Zagreb 10000, Croatia. Univ Zagreb, Hosp Ctr, Dept Neuropathol, Zagreb 10000, Croatia. Univ Zagreb, Hosp Ctr, Dept Radiol, Zagreb 10000, Croatia. Univ Zagreb, Hosp Ctr, Dept Pathol, Zagreb 10000, Croatia. Univ Zagreb, Hosp Ctr, Clin Inst Lab Diag, Zagreb 10000, Croatia. NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. Rudjer Boskovic Inst, Dept Mol Med, Zagreb 10000, Croatia. Univ Colorado, Hlth Sci Ctr, Div Hematol, Denver, CO 80262 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Zagreb, Childrens Hosp, Zagreb 10000, Croatia. Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72202 USA. George Washington Univ, Washington, DC 20422 USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. Univ Heidelberg, Childrens Hosp, D-69120 Heidelberg, Germany. Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA. Dept Vet Affairs Med Ctr, Nashville, TN 37232 USA. RP Baric, I (reprint author), Univ Zagreb, Hosp Ctr, Dept Pediat, Kispaticeva 12, Zagreb 10000, Croatia. EM ibaric@kbc-zagreb.hr FU NIDDK NIH HHS [DK 15289, DK 55865, R37 DK015289, DK 54849, R01 DK015289, R01 DK055865] NR 52 TC 105 Z9 110 U1 0 U2 12 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 23 PY 2004 VL 101 IS 12 BP 4234 EP 4239 DI 10.1073/pnas.0400658101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 806ZQ UT WOS:000220472200045 PM 15024124 ER PT J AU Manjanatha, MG Shelton, SD Bishop, M Shaddock, JG Dobrovolsky, VN Heflich, RH Webb, PJ Blankenship, LR Beland, FA Greenlees, KJ Culp, SJ AF Manjanatha, MG Shelton, SD Bishop, M Shaddock, JG Dobrovolsky, VN Heflich, RH Webb, PJ Blankenship, LR Beland, FA Greenlees, KJ Culp, SJ TI Analysis of mutations and bone marrow micronuclei in Big Blue (R) rats fed leucomalachite green SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE leucomalachite green; lacI; Big Blue rats; mutant frequency; mutation frequency ID LACI TRANSGENIC MICE; DNA ADDUCT FORMATION; MOLECULAR ANALYSIS; MALACHITE GREEN; MUTAGENICITY; SEQUENCE; SPECTRA; TISSUE; LIVER; GENE AB Leucomalachite green (LMG) is the major metabolite of malachite green (MG), a triphenylmethane dye that has been used widely as an antifungal agent in the fish industry. Concern over MG and LMG is due to the potential for consumer exposure, suggestive evidence of tumor promotion in rodent liver, and suspicion of carcinogenicity based on structure-activity relationships. In order to evaluate the risks associated with exposure to LMG, female Big Blue rats were fed up to 543 ppm LMG; groups of these rats were killed after 4, 16, or 32 weeks of exposure and evaluated for genotoxicity. We previously reported that this treatment resulted in a dose-dependent induction of liver DNA adducts, and that the liver lacl mutant frequency (MF) was increased, but only in rats fed 543 ppm LMG for 16 weeks [Mutation Res. 506/507 (2002) 55-63]. In the present study, we report the results from lymphocyte Hprt mutant assays and bone marrow micronucleus assays performed on these same rats. In addition, we have determined the types of lacI mutations induced in the rats fed 543 ppm LMG for 16 weeks and the rats fed control diet. No significant increases in the frequency of micronuclei or Hprt mutants were observed for any of the doses or time points assayed. Molecular analysis of 80 liver lacI mutants from rats fed 543 ppm LMG for 16 weeks revealed that 21% (17/80) were clonal in origin and that most (55/63) of the independent mutations were base pair substitutions. The predominant type of mutation was G:C --> A:T transition (31/63) and the majority (68%) of these involved CpG sites. When corrected for clonality, the 16-week lacl mutation frequency ((36 +/- 10) X 10(-6)) in treated rats was not significantly different from the clonally corrected control frequency ((17 +/- 9) X 10(-6); p = 0.06). Furthermore, the lacI mutational spectrum in treated rats was not significantly different from that found for control rats (P = 0.09). Taken together, these data indicate that the DNA adducts produced by LMG in female rats do not result in detectable levels of genotoxicity, and that the increase in lacI MF observed previously in the liver of treated rats may be due to the disproportionate expansion of spontaneous lacI mutations. (C) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Manjanatha, MG (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM mmanjanatha@nctr.fda.gov NR 26 TC 9 Z9 12 U1 0 U2 2 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 22 PY 2004 VL 547 IS 1-2 BP 5 EP 18 DI 10.1016/j.mrfmmm.2003.11.009 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 806FD UT WOS:000220418900002 PM 15013694 ER PT J AU Mittelstaedt, RA Von Tungeln, LS Shaddock, JG Dobrovolsky, VN Beland, FA Heflich, RH AF Mittelstaedt, RA Von Tungeln, LS Shaddock, JG Dobrovolsky, VN Beland, FA Heflich, RH TI Analysis of mutations in the Tk gene of Tk(+/-) mice treated as neonates with 3 '-azido-3 '-deoxythymidine (AZT) SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE zidovudine; microsatellites; transgenic mouse model; loss of heterozygosity ID IMMUNODEFICIENCY-VIRUS TYPE-1; ZIDOVUDINE TREATMENT; DNA INCORPORATION; MUTANT FREQUENCY; OXIDATIVE DAMAGE; APRT LOCUS; HETEROZYGOSITY; CELLS; TRANSMISSION; GENOTOXICITY AB Mother-to-child transmission of the human immunodeficiency virus (HIV) is reduced by perinatal treatment with the antiretroviral nucleoside analogue 3'-azido-3-deoxythymidine (AZT, zidovudine). AZT, however, is genotoxic and carcinogenic in mice when administered either transplacentally or neonatally, suggesting a possible cancer risk for children later in life. In a previous study [Carcinogenesis 23 (2002) 1427-1432] we found that treating B6C3F1/Tk(+/-) mice on postnatal days I through 8 with intraperitoneal injections of 200 mg AZT per kg body weight per day significantly increased spleen lymphocyte mutant frequencies in the autosomal Tk gene. Allele-specific PCR of Tk mutants from treated mice indicated that 61 % had lost the Tk(+) allele (loss of heterozygosity; LOH), compared with 35% of Tk mutants from control mice, a difference that was significant. In the present study, Tk mutant lymphocyte clones were analyzed further using polymorphic microsatellite markers that flank the Tk gene along the length of mouse chromosome 11. The analysis indicated that allele-loss mutations in control mice were due to either total chromosome loss, mitotic recombination, or both. The pattern of marker loss in mutants from AZT-treated mice differed significantly from the control mice and was consistent with chromosome loss, mitotic recombination, interstitial deletion, gene conversion, and an unusual discontinuous LOH. The results indicate that AZT induced a unique pattern of mutations in the Tk gene of mice and that the major mechanisms of mutation by AZT involved deletion and recombination. (C) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Mittelstaedt, RA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM rmittelstaedt@nctr.fda.gov NR 18 TC 15 Z9 15 U1 0 U2 0 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 22 PY 2004 VL 547 IS 1-2 BP 63 EP 69 DI 10.1016/j.mrfmmm.2003.12.008 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 806FD UT WOS:000220418900008 PM 15013700 ER PT J AU Muthyala, RS Ju, YH Sheng, SB Williams, LD Doerge, DR Katzenellenbogen, BS Helferich, WG Katzenellenbogen, JA AF Muthyala, RS Ju, YH Sheng, SB Williams, LD Doerge, DR Katzenellenbogen, BS Helferich, WG Katzenellenbogen, JA TI Equol, a natural estrogenic metabolite from soy isoflavones: convenient preparation and resolution of R- and S-equols and their differing binding and biological activity through estrogen receptors alpha and beta SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID CANCER MCF-7 CELLS; BREAST-CANCER; ER-BETA; DIETARY PHYTOESTROGENS; INTESTINAL BACTERIA; SELECTIVE LIGANDS; AMMONIUM FORMATE; PHYTO-ESTROGENS; GUT MICROFLORA; HABITUAL DIET AB Equol is a metabolite produced in vivo from the soy phytoestrogen daidzein by the action of gut microflora. It is known to be estrogenic, so human exposure to equol could have significant biological effects. Equol is a chiral molecule that can exist as the enantiomers R-equol and S-equol. To study the biological activity of racemic (+/-)-equol, as well as that of its pure enantiomers, we developed an efficient and convenient method to prepare (+/-)-equol from available isollavanoid precursors. Furthermore, we optimized a method to separate the enantiomers of equol by chiral HPLC, and we studied for the first time, the activities of the enantiomers on the two estrogen receptors, ERalpha and ERbeta. In binding assays, S-equol has a high binding affinity, preferential for ERbeta (K-i[ERbeta] = 16 nM; beta/alpha = 13 fold), that is comparable to that of genistein (K-i[ERbeta] = 6.7 nM; beta/alpha= 16), whereas R-equol binds more weakly and with a preference for ERalpha (K-i[ERalpha] = 50 nM; beta/alpha = 0.29). All equol isomers have higher affinity for both ERs than does the biosynthetic precursor daidzein. The availability an the in vitro characterization of the equol enantiomers should enable their biological effects to be studied in detail. (C) 2004 Elsevier Ltd. All rights reserved. C1 Univ Illinois, Dept Chem, Urbana, IL 61801 USA. Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA. 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 Chem, 600 S Mathews Ave, Urbana, IL 61801 USA. EM helferic@staff.uiuc.edu; jkatzene@uiuc.edu RI Muthyala, Rajeev/H-5245-2013 OI Muthyala, Rajeev/0000-0003-0811-9877 FU NCI NIH HHS [5R01 CA19118, 5R01 CA77355]; NIDDK NIH HHS [5R37 DK15556] NR 68 TC 221 Z9 244 U1 2 U2 21 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 MAR 15 PY 2004 VL 12 IS 6 BP 1559 EP 1567 DI 10.1016/j.bmc.2003.11.035 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 803NM UT WOS:000220237800032 PM 15018930 ER PT J AU Begier, EM Burwen, DR Haber, P Ball, R AF Begier, EM Burwen, DR Haber, P Ball, R CA Vaccine Adverse Event Reporting Sy TI Postmarketing safety surveillance for typhoid fever vaccines from the Vaccine Adverse Event Reporting System, July 1990 through June 2002 SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID VI-CAPSULAR POLYSACCHARIDE; ENTERIC-COATED CAPSULES; SALMONELLA-TYPHI; UNITED-STATES; FIELD TRIAL; EFFICACY; IMMUNOGENICITY; IMMUNIZATION AB Vaccines against Salmonella enterica serotype Typhi are used for prophylaxis of international travelers and have potential use as counterbioterrorism agents. The Vaccine Adverse Event Reporting System (VAERS) cannot usually establish causal relationships between vaccines and reported adverse events without further research but has successfully detected unrecognized side effects of vaccine. We reviewed reports to VAERS for US-licensed typhoid fever vaccines for the period of July 1990 through June 2002. We received 321 reports for parenteral Vi capsular polysaccharide vaccine and 345 reports for live, oral, attenuated Ty21a vaccine, with 7.5% and 5.5%, respectively, describing death, hospitalization, permanent disability, or life-threatening illness. Unexpected frequently reported symptoms included dizziness and pruritus for Vi vaccine and fatigue and myalgia for Ty21a vaccine. Gastroenteritis-like illness after receipt of Ty21a vaccine and abdominal pain after receipt of Vi vaccine, which are previously recognized events, occasionally required hospitalization. Nonfatal anaphylaxis was reported after both vaccines. VAERS reports do not indicate any unexpected serious side effects that compromise these vaccines' use for travelers' prophylaxis. C1 US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Div Epidemiol,Vaccine Safety Branch, Rockville, MD 20852 USA. Ctr Dis Control & Prevent, Immunizat Safety Branch, Epidemiol & Surveillance Div, Natl Immunizat Program, Atlanta, GA USA. RP Ball, R (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Div Epidemiol,Vaccine Safety Branch, HFM-222,1401 Rockville Pike, Rockville, MD 20852 USA. EM ballr@cber.fda.gov NR 34 TC 21 Z9 25 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 15 PY 2004 VL 38 IS 6 BP 771 EP 779 DI 10.1086/381548 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 800QI UT WOS:000220042400008 PM 14999618 ER PT J AU Al-Khaldi, SF Villanueva, D Chizhikov, V AF Al-Khaldi, SF Villanueva, D Chizhikov, V TI Identification and characterization of Clostridium perfringens using single target DNA microarray chip SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Clostridium perfringens; single target DNA microarray chip; toxin genes ID ESCHERICHIA-COLI; ENTEROTOXIN GENE; PHOSPHOLIPASE-C; ALPHA-TOXIN; SEQUENCE; HOMOLOGY; BORNE AB A DNA microarray method was developed to identify the presence of toxin genes: encoding beta toxin (cpb), epsilon toxin (etx), enterotoxin (cpe), alpha toxin (cpa), and iota toxin (iA) in Clostridium perfringens. To build the DNA chip, each gene sequence was represented by one similar to 22-bp amino-modified oligonucleotide printed twice on aldehyde-coated slides. Multiplex PCR with Cy3 and Cy5-dCTP derivatized fluorescent nucleotides was used to label five genes and fluorescent probes were prepared. The PCR probes were denatured and single-strand-labeled DNAs were separated and purified using magnetic beads. The presence of toxin genes in C. perfringens was detected by hybridization of amplified ssDNA probes to oligonucleotides on the chip representing one target sequence of each toxin gene. The DNA chip was able to identify eight strains of C. perfringens. (C) 2003 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol Studies, HSF 517, College Pk, MD 20740 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Al-Khaldi, SF (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol Studies, HSF 517, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Sufian.Al-Khaldi@cfsan.fda.gov NR 14 TC 21 Z9 26 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD MAR 15 PY 2004 VL 91 IS 3 BP 289 EP 296 DI 10.1016/j.ijfoodmicro.2003.07.009 PG 8 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 800GW UT WOS:000220017900006 PM 14984776 ER PT J AU Bhattacharya, SS Kulka, M Lampel, KA Cebula, TA Goswami, BB AF Bhattacharya, SS Kulka, M Lampel, KA Cebula, TA Goswami, BB TI Use of reverse transcription and PCR to discriminate between infectious and non-infectious hepatitis A virus SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE hepatitis A virus; infectious; inactivated; discrimination by RT-PCR ID POLYMERASE CHAIN-REACTION; HUMAN ENTERIC VIRUSES; RT-PCR; ENVIRONMENTAL-SAMPLES; TEMPLATE PREPARATION; CAPTURE PCR; AMPLIFICATION; SHELLFISH; OYSTERS; FOODS AB Hepatitis A virus (HAV) is a major cause of infectious hepatitis worldwide. Detection of HAV in contaminated food or water is a priority research area in laboratories worldwide. Our laboratory has reported previously the development of reverse transcription-polymerase chain reaction (RT-PCR) based detection and typing methods for HAV in contaminated shellfish and produce. It is commonly held that RT-PCR can detect viral genome, but cannot distinguish between infectious and inactivated virus. Therefore, signals obtained after PCR should be considered as false positives unless it can be shown that the sample contains virus capable of infecting a suitable host cell line in culture. We present data to show that this general assumption is not valid. Evidence is provided that demonstrate that signals generated after RT-PCR amplification of viral genome correlated well with the presence of infectious virus in the sample. Viral samples inactivated by heat or UV treatment produced significantly lower signal strength that paralleled infectivity of the sample in cultured cells. The loss of signal strength is most likely the result of damage to the viral RNA that renders it unsuitable for RT-PCR. The correlation between PCR signal and infectivity was better following UV inactivation than heat treatment. The procedure may be adapted to other viruses and inactivating agents. Published by Elsevier B.V. C1 US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, Laurel, MD 20708 USA. RP Goswami, BB (reprint author), US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, HFS-025,8301 Muirkirk Rd, Laurel, MD 20708 USA. EM bgoswami@cfsan.fda.gov NR 22 TC 41 Z9 42 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD MAR 15 PY 2004 VL 116 IS 2 BP 181 EP 187 DI 10.1016/j.jviromet.2003.11.008 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 776AP UT WOS:000189093100011 PM 14738986 ER PT J AU Karrow, NA Guo, TL Delclos, KB Newbold, RR Weis, C Germolec, DR White, KL McCay, JA AF Karrow, NA Guo, TL Delclos, KB Newbold, RR Weis, C Germolec, DR White, KL McCay, JA TI Nonylphenol alters the activity of splenic NK cells and the numbers of leukocyte subpopulations in Sprague-Dawley rats: a two-generation feeding study SO TOXICOLOGY LA English DT Article DE nonylphenol (NP); in utero exposure; immunomodulation; rat; feeding study ID ESTROGENIC ACTIVITY; RAINBOW-TROUT; EXPOSURE; 4-NONYLPHENOL; TOXICOLOGY; TOXICITY; IMMUNITY AB Nonylphenol (NP) has been identified at low levels in surface waters throughout North America. This industrial chemical is primarily used for the production of certain non-ionic surfactants, and has been reported to have weak estrogen-like activity. As estrogen has immunoregulatory properties and is crucial for normal fetal development, it was hypothesized that adult and developmental exposures to NP had the potential to adversely affect the immune system. Furthermore, developmental exposure to NP might also produce differential immunomodulation in F-1 male and female rats. Thus, a two-generation feeding study was conducted to evaluate the potential for NP to modulate certain immune parameters. Pregnant female Sprague-Dawley rats were exposed to NP (0, 25, 500, and 2000 ppm) in their feed for 65 days, beginning 7 days into gestation. The F-1 generation male and female offspring were exposed in utero at the respective treatment levels, commencing the 7th day of gestation, and continuing through to 64 days of age. Changes in splenic antibody-forming cell response, natural killer cell activity, and leukocyte numbers were used to evaluate NP immunotoxicity. The results from the present study indicate that dietary exposure to NP can increase splenic natural killer (NK) cell activity and splenocyte subpopulation numbers in the F-1 generation rats, without similar changes to the F-0 generation. The immunological changes that were observed in the F-1 generation also appeared to be gender-specific. (C) 2003 Elsevier Ireland 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 White, KL (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Med Coll Virginia Campus, Richmond, VA 23298 USA. EM kwhite@hsc.vcu.edu FU NIEHS NIH HHS [ES 55094] NR 23 TC 20 Z9 24 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD MAR 15 PY 2004 VL 196 IS 3 BP 237 EP 245 DI 10.1016/j.tox.2003.11.009 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 800EE UT WOS:000220010900007 PM 15036750 ER PT J AU Younick, JJ Koenig, ML Yourick, DL Bronaugh, RL AF Younick, JJ Koenig, ML Yourick, DL Bronaugh, RL TI Fate of chemicals in skin after dermal application: does the in vitro skin reservoir affect the estimate of systemic absorption? SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE chemicals; skin; absorption ID INVITRO PERCUTANEOUS-ABSORPTION; CARBONYL-COMPOUNDS; DIHYDROXYACETONE; MUTAGENICITY; INDUCTION; DNA AB Recent international guidelines for the conduct of in vitro skin absorption studies put forward different approaches for addressing the status of chemicals remaining in the stratum corneum and epidermis/dermis at the end of a study. The present study investigated the fate of three chemicals [dihydroxyacetone (DHA), 7-(2H-naphtho[1,2-d]triazol-2-yl)-3-phenylcoumarin (7NTPC), and disperse blue 1 (DB1)] in an in vitro absorption study. In these studies, human and fuzzy rat skin penetration and absorption were determined over 24 or 72 h in flow-through diffusion cells. Skin penetration of these chemicals resulted in relatively low receptor fluid levels but high skin levels. For DHA, penetration studies found approximately 22% of the applied dose remaining in the skin (in both the stratum corneum and viable tissue) as a reservoir after 24 h. Little of the DHA that penetrates into skin is actually available to become systemically absorbed. 7NTPC remaining in the skin after 24 h was approximately 14.7% of the applied dose absorbed. Confocal laser cytometry studies with 7NTPC showed that it is present across skin in mainly the epidermis and dermis with intense fluorescence around hair. For DB1, penetration studies found approximately 10% (ethanol vehicle) and 3% (formulation vehicle) of the applied dose localized in mainly the stratum corneum after 24 h. An extended absorption study (72 h) revealed that little additional DB1 was absorbed into the receptor fluid. Skin levels should not be considered as absorbed material for DHA or DB1, while 7NTPC requires further investigation. These studies illustrate the importance of determining the fate of chemicals remaining in skin, which could significantly affect the estimates of systemically available material to be used in exposure estimates. We recommend that a more conclusive means to determine the fate of skin levels is to perform an extended study as conducted for DB1. Published by Elsevier Inc. C1 US FDA, Skin Absorpt & Metab Sect, Cosmet Toxicol Branch, Off Cosmet & Colors, Laurel, MD 20708 USA. Walter Reed Army Inst Res, Div Neurosci, Silver Spring, MD 20910 USA. RP Younick, JJ (reprint author), US FDA, Skin Absorpt & Metab Sect, Cosmet Toxicol Branch, Off Cosmet & Colors, 8301 Muirkirk Rd,Bldg BRF,HFS-128, Laurel, MD 20708 USA. EM jyourick@cfsan.fda.gov RI Yourick, Debra/A-2121-2011 NR 34 TC 29 Z9 31 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAR 15 PY 2004 VL 195 IS 3 BP 309 EP 320 DI 10.1016/j.taap.2003.07.015 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 804FO UT WOS:000220284800006 ER PT J AU Wang, ZH Plakas, SM El Said, KR Jester, ELE Granade, HR Dickey, RW AF Wang, ZH Plakas, SM El Said, KR Jester, ELE Granade, HR Dickey, RW TI LC/MS analysis of brevetoxin metabolites in the Eastern oyster (Crassostrea virginica) SO TOXICON LA English DT Article DE brevetoxins; metabolism; Eastern oyster; cytotoxicity; liquid chromatography/mass spectrometry ID RED TIDE; CYTOTOXICITY; TOXINS AB Brevetoxin (PbTx) metabolism was examined in the Eastern oyster (Crassostrea virginica) following exposure to a Karenia brevis red tide. by using, LC/MS(/MS) and cytotoxicity assay. Metabolites observed in field-exposed oysters were confirmed in oysters exposed to K. brevis Cultures in the laboratory. Previously, we identified a cysteine conjugate and its sulfoxide (MH+: m/z 1018 and 1034) as metabolites of the brevetoxin congener PbTx-2. In the present study, we found a cysteine conjugate and its sulfoxide with A-type brevetoxin backbone structure (MH+ : m/z 990 and 1006), as probable derivatives of PbTx- 1. We also found glycine-cysteine-PbTx (m/z 1047 and 1075), gamma-glutamyl-cysteine-PbTx (m/z 1147), and glutathione-PbTx (m/z 1176 and 1204) conjugates with A- and B-type backbone structures. Amino acid-PbTx conjugates react with fatty acids through amide linkage to form a series of fatty acid-amino acid-PbTx conjugates. These fatty acid conjugates are major contributors to the composite cytototoxic responses obtained in extracts of brevetoxin-contaminated oysters. Other brevetoxin derivatives found in oysters are consistent with hydrolytic ring-opening and oxidation/reduction reactions. Published by Elsevier Ltd. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Plakas, SM (reprint author), US FDA, Gulf Coast Seafood Lab, POB 158,1 Iberville Dr, Dauphin Isl, AL 36528 USA. EM splakas@cfsan.fda.gov NR 9 TC 56 Z9 59 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD MAR 15 PY 2004 VL 43 IS 4 BP 455 EP 465 DI 10.1016/j.toxicon.2004.02.017 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 815CW UT WOS:000221021400013 PM 15051410 ER PT J AU Ruley, KM Ansede, JH Pritchett, CL Talaat, AM Reimschuessel, R Trucksis, M AF Ruley, KM Ansede, JH Pritchett, CL Talaat, AM Reimschuessel, R Trucksis, M TI Identification of Mycobacterium marinum virulence genes using signature-tagged mutagenesis and the goldfish model of mycobacterial pathogenesis SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE Mycobacterium marinum; signature-tagged mutagenesis; mycobacterium; virulence; pathogenesis; goldfish model ID TRANSPOSON MUTAGENESIS; TUBERCULOSIS; DNA; SEQUENCE; GENOME; ACIDS AB Mycobacterium marinum, a causative agent of fish tuberculosis, is one of the most closely related Mycobacterium species (outside the M. tuberculosis complex) to M. tuberculosis, the etiologic agent of human tuberculosis. Signature-tagged mutagenesis was used to identify genes of M. marinum required for in vivo survival in a goldfish model of mycobacterial pathogenesis. Screening the first 1008 M. marinum mutants led to the identification of 40 putative virulence mutants. DNA sequence analysis of these 40 mutants identified transposon insertions in 35 unique loci. Twenty-eight out of 33 (85%) loci encoding putative virulence genes have homologous genes in M. tuberculosis. (C) 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved. C1 Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. US FDA, Ctr Vet Med, Laurel, MD 20857 USA. Univ Maryland, Sch Med, Med Serv, Vet Affairs Med Ctr, Baltimore, MD 21201 USA. RP Trucksis, M (reprint author), Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA. EM michele.trucksis@umassmed.edu NR 22 TC 25 Z9 27 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD MAR 12 PY 2004 VL 232 IS 1 BP 75 EP 81 DI 10.1016/S0378-1097(04)00017-5 PG 7 WC Microbiology SC Microbiology GA 805DJ UT WOS:000220346700011 PM 15019737 ER PT J AU Muthukkumar, S Stein, KE AF Muthukkumar, S Stein, KE TI Immunization with meningococcal polysaccharide-tetanus toxoid conjugate induces polysaccharide-reactive T cells in mice SO VACCINE LA English DT Article DE meningococcal group C polysaccharide; tetanus toxoid; T cell cones ID MAJOR HISTOCOMPATIBILITY COMPLEX; B-CELLS; CAPSULAR POLYSACCHARIDE; LISTERIA-MONOCYTOGENES; DENDRITIC CELLS; IMMUNE-RESPONSE; II COLLAGEN; TNP-FICOLL; RECOGNITION; ANTIGEN AB T cell clones were generated from mice immunized with a meningococcal group C (alpha2 --> 9-sialic acid) polysaccharide-tetanus toxoid (MCPS-TT) conjugate. Many clones were found to be specific for tetanus toxoid (TT), however, clones reactive with MCPS-TT and polysaccharide (PS) were isolated. Two clones were specific for MCPS and two cross-reacted with Escherichia coli K1-PS (alpha2 --> 8-sialic acid). Both TT and PS reactive clones were CD4(+) and CD8(-). TT and MCPS-TT-specific T cell clones were major histocompatibility complex (MHC) restricted, however, the PS-reactive clones were not. Both MHC-restricted TT clones and non-restricted PS clones, however, were dependent on contact with antigen presenting cells (APC) for maximal stimulation. The data suggest that multivalent repeating epitopes on PS antigen (Ag) can overcome the need for MHC restricted interactions, but not the requirement for cell-cell contact. Published by Elsevier Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. RP Muthukkumar, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM muthukkumar@cber.fda.gov NR 58 TC 15 Z9 19 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAR 12 PY 2004 VL 22 IS 9-10 BP 1290 EP 1299 DI 10.1016/j.vaccine.2003.08.047 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 804WF UT WOS:000220328100027 PM 15003659 ER PT J AU Landry, R Wolffe, M Burrows, C Rassow, B Byrnes, G AF Landry, R Wolffe, M Burrows, C Rassow, B Byrnes, G TI Study of the effect of involuntary user movement on the potential light hazards from some ophthalmic instruments SO APPLIED OPTICS LA English DT Article ID EXTRACAPSULAR CATARACT-EXTRACTION; INTRAOCULAR-LENS IMPLANTATION; INDUCED MACULOPATHY; OPERATING MICROSCOPE; PHOTIC MACULOPATHY; PENETRATING KERATOPLASTY; RETINAL DAMAGE; SURGERY; RECOVERY AB A study was undertaken to determine whether involuntary user movement provides a basis for relaxing the measurement conditions for evaluating the potential optical radiation hazards to the eye from slit lamps and indirect ophthalmoscopes. This was accomplished by assessment of the extent to which light from these devices can be maintained in focus on a 1-mm-diameter fiber-optic cable for 45 s. The results suggest that, although involuntary user movements can be significant, they do not provide a basis for relaxing the measurement conditions for evaluating the potential optical radiation hazards to the cornea and lens from slit lamps and indirect ophthalmoscopes. (C) 2004 Optical Society of America. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. Keeler Ltd, Windsor SL4 4AA, Berks, England. Augen & Poliklin, D-20242 Hamburg, Germany. RP Landry, R (reprint author), US FDA, Ctr Devices & Radiol Hlth, 9200 Corp Blvd, Rockville, MD 20850 USA. EM ijl@cdrh.fda.gov NR 21 TC 2 Z9 2 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD MAR 10 PY 2004 VL 43 IS 8 BP 1643 EP 1647 DI 10.1364/AO.43.001643 PG 5 WC Optics SC Optics GA 800YZ UT WOS:000220064900006 PM 15046166 ER PT J AU Miller, SA Landry, RJ Byrnes, GA AF Miller, SA Landry, RJ Byrnes, GA TI Endoilluminators: evaluation of potential retinal hazards SO APPLIED OPTICS LA English DT Article ID MACULAR HOLE SURGERY; PIGMENT EPITHELIOPATHY; VITRECTOMY; LIGHT; INJURY; DAMAGE; TRIAL AB The potential for retinal photic injury from exposure to endoilluminators was evaluated. The spectral irradiance for each endoilluminator configuration was weighted with the American Conference of Government Industrial Hygienists (ACGIH) aphakic action spectrum. The result was compared with the threshold limit value (TLV) published by the ACGIH and a time to TLV (time(TLV)) was calculated for each configuration. The calculated time(TLV) ranged from 0.27 to 3.5 min, times that are significantly shorter than typical operating times. The effects of incorporating short-wavelength cutoff filters were evaluated and found to significantly increase the time(TLV). Exposure reduction techniques for use during surgery are discussed. (C) 2004 Optical Society of America. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. USN, Med Res Inst, Dept Ophthalmol, Bethesda, MD 20889 USA. RP Miller, SA (reprint author), US FDA, Ctr Devices & Radiol Hlth, 9200 Corp Blvd, Rockville, MD 20850 USA. EM sym@cdrh.fda.gov; rjl@cdrh.fda.gov NR 18 TC 8 Z9 10 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD MAR 10 PY 2004 VL 43 IS 8 BP 1648 EP 1653 DI 10.1364/AO.43.001648 PG 6 WC Optics SC Optics GA 800YZ UT WOS:000220064900007 PM 15046167 ER PT J AU Eswaramoorthy, S Kumaran, D Keller, J Swaminathan, S AF Eswaramoorthy, S Kumaran, D Keller, J Swaminathan, S TI Role of metals in the biological activity of clostridium botulinum neurotoxins SO BIOCHEMISTRY LA English DT Article ID BACTERIAL PROTEIN TOXINS; LIGHT-CHAIN; NEUROTRANSMITTER RELEASE; CRYSTAL-STRUCTURE; TETANUS TOXIN; ZINC-BINDING; DIFFRACTION DATA; SPINAL-CORD; PH; THERMOLYSIN AB Clostridium botulinum neurotoxins are the most potent toxins to humans and cause paralysis by blocking neurotransmitter release at the presynaptic nerve terminals. The toxicity involves four steps, viz., binding to neuronal cells, internalization, translocation, and catalytic activity. While the catalytic activity is a zinc endopeptidase activity on the SNARE complex proteins, the translocation is believed to be a pH-dependent process allowing the translocation domain to change its conformation to penetrate the endosomal membrane. Here, we report the crystal structures of botulinum neurotoxin type B at various pHs and of an apo form of the neurotoxin, and discuss the role of metal ions and the effect of pH variation in the biological activity. Except for the perturbation of a few side chains, the conformation of the catalytic domain is unchanged in the zinc-depleted apotoxin, suggesting that zinc's role is catalytic. We have also identified two calcium ions in the molecule and present biochemical evidence to show that they play a role in the translocation of the light chain through the membrane. C1 Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. US FDA, Lab Bacterial Toxins, Bethesda, MD 20892 USA. RP Swaminathan, S (reprint author), Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. EM swami@bnl.gov NR 53 TC 39 Z9 39 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 2 PY 2004 VL 43 IS 8 BP 2209 EP 2216 DI 10.1021/bi035844k PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 777PA UT WOS:000189185700008 PM 14979717 ER PT J AU Voegtlin, DJ Halbert, SE Qiao, GX AF Voegtlin, DJ Halbert, SE Qiao, GX TI A guide to separating Aphis glycines Matsumura and morphologically similar species that share its hosts SO ANNALS OF THE ENTOMOLOGICAL SOCIETY OF AMERICA LA English DT Article DE Aphis glycines; Aphis nasturtii; Aphis gossypii; Rhamnus cathartica; morphology AB Aphis glycines Matsumura shares its hosts with two other aphid species, Aphis nasturtii Kaltenbach and Aphis gossypii Glover. Tables of characters and photographs are provided to assist in the separation of these three species. A photographic plate showing a gynopara, male, ovipara, and late summer apterous vivipara of A. glycines is included. C1 Illinois Nat Hist Survey, Ctr Econ Entomol, Champaign, IL 61820 USA. FDACS, Div Plant Ind, Gainesville, FL 32614 USA. Chinese Acad Sci, Inst Zool, Beijing 100080, Peoples R China. RP Voegtlin, DJ (reprint author), Illinois Nat Hist Survey, Ctr Econ Entomol, Champaign, IL 61820 USA. EM dvoegtli@uiuc.edu NR 6 TC 23 Z9 23 U1 1 U2 5 PU ENTOMOL SOC AMER PI LANHAM PA 9301 ANNAPOLIS RD, LANHAM, MD 20706 USA SN 0013-8746 J9 ANN ENTOMOL SOC AM JI Ann. Entomol. Soc. Am. PD MAR PY 2004 VL 97 IS 2 BP 227 EP 232 DI 10.1603/0013-8746(2004)097[0227:AGTSAG]2.0.CO;2 PG 6 WC Entomology SC Entomology GA 803AI UT WOS:000220203600005 ER PT J AU Li, XL Ljungdahl, LG Ximenes, EA Chen, HH Felix, CR Cotta, MA Dien, BS AF Li, XL Ljungdahl, LG Ximenes, EA Chen, HH Felix, CR Cotta, MA Dien, BS TI Properties of a recombinant beta-glucosidase from polycentric anaerobic fungus Orpinomyces PC-2 and its application for cellulose hydrolysis SO APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY LA English DT Article; Proceedings Paper CT 25th Symposium on Biotechnology for Fuels and Chemicals CY MAY 04-07, 2003 CL Breckenridge, CO SP US DOE, Off Biomass Program, Natl Renewable Energy Lab, Oak Ridge Natl Lab, Argonne Natl Lab, Idaho Natl Engn & Envirnom Lab, Pacific NW Natl Lab, USDA, Alltech, Archer Daniels Midland, BBI Int, Biotechnol Ind Org, Breckenridge Brewery, Cargill Inc, Cargill Dow LLC, Coors Brewing Co, Corn Refiners Assoc, E I Du Pont Nemours & Co Inc, Genencor Int, Iogen Corp, Katzen Int, Nat Resources Canada, Novozymes Biotech, Proctor & Gamble, Syngenta, Tate & Lyle, Tembec Ind DE cellulose; cellulase; beta-glucosiclase; Orpinomyces; cellobiase ID NEOCALLIMASTIX-FRONTALIS EB188; SP STRAIN PC-2; SACCHAROMYCES-CEREVISIAE; GLYCOSYL HYDROLASES; SEQUENCE-ANALYSIS; DOCKING DOMAINS; GENE; PURIFICATION; CELLULASES; SECRETION AB A beta-glucosidase (Bg1A, EC 3.2.1.21) gene from the polycentric anaerobic fungus Orpinomyces PC-2 was cloned and sequenced. The enzyme containing 657 amino acid residues was homologous to certain animal, plant, and bacterial beta-glucosidases but lacked significant similarity to those from aerobic fungi. Neither cellulose- nor protein-binding domains were found in BgIA. When expressed in Saccharomyces cerevisiae, the enzyme was secreted in two forms with masses of about 110 kDa and also found in two forms associated with the yeast cells. K-m and V-max values of the secreted Bg1A were 0.762 mM and 8.20 mumol/(min(.)mg), respectively, with p-nitrophenyl-beta-D-glucopyranoside (pNPG) as the substrate and 0.310 mM and 6.45 mumol/(min(.)mg), respectively, for the hydrolysis of cellobiose. Glucose competitively inhibited the hydrolysis of pNPG with a K-i of 3.6 mM. beta-Glucosidase significantly enhanced the conversion of cellulosic materials into glucose by Trichoderma reesei cellulase preparations, demonstrating its potential for use in biofuel and feedstock chemical production. C1 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. Univ Brasilia, Dept Biol Celular, Lab Enzimol, BR-70910900 Brasilia, DF, Brazil. US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP USDA ARS, Natl Ctr Agr Utilizat Res, Fermentat Biotechnol Res Unit, 1815 N Univ St, Peoria, IL 61604 USA. EM lix@ncaur.usda.gov OI Ximenes, Eduardo/0000-0001-9087-0218; Cotta, Michael/0000-0003-4565-7754 NR 49 TC 12 Z9 13 U1 0 U2 11 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0273-2289 EI 1559-0291 J9 APPL BIOCHEM BIOTECH JI Appl. Biochem. Biotechnol. PD SPR PY 2004 VL 113 BP 233 EP 250 DI 10.1385/ABAB:113:1-3:233 PG 18 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 817OG UT WOS:000221186200021 PM 15054209 ER PT J AU Markovic, I Stantchev, TS Fields, KH Tiffany, LJ Tomic, M Weiss, CD Broder, CC Strebel, K Clouse, KA AF Markovic, I Stantchev, TS Fields, KH Tiffany, LJ Tomic, M Weiss, CD Broder, CC Strebel, K Clouse, KA TI Thiol/disulfide exchange is a prerequisite for CXCR4-tropic HIV-1 envelope-mediated T-cell fusion during viral entry SO BLOOD LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN-DISULFIDE-ISOMERASE; MEMBRANE-FUSION; PLASMA-MEMBRANE; INFLUENZA HEMAGGLUTININ; DETERGENT-RESISTANT; SURFACE ASSOCIATION; LIPID RAFTS; CD4; MICRODOMAINS AB Attachment of gp120 to CD4 during HIV-1 entry triggers structural rearrangement in gp120 that enables binding to an appropriate coreceptor. Following coreceptor engagement, additional conformational changes occur in the envelope (Env), resulting in fusion of virion and cell membranes. Catalysts with redox-isomerase activity, such as protein disulfide isomerase (PDI), facilitate Env conversion from its inactive to its fusion-competent conformation. We report here that anti-PDI agents effectively block CXCR4 Env-mediated fusion and spread of virus infection. Exogenously added PDI, in turn, can rescue fusion from this blockade. We further find that PDI facilitates thiol/disulfide rearrangement in gp120 during conformational change, whereas inhibition of this redox shuffling prevents gp41 from assuming the fusogenic 6-helix bundle conformation. At the virus-cell contact site, gp120 induces assembly of PDI, CD4, and CXCR4 into a tetramolecular protein complex serving as a portal for viral entry. Our findings support the hypothesis that Env conformational change depends on a well-coordinated action of a tripartite system in which PDI works in concert with the receptor and the coreceptor to effectively lower the activation energy barrier required for Env conformational rearrangement. (C) 2004 by The American Society of Hematology. C1 CDER, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Bethesda, MD 20814 USA. NICHHD, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Markovic, I (reprint author), Bldg 29B,Rm 3E18,29 Lincoln Dr, Bethesda, MD 20892 USA. EM markovic@cber.fda.gov RI Weiss, Carol/F-6438-2011; Tomic, Melanija/C-3371-2016 OI Weiss, Carol/0000-0002-9965-1289; NR 44 TC 90 Z9 96 U1 0 U2 7 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 MAR 1 PY 2004 VL 103 IS 5 BP 1586 EP 1594 DI 10.1182/blood-2003-05-1390 PG 9 WC Hematology SC Hematology GA 778NM UT WOS:000189247700013 PM 14592831 ER PT J AU Sherman, ME Mink, PJ Curtis, R Cote, TR Brooks, S Hartge, P Devesa, S AF Sherman, ME Mink, PJ Curtis, R Cote, TR Brooks, S Hartge, P Devesa, S TI Survival among women with borderline ovarian tumors and ovarian carcinoma - A population-based analysis SO CANCER LA English DT Article DE ovary; neoplasia; borderline; low malignant potential; survival; serous; mucinous ID MICROPAPILLARY SEROUS CARCINOMA; K-RAS MUTATIONS; PSEUDOMYXOMA-PERITONEI; CIGARETTE-SMOKING; MUCINOUS TUMORS; RISK-FACTORS; CLINICOPATHOLOGICAL ANALYSIS; HISTOLOGIC TYPE; INTESTINAL-TYPE; UNITED-STATES AB BACKGROUND. Serous and mucinous ovarian tumors of low malignant potential (LMP-S and LMP-M, respectively) are noninvasive tumors that portend excellent survival when confined to the ovary. Comparison of the survival for women with LMP tumors staged as distant with women who have carcinoma may have important implications for diagnostic terminology and clinical management. METHODS. The authors compared relative survival rates among patients diagnosed with ovarian tumors during the period 1988-1999 (with follow-up through 2000) by histologic type, disease stage, tumor grade (for carcinomas), and patient age, using data from the Surveillance, Epidemiology, and End Results Program. RESULTS. The overall relative survival rate at 10 years (+/- 1.96 standard errors) was 96.9% +/- 2.3% for women with LMP-S tumors, 30.4% +/- 1.7% for women with serous carcinoma (CA-S); 94.0% +/- 3.1% for women with LMP-M tumors, and 64.7% +/- 3.4% for women with mucinous carcinoma (CA-M). The survival rate at 10 years for women with distant-stage LMP-S tumors was 89.9% +/- 5.3%, compared with 96.1% +/- 8.6% for women with well differentiated, localized CA-S. The survival rate for women with distant-stage LMP-M tumors at 5 years was 85.5% +/- 9.0%, compared with 95.5% +/- 3.4% for women with well differentiated, localized CA-M (data for 10 years were limited). Mucinous ovarian neoplasms were associated with all excess of second malignancies of the digestive tract. CONCLUSIONS. Relative survival among women with distant-stage LMP tumors was not 100% and resembled the survival of women who had carcinoma exhibiting favorable prognostic features (localized stage). Future studies of women with high-stage LMP tumors are required to clarify the pathogenesis of extraovarian lesions and their implications for management and prognosis. Published 2004 by the American Cancer Society.* C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Exponent, Washington, DC USA. US FDA, Therapeut & Blood Safety Branch, Rockville, MD 20857 USA. Univ Maryland, Sch Med, Dept Obstet & Gynecol, Baltimore, MD 21201 USA. RP Sherman, ME (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7080, Bethesda, MD 20892 USA. EM shermanm@mail.nih.gov NR 47 TC 78 Z9 82 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 1 PY 2004 VL 100 IS 5 BP 1045 EP 1052 DI 10.1002/cncr.20080 PG 8 WC Oncology SC Oncology GA 775XB UT WOS:000189085000022 PM 14983501 ER PT J AU Toraason, M Albertini, R Bayard, S Bigbee, W Blair, A Boffetta, P Bonassi, S Chanock, S Christiani, D Eastmond, D Hanash, S Henry, C Kadlubar, F Mirer, F Nebert, D Rapport, S Rest, K Rothman, N Ruder, A Savage, R Schulte, P Siemiatycki, J Shields, P Smith, M Tolbert, P Vermeulen, R Vineis, P Wacholder, S Ward, E Waters, M Weston, A AF Toraason, M Albertini, R Bayard, S Bigbee, W Blair, A Boffetta, P Bonassi, S Chanock, S Christiani, D Eastmond, D Hanash, S Henry, C Kadlubar, F Mirer, F Nebert, D Rapport, S Rest, K Rothman, N Ruder, A Savage, R Schulte, P Siemiatycki, J Shields, P Smith, M Tolbert, P Vermeulen, R Vineis, P Wacholder, S Ward, E Waters, M Weston, A TI Applying new biotechnologies to the study of occupational cancer - A workshop summary SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE biomarkers; chemical exposure; epidemiology; gene-environment interactions; genomics; occupational cancer; polymorphisms; proteomics; risk assessment; toxicogenomics AB As high-throughput technologies in genomics, transcriptomics, and proteomics evolve, questions arise about their use in the assessment of occupational cancers. To address these questions, the National Institute for Occupational Safety and Health, the National Cancer Institute, the National Institute of Environmental Health Sciences, and the American Chemistry Council sponsored a workshop 8-9 May 2002 in Washington, DC. The workshop brought together 80 international specialists whose objective was to identify the means for best exploiting new technologies to enhance methods for laboratory investigation, epidemiologic evaluation, risk assessment, and prevention of occupational cancer. The workshop focused on identifying and interpreting markers for early biologic effect and inherited modifiers of risk. C1 NIOSH, Cincinnati, OH 45226 USA. Univ Vermont, Burlington, VT USA. Occupat Safety & Hlth Adm, Washington, DC USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. NCI, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Int Agcy Res Canc, F-69372 Lyon, France. Natl Inst Canc Res, Genoa, Italy. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Calif Riverside, Riverside, CA 92521 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Amer Chem Council, Arlington, VA USA. Natl Ctr Toxicol Res, Jefferson, AR USA. United Auto Workers Union, Int Union, Hlth & Safety Dept, Detroit, MI USA. Univ Cincinnati, Cincinnati, OH USA. Univ N Carolina, Chapel Hill, NC USA. NIOSH, Washington, DC USA. Univ Montreal, Montreal, PQ, Canada. Georgetown Univ, Washington, DC USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. Emory Univ, Atlanta, GA 30322 USA. Univ Turin, Turin, Italy. Amer Canc Soc, Atlanta, GA 30329 USA. NIEHS, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. NIOSH, Morgantown, WV 26505 USA. RP Toraason, M (reprint author), NIOSH, C23,4676 Columbia Pkwy, Cincinnati, OH 45226 USA. EM mtoraason@cdc.gov RI Waters, Martha/B-7441-2011; Shields, Peter/I-1644-2012; Ruder, Avima/I-4155-2012; Tolbert, Paige/A-5676-2015; Vermeulen, Roel/F-8037-2011; OI Ruder, Avima/0000-0003-0419-6664; Vermeulen, Roel/0000-0003-4082-8163; bonassi, stefano/0000-0003-3833-6717 NR 5 TC 21 Z9 23 U1 0 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2004 VL 112 IS 4 BP 413 EP 416 DI 10.1289/txg.6343 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 807BS UT WOS:000220477600012 PM 15033588 ER PT J AU Kramer, JA Pettit, SD Amin, RP Bertram, TA Car, B Cunningham, M Curtiss, SW Davis, JW Kind, C Lawton, M Naciff, JM Oreffo, V Roman, RJ Sistare, FD Stevens, J Thompson, K Vickers, AE Wild, S Afsharif, CA AF Kramer, JA Pettit, SD Amin, RP Bertram, TA Car, B Cunningham, M Curtiss, SW Davis, JW Kind, C Lawton, M Naciff, JM Oreffo, V Roman, RJ Sistare, FD Stevens, J Thompson, K Vickers, AE Wild, S Afsharif, CA TI Overview of the application of transcription profiling using selected nephrotoxicants for toxicology assessment SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cisplatin; gentamicin; nephrotoxicity; puromycin; risk assessment ID GENTAMICIN AB Microarrays allow for the simultaneous measurement of changes in the levels of thousands of messenger RNAs within a single experiment. As such, the potential for the application of transcription profiling to preclinical safety assessment and mechanism-based risk assessment is profound. However, several practical and technical challenges remain. Among these are nomenclature issues, platform-specific data formats, and the lack of uniform analysis methods and tools. Experiments were designed to address biological, technical, and methodological variability, to evaluate different approaches to data analysis, and to understand the application of the technology to other profiling methodologies and to mechanism-based risk assessment. These goals were addressed using experimental information derived from analysis of the biological response to three mechanistically distinct nephrotoxins: cisplatin, gentamicin, and puromycin aminonucleoside. In spite of the technical challenges, the transcription profiling data yielded mechanistically and topographically valuable information. The analyses detailed in the articles from the Nephrotoxicity Working Group of the International Life Sciences Institute Health and Environmental Sciences Institute suggest at least equal sensitivity of microarray technology compared to traditional end points. Additionally, microarray analysis of these prototypical nephrotoxicants provided an opportunity for the development of candidate bridging biomarkers of nephrotoxicity. The potential future extension of these applications for risk assessment is also discussed. C1 ILSI Hlth & Environm Sci Inst, Washington, DC 20005 USA. Pfizer Inc, St Louis, MO USA. Pfizer Inc, Groton, CT 06340 USA. NIEHS, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC USA. Bristol Myers Squibb Co, Wilmington, DE USA. Schering Plough Res Inst, Lafayette, NJ USA. AstraZeneca, Charnwood, Leics, England. Procter & Gamble Co, Miami Valley Labs, Cincinnati, OH USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. US FDA, Ctr Drug Evaluat & Res, Laurel, MD USA. Eli Lilly & Co, Greenfield, IN 46140 USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. Amgen Inc, Thousand Oaks, CA 91320 USA. RP Pettit, SD (reprint author), ILSI Hlth & Environm Sci Inst, 1 Thomas Circle NW,9th Floor, Washington, DC 20005 USA. EM spettit@ilsi.org NR 16 TC 39 Z9 47 U1 1 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2004 VL 112 IS 4 BP 460 EP 464 DI 10.1289/txg.6673 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 807BS UT WOS:000220477600020 PM 15033596 ER PT J AU Amin, RA Vickers, AE Sistare, F Thompson, KL Roman, RJ Lawton, M Kramer, J Hamadeh, HK Collins, J Grissom, S Bennett, L Tucker, CJ Wild, S Kind, C Oreffo, V Davis, JW Curtiss, S Naciff, JM Cunningham, M Tennant, R Stevens, J Car, B Bertram, TA Afsharil, CA AF Amin, RA Vickers, AE Sistare, F Thompson, KL Roman, RJ Lawton, M Kramer, J Hamadeh, HK Collins, J Grissom, S Bennett, L Tucker, CJ Wild, S Kind, C Oreffo, V Davis, JW Curtiss, S Naciff, JM Cunningham, M Tennant, R Stevens, J Car, B Bertram, TA Afsharil, CA TI Identification of putative gene-based markers of renal toxicity SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE biomarkers; cisplatin; gentamicin; microarrays; nephrotoxicity; proximal tubule; puromycin; toxicogenomics ID PROSTAGLANDIN-D SYNTHASE; KIDNEY INJURY MOLECULE-1; LIPOCALIN PROTEIN FAMILY; RETINOL-BINDING PROTEIN; BETA-TRACE PROTEIN; MESSENGER-RNA; OSTEOPONTIN EXPRESSION; INDUCED NEPHROTOXICITY; MICROARRAY ANALYSIS; EPITHELIAL-CELLS AB This study, designed and conducted as part of the International Life Sciences Institute working group on the Application of Genomics and Proteomics, examined the changes in the expression profile of genes associated with the administration of three different nephrotoxicants-cisplatin, gentamicin, and puromycin-to assess the usefulness of microarrays in the understanding of mechanism(s) of nephrotoxicity. Male Sprague-Dawley rats were treated with daily doses of puromycin (5-20 mg/kg/day for 21 days), gentamicin (2-240 mg/kg/day for 7 days), or a single dose of cisplatin (0.1-5 mg/kg). Groups of rats were sacrificed at various times after administration of these compounds for standard clinical chemistry, urine analysis, and histological evaluation of the kidney. RNA was extracted from the kidney for microarray analysis. Principal component analysis and gene expression-based clustering of compound effects confirmed sample separation based on dose, time, and degree of renal toxicity. In addition, analysis of the profile components revealed some novel changes in the expression of genes that appeared to be associated with injury in specific portions of the nephron and reflected the mechanism of action of these various nephrotoxicants. For example, although puromycin is thought to specifically promote injury of the podocytes in the glomerulus, the changes in gene expression after chronic exposure of this compound suggested a pattern similar to the known proximal tubular nephrotoxicants cisplatin and gentamicin; this prediction was confirmed histologically. We conclude that renal gene expression profiling coupled with analysis of classical end points affords promising opportunities to reveal potential new mechanistic markers of renal toxicity. C1 NIEHS, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. US FDA, Ctr Drug Evaluat & Res, Laurel, MD USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Physiogenix Inc, Milwaukee, WI USA. Pfizer Inc, St Louis, MO USA. Pfizer Inc, Groton, CT 06340 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Schering Plough Res Inst, Lafayette, NJ USA. Procter & Gamble Co, Miami Valley Labs, Cincinnati, OH USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Bristol Myers Squibb Co, Wilmington, DE USA. RP Afsharil, CA (reprint author), NIEHS, Dept Hlth & Human Serv, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM cafshari@amgen.com NR 80 TC 155 Z9 174 U1 1 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 2004 VL 112 IS 4 BP 465 EP 479 DI 10.1289/txg.6683 PG 15 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 807BS UT WOS:000220477600021 PM 15033597 ER PT J AU Rosenzweig, BA Pine, PS Domon, OE Morris, SM Chen, JJ Sistare, FD AF Rosenzweig, BA Pine, PS Domon, OE Morris, SM Chen, JJ Sistare, FD TI Dye-bias correction in dual-labeled cDNA microarray gene expression measurements SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cDNA; dye bias; dye swap; genomics; microarray ID NORMALIZATION; MODELS AB A significant limitation to the analytical accuracy and precision of dual-labeled spotted cDNA microarrays is the signal error due to dye bias. Transcript-dependent dye bias may be due to gene-specific differences of incorporation of two distinctly different chemical dyes and the resultant differential hybridization efficiencies of these two chemically different targets for the same probe. Several approaches were used to assess and minimize the effects of dye bias on fluorescent hybridization signals and maximize the experimental design efficiency of a cell culture experiment. Dye bias was measured at the individual transcript level within each batch of simultaneously processed arrays by replicate dual-labeled split-control sample hybridizations and accounted for a significant component of fluorescent signal differences. This transcript-dependent dye bias alone could introduce unacceptably high numbers of both false-positive and false-negative signals. We found that within a given set of concurrently processed hybridizations, the bias is remarkably consistent and therefore measurable and correctable. The additional microarrays and reagents required for paired technical replicate dye-swap corrections commonly performed to control for dye bias could be costly to end users. Incorporating split-control microarrays within a set of concurrently processed hybridizations to specifically measure dye bias can eliminate the need for technical dye swap replicates and reduce microarray and reagent costs while maintaining experimental accuracy and technical precision. These data support a practical and more efficient experimental design to measure and mathematically correct for dye bias. C1 US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Silver Spring, MD 20993 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Rosenzweig, BA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, HFD-910,10903 New Hapshire Ave,Life Sci Bldg 64, Silver Spring, MD 20993 USA. EM rosenzweigb@cder.fda.gov NR 14 TC 58 Z9 60 U1 0 U2 4 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2004 VL 112 IS 4 BP 480 EP 487 DI 10.1289/txg.6694 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 807BS UT WOS:000220477600022 PM 15033598 ER PT J AU Thompson, KL Afshari, CA Amin, RA Bertram, TA Car, B Cunningham, M Kind, C Kramer, JA Lawton, M Mirsky, M Naciff, JM Oreffo, V Pine, PS Sistare, FD AF Thompson, KL Afshari, CA Amin, RA Bertram, TA Car, B Cunningham, M Kind, C Kramer, JA Lawton, M Mirsky, M Naciff, JM Oreffo, V Pine, PS Sistare, FD TI Identification of platform-independent gene expression markers of cisplatin nephrotoxicity SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cisplatin; cross-platform; kidney; microarrays; nephrotoxicity ID GLOBAL ANALYSIS; PROFILES AB Within the International Life Sciences Institute Committee on Genomics, a working group was formed to focus on the application of microarray technology to preclinical assessments of drug-induced nephrotoxicity. As part of this effort, Sprague-Dawley rats were treated with the nephrotoxicant cisplatin at doses of 0.3-5 mg/kg over a 4- to 144-hr time course. RNA prepared from these animals was run on a variety of microarray formats at multiple sites. A set of 93 differentially expressed genes associated with cisplatin-induced renal injury was identified on the National Institute of Environmental Health Sciences (NIEHS) custom cDNA microarray platform using quadruplicate measurements of pooled animal RNA. The reproducibility of this profile of statistically significant gene changes on other platforms, in pooled and individual animal replicate samples, and in an independent study was investigated. A good correlation in response between platforms was found among the 48 genes in the NIEHS data set that could be matched to probes on the Affymetrix RGU34A array by UniGene identifier or sequence alignment. Similar results were obtained with genes that could be linked between the NIEHS and Incyte or PHASE-1 arrays. The degree of renal damage induced by cisplatin in individual animals was commensurate with the number of differentially expressed genes in this data set. These results suggest that gene profiles linked to specific types of tissue injury or mechanisms of toxicity and identified in well-performed replicated microarray experiments may be extrapolatable across platform technologies, laboratories, and in-life studies. C1 US FDA, CDER, Div Appl Pharmacol Res, Silver Spring, MD 20993 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. NIEHS, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. Pfizer Inc, St Louis, MO USA. Pfizer Inc, Groton, CT 06340 USA. Bristol Myers Squibb Co, Wilmington, DE USA. AstraZeneca Res & Dev, Charnwood, Leics, England. Procter & Gamble Co, Cincinnati, OH USA. RP Thompson, KL (reprint author), US FDA, CDER, Div Appl Pharmacol Res, HFD-910,Life Sci Bldg 64,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Thompsonk@cder.fda.gov NR 19 TC 54 Z9 59 U1 0 U2 2 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 2004 VL 112 IS 4 BP 488 EP 494 DI 10.1289/txg.6676 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 807BS UT WOS:000220477600023 PM 15033599 ER PT J AU Sreenivas, G Singh, R Selvapandiyan, A Negi, NS Nakhasi, HL Salotra, P AF Sreenivas, G Singh, R Selvapandiyan, A Negi, NS Nakhasi, HL Salotra, P TI Arbitrary-primed PCR for genomic fingerprinting and identification of differentially regulated genes in Indian isolates of Leishmania donovani SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Leishmania donovani; AP-PCR; arbitrary-primed polymerase chain reaction; genomic fingerprinting; polymorphic fragment; differentially expressed genes ID POLYMERASE CHAIN-REACTIONS; POLYMORPHIC DNA; AMASTIGOTES; EXPRESSION; MEXICANA; CLONING; ELECTROPHORESIS; STRAINS; COMPLEX AB The arbitrary-primed PCR (AP-PCR) technique was employed with the twin goals of identifying genetic polymorphisms within the Indian isolates and to identify differentially expressed gene sequences. The parasite isolates from Indian Kala-azar patients could be differentiated from Leishmania donovani isolates from distinct geographic regions. Moreover, differences within the Indian isolates could also be identified. A majority (17/19) of the Indian isolates gave identical AP-PCR pattern, while two isolates gave consistently divergent pattern. The distinctive AP-PCR fragments obtained with Indian isolates were used as probes in Northern blot analysis. Three such fragments were found to represent transcribed sequences that were differentially expressed in the two stages of the parasite. These sequences led to cloning and characterization of Leishmania Centrin gene and a novel gene termed A-1 that is over-expressed in amastigote stage of the parasite. The study demonstrates the utility of random genome sampling methods in genomic fingerprinting and in identifying differentially transcribed sequences that could potentially contribute to parasite virulence. (C) 2004 Elsevier Inc. All rights reserved. C1 Safdarjang Hosp, ICMR, Inst Pathol, New Delhi 110029, India. US FDA, CBER, OBRR, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA. Safdarjang Hosp, Dept Med, New Delhi 110029, India. RP Salotra, P (reprint author), Safdarjang Hosp, ICMR, Inst Pathol, New Delhi 110029, India. EM salotra@vsnl.com OI Singh, Ruchi/0000-0001-8094-4703 NR 37 TC 9 Z9 10 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 EI 1090-2449 J9 EXP PARASITOL JI Exp. Parasitol. PD MAR-APR PY 2004 VL 106 IS 3-4 BP 110 EP 118 DI 10.1016/j.exppara.2004.03.011 PG 9 WC Parasitology SC Parasitology GA 828SD UT WOS:000221992300006 PM 15172218 ER PT J AU Smith, JS Tian, J Muller, J Byrnes, AP AF Smith, JS Tian, J Muller, J Byrnes, AP TI Unexpected pulmonary uptake of adenovirus vectors in animals with chronic liver disease SO GENE THERAPY LA English DT Article DE adenovirus; reticuloendothelial system; biodistribution; pulmonary intravascular macrophage; cirrhosis ID MEDIATED GENE-TRANSFER; CIRRHOTIC RAT LIVERS; KUPFFER CELL; IN-VIVO; INTRAVASCULAR MACROPHAGES; ALVEOLAR MACROPHAGES; LUNG UPTAKE; OBSTRUCTIVE-JAUNDICE; RESPIRATORY-TRACT; EXPRESSION AB When adenovirus vectors are injected intravenously, most of the virions are quickly taken up by the reticuloendothelial system, primarily by the liver macrophages known as Kupffer cells. However, little is known about the behavior of adenovirus vectors when there is pre-existing liver disease. To study this, we examined the biodistribution of intravenously injected vector in a rat model of cirrhosis induced by bile duct ligation. Using quantitative PCR and fluorescently tagged adenovirus vectors, we observed a significant reduction in vector uptake by the cirrhotic liver and increased accumulation in the lungs. Immunocytochemistry and electron microscopy demonstrated that this was due to changes in the reticuloendothelial system, with the vector being taken up by large numbers of pulmonary intravascular macrophages in the lungs of cirrhotic rats. Interestingly, expression of vector-encoded luciferase was significantly reduced in the livers of cirrhotic rats, but was not increased in the lungs. These data demonstrate that the biodistribution of adenovirus vectors in rats is altered by cirrhosis, which suggests the possibility that these vectors might behave unexpectedly in patients with pre-existing liver conditions, particularly since pulmonary reticuloendothelial changes are known to occur in human disease. C1 FDA Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA. RP Byrnes, AP (reprint author), FDA Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, HFM-725,8800 Rockville Pike,29B-2E20, Bethesda, MD 20892 USA. RI Byrnes, Andrew/D-2808-2013 OI Byrnes, Andrew/0000-0003-1135-2629 NR 57 TC 35 Z9 37 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 MAR PY 2004 VL 11 IS 5 BP 431 EP 438 DI 10.1038/sj.gt.3302149 PG 8 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 774WE UT WOS:000189008600002 PM 14973536 ER PT J AU Marti, GE AF Marti, GE TI Familial lymphoid neoplasms in patients with mantle cell lymphoma SO HAEMATOLOGICA LA English DT Editorial Material ID CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CLL; MONOCLONAL LYMPHOCYTOSIS; RELATIVES C1 US FDA, Div Cell Gene Therapy, Lab Med & Mol Genet, Flow & Image Cytometry Sect, Bethesda, MD 20892 USA. RP Marti, GE (reprint author), US FDA, Div Cell Gene Therapy, Lab Med & Mol Genet, Flow & Image Cytometry Sect, Bethesda, MD 20892 USA. NR 22 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD MAR PY 2004 VL 89 IS 3 BP 262 EP 263 PG 2 WC Hematology SC Hematology GA 801VT UT WOS:000220124100002 PM 15020260 ER PT J AU Derrick, SC Repique, C Snoy, P Yang, AL Morris, S AF Derrick, SC Repique, C Snoy, P Yang, AL Morris, S TI Immunization with a DNA vaccine cocktail protects mice lacking CD4 cells against an aerogenic infection with Mycobacterium tuberculosis SO INFECTION AND IMMUNITY LA English DT Article ID CD8(+) T-CELLS; TOLL-LIKE RECEPTORS; CD8-T-CELL MEMORY; CD4-T-CELL HELP; CUTTING EDGE; RESPONSES; IMMUNITY; IMMUNOGENICITY; PROTEINS AB Tuberculosis (TB) is the most common opportunistic disease and a potentially fatal complication among immunocompromised individuals infected with human immunodeficiency virus (HIV). Effective vaccination against TB in persons with HIV has been considered unlikely because of the central role that CD4 cells play in controlling tuberculous infections. Here we show that the vaccination of CD8(-/-) mice with a TB DNA vaccine cocktail did not significantly enhance protective responses to a Mycobacterium tuberculosis infection. In contrast, immunization with a DNA vaccine cocktail or with the current TB vaccine, Mycobacterium bovis BCG, induced considerable antituberculosis protective immunity in immune-deficient mice lacking CD4 cells. In vaccinated CD4(-/-) animals, substantially reduced bacterial burdens in organs and much improved lung pathology were seen I month after an aerogenic M. tuberculosis challenge. Importantly, the postchallenge mean times to death of vaccinated CD4(-/-) mice were significantly extended (mean with DNA cocktail, 172 +/- days; mean with BCG, 156 +/- 22 days) compared to that of naive CD4(-/-) mice (33 +/- 6 days). Furthermore, the treatment of DNA-vaccinated CD4(-/-) mice with an anti-CD8 or anti-gamma interferon (IFN-gamma) antibody significantly reduced the effect of immunization, and neither IFN-gamma(-/-) nor tumor necrosis factor receptor-deficient mice were protected by DNA immunization; therefore, the primary vaccine-induced protective mechanism in these immune-deficient mice likely involves the secretion of cytokines from activated CD8 cells. The substantial CD8-mediated protective immunity that was generated in the absence of CD4 cells suggests that it may be possible to develop effective TB vaccines for use in HIV-infected populations. C1 US FDA, Ctr Biol Evaluat & Res, LMDCI, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Vet Sci, Bethesda, MD 20892 USA. RP Morris, S (reprint author), US FDA, Ctr Biol Evaluat & Res, LMDCI, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM morris@cber.fda.gov NR 36 TC 52 Z9 61 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 2004 VL 72 IS 3 BP 1685 EP 1692 DI 10.1128/IAI.72.3.1685-1692.2004 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 778ZH UT WOS:000189270800055 PM 14977976 ER PT J AU Yoshitomi, K AF Yoshitomi, K TI Alkaline phosphatase activity in cheeses measured by fluorometry SO INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY LA English DT Article DE 4-methylumbelliferyl phosphate; ALP; fluorometric screening; pasteurization ID MILK C1 US FDA, Pacific Reg Lab NW, Seafood Prod Res Ctr, Bothell, WA 98021 USA. RP Yoshitomi, K (reprint author), US FDA, Pacific Reg Lab NW, Seafood Prod Res Ctr, 22201 23rd Dr SE, Bothell, WA 98021 USA. EM ken.yoshitomi@fda.gov NR 14 TC 11 Z9 11 U1 1 U2 5 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-5423 J9 INT J FOOD SCI TECH JI Int. J. Food Sci. Technol. PD MAR PY 2004 VL 39 IS 3 BP 349 EP 353 DI 10.1111/j.1365-2621.2004.00786.x PG 5 WC Food Science & Technology SC Food Science & Technology GA 774NX UT WOS:000188990300015 ER PT J AU Kim, YH Heinze, TM Beger, R Pothuluri, JV Cerniglia, CE AF Kim, YH Heinze, TM Beger, R Pothuluri, JV Cerniglia, CE TI A kinetic study on the degradation of erythromycin A in aqueous solution SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE acid-catalysis; base-catalysis; erythromycin; kinetics ID CHROMATOGRAPHY; DECOMPOSITION; DERIVATIVES; STEREOCHEMISTRY; ERYTHRONOLIDE; CONFORMATION; MACROLIDES; STABILITY; AGLYCONE AB The pH is a critical factor determining the rate of the degradation of erythromycin A in aqueous solutions. However, the kinetics of the acid- and base-catalyzed degradation is still uncertain. This study used a sensitive coulometric detection method to determine concentrations of erythromycin A and its degradation products. To determine the buffer-independent rate constants, sodium acetate (0.05-0.2 M) and Tris-HCl (0.1-0.5 M) were used in a pH range of 3.5-5.5 and 7.0-9.0, respectively. In acidic conditions, anhydroerythromycin A appeared to be produced directly through an internal dehydration of erythromycin A-6,9-hemiketal which simultaneously established an equilibrium with erythromycin A enol ether on the other hand. In weakly alkaline conditions, hydroxide ion appeared to catalyze the hydrolysis of the lactonyl ester bond of erythromycin A-6,9-hemiketal by the pseudo-first-order kinetics, and the C13 --> C11 translactonization and internal dehydration reactions subsequently occurred to form pseudoerythromycin A enol ether. We suggest here a predictive model for reasonable interpretation of the kinetics of erythromycin A degradation in aqueous solutions, in which the observed rate constant was expressed by the sum of the partial reaction rate constants for the acid- and base-catalyzed degradation of erythromycin A-6,9-hemiketal as a function of pH in a range of 3.0-10.0. (C) 2003 Elsevier B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM ccerniglia@nctr.fda.gov NR 25 TC 35 Z9 37 U1 2 U2 25 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 MAR 1 PY 2004 VL 271 IS 1-2 BP 63 EP 76 DI 10.1016/j.ijpharm.2003.10.023 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 778NQ UT WOS:000189248000008 PM 15129974 ER PT J AU Bohlke, K Davis, RL DeStefano, F Marcy, SM Braun, MM Thompson, RS AF Bohlke, K Davis, RL DeStefano, F Marcy, SM Braun, MM Thompson, RS CA Vaccine Safety Datalink Team TI Epidemiology of anaphylaxis among children and adolescents enrolled in a health maintenance organization SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE anaphylaxis; children; adolescents; epidemiology ID VACCINE SAFETY DATALINK; EMERGENCY; TREND AB Background: There is little information about the incidence of anaphylaxis from all causes. Objective: The objects of this study were (1) to estimate the incidence of anaphylaxis; (2) to explore the range of diagnoses attributed to an anaphylactic episode; and (3) to describe the clinical features of anaphylaxis. Methods: The study population consisted of children and adolescents enrolled at a health maintenance organization. We identified potential episodes of anaphylaxis occurring between 1991 and 1997 from automated databases and reviewed the medical record to confirm the diagnosis. We reviewed all diagnoses specific for anaphylaxis (eg, ICD-9 995.0, anaphylactic shock) and sampled from among other related diagnoses (eg, ICD-9 995.3, allergy unspecified). Estimation of the incidence of provider-diagnosed anaphylaxis was based on cases confirmed from among the specific diagnosis codes. Description of the clinical features of anaphylaxis involved all confirmed cases regardless of diagnosis. Results: We identified 67 episodes of anaphylaxis among children with diagnosis codes specific for anaphylaxis (10.5 episodes per 100,000 person-years). There was no increase in incidence over time. Review of samples of diagnoses not specific for anaphylaxis yielded an additional 18 episodes. Among all identified episodes (n = 85), mucocutaneous and respiratory manifestations were the most common. Seventy-one percent of episodes were treated in the emergency department. Nine episodes (11%) resulted in hospitalization. Conclusions: The incidence of anaphylaxis did not increase during these years. A majority of episodes were treated in the emergency department. Anaphylaxis in this population was frequently diagnosed as another related condition, and the basis and implications of diagnostic practices in this disorder warrant further exploration. C1 Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Grp Hlth Cooperat Puget Sound, Dept Prevent Care, Seattle, WA 98101 USA. US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Kaiser Fdn Hosp, Panorama City, CA USA. Ctr Dis Control & Prevent, Natl Immunizat Program, Atlanta, GA USA. Univ Washington, Sch Med, Dept Epidemiol, Seattle, WA USA. Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. RP Bohlke, K (reprint author), Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. FU PHS HHS [200-0957] NR 22 TC 162 Z9 168 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 MAR PY 2004 VL 113 IS 3 BP 536 EP 542 DI 10.1016/j.jaci.2003.11.033 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 802DM UT WOS:000220144200028 PM 15007358 ER PT J AU Letarte, S Morency, D Wilkes, J Bertrand, MJ AF Letarte, S Morency, D Wilkes, J Bertrand, MJ TI Py-MAB-Tof detection and identification of microorganisms in urine SO JOURNAL OF ANALYTICAL AND APPLIED PYROLYSIS LA English DT Article DE pyrolysis; microorganisms; bacteria; MAB; mass spectrometry; urine; diagnostic ID PYROLYSIS MASS-SPECTROMETRY; CHEMICAL-IONIZATION; BACTERIA; DIFFERENTIATION; ELECTRON AB Rapid detection and identification of bacteria and other microorganisms has become a field where new analytical methods are needed. An approach, based on the use of pyrolysis coupled to mass spectrometry (Py-MS), for the detection and identification of bacteria in urine and other aqueous samples is described. In this procedure, the sample is placed on a direct insertion probe and pyrolysis is conducted directly into the ion source of the mass spectrometer. Ionization is achieved with a metastable atom bombardment source (MAB). In contrast to electron ionization, this novel ionization source, by providing discrete ionization energies, allows selective ionization and control over fragmentation. The MAB source is coupled to a time-of-flight (Tof) mass analyzer that provides high sensitivity and fast spectral acquisition. Experiments conducted with a number of uropathogenic bacteria, such as Escherichia coli, Citrobacter freundii, Proteus mirabilis and Pseudomonas aeruginosa, reveal that they provide discernable fingerprints when analyzed in urine samples by Py-MAB-Tof. Results can be obtained in minutes and the sensitivity is such that 10(4) bacteria on the pyrolysis probe are required for analysis. (C) 2003 Published by Elsevier B.V. C1 Univ Montreal, Dept Chem, Reg Ctr Mass Spectrometry, Montreal, PQ H3C 3J7, Canada. Univ Montreal, Dept Microbiol & Immunol, Montreal, PQ H3C 3J7, Canada. Natl Ctr Toxicol Res, Jefferson, AK USA. RP Bertrand, MJ (reprint author), Univ Montreal, Dept Chem, Reg Ctr Mass Spectrometry, CP 6128, Montreal, PQ H3C 3J7, Canada. EM michelj.bertrand@sympatico.ca NR 18 TC 6 Z9 6 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2370 J9 J ANAL APPL PYROL JI J. Anal. Appl. Pyrolysis PD MAR PY 2004 VL 71 IS 1 BP 13 EP 25 DI 10.1016/S0165-2370(03)00095-0 PG 13 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 813BE UT WOS:000220881800002 ER PT J AU Shah, M Kannamkumarath, SS Wuilloud, JCA Wuilloud, RG Caruso, JA AF Shah, M Kannamkumarath, SS Wuilloud, JCA Wuilloud, RG Caruso, JA TI Identification and characterization of selenium species in enriched green onion (Allium fistulosum) by HPLC-ICP-MS and ESI-ITMS SO JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRIC DETECTION; CANCER PREVENTION; SUPPLEMENTS; SPECIATION; ACID; YEAST AB In this study speciation of selenium in selenium-enriched green onions (Allium fistulosum) was done with reversed-phase ion-pairing high performance liquid chromatography (RP-IP-HPLC) and size-exclusion chromatography (SEC) coupled on-line to ICP-MS for selenium specific detection. The plant extract obtained using sodium hydroxide (0.1 mol l(-1)) analyzed by SEC (CAPS 10 mmol l(-1), pH 10.0) with ICP-MS detection showed the incorporation of selenium in both high (similar to 12 kDa) and low molecular weight (0.36-2 kDa) fractions. Presumably protein bound selenoamino acids were released using enzymes (Proteinase K and Protease XIV) and selenoamino acids found in cytosol in their free form were extracted using 0.1 M HCl. The extracts were analyzed for speciation studies by RP-IP-HPLC [0.1% (v/v) heptafluorobutyric acid, 5% (v/v) methanol, pH 2.5]. Matching the chromatographic retention times with commercially available standards provided evidence for the presence of Se-cystine, methylselenocysteine, Se-methionine, and inorganic selenium. Electrospray ionization ion trap mass spectrometry (ESI-ITMS) confirmed the presence Of gamma-glutamyl-Semethylselenocysteine in green onions as has been reported in other onion types. C1 Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Caruso, JA (reprint author), Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. EM joseph.caruso@uc.edu RI Wuilloud, Rodolfo/N-6821-2014 OI Wuilloud, Rodolfo/0000-0002-2962-7718 NR 16 TC 65 Z9 68 U1 1 U2 17 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. PD MAR PY 2004 VL 19 IS 3 BP 381 EP 386 DI 10.1039/b312320k PG 6 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 808AS UT WOS:000220542600007 ER PT J AU Trucksess, MW Brewer, VA Williams, KM Westphal, CD Heeres, JT AF Trucksess, MW Brewer, VA Williams, KM Westphal, CD Heeres, JT TI Preparation of peanut butter suspension for determination of peanuts using enzyme-linked immunoassay kits SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ALLERGY AB Peanuts are one of the 8 most common allergenic foods and a large proportion of peanut-allergic individuals have severe reactions, some to minimal exposure. Specific protein constituents in the peanuts are the cause of the allergic reactions in sensitized individuals who ingest the peanuts. To avoid accidental ingestion of peanut-contaminated food, methods of analysis for the determination of the allergenic proteins in foods are important tools. Such methods could help identify foods inadvertently contaminated with peanuts, thereby reducing the incidence of allergic reactions to peanuts. Commercial immunoassay kits are available but need study for method performance, which requires reference materials for within- and between-laboratory validations. In this study, National Institute of Standards and Technology Standard Reference Material 2387 peanut butter was used. A polytron homogenizer was used to prepare a homogenous aqueous Peanut Butter suspension for the evaluation of method performance of some commercially available immunoassay kits such as Veratox for Peanut Allergen Test (Neogen Corp.), Ridascreen Peanut (R-Biopharm GmbH), and Bio-Kit Peanut Protein Assay Kit (Tepnel). Each gram of the aqueous peanut butter suspension contained 20 mg carboxymethylcellulose sodium salt, 643 mug peanut, 0.5 mg thimerosal, and 2.5 mg bovine serum albumin. The suspension was homogenous, stable, reproducible, and applicable for adding to ice cream, cookies, breakfast cereals, and chocolate for recovery studies at spike levels ranging from 12 to 90 mug/g. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Trucksess, MW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM mary.trucksess@cfsan.fda.gov NR 7 TC 11 Z9 12 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 MAR-APR PY 2004 VL 87 IS 2 BP 424 EP 428 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 818DK UT WOS:000221225600016 PM 15164837 ER PT J AU Mossoba, MM Yurawecz, MP Delmonte, P Kramer, JKG AF Mossoba, MM Yurawecz, MP Delmonte, P Kramer, JKG TI Overview of infrared methodologies for trans fat determination SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID RAPID-DETERMINATION; VEGETABLE-OILS; METHYL-ESTERS; LINOLEIC-ACID; DOUBLE-BONDS; HUMAN-MILK; SPECTROSCOPY; ISOMERS; SPECTROPHOTOMETRY; CHROMATOGRAPHY AB trans Fatty acids are present in a variety of foods like dairy products, but the major sources are products that contain commercially hydrogenated fats. Some studies have shown that trans fatty acids elevate levels of serum low-density lipoprotein (LDL)-cholesterol and lower high-density lipoprotein (HDL)-cholesterol. The quantitation and identification of trans fatty acid isomers is difficult because of the wide range of positional monoene, diene, and triene fatty acid isomers present in hydrogenated oils. This is complicated by the cis positional isomers that are also present, as well as the lack of commercial chromatographic standards for many fatty acid isomers. In this review, infrared methodologies for the determination of total trans fat are presented. Using an attenuated total reflection (ATR) infrared cell, a novel Fourier transform infrared (FTIR) spectroscopic method that was developed for the rapid (5 min) quantitation of the total trans fatty acid levels in neat (without solvent) fats and oils measured as triacylglycerols (TAG) Is discussed. TAG required no derivatization, but had to be melted prior to measurement. The lower limit of trans quantitation was 5% of total fat. The precision of this ATR method was found to be superior to that of transmission infrared official methods. Accuracy was enhanced by generating a symmetric absorption trans infrared band at 966 cm(-1) on a horizontal background. This was achieved by "ratioing" the single-beam spectrum of the trans-containing fat or oil against that of a reference oil or standard having only cis double bonds. Attempts to apply this ATR-FTIR method to food matrixes with low trans fat and/or low total fat content were not satisfactory due to interfering infrared absorptions in the trans region. To overcome this interference, the method was modified by applying the standard addition technique to the ATR-FTIR determination. The modified procedure required more time, but eliminated any adverse impact on accuracy arising from interfering minor food components having absorption bands near 966 cm(-1). C1 US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, College Pk, MD 20740 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Nutr Prod Labeling & Dietary Supplements, College Pk, MD 20740 USA. Agr & Agri Food Canada, Food Res Program, Guelph, ON, Canada. RP Mossoba, MM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, HFS 717,BE-012,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM mmossoba@cfsan.fda.gov NR 36 TC 25 Z9 25 U1 1 U2 13 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2004 VL 87 IS 2 BP 540 EP 544 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 818DK UT WOS:000221225600031 PM 15164852 ER PT J AU Cruz-Hernandez, C Deng, ZY Zhou, JQ Hill, AR Yurawecz, MP Delmonte, P Mossoba, MM Dugan, MER Kramer, JKG AF Cruz-Hernandez, C Deng, ZY Zhou, JQ Hill, AR Yurawecz, MP Delmonte, P Mossoba, MM Dugan, MER Kramer, JKG TI Methods for analysis of conjugated linoleic acids and trans-18 : 1 isomers in dairy fats by using a combination of gas chromatography, silver-ion thin-layer chromatography/gas chromatography, and silver-ion liquid chromatography SO JOURNAL OF AOAC INTERNATIONAL LA English DT Review ID HUMAN-MILK LIPIDS; COWS FED CANOLA; OCTADECENOIC ACIDS; VACCENIC ACID; CLA ISOMERS; POSITIONAL ISOMERS; ADIPOSE-TISSUE; METHYL-ESTERS; RUMENIC ACID; BOVINE-MILK AB Conjugated linoleic acids (CLA) are octadecadienoic acids (18:2) that have a conjugated double-bond system. Interest in these compounds has expanded since CLA were found to be associated with a number of physiological and pathological responses such as cancer, metastases, atherosclerosis, diabetes, immunity, and body fat/protein composition. The main sources of these conjugated fatty acids are dairy fats. Rumen bacteria convert polyunsaturated fatty acids, especially linoleic and linolenic acids, to CLA and numerous trans-containing mono- and diunsaturated fatty acids. It has been established that an additional route of CLA synthesis in ruminants and monogastric animals, including humans, occurs via Delta9 desaturation of the trans-18:1 isomers. To date, a total of 6 positional CLA isomers have been found in dairy fats, each occurring in 4 geometric forms (cis,trans; trans,cis; cis,cis; and trans,trans) for a total of 24. All of these CLA isomers can be resolved only by a combination of gas chromatography (GC), using 100 m highly polar capillary columns, and silver-ion liquid chromatography, using 3 of these 25 cm columns in series. Complete analysis of all the trans-18:1 isomers requires prior isolation of trans monoenes by silver-ion thin-layer chromatography (TLC), followed by GC analysis using the same 100 m capillary columns operated at low temperatures starting from 120degreesC. These analytical techniques are required to assess the purity of commercial CLA preparations, because their purity will affect the interpretation of any physiological and/or biochemical response obtained. Prior assessment of CLA preparations by TLC is also recommended to determine the presence of any other impurities. The availability of pure CLA isomers will permit the evaluation and analysis of individual CLA isomers for their nutritional and biological activity in model systems, animals, and humans. These techniques are also essential to evaluate dairy fats for their content of specific CLA isomers and to help design experimental diets to increase the level of the desired CLA isomers in dairy fats. These improved techniques are further required to evaluate the CLA profile in monogastric animals fed commercial CLA preparations for CLA enrichment of animal products. This is particularly important because absorption and metabolism will alter the ingested-CLA profile in the animal fed. C1 Agr & Agri Food Canada, Food Res Program, Guelph, ON, Canada. Univ Guelph, Dept Food Sci, Guelph, ON N1G 2W1, Canada. Univ Nanching, Dept Food Sci, Nanchang, Peoples R China. US FDA, College Pk, MD USA. Agr & Agri Food Canada, Lacombe Res Ctr, Lacombe, AB, Canada. RP Kramer, JKG (reprint author), Agr & Agri Food Canada, Food Res Program, 93 Stone Rd W, Guelph, ON, Canada. EM kramej@agr.gc.ca OI deng, zeyuan/0000-0001-5650-1507 NR 142 TC 190 Z9 199 U1 5 U2 47 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 2004 VL 87 IS 2 BP 545 EP 562 PG 18 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 818DK UT WOS:000221225600032 PM 15164853 ER PT J AU Delmonte, P Yurawecz, MP Mossoba, MM Cruz-Hernandez, C Kramer, JKG AF Delmonte, P Yurawecz, MP Mossoba, MM Cruz-Hernandez, C Kramer, JKG TI Improved identification of conjugated linoleic acid isomers using silver-ion HPLC separations SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; FATTY-ACIDS; DERIVATIVES; CLA AB Silver-ion high-performance liquid chromatography (Ag+-HPLC) has been shown to be effective in the resolution of most of the isomers of conjugated octadecadienoic acids (18:2), also, known as conjugated linoleic acid (CLA). The CLA isomers identified in natural fats from ruminants; are a mixture of numerous positional and geometric isomers from 7,9- to 12,14-18:2. Ag+-HPLC separates both geometric (trans,trans < cis/trans < cis,cis) and positional CLA isomers using the mobile phase hexane/acetonitrile (99.9:0.1). The elution volumes for the CLA isomers were not only affected by the concentration of acetonitrile (in the prepared mobile phase) but also with successive runs during the day using a prepared mobile phase batch, due to the partial solubility of acetonitrile in hexane. However, this drift does not affect the relative resolution of the CLA isomers. The addition of diethyl ether to the mobile phase partly stabilizes the solvent mixture. In order to facilitate the interpretation of Ag-+HPLC chromatograms, the relative retention volumes (RRV) were calculated for each CLA isomer. Toluene was added to all the test portions and served as an estimator of dead volume, whereas the elution of the ubiquitous 9c,11t-CLA isomer was chosen as unity (1.00). Expressing the elution of all the CLA isomers as their RRV greatly helped to standardize each CLA isomer, resulting in relatively small coefficients of variation (% CV) for the trans,trans (<1.5%) and cis/trans (<0.5%) CLA isomers. The identification of the CLA isomers was further facilitated by synthesis of authentic CLA isomers. All the geometric CLA fatty acid methyl esters (FAME) from positions 6,8- to 13,15-CLA were commercially available or synthesized by a combination of partial hydrazine reduction of known polyunsaturated fatty acids followed by alkali isomerization, isolation of products, and further iodine-catalyzed geometric isomerization. Based on expressing the elution volume as RRV and the availability of the synthetic CLA isomers, a unique reversal of the elution order of the c/t CLA isomers was found. It is also proposed that the retention times of CLA isomers by gas chromatography (GC) should be expressed as their relative retention times (RRT) relative to methyl gamma-linoleneate. The availability of CLA reference materials and the application of RRV and RRT to Ag+-HPLC and GC separations, respectively, will greatly improve in the identifications of CLA isomers. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Agr & Agri Food Canada, Food Res Program, Guelph, ON, Canada. RP Yurawecz, MP (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM mpy@cfsan.fda.gov NR 16 TC 17 Z9 17 U1 1 U2 9 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2004 VL 87 IS 2 BP 563 EP 568 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 818DK UT WOS:000221225600033 PM 15164854 ER PT J AU Baldwin, AL Wiley, EB Alayash, AI AF Baldwin, AL Wiley, EB Alayash, AI TI Differential effects of sodium selenite in reducing tissue damage caused by three hemoglobin-based oxygen carriers SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE rat mesentery; mast cell degranulation; intestinal mucosal epithelium ID CROSS-LINKED HEMOGLOBIN; GLUTATHIONE-PEROXIDASE ACTIVITY; BLOOD SUBSTITUTES; INTESTINAL-MUCOSA; LIPID-PEROXIDATION; RAT MESENTERY; IN-VIVO; SITE; METHEMOGLOBIN; OXIDATION AB Three "blood substitutes," a diaspirin crosslinked human hemoglobin (DBBF-Hb), a bovine polymerized hemoglobin (PolyHbBv), and a human polymerized hemoglobin (O-R-PolyHbA(0)), that have undergone clinical trials are used in this study. Previously, we showed in the rat that coadministration of sodium selenite (Na2SeO3) and DBBF-Hb significantly decreased mesenteric venular leakage and epithelial disruption produced by DBBF-Hb alone but did not reduce mast cell degranulation unless given orally. The purpose of this study was to determine whether Na2SeO3 produced similar beneficial responses when used with PolyHbBv and O-R-PolyHbA(0). In anesthetized Sprague-Dawley rats, the mesenteric microvasculature was perfused with PolyHbBv or O-R-PolyHbA(0), with and without Na2SeO3 in the perfusate and suffusate, for 10 min, followed by FITC-albumin for 3 min, and then fixed for microscopy. Na2SeO3 did not reduce leak number or area in preparations perfused with PolyHbBv and only reduced leak number (but not significantly) in preparations perfused with O-R-PolyHbA(0). Na2SeO3 significantly increased mesenteric mast cell degranulation and impaired epithelial integrity in animals treated with PolyHbBv. In vitro, Na2SeO3 significantly reduced the oxidation rate of DBBF-Hb in the presence of oxidants, had little effect on PolyHbBv, and increased the oxidation rate of O-R-PolyHbA(0). These results suggest that Na2SeO3 moderates hemoglobin-induced damage, at least partly, through its redox interactions with the heme sites in the hemoglobin molecules studied and that accessibility of the heme site to Na2SeO3 governs those interactions. C1 Univ Arizona, Coll Med, Dept Physiol, Tucson, AZ 85724 USA. US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Baldwin, AL (reprint author), Univ Arizona, Coll Med, Dept Physiol, Tucson, AZ 85724 USA. EM abaldwin@u.arizona.edu FU NHLBI NIH HHS [HL-53047] NR 37 TC 12 Z9 13 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAR 1 PY 2004 VL 96 IS 3 BP 893 EP 903 DI 10.1152/japplphysiol.00615.2003 PG 11 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 771AM UT WOS:000188763400010 PM 14555684 ER PT J AU Buzatu, DA Nguyen, FT Reddy, SN Darsey, JA AF Buzatu, Dan A. Nguyen, Freddy T. Reddy, Shreedhar N. Darsey, Jerry A. TI Computational Analysis of Transition Metal Doped Nanotubes and Their Application to Molecular Electronics SO JOURNAL OF COMPUTATIONAL AND THEORETICAL NANOSCIENCE LA English DT Article DE Metal Doped Nanotubes; Molecular Electronics; DFT-SCF Calculations; Nanotube Transistor; Nanowires; Nanocircuits AB We have previously proposed molecular circuits designed from polyaniline polymer strands, polyacetylene polymer strands and charge transfer salts acting as transistors. Due to unique properties that are demonstrated in this manuscript, we propose the use of carbon single wall nanotubes and transition metal endohedrally doped single wall carbon nanotubes (SWNTs) for utilization in molecular electronics. Different transition metals were used in a systematic fashion to manipulate the molecular orbital energy gap (HOMO-LUMO gap) of metallic (C(h) = (n = m)) nanotubes. Gradient corrected, Density Functional Theory (DFT) Self Consistent Field (SCF) calculations were used to calculate molecular orbital energy levels, HOMO-LUMO gaps, electron affinities, ionization energies and other electronic properties for these molecules. The effect that a SWNTs length has on its HOMO-LUMO gap was investigated. DFT-SCF calculations were also used to demonstrate how multiple metal filled nanotubes could be used to construct a molecular nanotube based transistor. C1 [Reddy, Shreedhar N.; Darsey, Jerry A.] Univ Arkansas, Dept Chem, Little Rock, AR 72204 USA. [Buzatu, Dan A.] Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. [Nguyen, Freddy T.] MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. RP Darsey, JA (reprint author), Univ Arkansas, Dept Chem, 2801 S Univ Ave, Little Rock, AR 72204 USA. RI Nguyen, Freddy/A-2541-2008 OI Nguyen, Freddy/0000-0003-0106-8114 NR 17 TC 2 Z9 2 U1 0 U2 2 PU AMER SCIENTIFIC PUBLISHERS PI STEVENSON RANCH PA 25650 NORTH LEWIS WAY, STEVENSON RANCH, CA 91381-1439 USA SN 1546-1955 J9 J COMPUT THEOR NANOS JI J. Comput. Theor. Nanosci. PD MAR PY 2004 VL 1 IS 1 BP 99 EP 105 DI 10.1166/jctn.2004.012 PG 7 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA V03TK UT WOS:000207012900012 ER PT J AU Borucinska, JD Harshbarger, JC Reimschuessel, R Bogicevic, T AF Borucinska, JD Harshbarger, JC Reimschuessel, R Bogicevic, T TI Gingival neoplasms in a captive sand tiger shark, Carcharias taurus (Rafinesque), and a wild-caught blue shark, Prionace glauca (L.) SO JOURNAL OF FISH DISEASES LA English DT Article DE elasmobranchs; epulis; neoplasia; oral tumours; sharks ID PAPILLOMA; FISH C1 Univ Hartford, Dept Biol, Hartford, CT 06117 USA. George Washington Univ, Med Ctr, Dept Pathol, Washington, DC 20037 USA. US FDA, Res Off, Laurel, MD USA. RP Borucinska, JD (reprint author), Univ Hartford, Dept Biol, 200 Bloomfield Ave, Hartford, CT 06117 USA. EM borucinsk@hartford.edu NR 37 TC 10 Z9 10 U1 0 U2 7 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0140-7775 J9 J FISH DIS JI J. Fish Dis. PD MAR PY 2004 VL 27 IS 3 BP 185 EP 191 DI 10.1111/j.1365-2761.2004.00532.x PG 7 WC Fisheries; Marine & Freshwater Biology; Veterinary Sciences SC Fisheries; Marine & Freshwater Biology; Veterinary Sciences GA 801AN UT WOS:000220068900009 PM 15009246 ER PT J AU Jones, RC Gerber, SI Diaz, PS Williams, LL Dennis, SB Parish, ES Paul, WS AF Jones, RC Gerber, SI Diaz, PS Williams, LL Dennis, SB Parish, ES Paul, WS TI Intensive investigation of bacterial foodborne disease outbreaks: Proposed guidelines and tools for the collection of dose-response data by local health departments SO JOURNAL OF FOOD PROTECTION LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the Infectious-Diseases-Society-of-America CY SEP 06-11, 2000 CL NEW ORLEANS, LOUISIANA SP Infect Dis Soc Amer ID LISTERIA-MONOCYTOGENES; SALMONELLA-ENTERITIDIS; INCUBATION PERIOD; RISK-ASSESSMENT; CHEDDAR CHEESE; MILK; FOOD; SEVERITY AB Local health departments that investigate foodborne disease outbreaks do not have adequate guidelines for collecting data that could be used to estimate dose-response relationships, a key component of hazard characterization in quantitative microbial risk assessment. To meet this need, criteria and a questionnaire template for the collection of appropriate dose-response data in the context of outbreaks were developed and applied in the investigation of a point-source outbreak linked to Salmonella serotype Enteritidis in a salmon entree in February 2000. In this outbreak, the attack rate and risk of hospitalization increased with the amount of salmon entree consumed, and detailed data were obtained on illness severity measures and host susceptibility factors. Local health departments might consider broadening investigations to include the collection of additional data when investigating outbreaks that have met a specific set of conditions. These data could provide information needed by federal regulatory agencies and other organizations for quantitative microbial risk assessment. Intensive investigations of outbreaks could prevent future illnesses by providing information needed to develop approaches to minimizing risk. C1 Chicago Dept Publ Hlth, Chicago, IL 60612 USA. Illinois Dept Publ Hlth, Chicago, IL 60612 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Jones, RC (reprint author), Chicago Dept Publ Hlth, 2160 W Ogden Ave, Chicago, IL 60612 USA. EM Jones_Roderick@cdph.org NR 30 TC 8 Z9 8 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 2004 VL 67 IS 3 BP 616 EP 623 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 801DS UT WOS:000220077200032 PM 15035384 ER PT J AU Zink, DL AF Zink, DL TI Agroterrorism: Issues of reality SO JOURNAL OF FOOD SCIENCE LA English DT Article; Proceedings Paper CT Conference on Agroterrorism held in Conjunction with the 12th World Congress of Food Science and Technology CY JUL 16-20, 2003 CL Inst Food Technol, Chicago, IL SP Int Union Food Sci & Technol HO Inst Food Technol AB In the past, deliberate contamination of foods in the U.S. has been committed by individual criminals, disgruntled employees, or political activists with a narrow agenda. After September 11, 2001, every nation has had to consider a much wider range of food security issues. Food is a global commodity and nearly every country both exports and imports foods. Every nation must consider the security of its domestic production and look beyond its borders to its trading partners to assure the safety of its food supply. In the nearly 2 years since September 11, 2001, many steps have been taken to improve food security. New legislation has been enacted to strengthen the ability of government to respond to terrorist threats. New relationships have been forged between food security agencies, law enforcement, and the intelligence community. Virtually every segment of the domestic and. imported food supply has come under scrutiny in an effort to identify points of weakness and appropriate protective measures. Gaps in our knowledge about specific agents and food processes have been identified and research to fill these gaps has been initiated. This effort will continue for the foreseeable future and could have a wide range of benefits, including improvements to food safety, a reduction in product counterfeiting, and a reduction in the "gray market" food trade. The scale and diversity of the U.S. food supply makes it an attractive target, but at the same time makes it very resilient and responsive to emerging threats. C1 US FDA, CFSAN OPDFB, College Pk, MD USA. RP Zink, DL (reprint author), US FDA, CFSAN OPDFB, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA 525 WEST VAN BUREN, STE 1000, CHICAGO, IL 60607-3814 USA SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD MAR PY 2004 VL 69 IS 2 BP R47 EP R47 PG 1 WC Food Science & Technology SC Food Science & Technology GA 848TE UT WOS:000223489200008 ER PT J AU Weinberg, WC Yamashita, T Tokino, T Young, M Ponnamperuma, R King, K AF Weinberg, WC Yamashita, T Tokino, T Young, M Ponnamperuma, R King, K TI Delta Np63 isotypes differentially regulate keratinocyte proliferation and differentiation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 OBP FDA, Immunobiol Lab, Bethesda, MD USA. Sapporo Med Univ, Sapporo, Hokkaido, Japan. NIDCR, NIH, Bethesda, MD USA. RI Weinberg, Wendy/A-8920-2009 NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 134 BP A23 EP A23 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500189 ER PT J AU Petricoin, E Wulfkuhle, J Espina, V Liotta, LA AF Petricoin, E Wulfkuhle, J Espina, V Liotta, LA TI Clinical proteomics: Revolutionizing disease detection and patient tailoring therapy SO JOURNAL OF PROTEOME RESEARCH LA English DT Review DE proteomics; pharmacoproteomics; patterns; mass spectrometry; protein microarrays ID PROTEIN IDENTIFICATION TECHNOLOGY; TYROSINE KINASE INHIBITOR; IMMOBILIZED PH GRADIENTS; OVARIAN-CANCER; MASS-SPECTROMETRY; PROSTATE-CANCER; BREAST-CANCER; 2-DIMENSIONAL ELECTROPHORESIS; TRASTUZUMAB HERCEPTIN; MYELOID-LEUKEMIA AB The evolving discipline of Clinical Proteomics is more than simply describing and enumerating the systematic changes in the protein constituency of a cell, or just generating lists of proteins that increase or decrease in expression as a cause or consequence of disease. Clinical applications of proteomics involve the use of proteomic technologies at the bedside with the ultimate goal to characterize the information flow through the intra- and extracellular molecular protein networks that interconnect organ and circulatory systems together. These networks are both new targets for therapeutics themselves as well as underpin the dynamic changes that give rise to cascades of new diagnostic biomarkers. The analysis of human cancer can be used as a model for how clinical proteomics is having an impact at the bedside for early detection, rational therapeutic targeting, and patient-tailored therapy. C1 US FDA, NCI FDA Clin Proteom Program, Off Cell & Gene Therapy, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, NCI FDA Clin Proteom Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Petricoin, E (reprint author), US FDA, NCI FDA Clin Proteom Program, Off Cell & Gene Therapy, Ctr Biol Evaluat & Res, Bldg 29A-2D12,8800 Rockville Pike, Bethesda, MD 20892 USA. EM petricoin@cber.fda.gov; liottal@mail.nih.gov OI Espina, Virginia/0000-0001-5080-5972 NR 82 TC 68 Z9 76 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD MAR-APR PY 2004 VL 3 IS 2 BP 209 EP 217 DI 10.1021/pr049972m PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 812IK UT WOS:000220833000006 PM 15113096 ER PT J AU Shvartsburg, AA Jones, RC AF Shvartsburg, AA Jones, RC TI Attachment of metal trications to peptides SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID IONIZATION MASS-SPECTROMETRY; GAS-PHASE; ELECTROSPRAY-IONIZATION; ARGENTINATED PEPTIDES; COMPLEXES; IONS; COORDINATION; DISSOCIATION; ACETONITRILE; CHEMISTRY AB Gas-phase complexes of triply charged metal ions with peptides may be readily produced using electrospray ionization, including for small peptides such as bradykinin and peptides with no basic residues such as insulin chain A. Attachment without charge-reduction is demonstrated for all trications studied: La3+, Al3+, Ga3+, Fe3+, V3+, and Cr3+. The intensities of adducts are often comparable to, or even exceed, those of protonated analogs in any charge state. (C) 2004 American Society for Mass Spectrometry. C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR USA. RP Shvartsburg, AA (reprint author), Pacific NW Natl Lab, MSIN K8-98,3335 Q Ave, Richland, WA 99352 USA. EM alexandre.shvartsburg@pnl.gov NR 30 TC 16 Z9 16 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD MAR PY 2004 VL 15 IS 3 BP 406 EP 408 DI 10.1016/j.jasms.2003.11.005 PG 3 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 800JB UT WOS:000220023500014 PM 14998543 ER PT J AU Foreman, JH Constable, PD Waggoner, AL Levy, M Eppley, RM Smith, GW Tumbleson, ME Haschek, WM AF Foreman, JH Constable, PD Waggoner, AL Levy, M Eppley, RM Smith, GW Tumbleson, ME Haschek, WM TI Neurologic abnormalities and cerebrospinal fluid changes in horses administered fumonisin B-1 intravenously SO JOURNAL OF VETERINARY INTERNAL MEDICINE LA English DT Article DE cerebrospinal fluid; equine leukoencephalomalacia; Fusarium; moldy corn poisoning; mycotoxin ID EQUINE LEUKOENCEPHALOMALACIA; FUSARIUM-MONILIFORME; CONSCIOUS HORSES; CULTURE MATERIAL; SPHINGOSINE; PONIES; FEEDS; PROLIFERATUM; SPHINGANINE; TOXICOSIS AB The objective of this experiment was to characterize a dose-dependent toxic effect of fumonisin B-1 (FB1) and to document initial neurologic signs, clinical progression, and terminal cerebrospinal fluid (CSF) changes in horses administered FB1 IV. Seventeen healthy horses were administered 0.00 (n = 4), 0.01 (n = 3), 0.05 (n = 3), 0.10 (n 3), or 0.20 mg (n = 4) of purified FB1 IV q24h. When neurologic abnormalities observed by a masked observer became severe, atlanto-occipital CSF taps were performed and CSF pressure, cell count, cytology, protein, albumin and glucose concentrations, and creatine kinase activity were measured. Changes in CSF and number of days to 1st observation of neurologic abnormalities were compared between doses by ANOVA, with the level of significance set at P < .05. Control horses and low-dose horses (0.01 mg/kg) remained neurologically normal. In higher dose FB1-treated horses (n = 10), initial clinical signs (days 4-10) included hindlimb ataxia, delayed forelimb placing, and decreased tongue tone and movement. Hindlimb and trunkal ataxia, depression, hyperesthesia, and intermittent dementia gradually became apparent. When data from all horses with neurologic abnormalities were pooled (0.05-0.20 mg/kg FB1), mild clinical signs (mean day 6.3) occurred significantly earlier than did more severe (mean day 8.9) clinical signs (P = .009). Neurologic horses had high CSF protein, albumin, and IgG concentrations and increased albumin quotients (P < .05). It was concluded that FB1-induced neurologic and CSF changes in a dose-dependent manner, with a no-observable-limit of 0.01 mg FB1/kg IV q24h for 28 days. The neurologic and CSF changes were consistent with vasogenic cerebral edema. C1 Univ Illinois, Coll Vet Med, Dept Vet Clin Med, Urbana, IL 61802 USA. Univ Illinois, Coll Vet Med, Dept Vet Pathobiol, Urbana, IL 61802 USA. Univ Illinois, Coll Vet Med, Dept Vet Biosci, Urbana, IL 61802 USA. US FDA, Washington, DC 20204 USA. Purdue Univ, W Lafayette, IN 47907 USA. RP Foreman, JH (reprint author), Univ Illinois, Coll Vet Med, Dept Vet Clin Med, 1008 W Hazelwood Dr, Urbana, IL 61802 USA. EM jforeman@cvm.uiuc.edu NR 57 TC 16 Z9 17 U1 0 U2 8 PU AMER COLL VETERINARY INTERNAL MEDICINE PI LAKEWOOD PA 7175 W JEFFERSON AVE, STE 2125, LAKEWOOD, CO 80235 USA SN 0891-6640 J9 J VET INTERN MED JI J. Vet. Intern. Med. PD MAR-APR PY 2004 VL 18 IS 2 BP 223 EP 230 DI 10.1892/0891-6640(2004)18<223:NAACFC>2.0.CO;2 PG 8 WC Veterinary Sciences SC Veterinary Sciences GA 802TX UT WOS:000220186900015 PM 15058775 ER PT J AU de Rosny, E Vassell, R Jiang, S Kunert, R Weiss, CD AF de Rosny, E Vassell, R Jiang, S Kunert, R Weiss, CD TI Binding of the 2F5 monoclonal antibody to native and fusion-intermediate forms of human immunodeficiency virus type 1 gp41: Implications for fusion-inducing conformational changes SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSMEMBRANE PROTEIN GP41; CELL-CELL FUSION; ENVELOPE GLYCOPROTEIN; HIV-1 GP41; NEUTRALIZING EPITOPE; INHIBITORY PEPTIDE; SYNTHETIC PEPTIDE; ATOMIC-STRUCTURE; ENTRY; ECTODOMAIN AB We investigated how the broadly neutralizing monoclonal antibody 2F5 affects the human immunodeficiency virus type 1 envelope glycoprotein as it undergoes receptor-induced conformational changes and show that 2F5 binds both native and fusion-intermediate conformations, suggesting inhibition of a late step in virus entry. We also demonstrate conformational changes in the C heptad of gp41. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. New York Blood Ctr, Lindsley F Kimball Res Inst, New York, NY 10021 USA. Univ Nat Resources & Appl Life Sci Vienna, Inst Appl Microbiol, A-1180 Vienna, Austria. RP Weiss, CD (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-466,Bldg 29,Room 532,8800 Rockville Pike, Bethesda, MD 20892 USA. EM cdweiss@helix.nih.gov RI Weiss, Carol/F-6438-2011; Jiang, Shibo/L-4500-2014 OI Weiss, Carol/0000-0002-9965-1289; NR 41 TC 69 Z9 70 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 MAR PY 2004 VL 78 IS 5 BP 2627 EP 2631 DI 10.1128/JVI.78.5.2627-2631.2004 PG 5 WC Virology SC Virology GA 775AV UT WOS:000189019300053 PM 14963170 ER PT J AU Czarneski, J Lin, YC Chong, S McCarthy, B Fernandes, H Parker, G Mansour, A Huppi, K Marti, GE Raveche, E AF Czarneski, J Lin, YC Chong, S McCarthy, B Fernandes, H Parker, G Mansour, A Huppi, K Marti, GE Raveche, E TI Studies in NZB IL-10 knockout mice of the requirement of IL-10 for progression of B-cell lymphoma SO LEUKEMIA LA English DT Article DE B-lymphocytes; cytokines; knockout ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA; IN-VIVO; B-1 CELLS; SPEED CONGENICS; INTERLEUKIN-10; APOPTOSIS; GROWTH; EXPRESSION; INHIBITION AB NZB mice develop an age-related malignant expansion of a subset of B cells, B-1 cells, with autocrine production of IL-10. IL-10, a pleiotropic cytokine with anti-inflammatory properties, is a potent growth and survival factor for malignant B cells. To further examine the in vivo requirement for IL-10 in the development and expansion of malignant B-1 clones in NZB mice, we developed a strain of homozygous IL-10 knockout (KO) mice on an NZB background. The NZB IL-10 KO mice develop peritoneal B-1 cells with approximately the same frequency as heterozygous and wild-type littermates. In contrast, the development of malignant B-1 cells in the peripheral blood and spleen, observed in wild-type NZB, rarely occurred in the NZB IL-10 KO. Phenotypic analysis of surface marker expression in splenic B cells indicated that, in contrast to the NZB with malignant B-1 splenic lymphoma, the surface marker expression of NZB IL-10 KO splenic B cells indicated that the majority of the B cells were typical B-2 cells. In the absence of IL-10, spontaneously activated B cells and antiapoptotic gene expression were reduced and lymphoma incidence was decreased. These results indicate that IL-10 is a critical factor for the progression of this B-cell malignant disease. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pathol, Newark, NJ 07103 USA. NCI, Canc Prevent Studies Branch, NIH, Rockville, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Raveche, E (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pathol, 185 S Orange Ave, Newark, NJ 07103 USA. EM raveches@umdnj.edu FU NCI NIH HHS [R01 CA 71478-11] NR 40 TC 38 Z9 39 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 MAR PY 2004 VL 18 IS 3 BP 597 EP 606 DI 10.1038/sj.leu.2403244 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 777UT UT WOS:000189197800029 PM 14712288 ER PT J AU Slater, JE AF Slater, JE TI Recombinant allergens in the US SO METHODS LA English DT Article ID EXTRACTS; POTENCY AB Recombinant allergens may increase the safety and efficacy of allergen immunodiagnostics and immunotherapy, and may prove to be excellent tools for the standardization of existing, natural allergens. However, there are several biological and regulatory issues that need to be addressed as these products are moved from bench to bedside. This article discusses some of these issues. (C) 2003 Elsevier Inc. All rights reserved. C1 US FDA, Lab Immunobiochem, Div Bacterial Parasit & Allergen Prod, Off Vaccines Regulat & Res,Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Slater, JE (reprint author), US FDA, Lab Immunobiochem, Div Bacterial Parasit & Allergen Prod, Off Vaccines Regulat & Res,Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 7 TC 1 Z9 1 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 1046-2023 J9 METHODS JI Methods PD MAR PY 2004 VL 32 IS 3 BP 209 EP 211 DI 10.1016/j.ymeth.2003.08.002 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 777MC UT WOS:000189181300002 PM 14962753 ER PT J AU Kamp, HG Turesky, R Schlatter, J Eisenbrand, G Janzowski, C AF Kamp, HG Turesky, R Schlatter, J Eisenbrand, G Janzowski, C TI Ochratoxin A: Induction of oxidative DNA damage in primary rat tubular cells and in rats SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 45th Spring Meeting of the German-Society-for-Experimental-and-Clinical-Pharmacology-and-Toxicology CY MAR 09-11, 2004 CL Mainz, GERMANY SP German Soc Exptl & Clin Pharmacol & Toxicol C1 Univ Kaiserslautern, Dept Chem, Div Food Chem & Environm Toxicol, Kaiserslautern, 72079, Germany. Natl Ctr Toxicol Res, Jefferson, AR USA. Swiss Fed Off Publ Hlth, Bern, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAR PY 2004 VL 369 SU 1 MA 495 BP R124 EP R124 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 808UA UT WOS:000220592800496 ER PT J AU Cisneros, FJ Branch, S AF Cisneros, FJ Branch, S TI Transplacental exposure to the DNA demethylating agent, 5-AZA-CdR, affects the sexual behavior of CD-1 male mice SO NEUROTOXICOLOGY LA English DT Article DE 5-AZA-2 '-deoxycytidine (5-AZA-CdR); daily sperm production; Sry gene; reproductive behavior; reproductive toxicity ID DE-NOVO METHYLATION; MAMMALIAN DEVELOPMENT; MOUSE FETUSES; GENE; 5-AZA-2'-DEOXYCYTIDINE; SRY; REPRODUCTION; EXPRESSION; MUTATION; DYSMORPHOGENESIS AB Intrauterine exposure to 5-AZ4-2'-deoxycytidine (5-AZ4-CdR) alters gene expression causing malformations, abnormal post-natal growth and altered reproductive capacity. To elucidate whether the phenomenon observed in 5-AZA-CdR in utero exposed male mice was a behavioral alteration, at gestation day (GD) 10, CD-1 pregnant mice were administered 1 mg/kg i.p. of 5-AZ4-CdR or saline solution. After parturition, the number and sex of pups were recorded. While litter size was not affected, the ratio of male to female offspring was altered in treated mice. To determine whether the phenotypic observation of male gender corresponded to the appropriate genotype, presence of Sry gene in 5-AZA-CdR F1 males was determined. At 3 months of age, the male sexual behavior test outlined by Chubb was conducted. Presence of vaginal plug and pregnancy were determined in the natural breeding phase. Mount latency and number of mounts per mouse were assessed in the behavioral test phase. In utero exposed male mice resulted in diminished mating behavior (as measured by vaginal plug presence, mount latency and number of mounts) and reduced sexual interest while exposed to a receptive female. While normal presence of Sry gene was observed, mating behavior was altered in exposed males suggesting that the reproductive alteration could be attributed to a behavioral phenomenon. (C) 2003 Elsevier Inc. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. RP Cisneros, FJ (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM fcisneros@nctr.fda.gov RI Matthews Branch, Stacy/E-6200-2017 OI Matthews Branch, Stacy/0000-0002-1048-6097 FU NIEHS NIH HHS [ES08452] NR 52 TC 4 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD MAR PY 2004 VL 25 IS 3 BP 411 EP 417 DI 10.1016/j.neuro.2003.09.002 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 803XF UT WOS:000220263100008 PM 15019304 ER PT J AU Scallet, AC Kowalke, PK Rountree, RL Thorn, BT Binienda, ZK AF Scallet, AC Kowalke, PK Rountree, RL Thorn, BT Binienda, ZK TI Electroencephalographic, behavioral, and c-fos responses to acute dombic acid exposure SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE limbic system; hippocampus; olfactory bulb; amnesia; excitotoxins; algal blooms; shellfish toxins; electrocorticogram; fast fourier transformation; electroencephalogram; epilepsy; seizures ID KAINATE RECEPTOR ACTIVATION; RAT DORSAL HIPPOCAMPUS; TEMPORAL-LOBE EPILEPSY; DOMOIC ACID; GENE-EXPRESSION; PROTEIN IMMUNOHISTOCHEMISTRY; MONOAMINE CONCENTRATIONS; MEDIATED EXCITOTOXICITY; REDUCED PERFUSION; INDUCED SEIZURES AB Domoic acid, a potent excitotoxic analogue of glutamate and kainate, may cause seizures, amnesia, and sometimes death in humans consuming contaminated shellfish. Continuous behavioral observations and recordings of the electrocorticogram (ECoG, via bipolar, epidural electrodes) were obtained from nonanesthetized rats for 2 h after intraperitoneal injection with either saline, 2.2, or 4.4 mg/kg of domoic acid. Rats were then sacrificed for c-fos immunohistochemistry. Fast Fourier transformation (FFT) of the ECoG data to obtain the voltage as a function of frequency indicated that the lower frequency bands (theta, 4.75-6.75 Hz and delta, 1.25-4.50 Hz) were the first to respond, with a significant elevation by 30 min after the high dose of domoic acid. The lower dose of domoic, acid also caused a significant elevation of ECoG voltage, but not until later in the session. Sixty minutes after dosing the behavioral biomarkers of "ear scratching" and "rearing, praying" (RP) seizures became significantly elevated in the high-dose rats. The low-dose rats showed no significant alterations in behavior at any time during the session. In postmortem brains obtained immediately after, the sessions, c-fos was activated in the anterior olfactory nucleus by both the low and high doses of domoic acid. However, only the high dose increased c-fos immunoreactivity in the hippocampus, affecting both the granule and pyramidal neurons. These data indicate that electroencephalographic and c-fos responses can be obtained at a dose of domoic acid that fails to activate the behavioral response most commonly used as a bioassay, for this marine toxin: ear scratching with the ipsilateral foot. (C) 2004 Published by Elsevier Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Scallet, AC (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM AScallet@nctr.fda.gov NR 85 TC 21 Z9 23 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAR-APR PY 2004 VL 26 IS 2 BP 331 EP 342 DI 10.1016/j.ntt.2003.10.004 PG 12 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 806OY UT WOS:000220444400016 PM 15019966 ER PT J AU Ferguson, SA Cada, AM AF Ferguson, SA Cada, AM TI Spatial learning/memory and social and nonsocial behaviors in the spontaneously hypertensive, Wistar-Kyoto and Sprague-Dawley rat strains SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE spontaneously hypertensive; Wistar-Kyoto; play behavior; dominance; spatial learning; memory; motor coordination; acoustic startle; prepulse inhibition ID ELEVATED PLUS-MAZE; CENTRAL NICOTINIC RECEPTORS; MORRIS WATER MAZE; NORMOTENSIVE RATS; ANIMAL-MODEL; WKY RATS; COGNITIVE IMPAIRMENT; AUDITORY STARTLE; WORKING-MEMORY; SHR AB The Spontaneously Hypertensive rat (SHR) is often described as less behaviorally reactive than its normotensive strain, the Wistar-Kyoto (WKY), although results are somewhat inconsistent across studies. In part, this may be due to the lack of a definitive characterization of "reactivity." Still, results from identical behavioral tests of SHR and WXY across studies are sometimes conflicting. Further, few comparisons with other rodent strains are available and these might provide guidance in outlining the meaning of reactivity. Here, social and nonsocial behaviors and spatial learning and memory were measured in male and female SHR, WKY, and Sprague-Dawley (SD) rats. Systolic blood pressure measurements at adulthood confirmed hypertension in the SHR. Juvenile play behavior indicated that SHRs were more sensitive to the strain of their play partner than were the WKY or SD, playing less with different strain partners than with same strain partners. However, adult dominance behavior (restricted access in a water competition test) indicated no strain differences. The SHR appeared to exhibit attenuated acoustic startle relative to the WXY and SD and their prepulse inhibition was substantially less at higher prepulse decibel intensities; however, this decreased prepulse inhibition was not the result of decreased startle during the test. Anxiety-related behavior in the elevated plus maze was most prominent in the SD strain, possibly as a result of poorer motor coordination as measured by rotarod performance. Elevated plus maze behavior as well as motor coordination did not differ between the SHR and WKY strains. Performance in the NCTR complex maze and the Morris water maze was significantly better in the SHR. These results do not support hypotheses of decreased behavioral reactivity in the SHR strain. Rather, they suggest complex interactions between social and nonsocial environments and the behavioral capabilities and requirements of the rat strain. (C) 2004 Elsevier Inc. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM sferguson@nctr.fda.gov NR 67 TC 66 Z9 66 U1 0 U2 5 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 2004 VL 77 IS 3 BP 583 EP 594 DI 10.1016/j.pbb.2003.12.014 PG 12 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 803ZD UT WOS:000220268100020 PM 15006470 ER PT J AU Powell, JR AF Powell, JR TI Clinical pharmacists save thousands of lives: Big decrease in dose-related adverse effects SO PHARMACOTHERAPY LA English DT Editorial Material ID PHYSICIANS C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. RP Powell, JR (reprint author), 7620 Old Georgetown Rd,Apartment 813, Bethesda, MD 20814 USA. EM bobpowell@comcast.net NR 6 TC 1 Z9 1 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD MAR PY 2004 VL 24 IS 3 BP 422 EP 425 DI 10.1592/phco.24.4.422.33176 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 779QY UT WOS:000189312800017 PM 15040659 ER PT J AU Hanna, GM AF Hanna, GM TI NMR regulatory analysis: determination and characterization of chinese-herb aristolochic acids SO PHARMAZIE LA English DT Article ID RENAL-FAILURE; UROTHELIAL CARCINOMA; SLIMMING REGIMEN; RAT FORESTOMACH; NEPHROPATHY; IDENTIFICATION; MUTAGENICITY; MEDICINE; TOXICITY; FANGCHI AB H-1 NMR methodology for the simultaneous determination and characterization of the nephrotoxic components of Aristolochia plants aristolochic acid I (AA-I) and aristolochic acid II (AA-II) was developed utilizing a 400 MHz spectrometer without the need of reference standards. The developed methodology is able to differentiate and assess chemical structures of these toxic injurious compounds. The quantity of each was calculated on the basis of the integrals for the signals of the H-7 and H-8 of the phenanthrene ring of AA-I and AA-II at delta7.38 and delta8.31, respectively, and the vinylic protons of the internal standard maleic acid at delta6.06. The accuracy of the method was established through the analysis of synthetic mixtures containing the internal standard maleic acid, with purified AA-I or combined AA-I and AA-II sodium salts. Excellent agreements were verified between the assay results and the quantities in the mixtures. The mean +/- SD recovery values for purified AA-I and combined AA-I and AA-II from two sets of 10 synthetic mixtures were 99.8 +/- 0.6% and 99.6 +/- 0.8%, respectively. The assay of 4 lots of commercial aristolochic acid by H-1 NMR spectroscopy indicated AA-I and AA-II contents in the ranges 45.3-97.1% and 0-15.4%, respectively. C1 US FDA, NE Reg Lab, Dept Hlth & Human Serv, Jamaica, NY 11433 USA. RP Hanna, GM (reprint author), US FDA, NE Reg Lab, Dept Hlth & Human Serv, 158-15 Liberty Ave, Jamaica, NY 11433 USA. EM ghanna@ora.fda.gov NR 29 TC 4 Z9 5 U1 1 U2 1 PU GOVI-VERLAG GMBH PI ESCHBORN PA PHARMAZEUTISCHER VERLAG GINNHEIMER STRASSE 26, D-65760 ESCHBORN, GERMANY SN 0031-7144 J9 PHARMAZIE JI Pharmazie PD MAR PY 2004 VL 59 IS 3 BP 170 EP 174 PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 804PY UT WOS:000220311800002 PM 15074585 ER PT J AU Leak, LV Liotta, LA Krutzsch, H Jones, M Fusaroa, VA Ross, SJ Zhaos, YM Petricoin, EF AF Leak, LV Liotta, LA Krutzsch, H Jones, M Fusaroa, VA Ross, SJ Zhaos, YM Petricoin, EF TI Proteomic analysis of lymph SO PROTEOMICS LA English DT Article DE biomarkers; cancer; lymph; surface-enhanced laser desorption/ionization-time of flight-mass spectrometry ID HUMAN PROSTATE-CANCER; HUMAN-PLASMA PROTEINS; MASS-SPECTROMETRY; 2-DIMENSIONAL ELECTROPHORESIS; ANCHORING FILAMENTS; HEMOSTATIC FACTORS; DENDRITIC CELLS; FLUID; IMMUNODETECTION; GLYCOPROTEIN AB This report provides the first proteomic analysis of normal ovine lymph. By establishing the fact that lymph is more than an ultrafiltrate of blood plasma, it documents that the lymph proteome contains an array of proteins that differentiates it from plasma. The protein chip technology, surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS), two-dimensional gel electrophoresis (2-D PAGE) and MS, were employed to examine the protein expression profiles of ovine lymph. Using a weak cation exchange chip surface to assay lymph and plasma samples by SELDI-TOF-MS showed that the analysis of peak maps from lymph contained three protein peaks that were found only in lymph, while analysis of peak maps from plasma samples showed that five protein peaks were found only in plasma. Lymph and plasma samples showed eight peaks that were common to both. There were also more ions present in plasma than in lymph, which is consistent with the 2-D PAGE analysis. MS analysis of a large number of protein spots from 2-D PAGE gels of lymph produced MS/MS sequences for 18 proteins that were identified by searching against a comprehensive protein sequence database. As in plasma, large protein spots of albumin dominated the protein pattern in lymph. Other major proteins identified in 2-D PAGE gels of lymph included, fibrinogen alpha- and beta-chains, immunoglobulin G (IgG) heavy chain, serotransferrin precursor, lactoferrin, and apolipoprotein A-1. Two Proteins that were identified and were differentially expressed in lymph were glial fibrillary astrocyte acidic protein and neutrophil cytosol factor-1. By bringing the technologies of proteomics to bear on the analysis of lymph, it is possible to detect proteins in lymph that are quantitatively and qualitatively differentially expressed from those of plasma. C1 US FDA, Ctr Biol Evaluat & Res, Clin Proteom Program Therapeut Prot, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Howard Univ, Coll Med, Ernest E Just Lab Cellular Med, Washington, DC 20059 USA. NHLBI, Lab Anim Surg, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75230 USA. RP Petricoin, EF (reprint author), US FDA, Ctr Biol Evaluat & Res, Clin Proteom Program Therapeut Prot, 800 Rockville Pike,Bldg 29A,Room 2A17, Bethesda, MD 20892 USA. EM petricoin@cber.fda.gov NR 50 TC 48 Z9 51 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD MAR PY 2004 VL 4 IS 3 BP 753 EP 765 DI 10.1002/pmic.200300573 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 802QX UT WOS:000220179100019 PM 14997497 ER PT J AU Alexe, G Alexe, S Liotta, LA Petricoin, E Reiss, M Hammer, PL AF Alexe, G Alexe, S Liotta, LA Petricoin, E Reiss, M Hammer, PL TI Ovarian cancer detection by logical analysis of proteomic data SO PROTEOMICS LA English DT Article DE logical analysis of data; ovarian cancer ID PROSTATE-CANCER; BREAST-CANCER; SERUM; PATTERNS; IDENTIFICATION; PREDICTION; CARCINOMA; MARKERS; RISK AB A new type of efficient and accurate proteomic ovarian cancer diagnosis systems is proposed. The system is developed using the combinatorics and optimization-based methodology of logical analysis of data (LAD) to the Ovarian Dataset 8-7-02 (http://clinicalproteomics.steem.com), which updates the one used by Petricoin et al, in The Lancet 2002, 359, 572-577. This mass spectroscopy-generated dataset contains expression profiles of 15154 peptides defined by their mass/charge ratios (m/z) in serum of 162 ovarian cancer and 91 control cases. Several fully reproducible models using only 7-9 of the 15 154 peptides were constructed, and shown in multiple cross-validation tests (k-folding and leave-one-out) to provide sensitivities and specificities of up to 100%. A special diagnostic system for stage I ovarian cancer patients is shown to have similarly high accuracy. Other results: (i) expressions of peptides with relatively low m/z values in the dataset are shown to be better at distinguishing ovarian cancer cases from controls than those with higher m/z values; (ii) two large groups of patients with a high degree of similarities among their formal (mathematical) profiles are detected; (iii) several peptides with a blocking or promoting effect on ovarian cancer are identified. C1 Rutgers State Univ, Rutgers Ctr Operat Res, RUTCOR, Piscataway, NJ 08854 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, NIH, Clin Proteom Program,Dept Therapeut, Bethesda, MD 20014 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Inst Canc, Dept Med, New Brunswick, NJ USA. RP Hammer, PL (reprint author), Rutgers State Univ, Rutgers Ctr Operat Res, RUTCOR, 640 Bartholomew Rd, Piscataway, NJ 08854 USA. EM hammer@rutcor.rutgers.edu RI Reiss, Michael/A-8314-2009 NR 38 TC 54 Z9 56 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD MAR PY 2004 VL 4 IS 3 BP 766 EP 783 DI 10.1002/pmic.200300574 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 802QX UT WOS:000220179100020 PM 14997498 ER PT J AU Berman, DM Shih, LM Burke, LA Veenstra, TD Zhao, YM Conrads, TP Kwon, SW Hoang, V Yu, LR Zhou, M Kurman, RJ Petricoin, EF Liotta, LA AF Berman, DM Shih, LM Burke, LA Veenstra, TD Zhao, YM Conrads, TP Kwon, SW Hoang, V Yu, LR Zhou, M Kurman, RJ Petricoin, EF Liotta, LA TI Profiling the activity of G proteins in patient-derived tissues by rapid affinity-capture of signal transduction proteins (GRASP) SO PROTEOMICS LA English DT Article DE affinity capture; G protein signal transduction; mass spectrometry; ovarian carcinoma; protein-protein interactions ID GUANINE-NUCLEOTIDE EXCHANGE; GTP-BINDING PROTEIN; RHO-GTPASES; PROTEOMIC ANALYSIS; CANCER; SPECIFICITY; PATHWAYS; BIOLOGY AB The next phase in molecular medicine will require the ability to identify signal transduction events inside a cell, in the biologic context of the disease-host interface and at a given point in time. New technologies are needed to profile the activity of these signaling pathways in patient tissue rather than cultured cell lines since the tumor-host microenvironment influences the cellular proteome. We introduce such a technology, rapid affinity capture of signaling proteins (GRASP), to investigate the activity of signaling pathways from patient-derived carcinomas and benign epithelial surfaces and apply it to studying important signaling events in ovarian carcinoma. During the progression from benign ovarian epithelium to invasive carcinoma, there is loss of repression of Rho A as evidenced by its dissociation from its inhibitor, Rho Guanine Nucleotide Dissociation Inhibitor (RhoGDI). GRASP is more informative than simply profiling transcript or protein levels. Furthermore, GRASP coupled with mass spectrometry allowed us to identify a protein-binding partner of RhoGDI, demonstrating the power of this technology in the discovery of potentially novel protein-protein interactions. GRASP represents an advance in the field of proteomics as it detects protein interactions present in cells as they exist in their native tissue microenvironment. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21218 USA. NCI, SAIC Frederick, Frederick, MD 21701 USA. Univ Texas, SW Med Sch, Dept Biochem, Dallas, TX USA. US FDA, Ctr Biol Evaluat & Res, NCI, Clin Proteom Program, Bethesda, MD 20014 USA. RP Berman, DM (reprint author), NCI, Pathol Lab, NIH, 10-2N212,Ctr Dr, Bethesda, MD 20892 USA. EM bermand@mail.nih.gov RI Burke, Luke/C-7655-2011 NR 27 TC 11 Z9 11 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD MAR PY 2004 VL 4 IS 3 BP 812 EP 818 DI 10.1002/pmic.200300579 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 802QX UT WOS:000220179100023 PM 14997501 ER PT J AU Li, H AF Li, H TI A widely applicable extension of the random effects two-way layout: Its definition and statistical analysis based on group invariance SO PSYCHOMETRIKA LA English DT Article; Proceedings Paper CT Conference and Workshop on Random Utility and Probabilistic Measurement Theory CY AUG 03-08, 2000 CL Duke Univ, Durham, NC SP Natl Sci Fdn, Fuqua Sch Business, Ctr Int Business Educ & Res HO Duke Univ DE disattenuation; group invariance; measurement error; reliability ID STRATIFIED-PARALLEL TESTS; CORRELATION-COEFFICIENTS; MAXIMAL-RELIABILITY; MODELS; VARIANCE; SYMMETRY; DESIGNS AB A type of data layout that may be considered as an extension of the two-way random effects analysis of variance is characterized and modeled based on group invariance. The data layout seems to be suitable for several scenarios in psychometrics, including the one in which multiple measurements are taken on each of a set of variables, and the measurements can be divided into exchangeable subsets. The algebraic structure of the model is studied, which leads to results that are applicable to such problems as estimating correlation matrix corrected for attenuation and testing symmetry hypotheses. C1 Univ Rochester, Rochester, NY 14627 USA. RP Li, H (reprint author), FDA CDRH, HRZ 550,1350 Piccard Dr, Rockville, MD 20850 USA. NR 26 TC 0 Z9 0 U1 0 U2 0 PU PSYCHOMETRIC SOC PI WILLIAMSBURG PA COLLEGE OF WILLIAM AND MARY DEPT PSYCHOLOGY, WILLIAMSBURG, VA 23185 USA SN 0033-3123 J9 PSYCHOMETRIKA JI Psychometrika PD MAR PY 2004 VL 69 IS 1 BP 55 EP 64 DI 10.1007/BF02295839 PG 10 WC Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods; Psychology, Mathematical SC Mathematics; Mathematical Methods In Social Sciences; Psychology GA 858KF UT WOS:000224190000003 ER PT J AU Feldman, AL Espina, V Petricoin, EF Liotta, LA Rosenblatt, KP AF Feldman, AL Espina, V Petricoin, EF Liotta, LA Rosenblatt, KP TI Use of proteomic patterns to screen for gastrointestinal malignancies SO SURGERY LA English DT Review ID COLORECTAL-CANCER; PROTEIN MICROARRAYS; MARKERS; SERUM C1 NCI, Pathol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Feldman, AL (reprint author), NCI, Pathol Lab, Canc Res Ctr, NIH, Bldg 10,Rm 2A33,10 Ctr Dr, Bethesda, MD 20892 USA. RI Feldman, Andrew/D-5028-2012; OI Espina, Virginia/0000-0001-5080-5972 NR 15 TC 22 Z9 22 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAR PY 2004 VL 135 IS 3 BP 243 EP 247 DI 10.1016/j.surg.2003.08.019 PG 5 WC Surgery SC Surgery GA 779QE UT WOS:000189310900001 PM 14976472 ER PT J AU Krieg, RC Liotta, LA Petricoin, EF Herrmann, PC AF Krieg, RC Liotta, LA Petricoin, EF Herrmann, PC TI Trapping radioactive carbon dioxide during cellular metabolic assays under standard culture conditions: description of a unique gas-capturing device SO JOURNAL OF BIOCHEMICAL AND BIOPHYSICAL METHODS LA English DT Article DE metabolism; physiological; carbon dioxide; radioactivity ID DECARBOXYLATION; GLUCOSE; CELLS AB Measurement of carbon dioxide levels has been employed to follow cellular metabolic reactions for quite some time. By radio-labeling substrate molecules and evaluating the radioactivity levels of the carbon dioxide released, insight into metabolic pathways can be gleaned. Currently, no carbon dioxide capturing device is available that can be used with large volume cell monolayers growing under standard conditions within a regular commercially available culture flask. In this note we describe a simple device for collecting radio-labeled carbon dioxide from a standard culture flask. The device is independent of the culture flask, but can be attached for metabolic measurements allowing cells to be grown under standard conditions prior to study. The presented design permits convenient transfer of the device between flasks without contaminating or disturbing cells growing within the flasks. Data are presented demonstrating the reproducibility of measurements made with multiple devices with different substrate concentrations and varying periods of time, ranging up to 3 h. Published by Elsevier B.V. C1 NCI, FDA, Clin Proteom Program, Pathol Lab,NIH, Bethesda, MD 20892 USA. US FDA, CBER, Off Director, Clin Proteom Program, Bethesda, MD 20892 USA. RP Herrmann, PC (reprint author), NCI, FDA, Clin Proteom Program, Pathol Lab,NIH, 10 Ctr Dr,Bldg 10 Room 2n212, Bethesda, MD 20892 USA. EM herrmanp@mail.nih.gov NR 8 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-022X J9 J BIOCHEM BIOPH METH JI J. Biochem. Biophys. Methods PD FEB 27 PY 2004 VL 58 IS 2 BP 119 EP 124 DI 10.1016/j.jbbm.2003.10.002 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 801SF UT WOS:000220114900003 PM 14980785 ER PT J AU Watabe, H Valencia, JC Yasumoto, K Kushimoto, T Ando, H Muller, J Vieira, WD Mizoguchi, M Appella, E Hearing, VJ AF Watabe, H Valencia, JC Yasumoto, K Kushimoto, T Ando, H Muller, J Vieira, WD Mizoguchi, M Appella, E Hearing, VJ TI Regulation of tyrosinase processing and trafficking by organellar pH and by proteasome activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HERMANSKY-PUDLAK-SYNDROME; MOUSE MELANOMA-CELLS; B-16 MURINE MELANOMA; VACUOLAR H+-ATPASE; ENDOPLASMIC-RETICULUM; OCULOCUTANEOUS ALBINISM; MAMMALIAN TYROSINASE; GENE-PRODUCT; HUMAN-SKIN; INTRACELLULAR TRAFFICKING AB Pigmentation of the hair, skin, and eyes of mammals results from a number of melanocyte-specific proteins that are required for the biosynthesis of melanin. Those proteins comprise the structural and enzymatic components of melanosomes, the membrane-bound organelles in which melanin is synthesized and deposited. Tyrosinase (TYR) is absolutely required for melanogenesis, but other melanosomal proteins, such as TYRP1, DCT, and gp100, also play important roles in regulating mammalian pigmentation. However, pigmentation does not always correlate with the expression of TYR mRNA/protein, and thus its function is also regulated at the post-translational level. Thus, TYR does not necessarily exist in a catalytically active state, and its post-translational activation could be an important control point for regulating melanin synthesis. In this study, we used a multidisciplinary approach to examine the processing and sorting of TYR through the endoplasmic reticulum ( ER), Golgi apparatus, coated vesicles, endosomes and early melanosomes because those organelles hold the key to understanding the trafficking of TYR to melanosomes and thus the regulation of melanogenesis. In pigmented cells, TYR is trafficked through those organelles rapidly, but in amelanotic cells, TYR is retained within the ER and is eventually degraded by proteasomes. We now show that TYR can be released from the ER in the presence of protonophore or proton pump inhibitors which increase the pH of intracellular organelles, after which TYR is transported correctly to the Golgi, and then to melanosomes via the endosomal sorting system. The expression of TYRP1, which facilitates TYR processing in the ER, is down-regulated in the amelanotic cells; this is analogous to a hypopigmentary disease known as oculocutaneous albinism type 3 and further impairs melanin production. The sum of these results shows that organellar pH, proteasome activity, and down-regulation of TYRP1 expression all contribute to the lack of pigmentation in TYR-positive amelanotic melanoma cells. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Div Viral Prod, Rockville, MD 20852 USA. St Marianna Univ, Sch Med, Dept Dermatol, Kawasaki, Kanagawa 2168511, Japan. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Rm 1B25, Bethesda, MD 20892 USA. EM hearingv@nih.gov NR 81 TC 74 Z9 75 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 27 PY 2004 VL 279 IS 9 BP 7971 EP 7981 DI 10.1074/jbc.M309714200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 776EG UT WOS:000189103300075 PM 14634018 ER PT J AU Puig, M Major, ME Mihalik, K Feinstone, SM AF Puig, M Major, ME Mihalik, K Feinstone, SM TI Immunization of chimpanzees with an envelope protein-based vaccine enhances specific humoral and cellular immune responses that delay hepatitis C virus infection SO VACCINE LA English DT Article DE hepatitis C; vaccine; envelope ID RECOVERED CHIMPANZEES; FOLLOW-UP; CELLS; ANTIBODY; E2; TRANSMISSION; RECHALLENGE; PERSISTENCE; CLEARANCE; BINDING AB Two chimpanzees, one naive (Ch1601) and one recovered from hepatitis C virus (HCV) acute infection (Ch1587), were vaccinated with recombinant envelope glycoproteins (E1E2) and then challenged with 100 CID50 of HCV. Results of the challenge were compared to infection in a non-vaccinated control animal. Immunization generated high antibody titers to E1E2 including antibody specifically directed to the hypervariable region 1 (HVR1) in addition to strong and specific HVR1 T-cell proliferative responses. Upon challenge with HCV, viremia was delayed 3 weeks in both vaccinated animals compared to the non-immunized (control) animal. Ch1601 HCV RNA titers were maintained below 5 x 10(4) copies/ml, and alanine aminotransferase levels were only minimally elevated. An increase in intrahepatic cytokine mRNA levels coincided with a fall in HCV RNA to non-quantifiable levels. Despite this apparent control of virus replication the animal became persistently infected. Ch1587 had a significantly shorter and milder viremia, compared to the re-infection of the non-vaccinated control animal. This data indicates that a strategy inducing a T-cell immune response combined with antibody responses to E1E2 would make a viable candidate for an HCV vaccine.. Published by Elsevier Ltd. C1 US FDA, CBER, Div Viral Prod, Lab Hepatitis Viruses, Bethesda, MD 20892 USA. RP Feinstone, SM (reprint author), US FDA, CBER, Div Viral Prod, Lab Hepatitis Viruses, Bldg 29A,Room 1D02,8800 Rockville Pike, Bethesda, MD 20892 USA. EM feinstone@cber.fda.gov FU NCI NIH HHS [CA85883] NR 30 TC 54 Z9 58 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 FEB 25 PY 2004 VL 22 IS 8 BP 991 EP 1000 DI 10.1016/j.vaccine.2003.09.010 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 778XN UT WOS:000189266800010 PM 15161076 ER PT J AU Passerini, AG Polacek, DC Shi, CZ Francesco, NM Manduchi, E Grant, GR Pritchard, WF Powell, S Chang, GY Stoeckert, CJ Davies, PF AF Passerini, AG Polacek, DC Shi, CZ Francesco, NM Manduchi, E Grant, GR Pritchard, WF Powell, S Chang, GY Stoeckert, CJ Davies, PF TI Coexisting proinflammatory and antioxidative endothelial transcription profiles in a disturbed flow region of the adult porcine aorta SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NF-KAPPA-B; LAMINAR SHEAR-STRESS; ADHESION MOLECULE-1 EXPRESSION; GENE-EXPRESSION; ATHEROSCLEROTIC LESIONS; VASCULAR ENDOTHELIUM; RESPONSE ELEMENT; CELLS; ATHEROGENESIS; ACTIVATION AB In the arterial circulation, regions of disturbed flow (DF), which are characterized by flow separation and transient vortices, are susceptible to atherogenesis, whereas regions of undisturbed laminar flow (UF) appear protected. Coordinated regulation of gene expression by endothelial cells (EC) may result in differing regional phenotypes that either favor or inhibit atherogenesis. Linearly amplified RNA from freshly isolated EC of DF (inner aortic arch) and UF (descending thoracic aorta) regions of normal adult pigs was used to profile differential gene expression reflecting the steady state in vivo. By using human cDNA arrays, approximate to2,000 putatively differentially expressed genes were identified through false-discovery-rate statistical methods. A sampling of these genes was validated by quantitative real-time PCR and/or immunostaining en face. Biological pathway analysis revealed that in DF there was up-regulation of several broad-acting inflammatory cytokines and receptors, in addition to elements of the NF-kappaB system, which is consistent with a proinflammatory phenotype. However, the NF-kappaB complex was predominantly cytoplasmic (inactive) in both regions, and no significant differences were observed in the expression of key adhesion molecules for inflammatory cells associated with early atherogenesis. Furthermore, there was no histological evidence of inflammation. Protective profiles were observed in DF regions, notably an enhanced antioxidative gene expression. This study provides a public database of regional EC gene expression in a normal animal, implicates hemodynamics as a contributory mechanism to athero-susceptibility, and reveals the coexistence of pro- and antiatherosclerotic transcript profiles in susceptible regions. The introduction of additional risk factors may shift this balance to favor lesion development. C1 Univ Penn, Inst Med & Engn, Vagelos Labs 1010, Philadelphia, PA 19104 USA. Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioinformat, Philadelphia, PA 19104 USA. US FDA, Rockville, MD 20852 USA. AstraZeneca Pharmaceut, Macclesfield SK10 4TG, Cheshire, England. RP Davies, PF (reprint author), Univ Penn, Inst Med & Engn, Vagelos Labs 1010, 3340 Smith Walk, Philadelphia, PA 19104 USA. EM pfd@pobox.upenn.edu FU NHGRI NIH HHS [K25 HG002296, K25 HG000052, K25-HG-00052, K25-HG-02296]; NHLBI NIH HHS [HL62250, HL70128, P01 HL062250, P50 HL070128] NR 49 TC 221 Z9 224 U1 1 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 FEB 24 PY 2004 VL 101 IS 8 BP 2482 EP 2487 DI 10.1073/pnas.0305938101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 802CA UT WOS:000220140400046 PM 14983035 ER PT J AU Raw, AS Yu, LX AF Raw, AS Yu, LX TI Pharmaceutical solid polymorphism in drug development and regulation - Preface SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, MD 20855 USA. RP Raw, AS (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Metro Pk N 2,Room E204,7500 Standish Pl, Rockville, MD 20855 USA. EM rawa@cder.fda.gov; yul@cder.fda.gov RI Yu, Lawrence/L-6280-2016 NR 3 TC 22 Z9 25 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD FEB 23 PY 2004 VL 56 IS 3 BP 235 EP 236 DI 10.1016/j.addr.2003.10.004 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 778FG UT WOS:000189228300001 ER PT J AU Yu, LX Lionberger, RA Raw, AS D'Costa, R Wu, HQ Hussain, AS AF Yu, LX Lionberger, RA Raw, AS D'Costa, R Wu, HQ Hussain, AS TI Applicatlons of process analytical technology to crystallization processes SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE process analytical technology; polymorphism; crystallization; in situ; modeling; simulation; control ID PROCESS ANALYTICAL-CHEMISTRY; SODIUM-CHLORATE CRYSTALS; SITU RAMAN-SPECTROSCOPY; ATR-FTIR SPECTROSCOPY; PHARMACEUTICAL CRYSTALLIZATION; INFRARED-SPECTROSCOPY; CONCENTRATION PREDICTION; COLLOIDAL SUSPENSIONS; DITHIONATE IMPURITY; POLYMORPHIC FORMS AB Crystallizations of pharmaceutical active ingredients, particularly those that posses multiple polymorphic forms, are among the most critical and least understood pharmaceutical manufacturing processes. Many process and product failures can be traced to a poor understanding and control of crystallization processes. The Food and Drug Administration's process analytical technology (PAT) initiative is a collaborative effort with industry to introduce new and efficient manufacturing technologies into the pharmaceutical industry. PAT's are systems for design, analysis, and control of manufacturing processes. They aim to assure high quality through timely measurements of critical quality and performance attributes of raw materials, in-process materials, and final products. Implementation of PAT involves scientifically based process design and optimization, appropriate sensor technologies, statistical and information tools (chemometrics), and feedback process control strategies working together to produce quality products. This review introduces the concept of PAT and discusses its application to crystallization processes through review of several case studies. A variety of in situ analytical methods combined with chemometric tools for analysis of multivariate process information provide a basis for future improvements in modeling, simulation, and control of crystallization processes. (C) 2003 Elsevier B.V. All fights reserved. C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Off Gener Drugs, Rockville, MD 20857 USA. RP Hussain, AS (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, 5600 Fishers Lane, Rockville, MD 20857 USA. EM hussaina@cder.fda.gov NR 48 TC 162 Z9 165 U1 5 U2 75 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD FEB 23 PY 2004 VL 56 IS 3 BP 349 EP 369 DI 10.1016/j.addr.2003.10.012 PG 21 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 778FG UT WOS:000189228300008 PM 14962586 ER PT J AU Raw, AS Furness, MS Gill, DS Adams, RC Holcombe, FO Yu, LX AF Raw, AS Furness, MS Gill, DS Adams, RC Holcombe, FO Yu, LX TI Regulatory considerations of pharmaceutical solid polymorphism in abbreviated new drug applications (ANDAs) SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE polymorphism; polymorph; abbreviated new drug application (ANDA); drug substance; drug product; pharmaceutical solid ID ENALAPRIL MALEATE; SOLUTION CALORIMETRY; TABLET FORMULATION; FORM-II; CARBAMAZEPINE; BIOAVAILABILITY; TRANSFORMATION; CLASSIFICATION; STABILIZATION; SPECTROSCOPY AB A sponsor of an Abbreviated New Drug Application (ANDA) must have information to show that the proposed generic product and the innovator product are both pharmaceutically equivalent and bioequivalent, and therefore, therapeutically equivalent. Many pharmaceutical solids exist in several crystalline forms and thus exhibit polymorphism. Polymorphism may result in differences in the physico-chemical properties of the active ingredient and variations in these properties may render a generic drug product to be bioinequivalent to the innovator brand. For this reason, in ANDAs, careful attention is paid to the effect of polymorphism in the context of generic drug product equivalency. This review discusses the impact of polymorphism on drug product manufacturability, quality, and performance. Conclusions from this analysis demonstrate that pharmaceutical solid polymorphism has no relevance to the determination of drug substance "sameness" in ANDAs. Three decision trees for solid oral dosage forms or liquid suspensions are provided for evaluating when and how polymorphs of drug substances should be monitored and controlled in ANDA submissions. Case studies from ANDAs are provided which demonstrate the irrelevance of polymorphism to the determination of drug substance "sameness". These case studies also illustrate the conceptual framework from these decision trees and illustrate how their general principles are sufficient to assure both the quality and the therapeutic equivalence of marketed generic drug products. (C) 2003 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, MD 20855 USA. RP Raw, AS (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Metro Pk N 2,Room E204,7500 Standish Pl, Rockville, MD 20855 USA. EM rawa@cder.fda.gov RI Yu, Lawrence/L-6280-2016 NR 64 TC 73 Z9 80 U1 7 U2 35 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD FEB 23 PY 2004 VL 56 IS 3 BP 397 EP 414 DI 10.1016/j.addr.2003.10.011 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 778FG UT WOS:000189228300011 PM 14962589 ER PT J AU Lopez, H Beer, JZ Miller, SA Zmudzka, BZ AF Lopez, H Beer, JZ Miller, SA Zmudzka, BZ TI Ultrasound measurements of skin thickness after UV exposure: a feasibility study SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article DE ultraviolet radiation; ultrasound; human skin; skin exposure; dermis; epidermis; skin thickness ID HIGH-FREQUENCY ULTRASOUND; ULTRAVIOLET-IRRADIATION; IN-VIVO; ERYTHEMA; PIGMENTATION; INFLAMMATION; RADIATION; HUMANS; AGE; US AB High-frequency ultrasound images were used to measure the thickness of the dermis and epidermis of four human subjects. These measurements were performed before and after a single exposure to ultraviolet radiation (UV). Doses ranging from 0.5 to 3 minimal erythema doses (MED) were delivered to the skin of the back of four human subjects, and thickness measurements were made over a period of 16 days. We found: (1) exposures greater than or equal to 2 MED caused a 10-30% increase in the thickness of the dermis-epidermis layer; (2) the thickening response was not always in direct proportion to the UV dose; (3) maximum thickening response time was 48 h for the 2.8-3.0 MED exposure levels; (4) "diffusion" or spreading of the thickening response to neighboring areas occurred in some cases, as far as 4 cm from the exposed region (center-to-center), with changes ranging from 12% to 17%; (5) decreased thickness of the dermis-epidermis layer of up to 12% was observed for 3 out of 4 of the subjects. (C) 2003 Elsevier B.V. All rights reserved. C1 US FDA, Dept Hlth & Human Serv, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20850 USA. RP Lopez, H (reprint author), US FDA, Dept Hlth & Human Serv, Ctr Devices & Radiol Hlth, Off Sci & Technol, 9200 Corp Blvd,HFZ-132, Rockville, MD 20850 USA. EM hx18@cdrh.fda.gov NR 24 TC 3 Z9 3 U1 2 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 20 PY 2004 VL 73 IS 3 BP 123 EP 132 DI 10.1016/j.jphotobiol.2003.11.004 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 800TN UT WOS:000220050700001 PM 14975400 ER PT J AU Walker, RI Blanchard, T Braun, JM Cebra, JJ Cross, AS Fattom, A Giannasca, PJ Holder, IA Huebner, J Matthews, R Pier, GB Romani, L von Specht, BU AF Walker, RI Blanchard, T Braun, JM Cebra, JJ Cross, AS Fattom, A Giannasca, PJ Holder, IA Huebner, J Matthews, R Pier, GB Romani, L von Specht, BU TI Meeting summary - Possibilities for active and passive vaccination against opportunistic infections SO VACCINE LA English DT Editorial Material C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20851 USA. RP Walker, RI (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 425, Rockville, MD 20851 USA. EM walkerri@cber.fda.gov RI Braun, Jan/B-1001-2009; OI Pier, Gerald/0000-0002-9112-2331 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD FEB 17 PY 2004 VL 22 IS 7 BP 801 EP 804 DI 10.1016/j.vaccine.2003.11.042 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 778GL UT WOS:000189231100001 PM 15040930 ER PT J AU Kirma, N Ferreira, JL Baumstark, BR AF Kirma, N Ferreira, JL Baumstark, BR TI Characterization of six type A strains of Clostridium botulinum that contain type B toxin gene sequences SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE Clostridium botulinum; neurotoxin gene sequence; polymerase chain reaction ID NUCLEOTIDE-SEQUENCE; INFANT BOTULISM; NEUROTOXIN GENE; CLONING AB Six Clostridium botulinum isolates exhibiting type A toxicity as measured by the mouse bioassay were found to contain both type A and type B neurotoxin DNA sequences. The six strains were divided into three groups based on the DNA sequence of the type B neurotoxin gene. Members of each group exhibited 100% sequence identity over the 3876 by type B toxin open reading frame. The type B toxin sequence of all groups differed at more than 60 positions when compared to the BGB control strain. (C) 2003 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved. C1 Georgia State Univ, Dept Biol, Atlanta, GA 30302 USA. Food & Drug Adm, Atlanta, GA 30309 USA. RP Kirma, N (reprint author), Emory Univ, Sch Med, Div Endocrinol & Metab, 1639 Pierce Dr,WMB 1331, Atlanta, GA 30322 USA. EM nkirma@emory.edu NR 17 TC 20 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD FEB 16 PY 2004 VL 231 IS 2 BP 159 EP 164 DI 10.1016/S0378-1097(03)00911-X PG 6 WC Microbiology SC Microbiology GA 778LN UT WOS:000189243200002 PM 14987759 ER PT J AU Williams, TL Callahan, JH Monday, SR Feng, PCH Musser, SM AF Williams, TL Callahan, JH Monday, SR Feng, PCH Musser, SM TI Relative quantitation of intact proteins of bacterial cell extracts using coextracted proteins as internal standards SO ANALYTICAL CHEMISTRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; DESORPTION/IONIZATION MASS-SPECTROMETRY; NONPOROUS RP HPLC; COMPARATIVE PROTEOMICS; RAPID IDENTIFICATION; GEL-ELECTROPHORESIS; MAPPING METHOD; PHASE; SEPARATION; EXPRESSION AB A method for quantitating protein expression using LC/MS of whole proteins is described. This method is based on the fact that some proteins present in cells are abundant universal proteins whose expression levels exhibit little variation. This method demonstrates that these coextracted proteins can be used as internal standards to which the other proteins in the sample can be compared. By comparing the intensities of a selected protein to marker proteins, or internal standards, a relative ratio is obtained. This ratio can then be used to determine the relative amount of protein expression between cellular extracts. The validity of this approach is described for a standard protein mixture, as well as, E. coli cells that were known to differentially express green fluorescent protein. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Williams, TL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM tracie.williams@cfsan.fda.gov NR 29 TC 12 Z9 12 U1 0 U2 6 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 FEB 15 PY 2004 VL 76 IS 4 BP 1002 EP 1007 DI 10.1021/ac034820g PG 6 WC Chemistry, Analytical SC Chemistry GA 776QC UT WOS:000189127100018 PM 14961731 ER PT J AU Cohen, MH Williams, GA Sridhara, R Chen, G McGuinn, WD Morse, D Abraham, S Rahman, A Liang, CY Lostritto, R Baird, A Pazdur, R AF Cohen, MH Williams, GA Sridhara, R Chen, G McGuinn, WD Morse, D Abraham, S Rahman, A Liang, CY Lostritto, R Baird, A Pazdur, R TI United States Food and Drug Administration drug approval summary: Gefitinib (ZD1839; Iressa) tablets SO CLINICAL CANCER RESEARCH LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; INHIBITOR; ANTISENSE; CARCINOMA AB On May 5, 2003, gefitinib (Iressa; ZD1839) 250-mg tablets (AstraZeneca Inc.) received accelerated approval by the United States Food and Drug Administration as monotherapy for patients with locally advanced or metastatic non-small cell lung cancer after failure of both platinum-based and docetaxel chemotherapies. Information provided in this summary includes chemistry manufacturing and controls, clinical pharmacology, and clinical trial efficacy and safety results. Gefitinib is an anilinoquinazoline compound with the chemical name 4-quinazolinamine,N-(3-chloro-4-flurophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]. It has the molecular formula C22H24ClFN4O3. Gefitinib is often referred to as a "specific" or "selective" inhibitor of epidermal growth factor receptor. Studies demonstrate, however, that gefitinib inhibits the activity of other intracellular transmembrane tyrosine-specific protein kinases at concentrations similar to those at which it inhibits the epidermal growth factor signal. Maximum plasma concentrations resulting from clinically relevant doses are 0.5-1 mum or more, well within the IC50 values of several tyrosine kinases. No clinical studies have been performed that demonstrate a correlation between epidermal growth factor receptor expression and response to gefitinib. Gefitinib is 60% available after oral administration and is widely distributed throughout the body. Gefitinib is extensively metabolized in the liver by cytochrome P450 3A4 enzyme. Over a 10-day period., approximately 86% of an orally administered radioactive dose is recovered in the feces, with <4% of the dose in the urine. After daily oral administration, steady-state plasma levels are reached in 10 days and are 2-fold higher than those achieved after single doses. Gefitinib effectiveness was demonstrated in a randomized, double-blind, Phase II, multicenter trial comparing two oral doses of gefitinib (250 versus 500 mg/day). A total of 216 patients were enrolled. The 142 patients who were refractory to or intolerant of a platinum and docetaxel comprised the evaluable population for the efficacy analysis. A partial tumor response occurred in 14% (9 of 66) of patients receiving 250 mg/day gefitinib and in 8% (6 of 76) of patients receiving 500 mg/day gefitinib. The overall objective response rate (RR) for both doses combined was 10.6% (15 of 142 patients; 95% confidence interval, 6.0-16.8%). Responses were more frequent in females and in nonsmokers. The median duration of response was 7.0 months (range, 4.6-18.6+ months). Other submitted data included the results of two large trials conducted in chemotherapy-naive, stage III and IV non-small cell lung cancer patients. Patients were randomized to receive gefitinib (250 or 500 mg daily) or placebo, in combination with either gemcitabine plus cisplatin (n = 1093) or carboplatin plus paclitaxel (n = 1037). Results from this study showed no benefit (RR, time to progression, or survival) from adding gefitinib to chemotherapy. Consequently, gefinitib is only recommended for use as monotherapy. Common adverse events associated with gefitinib treatment included diarrhea, rash, acne, dry skin, nausea, and vomiting. Interstitial lung disease has been observed in patients receiving gefitinib. Worldwide, the incidence of interstitial lung disease was about 1% (2% in the Japanese postmarketing experience and about 0.3% in a United States expanded access program). Approximately one-third of the cases have been fatal. Gefitinib was approved under accelerated approval regulations on the basis of a surrogate end point, RR. No controlled gefitinib trials, to date, demonstrate a clinical benefit, such as improvement in disease-related symptoms or increased survival. Accelerated approval regulations require the sponsor to conduct additional studies to verify that gefitinib therapy produces such benefit. C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & res, Rockville, MD 20857 USA. RP US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & res, HFD 150,5600 Fishers Lane, Rockville, MD 20857 USA. EM cohenma@cder.fda.gov NR 14 TC 304 Z9 316 U1 0 U2 19 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 15 PY 2004 VL 10 IS 4 BP 1212 EP 1218 DI 10.1158/1078-0432.CCR-03-0564 PG 7 WC Oncology SC Oncology GA 776JE UT WOS:000189112200003 PM 14977817 ER PT J AU Liang, XJ Yin, JJ Zhou, JW Wang, PC Taylor, B Cardarelli, C Kozar, M Forte, R Aszalos, A Gottesman, MM AF Liang, XJ Yin, JJ Zhou, JW Wang, PC Taylor, B Cardarelli, C Kozar, M Forte, R Aszalos, A Gottesman, MM TI Changes in biophysical parameters of plasma membranes influence cisplatin resistance of sensitive and resistant epidermal carcinoma cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE cisplatin resistance; heptadecanoic acid; plasma membrane fluidity; membrane potential; fluorescence polarization; human epidermal carcinoma KB cells ID MULTIDRUG-RESISTANCE; INDUCED APOPTOSIS; DNA DAMAGE; LINES; ACCUMULATION; PACKING; DRUGS; ACID AB The mechanism of resistance of cancer cells to the anticancer drug cisplatin is not fully understood. Using cisplatin-sensitive KB-3-1 and -resistant KCP-20 cells, we found that the resistant cells have higher membrane potential, as determined by membrane potential sensing oxonol dye. Electron spin resonance and fluorescence polarization studies revealed that the-resistant cells have more "fluid" plasma membranes than the sensitive cells. Because of this observed difference in membrane "fluidity," we attempted modification of the plasma membrane fluidity by the incorporation of heptadecanoic acid into KB-3-1 and KCP-20 cell membranes. We found that such treatment resulted in increased heptadecanoic acid content and increased fluidity in the plasma membranes of both cell types, and also resulted in increased cisplatin resistance in the KCP-20 cells. This finding is in accord with our results, which showed that the cisplatin-resistant KCP-20 cells have more fluid membranes than the cisplatin-sensitive KB-3-1 cells. It remains to be determined whether the observed differences in biophysical status and/or fatty acid composition alone, or the secondary effect of these differences on the structure or function of some transmembrane protein(s), is the reason for increased cisplatin resistance. (C) 2003 Elsevier Inc. All rights reserved. C1 NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. US FDA, Instrumentat & Biophys Branch, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Howard Univ, Dept Radiol, Washington, DC 20060 USA. Walter Reed Army Inst Res, Div Expt Therapeut, Silver Spring, MD 20910 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Canc Res Ctr, NIH, Room 1A-09,37 Convent Dr, Bethesda, MD 20892 USA. EM mgottesman@nih.gov RI Kozar, Michael/A-9155-2011; Yin, Jun Jie /E-5619-2014 NR 31 TC 18 Z9 26 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD FEB 15 PY 2004 VL 293 IS 2 BP 283 EP 291 DI 10.1016/j.yexcr.2003.10.012 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 767QB UT WOS:000188462700011 PM 14729466 ER PT J AU Nayak, R Stewart, T Wang, RF Lin, J Cerniglia, CE Kenney, PB AF Nayak, R Stewart, T Wang, RF Lin, J Cerniglia, CE Kenney, PB TI Genetic diversity and virulence gene determinants of antibiotic-resistant Salmonella isolated from preharvest turkey production sources SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Salmonella; molecular typing; antibiotic resistance; Turkey ID POLYMERASE CHAIN-REACTION; PRODUCTION FACILITY; FOOD ANIMALS; TYPHIMURIUM; ENTERITIDIS; ENTERICA; INVA; PCR; SEQUENCE; SEROVARS AB This study evaluated the molecular diversity of 29 Salmonella serotypes isolated from turkey ceca and the production environment. Isolates were resistant to bacitracin (100%), erythromycin (100%), novobiocin (100%), rifampin (100%), streptomycin (62%), gentamicin (52%), spectinomycin (48%), tetracycline (31%), sulfamethoxazole/trimethoprim (SXT) (3%) and tobramycin (3%). The minimum inhibitory concentration (MIC) values ranged from 32 to greater than or equal to 1024 mug/ml. The pulsed-field gel electrophoresis (PFGE) and ribotyping patterns were identical within each of the scrotypes Heidelberg, Worthington and Muenster. The plasmid profiles were identical within each of the Salmonella serotypes. Two different clones of Salmonella anatum were differentiated by PFGE typing but not by ribotyping. Heidelberg isolates from nine turkey ceca and three drinker samples had identical antibiotic resistance, PFGE, ribotype and plasmid patterns, Suggesting that transmission of this particular clone may have occurred between the birds and the drinkers. Identical PFGE, ribotype and plasmid patterns were observed ill one Salmonella worthington isolate from turkey ceca in one flock and two S. worthington isolates front feeder contents and drinkers from a subsequent flock, suggesting transmission of this pathogen between flocks. Individual and Multiple polymerase chain reaction (PCR) analyses revealed the presence of the virulence genes invA, aceK and sopB and the absence of the h-1i gene in all isolates. A combination of genotypic and phenotypic markers can be useful in studying genetic variation among natural salmonellae Populations in turkey production and delineating possible transmission pathways. (C) 2003 Elsevier B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Pacific Reg Lab SW, Los Angeles, CA 90015 USA. W Virginia Univ, Div Anim & Vet Sci, Morgantown, WV 26505 USA. RP Nayak, R (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM RNayak@nctr.fda.gov NR 39 TC 41 Z9 43 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD FEB 15 PY 2004 VL 91 IS 1 BP 51 EP 62 DI 10.1016/S0168-1605(03)00330-1 PG 12 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 780PG UT WOS:000189389700006 PM 14967560 ER PT J AU Sheikh, F Baurin, VV Antes, A Shah, NK Smirnov, SV Anantha, S Dickensheets, H Dumoutier, L Renauld, JC Zdanov, A Donnelly, RP Kotenko, SV AF Sheikh, F Baurin, VV Antes, A Shah, NK Smirnov, SV Anantha, S Dickensheets, H Dumoutier, L Renauld, JC Zdanov, A Donnelly, RP Kotenko, SV TI Cutting edge: IL-26 signals through a novel receptor complex composed of IEL-20 receptor 1 and IL-10 receptor 2 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID II CYTOKINE RECEPTOR; INDUCIBLE FACTOR; INTERLEUKIN-10; IDENTIFICATION; CLONING; FAMILY; HOMOLOG; CHAIN; CELLS C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. NCI, Prot Struct Sect, Macromol Crystallog Lab, Canc Res Ctr,NIH, Ft Detrick, MD 21702 USA. Univ Louvain, Ludwig Inst Canc Res, Brussels, Belgium. Univ Louvain, Expt Med Unit, Christian De Duvre Inst Cellular Pathol, Brussels, Belgium. RP Kotenko, SV (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, 185 S Orange Ave,Room E-641, Newark, NJ 07103 USA. EM kotenkse@umdnj.edu FU NIAID NIH HHS [R01 AI51139, R01 AI051139] NR 22 TC 93 Z9 106 U1 1 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 2004 VL 172 IS 4 BP 2006 EP 2010 PG 5 WC Immunology SC Immunology GA 771LZ UT WOS:000188788600004 PM 14764663 ER PT J AU Yu, LX Carlin, AS Amidon, GL Hussain, AS AF Yu, LX Carlin, AS Amidon, GL Hussain, AS TI Feasibility studies of utilizing disk intrinsic dissolution rate to classify drugs SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE disk intrinsic dissolution rate; biopharmaceutics classification system; dissolution; solubility ID CLASSIFICATION AB The purpose of this report was to investigate the feasibility of using disk intrinsic dissolution rate (DIDR) to determine solubility class membership. We employed a VanKel dissolution apparatus fitted with a Wood's intrinsic dissolution die. To test the robustness of the method, variations of DIDR with compression force, dissolution volume, distance of the drug disk from the bottom of the dissolution vessel, and drug disk rotation speed were studied using furosemide and metoprolol in pH 4.5 acetate buffer as a model system. The DIDRs of six low solubility and nine high solubility model drugs were then determined at pH 1.2, 4.5, and 6.8 and compared to their BCS solubility class membership. It was found that the compression force, dissolution medium volume, and die position had no significant effect on DIDR for the system studied. The proposed compression force, dissolution volume, die position, and rotation speed are 2000 psi, 900 ml, 0.5 in., and 100 rpm, respectively. The test results obtained from 15 model BCS drugs show a good relationship between the DIDR and BCS solubility classification with 0.1 mg/min/cm(2) as a class boundary unless the dose is either extremely low or high where discrepancies may exist between the solubility and DIDR methods. Therefore, more scientific research and debates are needed before considered for regulatory purpose. (C) 2003 Published by Elsevier B.V. C1 US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Univ Michigan, Coll Pharm, Dept Pharmaceut, Ann Arbor, MI 48109 USA. RP Yu, LX (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, 5600 Fishers Lane, Rockville, MD 20857 USA. EM yul@cder.fda.gov NR 14 TC 80 Z9 84 U1 2 U2 16 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 FEB 11 PY 2004 VL 270 IS 1-2 BP 221 EP 227 DI 10.1016/j.ijpharm.2003.10.016 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 768BY UT WOS:000188509400021 PM 14726137 ER PT J AU Yu, HN Yin, JJ Shen, SR AF Yu, HN Yin, JJ Shen, SR TI Growth inhibition of prostate cancer cells by epigallocatechin gallate in the presenceof Cu2+ SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Epigallocatechin gallate Cu2+; PCA cells; chemiluminescence intensity; free radicals ID GREEN TEA; (-)-EPIGALLOCATECHIN GALLATE; METAL-IONS; CATECHINS; CONSTITUENT; COPPER AB Green tea is an effective chemopreventive agent to human prostate cancer adenoma (PCA). Epigallocatechin gallate (EGCG) inhibited the growth of PCA cells and induced apoptosis. Cu2+ is a trace element necessary to our health. Many studies proved that bioactivity of EGCG is altered in the presence of Cu2+. We investigated the effects of EGCG on PCA cells in the presence of Cu2+. Also, we explored potential mechanisms via measurement of the relative chemiluminescence of growth medium for PCA cells. Chemiluminscence can be an indication of free radicals. Our test results showed that the addition of EGCG and Cu2+ to the growth medium decreased the relative viability of androgen-sensitive and androgen-insensitive human prostate cancer cells. However, the effects of EGCG on PCA cells depended on (1) the relative concentrations of added EGCG and Cu2+ and (2) their order of addition. Our results indicated that few free radicals may be generated in vitro. If so, free radicals generated intracellularly may be a major factor behind apoptosis and growth inhibition observed in the PCA cells. Thus, EGCG might exert its effects intracellularly. 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 24 TC 30 Z9 36 U1 0 U2 2 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 11 PY 2004 VL 52 IS 3 BP 462 EP 466 DI 10.1021/jf035057u PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 772FH UT WOS:000188830300010 PM 14759133 ER PT J CA US Dept Agr US Food Drug Adm CDC TI Bovine spongiform encephalopathy in a dairy cow - Washington State, 2003 (Reprinted from MMWR, vol 52, pg 1280-1285, 2004) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Anim & Plant Hlth Inspect Serv, USDA, Washington, DC 20250 USA. Food Safety & Inspect Serv, USDA, Washington, DC 20250 USA. CDC, Div Vital Stat, Natl Ctr Hlth Stat, Atlanta, GA 30333 USA. CDC, Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. US FDA, Rockville, MD 20857 USA. RP Anim & Plant Hlth Inspect Serv, USDA, Washington, DC 20250 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 4 PY 2004 VL 291 IS 5 BP 553 EP 555 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 769LC UT WOS:000188650700006 ER PT J AU Duffy, PH Lewis, SM Mayhugh, MA Trotter, RW Thorn, BT Feuers, RJ Turturro, A AF Duffy, PH Lewis, SM Mayhugh, MA Trotter, RW Thorn, BT Feuers, RJ Turturro, A TI The effects of different levels of dietary restriction on non-neoplastic diseases in male Sprague-Dawley rats SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE aging; dietary restriction; non-neoplastic diseases; rats ID CHRONIC CALORIC RESTRICTION; FISCHER-344 RATS; BODY-WEIGHT; DOSE LEVELS; AD-LIBITUM; LIFE-SPAN; SURVIVAL; PATHOLOGY; GROWTH; INITIATION AB Background and aims: The primary purpose of the present study was to investigate the effects of 10, 25, and 40% dietary restriction (DR) on non-neoplastic diseases in rodents at 58 and 110 weeks of age, and to determine whether low-level DR (10 and 25%) can increase the survival rate and decrease variability in chronic bioassay studies. Methods: Male Sprague-Dawley (SD) rats (NCTR colony) were divided into four nutritional groups, consisting of an ad libitum (AL) group with unlimited access to the NIH-31 diet, and three dietary restricted (DR) groups given the NIH-31 diet reduced in amount by 10, 25, and 40%. Results: At 110 weeks of age, the incidence of cardiomyopathy was 95, 75, 45, and 15% for AL and 10, 25, and 40% DR rats, respectively; the incidence of nephropathy was 55, 20, 15, and 0% for AL and 10, 25, and 40% DR rats, respectively. The severity of chronic heart and kidney diseases was significantly reduced in all DR rat groups, with significant DR-dependent linear trends for these diseases. Moreover, DR prevented the progression of skin irritation to foot ulcers, and reduced the age-related degeneration in the adrenal, lacrimal, and thymus glands, and the liver. Conclusions: These results clearly indicate that even low DR levels were effective in preventing or slowing the progression of these non-neoplastic diseases. (C) 2004, Editrice Kurtis. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Bionet Corp, Jefferson, AR USA. Pathol Associates Int, Jefferson, AR USA. ROW Sci Inc, Jefferson, AR USA. US FDA, Natl Ctr Toxicol Res, Div Biometry, Jefferson, AR 72079 USA. US FDA, Div Chem, Jefferson, AR 72079 USA. RP Duffy, PH (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM pduffy@nctr.fda.gov NR 31 TC 11 Z9 11 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1594-0667 J9 AGING CLIN EXP RES JI Aging Clin. Exp. Res. PD FEB PY 2004 VL 16 IS 1 BP 68 EP 78 PG 11 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 810RN UT WOS:000220721500012 PM 15132295 ER PT J AU Wuilloud, JCA Gratz, SR Gamble, BM Wolnik, KA AF Wuilloud, JCA Gratz, SR Gamble, BM Wolnik, KA TI Simultaneous analysis of hepatotoxic pyrrolizidine alkaloids and N-oxides in comfrey root by LC-ion trap mass spectrometry SO ANALYST LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; COUNTERCURRENT CHROMATOGRAPHY; RUSSIAN COMFREY; BORAGINACEAE AB The purpose of the current study was to develop a LC-MSn method for the analysis of pyrrolizidine alkaloids (PAs) in comfrey. Published data presents an extensive list of PAs and their N-oxides present in comfrey. However, standards are not commercially available for any of the PAs typically present in cornfrey. Those PAs that are not stereoisomers were readily resolved on a C-18 column using a water-acetonitrile gradient as the mobile phase. The use of a selective technique, LC-MS/MS, allowed us to identify groups of PAs and their N-oxides, as well as identify the number of PAs present in each group, including those that were not completely resolved chromatographically. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Wuilloud, JCA (reprint author), US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. EM sgratz@ora.fda.gov NR 23 TC 23 Z9 23 U1 2 U2 11 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0003-2654 J9 ANALYST JI Analyst PD FEB PY 2004 VL 129 IS 2 BP 150 EP 156 DI 10.1039/b311030c PG 7 WC Chemistry, Analytical SC Chemistry GA 779MC UT WOS:000189303500013 PM 14752559 ER PT J AU Grant, MA AF Grant, MA TI Improved laboratory enrichment for enterohemorrhagic Escherichia coli by exposure to extremely acidic conditions SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID O157-H7; PREVALENCE; STRESS AB Analysis of food samples for E. coli O157:H7 using the standard U.S. Food and Drug Administration procedure is frequently complicated by overgrowth of nontarget microorganisms. A new procedure was developed for enrichment of enterohemorrhagic E. coli (EHEC) which utilizes exposure to pH 2.00 for 2 h. This procedure yielded larger populations of EHEC than the standard method by factors ranging from 2.7 to 7.7 and, when age-stressed cultures were used, by factors ranging from 2.7 to 11.5. Cultures of competing enterics were more effectively inhibited by the new enrichment protocol as well. C1 US FDA, Bothell, WA 98021 USA. RP Grant, MA (reprint author), US FDA, 22201 23rd Dr SE, Bothell, WA 98021 USA. EM mgrant@ora.fda.gov NR 20 TC 14 Z9 14 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD FEB PY 2004 VL 70 IS 2 BP 1226 EP 1230 DI 10.1128/AEM.70.2.1226-1230.2004 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 772RK UT WOS:000188854900074 PM 14766610 ER PT J AU Nowell, S Ratnasinghe, DL Ambrosone, CB Williams, S Teague-Ross, T Trimble, L Runnels, G Carrol, A Green, B Stone, A Johnson, D Greene, G Kadlubar, FF Lang, NP AF Nowell, S Ratnasinghe, DL Ambrosone, CB Williams, S Teague-Ross, T Trimble, L Runnels, G Carrol, A Green, B Stone, A Johnson, D Greene, G Kadlubar, FF Lang, NP TI Association of SULT1A1 phenotype and genotype with prostate cancer risk in African-Americans and Caucasians SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HETEROCYCLIC AMINES; BREAST-CANCER; HUMAN-PLATELET; IMMUNOHISTOCHEMICAL DETECTION; CYTOSOLIC SULFOTRANSFERASES; SULFATION PHARMACOGENETICS; BIOCHEMICAL-PROPERTIES; HEALTH-PROFESSIONALS; METABOLIC-ACTIVATION; COLORECTAL-CANCER AB Exposure to heterocyclic amines may increase prostate cancer risk. Human sulfotransferase 1A1 (SULT1A1) is involved in the bioactivation of some dietary procarcinogens, including the N-hydroxy metabolite of the food-borne heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo(4,5-b) pyridine. This study compares a polymorphism in the SULT1A1 gene, SULT1A1 enzyme activity, meat consumption, and the risk of prostate cancer in a population based case-control study. Prostate cancer patients (n = 464) and control individuals (n = 459), frequency matched on age and ethnicity, provided informed consent, answered a survey, and provided a blood sample. Platelets were isolated for phenotype analysis, and DNA was isolated from lymphocytes for genotype determination. Meat consumption was assessed using a dietary questionnaire. Caucasians homozygous for the SULT1A1*1 high activity allele were at increased risk for prostate cancer [odds ratio (OR), 1.68; 95% confidence interval (CI), 1.05-2.68] compared with individuals homozygous for the low-activity allele. The association between SULT1A1 genotype and prostate cancer risk in African-Americans did not reach significance (OR, 1.60; 95% CI, 0.46-5.62). When SULT1A1 activity was considered, there was a strong association between increased SULT1A1 activity and prostate cancer risk in Caucasians (OR, 3.04; 95% CI, 1.8-5.1 and OR, 4.96; 95% CI, 3.0-8.3, for the second and third tertiles of SULT1A1 activity, respectively) compared with individuals in the low enzyme activity tertile. A similar association was also found in African-American patients, with ORs of 6.7 and 9.6 for the second and third tertiles of SULT1A1 activity (95% CI, 2.1-21.3 and 2.9-31.3, respectively). When consumption of well-done meat was considered, there was increased risk of prostate cancer (OR, 1.42; 95% CI, 1.01-1.99 and OR, 1.68; 95% CI, 1.20-2.36 for the second and third tertiles, respectively). When SULT1A1 activity was stratified by tertiles of meat consumption, there was greater risk of prostate cancer in the highest tertile of meat consumption. These results indicate that variations in SULT1A1 activity contributes to prostate cancer risk and the magnitude of the association may differ by ethnicity and be modified by meat consumption. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Cent Arkansas Hlth Care Syst, Little Rock, AR USA. Roswell Pk Canc Inst, Div Canc Prevent & Populat Sci, Buffalo, NY 14263 USA. Univ Arkansas Med Sci, Coll Med, Dept Surg, Little Rock, AR 72205 USA. Arkansas Canc Res Ctr, Little Rock, AR USA. RP Nowell, S (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM snowell@nctr.fda.gov FU NCI NIH HHS [R01CA55751]; NIA NIH HHS [R01 AG15722-02] NR 57 TC 59 Z9 64 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2004 VL 13 IS 2 BP 270 EP 276 DI 10.1158/1055-9965.EPI-03-0047 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 774XG UT WOS:000189011200014 PM 14973106 ER PT J AU Pack, SD Alper, OM Stromberg, K Augustus, M Ozdemirli, M Miermont, AM Klus, G Rusin, M Slack, R Hacker, NF Ried, T Szallasi, Z Alper, O AF Pack, SD Alper, OM Stromberg, K Augustus, M Ozdemirli, M Miermont, AM Klus, G Rusin, M Slack, R Hacker, NF Ried, T Szallasi, Z Alper, O TI Simultaneous suppression of epidermal growth factor receptor and c-erbB-2 reverses aneuploidy and malignant phenotype of a human ovarian carcinoma cell line SO CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; CANCER CELLS; ZD1839 IRESSA; PROLIFERATION; AMPLIFICATION; APOPTOSIS; DOMAIN; PARP AB Coexpression of epidermal growth factor receptor (EGFR) and c-erbB-2 in 47-68% of ovarian cancer cells indicate their strong association with tumor formation. We examined the effects of simultaneous antisense- or immunosuppression of EGFR and c-erbB-2 expression on the invasive phenotype, aneuploidy, and genotype of cultured human ovarian carcinoma cells (NIH:OVCAR-8). We report here that suppression of both EGFR and c-erbB-2 results in regression of aneuploidy and genomic imbalances in NIH:OVCAR-8 cells, restores a more normal phenotype, and results in a more normal gene expression profile. Combined with cytogenetic analysis, our data demonstrate that the regression of aneuploidy is due to the selective apoptosis of double antisense transfected cells with highly abnormal karyotype. C1 NCI, NIH, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. NIAID, Immunopathol Lab, Bethesda, MD 20892 USA. US FDA, Div Therapeut Prot,NCI,NIH, Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Bethesda, MD 20014 USA. NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD USA. Georgetown Univ, Sch Med, Inst Mol & Human Genet, Vincent T Lombardi Canc Ctr, Washington, DC USA. Georgetown Univ, Sch Med, Pathol Lab, Vincent T Lombardi Canc Ctr, Washington, DC USA. Georgetown Univ, Sch Med, Dept Oncol, Vincent T Lombardi Canc Ctr, Washington, DC USA. Georgetown Univ, Sch Med, Dept Biostat, Vincent T Lombardi Canc Ctr, Washington, DC USA. Harvard Univ, Sch Med, Childrens Hosp Informat Program, Boston, MA 02115 USA. RP Alper, OM (reprint author), NCI, NIH, Human Carcinogenesis Lab, Bldg 10,Room 5D37,9000 Rockville Pike, Bethesda, MD 20892 USA. EM oa4@georgetown.edu RI Pack, Svetlana/C-2020-2014 FU NCI NIH HHS [2P30-CA-51008]; NCRR NIH HHS [1S10RR15768-01] NR 19 TC 26 Z9 28 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2004 VL 64 IS 3 BP 789 EP 794 DI 10.1158/0008-5472.CAN-03-1982 PG 6 WC Oncology SC Oncology GA 771VF UT WOS:000188806200002 PM 14871800 ER PT J AU Horn, EJ Albor, A Liu, YG El-Hizawi, S Vanderbeek, GE Babcock, M Bowden, GT Hennings, H Lozano, G Weinberg, WC Kulesz-Martin, M AF Horn, EJ Albor, A Liu, YG El-Hizawi, S Vanderbeek, GE Babcock, M Bowden, GT Hennings, H Lozano, G Weinberg, WC Kulesz-Martin, M TI RING protein Trim32 associated with skin carcinogenesis has anti-apoptotic and E3-ubiquitin ligase properties SO CARCINOGENESIS LA English DT Article ID INDUCED TERMINAL DIFFERENTIATION; MOUSE EPIDERMAL-CELLS; B-RADIATION; KERATINOCYTE APOPTOSIS; UBIQUITIN LIGASE; GENE-EXPRESSION; WILD-TYPE; P53; GROWTH; LOCALIZATION AB (Tri) under bar partite (m) under bar otif protein 32, Trim32, mRNA and protein expression was elevated in independently transformed and tumorigenic keratinocytes of a mouse epidermal carcinogenesis model, in ultraviolet B (UVB)-induced squamous cell carcinomas (SCC), and in similar to20-25% of chemically induced mouse papillomas and human head and neck SCCs. This suggests that elevated Trim32 expression occurs frequently in experimental epidermal carcinogenesis and is relevant to human cancer. Transduced Trim32 increased colony number in an epidermal in vitro transformation assay and epidermal thickening in vivo when skin-grafted to athymic nu/nu mice. These effects were not associated with proliferation and were not sufficient for tumorigenesis, even with 12-O-tetradecanoylphorbol-13-acetate treatment or defects in the tumor suppressor p53. However, transduced Trim32 inhibited the synergistic effect of tumor necrosis factor alpha (TNFalpha) on UVB-induced apoptosis of keratinocytes in vitro and the apoptotic response of keratinocyte grafts exposed to UVB-light in vivo. Consistent with its RING domain, Trim32 exhibited characteristics of E3-ubiquitin ligases, including being ubiquitylated itself and interacting with ubiquitylated proteins, with increases in these properties following treatment of cultured keratinocytes with TNFalpha/UVB. Interestingly, missense point mutation of human TRIM32 has been reported in Limb-Girdle Muscular Dystrophy Type 2H, an autosomal recessive disease. We propose a model in which Trim32 activities as an E3-ubiquitin ligase favor initiated cell survival in carcinogenesis by blocking UVB-induced TNFalpha apoptotic signaling. C1 Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Cell & Dev Biol, Portland, OR 97239 USA. SUNY Buffalo, Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA. Univ Arizona, Dept Radiat Oncol, Tucson, AZ 85724 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. US FDA, Immunobiol Lab, Rockville, MD 20857 USA. RP Kulesz-Martin, M (reprint author), Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97239 USA. EM kuleszma@ohsu.edu RI Weinberg, Wendy/A-8920-2009 FU NCI NIH HHS [CA16056, R01 CA098577, CA69533, CA31101] NR 43 TC 67 Z9 73 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 2004 VL 25 IS 2 BP 157 EP 167 DI 10.1093/carcin/bgh003 PG 11 WC Oncology SC Oncology GA 771NQ UT WOS:000188792800001 PM 14578165 ER PT J AU Allred, CD Allred, KF Ju, YH Clausen, LM Doerge, DR Schantz, SL Korol, DL Wallig, MA Helferich, WG AF Allred, CD Allred, KF Ju, YH Clausen, LM Doerge, DR Schantz, SL Korol, DL Wallig, MA Helferich, WG TI Dietary genistein results in larger MNU-induced, estrogen-dependent mammary tumors following ovariectomy of Sprague-Dawley rats SO CARCINOGENESIS LA English DT Article ID HORMONE REPLACEMENT THERAPY; BREAST-CANCER CELLS; POSTMENOPAUSAL WOMEN; N-NITROSOMETHYLUREA; STIMULATE GROWTH; MCF-7 TUMORS; SOY PROTEIN; INDUCTION; CHEMOPREVENTION; TUMORIGENESIS AB Due to the estrogenic properties of soy-derived isoflavones, many postmenopausal women are using these compounds as a natural alternative to hormone replacement therapy (HRT). How isoflavones impact breast cancer in postmenopausal women is important, because a majority of breast cancer cases occur in this age group. Chemical induction of mammary tumors in female rats has been used to determine that exposure of the mammary gland to soy isoflavones prior to tumor induction is protective against tumor formation. Here we investigate the effect of dietary genistein on mammary tumors that have already formed. The study was designed to determine the action of dietary genistein in a low endogenous estrogen environment as is observed in postmenopausal women. Animals were ovariectomized (OVX) after mammary tumor development and were then placed into one of three treatment groups: positive-control (OVX+ estradiol implant), genistein (OVX+ 750 p.p.m. genistein) and negative-control (OVX alone). Tumors were distinguished as malignant or benign by histopathological examination and were further characterized as either estrogen-dependent or estrogen-independent using immunohistochemistry to identify the presence of both estrogen receptor (ER) alpha and the progesterone receptor (PR). Genistein at 750 p.p.m. increased the weight of estrogen-dependent adenocarcinomas in ovariectomized rats compared with the negative-control animals. Genistein treatment also resulted in a higher percentage of proliferative cells in tumors and increased uterine weights when compared with negative-control animals. Collectively, these effects are probably due to the estrogenic activity of genistein. Plasma genistein concentrations in animals fed the isoflavone-containing diet were at physiological levels relevant to human exposure. Estradiol concentrations in ovariectomized animals not receiving an estradiol supplement were similar to those observed in postmenopausal women. The data suggest that in an endogenous estrogen environment similar to that of a postmenopausal woman, dietary genistein can stimulate the growth of a mammary carcinogen MNU-induced estrogen-dependent mammary tumors. C1 Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Illinois, Dept Vet Biosci, Urbana, IL 61802 USA. Univ Illinois, Dept Psychol, Champaign, IL 61820 USA. Univ Illinois, Dept Vet Pathobiol, Urbana, IL 61802 USA. RP Helferich, WG (reprint author), Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. EM helferic@uiuc.edu FU NCI NIH HHS [CA77355]; NIEHS NIH HHS [T32 ES 07320] NR 39 TC 91 Z9 101 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 2004 VL 25 IS 2 BP 211 EP 218 DI 10.1093/carcin/bgg198 PG 8 WC Oncology SC Oncology GA 771NQ UT WOS:000188792800007 PM 14578162 ER PT J AU Geho, DH Petricoin, EF Liotta, LA AF Geho, DH Petricoin, EF Liotta, LA TI Blasting into the microworld of tissue proteomics: A new window on cancer - Commentary re S. A. Schwartz et al, protein profiling in brain tumors using mass spectrometry: Feasibility of a new technique for the analysis of protein expression. Clin. Cancer Res., 10 : 981-987, 2004. SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID IMMOBILIZED PH GRADIENTS; PROSTATE-CANCER; 2-DIMENSIONAL ELECTROPHORESIS; PATTERNS; SERUM; MICROARRAYS C1 NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Food & Drug Adm, Ctr Biol Evaluat & Res, Bethesda, MD USA. Clin Proteom Program, Food & Drug Adm, NCI, Bethesda, MD USA. RP Liotta, LA (reprint author), NCI, Pathol Lab, Ctr Canc Res, Room 2A33,10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA. EM lance@helix.nih.gov NR 26 TC 15 Z9 15 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 1 PY 2004 VL 10 IS 3 BP 825 EP 827 DI 10.1158/1078-0432.CCR-1223-3 PG 3 WC Oncology SC Oncology GA 774MF UT WOS:000188982700003 PM 14871957 ER PT J AU Grube, M Rezvani, K Wiestner, A Fujiwara, H Sconocchia, G Melenhorst, JJ Hensel, N Marti, GE Kwak, LW Wilson, W Barrett, JA AF Grube, M Rezvani, K Wiestner, A Fujiwara, H Sconocchia, G Melenhorst, JJ Hensel, N Marti, GE Kwak, LW Wilson, W Barrett, JA TI Autoreactive, cytotoxic T lymphocytes specific for peptides derived from normal B-cell differentiation antigens in healthy individuals and patients with B-cell malignancies SO CLINICAL CANCER RESEARCH LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; RECEPTOR TRANSGENIC MICE; CANCER-IMMUNOTHERAPY; DENDRITIC CELLS; EXPRESSION; TOLERANCE; VACCINATION; LYMPHOMA; INDUCTION; THERAPY AB Purpose: To investigate potential immunotherapeutic strategies in B lymphocytic malignancies we looked for CTLs recognizing CD19 and CD20 epitopes. Experimental Design: Three CD19 and CD20 peptides binding to HLA-A*0201 were identified and used to detect peptide specific CTLs by a quantitative real-time PCR to measure IFN-gamma mRNA expression in 23 healthy individuals and 28 patients (18 chronic lymphocytic leukemia (CLL), 7 follicular lymphoma, 2 acute lymphocytic leukemia, and 1 large cell lymphoma). Peptide-specific CTLs were expanded in culture with CD40-activated B cells to test lytic activity in three patients. Results: In healthy individuals, CD8(+) T-cell responses were detected in one to CD19(74-82) in three to CD20(127-135), and three to CD20(188-196). Seven of 27 patients (6 with CLL) had CD8(+) T cells recognizing CD19(74-82). Seven patients responded to CD20(127-135) and three to CD20(188-196). All were CLL patients. CD1974-12-specific CTLs from three patients were expanded over 4 weeks. These cells were HLAA*0201 specific and lytic for peptide-loaded antigen-presenting cells but not to malignant or unpulsed B cells. Conclusions: CTLs that recognize CD19 and CD20 epitopes exist in healthy individuals and may be increased in CLL patients. They are of low avidity and require high doses of peptide for activation. Strategies to increase T-cell avidity would be necessary for T-cell immunotherapeutic approaches using the peptides studied. C1 NHLBI, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20892 USA. RP Barrett, JA (reprint author), NIH, Hematol Branch, Bldg 10,9000 Rockville Pike,Room 7C 103,, Bethesda, MD 20892 USA. EM barrettj@nih.gov NR 65 TC 12 Z9 12 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 1 PY 2004 VL 10 IS 3 BP 1047 EP 1056 DI 10.1158/1078-0432.CCR-03-0075 PG 10 WC Oncology SC Oncology GA 774MF UT WOS:000188982700030 PM 14871984 ER PT J AU Averbuch, M Katzper, M AF Averbuch, M Katzper, M TI Assessment of visual analog versus categorical scale for measurement of osteoarthritis acute pain. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 24-27, 2004 CL Miami Beach, FL SP Amer Soc Clin Pharmacol Therapeut C1 Tel Aviv Sourasky Med ctr, Tel Aviv, Israel. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2004 VL 75 IS 2 BP P4 EP P4 DI 10.1016/j.clpt.2003.11.012 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 774MA UT WOS:000188982200011 ER PT J AU Coster, TS Szarfman, A AF Coster, TS Szarfman, A TI Data mining analysis of psychosis with mefloquine and other antimalarial drugs. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 24-27, 2004 CL Miami Beach, FL SP Amer Soc Clin Pharmacol Therapeut C1 Walter Reed Army Inst Res, Silver Spring, MD USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2004 VL 75 IS 2 BP P77 EP P77 DI 10.1016/j.clpt.2003.11.290 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 774MA UT WOS:000188982200285 ER PT J AU James, AJ Sun, H Parekh, A Doddapaneni, S Zhao, H Lee, P Hunt, J Malinowski, H Huang, S Lesko, L AF James, AJ Sun, H Parekh, A Doddapaneni, S Zhao, H Lee, P Hunt, J Malinowski, H Huang, S Lesko, L TI Exposure-response relationship in adults and children for pediatric dose adjustment. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 24-27, 2004 CL Miami Beach, FL 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 2004 VL 75 IS 2 BP P75 EP P75 DI 10.1016/j.clpt.2003.11.284 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 774MA UT WOS:000188982200279 ER PT J AU Kenna, LA Parekh, A Jarugula, V Chatterjee, DJ Sun, H Kim, MJ Ortiz, S Hunt, JP Malinowski, H AF Kenna, LA Parekh, A Jarugula, V Chatterjee, DJ Sun, H Kim, MJ Ortiz, S Hunt, JP Malinowski, H TI Experience evaluating QT prolongation data. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 24-27, 2004 CL Miami Beach, FL 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 2004 VL 75 IS 2 BP P7 EP P7 DI 10.1016/j.clpt.2003.11.026 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 774MA UT WOS:000188982200025 ER PT J AU Lee, SH Sun, H Chen, P Doddapaneni, S Hunt, J Malinowski, H AF Lee, SH Sun, H Chen, P Doddapaneni, S Hunt, J Malinowski, H TI Sensitivity/reliability of the time-matched baseline subtraction method in assessment of QTc interval prolongation. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 24-27, 2004 CL Miami Beach, FL SP Amer Soc Clin Pharmacol Therapeut C1 US FDA, 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 2004 VL 75 IS 2 BP P56 EP P56 DI 10.1016/j.clpt.2003.11.211 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 774MA UT WOS:000188982200206 ER PT J AU Sun, H Chen, P Kenna, L Lee, P AF Sun, H Chen, P Kenna, L Lee, P TI The chaotic QT interval variabilities on risk assessment trial designs. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 24-27, 2004 CL Miami Beach, FL SP Amer Soc Clin Pharmacol Therapeut C1 US FDA, CDER, OCPB, 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 2004 VL 75 IS 2 BP P55 EP P55 DI 10.1016/j.clpt.2003.11.210 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 774MA UT WOS:000188982200205 ER PT J AU Sun, H Chen, P Hunt, J Malinowski, H AF Sun, H Chen, P Hunt, J Malinowski, H TI Frequency of QT recording and the reliability of QT prolongation assessments. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 24-27, 2004 CL Miami Beach, FL SP Amer Soc Clin Pharmacol Therapeut C1 US FDA, CDER, OCPB, 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 2004 VL 75 IS 2 BP P48 EP P48 DI 10.1016/j.clpt.2003.11.182 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 774MA UT WOS:000188982200177 ER PT J AU Sun, H Lau, SW Louis, A Lee, P Hunt, J Malinowski, H Lesko, L AF Sun, H Lau, SW Louis, A Lee, P Hunt, J Malinowski, H Lesko, L TI Survey based FDA experience on submissions with population analysis and/or studies. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 24-27, 2004 CL Miami Beach, FL SP Amer Soc Clin Pharmacol Therapeut C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 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 2004 VL 75 IS 2 BP P8 EP P8 DI 10.1016/j.clpt.2003.11.031 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 774MA UT WOS:000188982200029 ER PT J AU Petricoin, EF Liotta, LA AF Petricoin, EF Liotta, LA TI SELDI-TOF-based serum proteomic pattern diagnostics for early detection of cancer SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID MOLECULAR WEIGHT PROTEINS; PROSTATE-CANCER; IDENTIFICATION; DISCOVERY AB Proteomics is more than just generating lists of proteins that increase or decrease in expression as a cause or consequence of pathology. The goal should be to characterize the information flow through the intercellular protein circuitry that communicates with the extracellular microenvironment and then ultimately to the serum/plasma macroenvironment. The nature of this information can be a cause, or a consequence, of disease and toxicity-based processes. Serum proteomic pattern diagnostics is a new type of proteomic platform in which patterns of proteomic signatures from high dimensional mass spectrometry data are used as a diagnostic classifier. This approach has recently shown tremendous promise in the detection of early-stage cancers. The biomarkers found by SELDI-TOF-based pattern recognition analysis are mostly low molecular weight fragments produced at the specific tumor microenvironment. C1 US FDA, Ctr Biol Evaluat & Res, Off Cell & Gene Teherapies, FDA NCI Clin Proteom Program, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Pathol Lab, FDA NCI Clin Proteom Program,NIH, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Cell & Gene Teherapies, FDA NCI Clin Proteom Program, Bethesda, MD 20892 USA. EM petricoin@cber.fda.gov NR 22 TC 228 Z9 255 U1 2 U2 10 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD FEB PY 2004 VL 15 IS 1 BP 24 EP 30 DI 10.1016/j.copbio.2004.01.005 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 780EC UT WOS:000189358300005 PM 15102462 ER PT J AU Ginsberg, G Slikker, W Bruckner, J Sonawane, B AF Ginsberg, G Slikker, W Bruckner, J Sonawane, B TI Incorporating children's toxicokinetics into a risk framework SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE children; dosimetry; risk assessment; toxicokinetics ID PHYSIOLOGICALLY-BASED MODELS; BONE-SEEKING ELEMENTS; AGE-RELATED-CHANGES; HUMAN-LIVER; PLACENTAL-TRANSFER; RAT-LIVER; DEVELOPMENTAL EXPRESSION; CLINICAL PHARMACOKINETICS; CYTOCHROME-P450 ENZYMES; POSTNATAL-DEVELOPMENT AB Children's responses to environmental toxicants will be affected by the way in which their systems absorb, distribute, metabolize, and excrete chemicals. These toxicokinetic factors vary during development, from in utero where maternal and placental processes play a large role, to the neonate in which emerging metabolism and clearance pathways are key determinants. Toxicokinetic differences between neonates and adults lead to the potential for internal dosimetry differences and increased or decreased risk, depending on the mechanisms for toxicity and clearance of a given chemical. This article raises a number of questions that need to be addressed when conducting a toxicokinetic analysis of in utero or childhood exposures. These questions are organized into a proposed framework for conducting the assessment that involves problem formulation (identification of early life stage toxicokinetic factors and chemical-specific factors that may raise questions/concerns for children); data analysis (development of analytic approach, construction of child/adult or child/animal dosimetry comparisons); and risk characterization (evaluation of how children's toxicokinetic analysis can be used to decrease uncertainties in the risk assessment). The proposed approach provides a range of analytical options, from qualitative to quantitative, for assessing children's dosimetry. Further, it provides background information on a variety of toxicokinetic factors that can vary as a function of developmental stage. For example, the ontology of metabolizing systems is described via reference to pediatric studies involving therapeutic drugs and evidence from in vitro enzyme studies. This type of resource information is intended to help the assessor begin to address the issues raised in this paper. C1 Connecticut Dept Publ Hlth, Hartford, CT 06134 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Georgia, Athens, GA 30602 USA. US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Washington, DC 20460 USA. RP Ginsberg, G (reprint author), Connecticut Dept Publ Hlth, 410 Capitol Ave,Mail Stop 11CHA, Hartford, CT 06134 USA. EM gary.ginsberg@po.state.ct.us NR 156 TC 41 Z9 42 U1 1 U2 5 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 FEB PY 2004 VL 112 IS 2 BP 272 EP 283 DI 10.1289/ehp.6013 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 776ZQ UT WOS:000189149800044 PM 14754583 ER PT J AU Baldwin, RL Chelonis, JJ Flake, RA Edwards, MC Feild, CR Meaux, JB Paule, MG AF Baldwin, RL Chelonis, JJ Flake, RA Edwards, MC Feild, CR Meaux, JB Paule, MG TI Effect of methylphenidate on time perception in children with attention-deficit/hyperactivity disorder SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Association-for-Behavior-Analysis CY MAY, 2002 CL TORONTO, CANADA SP Assoc Behav Anal ID DEFICIT HYPERACTIVITY DISORDER; BEHAVIORAL-TEST BATTERY; MEMORY; ADHD; PERFORMANCE; ADOLESCENTS; AMPHETAMINE AB The effects of methylphenidate (MPH) on performance of a time-production task were studied in 17 children with attention-deficit/hyperactivity disorder who participated in 1 test session on and 1 off MPH. Participants held a response lever down for at least 10 but no longer than 14 s. Administration of MPH had no effect on the number of correct responses or on the mean duration of lever holds. MPH administration significantly decreased timing response variability, increased holds of 10- to 11-s duration, and decreased lever holds of extremely short durations. These results indicate that administration of MPH resulted in more precise timing performance without changing the mean duration of lever holds, suggesting an enhancement in working memory. C1 Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Pediat, Little Rock, AR 72202 USA. Univ Arkansas, Dept Psychol, Little Rock, AR 72204 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Cent Arkansas, Dept Nursing, Conway, AR 72035 USA. RP Baldwin, RL (reprint author), Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Pediat, 800 Marshall St, Little Rock, AR 72202 USA. EM baldwinronaldL@uams.edu NR 35 TC 28 Z9 29 U1 1 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD FEB PY 2004 VL 12 IS 1 BP 57 EP 64 DI 10.1037/1064-1297.12.1.57 PG 8 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 770GB UT WOS:000188713900010 PM 14769100 ER PT J AU Buchanan, RL Edelson-Mammel, SG Boyd, G Marmer, BS AF Buchanan, RL Edelson-Mammel, SG Boyd, G Marmer, BS TI Influence of acidulant identity on the effects of pH and acid resistance on the radiation resistance of Escherichia coli O157 : H7 SO FOOD MICROBIOLOGY LA English DT Article DE organic acids; cross-protection; acid tolerance; irradiation ID STATIONARY-PHASE; ORGANIC-ACIDS; FRUIT JUICES; APPLE JUICE; REDUCED PH; TOLERANCE; SURVIVAL; INACTIVATION; IRRADIATION; SALMONELLA AB The effects of pH (4.0-5.5), acid identity (acetic, citric, lactic, malic, and hydrochloric), and the induction of pH-dependent stationary phase acid resistance on the radiation resistance of E. coli 0 1 57:H7 Ent-C9490 was studied using cells grown in Tryptic Soy Broth with and without dextrose (induced and non-induced to acid resistance) and then resuspended in brain-heart infusion broth containing 5 g/l of an organic acid and acidified with concentrated hydrochloric acid. After treatment with gamma radiation, the number of survivors was determined by plating on brain-heart infusion agar (injured and non-injured cells) and MacConkey agar (non-injured cells), and the data used to calculate radiation D-values. The induction of pH-dependent stationary phase acid resistance consistently provided the enterohemorrhagic E. coli strain cross-protection from subsequent irradiation, increasing radiation D-values by 1.2-3.3-fold, depending on the organic acid present. The radiation resistance of E. coli varied with acid identity, but was largely unaffected by pH within the range examined. The results indicate that induction of cross-protection resulting from induction of acid resistance is a factor that should be considered to accurately determine the radiation dose needed to inactivate enterohemorrhagic E. coli in foods. (C) 2003 Elsevier Ltd. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. USDA ARS, ERRC, Wyndmoor, PA 19038 USA. RP Buchanan, RL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 14 TC 20 Z9 20 U1 0 U2 6 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 FEB PY 2004 VL 21 IS 1 BP 51 EP 57 DI 10.1016/S0740-0020(03)00039-X PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 759WP UT WOS:000187774400007 ER PT J AU Fleischman, GJ Ravishankar, S Balasubramaniam, VM AF Fleischman, GJ Ravishankar, S Balasubramaniam, VM TI The inactivation of Listeria monocytogenes by pulsed electric field (PEF) treatment in a static chamber SO FOOD MICROBIOLOGY LA English DT Article DE gellan gum; gel; Listeria; pulsed electric field; static chamber; milk ID ESCHERICHIA-COLI O157-H7; LACTOBACILLUS-BREVIS; SKIM MILK; KINETICS; INNOCUA AB An experimental analysis of the effect of pulsed electric field (PEF) energy on the inactivation of Listeria monocytogenes was conducted using a custom-designed static chamber and a gel suspension medium for treatment. This allowed PEF energy to be delivered to the suspension under near isothermal conditions. The effects of variations in the number of pulses (5-50 pulses), electric field strength (15-30 kV/cm), temperature (0-60degreesC) and media bases (water and skim milk) on the inactivation of L. monocytogenes were examined. At temperatures less than 50degreesC a maximum of I log reduction was obtained for L. monocytogenes regardless of pulse number or electric field strength within the ranges examined. In skim milk no reduction occurred. At 50degreesC and 55degreesC synergy between PEF and thermal energy was observed. The experimental approach separated the contribution of PEF and thermal energy to total kill and thus allowed this synergy to be quantified. At 55degreesC the kill due to PEF energy increased to 4.5 logs with another 4.5 logs reduction attributable to thermal energy. It appears that under the conditions of this study PEF alone has a very limited effect on the reduction of L. monocytogenes. However, the addition of thermal energy not only contributed to the kill, but also increased the susceptibility of L. monocytogenes to PEF energy. Published by Elsevier Science Ltd. C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Fleischman, GJ (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. RI Balasubramaniam, VM Bala/A-2576-2008 OI Balasubramaniam, VM Bala/0000-0002-1540-4273 NR 12 TC 35 Z9 37 U1 2 U2 11 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 FEB PY 2004 VL 21 IS 1 BP 91 EP 95 DI 10.1016/S0740-0020(03)00015-7 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 759WP UT WOS:000187774400013 ER PT J AU Buntin, MB Garber, AM McClellan, M Newhouse, JP AF Buntin, MB Garber, AM McClellan, M Newhouse, JP TI The costs of decedents in the Medicare program: Implications for payments to Medicare plus choice plans SO HEALTH SERVICES RESEARCH LA English DT Article DE Medicare; risk adjustment; managed care; end-of-life costs ID FEE-FOR-SERVICE; LAST YEAR; DEATH; LIFE; BENEFICIARIES; HOSPICE; CANCER; CARE; DIE; HMO AB Objective. To discuss and quantify the incentives that Medicare managed care plans have to avoid (through selective enrollment or disenrollment) people who are at risk for very high costs, focusing on Medicare beneficiaries in the last year of life-a group that accounts for more than one-quarter of Medicare's annual expenditures. Data Source. Medicare administrative claims for 1994 and 1995. Study Design. We calculated the payment a plan would have received under three risk-adjustment systems for each beneficiary in our 1995 sample based on his or her age, gender, county of residence, original reason for Medicare entitlement, and principal inpatient diagnoses received during any hospital stays in 1994. We compared these amounts to the actual costs incurred by those beneficiaries. We then looked for clinical categories that were predictive of costs, including costs in a beneficiary's last year of life, not accounted for by the risk adjusters. Data Extraction Methods. The analyses were conducted using claims for a 5 percent random sample of Medicare beneficiaries who died in 1995 and a matched group of survivors. Principal Findings. Medicare is currently implementing the Principal Inpatient Diagnostic Cost Groups (PIP-DCG) risk adjustment payment system to address the problem of risk selection in the Medicare+Choice program. We quantify the strong financial disincentives to enroll terminally ill beneficiaries that plans still have under this risk adjustment system. We also show that up to one-third of the selection observed between Medicare HMOs and the traditional fee-for-service system could be due to differential enrollment of decedents. A risk adjustment system that incorporated more of the available diagnostic information would attenuate this disincentive; however, plans could still use clinical information (not included in the risk adjustment scheme) to identify beneficiaries whose expected costs exceed expected payments. Conclusions. More disaggregated prospective risk adjustment methods and alternative payment systems that compensate plans for delivering care to certain classes of patients should be considered to ensure access to high-quality managed care for all beneficiaries. C1 RAND Hlth, Arlington, VA 22202 USA. Dept Vet Affairs, Palo Alto, CA USA. Stanford Univ, Stanford, CA 94305 USA. Food & Drug Adm, Rockville, MD USA. Harvard Univ, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Buntin, MB (reprint author), RAND Hlth, 1200 S Hayes St, Arlington, VA 22202 USA. RI Garber, Alan/F-1476-2010 FU NIA NIH HHS [AG 17253, AG05842, P01 AG005842, P30 AG017253] NR 22 TC 12 Z9 12 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD FEB PY 2004 VL 39 IS 1 BP 111 EP 130 PG 20 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 770YB UT WOS:000188758000009 PM 14965080 ER PT J AU Kumar, S Jones, TR Oakley, MS Zheng, H Kuppusamy, SP Taye, A Krieg, AM Stowers, AW Kaslow, DC Hoffman, SL AF Kumar, S Jones, TR Oakley, MS Zheng, H Kuppusamy, SP Taye, A Krieg, AM Stowers, AW Kaslow, DC Hoffman, SL TI CpG oligodeoxynucleotide and montanide ISA 51 adjuvant combination enhanced the protective efficacy of a subunit malaria vaccine SO INFECTION AND IMMUNITY LA English DT Article ID MEROZOITE SURFACE PROTEIN-1; CARBOXYL-TERMINAL FRAGMENT; PLASMODIUM-FALCIPARUM; AOTUS MONKEYS; INTERFERON-GAMMA; MONOCLONAL-ANTIBODIES; IMMUNE-RESPONSE; C-TERMINUS; NK CELLS; IN-VIVO AB Unmethylated CpG dinucleotide motifs present in bacterial genomes or synthetic oligodeoxynucleotides (ODNs) serve as strong immunostimulatory agents in mice, monkeys and humans. We determined the adjuvant effect of murine CpG ODN 1826 on the immunogenicity and protective efficacy of the Saccharomyces cerevisiae-expressed 19-kDa C-terminal region of merozoite surface protein 1 (yMSP1(19)) of the murine malaria parasite Plasmodium yoelli. We found that in C57BL/6 mice, following sporozoite challenge, the degree of protective immunity against malaria induced by yMSP1(19) in a formulation of Montanide ISA 51 (ISA) plus CpG ODN 1826 was similar or superior to that conferred by yMSP1(19) emulsified in complete Freund's adjuvant (CFA/incomplete Freund's adjuvant). In total, among mice immunized with yMSP1(19), 22 of 32 (68.7%) with ISA plus CpG 1826, 0 of 4 (0%) with CFA/incomplete Freund's adjuvant, 0 of 4 (0%) with CpG 1826 mixed with ISA (no yMSP1(19)), and 0 of 11 (0%) with CpG 1826 alone were completely protected against development of erythrocytic stage infection after sporozoite challenge. The adjuvant effect of CpG ODN 1826 was manifested as both significantly improved complete protection from malaria (defined as the absence of detectable erythrocytic form parasites) (P = 0.007, chi square) and reduced parasite burden in infected mice. In vivo depletions of interleukin-12 and gamma interferon cytokines and CD4(+) and CD8(+) T cells in vaccinated mice had no significant effect on immunity. On the other hand, immunoglobulin G (IgG) isotype levels appeared to correlate with protection. Inclusion of CpG ODN 1826 in the yMSP1(19) plus ISA vaccine contributed towards the induction of higher levels of IgG2a and IgG2b (Th1 type) antibodies, suggesting that CpG ODN 1826 caused a shift towards a Th1 type of immune response that could be responsible for the higher degree of protective immunity. Our results indicate that this potent adjuvant formulation should be further evaluated for use in clinical trials of recombinant malarial vaccine candidates. C1 Naval Med Res Ctr, Malaria Program, Silver Spring, MD 20910 USA. Johns Hopkins Univ, Bloomberg Sch Hyg & Publ Hlth, Dept Microbiol & Immunol, Baltimore, MD 21205 USA. Coley Pharmaceut Grp, Wellesley, MA 02481 USA. Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. NIAID, Malaria Vaccine Dev Unit, Bethesda, MD 20892 USA. RP Kumar, S (reprint author), US FDA, Bacterial & Parasit Dis Sect, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, HFM-313,1401 Rockville Pike, Rockville, MD 20852 USA. EM kumarS@cber.fda.gov NR 45 TC 45 Z9 48 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 2004 VL 72 IS 2 BP 949 EP 957 DI 10.1128/IAI.72.2.949-957.2004 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 771BV UT WOS:000188766400040 PM 14742540 ER PT J AU Debrabant, A Joshi, MB Pimenta, PFP Dwyer, DM AF Debrabant, A Joshi, MB Pimenta, PFP Dwyer, DM TI Generation of Leishmania donovani axenic amastigotes: their growth and biological characteristics SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Australian-Society-for-Parasitology CY 2003 CL Darwin, AUSTRALIA DE trypanosomatid; leishmaniasis; parasite; culture system; infectivity; virulence ID PROTOZOAN PARASITE LEISHMANIA; SECRETORY ACID-PHOSPHATASES; PROGRAMMED CELL-DEATH; FUNCTIONAL DOMAINS; GENE-EXPRESSION; PROMASTIGOTES; IDENTIFICATION; TRANSPORTER; PROTEIN; FAMILY AB In this report, we describe an in vitro culture system for the generation and propagation of axenic amastigotes from the well characterised 1S-CL2D line of Leishmania donovani. Fine structure analyses of these in vitro-grown amastigotes demonstrated that they possessed morphological features characteristic of L. donovani tissue-derived amastigotes. Further, these axenic amastigotes (LdAxAm) were shown to synthesise and release a secretory acid phosphatase isoform similar to that produced by intracellular amastigotes. Such LdAxAm also expressed surface membrane 3'-nucleotidase enzyme activity similar to that of tissue-derived amastigotes. Moreover, LdAxAm, in contrast to promastigotes, expressed significant levels of the amastigote-specific A2 proteins. In addition, LdAxAm, derived from long term cultures of Ld 1S-CL2D promastigotes, had significant infectivity for both human macrophages in vitro and for hamsters in vivo. Thus, the in vitro culture system described herein provides a useful tool for the generation of large quantities of uniform populations of axenic amastigotes of the L. donovani 1S-CL2D line. The availability of such material should greatly facilitate studies concerning the cell and molecular biology of this parasite developmental stage. (C) 2003 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved. C1 NIAID, Cell Biol Sect, Parasit Dis Lab, Div Intramural Res,NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Bethesda, MD USA. Fdn Oswaldo Cruz, Ctr Pesquisas Rene Rachou, Lab Med Entomol, Belo Horizonte, MG, Brazil. RP Dwyer, DM (reprint author), NIAID, Cell Biol Sect, Parasit Dis Lab, Div Intramural Res,NIH, Bldg 4,Room 126, Bethesda, MD 20892 USA. EM ddwyer@niaid.nih.gov NR 44 TC 131 Z9 137 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0020-7519 J9 INT J PARASITOL JI Int. J. Parasit. PD FEB PY 2004 VL 34 IS 2 BP 205 EP 217 DI 10.1016/j.ijpara.2003.10.011 PG 13 WC Parasitology SC Parasitology GA 801FU UT WOS:000220082600008 PM 15037106 ER PT J AU Vann, WF Daines, DA Murkin, AS Tanner, ME Chaffin, DO Rubens, CE Vionnet, J Silver, RP AF Vann, WF Daines, DA Murkin, AS Tanner, ME Chaffin, DO Rubens, CE Vionnet, J Silver, RP TI The NeuC protein of Escherichia coli K1 is a UDP N-acetylglucosamine 2-epimerase SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ACETYLNEURAMINIC ACID SYNTHETASE; POLYSACCHARIDE BIOSYNTHESIS; POLYSIALIC ACID; SIALIC-ACID; 2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE; NEISSERIA-MENINGITIDIS; GENE-PRODUCT; RAT-LIVER; EXPRESSION; SEQUENCE AB The K1 capsule is an essential virulence determinant of Escherichia coli strains that cause meningitis in neonates. Biosynthesis and transport of the capsule, an alpha-2,8-linked polymer of sialic acid, are encoded by the 17-kb kps gene cluster. We deleted neuC, a K1 gene implicated in sialic acid synthesis, from the chromosome of EV36, a K-12-K1 hybrid, by allelic exchange. Exogenously added sialic acid restored capsule expression to the deletion strain (DeltaneuC), confirming that NeuC is necessary for sialic acid synthesis. The deduced amino acid sequence of NeuC showed similarities to those of UDP-N-acetylglucosamine (GlcNAc) 2-epimerases from both prokaryotes and eukaryotes. The NeuC homologue from serotype III Streptococcus agalactiae complements DeltaneuC. We cloned the neuC gene into an intein expression vector to facilitate purification. We demonstrated by paper chromatography that the purified neuC gene product catalyzed the formation of [2-C-14]acetamidoglucal and [N-C-14]acetylmannosamine (ManNAc) from UDP-[C-14]GlcNAc. The formation of reaction intermediate 2-acetamidoglucal with the concomitant release of UDP was confirmed by proton and phosphorus nuclear magnetic resonance spectroscopy. NeuC could not use GlcNAc as a substrate. These data suggest that neuC encodes an epimerase that catalyzes the formation of ManNAc from UDP-GlcNAc via a 2-acetamidoglucal intermediate. The unexpected release of the glucal intermediate and the extremely low rate of ManNAc formation likely were a result of the in vitro assay conditions, in which a key regulatory molecule or protein was absent. C1 US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Toxins, Bethesda, MD 20892 USA. Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA. Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada. Univ Washington, Childrens Hosp & Reg Med Ctr, Dept Pediat, Seattle, WA 98105 USA. RP Vann, WF (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Toxins, Bethesda, MD 20892 USA. EM wvann@helix.nih.gov RI Murkin, Andrew/K-3146-2012 OI Murkin, Andrew/0000-0002-2559-4605 FU NIAID NIH HHS [AI22498, AI25152, AI39615, AI07362, R01 AI022498, T32 AI007362] NR 43 TC 25 Z9 26 U1 1 U2 6 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 2004 VL 186 IS 3 BP 706 EP 712 DI 10.1128/JB.186.3.706-712.2004 PG 7 WC Microbiology SC Microbiology GA 766HU UT WOS:000188371600014 PM 14729696 ER PT J AU Spencer, SE Valentin-Bon, IE Whaley, K Jerse, AE AF Spencer, SE Valentin-Bon, IE Whaley, K Jerse, AE TI Inhibition of Neisseria gonorrhoeae genital tract infection by leading-candidate topical microbicides in a mouse model SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 3rd Workshop on Topical Microbicides Pre-Clinical CY JAN 31-FEB 01, 2001 CL BALTIMORE, MARYLAND ID SEXUALLY-TRANSMITTED-DISEASES; HUMAN-IMMUNODEFICIENCY-VIRUS; HERPES-SIMPLEX-VIRUS; CELLULOSE SULFATE; VAGINAL MICROBICIDES; BACTERIAL VAGINOSIS; PRO 2000; PHASE-I; PREVENTION; TOLERANCE AB The development of effective vaginal microbicides is paramount in the fight against the spread of sexually transmitted infections. Preclinical testing of candidate microbicides for the prevention of gonorrhea has been seriously hindered by the lack of an animal model. We assessed the efficacy of 7 promising formulated agents CarraGuard, Ushercell, [poly] sodium 4-styrene sulfonate (T-PSS), PRO 2000, ACIDFORM, cellulose acetate phthalate (CAP), and BufferGel - by use of a mouse model of Neisseria gonorrhoeae genital tract infection. Mice received test agent, relevant placebo, or no treatment, followed by intravaginal N. gonorrhoeae challenge. N. gonorrhoeae colonization was tested by vaginal culture. CarraGuard, Ushercell, and T-PSS demonstrated significant protection, compared with control agents and no treatment. PRO 2000, ACIDFORM, and CAP showed significant protection, compared with no treatment but not compared with respective control agents. Mice that received BufferGel were provided significant protection, compared with untreated control mice; no placebo was tested. The findings of the present study suggest that topical agents may effectively reduce N. gonorrhoeae infection and that further evaluation is warranted. C1 Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. US FDA, Rockville, MD 20857 USA. Johns Hopkins Univ, Dept Biophys, Baltimore, MD USA. ReProtect, Baltimore, MD USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Epicyte Pharmaceut, San Diego, CA USA. RP Spencer, SE (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM SSpencerMD@comcast.net; ajerse@usuhs.mil FU NIAID NIH HHS [AI45967] NR 60 TC 37 Z9 38 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 2004 VL 189 IS 3 BP 410 EP 419 DI 10.1086/381125 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 767TC UT WOS:000188467900008 PM 14745698 ER PT J AU Sawant, SP Dnyanmote, AV Shankar, K Limaye, PB Latendresse, JR Mehendale, HM AF Sawant, SP Dnyanmote, AV Shankar, K Limaye, PB Latendresse, JR Mehendale, HM TI Potentiation of carbon tetrachloride hepatotoxicity and lethality in type 2 diabetic rats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID THIOACETAMIDE HEPATOTOXICITY; CYTOCHROME-P450 2E1; INSULIN-RESISTANCE; HEPATIC-FAILURE; TISSUE-REPAIR; LIVER; INJURY; MODEL; BIOTRANSFORMATION; TOXICOLOGY AB There is a need for well characterized and economical type 2 diabetic model that mimics the human disease. We have developed a type 2 diabetes rat model that closely resembles the diabetic patients and takes only 24 days to develop robust diabetes. Nonlethal doses of allyl alcohol (35 mg/kg i.p.), CCl4 (2 ml/kg i.p.), or thioacetamide (300 mg/kg i.p.) yielded 80 to 100% mortality in diabetic rats. The objective of the present study was to investigate two hypotheses: higher CCl4 bioactivation and/or inhibited compensatory tissue repair were the underlying mechanisms for increased CCl4 hepatotoxicity in diabetic rats. Diabetes was induced by feeding high fat diet followed by a single dose of streptozotocin on day 14 (45 mg/kg i.p.) and was confirmed on day 24 by hyperglycemia, normoinsulinemia, and oral glucose intolerance. Time course studies (0-96 h) of CCl4 (2 ml/kg i.p.) indicated that although initial liver injury was the same in nondiabetic and diabetic rats, it progressed only in the latter, culminating in hepatic failure, and death. Hepatomicrosomal CYP2E1 protein and activity, lipid peroxidation, glutathione, and (CCl4)-C-14 covalent binding to liver tissue were the same in both groups, suggesting that higher bioactivation-based injury is not the mechanism. Inhibited tissue repair resulted in progression of injury and death in diabetic rats, whereas in the nondiabetic rats robust tissue repair resulted in regression of injury and survival after CCl4 administration. These studies show high sensitivity of type 2 diabetes to model hepatotoxicants and suggest that CCl4 hepatotoxicity is potentiated due to inhibited tissue repair. C1 Univ Louisiana, Sch Pharm, Dept Toxicol, Monroe, LA 71209 USA. Pathol Associates Int, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Mehendale, HM (reprint author), Univ Louisiana, Sch Pharm, Dept Toxicol, 700 Univ Ave, Monroe, LA 71209 USA. EM mehendale@ulm.edu RI Latendresse, John/A-9215-2009 NR 40 TC 34 Z9 35 U1 1 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB 1 PY 2004 VL 308 IS 2 BP 694 EP 704 DI 10.1124/jpet.103.058834 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 767TB UT WOS:000188467800037 PM 14610242 ER PT J AU Uhl, K Kennedy, DL Gilliland, WR AF Uhl, K Kennedy, DL Gilliland, WR TI Disease modifying antirheumatic drugs and pregnancy SO JOURNAL OF RHEUMATOLOGY LA English DT Letter C1 US FDA, Pregnancy Labeling Task Force, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. Uniformed Serv Univ Hlth Sci, Dept Rheumatol, Bethesda, MD 20814 USA. RP Uhl, K (reprint author), US FDA, Pregnancy Labeling Task Force, Ctr Drug Evaluat & Res, 1451 Rockville Pike,HFD-020, Rockville, MD 20852 USA. EM uhlk@cder.fda.gov NR 6 TC 3 Z9 3 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD FEB PY 2004 VL 31 IS 2 BP 400 EP 401 PG 2 WC Rheumatology SC Rheumatology GA 770MU UT WOS:000188735200036 PM 14760818 ER PT J AU Anderson, JB Shuster, TA Hansen, KE Levy, AS Volk, A AF Anderson, JB Shuster, TA Hansen, KE Levy, AS Volk, A TI A camera's view of consumer food-handling behaviors SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID SAFETY; KNOWLEDGE; HOME AB Objective To compare consumer food-handling behaviors with the Fight BAC! consumer food-safety recommendations. Design Subjects were videotaped in their home while preparing a meal. Videotapes were coded according to Fight BAC! recommendations. A food-safety survey was administered and temperature data was collected. Subjects/Setting A market research company randomly recruited subjects by telephone. Ninety-nine consumers participated (92 women, seven men). Statistical Analysis Performed Descriptive statistics were used. Results Overall, subjects did not follow the Fight BAC! recommendations for safe food handling. Handwashing,was inadequate. The average hand wash length was significantly lower than the 20-second recommendation. Only one-third of subjects' hand wash attempts were with soap. Surface cleaning was inadequate with only one-third of surfaces thoroughly cleaned. Moreover, one-third of subjects did not attempt to clean surfaces during food preparation. Nearly all subjects cross-contaminated raw meat, poultry, seafood, eggs, and/or unwashed vegetables with ready-to-eat foods multiple times during food preparation. Unwashed hands were the most common cross-contamination agent. Many subjects undercooked the meat and poultry entrees. Very few subjects used a food thermometer. Applications /Conclusions Consumers make many food-handling errors during food preparation, increasing their risk of foodborne illness. Dietetics professionals need to familiarize themselves with the Fight BAC! consumer food-safety recommendations; understand where consumers are making food-handling errors; increase food safety awareness; and educate consumers, especially those in high-risk populations, about safe food handling at home. C1 Utah State Univ, Logan, UT 84322 USA. Spectrum Consulting, N Logan, UT USA. Safe Food Inst, N Logan, UT USA. US FDA, Consumers Studies Branch, Ctr Food Safety & Appl Nutr, College Pk, MD USA. Volk Enterprises, Norcross, GA USA. RP Hansen, KE (reprint author), 1770 N Res Pkwy, N Logan, UT 84341 USA. EM hansen@safefoodinstitute.org NR 15 TC 70 Z9 72 U1 2 U2 14 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD FEB PY 2004 VL 104 IS 2 BP 186 EP 191 DI 10.1016/j.jada.2003.11.010 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 773ZX UT WOS:000188956200008 PM 14760565 ER PT J AU Fishman, DA Hao, ZQ Pelt, V Petricoin, EF Liotta, LA Wiggins, WS Seshaiah, P Coleman, TA Hitt, BA AF Fishman, DA Hao, ZQ Pelt, V Petricoin, EF Liotta, LA Wiggins, WS Seshaiah, P Coleman, TA Hitt, BA TI High throughput multidimensional mass spectrometry analysis for the detection of early stage epithelial ovarian cancer: A serum test for ovarian cancer. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Northwestern Univ, Chicago, IL 60611 USA. Advion Biosci, Ithaca, NY USA. NCI FDA, Clin Proteom Program, Bethesda, MD USA. Correl Syst Inc, Bethesda, MD 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 246 BP 154A EP 154A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500245 ER PT J AU Pritchard, WF Wray-Cahen, D Karanian, JW Hilbert, S Wood, BJ AF Pritchard, WF Wray-Cahen, D Karanian, JW Hilbert, S Wood, BJ TI Radiofrequency cauterization with biopsy introducer needle SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID PERCUTANEOUS LIVER-BIOPSY; FIBRIN SEALANT; TRACT IMPLANTATION; CANINE MODEL; EMBOLIZATION; HEMATOMAS AB PURPOSE: The principal risks of needle biopsy are hemorrhage and implantation of tumor cells in the needle tract. This study compared hemorrhage after liver and kidney biopsy with and without radiofrequency (RF) ablation of the needle tract. MATERIALS AND METHODS: Biopsies of liver and kidney were performed in swine through introducer needles modified to allow RF ablation with the distal 2 cm of the needle. After each biopsy, randomization determined whether the site was to undergo RF ablation during withdrawal of the introducer needle. Temperature was measured with a thermistor stylet near the needle tip, with a target temperature of 70 degrees C-100 degrees C with RF ablation. Blood loss was measured as grams of blood absorbed in gauze at the puncture site for 2 minutes after needle withdrawal. Selected specimens were cut for gross examination. RESULTS: RF ablation reduced bleeding compared with absence of RF ablation in liver and kidney (P <.01), with mean blood loss reduced 63% and 97%, respectively. Mean amounts of blood loss (+/- SD) in the liver in the RF and no-RF groups were 2.03 g +/- 4.03 (CI, 0.53-3.54 g) and 5.50 g +/- 5.58 (CI, 3.33-7.66 g), respectively. Mean amounts of blood loss in the kidney in the RF and no-RF groups were 0.26 g +/- 0.32 (CI, -0.01 to 0.53 g) and 8.79 g +/- 7.72 (CI, 2.34-15.24 g), respectively. With RF ablation, thermal coagulation of the tissue surrounding the needle tract was observed. CONCLUSION: RF ablation of needle biopsy tracts reduced hemorrhage after biopsy in the liver and kidney and may reduce complications of hemorrhage as well as implantation of tumor cells in the tract. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Special Procedures Div, Bethesda, MD 20892 USA. RP Pritchard, WF (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. EM wfp@cdrh.fda.gov FU Intramural NIH HHS [Z99 CL999999] NR 17 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD FEB PY 2004 VL 15 IS 2 BP 183 EP 187 DI 10.1097/01.RVI.000019398.74740.69 PN 1 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 919EF UT WOS:000228600400011 PM 14963187 ER PT J AU Zha, HB Raffeld, M Charboneau, L Pittaluga, S Kwak, LW Petricoin, E Liotta, LA Jaffe, ES AF Zha, HB Raffeld, M Charboneau, L Pittaluga, S Kwak, LW Petricoin, E Liotta, LA Jaffe, ES TI Similarities of prosurvival signals in Bcl-2-positive and Bcl-2-negative follicular lymphomas identified by reverse phase protein microarray SO LABORATORY INVESTIGATION LA English DT Article DE apoptosis; follicular lymphoma; Bcl-2; protein microarray; proteomics ID LASER CAPTURE MICRODISSECTION; NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; NF-KAPPA-B; BCL-2 FAMILY; CHROMOSOMAL-ABNORMALITIES; TRANSCRIPTION FACTOR; UP-REGULATION; EXPRESSION; SURVIVAL AB Overexpression of Bcl-2 protein has been known to play a role in the pathogenesis of follicular lymphoma (FL). However, 10-15% of FLs are negative for Bcl-2 by immunohistochemistry, raising the possibility that another gene product(s) may provide prosurvival signal(s). We used reverse phase protein microarray to analyze lysates of follicle center cells isolated by laser capture microdissection from: Bcl-2+ FL, Bcl-2- FL and reactive follicular hyperplasia (FH) (nine cases each group). TUNEL assay confirmed similar and reduced levels of apoptosis in Bcl-2+ FL and Bcl-2- FL, indicating the likelihood of Bcl-2-independent inhibition of apoptosis. Arrays were quantitatively analyzed with antibodies to proteins involved in the apoptotic pathway. As expected, Bcl-2 levels were up to eight-fold higher in Bcl-2+ FL than in FH and Bcl-2- FL. However, there was no difference in levels of Mcl-1 and survivin among these three groups. Bcl-X-L showed a trend for increased expression in Bcl-2- FL as compared with Bcl-2+ FL, although the differences did not reach statistical significance (P>0.1). The increase in Bcl-X-L may provide an alternative antiapoptotic signal in FL negative for Ill protein. Interestingly, Bax expression was higher in FL (Bcl-2+ or -) than in FH (P=0.001). Notably, phospho-Akt (Ser-473) was increased in FL (Bcl-2+ or -) (P<0.03) with increased phospho-Bad (Ser-136), as compared with levels in FH. The activation of the Akt/Bad pathway provides further evidence of prosurvival signals in FL, independent of Bcl-2 alone. These data suggest that nodal FL represents a single disease with a final common biochemical pathway. C1 NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Jaffe, ES (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10,Room 2N202,MSC-1500, Bethesda, MD 20892 USA. EM ejaffe@mail.nih.gov NR 66 TC 63 Z9 68 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2004 VL 84 IS 2 BP 235 EP 244 DI 10.1038/labinvest.3700051 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 840BW UT WOS:000222833000013 PM 14767488 ER PT J AU Delmonte, P Roach, JAG Mossoba, MM Losi, G Yurawecz, MP AF Delmonte, P Roach, JAG Mossoba, MM Losi, G Yurawecz, MP TI Synthesis, isolation, and GC analysis of all the 6,8-to 13,15-cis/trans conjugated linoleic acid isomers SO LIPIDS LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; OCTADECADIENOIC ACID; METHYL-ESTERS; SEPARATION; IDENTIFICATION; CLA AB Octadecadienoic acids with conjugated double bonds are often referred to as conjugated linoleic acid, or CLA. CLA is of considerable interest because of potentially beneficial effects reported from animal studies. Analysis of CLA is usually carried out by GC elution of FAME. If the presence of low-level isomers is of interest, a complementary technique such as silver-ion HPLC is also used. These analyses have been hindered by a lack of well-characterized commercially available reference materials. Described here are the synthesis and isolation of selected 6,8- through 13,15-positional CLA isomers, followed by isomerization of these CLA isomers with iodine to produce all the possible cis,cis, cis,trans, trans,cis, and trans,trans combinations. Also present are the GC retention times of the CLA FAME relative to gamma-linolenic acid (6c,9c,12c-octadecatrienoic acid) FAME using a 100-m CP Sil-88 capillary column (Varian Inc., Lake Forest, CA). These data include all the CLA isomers that have been identified thus far in foods and dietary supplements and should greatly aid in the future analysis of CLA in these products. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Univ Bologna, DIPROVAL, Bologna, Italy. RP Yurawecz, MP (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branck Pkwy,HFS-840,Room IE009, College Pk, MD 20740 USA. EM mpy@cfsan.fda.gov NR 18 TC 33 Z9 34 U1 0 U2 10 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 221 W BRADLEY AVE, CHAMPAIGN, IL 61821-1827 USA SN 0024-4201 J9 LIPIDS JI Lipids PD FEB PY 2004 VL 39 IS 2 BP 185 EP 191 PG 7 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 813FQ UT WOS:000220893400012 PM 15134147 ER PT J AU Taitt, CR Golden, JP Shubin, YS Shriver-Lake, LC Sapsford, KE Rasooly, A Ligler, FS AF Taitt, CR Golden, JP Shubin, YS Shriver-Lake, LC Sapsford, KE Rasooly, A Ligler, FS TI A portable array biosensor for detecting multiple analytes in complex samples SO MICROBIAL ECOLOGY LA English DT Article; Proceedings Paper CT International Workshop on Microbial Ecology and the Space Environment CY NOV 18-19, 2002 CL Tokyo, JAPAN SP Int Space Life Sci Working Grp ID SALMONELLA-ENTERITIDIS INFECTION; FIBER-OPTIC BIOSENSOR; LISTERIA-MONOCYTOGENES; RAPID DETECTION; FOODS; IDENTIFICATION; IMMUNOSENSOR; IMMUNOASSAY; ANTIBODIES; SURFACES AB The Multi-Analyte Array Biosensor (MAAB) has been developed at the Naval Research Laboratory (NRL) with the goal of simultaneously detecting and identifying multiple target agents in complex samples with minimal user manipulation. This paper will focus on recent improvements in the biochemical and engineering aspects of this instrument. These improvements have enabled the expansion of the repertoire of analytes detected to include Salmonella typhimurium and Listeria monocytogenes, and also expanded the different sample matrices tested. Furthermore, all components of the biochemical assays could be prepared well in advance of sample testing, resulting in a "plug-and-play" methodology. Simultaneous detection of three toxins (ricin, staphylococcal enterotoxin B, and cholera toxin) was demonstrated using a novel fluidics cube module that limits the number of manipulations to only the initial sample loading. This work demonstrates the utility of the MAAB for rapid analysis of complex samples with multianalyte capability, with a minimum of operator manipulations required for either sample preparation or final analysis. C1 USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. Geocenters Inc, Suitland, MD USA. George Mason Univ, Arlington, VA USA. US FDA, CFSAN, College Pk, MD USA. RP Taitt, CR (reprint author), USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. EM crtaitt@cbmse.nrl.navy.mil NR 73 TC 66 Z9 70 U1 0 U2 9 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0095-3628 J9 MICROBIAL ECOL JI Microb. Ecol. PD FEB PY 2004 VL 47 IS 2 BP 175 EP 185 DI 10.1007/s00248-003-1011-1 PG 11 WC Ecology; Marine & Freshwater Biology; Microbiology SC Environmental Sciences & Ecology; Marine & Freshwater Biology; Microbiology GA 818CL UT WOS:000221223100010 PM 14765282 ER PT J AU Kawakami, K Kawakami, M Puri, RK AF Kawakami, K Kawakami, M Puri, RK TI Specifically targeted killing of interleukin-13 (IL-13) receptor-expressing breast cancer by IL-13 fusion cytotoxin in animal model of human disease SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CELL CARCINOMA-CELLS; PSEUDOMONAS EXOTOXIN; SIGNAL-TRANSDUCTION; CHIMERIC PROTEIN; ALPHA-2 CHAIN; (IL)-13 BINDING; TUMOR IMMUNOSURVEILLANCE; ANTITUMOR-ACTIVITY; SYSTEMIC DELIVERY; MALIGNANT GLIOMA AB Interleukin-13 receptor (IL-13R) alpha2 chain binds IL-13 with high affinity and can internalize after binding to ligand. We have exploited this property of IL-13Ralpha2 chain by receptortargeted breast cancer therapy. Previous studies have demonstrated that in vivo intraturnoral (i.t.) gene transfer of this chain followed by IL-13 cytotoxin [comprised of IL-13 and Pseudomonas exotoxin (IL13-PE38QQR)] therapy causes regression of established human tumors in xenografted models. Breast carcinoma cells do not express IL-13Ralpha2 chain and are resistant to the antitumor effect of IL-13 cytotoxin. To determine whether IL-13Ralpha2 chain can render sensitivity of breast cancer to IL-13 cytotoxin, we injected IL-13Ralpha2 plasmid in s.c. established tumors by i.t. route, followed by systemic or i.t. IL-13 cytotoxin administration. This combination approach showed profound antitumor activity against human breast tumors in xenografted immunodeficient mice. Interestingly, there was dominant infiltration of inflammatory cells in regressing tumors, which were identified to be macrophages producing nitric oxide (NO) and natural killer cells. The partial role of inducible nitric oxide synthase (iNOS)-positive macrophages was confirmed by in vivo macrophage depletion experiments. Serum chemistry, hematology, and organ histology from treated mice did not show any remarkable toxicity resulting from the combination therapy. Taken together, local gene transfer of IL-13Ralpha2 followed by receptor-targeted IL-13 cytotoxin therapy may be applied safely and effectively to the treatment of localized breast cancer. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. EM puri@cber.fda.gov NR 50 TC 16 Z9 19 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD FEB PY 2004 VL 3 IS 2 BP 137 EP 147 PG 11 WC Oncology SC Oncology GA 778ME UT WOS:000189244700005 PM 14985454 ER PT J AU Alayash, AI AF Alayash, AI TI Oxygen therapeutics: Can we tame haemoglobin? SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID CROSS-LINKED HEMOGLOBIN; CELL-FREE HEMOGLOBIN; TRAUMATIC HEMORRHAGIC-SHOCK; MYOGLOBIN REDOX CYCLE; NITRIC-OXIDE; BLOOD SUBSTITUTE; HYDROGEN-PEROXIDE; HEME DEGRADATION; POLYOXYETHYLENE CONJUGATE; RECOMBINANT HEMOGLOBIN AB Chemically modified or genetically engineered haemoglobins (Hbs) developed as oxygen therapeutics (often termed 'blood substitutes') are designed to correct oxygen deficit due to ischaemia in a variety of clinical settings. These modifications are intended to stabilize Hb outside its natural environment - red blood cells - in a functional tetrameric and/or polymeric form. Uncontrolled haem-mediated oxidative reactions of cell-free Hb and its reactions with various oxidant/antioxidant and cell signalling systems have emerged as an important pathway of toxicity. Current protective strategies designed to produce safe Hb-based products are focused on controlling or suppressing the 'radical' nature of Hb while retaining its oxygen-carrying function. C1 US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, 8800 Rockville Pike,NIH Bldg 29,Room 112, Bethesda, MD 20892 USA. EM alayash@cber.fda.gov NR 85 TC 176 Z9 183 U1 2 U2 26 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD FEB PY 2004 VL 3 IS 2 BP 152 EP 159 DI 10.1038/nrd1307 PG 8 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 768ZP UT WOS:000188601800013 PM 15043006 ER PT J AU Taylor, CL AF Taylor, CL TI Regulatory frameworks for functional foods and dietary supplements SO NUTRITION REVIEWS LA English DT Review DE regulations; foods; dietary supplements AB An understanding of the legal and regulatory requirements for foods, including dietary supplements and so-called functional foods, helps to focus attention on the special challenges that exist, which range from safety determinations to claim substantiation and consumer understanding. This article provides an overview of the Food and Drug Administration's regulatory framework for these products, it also highlights issues that are emerging and will require consideration and dialog. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Nutrit Prod Labeling & Dietary Supplements, College Pk, MD 20704 USA. RP Taylor, CL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Nutrit Prod Labeling & Dietary Supplements, 5100 Paint Branch Pkwy, College Pk, MD 20704 USA. NR 3 TC 8 Z9 11 U1 2 U2 3 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 FEB PY 2004 VL 62 IS 2 BP 55 EP 59 DI 10.1301/nr.2004.feb.55-59 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 903NU UT WOS:000227433600001 PM 15080366 ER PT J AU Koller, EA Cross, JT Schneider, B AF Koller, EA Cross, JT Schneider, B TI Risperidone-associated diabetes mellitus in children SO PEDIATRICS LA English DT Letter ID ATYPICAL ANTIPSYCHOTIC-DRUGS; HYPERGLYCEMIA C1 US FDA, Div Metab & Endocrine Drug Prod, Ctr Drug Evaluat & Review, Rockville, MD 20857 USA. RP Koller, EA (reprint author), US FDA, Div Metab & Endocrine Drug Prod, Ctr Drug Evaluat & Review, Rockville, MD 20857 USA. NR 6 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 FEB 1 PY 2004 VL 113 IS 2 BP 421 EP 421 DI 10.1542/peds.113.2.421 PG 1 WC Pediatrics SC Pediatrics GA 769AK UT WOS:000188603800046 PM 14754964 ER PT J AU Takeshita, F Gursel, I Ishii, KJ Suzuki, K Gursel, M Klinman, DM AF Takeshita, F Gursel, I Ishii, KJ Suzuki, K Gursel, M Klinman, DM TI Signal transduction pathways mediated by the interaction of CpG DNA with Toll-like receptor 9 SO SEMINARS IN IMMUNOLOGY LA English DT Review DE CpG DNA; TLR 9; PAMP; signal transduction ID NF-KAPPA-B; ACTIVATED PROTEIN-KINASES; ANTIGEN-PRESENTING CELLS; BACTERIAL-DNA; CUTTING EDGE; INTERFERON-GAMMA; GENE-EXPRESSION; IFN-BETA; RECOGNITION; REQUIRES AB Synthetic oligodeoxynucleotides (ODN) expressing non-methylated "CpG motifs" patterned after those present in bacterial DNA have characteristic immunomodulatory effects. CpG DNA is recognized as a pathogen-associated molecular pattern, and triggers a rapid innate immune response. CpG ODN are being harnessed for a variety of therapeutic uses, including as immune adjuvants, for cancer therapy, as anti-allergens, and as immunoprotective agents. The signal transduction pathway mediated by the engagement of CpG DNA with Toll-like receptor 9 (TLR9) is shared with other members of the TLR family. Recent studies demonstrate that formation and maturation of CpG DNA-containing endosomes are regulated by phosphatidylinositol 3 kinases and the Ras-associated GTP-binding protein, Rab5, which are essential for the initiation of TLR9-mediated signaling. (C) 2003 Elsevier Ltd. All rights reserved. C1 CBER, FDA, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), CBER, FDA, Bldg 29A,Rm 3D10, Bethesda, MD 20892 USA. EM Klinman@cber.fda.gov RI Gursel, Mayda /H-1812-2012; Ishii, Ken/B-1685-2012; OI Ishii, Ken/0000-0002-6728-3872; Gursel, Ihsan/0000-0003-3761-1166; Gursel, Mayda/0000-0003-0044-9054 NR 43 TC 115 Z9 120 U1 6 U2 20 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD FEB PY 2004 VL 16 IS 1 BP 17 EP 22 DI 10.1016/j.smim.2003.10.009 PG 6 WC Immunology SC Immunology GA 774VC UT WOS:000189005300004 PM 14751759 ER PT J AU MacDonald, J French, JE Gerson, RJ Goodman, J Inoue, T Jacobs, A Kasper, P Keller, D Lavin, A Long, G McCullough, B Sistare, FD Storer, R van der Laan, JW AF MacDonald, J French, JE Gerson, RJ Goodman, J Inoue, T Jacobs, A Kasper, P Keller, D Lavin, A Long, G McCullough, B Sistare, FD Storer, R van der Laan, JW TI The utility of genetically modified mouse assays for identifying human carcinogens: A basic understanding and path forward SO TOXICOLOGICAL SCIENCES LA English DT Article DE carcinogenicity; p53(+/-) knockout mouse; regulatory perspective; risk assessment; Tg.rasH2 transgenic mouse; genetically modified mice ID TUMORS AB The Alternatives to Carcinogenicity Testing Committee of the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) conducted a large-scale, multinational collaborative research program to evaluate several genetically modified mouse assays for assessing the human carcinogenic potential of compounds. The data from this testing program have made an important contribution to the general understanding of how these models can be best applied in hazard identification; however, questions still exist regarding methodology and data interpretation. To address these issues, ILSI HESI hosted a February 2003 workshop on the Utility of Transgenic Assays for Risk Assessment. The purpose of this workshop was to reach an understanding of how data from genetically modified mouse models are viewed by different regulatory bodies in the pharmaceutical sector and, based on this understanding, to identify areas in which more experimental work may be needed to increase the utility of data derived from these assays. In the course of discussions, various data gaps related to model selection and protocol issues were identified. Based on the outcome of the workshop, various studies are proposed to provide data to improve the utility of currently available assays for cancer hazard identification and risk assessment purposes. C1 ILSI HESI, Washington, DC 20005 USA. Schering Plough Res Inst, Kenilworth, NJ 07033 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Endo Pharmaceut, Chadds Ford, PA 19352 USA. Michigan State Univ, E Lansing, MI 48824 USA. Natl Inst Hlth Sci, Tokyo 1588501, Japan. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Fed Inst Drugs & Med Devices BfArM, D-53175 Berlin, Germany. Sanofi Synthelabo Res, Malvern, PA 19355 USA. Eli Lilly & Co, Greenfield, IN 46140 USA. Aventis Pharmaceut Inc, Bridgewater, NJ 08807 USA. Merck Res Labs, W Point, PA 19486 USA. Natl Inst Publ Hlth & Environm RIVM, NL-3720 BA Bilthoven, Netherlands. RP Lavin, A (reprint author), ILSI HESI, 1 Thomas Circle,9th Floor, Washington, DC 20005 USA. EM alavin@ilsi.org OI Keller, Douglas/0000-0002-6186-2881 NR 7 TC 43 Z9 45 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD FEB PY 2004 VL 77 IS 2 BP 188 EP 194 DI 10.1093/toxsci/kfh037 PG 7 WC Toxicology SC Toxicology GA 774ML UT WOS:000188987000003 PM 14657512 ER PT J AU Scofield, TL Miller, JP Storry, JR Rios, M Reid, ME AF Scofield, TL Miller, JP Storry, JR Rios, M Reid, ME TI Evidence that Hy-RBCs express weak Jo(a) antigen SO TRANSFUSION LA English DT Article ID BLOOD-GROUP ANTIGEN; GROUP SYSTEM; JOA; GLYCOPROTEIN; PHENOTYPES; EXAMPLE; GY(A); GYA AB BACKGROUND: RBCs of the Hy- phenotype have, in the past, been typed as Gy(a+(w)), Hy-, Jo(a-), and RBCs with the Jo(a-) phenotype type Gy(a+), Hy-(w), and Jo(a-). Anti-Hy and anti-Jo(a) are difficult to identify mainly because appropriate reagent R6Cs are poorly characterized. Historically, anti-Jo(a) has not reacted with RBCs with either phenotype. This report describes a case of an anti-Jo(a) that shows Hy- RBCs express some Jo(a) antigen, albeit weakly. CASE REPORT: Anti-Jo(a) was identified in a serum sample of a 71-year-old woman. The antibody reacted 1+ to 2+ by the IAT with all untreated and ficin-treated panel RBCs and did not react with Gy(a-) RBCs and Jo(a-) RBCs. Unexpectedly, the serum sample reacted weakly with six of eight RBC samples with the Hy- phenotype. The anti_Jo(a) was adsorbed onto and eluted from Hy- RBCs, indicating the presence of weak Jo(a) antigen. The patient's RBCs typed Gy(a+), Hy+, Jo(a-). DNA studies using PCR-RFLP analysis showed the patient to be homozygous for the JO allele, which is consistent with the serologically determined Jo(a-) status. CONCLUSION: The DNA and serologic evidence of this case show that Hy- RBCs may express low levels of Jo(a) antigen, which contradicts previously published data concerning the Jo(a) type of Hy- RBCs. C1 Amer Red Cross, N Cent Blood Serv, St Paul, MN 55107 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Univ Hosp, Skane Blood Ctr, Lund, Sweden. New York Blood Ctr, Immunohematol Lab, New York, NY 10021 USA. RP Scofield, TL (reprint author), Amer Red Cross, N Cent Blood Serv, 100 S Robert St, St Paul, MN 55107 USA. EM scofieldt@usa.redcross.org FU NHLBI NIH HHS [HL54459] NR 15 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD FEB PY 2004 VL 44 IS 2 BP 170 EP 172 DI 10.1111/j.1537-2995.2004.00627.x PG 3 WC Hematology SC Hematology GA 775RH UT WOS:000189055900006 PM 14962307 ER PT J AU Orton, SL Stramer, SL Dodd, RY Alter, MJ AF Orton, SL Stramer, SL Dodd, RY Alter, MJ TI Risk factors for HCV infection among blood donors confirmed to be positive for the presence of HCV RNA and not reactive for the presence of anti-HCV SO TRANSFUSION LA English DT Article ID HEPATITIS-C VIRUS; NON-B HEPATITIS; UNITED-STATES; HEALTH-CARE; NON-A; DISEASE; EPIDEMIOLOGY; POPULATION; IDENTIFY; VIREMIA AB BACKGROUND: In 1999, NAT of blood donations was implemented to detect "window-period" infections. Blood donors who have confirmed NAT results positive for the presence of HCV in the absence of anti-HCV are likely to have been recently infected. Of over 26.8 million donations tested between March 3, 1999, and March 31, 2003, 810 were HCV-reactive by NAT. A subset of these donors was assessed for recent exposure risk. STUDY DESIGN AND METHODS: All anti-HCV-blood donors with reactive, unconfirmed HCV NAT results were invited to participate in a study that included an extensive demographic and risk questionnaire. Confirmed HCV+ cases were compared to HCV- (falsely positive) controls for histories of potential risk factors during the 6 months before donation. RESULTS: Recent injection drug use (IDU) was independently associated with HCV infection (29.2% vs. 0% of cases vs. controls, p < 0.001). In addition, likely sources were identified for three other cases (4.6%), including occupational exposure, sexual contact with an HCV-infected partner (who was an IDU), and perinatal exposure, none of which was known to the donors at the time of donation. Incarceration was independently associated with HCV infection among the group not reporting IDU and after removal of the three donors with likely sources of risk (14.6% vs. 1.3% of cases vs. controls, p < 0.001). CONCLUSIONS: A likely risk, primarily IDU, was found for 43 percent of HCV+ donors whose infections were identified solely by NAT. Because the maximum efficiency of the donor history questions may have been reached, NAT will continue to be an important measure to interdict recently infected blood donors. C1 Amer Red Cross, Gaithersburg, MD USA. Amer Red Cross, Rockville, MD USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Orton, SL (reprint author), CBER, OBRR, Div Blood Applicat, Rockville, MD 20852 USA. EM Orton@cber.fda.gov NR 22 TC 38 Z9 40 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD FEB PY 2004 VL 44 IS 2 BP 275 EP 281 DI 10.1111/j.1537-2995.2004.00623.x PG 7 WC Hematology SC Hematology GA 775RH UT WOS:000189055900019 PM 14962320 ER PT J AU Raker, CA Tabor, E Okayama, A Yu, MYW Kohara, M Mueller, NE Tsubouchi, H Stuver, SO AF Raker, CA Tabor, E Okayama, A Yu, MYW Kohara, M Mueller, NE Tsubouchi, H Stuver, SO TI HCV core antigen as an alternative to NAT to detect HCV viremia SO TRANSFUSION LA English DT Letter ID ENZYME-IMMUNOASSAY; INFECTION C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Miyazaki Med Coll, Dept Internal Med 2, Miyazaki 88916, Japan. Tokyo Metropolitan Inst Med Sci, Dept Microbiol & Cell Biol, Tokyo 113, Japan. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Raker, CA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM craker@hsph.harvard.edu FU NCI NIH HHS [T32 CA09001-27, CA38450] NR 5 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD FEB PY 2004 VL 44 IS 2 BP 307 EP 308 DI 10.1111/j.1537-2995.2004.00649.x PG 2 WC Hematology SC Hematology GA 775RH UT WOS:000189055900024 PM 14962325 ER PT J AU Petricoin, EF Liotta, LA AF Petricoin, EF Liotta, LA TI Proteomic approaches in cancer risk and response assessment SO TRENDS IN MOLECULAR MEDICINE LA English DT Article ID PROTEIN IDENTIFICATION TECHNOLOGY; TYROSINE KINASE INHIBITOR; IMMOBILIZED PH GRADIENTS; OVARIAN-CANCER; MASS-SPECTROMETRY; BREAST-CANCER; 2-DIMENSIONAL ELECTROPHORESIS; TRASTUZUMAB HERCEPTIN; CLINICAL PROTEOMICS; MYELOID-LEUKEMIA AB Proteomics is more than just a list-generating exercise where increases or decreases in protein expression are identified. Proteomic technologies will ultimately characterize information-flow through the protein circuitry that interconnects the extracellular microenvironment to the serum or plasma macroenvironment through intracellular signaling systems and their control of gene transcription. The nature of this information can be a cause or a consequence of disease processes and how patients respond to therapy. Analysis of human cancer as a model for how proteomics can have an impact at the bedside can take advantage of several promising new proteomic technologies. These technologies are being developed for early detection and risk assessment, therapeutic targeting and patient-tailored therapy. C1 NCI, FDA, Clin Proteom Program, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), NCI, FDA, Clin Proteom Program, Bldg 29A,Room 2D12,8800 Rockville Pike, Bethesda, MD 20892 USA. EM petricoin@cber.fda.gov NR 70 TC 40 Z9 41 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD FEB PY 2004 VL 10 IS 2 BP 59 EP 64 DI 10.1016/j.molmed.2003.12.006 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 780BE UT WOS:000189350600004 PM 15102358 ER PT J AU Goldsmith, JC Eller, N Mikolajczyk, M Manischewitz, J Golding, H Scott, DE AF Goldsmith, JC Eller, N Mikolajczyk, M Manischewitz, J Golding, H Scott, DE TI Intravenous immunoglobulin products contain neutralizing antibodies to vaccinia SO VOX SANGUINIS LA English DT Article DE anti-vaccinia virus antibodies; immune globulin (intravenous, human); primary immune deficiency; smallpox vaccination ID SMALLPOX VACCINATION; VIRUS; COMPLICATIONS AB Background and Objectives Individuals with primary or secondary immune-deficiency diseases may be at risk for vaccinia infection if widespread smallpox-immunization programmes are implemented in the United States of America (USA) for bioterrorism preparedness. The objective of this study was to determine whether commercial immune globulin (intravenous, human) products contain biologically active antibodies to vaccinia that have the potential to protect people, with immune deficiencies, from complications of vaccinia. Materials and Methods Eight currently United States (US)-licensed and two European intravenous immunoglobulin (IVIG) products were tested in a vaccinia plaque-reduction neutralization assay. The in vivo activity of five of these lots was assessed in severely immune-deficient mice. Results All tested products contained neutralizing anti-vaccinia activity, in vitro and in vivo. Conclusions The use of IVIG by individuals with inherited or acquired humoral immune deficiencies may provide some protection if they are inadvertently exposed to vaccinia. C1 Immune Deficiency Fdn, Towson, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Goldsmith, JC (reprint author), 40 W Chesapeake Ave,Suitte 308, Towson, MD 21204 USA. EM jgoldsmith@primaryimmune.org NR 24 TC 12 Z9 13 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD FEB PY 2004 VL 86 IS 2 BP 125 EP 129 DI 10.1111/j.0042-9007.2004.00397.x PG 5 WC Hematology SC Hematology GA 810HW UT WOS:000220696400007 PM 15023182 ER PT J AU Rodrigues, A Rios, M Costa, FF Saad, STO Pellegrino, J Castilho, L AF Rodrigues, A Rios, M Costa, FF Saad, STO Pellegrino, J Castilho, L TI Weakened expression of 'e' owing to concomitant occurrence of Cys16 and Val245 (VS antigen) SO VOX SANGUINIS LA English DT Article DE e antigen; RHCE ce; SCD patients; VS antigen ID BLOOD-GROUP SYSTEM; MOLECULAR-BIOLOGY; BLACK INDIVIDUALS; RHCE GENE; POLYMORPHISMS; POLYPEPTIDES; INSIGHTS AB Background and Objectives The 48 G>C transversion in exon 1 of the RHCE gene leads to Trp16Cys, usually present in the conventional RHCE Ce, while Trp 16 is associated with RHCE ce. The presence of Cys16 in RHCE ce is associated with the R-0 (Dce) haplotype in Africans, leading to a weak 'e' antigen expression on red blood cells (RBCs). VS is a common red cell antigen in individuals of African descent and results from a single point mutation in exon 5 of the RHCE (733C>G), leading to Leu245Val substitution; VS positivity is also associated with weak expression of 'e'. This study investigated the association of Cys16 and/or VS with the RHCE ce alleles in a cohort of sickle cell disease (SCD) patients phenotyped as R(0)r or R0R0 and rr. Materials and Methods DNA samples from 58 SCD patients were tested for the 48 G>C transversion, encoding Cys16, by allele-specific polymerase chain reaction (PCR). We also amplified exon 5 of the RHCE by PCR and subjected the amplified product to restriction fragment length polymorphism analysis, using BfaI, in order to determine the VS status. Further cDNA analysis was performed on three samples to verify whether the mutations were located on the same or on different alleles. Results Fifty-six of the 58 SCD patients studied (97%) were heterozygous for 48G/48C (Cys16). Of these, 18 (32%) were also heterozygous for 733C/G (245Val). All of these 18 samples showed weak 'e' expression on RBCs when tested with at least one monoclonal antibody to e antigen. cDNA sequencing of three of 18 patient samples showed that the genes encoding Cys16 and Val245 (VS) were on different alleles. Conclusions We found a high incidence of Cys16 associated with the RHCE ce in our SCD cohort. A high percentage of these patients were also found to be heterozygous for VS. cDNA analysis showed that, in at least three samples, the two mutations were on different alleles, with consequent weakening of expression of the e antigen on RBCs. C1 UNICAMP, Hemoctr, BR-13081970 Campinas, SP, Brazil. US FDA, CBER, DETTD, Rockville, MD 20857 USA. RP Castilho, L (reprint author), UNICAMP, Hemoctr, Rua Carlos Chagas 480,Caixa Postal 6198, BR-13081970 Campinas, SP, Brazil. EM castilho@unicamp.br RI Costa, Fernando/D-1566-2012; Castilho, Lilian/F-6123-2012 OI Castilho, Lilian/0000-0002-3104-647X NR 22 TC 5 Z9 5 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD FEB PY 2004 VL 86 IS 2 BP 136 EP 140 DI 10.1111/j.0042-9007.2004.00399.x PG 5 WC Hematology SC Hematology GA 810HW UT WOS:000220696400009 PM 15023184 ER PT J AU Sakamoto, S Qin, JZ Navarro, A Gamero, A Potla, R Yi, TL Zhu, W Baker, DP Feldman, G Larner, AC AF Sakamoto, S Qin, JZ Navarro, A Gamero, A Potla, R Yi, TL Zhu, W Baker, DP Feldman, G Larner, AC TI Cells previously desensitized to type 1 interferons display different mechanisms of activation of stat-dependent gene expression from naive cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; STIMULATED JAK/STAT PATHWAY; GAMMA-INTERFERON; TRANSCRIPTIONAL INDUCTION; BETA-INTERFERON; PHOSPHORYLATED STAT1; BINDING PROTEIN; DNA; INHIBITION; ALPHA AB Over the past decade, a wealth of knowledge has been obtained concerning the mechanisms by which interferons (IFNs) and other cytokines activate or down-regulate immediate early genes via the Jak/Stat pathway. In contrast, little information is available on interferon-activated gene expression in naive cells compared with cells that have been desensitized and subsequently resensitized to the actions of these cytokines. In naive cells, the ISG54 gene is activated via IFN beta-stimulated formation of ISGF3, a heterotrimeric DNA binding complex consisting of p48 (IRF9) and tyrosine-phosphorylated Stat1 and Stat2. In contrast, in previously desensitized cells IFNbeta weakly stimulates the assembly of an ISGF3-like complex that lacks Stat1, even though ISG54 mRNA induction is the same as in naive cells. The lack of Stat1 tyrosine phosphorylation and DNA binding is due to increased activity of a protein-tyrosine phosphatase. In cells that do not express the tyrosine phosphatase Tc-PTP, the rate of Stat1 dephosphorylation is the same in naive and previously desensitized cells. These results implicate Tc-PTP in a novel role in the regulation of type 1 interferon-stimulated gene expression. C1 Lerner Res Inst, Dept Immunol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Canc Biol, Cleveland, OH 44195 USA. Biogen Inc, Cambridge, MA 02142 USA. US FDA, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Larner, AC (reprint author), Lerner Res Inst, Dept Immunol, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM larnera@ccf.iorg FU NCI NIH HHS [CA77366] NR 44 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 30 PY 2004 VL 279 IS 5 BP 3245 EP 3253 DI 10.1074/jbc.M309631200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 766MF UT WOS:000188379600015 PM 14600148 ER PT J AU Moody, TW Dudek, J Zakowicz, H Walters, J Jensen, RT Petricoin, E Couldrey, C Green, JE AF Moody, TW Dudek, J Zakowicz, H Walters, J Jensen, RT Petricoin, E Couldrey, C Green, JE TI VIP receptor antagonists inhibit mammary carcinogenesis in C3(1)SV40T antigen mice SO LIFE SCIENCES LA English DT Article DE VIP receptor antagonist; mammary carcinogenesis; transgenic mice; chemoprevention; proteomics ID VASOACTIVE INTESTINAL POLYPEPTIDE; BREAST-CANCER-CELLS; FUNCTIONAL EXPRESSION; PEPTIDE RECEPTORS; TRANSGENIC MICE; PACAP RECEPTOR; HUMAN TUMORS; LUNG-CANCER; GROWTH; IDENTIFICATION AB The effects of a vasoactive intestinal peptide (VIP) receptor antagonist on mammary carcinogenesis were investigated using the C3(1)SV40T antigen (ag) mice. Ten mug/day VIPhybrid (VIPhyb) administered daily subcutaneously increased significantly the survival of C3(1)SV40Tag mice. At 5.2 months, VIPhyb significantly reduced the mammary tumor burden in C3(1)SV40Tag mice relative to control animals. I-125-VIP bound with high affinity to mouse mammary tumor homogenate. Because (Lys(15), Arg(16), Leu(27))VIP(1-7)GRF(8-27) (VPAC(1) selective) but not Ro25-1553 (VPAC(2) selective) inhibited specific I-125-VIP binding to mammary tumor membranes with high affinity, VPAC(1) receptors predominate. By RT-PCR, VPAC(1) receptor mRNA was detected in mammary tumors. By Western blot, a major 60 Kdalton band was detected in mammary tumor extracts using VPAC(1) receptor antisera. By immunocytochemistry, VPAC(1)-R immunostaining was detected in the cytosol and plasma membrane but not the nucleus of fixed mammary tumor tissue. Using laser capture microdissected tumor cells and surface enhanced laser desorption/ionization (SELDI) techniques on mammary tumor cells, the proteomic profile was altered in mice treated with VIPhyb. Because VPAC(1) receptor antagonists increase the survival and reduce the tumor burden in C3(1)SV40Tag mice, they may function as chemopreventive agents in mammary cancer. (C) 2003 Elsevier Inc. All rights reserved. C1 NCI, Dept Hlth & Human Serv, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. George Washington Univ, Genet Program, Washington, DC 20037 USA. NIDDK, Digest Dis Branch, Bethesda, MD USA. CBER FDA, Div Cytokine Biol, Bethesda, MD USA. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Moody, TW (reprint author), NCI, Dept Hlth & Human Serv, Ctr Canc Res, NIH, Bldg 31,Rm 3A34,31 Ctr Dr, Bethesda, MD 20892 USA. EM moodyt@mail.nih.gov NR 37 TC 17 Z9 18 U1 0 U2 0 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 JAN 30 PY 2004 VL 74 IS 11 BP 1345 EP 1357 DI 10.1016/j.lfs.2003.07.043 PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 763NJ UT WOS:000188092000004 PM 14706566 ER PT J AU Ellenberg, SS AF Ellenberg, SS TI Analytical, practical and regulatory issues in prevention studies SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT 2nd International Conference on Statistical Methodology on Alzheimers Disease Research CY MAY 10-12, 2002 CL LEXINGTON, KENTUCKY DE disease prevention; clinical trials; surrogate endpoints; missing data; safety monitoring ID CLINICAL-TRIALS; CARDIOVASCULAR-DISEASE; SURROGATE MARKERS; RANDOMIZED TRIALS; BETA-CAROTENE; LUNG-CANCER; HEART; ADHERENCE; HEALTH; DROPOUTS AB Prevention studies, as distinguished from studies investigating treatments for established disease, present some distinct challenges. Perhaps the most extensive experience with preventive agents is in the area of infectious diseases; vaccines have been extremely effective in preventing many such diseases. Vaccines have been, and continue to be, studied in other disease areas such as certain cancers, but as yet have not achieved success outside of infectious disease prevention. One obvious and important feature of prevention studies is that they enrol healthy individuals; thus such studies require particularly high standards for the safety of those enrolled (and those who might ultimately receive the product being tested). Prevention studies often need to be quite large, as the types of diseases most important to prevent tend to be uncommon. Large studies usually require simplified approaches; to ensure high quality of data on the key variables it may be necessary to compromise on the amount of data collected, frequency of data collection, and other aspects of trial design. The reliability of randomization and blinding may be especially important in these large studies, as bias could easily overwhelm the small effects that are usually sought. Often, biomarkers thought to indicate developing but as yet subclinical disease, will be important to evaluate; whether such markers can serve as primary endpoints in prevention studies has been a contentious issue in many contexts. Studies in older populations, such as those at risk for Alzheimer's Disease, raise challenges such as accounting for competing risks, and considering potential interactions of preventive agents with multiple medications often used by the elderly. Published in 2004 by John Wiley Sons, Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Rockville, MD 20852 USA. RP Ellenberg, SS (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, 1401 Rockville Pike,HFM-210, Rockville, MD 20852 USA. EM ellenberg@cber.fda.gov NR 34 TC 4 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 30 PY 2004 VL 23 IS 2 BP 297 EP 303 DI 10.1002/sim.1717 PG 7 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 763TW UT WOS:000188117400013 PM 14716730 ER PT J AU Mani, RB AF Mani, RB TI The evaluation of disease modifying therapies in Alzheimer's disease: a regulatory viewpoint SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT 2nd International Conference on Statistical Methodology on Alzheimers Disease Research CY MAY 10-12, 2002 CL LEXINGTON, KY DE Alzheimer's disease; prevention; drug; clinical trials; surrogate markers; brain imaging ID INTERNATIONAL WORKING GROUP; DEMENTIA DRUG GUIDELINES; SURROGATE END-POINTS; CLINICAL-TRIALS; POSITION PAPER; PROGRESSION; HARMONIZATION; VALIDATION; CRITERIA AB Several drugs have received marketing approval in this country for the treatment of dementia of the Alzheimer's type. Their approval has been based on clinical trial designs that do not permit a distinction to be made between an effect of the drug on the symptoms of that disease, and an effect on the pathophysiological mechanisms that underlie that disorder. The latter effect has been referred to as 'disease-modifying.' In recent years there has been considerable interest in developing disease-modifying treatments for Alzheimer's disease (AD), using either specific clinical designs, or surrogate markers, such as brain imaging modalities. This paper outlines the regulatory framework governing how the Food and Drug Administration addresses new drug claims, the current basis for approving drugs for the treatment of AD, clinical trial designs that have been proposed as a means of demonstrating disease-modifying effects, a general and regulatory background to the use of surrogate markers in drug development, and, finally, views about the possible role of surrogate markers, especially brain imaging, as outcome measures in clinical trials intended to produce disease-modifying effects in Alzheimer's Disease. Copyright (C) 2004 John Wiley Sons, Ltd. C1 US FDA, Div Neuropharmacol Drug Prod, Rockville, MD 20852 USA. RP Mani, RB (reprint author), US FDA, Div Neuropharmacol Drug Prod, HFD-120,1451 Rockville Pike,Room 4040, Rockville, MD 20852 USA. EM manir@cder.fda.gov NR 21 TC 49 Z9 49 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD JAN 30 PY 2004 VL 23 IS 2 BP 305 EP 314 DI 10.1002/sim.1718 PG 10 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 763TW UT WOS:000188117400014 PM 14716731 ER PT J AU Acheson, DWK Fiore, AE AF Acheson, DWK Fiore, AE TI Preventing foodborne disease - What clinicians can do SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Ctr Dis Control & Prevent, Div Viral Hepatitis, Natl Ctr Infect Dis, Atlanta, GA USA. RP Acheson, DWK (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 0 TC 17 Z9 17 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 29 PY 2004 VL 350 IS 5 BP 437 EP 440 DI 10.1056/NEJMp038213 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 767QJ UT WOS:000188463900004 PM 14749450 ER PT J AU Marcy, SM Kohl, KS Dagan, R Nalin, D Blum, M Jones, MC Hansen, J Labadie, J Lee, L Martin, BL O'Brien, K Rothstein, E Vermeer, P AF Marcy, SM Kohl, KS Dagan, R Nalin, D Blum, M Jones, MC Hansen, J Labadie, J Lee, L Martin, BL O'Brien, K Rothstein, E Vermeer, P CA Brighton Collaboration Fever Worki TI Fever as an adverse event following immunization: case definition and guidelines of data collection, analysis, and presentation SO VACCINE LA English DT Article DE fever; adverse events following immunization; case definition; guidelines ID TYMPANIC MEMBRANE TEMPERATURES; INFRARED EAR THERMOMETRY; RECTAL TEMPERATURE; BODY-TEMPERATURE; NEWBORN-INFANTS; YOUNG-CHILDREN; AXILLARY; PALPATION; DIFFERENCE; ACCURACY C1 Ctr Dis Control & Prevent, Natl Immunizat Program, Atlanta, GA 30333 USA. Harbor UCLA Med Ctr, Los Angeles, CA USA. Soroka Med Ctr, IL-84101 Beer Sheva, Israel. Merck & Co Inc, West Point, PA USA. Wyeth Res, Collegeville, PA USA. Calif DHS Immunizat Branch, Berkeley, CA USA. Kaiser Permanente Hlth Care Program, Oakland, CA USA. Netherlands Pharmacovigilance Ctr Lareb, sHertogenbosch, Netherlands. US FDA, Rockville, MD 20857 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Pennridge Pediat Associates, Sellersville, PA USA. Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Basel, Childrens Hosp, Basel, Switzerland. RP Kohl, KS (reprint author), Ctr Dis Control & Prevent, Natl Immunizat Program, 1600 Clifton Rd,Mailstop E-61, Atlanta, GA 30333 USA. EM secretariat@brightoncollaboration.org NR 62 TC 67 Z9 68 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD JAN 26 PY 2004 VL 22 IS 5-6 BP 551 EP 556 DI 10.1016/j.vaccine.2003.09.007 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 775YB UT WOS:000189087300002 PM 14741143 ER PT J AU Bonhoeffer, J Gold, MS Heijbel, H Vermeer, P Blumberg, D Braun, M de Souza-Brito, G Davis, RL Halperin, S Heininger, U Khuri-Bulos, N Menkes, J Nokleby, H AF Bonhoeffer, J Gold, MS Heijbel, H Vermeer, P Blumberg, D Braun, M de Souza-Brito, G Davis, RL Halperin, S Heininger, U Khuri-Bulos, N Menkes, J Nokleby, H CA Brighton Collaboration HHE Working TI Hypotonic-Hyporesponsive Episode (HHE) as an adverse event following immunization: case definition and guidelines for data collection, analysis, and presentation SO VACCINE LA English DT Article ID ACELLULAR PERTUSSIS VACCINES; WHOLE-CELL; VACCINATION; CHILDREN; DIPHTHERIA; INFANTS; EXPERIENCE C1 Univ Basel, Childrens Hosp, Basel, Switzerland. Univ Adelaide, Dept Paediat, Adelaide, SA, Australia. Swedish Inst Infect Dis Control, Lund, Sweden. Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. US FDA, Rockville, MD 20857 USA. Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. Univ Washington, Seattle, WA 98195 USA. Dalhousie Univ, Halifax, NS, Canada. Jordan Univ Hosp, Amman, Jordan. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Natl Inst Publ Hlth, Oslo, Norway. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Bonhoeffer, J (reprint author), Univ Basel, Childrens Hosp, Basel, Switzerland. EM secretariat@brightoncollaboration.org RI Bonhoeffer, Jan/E-5903-2014 NR 20 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JAN 26 PY 2004 VL 22 IS 5-6 BP 563 EP 568 DI 10.1016/j.vaccine.2003.09.009 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 775YB UT WOS:000189087300004 PM 14741145 ER PT J AU Bines, JE Kohl, KS Forster, J Zanardi, LR Davis, RL Hansen, J Murphy, TM Music, S Niu, M Varricchio, F Vermeer, P Wong, EJC AF Bines, JE Kohl, KS Forster, J Zanardi, LR Davis, RL Hansen, J Murphy, TM Music, S Niu, M Varricchio, F Vermeer, P Wong, EJC CA Brighton Collaboration Intussuscep TI Acute intussusception in infants and children as an adverse event following immunization: case definition and guidelines of data collection, analysis, and presentation SO VACCINE LA English DT Article DE intussusception; adverse events following immunization; care definition; data guidelines ID VACCINE C1 Ctr Dis Control & Prevent, Natl Immunizat Program, Atlanta, GA 30333 USA. Royal Childrens Hosp, Parkville, Vic 3052, Australia. St Josefs Hosp, Freiburg, Germany. Univ Washington, Seattle, WA 98195 USA. Kaiser Permanente Hlth Care Program, Oakland, CA USA. Merck Res Labs, W Point, PA USA. US FDA, Rockville, MD 20857 USA. Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. Harbor UCLA Med Ctr, Torrance, CA 90509 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Basel, Childrens Hosp, Basel, Switzerland. RP Kohl, KS (reprint author), Ctr Dis Control & Prevent, Natl Immunizat Program, 1600 Clifton Rd,Mailstop E-61, Atlanta, GA 30333 USA. EM secretariat@brightoncollaboration.org NR 7 TC 100 Z9 105 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 JAN 26 PY 2004 VL 22 IS 5-6 BP 569 EP 574 DI 10.1016/j.vaccine.2003.09.016 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 775YB UT WOS:000189087300005 PM 14741146 ER PT J AU Rothstein, E Kohl, KS Ball, L Halperin, SA Halsey, N Hammer, SJ Heath, PT Hennig, R Kleppinger, C Labadie, J Varricchio, F Vermeer, P Walop, W AF Rothstein, E Kohl, KS Ball, L Halperin, SA Halsey, N Hammer, SJ Heath, PT Hennig, R Kleppinger, C Labadie, J Varricchio, F Vermeer, P Walop, W CA Brighton Collaboration Local React TI Nodule at injection site as an adverse event following immunization: case definition and guidelines for data collection, analysis, and presentation SO VACCINE LA English DT Article ID ACELLULAR PERTUSSIS-VACCINE; PNEUMOCOCCAL POLYSACCHARIDE VACCINE; HEPATITIS-A VACCINE; DIPHTHERIA-TETANUS; HEALTHY-ADULTS; IMMUNOGENICITY; ALUMINUM; SAFETY; CHILDREN; GRANULOMA C1 Ctr Dis Control & Prevent, Natl Immunizat Program, Atlanta, GA 30333 USA. Pennridge Pediatr Associates, Sellersville, PA USA. US FDA, Rockville, MD 20857 USA. Dalhousie Univ, Halifax, NS, Canada. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Calif Dept Hlth Serv, Berkeley, CA 94704 USA. St George Hosp, Sch Med, London, England. Chiron Behring GmbH & Co, Marburg, Germany. US FDA, Rockville, MD 20857 USA. Netherlands Pharmacovigilance Ctr Lareb, sHertogenbosch, Netherlands. Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. Hlth Canada, Ottawa, ON K1A 0L2, Canada. Univ Basel, Childrens Hosp, Basel, Switzerland. RP Kohl, KS (reprint author), Ctr Dis Control & Prevent, Natl Immunizat Program, 1600 Clifton Rd,Mailstop E-61, Atlanta, GA 30333 USA. EM secretariat@brightoncollaboration.org NR 42 TC 28 Z9 28 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 JAN 26 PY 2004 VL 22 IS 5-6 BP 575 EP 585 DI 10.1016/j.vaccine.2003.09.005 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 775YB UT WOS:000189087300006 PM 14741147 ER PT J AU Samore, MH Evans, RS Lassen, A Gould, P Lloyd, J Gardner, RM Abouzelof, R Taylor, C Woodbury, DA Willy, M Bright, RA AF Samore, MH Evans, RS Lassen, A Gould, P Lloyd, J Gardner, RM Abouzelof, R Taylor, C Woodbury, DA Willy, M Bright, RA TI Surveillance of medical device - Related hazards and adverse events in hospitalized patients SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CLOSED CLAIMS ANALYSIS; INTENSIVE-CARE-UNIT; DRUG EVENTS; QUALITY IMPROVEMENT; SAFETY; ANESTHESIA; DESIGN AB Context Although adverse drug events have been extensively evaluated by computer-based surveillance, medical device errors have no comparable surveillance techniques. Objectives To determine whether computer-based surveillance can reliably identify medical device-related hazards (no known harm to patient) and adverse medical device events (AMDEs; patient experienced harm) and to compare alternative methods of detection of device-related problems. Design, Setting, and Participants This descriptive study was conducted from January through September 2000 at a 520-bed tertiary teaching institution in the United States with experience in using computer tools to detect and prevent adverse drug events. All 20441 regular and short-stay patients (excluding obstetric and newborn patients) were included. Main Outcome Measures Medical device events as detected by computer-based flags, telemetry problem checklists, International Classification of Diseases, Ninth Revision (ICD-9) discharge code (which could include AMDEs present at admission), clinical engineering work logs, and patient survey results were compared with each other and with routine voluntary incident reports to determine frequencies, proportions, positive predictive values, and incidence rates by each technique. Results Of the 7059 flags triggered, 552 (7.8%) indicate a device-related hazard or AMDE. The estimated 9-month incidence rates (number per 1000 admissions [95% confidence intervals]) for AMDEs were 1.6 (0.9-2.5) for incident reports, 27.7 (24.9-30.7) for computer flags, and 64.6 (60.4-69.1) for ICD-9 discharge codes. Few of these events were detected by more than 1 surveillance method, giving an overall incidence of AMDE detected by at least 1 of these methods of 83.7 per 1000 (95% confidence interval, 78.8-88.6) admissions. The positive predictive value of computer flags for detecting device-related hazards and AMDEs ranged from 0% to 38%. Conclusions More intensive surveillance methods yielded higher rates of medical device problems than found with traditional voluntary reporting, with little overlap between methods. Several detection methods had low efficiency in detecting AMDEs. The high rite of AMDEs suggests that AMDEs are an important patient safety issue, but additional research is necessary to identify optimal AMIDE detection strategies. C1 Univ Utah, Sch Med, Salt Lake City, UT 84132 USA. LDS Hosp Intermt Hlth Care, Salt Lake City, UT USA. Vet Affairs Salt Lake City Hlth Care Syst, Salt Lake City, UT USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Samore, MH (reprint author), Univ Utah, Sch Med, 50 N Med Dr,Room AC104, Salt Lake City, UT 84132 USA. RI Bright, Roselie/D-2240-2016 FU PHS HHS [223-99-6101] NR 36 TC 62 Z9 62 U1 2 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 21 PY 2004 VL 291 IS 3 BP 325 EP 334 DI 10.1001/jama.291.3.325 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 764ZZ UT WOS:000188243100032 PM 14734595 ER PT J AU Keller, JE Cai, F Neale, EA AF Keller, JE Cai, F Neale, EA TI Uptake of botulinum neurotoxin into cultured neurons SO BIOCHEMISTRY LA English DT Article ID SYNAPTIC PROTEIN SNAP-25; E DERIVATIVE TOXIN; SPINAL-CORD CELLS; CLOSTRIDIAL NEUROTOXINS; NEUROMUSCULAR-JUNCTION; TYROSINE PHOSPHORYLATION; LIPID BILAYERS; ION CHANNELS; HEAVY-CHAIN; SEROTYPE-A AB Botulinum neurotoxins (BoNTs) act within the synaptic terminal to block neurotransmitter release. The toxin enters the neuron by binding to neuronal membrane receptor(s), being taken up into an endosome-like compartment, and penetrating the endosome membrane via a pH-dependent translocation process. Once within the synaptic cytoplasm, BoNT serotypes A and E cleave separate sites on the C-terminus of the neuronal protein SNAP-25, one of the SNARE proteins required for synaptic vesicle fusion. In this study, we measured the effect of brief toxin exposure on SNAP-25 proteolysis in neuronal cell cultures as an indicator of toxin translocation. The results indicate that (1) uptake of both BoNT-A and -E is enhanced with synaptic activity induced by K+ depolarization in the presence of Ca2+ and (2) translocation of BoNT-A from the acidic endosomal compartment is slow relative to that of BoNT-E. Polyclonal antisera against each toxin protect cells when applied with the toxin during stimulation but has no effect when added immediately after toxin exposure, indicating that toxin endocytosis occurs with synaptic activity. Both serotypes cleave SNAP-25 at concentrations between 50 pM and 4 nM. IC50 values for SNAP-25 cleavage are approximately 0.5 nM for both serotypes. Inhibition of the pH-dependent translocation process by pretreating cultures with concanamycin A (Con A) prevents cleavage of SNAP-25 with IC50 values of similar to25 nM. Addition of Con A at times up to 15 min after toxin exposure abrogated BoNT-A action; however, addition of Con A after 40 min was no longer protective. In contrast, Con A inhibited, but did not prevent, translocation of BoNT-E even when added immediately after toxin exposure, indicating that pH-dependent translocation of BoNT-E is rapid relative to that of BoNT-A. This study demonstrates that uptake of both BoNT-A and -E is enhanced with synaptic activity and that translocation of the toxin catalytic moiety into the cytosol occurs at different rates for these two serotypes. C1 US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Toxins, Bethesda, MD 20892 USA. NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Keller, JE (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Toxins, Bethesda, MD 20892 USA. EM kellerj@cber.fda.gov NR 50 TC 101 Z9 106 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 20 PY 2004 VL 43 IS 2 BP 526 EP 532 DI 10.1021/bi0356698 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 763RH UT WOS:000188113900027 PM 14717608 ER PT J AU Sapsford, KE Rasooly, A Taitt, CR Ligler, FS AF Sapsford, KE Rasooly, A Taitt, CR Ligler, FS TI Detection of Campylobacter and Shigella species in food samples using an array biosensor SO ANALYTICAL CHEMISTRY LA English DT Article ID ENTEROINVASIVE ESCHERICHIA-COLI; LINKED-IMMUNOSORBENT-ASSAY; POLYMERASE-CHAIN-REACTION; RAPID DETECTION; ENRICHMENT CULTURE; ENZYME-IMMUNOASSAY; POULTRY SAMPLES; PCR ASSAY; JEJUNI; IDENTIFICATION AB Campylobacter and Shigella bacteria are common causes of food- and water-borne illness worldwide. There is a current need in food, medical, environmental, and military markets for a rapid and user-friendly method of detecting such pathogens. The array biosensor developed at the NRL encompasses these qualities. In this study, 25-min, sandwich immunoassays were developed for the detection of Campylobacter and Shigella species in both buffer and a variety of food and beverage samples. The limit of detection for Shigella dysenteriae in buffer and chicken carcass wash was 4.9 x 10(4) cfu mL(-1), whereas Campylobacter jejuni could be measured at concentrations as low as 9.7 x 10(2) cfu mL(-1). The limits of detection and dynamic range were found to vary depending on the sample matrix, but could be improved by running the sample over the waveguide surface for longer periods of time. Samples were run with no preconcentration or enrichment steps and little-to-no sample pretreatment prior to analysis. C1 USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. US FDA, College Pk, MD 20740 USA. George Mason Univ, Manassas, VA USA. RP Ligler, FS (reprint author), USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. EM fligler@cbmse.nrl.navy.mil NR 28 TC 65 Z9 71 U1 2 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JAN 15 PY 2004 VL 76 IS 2 BP 433 EP 440 DI 10.1021/ac035122z PG 8 WC Chemistry, Analytical SC Chemistry GA 764GJ UT WOS:000188198800027 PM 14719894 ER PT J AU Powers, JH Albrecht, R AF Powers, JH Albrecht, R TI Lipid amphotericin B formulations as comparators in clinical trials SO CLINICAL INFECTIOUS DISEASES LA English DT Letter ID NEUTROPENIA; TIME C1 US FDA, Ctr Drug Evaluat & Res, Div Special Pathogen & Immunol Drug Prod, Rockville, MD 20857 USA. US FDA, Off Drug Evaluat IV, Rockville, MD 20857 USA. RP Powers, JH (reprint author), 9201 Corp Blvd,HFD-104, Rockville, MD 20850 USA. NR 7 TC 1 Z9 1 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 15 PY 2004 VL 38 IS 2 BP 305 EP 306 DI 10.1086/381269 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 757NN UT WOS:000187568500023 PM 14699471 ER PT J AU Karginov, VA Robinson, TM Riemenschneider, J Golding, B Kennedy, M Shiloach, J Alibek, K AF Karginov, VA Robinson, TM Riemenschneider, J Golding, B Kennedy, M Shiloach, J Alibek, K TI Treatment of anthrax infection with combination of ciprofloxacin and antibodies to protective antigen of Bacillus anthracis SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE anthrax treatment; anti-protective antigen antibody; ciprofloxacin; mouse model ID DELIVERED POLYCLONAL ANTIBODIES; PSEUDOMONAS-AERUGINOSA; GUINEA-PIGS; IMMUNOGLOBULIN; PROPHYLAXIS; EFFICACY; SPORES; MICE AB Currently there is no effective treatment for inhalational anthrax beyond administration of antibiotics shortly after exposure. There is need for new, safe and effective treatments to supplement traditional antibiotic therapy. Our study was based on the premise that simultaneous inhibition of lethal toxin action with antibodies and blocking of bacterial growth by antibiotics will be beneficial for the treatment of anthrax. In this study, we tested the effects of a combination treatment using purified rabbit or sheep anti-protective antigen (PA) antibodies and the antibiotic ciprofloxacin in a rodent anthrax model. In mice infected with a dose of Bacillus anthracis Sterne strain corresponding to 10 LD50, antibiotic treatment with ciprofloxacin alone only cured 50% of infected animals. Administration of anti-PA IgG in combination with ciprofloxacin produced 90-100% survival. These data indicate that a combination of antibiotic/immunoglobulin therapy is more effective than antibiotic treatment alone in a rodent anthrax model. (C) 2003 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved. C1 Adv Biosyst Inc, Manassas, VA 20110 USA. CBER, FDA, Bethesda, MD USA. NIDDK, NIH, Bethesda, MD USA. George Mason Univ, Ctr Biodef, Manassas, VA USA. RP Karginov, VA (reprint author), Adv Biosyst Inc, 10900 Univ Blvd, Manassas, VA 20110 USA. EM vladimir.karginov@analex.com NR 14 TC 38 Z9 41 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD JAN 15 PY 2004 VL 40 IS 1 BP 71 EP 74 DI 10.1016/S0928-8244(03)00302-X PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 769FL UT WOS:000188615700009 PM 14734189 ER PT J AU Hampshire, V AF Hampshire, V TI Emerging issues regarding informed consent - Consumers calling hotline with concerns SO JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT News Item C1 FDA Ctr Vet Med, Off Surveillance & Compliance, Rockville, MD 20857 USA. RP Hampshire, V (reprint author), FDA Ctr Vet Med, Off Surveillance & Compliance, Rockville, MD 20857 USA. EM VHampshi@CVM.FDA.GOV NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 JAVMA-J AM VET MED A JI JAVMA-J. Am. Vet. Med. Assoc. PD JAN 15 PY 2004 VL 224 IS 2 BP 177 EP 177 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 802BP UT WOS:000220139300006 PM 14736049 ER PT J AU McDermott, MK Schroeder, LW Balsis, SL Paradiso, NA Byrne, ML Briber, RM AF McDermott, MK Schroeder, LW Balsis, SL Paradiso, NA Byrne, ML Briber, RM TI Mechanical properties of polyurethane film exposed to solutions of nonoxynol-9 surfactant and poly(ethylene glycol) SO JOURNAL OF APPLIED POLYMER SCIENCE LA English DT Article DE polyurethanes; mechanical properties; surfactants; swelling; thermal properties ID ORGANIC LIQUIDS; MULTICOMPONENT DIFFUSION; THERMAL TECHNIQUES; POLYMER MEMBRANES; LATEX ALLERGENS; SORPTION; CONDOMS; RUBBER; DETERIORATION; DISSOLUTION AB Mechanical properties of two polyether urethane films (Estane and Tecoflex) were studied after exposure to solutions of nonoxynol 9 (N9) surfactant and poly(ethylene glycol) 400 (PEG) for various times. Large amounts of N9 were absorbed from N9/PEG solutions, resulting in soft-segment plasticization and lower mechanical properties. As the N9 concentration increased, Estane absorbed more liquid and its mechanical properties decreased more compared to Tecoflex, although the mechanical properties of Estane were higher than Tecoflex at low concentrations of N9. Hard-segment domain disruption is probably not occurring because the relationship between the elastic modulus and polymer volume fraction followed Flory's theory for swollen elastic rubber networks and the liquids do not fully dissolve the polymers. The diffusion behavior of N9 and PEG was observed to follow Fickian behavior. Most of the absorption and decrease in mechanical properties occurred within the first 20 h after soaking, implying that additional loss in strength over longer times would be minimal. Mechanical property anisotropy suggests that condoms should be cut from Estane film in an orientation that optimizes the property-orientation relationship for specific end uses. (C) 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 1086-1096, 2004. C1 US FDA, Div Mech & Mat Sci, Off Sci & Technol, Rockville, MD 20850 USA. Marquette Univ, Dept Biomed Engn, Milwaukee, WI 53201 USA. Univ Maryland, Dept Mat & Nucl Engn, College Pk, MD 20742 USA. RP McDermott, MK (reprint author), US FDA, Div Mech & Mat Sci, Off Sci & Technol, 9200 Corp Blvd,HFZ-150, Rockville, MD 20850 USA. RI Briber, Robert/A-3588-2012 OI Briber, Robert/0000-0002-8358-5942 NR 71 TC 7 Z9 7 U1 2 U2 16 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 JAN 15 PY 2004 VL 91 IS 2 BP 1086 EP 1096 DI 10.1002/app.13285 PG 11 WC Polymer Science SC Polymer Science GA 749JA UT WOS:000186915200050 ER PT J AU Walsh, DL Schwerin, MR Kisielewski, RW Kotz, RM Chaput, MP Varney, GW To, TM AF Walsh, DL Schwerin, MR Kisielewski, RW Kotz, RM Chaput, MP Varney, GW To, TM TI Abrasion resistance of medical glove materials SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE glove; abrasion; tear; viral penetration; durability ID BIOMECHANICAL PERFORMANCE; CLINICAL SETTINGS; LATEX; VINYL; PENETRATION; LEAKAGE; PERMEABILITY; INTEGRITY; FATIGUE AB Due to the increasing demand for nonlatex medical gloves in the health-care community, there is a need to assess the durability of alternative glove materials. This study examines durability characteristics of various glove materials by abrasion resistance testing. Natural rubber latex (latex), polyvinyl chloride (vinyl), acrylonitrile butadiene (nitrile), polychloroprene (neoprene), and a styrene-ethylenetbutylene-styrene block copolymer (SEBS) were tested. All test specimens, with the exception of the vinyl, were obtained from surgical gloves. Unaged out-of-the-box specimens as well as those subjected to various degrees of artificial aging were included in the study. After the abrasion sequence, the barrier integrity of the material was assessed through the use of a static leak test. Other traditional tests performed on these materials were viral penetration to validate the abrasion data and tear testing for comparative purposes. The results indicate that specific glove-material performance is dependent upon the particular test under consideration. Most notably, abrasion, even in controlled nonsevere conditions, may compromise to varying degrees the barrier integrity of latex, vinyl, SEBS, nitrile, and neoprene glove materials. However, as evidenced by the results of testing three brands of neoprene gloves, the abrasion resistance of any one glove material may be significantly affected by variations in production processes. (C) 2003 Wiley Periodicals. Inc. C1 US FDA, CDRH, OST, DMMS, Rockville, MD 20850 USA. US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, HFZ 542, Rockville, MD 20852 USA. US FDA, Off Regulat Affairs, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. RP Walsh, DL (reprint author), US FDA, CDRH, OST, DMMS, 9200 Corp Blvd,HFZ 150, Rockville, MD 20850 USA. FU ODCDC CDC HHS [U60/CCU015989-01] NR 27 TC 13 Z9 13 U1 1 U2 9 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD JAN 15 PY 2004 VL 68B IS 1 BP 81 EP 87 DI 10.1002/jbm.b.10055 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 758UR UT WOS:000187669200011 PM 14689500 ER PT J AU Feng, CG Collazo-Custodio, CM Eckhaus, M Hieny, S Belkaid, Y Elkins, K Jankovic, D Taylor, GA Sher, A AF Feng, CG Collazo-Custodio, CM Eckhaus, M Hieny, S Belkaid, Y Elkins, K Jankovic, D Taylor, GA Sher, A TI Mice deficient in LRG-47 display increased susceptibility to mycobacterial infection associated with the induction of lymphopenia SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; INDUCIBLY EXPRESSED GTPASE; INTERFERON-GAMMA; IFN-GAMMA; AVIUM INFECTION; TUBERCULOSIS INFECTION; T-CELLS; RESISTANCE; APOPTOSIS; IDENTIFICATION AB Although IFN-gamma is essential for host control of mycobacterial infection, the mechanisms by which the cytokine restricts pathogen growth are only partially understood. LRG-47 is an IFN-inducible GTP-binding protein previously shown to be required for IFN-gamma-dependent host resistance to acute Listeria monocytogenes and Toxoplasma gondii infections. To examine the role of LRG-47 in control of mycobacterial infection, LRG-47(-/-) and wild-type mice were infected with Mycobacterium avium, and host responses were analyzed. LRG-47 protein was strongly induced in livers of infected wild-type animals in an IFN-gamma-dependent manner. LRG-47(-/-) mice were unable to control bacterial replication, but survived the acute phase, succumbing 11-16 wk postinfection. IFN-gamma-primed, bone marrow-derived macrophages from LRG-47(-/-) and wild-type animals produced equivalent levels of TNF and NO upon M. avium infection in vitro and developed similar intracellular bacterial loads. In addition, priming for IFN-gamma production was observed in T cells isolated from infected LRG-47(-/-) mice. Importantly, however, mycobacterial granulomas in LRG-47(-/-) mice showed a marked lymphocyte deficiency. Further examination of these animals revealed a profound systemic lymphopenia and anemia triggered by infection. As LRG47(-/-) T lymphocytes were found to both survive and confer resistance to M. avium in recipient recombinase-activating gene-2(-/-) mice, the defect in cellular response and bacterial control in LRG-47(-/-) mice may also depend on a factor(s) expressed in a nonlymphocyte compartment. These findings establish a role for LRG-47 in host control of mycobacteria and demonstrate that in the context of the IFN-gamma response to persistent infection, LRG-47 can have downstream regulatory effects on lymphocyte survival. The Journal of Immunology, 2004, 172: 1163-1168. C1 NIAID, Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIH, Vet Resources Program, Off Res Serv, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Bacterial Allergen & Parasit Prod, Lab Mycobacterial Dis & Cellular Immun, Rockville, MD 20852 USA. Duke Univ, Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC 27710 USA. Duke Univ, Vet Affairs Med Ctr, Ctr Study Aging & Human Dev, Durham, NC 27710 USA. Duke Univ, Vet Affairs Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Vet Affairs Med Ctr, Dept Immunol, Durham, NC 27710 USA. RP Feng, CG (reprint author), NIAID, Immunol Sect, Parasit Dis Lab, NIH, Room 6148,Bldg 50,50 S Dr, Bethesda, MD 20892 USA. EM cfeng@niaid.niti.gov NR 33 TC 83 Z9 90 U1 1 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2004 VL 172 IS 2 BP 1163 EP 1168 PG 6 WC Immunology SC Immunology GA 762WM UT WOS:000188005200051 PM 14707092 ER PT J AU Wong-Chew, RM Islas-Romero, R Garcia-Garcia, MD 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, MD Beeler, JA Audet, S Santos-Preciado, JI Gans, H Lew-Yasukawa, L Maldonado, YA Arvin, AM Valdespino-Gomez, JL TI Induction of cellular and humoral immunity after aerosol or subcutaneous administration of Edmonston-Zagreb measles vaccine as a primary dose to 12-month-old children SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID RANDOMIZED-TRIAL; MMR VACCINATION; RESPONSES; ANTIBODY; INFANTS; SCHOOLCHILDREN; ROUTES AB Infants were immunized by aerosol (10(3.6) plaque-forming units [pfu]/dose) or subcutaneous (sc) (10(4.27) pfu/dose) administration of Edmonston-Zagreb measles vaccine. Measles-specific T cell proliferative responses with a stimulation index of greater than or equal to3 developed in 72% of children given aerosol-administered vaccine, compared with 87% given sc-administered vaccine (P = .06). Seroconversion rates were 90% after aerosol-administered vaccine and 100% after sc-administered vaccine (P = .01), and measles geometric mean titers were 237 milli-international units (mIU) (95% confidence interval [CI], 146-385 mIU) and 487 mIU (95% CI, 390-609 mIU) in each group, respectively (P = .01). Measles-specific T and B cell responses were weaker after aerosol than after sc vaccination, indicating a need to use a higher aerosol dose to achieve optimal immunogenicity. C1 Univ Nacl Autonoma Mexico, Fac Med, Dept Expt Med, Mexico City 06726, DF, Mexico. Ctr Nacl Salud Infancia & Adolescencia, Secretaria Salud, Mexico City, DF, Mexico. Inst Nacl Salud Publ, Cuernavaca, Morelos, Mexico. Stanford Univ, Sch Med, Stanford, CA 94305 USA. US FDA, Rockville, MD 20857 USA. RP Wong-Chew, RM (reprint author), Univ Nacl Autonoma Mexico, Fac Med, Dept Expt Med, Dr Balmis 148,Colonia Doctores, Mexico City 06726, DF, Mexico. EM rmwong@correo.unam.mx FU NICHD NIH HHS [HD01310, HD33698]; PHS HHS [A137127] NR 18 TC 39 Z9 41 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 15 PY 2004 VL 189 IS 2 BP 254 EP 257 DI 10.1086/380565 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 763QD UT WOS:000188097900012 PM 14722890 ER PT J AU Rockett, JC Burczynski, ME Fornace, AJ Herrmann, PC Krawetz, SA Dix, DJ AF Rockett, JC Burczynski, ME Fornace, AJ Herrmann, PC Krawetz, SA Dix, DJ TI Surrogate tissue analysis: monitoring toxicant exposure and health status of inaccessible tissues through the analysis of accessible tissues and cells SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE disease states; genomics; hair follicles; ionizing radiation; proteomics; peripheral blood lymphocytes; peripheral blood mononuclear cells; renal cell carcinoma; sperm; STA, surrogate tissue analysis; toxicity ID GENE-EXPRESSION SIGNATURES; IONIZING-RADIATION; PREDICT SURVIVAL; STRESS GENES; PROFILES; CANCER; BLOOD; DISEASE; IDENTIFICATION; MICROARRAY AB Genomics and proteomics have made it possible to define molecular physiology in exquisite detail, when tissues are accessible for sampling. However, many tissues are not accessible for human diagnostic evaluations or experimental studies, creating the need for surrogates that afford insight into exposures and effects in such tissues. Surrogate tissue analysis (STA) incorporating contemporary genomic and proteomic technologies may be useful in determining toxicant exposure and effect, or disease state, in target tissues at the pre- or early clinical stage. We present here a discussion of STA based on presentations given at the Society of Toxicology's 2003 annual meeting's "Innovations in Applied Toxicology" symposium. Speakers at the symposium (Box 1) discussed various potential applications of STA, including the use of peripheral blood lymphocytes (PBLs) as a source of genetic biomarkers to monitor radiation exposure; the use of gene expression analysis of PBLs and hair follicles as a means to monitor the impact of toxicants on inaccessible organs; the characterization of disease-associated gene signatures in peripheral blood mononuclear cells (PBMCs) of renal cell carcinoma (RCC) patients; the use of sperm RNA to determine genetic and environmental effects on sperm development in the testis; and the use of serum protein profiles to monitor the development and progression of various cancers. Also discussed are some of the challenges that must be overcome if the utility of STA is to be proven, and thus permit researchers to move this concept from the laboratory to the clinical environment. Published by Elsevier Inc. C1 US EPA, Off Res & Dev, Natl Hlth & Environm Res Lab, Reprod Toxicol Div, Res Triangle Pk, NC 27711 USA. Wyeth Ayerst Res, Discovery Med, Andover, MA 01810 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Wayne State Univ, Reprod Med Network, NICHD, Inst Comp Sci, Detroit, MI 48201 USA. RP Rockett, JC (reprint author), US EPA, Off Res & Dev, Natl Hlth & Environm Res Lab, Reprod Toxicol Div, Res Triangle Pk, NC 27711 USA. EM rockett.john@epa.gov RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X FU NICHD NIH HHS [HD36512] NR 45 TC 48 Z9 51 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JAN 15 PY 2004 VL 194 IS 2 BP 189 EP 199 DI 10.1016/j.taap.2003.09.005 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 777AV UT WOS:000189152600009 PM 14736499 ER PT J AU Bos, J Crutcher, JM Cote, T Greenwald, MA Polder, J Srinivasan, A Arduino, M Jernigan, DB Beall, B Elliott, JA Facklam, RR Schuchat, A Van Beneden, C Lee, E Ferguson, D AF Bos, J Crutcher, JM Cote, T Greenwald, MA Polder, J Srinivasan, A Arduino, M Jernigan, DB Beall, B Elliott, JA Facklam, RR Schuchat, A Van Beneden, C Lee, E Ferguson, D TI Invasive Streptococcus pyogenes after allograft implantation - Colorado, 2003 (Reprinted from MMWR, vol 52, pg 1173-1176, 2003) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint ID DISEASE C1 Oklahoma Dept Hlth, Oklahoma City, OK 73117 USA. Colorado Dept Publ Hlth & Environm, Denver, CO 80246 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. CDC, Div Healthcare Qual Promot, Atlanta, GA 30333 USA. CDC, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. CDC, Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. RP Bos, J (reprint author), Oklahoma Dept Hlth, Oklahoma City, OK 73117 USA. RI Arduino, Matthew/C-1461-2012 OI Arduino, Matthew/0000-0001-7072-538X NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 14 PY 2004 VL 291 IS 2 BP 174 EP 176 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 762YZ UT WOS:000188040900009 ER PT J AU Kasim, NA Whitehouse, M Ramachandran, C Bermejo, M Lennernas, H Hussain, AS Junginger, HE Stavchansky, SA Midha, KK Shah, VP Amidon, GL AF Kasim, Nehal A. Whitehouse, Marc Ramachandran, Chandrasekharan Bermejo, Marival Lennernas, Hans Hussain, Ajaz S. Junginger, Hans E. Stavchansky, Salomon A. Midha, Kamal K. Shah, Vinod P. Amidon, Gordon L. TI Molecular properties of WHO essential drugs and provisional biopharmaceutical classification SO MOLECULAR PHARMACEUTICS LA English DT Article DE BCS; solubility; dose number; permeability; partition coefficient; WHO essential drugs; pK(a) AB The purpose of this study is to provisionally classify, based on the Biopharmaceutics Classification System (BCS), drugs in immediate-release dosage forms that appear on the World Health Organization (WHO) Essential Drug List. The classification in this report is based on the aqueous solubility of the drugs reported in commonly available reference literature and a correlation of human intestinal membrane permeability for a set of 29 reference drugs with their calculated partition coefficients. The WHO Essential Drug List consists of a total of 325 medicines and 260 drugs, of which 123 are oral drugs in immediate-release (IR) products. Drugs with dose numbers less than or equal to unity [Do = (maximum dose strength/250 mL)/solubility :5 1] are defined as high-solubility drugs. Drug solubility for the uncharged, lowest-solubility form reported in the Merck Index or USP was used. Of the 123 WHO oral drugs in immediate-release dosage forms, 67% (82) were determined to be high-solubility drugs. The classification of permeability is based on correlations of human intestinal permeability of 29 reference drugs with the estimated log P or CLogP lipophilicity values. Metoprolol was chosen as the reference compound for permeability and log P or CLogP. Log P and CLogP were linearly correlated (r(2) = 0.78) for 104 drugs. A total of 53 (43.1%) and 62 (50.4%) drugs on the WHO list exhibited log P and CLogP estimates, respectively, that were greater than or equal to the corresponding metoprolol value and are classified as high-permeability drugs. The percentages of the drugs in immediate-release dosage forms that were classified as BCS Class 1, Class 2, Class 3, and Class 4 drugs using dose number and log P were as follows: 23.6% in Class 1, 17.1% in Class 2, 31.7% in Class 3, and 10.6% in Class 4. The remaining 17.1% of the drugs could not be classified because of the inability to calculate log P values because of missing fragments. The corresponding percentages in the various BCS classes with dose number and CLogP criteria were similar: 28.5% in Class 1, 19.5% in Class 2, 35.0% in Class 3, and 9.8% in Class 4. The remaining 7.3% of the drugs could not be classified since CLogP could not be calculated. These results suggest that a satisfactory bioequivalence (BE) test for more than 55% of the high-solubility Class 1 and Class 3 drug products on the WHO Essential Drug List may be based on an in vitro dissolution test. The use of more easily implemented, routinely monitored, and reliable in vitro dissolution tests can ensure the clinical performance of drug products that appear on the WHO Essential Medicines List. C1 [Kasim, Nehal A.; Whitehouse, Marc; Ramachandran, Chandrasekharan; Amidon, Gordon L.] Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. [Kasim, Nehal A.] Univ Alexandria, Coll Pharm, Alexandria, Egypt. [Bermejo, Marival] Univ Valencia, Dept Pharm & Technol, Valencia, Spain. [Lennernas, Hans] Uppsala Univ, BMC, Dept Pharm, SE-75123 Uppsala, Sweden. [Hussain, Ajaz S.; Shah, Vinod P.] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Junginger, Hans E.] Leiden Amsterdam Ctr Drug Res, Div Pharmaceut Technol, NL-2300 RA Leiden, Netherlands. [Stavchansky, Salomon A.] Univ Texas Austin, Coll Pharm, Div Pharmaceut, Austin, TX 78712 USA. [Midha, Kamal K.] PharmaLytics Inc, Saskatoon, SK S7N 3R2, Canada. [Midha, Kamal K.] Univ Saskatchewan, Coll Med, Saskatoon, SK S7N 5E5, Canada. [Midha, Kamal K.] Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. RP Amidon, GL (reprint author), Univ Michigan, Coll Pharm, 428 Church St, Ann Arbor, MI 48109 USA. EM glamidon@umich.edu RI Bermejo, Marival/A-4163-2009 OI Bermejo, Marival/0000-0001-5022-0544 FU NASA [NAG5-3874]; NIH [R01-GM37188] FX This work was supported in part by NASA Grant NAG5-3874 and NIH Grant R01-GM37188. NR 24 TC 418 Z9 437 U1 8 U2 68 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 12 PY 2004 VL 1 IS 1 BP 85 EP 96 DI 10.1021/mp034006h PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA V54FP UT WOS:000203664900010 PM 15832504 ER PT J AU Yan, J Wang, L Fu, PP Yu, HT AF Yan, J Wang, L Fu, PP Yu, HT TI Photomutagenicity of 16 polycyclic aromatic hydrocarbons from the US EPA priority pollutant list SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE polycyclic aromatic hydrocarbons; photomutagemcity; light irradiation; Salmonella typhimurium TA102 and TA98 ID SINGLE-STRAND CLEAVAGE; INDUCED DNA CLEAVAGE; SKIN-CANCER; ULTRAVIOLET-RADIATION; UVA; PHOTOTOXICITY; PHOTOCHEMISTRY; MUTAGENICITY; GENOTOXICITY; ACTIVATION AB The photomutagenicity of 16 polycyclic aromatic hydrocarbons (PAHs), all on the United States Environmental Protection Agency (US EPA) priority pollutant list, was studied. Concomitant exposing the Salmonella typhimurium bacteria strain TA 102 to one of the PAHs and light (I. I J/cm(2) UVA + 2.1 J/cm(2) visible) without the activation enzyme S9, strong photomutagenic response is observed for anthracene, benz[a]anthracene, benzo[ghi]perylene, benzo[alpha]pyrene, indeno[1,2,3-cd]pyrene, and pyrene. Under the same conditions, acenaphthene, acenaphthylene, benzo[k]fluoranthene, chrysene, and fluorene are weakly photomutagenic. Benzo[b]fluoranthene, fluoranthene, naphthalene, phenanthrene, and dibenz[a,h]anthracene are not photomutagenic. These results indicate that PAHs can be activated by light and become mutagenic in Salmonella TA102 bacteria. At the same time, the mutagenicity for all the 16 PAHs was examined with the standard mutagenicity test with 10% S9 as the activation system. Benzo[b]fluoranthene, benzo[k]fluoranthene, chrysene, acenaphthylene, and fluorene are weakly mutagenic, while the rest of the PAHs are not. In general, the photomutagenicity of PAHs in TA102 does not correlate with their S9-activated mutagenicity in either TA102 or TA98/TA100 since they involve different activation mechanisms. (C) 2003 Elsevier B.V. All rights reserved. C1 Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Yu, HT (reprint author), Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. EM yu@ccaix.jsums.edu FU NCRR NIH HHS [G12 RR013459, G12RR13459]; NIGMS NIH HHS [S06 GM008047, S06 GM008047-290048, S06 GM08047] NR 50 TC 97 Z9 110 U1 4 U2 26 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD JAN 10 PY 2004 VL 557 IS 1 BP 99 EP 108 DI 10.1016/j.mrgentox.2003.10.004 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 768EM UT WOS:000188530700010 PM 14706522 ER PT J AU Lague, P Pastor, RW Brooks, BR AF Lague, P Pastor, RW Brooks, BR TI Pressure-based long-range correction for Lennard-Jones interactions in molecular dynamics simulations: Application to alkanes and interfaces SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; PARTICLE MESH EWALD; COMPUTER-SIMULATION; PHOSPHOLIPID MONOLAYER; LIPID-BILAYERS; WATER; FORCES; MOTION; GRAMICIDIN; DIFFUSION AB A straightforward method that accounts for the long-range Lennard-Jones (LJ) terms in constant pressure molecular dynamics simulations is presented. This long-range correction (LRC) consists of an additional applied pressure tensor which is periodically calculated from the difference of instantaneous pressures at the selected cutoff and a very long cutoff. It provides results that are nearly independent of the LJ cutoff distance at negligible additional calculation costs, and is particularly suited for anisotropic systems such as liquid/ liquid interfaces or heterogeneous macromolecules where approximations based on spherically symmetric radial distribution functions are expected to fail. The utility of the method is demonstrated for a series of alkanes and water, and for interfaces including a lipid bilayer. The LRC increases densities and decreases isothermal compressibilities, with the changes larger for alkanes than for water (where the long-range interactions are dominated by electrostatic interactions). While implementation of the LRC will not necessarily improve agreement with a particular experiment, it will provide a baseline for improvements in a parameter set that are consistent with the long-range Lennard-Jones interactions. C1 NIH, Struct Biol Lab, Div Comp Res & Technol, Bethesda, MD 20892 USA. US FDA, Biophys Lab, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Brooks, BR (reprint author), NIH, Struct Biol Lab, Div Comp Res & Technol, Bldg 10, Bethesda, MD 20892 USA. NR 28 TC 69 Z9 72 U1 1 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD JAN 8 PY 2004 VL 108 IS 1 BP 363 EP 368 DI 10.1021/jp030458y PG 6 WC Chemistry, Physical SC Chemistry GA 760MW UT WOS:000187838800049 ER PT J AU Meseda, CA Schmeisser, F Pedersen, R Woerner, A Weir, JP AF Meseda, CA Schmeisser, F Pedersen, R Woerner, A Weir, JP TI DNA immunization with a herpes simplex virus 2 bacterial artificial chromosome SO VIROLOGY LA English DT Article; Proceedings Paper CT 28th International Herpesvirus Workshop CY JUL 26-31, 2003 CL Madison, WI DE herpes simplex virus 2; BAC; thymidine kinase ID ESCHERICHIA-COLI; VIRUS GENOME; REPLICATION-COMPETENT; HERPESVIRUS GENOME; MAMMALIAN-CELLS; VECTORS; CLONING; MANIPULATION; MUTAGENESIS; SEQUENCES AB Construction of a herpes simplex virus 2 (HSV-2) bacterial artificial chromosome (BAC) is described. BAC vector sequences were inserted into the thymidine kinase gene of HSV-2 by homologous recombination. DNA from cells infected with the resulting recombinant virus was transformed into E. coli, and colonies containing the HSV-2 BAC (HSV2-BAC) were isolated and analyzed for the expected genotype. HSV2-BAC DNA was infectious when transfected back into mammalian cells and the resulting virus was thymidine kinase negative. When used to immunize mice, the HSV2-BAC DNA elicited a strong HSV-2 specific antibody response that was equal to or greater than live virus immunization. Further, HSV2-BAC immunization was protective when animals were challenged with a lethal dose of virus. The utility of the HSV2-13AC for construction of recombinant virus genomes was demonstrated by elimination of the HSV-2 glycoprotein D (gD) gene. A recombinant HSV-2 BAC with the gD gene deleted was isolated and shown to be incapable of producing infectious virus following transfection unless an HSV gD gene was expressed in a complementing cell line. Immunization of mice with the HSV2 gD-BAC also elicited an HSV-2 specific antibody response and was protective. The results demonstrate the feasibility of DNA immunization with HSV-2 bacterial artificial chromosomes for replicating and nonreplicating candidate HSV-2 vaccines, as well as the utility of BAC technology for construction and maintenance of novel HSV-2 vaccines. The results further suggest that such technology will be a powerful tool for dissecting the immune response to HSV-2. (C) 2003 Elsevier Inc. All rights reserved. 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 23 TC 19 Z9 20 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 5 PY 2004 VL 318 IS 1 BP 420 EP 428 DI 10.1016/j.virol.2003.09.033 PG 9 WC Virology SC Virology GA 778LL UT WOS:000189243000040 PM 14972567 ER PT J AU Kao, G Tsai, CM AF Kao, G Tsai, CM TI Quantification of O-acetyl, N-acetyl and phosphate groups and determination of the extent of O-acetylation in bacterial vaccine polysaccharides by high-performance anion-exchange chromatography with conductivity detection (HPAEC-CD) SO VACCINE LA English DT Article DE bacterial polysaccharides; O-acetylation; HPLC-conductivity detection ID PULSED-AMPEROMETRIC DETECTION; NUCLEAR-MAGNETIC-RESONANCE; MENINGITIDIS SEROGROUP-A; PNEUMONIAE TYPE 9V; NEISSERIA-MENINGITIDIS; CAPSULAR POLYSACCHARIDE; STRUCTURAL DETERMINATION; GROUP-B; ANTIGENS; RESPONSES AB The O-acetyl groups in meningococcal A and typhoid Vi polysaccharides (PSs) are functional immunogenic epitopes in humans. To quantify and determine the extent of O-acetylation in these and other bacterial vaccine PSs, anion-exchange HPLC methods have been developed for quantification of O-acetyl, N-acetyl, and phosphate groups in the PSs after these groups were hydrolyzed into anions. The O-acetylation in meningococcal A, C, Y and W-135, pneumococcal 9V and 18C and typhoid Vi PSs were analyzed. The O-acetyl group was selectively released from a PS as acetate by mild alkaline hydrolysis in 10 or 20 mM NaOH at 37degreesC until maximum release. The acetate in the hydrolysate was then quantified by high-performance anion-exchange chromatography with conductivity detection (HPAEC-CD) after removal of the PS by filtration with a 10,000 molecular-weight-cut-off membrane. Since the extent of O-acetylation on the PSs depends on bacterial species, strains and growth conditions, the N-acetyl group of amino-sugars, phosphate or monosaccharide components of the PSs were also quantified using HPAEC with conductivity or amperometry detection to determine the molar ratios of the O-acetyl group to these components. The average numbers of O-acetyl molecules in one PS repeating unit of the PSs were obtained from the molar ratios. Besides the O-acetyl determination, the pyruvate component in non-O-acetylated pneumococcal type 4 PS was analyzed by the HPAEC method. The HPAEC method can quantify the O-acetyl content in 0.2 mug of the meningococcal C PS and has a sensitivity at least 10 times higher than that of the colorimetric Hestrin assay. The method can be used for routine analysis of O-acetylation of PSs for quality control of vaccine PSs. Published by Elsevier Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Off Vaccine Res & Review, Rockville, MD 20852 USA. RP Tsai, CM (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Off Vaccine Res & Review, 1401 Rockville Pike HFM-428, Rockville, MD 20852 USA. EM tsai@cber.fda.gov NR 24 TC 10 Z9 15 U1 1 U2 13 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 2 PY 2004 VL 22 IS 3-4 BP 335 EP 344 DI 10.1016/j.vaccine.2003.08.008 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 765UF UT WOS:000188301600007 PM 14670314 ER PT S AU Ilev, IK Waynant, RW Gorman, E AF Ilev, IK Waynant, RW Gorman, E GP ieee TI A simple all-hollow-waveguide concept for efflicient CO2 laser delivery into precise tissue area SO 2004 IEEE LEOS ANNUAL MEETING CONFERENCE PROCEEDINGS, VOLS 1 AND 2 SE IEEE Lasers and Electro-Optics Society (LEOS) Annual Meeting LA English DT Proceedings Paper CT 17th Annual Meeting of the IEEE-Lasers-and-Electro-Optics-Society CY NOV 07-11, 2004 CL Rio Grande, PR SP IEEE Lasers & Electro Opt Soc, IEEE DE fiber optics; mid-infrared laser delivery; light propagation in tissue ID LASER DELIVERY; TAPER AB A novel and simple all-hollow-waveguide lens-free system for mid-infrared CO2 laser (10.6 mum) delivery into precise tissue area is presented. It includes a grazing-incidence-based uncoated hollow glass taper for direct laser-to-waveguide coupling and a multilayer hollow delivery waveguide. C1 US FDA, Ctr Devices & Radiol Hlth, Div Phys, Rockville, MD 20857 USA. RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Phys, Rockville, MD 20857 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1092-8081 BN 0-7803-8557-8 J9 IEEE LEOS ANN MTG PY 2004 BP 831 EP 832 PG 2 WC Optics SC Optics GA BBG19 UT WOS:000225390900414 ER PT S AU Pfefer, J AF Pfefer, J GP ieee TI Depth-selective fluorescence spectroscopy SO 2004 IEEE LEOS ANNUAL MEETING CONFERENCE PROCEEDINGS, VOLS 1 AND 2 SE IEEE Lasers and Electro-Optics Society (LEOS) Annual Meeting LA English DT Proceedings Paper CT 17th Annual Meeting of the IEEE-Lasers-and-Electro-Optics-Society CY NOV 07-11, 2004 CL Rio Grande, PR SP IEEE Lasers & Electro Opt Soc, IEEE AB Variations in the origin of detected fluorescence signals due to illumination/collection parameters were studied through Monte Carlo modeling. In many cases, proper design of normal- or oblique-incidence geometries may enable depth-selective interrogation of turbid media. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Pfefer, J (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12725 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1092-8081 BN 0-7803-8557-8 J9 IEEE LEOS ANN MTG PY 2004 BP 892 EP 893 PG 2 WC Optics SC Optics GA BBG19 UT WOS:000225390900445 ER PT B AU Bassen, H Casamento, J AF Bassen, H Casamento, J GP ieee TI High resolution computations and measurements of potential EMI with models of medical implants and radiating sources SO 2004 INTERNATIONAL SYMPOSIUM ON ELECTROMAGNETIC COMPATIBILITY, SYMPOSIUM RECORD 1-3 LA English DT Proceedings Paper CT IEEE International Symposium on Electromagnetic Compatibility (EMC 2004) CY AUG 09-13, 2004 CL Santa Clara, CA SP IEEE, EMC Soc, Rohde & Schwarz, AR Worldwide, Compliance Certificat Serv, ETS Lindgren, Murata Elect N A Inc, Sunol Sci, DLS Elect Syst Inc, Int Certificat Serv, Opt Filter, X-EMI DE medical device; computation; finite difference time domain; FDTD; measurement; pacemaker; defibrillator; cardiac; computer modeling AB We used high resolution finite difference time domain (FDTD) computer modeling to evaluate the potential of cellular phones to cause interference in an implanted cardiac pacemaker-defibrillator. The model consisted of a combination of an 835 MHz source which was either (1) a special boat-mounted cellular phone antenna (a sleeve dipole fed by a 3W amplifier) or (2) a standard EMI test model of a cellular phone handset (a dipole antenna placed 8 mm from the victim). The victim was a simplified model of a pacemaker-defibrillator with one insulated sensing/stimulation lead in a torso simulator. The handset model and the victim conformed to the AAMI PC69 standard for pacemaker-defibrillator EMI testing. We compared the EMI-induced voltage in the victim from the sleeve dipole source with the induced voltage from a cellular phone handset model. We performed experimental comparisons of the computed results using the actual antennas. We used a fiber-optically linked pacemaker-defibrillator simulator to measure induced voltage at the junction between the lead and the box of the pacemaker-defibrillator model. Our conclusions were that the sleeve dipole at 15 cm, driven with a 3 waft amplifier, is less capable of causing potential interference than the handset. The sleeve dipole, with its companion 3-W amplifier, produced 12.7 dB less induced voltage in the victim than the phone handset model driven with 0.6 W. Our results were validated since measured values differed by 1.7 dB or less from computed values. This is well within the uncertainties of the measurements and computations. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Bassen, H (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 4 TC 0 Z9 0 U1 1 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-8443-1 PY 2004 BP 75 EP 80 PG 6 WC Engineering, Electrical & Electronic SC Engineering GA BAU54 UT WOS:000223620100015 ER PT J AU Burgess, DJ Duffy, E Etzler, F Hickey, AJ AF Burgess, DJ Duffy, E Etzler, F Hickey, AJ TI Particle size analysis: AAPS workshop report, cosponsored by the food and drug administration and the united states pharmacopeia SO AAPS JOURNAL LA English DT Article ID FAILURE INVESTIGATION TREE C1 Univ Connecticut, Dept Pharmaceut Sci, Storrs, CT 06268 USA. US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20857 USA. Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA. RP Burgess, DJ (reprint author), Univ Connecticut, Dept Pharmaceut Sci, 372 Fairfield Rd, Storrs, CT 06268 USA. NR 3 TC 1 Z9 1 U1 1 U2 1 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 2004 VL 6 IS 3 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 005XI UT WOS:000234859300004 ER PT J AU Shah, RB Khan, MA AF Shah, RB Khan, MA TI Regional permeability of salmon calcitonin in isolated rat gastrointestinal tracts: Transport mechanism using Caco-2 cell monolayer SO AAPS JOURNAL LA English DT Article DE salmon calcitonin; regional permeability; stomach; duodenum; jejunum; ileum; colon; Caco-2 ID ABSORPTION; DELIVERY; BIOAVAILABILITY; RECEPTOR; PEPTIDE; INSULIN; GENE C1 US FDA, CDER, DPQR, Rockville, MD 20895 USA. Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Amarillo, TX 79106 USA. RP Khan, MA (reprint author), US FDA, CDER, DPQR, LS Bldg 64,HFD-940,5600 Fishers Lane, Rockville, MD 20895 USA. EM Khanm@cder.fda.gov NR 13 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 1550-7416 J9 AAPS J PY 2004 VL 6 IS 4 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 006GQ UT WOS:000234884900004 ER PT J AU Volpe, DA AF Volpe, DA TI Permeability classification of representative fluoroquinolones by a cell culture method SO AAPS PHARMSCI LA English DT Article DE permeability; Caco-2; biopharmaceutics classification system; fluoroquinolones ID LINE CACO-2; IN-VITRO; CIPROFLOXACIN; SECRETION; GREPAFLOXACIN; LEVOFLOXACIN AB This study was undertaken to categorize representative fluoroquinolone drug substance permeability based on the methods outlined in the Food and Drug Administration's biopharmaceutic classification system (BCS) Guidance for Industry. The permeability of ciprofloxacin, levofloxacin, lomefloxaciri, and ofloxacin was measured in an in vitro Caco-2 assay with previously demonstrated method suitability. The permeability class and efflux potential were ascertained by comparing test drug results with standard compounds (metoprolol, atenolol, labetalol, and rhodamine-123). All 4 quinolones drugs demonstrated concentration-dependent permeability, indicating active drug transport. In comparing absorptive versus secretive in vitro transport, the tested fluoroquinolones were found to be subject to efflux in varying degrees (ciprofloxacin > lornefloxacin > rhodamine 123 > levofloxacin > ofloxacin). Based on comparison to labetalol, the high permeability internal standard, ciprofloxacin was classified as a low permeability drug, whereas lomefloxacin, levofloxacin, and ofloxacin were classified as high permeability drugs. The in vitro permeability results matched human in vivo data based on absolute bioavailabilities. This laboratory exercise demonstrated the applicability of an in vitro permeability method for classifying drugs as outlined in the BCS Guidance. C1 US FDA, Div Prod Qual Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Volpe, DA (reprint author), US FDA, Div Prod Qual Res, Ctr Drug Evaluat & Res, LIfe Sci Bldg 64,HFD-940,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM volpe@cder.fda.gov NR 19 TC 14 Z9 15 U1 0 U2 0 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ALEXANDRIA PA 1650 KING ST, STE 200, ALEXANDRIA, VA 22314-2747 USA SN 1522-1059 J9 AAPS PHARMSCI JI AAPS Pharmsci PY 2004 VL 6 IS 2 AR 13 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 905ZZ UT WOS:000227611600001 ER PT J AU Bansal, SK Layloff, T Bush, ED Hamilton, M Hankinson, EA Landy, JS Lowes, S Nasr, MM St Jean, PA Shah, VP AF Bansal, SK Layloff, T Bush, ED Hamilton, M Hankinson, EA Landy, JS Lowes, S Nasr, MM St Jean, PA Shah, VP TI Qualification of analytical instruments for use in the pharmaceutical industry: A scientific approach SO AAPS PHARMSCITECH LA English DT Article; Proceedings Paper CT Workshop on A Scientific Approach to Analytical Instrument Validation CY MAR 03-05, 2003 CL Arlington, VA SP Amer Assoc Pharmaceut Sci, Int Pharmaceut Fed, Int Soc Pharmaceut Engn C1 Hoffmann La Roche Inc, Nutley, NJ 07110 USA. Management Sci Hlth, Granite City, IL 62040 USA. OSI Pharmaceut Inc, Boulder, CO 80301 USA. Bovis Lend Lease, Pharm Div, Surrey GU8 6LB, England. Aventis, Bridgewater, NJ 08807 USA. Advion BioSci, Ithaca, NY 14850 USA. US FDA, Rockville, MD 20852 USA. Waters Corp, Milford, MA 01757 USA. RP Bansal, SK (reprint author), Hoffmann La Roche Inc, 340 Kingsland St, Nutley, NJ 07110 USA. EM surendra.bansal@roche.com NR 11 TC 1 Z9 1 U1 0 U2 2 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 2004 VL 5 IS 1 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 881BJ UT WOS:000225838100020 ER PT J AU Palamakula, A Nutan, MTH Khan, MA AF Palamakula, A Nutan, MTH Khan, MA TI Response surface methodology for optimization and characterization of limonene-based Coenzyme Q10 self-nanoemulsified capsule dosage form SO AAPS PHARMSCITECH LA English DT Article DE response surface methodology; Box-Behnken design; coenzyme Q10; R-limonene; statistical modeling ID DRUG-DELIVERY SYSTEMS; STATISTICAL OPTIMIZATION; EXPERIMENTAL-DESIGN; FORMULATIONS; VARIABLES; TABLETS AB The aim of this study was to systematically obtain a model of factors that would yield an optimized self-nanoemulsified capsule dosage form (SNCDF) of a highly lipophilic model compound, Coenzyme Q10 (CoQ). Independent variables such as amount of R-(+)-limonene (X-1), surfactant (X-2), and cosurfactant (X-3), were optimized using a 3-factor, 3-level Box-Behnken statistical design. The dependent variables selected were cumulative percentage of drug released after 5 minutes (Y-1) with constraints on drug release in 15 minutes (Y-2), turbidity (Y-3), particle size (Y-4), and zeta potential (Y-5). A mathematical relationship obtained, Y-1 = 78.503 + 6.058X(1) + 13.738X(2) + 5.986X(3) - 25.831X(1)(2) + 9.12X(1)X(2) - 26.03 X1X3 - 38.67 X-2(2) + 11.02X(2)X(3) - 15.55 X-3(3) (r(2) = 0.97), explained the main and quadratic effects, and the interaction of factors that affected the drug release. Response surface methodology (RSM) predicted the levels of factors X-1, X-2, and X-3 (0.0344, 0.216, and 0.240, respectively), for a maximized response of Y-1 with constraints of >90% release on Y-2. The observed and predicted values of Y-1 were in close agreement. In conclusion, the Box-Behnken experimental design allowed us to obtain SNCDF with rapid (>90%) drug release within 5 minutes with desirable properties of low turbidity and particle size. C1 Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Amarillo, TX 79106 USA. RP Khan, MA (reprint author), US FDA, CDER, DPQR, White Oak,LS Bldg 64,HFD-940,5600 Fishers Lane, Rockville, MD 20895 USA. EM Khanm@cder.fda.gov RI Palamakula, Anitha/E-3741-2010 NR 20 TC 10 Z9 12 U1 0 U2 5 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 2004 VL 5 IS 4 AR 66 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 902KV UT WOS:000227356200017 ER PT J AU Gur, D Wagner, RF Chan, HP AF Gur, D Wagner, RF Chan, HP TI On the repeated use of databases for testing incremental improvement of computer-aided detection schemes SO ACADEMIC RADIOLOGY LA English DT Editorial Material ID FINITE-SAMPLE SIZE; CLASSIFIERS; PERFORMANCE; DIAGNOSIS C1 Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15213 USA. US FDA, Off Sci & Technol, Ctr Devices & Radiol Hlth, Rockville, MD USA. Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. RP Gur, D (reprint author), Univ Pittsburgh, Dept Radiol, Suite 4200,300 Halket St, Pittsburgh, PA 15213 USA. NR 7 TC 9 Z9 11 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 JAN PY 2004 VL 11 IS 1 BP 103 EP 105 DI 10.1016/S1076-6332(03)00511-7 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 759CR UT WOS:000187721200015 PM 14746409 ER PT J AU Shao, ZH Vanden Hoek, TL Li, CQ Schumacker, PT Becker, LB Chan, KC Qin, YM Yin, JJ Yuan, CS AF Shao, ZH Vanden Hoek, TL Li, CQ Schumacker, PT Becker, LB Chan, KC Qin, YM Yin, JJ Yuan, CS TI Synergistic effect of Scutellaria baicalensis and grape seed proanthocyanidins on scavenging reactive oxygen species in vitro SO AMERICAN JOURNAL OF CHINESE MEDICINE LA English DT Article DE Scutellaria baicalensis; grape seed proanthocyanidins; herbal medicine; hydroxyl radicals; suproxide; antioxidant; synergistic effect ID ATTENUATES OXIDANT STRESS; OXIDATIVE STRESS; CARDIOMYOCYTES; EXTRACT; INJURY; ANTIOXIDANT; REPERFUSION; FLAVONOIDS; ISCHEMIA; GEORGI AB Scutellaria baicalensis (SbE) is a commonly used Chinese herb medicine and grape seed proanthocyanidins is a popular herbal supplement in the United States. Both herbs have been shown to possess potent antioxidant effects. Using an in vitro model to produce the reactive oxygen species (ROS) generation (H2O2/FeSO4 for hydroxyl radicals, xanthine/ xanthine oxidase for suproxide), we observed that Scutellaria baicalensis and grape seed proanthocyanidins acted synergistically to scavenge ROS. Our data suggest that a combination of these two herbs can potentially enhance their antioxidant efficacy, allowing lower dosages of each drug to be used. This has the advantage of avoiding possible side effects that may arise when higher doses of a single herb are used in an attempt to achieve a maximum degree of antioxidant activity. C1 Univ Chicago, Pritzker Sch Med, Dept Anesthesia & Crit Care, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Tang Ctr Herbal Med Res, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Emergency Med & Emergency Resuscitat Ctr, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Comm Clin Pharmacol & Pharmacogen, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Dept Med, Chicago, IL 60637 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Yuan, CS (reprint author), Univ Chicago, Pritzker Sch Med, Dept Anesthesia & Crit Care, 5841 S Maryland Ave,MC 4028, Chicago, IL 60637 USA. EM cyuan@uchicago.edu RI Yin, Jun Jie /E-5619-2014 FU NCCIH NIH HHS [AT00381, AT00563, AT01575]; NHLBI NIH HHS [HL03779, HL35440] NR 20 TC 26 Z9 33 U1 1 U2 7 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA JOURNAL DEPT PO BOX 128 FARRER ROAD, SINGAPORE 912805, SINGAPORE SN 0192-415X J9 AM J CHINESE MED JI Am. J. Chin. Med. PY 2004 VL 32 IS 1 BP 89 EP 95 DI 10.1142/S0192415X04001722 PG 7 WC Integrative & Complementary Medicine; Medicine, General & Internal SC Integrative & Complementary Medicine; General & Internal Medicine GA 813XD UT WOS:000220938900009 PM 15154288 ER PT J AU Mehendale, SR Aung, HH Yin, JJ Lin, E Fishbein, A Wang, CZ Xie, JT Yuan, CS AF Mehendale, SR Aung, HH Yin, JJ Lin, E Fishbein, A Wang, CZ Xie, JT Yuan, CS TI Effects of antioxidant herbs on chemotherapy-induced nausea and vomiting in a rat-pica model SO AMERICAN JOURNAL OF CHINESE MEDICINE LA English DT Article DE chemotherapy; cisplatin; nausea and vomiting; emesis; free radical; antioxidant; Scutellaria baicalensis; american ginseng; ginseng berry; kaolin; pica; rat ID CISPLATIN-INDUCED EMESIS; ANTIEMETIC DRUGS; NK1 RECEPTOR; NEUROPHARMACOLOGICAL MECHANISMS; ANIMAL-MODEL; SUBSTANCE-P; INVOLVEMENT; RELEASE; EXTRACT; ANTAGONIST AB Nausea and vomiting are significant adverse effects of chemotherapeutic agents like cisplatin, and cause significant patient morbidity. Cisplatin treatment results in oxidant gut injury, which is postulated to be the primary cause of nausea and vomiting. We evaluated the effects of two antioxidant herbs, Scutellaria baicalensis and American ginseng berry, on cisplatin-induced nausea and vomiting using a rat model. Rats react to emetic or nausea-producing stimuli, such as cisplatin, with altered feeding habits, manifested by increased kaolin consumption (pica). We measured pica in rats to quantify cisplatin-induced nausea. We observed that pretreatment of rats with S. baicalensis or ginseng berry extracts resulted in a significant reduction in cisplatin-induced pica. The in vitro free radical scavenging ability of the herbal extract observed in the study, further confirmed the antioxidant action of the herb. We conclude that herbal antioxidants may have a role in attenuating cisplatin-induced nausea and vomiting. C1 Univ Chicago, Pritzker Sch Med, Tang Ctr Herbal Med Res, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Dept Anesthesia & Crit Care, Chicago, IL 60637 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Yuan, CS (reprint author), Univ Chicago, Pritzker Sch Med, Tang Ctr Herbal Med Res, 5841 S Maryland Ave,MC 4028, Chicago, IL 60637 USA. EM cyuan@airway.uchicago.edu RI Yin, Jun Jie /E-5619-2014 FU NCI NIH HHS [P30 CA14599] NR 36 TC 14 Z9 15 U1 0 U2 3 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0192-415X J9 AM J CHINESE MED JI Am. J. Chin. Med. PY 2004 VL 32 IS 6 BP 897 EP 905 DI 10.1142/S0192415X04002508 PG 9 WC Integrative & Complementary Medicine; Medicine, General & Internal SC Integrative & Complementary Medicine; General & Internal Medicine GA 886VH UT WOS:000226260400007 PM 15673195 ER PT J AU Mathews, F Youngman, L Neil, A AF Mathews, F Youngman, L Neil, A TI Maternal circulating nutrient concentrations in pregnancy: implications for birth and placental weights of term infants SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE pregnancy; nutrition; birth weight; placenta; smoking; human ID FETAL GROWTH; VITAMIN-A; HEMOGLOBIN CONCENTRATION; PROSPECTIVE COHORT; SMOKING STATUS; NUTRITION; RETARDATION; VOLUME; WOMEN AB Background: Compromised fetal growth may program chronic diseases of adulthood, and it has been suggested that maternal nutrition is a major determinant of fetal growth. We previously found no clinically significant associations between maternal diet and the size of the infant and placenta at birth in a large cohort of white women living in the United Kingdom. Objective: The objective was to examine the relations between indexes of maternal nutritional status in pregnancy and the birth and placental weights of infants born at term. Design: We conducted a prospective cohort study of 798 white nulliparous women with singleton pregnancies. Blood samples were obtained at approximate to 16 and 28 wk of gestation. Results: The concentration of most nutrients was not associated with pregnancy outcome. High retinol and hemoglobin concentrations in late, but not in early, pregnancy were strongly and independently associated with lower birth weight and smaller placental size at birth. Each 0.1-mumol increase in retinol predicted a 20.8-g (95% CL 9.2, 32.5 g) decrease in birth weight (P < 0.001), and each 0.1-g/L increase in hemoglobin predicted a 61.5-g (95% CI: 28.5, 94.4 g) decrease in birth weight (P < 0.001). Conclusions: We found negative associations between birth and placental weights and maternal retinol and hemoglobin concentrations. These relations may be causal or may reflect an underlying metabolic dysfunction, such as failure of plasma volume expansion. Our results provide no evidence that having high circulating nutrient concentrations, for example, through the use of supplements, would improve infant and placental growth. C1 Univ Oxford, Dept Zool, Oxford OX1 3PS, England. US FDA, Ctr Vet Med, Laurel, MD USA. Univ Oxford, Div Publ Hlth & Primary Hlth Care, Inst Hlth Sci, Oxford, England. RP Mathews, F (reprint author), Univ Oxford, Dept Zool, S Parks Rd, Oxford OX1 3PS, England. NR 37 TC 27 Z9 29 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 2004 VL 79 IS 1 BP 103 EP 110 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 757NZ UT WOS:000187569500017 PM 14684405 ER PT J AU Myers, MJ Farrell, DE Heller, DN Yancy, HF AF Myers, MJ Farrell, DE Heller, DN Yancy, HF TI Development of a polymerase chain reaction-based method to identify species-specific components in dog food SO AMERICAN JOURNAL OF VETERINARY RESEARCH LA English DT Article ID BOVINE-DERIVED MATERIALS; MITOCHONDRIAL GENOME; SPECTROMETRY; SEQUENCE; DNA AB Objectives-To determine whether there is a relationship between species-specific mitochondrial DNA (mtDNA), especially canine and feline mtDNA, and detectable amounts of pentobarbital in previously analyzed dog food samples. Sample Population-31 dog food samples previously analyzed for pentobarbital (limit of detection, 1 mug/kg). Procedure-Polymerase chain reaction (PCR) analysis was performed on dog food samples by use of PCR primers specific for either canine, feline, equine, bovine, porcine, ovine, or poultry mtDNA: Results-PCR amplicons specific for feline or canine mtDNA at a 0.007% (70 mug/g [wt/wt basis]) or 0.0007% (7 mug/g) level, respectively, were not found in the 31 dog food samples. Most of the 31 dog food samples had a PCR amplicon on PCR analysis when a PCR primer set capable of simultaneously detecting mtDNA of cows, pigs, sheep, goats, deer, elk, and horses was used. Results of PCR analysis by use of primers specific for bovine, swine, sheep and goat, or horse mtDNA revealed amplicons specific for bovine or swine mtDNA only in 27 of the 31 samples. Analysis of the remaining 4 samples failed to yield amplicons for any mammalian mtDNA. Pentobarbital was detected in 2 of these 4 samples. Results of PCR analysis correlated with the stated ingredient list for most, but not all samples. Conclusions and Clinical Relevance-Because canine and feline mtDNA were not found in a set of retail dog food samples, these results indicate that the source of pentobarbital in dog food is something other than proteins from rendered pet remains. C1 US FDA, Div Anim Res, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. RP Myers, MJ (reprint author), US FDA, Div Anim Res, Res Off, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 12 TC 12 Z9 12 U1 0 U2 11 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0002-9645 J9 AM J VET RES JI Am. J. Vet. Res. PD JAN PY 2004 VL 65 IS 1 BP 99 EP 103 DI 10.2460/ajvr.2004.65.99 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA 756TW UT WOS:000187500100016 PM 14719710 ER PT S AU Harris, GR Maruvada, S Gammell, PM AF Harris, GR Maruvada, S Gammell, PM BE Shaw, A TI Two efficient methods for measuring hydrophone frequency response in the 100 kHz to 2 MHz range SO AMUM 2004: Advanced Metrology for Ultrasound in Medicine 2004 SE JOURNAL OF PHYSICS CONFERENCE SERIES LA English DT Proceedings Paper CT Conference on Advanced Metrology for Ultrasound in Medicine (AMUN 2004) CY APR 27-28, 2004 CL Natl Phys Lab, Teddington, ENGLAND HO Natl Phys Lab AB As new medical applications of ultrasound emerge with operating frequencies in the hundreds of kilohertz to low megahertz region, it becomes more important to have convenient calibration methods for hydrophones in this frequency range. Furthermore, short diagnostic ultrasound pulses affected by finite amplitude distortion require that the hydrophone frequency response be known well below the center frequency. National standards laboratories can provide accurate calibration data at these frequencies, but the two methods now employed, laser interferometry and three-transducer reciprocity, are both single-frequency techniques, and they can be time-consuming procedures. Therefore, two efficient methods for generating a wideband acoustic pressure spectrum have been implemented to cover this frequency range. In one method a high-voltage pulse generator was used to excite a thick piezoelectric ceramic disk, producing a plane-wave acoustic pressure transient < 1 mu s in duration with peak amplitude of about 40 kPa. In the other technique, time delay spectrometry (TDS), a purpose-built 1-3 piezoelectric composite source transducer weakly focused at 20 cm was swept over the 0-2 MHz range. Its transmitting voltage response at 1 MHz was 11 kPa/V. The broadband pulse technique has the advantage of being simpler to implement, but TDS has a much greater signal-to-noise ratio because of the frequency-swept narrowband filter employed. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Harris, GR (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NR 13 TC 8 Z9 8 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1742-6588 J9 J PHYS CONF SER PY 2004 VL 1 BP 26 EP 31 DI 10.1088/1742-6596/1/1/008 PG 6 WC Automation & Control Systems; Biophysics; Medicine, Research & Experimental SC Automation & Control Systems; Biophysics; Research & Experimental Medicine GA BCE10 UT WOS:000228811800008 ER PT J AU Pazdur, R Williams, G Johnson, J Farrell, A Dagher, R AF Pazdur, Richard Williams, Grant Johnson, John Farrell, Ann Dagher, Ramzi TI Approval and access to caner drugs - U.S. Food and Drug Administration SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 [Pazdur, Richard; Williams, Grant; Johnson, John; Farrell, Ann; Dagher, Ramzi] US FDA, Rockville, MD 20857 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 2004 VL 15 SU 3 BP 9 EP 9 PG 1 WC Oncology SC Oncology GA V14FS UT WOS:000207720900029 ER PT J AU Rosenblatt, KP Bryant-Greenwood, P Killian, JK Mehta, A Geho, D Espina, V Petricoin, EE Liotta, LA AF Rosenblatt, KP Bryant-Greenwood, P Killian, JK Mehta, A Geho, D Espina, V Petricoin, EE Liotta, LA TI Serum proteomics in cancer diagnosis and management SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE proteomics; mass spectrometry; SELDI; protein profiling ID FLIGHT-MASS-SPECTROMETRY; OVARIAN-CANCER; PROSTATE-CANCER; IDENTIFICATION; BIOMARKERS; DISCOVERY; PATTERNS; CHALLENGES; INTERFACE; TIME AB Mass spectrometry-based diagnostics has the potential to revolutionize molecular medicine. Using modem mass-spectrometer technologies, clinical tests can be developed that are practical, robust, accurate, and inexpensive. Serum proteomic pattern profiling couples mass spectrometry with adaptive artificial-intelligence-based bioinformatics, which can now be employed to detect pathological states reflected in the serum proteome. With this approach, rapid and cost-effective tests with exquisite clinical sensitivity and specificity are emerging. These tools may dramatically change how disease is detected, monitored, and managed. C1 NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Hawaii, John A Burns Sch Med, Dept Pathol, Honolulu, HI 96822 USA. NCI, Food & Drug Adm, Clin Prote Program, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Rosenblatt, KP (reprint author), NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. EM rosenblk@nihexchange2.nih.gov OI Espina, Virginia/0000-0001-5080-5972 NR 46 TC 101 Z9 109 U1 2 U2 9 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2004 VL 55 BP 97 EP 112 DI 10.1146/annurev.med.55.091902.105237 PG 20 WC Medicine, General & Internal SC General & Internal Medicine GA 827RL UT WOS:000221918000006 PM 14746511 ER PT J AU Lian, JP Word, B Taylor, S Hammons, GJ Lyn-Cook, BD AF Lian, JP Word, B Taylor, S Hammons, GJ Lyn-Cook, BD TI Modulation of the constitutive activated STAT3 transcription factor in pancreatic cancer prevention: Effects of indole-3-carbinol (I3C) and genistein SO ANTICANCER RESEARCH LA English DT Article DE pancreatic cancer; prevention; STAT3 transcription factor; indole-3-carbinol; genistein ID PROSTATE CARCINOMA; CELLS; RECEPTOR; PROTEIN; APOPTOSIS; INHIBITION; EXPRESSION; RISK AB Background: The signal transducer and activator of transcription 3 (STAT3) is a latent transcription factor required in proliferation and differentiation. STAT3 is activated constitutively in a number of cancers. Materials and Methods: This study was conducted to assess the possible involvement of STAT3 activation in pancreatic cancer and the potential for this pathway as a target in chemopreventive strategy. Results: STAT3 was shown for the first time to be constitutively activated in human pancreatic carcinoma specimens but not in normal pancreatic tissues. Constitutively activated STAT3 was also found in pancreatic tumor cell lines (Panc-1 and MIA PaCa-2) which could be modulated by indole-3-carbinol (I3C) and genistein. At concentrations higher than 10 muM, STAT3 constitutive activation is inhibited by both agents. Induction of apoptosis by I3C was also demonstrated. Conclusion: Given its critical role in tumorigenesis, our results suggest that STAT3 activation provides an important and appropriate target for chemoprevention in pancreatic cancer treatment. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Lyn-Cook, BD (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, HFT-100, Jefferson, AR 72079 USA. EM Blyncook@nctr.fda.gov NR 34 TC 22 Z9 22 U1 0 U2 3 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JAN-FEB PY 2004 VL 24 IS 1 BP 133 EP 137 PG 5 WC Oncology SC Oncology GA 778ZV UT WOS:000189271900019 PM 15015587 ER PT J AU Chen, S Zhao, SH White, DG Schroeder, CM Lu, R Yang, HC McDermott, PF Ayers, S Meng, JH AF Chen, S Zhao, SH White, DG Schroeder, CM Lu, R Yang, HC McDermott, PF Ayers, S Meng, JH TI Characterization of multiple-antimicrobial-resistant Salmonella serovars isolated from retail meats SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID SEROTYPE TYPHIMURIUM DT104; AMPC BETA-LACTAMASE; ANTIBIOTIC-RESISTANCE; ESCHERICHIA-COLI; CLASS-1 INTEGRON; MOLECULAR CHARACTERIZATION; MULTIDRUG-RESISTANCE; UNITED-STATES; GENE-CLUSTER; FOOD ANIMALS AB A total of 133 Salmonella isolates recovered from retail meats purchased in the United States and the People's Republic of China were assayed for antimicrobial susceptibility, the presence of integrons and antimicrobial resistance genes, and horizontal transfer of characterized antimicrobial resistance determinants via conjugation. Seventy-three (82%) of these Salmonella isolates were resistant to at least one antimicrobial agent. Resistance to the following antibiotics was common among the United States isolates: tetracycline (68% of the isolates were resistant), streptomycin (61%), sulfamethoxazole (42%), and ampicillin (29%). Eight Salmonella isolates (6%) were resistant to ceftriaxone. Fourteen isolates (11%) from the People's Republic of China were resistant to nalidixic acid and displayed decreased susceptibility to ciprofloxacin. A total of 19 different antimicrobial resistance genes were identified in 30 multidrug-resistant Salmonella isolates. The bla(CMY-2) gene, encoding a class A AmpC beta-lactamase, was detected in all 10 Salmonella isolates resistant to extended-spectrum beta-lactams. Resistance to ampicillin was most often associated with a TEM-1 family beta-lactamase gene. Six aminoglycoside resistance genes, aadA1, aadA2, aacC2, Kn, aph(3)-IIa, and aac(3)-IVa, were commonly present in the Salmonella isolates. Sixteen (54%) of 30 Salmonella isolates tested had integrons ranging in size from 0.75 to 2.7 kb. Conjugation studies demonstrated that there was plasmid-mediated transfer of genes encoding CMY-2 and TEM-1-like beta-lactamases. These data indicate that Salmonella isolates recovered from retail raw meats are commonly resistant to multiple antimicrobials, including those used for treating salmonellosis, such as ceftriaxone. Genes conferring antimicrobial resistance in Salmonella are often carried on integrons and plasmids and could be transmitted through conjugation. These mobile DNA elements have likely played an important role in transmission and dissemination of antimicrobial resistance determinants among Salmonella strains. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. US FDA, Ctr Vet Med, Off Res, Div Anim & Food Microbiol, Laurel, MD USA. China Agr Univ, Beijing, Peoples R China. RP Meng, JH (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA. EM jm332@umail.umd.edu OI Chen, Sheng/0000-0003-3526-7808 NR 36 TC 219 Z9 249 U1 5 U2 43 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 JAN PY 2004 VL 70 IS 1 BP 1 EP 7 DI 10.1128/AEM.70.1.1-7.2004 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 763RY UT WOS:000188115300001 PM 14711619 ER PT J AU Moody, JD Freeman, JP Fu, PP Cerniglia, CE AF Moody, JD Freeman, JP Fu, PP Cerniglia, CE TI Degradation of benzo[a]pyrene by Mycobacterium vanbaalenii PYR-1 SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; SP STRAIN PYR-1; STEREOSELECTIVE METABOLISM; SELENASTRUM-CAPRICORNUTUM; PYRENE DEGRADATION; GREEN-ALGA; BENZOPYRENE; IDENTIFICATION; BACTERIUM; BIOREMEDIATION AB Metabolism of the environmental pollutant benzo[a]pyrene in the bacterium Mycobacterium vanbaalenii PYR-1 was examined. This organism initially oxidized benzo [a] pyrene with dioxygenases and monooxygenases at C-4,5, C-9,10, and C-11,12. The metabolites were separated by reversed-phase high-performance liquid chromatography (HPLC) and characterized by UV-visible, mass, nuclear magnetic resonance, and circular dichroism spectral analyses. The major intermediates of benzo[a]pyrene metabolism that had accumulated in the culture media after 96 h of incubation were cis-4,5-dihydro-4,5-dihydroxybenzo [a] pyrene (benzo [a] pyrene cis-4,5-dihydrodiol), cis-11,12-dihydro-11,12-dihydroxybenzo [a] pyrene (benzo[a]pyrene cis-11,12-dihydrodiol), trans-11,12-dihydro-11,12-dihydroxybenzo[a]pyrene (benzo[a]pyrene trans-11,12-dihydrodiol), 10-oxabenzo[def]chrysen-9-one, and hydroxymethoxy and dimethoxy derivatives of benzo[]pyrene. The ortho-ring fission products 4-formylchrysene-5-carboxylic acid and 4,5-chrysene-dicarboxylic acid and a monocarboxylated chrysene product were formed when replacement culture experiments were conducted with benzo[a]pyrene cis-4,5-dihydrodiol. Chiral stationary-phase HPLC analysis of the dihydrodiols indicated that benzo[a]pyrene cis-4,5-dihydrodiol had 30% 4S,5R and 70% 4R,5S absolute stereochemistry. Benzo[a]pyrene cis-11,12-dihydrodiol adopted an 11S,12R conformation with 100% optical purity. The enantiomeric composition of benzo[a] pyrene trans-11,12-dihydrodiol was an equal mixture of 11S,12S and 11R,12R molecules. The results of this study, in conjunction with those of previously reported studies, extend the pathways proposed for the bacterial metabolism of benzo[a]pyrene. Our study also provides evidence of the stereo- and regioselectivity of the oxygenases that catalyze the metabolism of benzo[a]pyrene in M. vanbaalenii PYR-1. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Div Chem, Jefferson, AR 72079 USA. US FDA, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, HFT-250, Jefferson, AR 72079 USA. EM ccerniglia@nctr.fda.gov NR 33 TC 72 Z9 96 U1 7 U2 29 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 JAN PY 2004 VL 70 IS 1 BP 340 EP 345 DI 10.1128/AEM.70.1.340-345.2004 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 763RY UT WOS:000188115300043 PM 14711661 ER PT J AU Umehara, H Bloom, ET Okazaki, T Nagano, Y Yoshie, O Imai, T AF Umehara, H Bloom, ET Okazaki, T Nagano, Y Yoshie, O Imai, T TI Fractalkine in vascular biology - From basic research to clinical disease SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Review DE fractalkine; endothelial cells; vascular biology; atherosclerosis; inflammation ID CD8(+) T-CELLS; RECEPTOR CX(3)CR1; CHEMOKINE RECEPTORS; CX3C CHEMOKINE; CRESCENTIC GLOMERULONEPHRITIS; RHEUMATOID-ARTHRITIS; CHLAMYDIA-PNEUMONIAE; ALLOGRAFT-REJECTION; LEUKOCYTE ADHESION; ENDOTHELIAL-CELLS AB Fractalkine (now also called CX3CL1) is a unique chemokine that functions not only as a chemoattractant but also as an adhesion molecule and is expressed on endothelial cells activated by proinflammatory cytokines, such as interferon-gamma and tumor necrosis factor-alpha. The fractalkine receptor, CX3CR1, is expressed on cytotoxic effector lymphocytes, including natural killer (NK) cells and cytotoxic T lymphocytes, which contain high levels of intracellular perforin and granzyme B, and on macrophages. Soluble fractalkine causes migration of NK cells, cytotoxic T lymphocytes, and macrophages, whereas the membrane-bound form captures and enhances the subsequent migration of these cells in response to secondary stimulation with other chemokines. Furthermore, stimulation through membrane-bound fractalkine activates NK cells, leading to increased cytotoxicity and interferon-gamma production. Recently, accumulating evidence has shown that fractalkine is involved in the pathogenesis of various clinical disease states or processes, such as atherosclerosis, glomerulonephritis, cardiac allograft rejection, and rheumatoid arthritis. In addition, polymorphisms in CX3CR1, which reduce its binding activity to fractalkine, have been reported to increase the risk of HIV disease and to reduce the risk of coronary artery disease. This review will examine new concepts underlying fractalkine-mediated leukocyte migration and tissue damage, focusing primarily on the pathophysiological roles of fractalkine in various clinical conditions, especially in atherosclerosis and vascular injury. C1 Kyoto Univ, Grad Sch Med, Dept Rheumatol & Clin Immunol, Sakyo Ku, Kyoto 6068507, Japan. Kyoto Univ, Grad Sch Med, Dept Hematol & Oncol, Kyoto 6068507, Japan. US FDA, Div Cellular & Gene Therapies HFM518, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Osaka Dent Univ, Dept Med, Osaka, Japan. Kinki Univ, Sch Med, Dept Microbiol, Osaka 589, Japan. Kan Res Inst, Kyoto, Japan. RP Umehara, H (reprint author), Kyoto Univ, Grad Sch Med, Dept Rheumatol & Clin Immunol, Sakyo Ku, 54 Shogoin Kawahara Cho, Kyoto 6068507, Japan. NR 84 TC 179 Z9 193 U1 1 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JAN PY 2004 VL 24 IS 1 BP 34 EP 40 DI 10.1161/01.ATV.0000095360.62479.1F PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 760BV UT WOS:000187791600007 PM 12969992 ER PT J AU Witter, J Dionne, RA AF Witter, J Dionne, RA TI What can chronic arthritis pain teach about developing new analgesic drugs? SO ARTHRITIS RESEARCH & THERAPY LA English DT Article DE analgesics; chronic pain; drug development; individual responses; pain mechanisms AB Chronic pain remains an important public health need with greater impact on the US economy than most other chronic conditions. Current pain management is largely limited to opioids and non-steroidal anti-inflammatory drugs, indicating a gap in the translation of new knowledge to the development of improved pain treatments. Strategies suggested include the re-evaluation of current drug screening methods, a recognition that molecular-genetic events occurring acutely contribute to the development of pain chronicity, the validation of analgesic targets in the intended patient population, consideration of the unique genetic profile that varies between individuals, and the introduction of individual response measures to improve the capture of outcomes in clinical trials. C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Dionne, RA (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. EM raymond.dionne@nih.gov NR 6 TC 3 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2004 VL 6 IS 6 BP 279 EP 281 DI 10.1186/ar1450 PG 3 WC Rheumatology SC Rheumatology GA 871US UT WOS:000225160100005 PM 15535840 ER PT J AU Hingorani, SR Petricoin, EF Maitra, A Rajapakse, V King, C Jacobetz, MA Ross, S Conrads, TP Veenstra, TD Hitt, BA Kawaguchi, Y Johann, D Liotta, LA Crawford, HC Putt, ME Jacks, T Wright, CVE Hruban, RH Lowy, AM Tuveson, DA AF Hingorani, SR Petricoin, EF Maitra, A Rajapakse, V King, C Jacobetz, MA Ross, S Conrads, TP Veenstra, TD Hitt, BA Kawaguchi, Y Johann, D Liotta, LA Crawford, HC Putt, ME Jacks, T Wright, CVE Hruban, RH Lowy, AM Tuveson, DA TI Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse (vol 4, pg 434, 2003) SO CANCER CELL LA English DT Correction C1 Univ Penn, Abramson Canc Ctr, Abramson Family Canc Res Inst, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Abramson Canc Ctr, Abramson Family Canc Res Inst, Dept Canc Biol, Philadelphia, PA 19104 USA. US FDA, Ctr Biol Evaluat & Res, NCI, Clin Proteom Program, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Dept Pathol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Dept Oncol, Baltimore, MD 21287 USA. NCI, US FDA, Clin Proteom Program,Lab Pathol, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Biomed Proteom Program, Analyt Chem Lab,Mass Spectrometry Ctr, SAIC Frederick Inc, Frederick, MD 21702 USA. Correlog Syst Inc, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Dept Cell & Dev Biol, Nashville, TN 37232 USA. SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Howard Hughes Med Inst, Ctr Canc Res, Cambridge, MA 02139 USA. Univ Cincinnati, Coll Med, Dept Surg, Div Surg Oncol, Cincinnati, OH 45219 USA. RP Tuveson, DA (reprint author), Univ Penn, Abramson Canc Ctr, Abramson Family Canc Res Inst, Dept Med, Philadelphia, PA 19104 USA. EM tuvesond@mail.med.upenn.edu RI Crawford, Howard/A-2874-2008 NR 1 TC 0 Z9 1 U1 2 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JAN PY 2004 VL 5 IS 1 BP 103 EP 103 DI 10.1016/S1535-6108(03)00335-0 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 766XH UT WOS:000188400300013 ER PT J AU Wu, AH Yu, MC Tseng, CC Twaddle, NC Doerge, DR AF Wu, AH Yu, MC Tseng, CC Twaddle, NC Doerge, DR TI Plasma isoflavone levels versus self-reported soy isoflavone levels in Asian-American women in Los Angeles County SO CARCINOGENESIS LA English DT Article ID BREAST-CANCER RISK; MASS-SPECTROMETRY; HUMAN URINE; PHYTOESTROGENS; CHROMATOGRAPHY; METABOLITES; POPULATION; PHARMACOKINETICS; QUESTIONNAIRE; FREQUENCY AB In a case-control study conducted among Asian-American women in Los Angeles County, we reported that the risk of breast cancer was significantly reduced in association with soy intake [Wu,A.H., Wan,P., Hankin,J. et al. (2002) Carcinogenesis, 23, 1491-1496]. In a subset of cases (n = 97) and controls (n = 97) we investigated the relationship between self-reported usual adult intake of soy isoflavones which was determined from a food frequency questionnaire and levels of plasma isoflavones (genistein and daidzein) and isoflavone metabolites (equol, dihydrogenistein and dihydrodaidzein) from a randomly timed blood specimen. In analyses conducted in cases and controls separately, levels of plasma genistein, daidzein and total isoflavones increased with increasing levels of self-reported intake of soy isoflavones. Breast cancer cases and control subjects did not differ in their respective associations between total plasma isoflavone levels and self-reported intake (P = 0.48). Among all subjects, there was a 3-fold difference in geometric mean plasma levels of total isoflavones [81.8 (95% CI = 53.4, 125.1) versus 26.4 nmol/l (95% CI = 16.6, 41.8)] between women in the highest quartile of soy isoflavone intake (>12.68 mg isoflavones/1000 kcal) compared with those in the lowest quartile of intake (less than or equal to1.79 mg isoflavones/1000 kcal), a difference that was statistically significant (P = 0.002). The present study provides independent corroboration that breast cancer cases and control subjects can reliably recall their usual soy intake and that there is no evidence of selective recall biases between breast cancer cases and controls. These results further strengthen our previous observation of an inverse association between soy intake and breast cancer risk in the Los Angeles Asian Breast Cancer Study. C1 Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Wu, AH (reprint author), Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, 1441 Eastlake Ave,MC 9175, Los Angeles, CA 90089 USA. EM annawu@hsc.usc.edu FU NCI NIH HHS [N01CN25403] NR 24 TC 37 Z9 39 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2004 VL 25 IS 1 BP 77 EP 81 DI 10.1093/carcin/bgg189 PG 5 WC Oncology SC Oncology GA 762MG UT WOS:000187975700009 PM 14555615 ER PT J AU Weber, DJ AF Weber, DJ TI FDA regulation of allogeneic islets as a biological product SO CELL BIOCHEMISTRY AND BIOPHYSICS LA English DT Article; Proceedings Paper CT 3rd Annual Rachmiel Levine Diabetes and Obesity Symposium CY OCT, 2002 CL Anaheim, CA DE somatic cell therapy; Food and Drug Administration; pancreatic islets; biologics license application; investigational new drug application; cGMP; comparability AB This article describes the Food and Drug Administration's recent manufacturing review experience with investigational new drug applications submitted for allogeneic pancreatic islets of Langerhans for the treatment of type 1 diabetes mellitus. In addition, considerations of islet preparation issues that will need to be resolved before the submission of a biologics license application are discussed. C1 US FDA, Ctr Biol Evaluat & Res, Off Cells Tissue & Gene Therapies, Div Celular & Gene Therapies, Rockville, MD 20857 USA. RP Weber, DJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Cells Tissue & Gene Therapies, Div Celular & Gene Therapies, Rockville, MD 20857 USA. EM dweber@bcg-usa.com NR 4 TC 4 Z9 4 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1085-9195 J9 CELL BIOCHEM BIOPHYS JI Cell Biochem. Biophys. PY 2004 SU S BP 19 EP 22 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 853SC UT WOS:000223846900003 ER PT J AU [Anonymous] AF [Anonymous] TI Regulation of islets as a biological product: FDA update SO CELL BIOCHEMISTRY AND BIOPHYSICS LA English DT Meeting Abstract RP US FDA, CBER, OTRR, Div Cell & Gene Therapy, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1085-9195 J9 CELL BIOCHEM BIOPHYS JI Cell Biochem. Biophys. PY 2004 SU S BP 233 EP 234 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 853SC UT WOS:000223846900046 ER PT J AU Fang, GC Wu, YS Fu, PPC Yang, IL Chen, MH AF Fang, GC Wu, YS Fu, PPC Yang, IL Chen, MH TI Polycyclic aromatic hydrocarbons in the ambient air of suburban and industrial regions of central Taiwan SO CHEMOSPHERE LA English DT Article DE BaP; industrial; suburban; T-test; ambient air; Taichung ID SUSPENDED PARTICULATE; URBAN ATMOSPHERE; PARTICLES; INDOOR; PAHS AB The concentrations of gas-phase and particle-bound polycyclic aromatic hydrocarbons (PAHs) were measured simultaneously at an industrial area (Taichung Industrial Park) and a suburban area (Tunghai University Campus) in Taichung, Taiwan. Twenty-four hours samplings for two consecutive days were performed between August and December 2002 at both sampling sites. Ambient air particle-bound PAHs were collected on quartz filters and gas-phase PAHs were collected on glass cartridges using a PUF Sampler, respectively. Both types of samples were extracted with a DCM/n-hexane mixture (50/50, v/v) for 24 h, then the extracts were subjected to gas chromatography-mass spectrometric (GC-MS) analysis. Total PAHs concentrations at the Taichung Industrial Park (TIP) sampling site and the Tunghai University Campus (THUC) sampling site were found to be 1232.3 +/- 963.6 and 609.8 +/- 356.3 ng/m(3), respectively. Stationary combustion processes were mainly responsible for PAHs sources at the TIP sampling site, while traffic vehicle exhaust was the largest contributor for PAHs sources at the THUC sampling site. (C) 2003 Elsevier Ltd. All rights reserved. C1 Hungkuang Univ, Dept Environm Engn, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Tunghai Univ, Dept Environm Sci, Taichung 407, Taiwan. RP Fang, GC (reprint author), Hungkuang Univ, Dept Environm Engn, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. NR 14 TC 40 Z9 41 U1 4 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD JAN PY 2004 VL 54 IS 4 BP 443 EP 452 DI 10.1016/S0045-6535(03)00706-9 PG 10 WC Environmental Sciences SC Environmental Sciences & Ecology GA 759NX UT WOS:000187744700001 PM 14581046 ER PT J AU Powers, JH Cooper, CK AF Powers, JH Cooper, CK TI Evaluating combination therapy in community-acquired pneumonia SO CHEST LA English DT Letter ID RANDOMIZED CONTROLLED TRIAL C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Powers, JH (reprint author), HFD-104,9201 Corp Blvd, Rockville, MD 20850 USA. EM POWERSJOH@cder.fda.gov NR 5 TC 2 Z9 2 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2004 VL 125 IS 1 BP 353 EP 353 DI 10.1378/chest.125.1.353 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 764QN UT WOS:000188217700067 PM 14718472 ER PT S AU Johann, DJ McGuigan, MD Patel, AR Tomov, S Ross, S Conrads, TP Veenstra, TD Fishman, DA Whiteley, GR Petricoin, EF Liotta, LA AF Johann, DJ McGuigan, MD Patel, AR Tomov, S Ross, S Conrads, TP Veenstra, TD Fishman, DA Whiteley, GR Petricoin, EF Liotta, LA BE Hoon, DSB Taback, B TI Clinical proteomics and biomarker discovery SO CIRCULATING NUCLEIC ACIDS IN PLASMA/SERUM III AND SERUM PROTEOMICS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 3rd International Symposium on Circulating Nucleic Acids in Plasma/Serum (CNAPS III) and Serum Proteomics CY NOV 09-12, 2003 CL Santa Monica, CA SP John Wayne Canc Inst, Dept Mol Oncol DE proteomics; bioinformatics; mass spectroscopy ID PROSTATE-CANCER; SERUM; PATTERNS AB Early detection of disease generally provides much-improved outcomes by a definitive medical procedure or through lifestyle modification along with specific medical management strategies. For serum biomarkers, which are central to the diagnosis of many diseases, to become truly useful sentinels of pathogenesis, their sensitivity and specificity in both early detection and recurrence monitoring must be improved. Currently, the detection and monitoring of disease markers is based on solitary proteins, and this approach is not always reliable. New classes of biomarkers derived from mass spectroscopy analysis of the low molecular weight proteome have shown improved abilities in the early detection of disease and hence in patient risk stratification and outcome. The development of a modular platform technology with sufficient flexibility and design abstractions allowing for concurrent experimentation, test, and refinement will help speed the progress of mass spectroscopy-derived proteomic pattern-based diagnostics from the scientific laboratory to the medical clinic. For acceptance by scientists, physicians, and regulatory personnel, new bioinformatic tools are essential system components for data management, analysis, and intuitive display of these new and complex data. Clinically engineered mass spectroscopy systems are essential for the further development and validation of multiplexed biomarkers that have shown tremendous promise for the early detection of disease. C1 NCI, NIH, Pathol Lab,Ctr Canc Res, FDA Clin Proteom Program, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Div Informat Technol, Upton, NY 11973 USA. NCI, NIH,Summer Student Program, Pathol Lab, FDA Clin Proteom Program, Bethesda, MD 20892 USA. SAIC Frederick Inc, Natl Canc Inst, Biomed Proteom Program, Analyt Chem Lab,Mass Spectrometry Ctr, Frederick, MD 21702 USA. Northwestern Univ, Sch Med, Natl Ovarian Canc Early Detect Program, Chicago, IL 60611 USA. SAIC Frederick, NCI, FDA Clin Proteom Program, Clin Proteom Reference Lab, Gaithersburg, MD USA. NCI, FDA Clin Proteom Program, Off Director, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Johann, DJ (reprint author), NCI, NIH, Pathol Lab,Ctr Canc Res, FDA Clin Proteom Program, 8800 Rockville Pike,Bldg 29A,Room 2A21, Bethesda, MD 20892 USA. EM johannd@mail.nih.gov NR 17 TC 57 Z9 57 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-551-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1022 BP 295 EP 305 DI 10.1196/annals.1318.045 PG 11 WC Biochemistry & Molecular Biology; Oncology; Medical Laboratory Technology; Medicine, Research & Experimental; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Oncology; Medical Laboratory Technology; Research & Experimental Medicine; Science & Technology - Other Topics GA BAN78 UT WOS:000223005300044 PM 15251975 ER PT J AU Hassan, R Williams-Gould, J Watson, T Pai-Scherf, L Pastan, I AF Hassan, R Williams-Gould, J Watson, T Pai-Scherf, L Pastan, I TI Pretreatment with rituximab does not inhibit the human immune response against the immunogenic protein LMB-1 SO CLINICAL CANCER RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODY THERAPY; B-CELLS; PHASE-I; DEPLETION; RICIN; IMMUNOTOXIN; IDEC-C2B8; INFUSION; TRIAL AB Purpose: Rituximab, a humanized monoclonal antibody directed to the CD20 antigen present on B lymphocytes, could potentially abrogate the humoral immune response to murine monoclonal antibodies or immunotoxins by depleting antibody-producing B cells. Experimental Design: A Phase II study of LMB-1, an immunotoxin targeting the Lewis Y tumor antigen, in combination with rituximab was conducted to test the hypothesis that rituximab could abolish or diminish the development of human antibodies to LMB-1. Five patients were treated in this study and received 375 mg/m(2) rituximab on days 1 and 7 followed by 45 mug/kg/day LMB-1 on days 10, 12, and 14. The development of human antibodies against LMB-1 was detected using a serum neutralization and ELISA. Results: All five of the patients had a total suppression of circulating CD20/CD19 B-cell population before the administration of the first dose of the immunotoxin. Before rituximab treatment, the mean percentage of CD20/CD19-positive B cells in the five treated patients was 19.8% (range, 4.5-29.8%) of the total peripheral lymphocytes. After two doses of rituximab, CD20/CD19-positive B lymphocytes constituted less than or equal to0.1% of the total peripheral lymphocytes. Despite absent circulating antibody-producing B cells, before and during LMB-1 treatment, all of the patients developed neutralizing antibodies to the immunotoxin by day 21 of drug administration, which prevented retreatment. Conclusions: Even though rituximah caused complete depletion of circulating CD20/CD19-positive B cells, it had no effect in suppressing the human antibody response to LMB-1 and may be of limited utility in suppressing human antibody responses to other immunogenic proteins. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Med Oncol Clin Res Unit, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Hassan, R (reprint author), NCI, Mol Biol Lab, NIH, 37 Convent Dr,Room 5116, Bethesda, MD 20892 USA. EM hassanr@mail.nih.gov NR 16 TC 28 Z9 29 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 JAN 1 PY 2004 VL 10 IS 1 BP 16 EP 18 DI 10.1158/1078-0432.CCR-1160-3 PN 1 PG 3 WC Oncology SC Oncology GA 765YM UT WOS:000188318700004 PM 14734446 ER PT J AU Jackson, AJ Robbie, G Marroum, P AF Jackson, AJ Robbie, G Marroum, P TI Metabolites and bioequivalence - Past and present SO CLINICAL PHARMACOKINETICS LA English DT Review ID LINEAR PHARMACOKINETICS; ACTIVE METABOLITE; PARENT DRUG; BIOAVAILABILITY; PHARMACODYNAMICS; ALLOPURINOL; GERMANY AB Although it is widely recognised that measurement of metabolite concentrations is crucial to understanding the clinical pharmacology characteristics of a new molecular entity, a clear consensus on the role of metabolites in the assessment of bioequivalence has never been achieved within the scientific community. However, a regulatory policy for the role of metabolites in bioavailability and bioequivalence has been established by the US FDA. One school of thought believes that the parent drug alone is sensitive to picking up formulation differences, whereas another school of thought believes that establishing bioequivalence criteria on all the species that contribute to safety and efficacy is the only way to ensure the switchability of two products. In this paper, a brief review of the pharmacokinetics of metabolites under different scenarios is presented and the history of the role of metabolites in the assessment of bioequivalence is summarised. Relevant examples from the literature illustrating conflicting opinions on the need for the measurement of metabolites in bioequivalence studies are given. Cases from the literature in which the parent drug is able to meet the 90% confidence intervals while the metabolite(s) fail to do so, and vice versa, are presented to illustrate the difficulty in choosing the pertinent entity to measure. The relevant current US FDA policy and guidelines related to bioavailability and bioequivalence are discussed and contrasted with the rules and regulations applicable in Canada and Europe. C1 Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Div Pharmaceut Evaluat, Rockville, MD 20852 USA. RP Jackson, AJ (reprint author), Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Div Pharmaceut Evaluat, Mailstop HFD 860, Rockville, MD 20852 USA. EM jacksonan@cder.fda.gov NR 39 TC 19 Z9 21 U1 0 U2 0 PU ADIS INT 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 2004 VL 43 IS 10 BP 655 EP 672 DI 10.2165/00003088-200443100-00002 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 841PC UT WOS:000222942100002 PM 15244496 ER PT J AU Huang, SM Hall, SD Watkins, P Love, LA Serabjit-Singh, C Betz, JM Hoffman, FA Honig, P Coates, PM Bull, J Chen, ST Kearns, GL Murray, MD AF Huang, SM Hall, SD Watkins, P Love, LA Serabjit-Singh, C Betz, JM Hoffman, FA Honig, P Coates, PM Bull, J Chen, ST Kearns, GL Murray, MD TI Drug interactions with herbal products and grapefruit juice: A conference report SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID ST-JOHNS-WORT; ALTERNATIVE MEDICINE USE; HYPERICUM-PERFORATUM; ORAL AVAILABILITY; UNITED-STATES; DIETARY-SUPPLEMENTS; BRUSSELS-SPROUTS; PHARMACOKINETICS; COMPLEMENTARY; CYP3A4 C1 Purdue Univ, Regenstrief Inst, Indianapolis, IN 46202 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Off Regulatory Affairs, Rockville, MD 20857 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Univ N Carolina, Ctr Med, Chapel Hill, NC USA. GlaxoSmithKline, Res Triangle Pk, NC USA. NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. Pfizer Inc, Pfizer Consumer Hlth Care, Morris Plains, NJ USA. Merck Res Labs, W Point, PA USA. Childrens Mercy Hosp & Clin, Kansas City, MO USA. RP Murray, MD (reprint author), Purdue Univ, Regenstrief Inst, 1050 Wishard Blvd,RG-6, Indianapolis, IN 46202 USA. EM mmurray@regenstrief.org NR 55 TC 54 Z9 58 U1 3 U2 7 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 JAN PY 2004 VL 75 IS 1 BP 1 EP 12 DI 10.1016/j.clpt.2003.07.002 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 765YJ UT WOS:000188318400001 PM 14749688 ER PT J AU Gorski, JC Huang, SM Pinto, A Hamman, MA Hilligoss, JK Zaheer, NA Desai, M Miller, M Hall, SD AF Gorski, JC Huang, SM Pinto, A Hamman, MA Hilligoss, JK Zaheer, NA Desai, M Miller, M Hall, SD TI The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID MENSTRUAL-CYCLE PHASE; ST-JOHNS-WORT; 3-MONTH INTRAINDIVIDUAL VARIABILITY; ALTERNATIVE MEDICINE USE; DRUG-INTERACTIONS; CYP3A ACTIVITY; HERBAL MEDICINES; XANTHINE-OXIDASE; HEPATIC CYP3A; METABOLISM AB Background: Echinacea is a widely available over-the-counter herbal remedy. Tinctures of echinacea have been shown to inhibit cytochrome P450 (CYP) in vitro. The effect of echinacea (Echinacea purpurea root) on CYP activity in vivo was assessed by use of the CYP probe drugs caffeine (CYP1A2), tolbutamide (CYP2C9), dextromethorphan (CYP2D6), and midazolam (hepatic and intestinal CYP3A). Methods: Twelve healthy subjects (6 men) completed this 2-period, open-label, fixed-schedule study. Caffeine, tolbutamide, dextromethorphan, and oral and intravenous midazolam were administered before and after a short course of echinacea (400 mg 4 times a day for 8 days) to determine in vivo CYP activities. Results: Echinacea administration significantly increased the systemic clearance of midazolam. by 34%, from 32 +/- 7 L/h to 43 +/- 16 L/h (P = .003; 90% confidence interval [CI], 116%-150%), and significantly reduced the midazolam area under the concentration-time curve by 23%, from 127 +/- 36 mug (.) h/L to 102 +/- 43 mug h/L (P = .024; 90% CI, 63%-88%). In contrast, the oral clearance of midazolam was not significantly altered (P = .655; 90% CI, 75%-124%), 137 +/- 19 L/h compared with 146 +/- 71 L/h. The oral availability of midazolam after echinacea dosing was significantly increased (P = .028; 90% CI, 108%-153%), from 0.23 +/- 0.06 to 0.33 +/- 0.13. Hepatic availability (0.72 +/- 0.08 versus 0.61 +/- 0.16; P = .006; 90% CI, 73%-90%) and intestinal availability (0.33 +/- 0.11 versus 0.61 +/- 0.38; P = .015; 90% CI, 125%-203%) were significantly altered in opposite directions. Echinacea dosing significantly reduced the oral clearance of caffeine, from 6.6 +/- 3.8 L/h to 4.9 +/- 2.3 L/h (P = .049; 90% CI, 58%-96%). The oral clearance of tolbutamide was reduced by 11%, from 0.81 +/- 0.18 L/h to 0.72 +/- 0.19 L/h, but this change was not considered to be clinically relevant because the 90% CIs were within the 80% to 125% range. The oral clearance of dextromethorphan in 11 CYP2D6 extensive metabolizers was not affected by echinacea dosing (1289 +/- 414 L/h compared with 1281 +/- 483 L/h; P = .732; 90% CI, 89%-108%). Conclusions: Echinacea (Epurpurea root) reduced the oral clearance of substrates of CYP1A2 but not the oral clearance of substrates of CYP2C9 and CYP2D6. Echinacea selectively modulates the catalytic activity of CYP3A at hepatic and intestinal sites. The type of drug interaction observed between echinacea and other CYP3A substrates will be dependent on the relative extraction of drugs at hepatic and intestinal sites. Caution should be used when echinacea is coadministered with drugs dependent on CYP3A or CYP1A2 for their elimination. C1 Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46204 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Off Commissioner, Rockville, MD 20857 USA. RP Gorski, JC (reprint author), Indiana Univ, Div Clin Pharmacol, Wishard Mem Hosp, Sch Med, WD Myers Bldg,W7123,1001 W 10th St, Indianapolis, IN 46202 USA. EM jcgorski@iupui.edu FU NCRR NIH HHS [M01-RR00750]; NIGMS NIH HHS [T32GM08425] NR 67 TC 143 Z9 152 U1 2 U2 13 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 JAN PY 2004 VL 75 IS 1 BP 89 EP 100 DI 10.1016/j.clpt.2003.09.013 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 765YJ UT WOS:000188318400008 PM 14749695 ER PT J AU Sun, DX Yu, LX Hussain, MA Wall, DA Smith, RL Amidon, GL AF Sun, DX Yu, LX Hussain, MA Wall, DA Smith, RL Amidon, GL TI In vitro testing of drug absorption for drug 'developability' assessment: Forming an interface between in vitro preclinical data and clinical outcome SO CURRENT OPINION IN DRUG DISCOVERY & DEVELOPMENT LA English DT Review DE biopharmaceutics classification system; fraction of drug absorbed; in vitro/in vivo correlation; maximum absorbable dose; permeability; prodrug ID BIOPHARMACEUTICS CLASSIFICATION-SYSTEM; CACO-2 CELLS; INTESTINAL-ABSORPTION; PERMEABILITY; BIOAVAILABILITY; DISSOLUTION; PREDICTION; HUMANS; MODEL AB Drug 'developability' assessment has become an increasingly important addition to traditional drug efficacy and toxicity evaluations, as pharmaceutical scientists strive to accelerate drug discovery and development processes in a time- and cost-effective manner. The fraction of drug absorbed and the maximum absorbable dose (MAD) can be estimated from in vivo clinical pharmacokinetics, mass balance studies or in vivo drug permeability in humans by different calculation methods. Unfortunately, in vivo data are usually unavailable at the early stages of drug discovery and development, and in vitro screening for the permeability, solubility, activity and toxicity of a drug has become a routine measurement in drug discovery and development. These in vitro data could be used to predict drug 'developability' with different calculation methods before selecting candidates for clinical evaluation. The fraction of drug absorbed in human could be predicted by in vivo human permeability or in vitro Caco2 permeability. For example, if drug permeability in Caco2 cells reaches 13.3 to 18.1 x 10(-6) cm/s, its predicted in vivo permeability in humans would reach 2 x 10(-4) cm/s, and its predicted fraction of drug absorbed would be > 90%, which is defined as highly permeable. The MAD could also be predicted with in vitro permeability, or calculated absorption rate constant. In addition, in vitro solubility and permeability data can also be used for the biopharmaceutics classification system (BCS) and, subsequently, to direct formulation optimization strategies. If drug 'developability' becomes an obstacle for drug delivery based on these in vitro data and predictions at the early stages of drug discovery and development, options such as prodrug approaches could be explored to enhance drug 'developability', in addition to different formulation methods. Therefore, in vitro absorption testing is a highly valuable tool in the decision-making process to select candidates for in vivo clinical studies at early-stage drug discovery and development. C1 Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA. Off Genet Drug, Ctr Drug Evalut & Res, Food & Drug Adm, Rockville, MD 20857 USA. Bristol Myers Squibb Co, Pharmaceut Res Inst, Exploratory Biopharmaceut & Stabil, New Brunswick, NJ 08903 USA. Univ Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA. RP Sun, DX (reprint author), Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA. EM sun.176@osu.edu RI Yu, Lawrence/L-6280-2016 NR 18 TC 74 Z9 81 U1 0 U2 18 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 2004 VL 7 IS 1 BP 75 EP 85 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 869MB UT WOS:000224986400007 PM 14982151 ER PT J AU Calderon, SN Coop, A AF Calderon, SN Coop, A TI SNC 80 and related delta opioid agonists SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID RECEPTOR-MEDIATED PHENOMENA; DISPLAYS SELECTIVE BINDING; MESSAGE-ADDRESS CONCEPT; (+)-4-<(ALPHA-R)-ALPHA-((2S,5R)-4-ALLYL-2,5-DIMETHYL-1-PIPERAZINYL)-3-ME THOXYBE SNC-80; PHARMACOLOGICAL CHARACTERIZATION; ANTAGONISTS; LIGANDS; PROBES; PEPTIDES; PHARMACOPHORE AB The discovery of the selective delta (delta) opioid agonists SNC 80 and BW373U86, which possess a diarylmethylpiperazine structure unique among opioids, was a major advance in the field of delta-opioid ligands. Much research has been performed to uncover the structure-activity relationships (SAR) of this class of ligands and also to compare the diarylmethylpiperazines with the traditional morphinan-based delta opioids. This review focuses on the development of the SAR of this unique series of ligands, and discusses questions which remain unanswered. C1 US FDA, CDER, Rockville, MD 20857 USA. Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. RP Calderon, SN (reprint author), US FDA, CDER, 5600 Fishers Lane, Rockville, MD 20857 USA. EM CALDERONS@cder.fda.gov FU NIDA NIH HHS [DA 13583] NR 54 TC 19 Z9 19 U1 1 U2 5 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2004 VL 10 IS 7 BP 733 EP 742 DI 10.2174/1381612043453054 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 780MA UT WOS:000189383400004 PM 15032699 ER PT J AU Anderson, HA Shacter, E AF Anderson, HA Shacter, E TI Natural anticoagulant proteins in the regulation of autoimmunity: Potential role of protein S SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE protein S; apoptosis; phagocytosis; autoimmunity; anticoagulant protein; coagulation; protein C; activated protein C ID HUMAN MONONUCLEAR PHAGOCYTES; RECEPTOR TYROSINE KINASE; TOLL-LIKE RECEPTORS; APOPTOTIC CELLS; SEVERE SEPSIS; MACROPHAGE RECOGNITION; BLOOD-COAGULATION; VITRONECTIN RECEPTOR; ACTIVATED RECEPTOR-1; IMMUNE-RESPONSES AB Autoimmunity results when the immune system fails to distinguish between self and non-self factors in the body. The cellular and biochemical mechanisms that underlie development of autoimmunity are only partly understood. One current theory is that autoimmunity can result when there is a failure to clear dying cells from a tissue before they undergo lysis of the plasma membrane. That is, cells that die by apoptosis are thought to be cleared from a tissue by neighboring phagocytic cells, such as macrophages, before the cells have lost their plasma membrane integrity. This rapid removal of early apoptotic cells is thought to prevent induction of an inflammatory response to intracellular macromolecules, thereby allowing for an immunologically silent removal of the dying cells. Hence, any factor or condition that inhibits phagocytosis of early apoptotic cells may trigger or promote an autoimmune response to intracellular components. Depletion of factors required for the efficient phagocytosis of dying cells would have a similar outcome. The recent discovery that the natural anticoagulant protein S is required for efficient uptake of apoptotic cells (Anderson, H.A., Maylock, C.A., Williams, J.A., Paweletz, C.P., Shu, H., and Shacter, E. (2003) Nature Immunology 4, 87-91) reveals a potential new linkage between autoimmunity and coagulation systems. This article will review the dual roles of protein S as an anticoagulant and in regulating phagocytosis of apoptotic cells, with emphasis on exposing a possible novel role in regulating autoimmunity. C1 Ctr Drug Evaluat & Res, Food & Drug Adm, Biochem Lab, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Shacter, E (reprint author), 29 Lincoln Dr,Bldg 29A,Room 2A-11, Bethesda, MD 20892 USA. EM emily.shacter@fda.gov NR 98 TC 9 Z9 9 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2004 VL 10 IS 8 BP 929 EP 937 DI 10.2174/1381612043452839 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 804BH UT WOS:000220273700012 PM 15032696 ER PT S AU Itzhak, Y Anderson, KL Ali, SF AF Itzhak, Y Anderson, KL Ali, SF BE Ali, SF Nabeshima, T Yanagita, T TI Differential response of nNOS knockout mice to MDMA ("ecstasy")- and methamphetamine-induced psychomotor sensitization and neurotoxicity SO CURRENT STATUS OF DRUG DEPENDENCE / ABUSE STUDIES: CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Current Status of Depedence and Abuse Studies CY JUL 30-AUG 01, 2003 CL Kyoto, JAPAN SP Int Soc Neurochem, Japanese Pharmacol Soc, Japanese Med Soc Alcohol& Drug Studies, Japanese Soc Neurochem, Japanese Soc Neuropsychopharmocol, Minist Educ, Culture, Sports, Sci & Technol, Nagoya Univ Fdn, Uehara Memorial Fdn, Sigma-Tau Hlth Sci, Natl Inst Drug Abuse, Natl Ctr Toxicol Res, US FDA DE nitric oxide (NO); knockout mice; locomotor activity; neurotoxicity; dopamine; serotonin ID NITRIC-OXIDE SYNTHASE; INDUCED DOPAMINERGIC NEUROTOXICITY; BEHAVIORAL SENSITIZATION; LOCOMOTOR-ACTIVITY; DEFICIENT MICE; 3,4-METHYLENEDIOXYMETHAMPHETAMINE; NEUROTRANSMISSION; 7-NITROINDAZOLE; STIMULATION; INHIBITION AB It has been shown that mice deficient in neuronal nitric oxide synthase (nNOS) gene are resistant to cocaine-induced psychomotor sensitization and methamphetamine (METH)-induced dopaminergic neurotoxicity. The present study was undertaken to investigate the hypothesis that nNOS has a major role in dopamine (DA)- but not serotonin (5-hydroxytryptamine; 5-HT)mediated effects of psychostimulants. The response of nNOS knockout (KO) and wild-type (WT) mice to the psychomotor-stimulating and neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") and METH were investigated. Repeated administration of MDMA for 5 days resulted in psychomotor sensitization in both WT and nNOS KO mice, while repeated administration of METH caused psychomotor sensitization in WT but not in KO mice. Sensitization to both MDMA and METH was persistent for 40 days in WT mice, but not in nNOS KO mice. These findings suggest that the induction of psychomotor sensitization to MDMA and METH is NO independent and NO dependent, respectively, while the persistence of sensitization to both drugs is NO dependent. For the neurochemical studies, a high dose of MDMA caused marked depletion of 5-HT in several brain regions of both WT and KO mice, suggesting that the absence of the nNOS gene did not afford protection against MDMA-induced depletion of 5-HT. Striatal dopaminergic neurotoxicity caused by high doses of MDMA and METH in WT mice was partially prevented in KO mice administered with MDMA, but it was fully precluded in KO mice administered with METH. The differential response of nNOS KO mice to the behavioral and neurotoxic effects of MDMA and METH suggests that the nNOS gene is required for the expression and persistence of DA-mediated effects of METH and MDMA, while 5-HT-mediated effects of MDMA (induction of sensitization and 5-HT depletion) are not dependent on nNOS. C1 Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Itzhak, Y (reprint author), Univ Miami, Sch Med, Dept Psychiat & Behav Sci, 1011 NW 15th St,Gautier Bldg 503, Miami, FL 33136 USA. EM yitzhak@med.miami.edu FU NIDA NIH HHS [R01 DA12867] NR 29 TC 18 Z9 18 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-522-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1025 BP 119 EP 128 DI 10.1196/annals.1316.015 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Substance Abuse; Multidisciplinary Sciences; Neurosciences SC Biochemistry & Molecular Biology; Cell Biology; Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology GA BBP90 UT WOS:000226975200015 PM 15542708 ER PT S AU Virmani, A Gaetani, F Binienda, Z Xu, A Duhart, H Ali, SF AF Virmani, A Gaetani, F Binienda, Z Xu, A Duhart, H Ali, SF BE Ali, SF Nabeshima, T Yanagita, T TI Role of mitochondrial dysfunction in neurotoxicity of MPP+ - Partial protection of PC12 cells by acetyl-L-carnitine SO CURRENT STATUS OF DRUG DEPENDENCE / ABUSE STUDIES: CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Current Status of Depedence and Abuse Studies CY JUL 30-AUG 01, 2003 CL Kyoto, JAPAN SP Int Soc Neurochem, Japanese Pharmacol Soc, Japanese Med Soc Alcohol& Drug Studies, Japanese Soc Neurochem, Japanese Soc Neuropsychopharmocol, Minist Educ, Culture, Sports, Sci & Technol, Nagoya Univ Fdn, Uehara Memorial Fdn, Sigma-Tau Hlth Sci, Natl Inst Drug Abuse, Natl Ctr Toxicol Res, US FDA DE L-carnitine; acetyl-L-carnitine; mitochondria; methamphetamine; MPTP; 1-methyl-4-phenylpyridinium (MPP+); Parkinson's; apoptosis; oxidative phosphorylation; respiratory chain mitochondrial permeability pores ID INDUCED DOPAMINERGIC NEUROTOXICITY; 1-METHYL-4-PHENYLPYRIDINIUM TOXICITY; PERMEABILITY TRANSITION; NEUROBLASTOMA-CELLS; PARKINSONS-DISEASE; METHAMPHETAMINE; SYNAPTOSOMES; INHIBITION; TRANSPORT; GLUTAMATE AB The damage to the central nervous system that is observed after administration of either methamphetamine (METH) or 1-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is known to be linked to dopamine (DA). The underlying neurotoxicity mechanism for both METH and MPPI seem to involve free radical formation and impaired mitochondrial function. The MPP+ is thought to selectively kill nigrostriatal dopaminergic neurons by inhibiting mitochondrial complex 1, with cell death being attributed to oxidative stress damage to these vulnerable DA neurons. In the present study, MPP+ was shown to significantly inhibit the response to MTT by cultured PC12 cells. This inhibitory action of MPPI could be partially reversed by the co-incubation of the cells with the acetylated form of carnitine, acetyl-L-carnitine (ALC). Since at least part of the toxic action of MPP+ is related to mitochondrial inhibition, the partial reversal of the inhibition of MTT response by ALC could involve a partial restoration of mitochondrial function. The role carnitine derivatives, such as ALC, play in attenuating MPPI and METH-evoked toxicity is still under investigation to elucidate the contribution of mitochondrial dysfunction in mechanisms of neurotoxicity. C1 Sigma Tau HealthSci SpA, Res & Dev, I-00040 Pomezia, Italy. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Virmani, A (reprint author), Sigma Tau HealthSci SpA, Res & Dev, I-00040 Pomezia, Italy. EM ashraf.virmani@st-hs.it NR 24 TC 31 Z9 34 U1 2 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-522-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1025 BP 267 EP 273 DI 10.1196/annals.1316.033 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Substance Abuse; Multidisciplinary Sciences; Neurosciences SC Biochemistry & Molecular Biology; Cell Biology; Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology GA BBP90 UT WOS:000226975200033 PM 15542726 ER PT S AU Pereira, FC Santos, SD Ribeiro, CF Ali, SF Macedo, TR AF Pereira, FC Santos, SD Ribeiro, CF Ali, SF Macedo, TR BE Ali, SF Nabeshima, T Yanagita, T TI A single exposure to morphine induces long-lasting hyporeactivity of rat caudate putamen dopaminergic nerve terminals SO CURRENT STATUS OF DRUG DEPENDENCE / ABUSE STUDIES: CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Current Status of Depedence and Abuse Studies CY JUL 30-AUG 01, 2003 CL Kyoto, JAPAN SP Int Soc Neurochem, Japanese Pharmacol Soc, Japanese Med Soc Alcohol& Drug Studies, Japanese Soc Neurochem, Japanese Soc Neuropsychopharmocol, Minist Educ, Culture, Sports, Sci & Technol, Nagoya Univ Fdn, Uehara Memorial Fdn, Sigma-Tau Hlth Sci, Natl Inst Drug Abuse, Natl Ctr Toxicol Res, US FDA DE morphine; single-injection; dopamine neurotransmission; caudate putamen; neuroadaptation ID DELTA-OPIOID RECEPTORS; SUBSTANTIA-NIGRA; OPIATE AGONISTS; LIMBIC DOPAMINE; RHESUS-MONKEYS; IN-VIVO; TOLERANCE; MICE; METABOLISM; RELEASE AB The long-lasting effects of exposure to drugs of abuse on the brain is a central theme in drug addiction research. This study was designed to evaluate whether enduring neurochemical adaptations within caudate putamen can be evoked by a single injection of a high dose of morphine. Rats were pretreated once with 10 mg/kg morphine. Seven days later the effect of another injection of 10 mg/kg morphine on total levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanilic acid (HVA) in caudate putamen was assessed in half the pretreated animals. An irreversible mu-opioid receptor antagonist, cloccinamox (C-CAM; 0.1 mg/kg), significantly antagonized the elevation of the HVA/DA ratio, but not the elevation of the DOPAC/DA ratio induced by morphine in the caudate putamen from drug-naive animals. Pretreatment with morphine blunted changes in the HVA/DA ratio induced by another morphine challenge, but it had no effect on the DOPAC/DA ratio within the caudate putamen. Therefore, a single dose of 10 mg/kg morphine hampered nigrostriatal DA release and extraneuronal metabolism, mu-opioid receptor mediated, on another 10 mg/kg morphine challenge. This confirms that the first exposure to morphine does not go without long-lasting neurochemical adaptations. C1 Univ Coimbra, Sch Med, Inst Farmacol & Terapeut, P-3004504 Coimbra, Portugal. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Pereira, FC (reprint author), Univ Coimbra, Sch Med, Inst Farmacol & Terapeut, P-3004504 Coimbra, Portugal. EM fredcp@ci.uc.pt OI Pereira, Frederico/0000-0002-9381-3320; Fontes Ribeiro, Carlos/0000-0002-9707-4895; santos, sandra/0000-0002-1871-3696 NR 37 TC 8 Z9 9 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-522-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1025 BP 414 EP 423 DI 10.1196/annals.1316.051 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Substance Abuse; Multidisciplinary Sciences; Neurosciences SC Biochemistry & Molecular Biology; Cell Biology; Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology GA BBP90 UT WOS:000226975200051 PM 15542744 ER PT S AU Dass, SB Ali, SF AF Dass, SB Ali, SF BE Ali, SF Nabeshima, T Yanagita, T TI Evaluation of gamma-hydroxybutyric acid for genotoxicity in the mouse micronucleus assay SO CURRENT STATUS OF DRUG DEPENDENCE / ABUSE STUDIES: CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Current Status of Depedence and Abuse Studies CY JUL 30-AUG 01, 2003 CL Kyoto, JAPAN SP Int Soc Neurochem, Japanese Pharmacol Soc, Japanese Med Soc Alcohol& Drug Studies, Japanese Soc Neurochem, Japanese Soc Neuropsychopharmocol, Minist Educ, Culture, Sports, Sci & Technol, Nagoya Univ Fdn, Uehara Memorial Fdn, Sigma-Tau Hlth Sci, Natl Inst Drug Abuse, Natl Ctr Toxicol Res, US FDA DE gamma-hydroxybutyric acid (GHB); drugs of abuse; micronucleus test; genotoxicity; micronucleated polychromatic erythrocytes; gamma-butyrolactone ID PERIPHERAL-BLOOD; SODIUM-BUTYRATE; ABERRATIONS; BRAIN; DRUGS; MICE AB gamma-Hydroxybutyric acid (GHB) is an endogenous compound found in the brain and other tissues of mammals. Neurotransmitter/neuromodulator functions have been ascribed to GHB, which has lately become a drug of abuse. In this study, we tested GHB for genotoxicity by measuring its ability to induce micronuclei in polychromatic erythrocytes (reticulocytes) in the peripheral blood of mice. Intraperitoneal injection with a dose of 25 mg/kg/day for 3 days or 50 mg/kg/day x 3 days resulted in a significant (by Donnell's test) increase of 1.9- to 2.1-fold in micronuclei. However, because increases were small and because no consistent dose-dependent increase in induced micronuclear frequency could be demonstrated, our results do not conclusively show that GHB is an in vivo genotoxicant in mammals. C1 Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Dass, SB (reprint author), Merck Res Labs, Mail Code RY34B-364,126 E Lincoln Ave, Rahway, NJ 07065 USA. NR 18 TC 1 Z9 1 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-522-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1025 BP 538 EP 542 DI 10.1196/annals.1316.066 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Substance Abuse; Multidisciplinary Sciences; Neurosciences SC Biochemistry & Molecular Biology; Cell Biology; Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology GA BBP90 UT WOS:000226975200066 PM 15542759 ER PT S AU Riegel, AC Ali, SF Torinese, S French, ED AF Riegel, AC Ali, SF Torinese, S French, ED BE Ali, SF Nabeshima, T Yanagita, T TI Repeated exposure to the abused inhalant toluene alters levels of neurotransmitters and generates peroxynitrite in nigrostriatal and mesolimbic nuclei in rat SO CURRENT STATUS OF DRUG DEPENDENCE / ABUSE STUDIES: CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Current Status of Depedence and Abuse Studies CY JUL 30-AUG 01, 2003 CL Kyoto, JAPAN SP Int Soc Neurochem, Japanese Pharmacol Soc, Japanese Med Soc Alcohol& Drug Studies, Japanese Soc Neurochem, Japanese Soc Neuropsychopharmocol, Minist Educ, Culture, Sports, Sci & Technol, Nagoya Univ Fdn, Uehara Memorial Fdn, Sigma-Tau Hlth Sci, Natl Inst Drug Abuse, Natl Ctr Toxicol Res, US FDA DE inhalant; toluene; neurotransmitter; dopamine; serotonin; oxidative stress; peroxynitrite; 3-nitrosotyrosine; nigrostriatal and mesolimbic nuclei; neurotoxicity ID MEDIATED LOCOMOTOR-ACTIVITY; SUBACUTE EXPOSURE; NEURONAL-ACTIVITY; DOPAMINE; BINDING; BRAIN AB Toluene, a volatile hydrocarbon found in a variety of chemical compounds, is misused and abused by inhalation for its euphorigenic effects. Toluene's reinforcing properties may share a common characteristic with other drugs of abuse, namely, activation of the mesolimbic dopamine system. Prior studies in our laboratory found that acutely inhaled toluene activated midbrain dopamine neurons in the rat. Moreover, single systemic injections of toluene in rats produced a dose-dependent increase in locomotor activity which was blocked by depletion of nucleus accumbens dopamine or by pretreatment with a D2 dopamine receptor antagonist. Here we examined the effects of seven daily intraperitoneal injections of 600 mg/kg toluene on the content of serotonin and dopamine in the caudate nucleus (CN) and nucleus accumbens (NAC), substantia nigra, and ventral tegmental area at 2, 4, and 24 h after the last injection. Also, the roles of nitric oxide, peroxynitrite, and the production of 3-nitrosotyrosine (3-NT), in the CN and NAC were assessed at the same time points. Toluene treatments increased dopamine levels in the CN and NAC, and serotonin levels in CN, NAC, and ventral tegmental area. Measurements of the dopamine metabolite dihydroxyphenylacetic acid (DOPAC) further suggested a change in transmitter utilization in CN and NAC. Lastly, 3-NT levels also showed a differential change between CN and NAC, but at different time points post-toluene injection. These results point out the complexity of action of toluene on neurotransmitter function following a course of chronic exposure. Changes in the production of 3-NT also suggest that toluene-induced neurotoxicity may mediate via generation of peroxynitrite. C1 Univ Arizona, Coll Med, Dept Pharmacol, Tucson, AZ 85724 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP French, ED (reprint author), Univ Arizona, Coll Med, Dept Pharmacol, Tucson, AZ 85724 USA. EM efrench@email.arizona.edu NR 17 TC 17 Z9 17 U1 1 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-522-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1025 BP 543 EP 551 DI 10.1196/annals.1316.079 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Substance Abuse; Multidisciplinary Sciences; Neurosciences SC Biochemistry & Molecular Biology; Cell Biology; Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology GA BBP90 UT WOS:000226975200067 PM 15542760 ER PT J AU Schwartz, A Gaigalas, AK Wang, LL Marti, GE Vogt, RF Fernandez-Repollet, E AF Schwartz, A Gaigalas, AK Wang, LL Marti, GE Vogt, RF Fernandez-Repollet, E TI Formalization of the MESF unit of fluorescence intensity SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE MESF; Molecules of Equivalent Soluble Fluorochrome; quantitation; fluorescence intensity AB This report summarizes the work performed during the past two years at the National Institute of Standards and Technology (NIST) in the refinement and formal definition of the MESF unit of fluorescence intensity. In addition to the theory underlying the MESF unit, considerations of error analysis are also presented. The details of this work may be found in the three publications of the NIST Journal of Research (www.nist.gov) listed as the references 2-4. The use of the fluorescence intensity unit provides a tool to compare quantitative fluorescence intensity measurements over time and across platforms. (C) 2003 Wiley-Liss, Inc. C1 Univ Puerto Rico, Sch Med, Dept Pharmacol, San Juan, PR 00936 USA. Ctr Dis Control, Div Sci Lab, Atlanta, GA 30333 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NIST, Div Biotechnol, Gaithersburg, MD 20899 USA. Ctr Quantitat Cytometry, San Juan, PR USA. RP Schwartz, A (reprint author), POB 194344, San Juan, PR 00919 USA. EM abe@quantcyte.org NR 4 TC 61 Z9 62 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD JAN PY 2004 VL 57B IS 1 BP 1 EP 6 DI 10.1002/cyto.b.10066 PG 6 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 760XQ UT WOS:000187860900001 PM 14696057 ER PT J AU Lunning, MA Zenger, VE Dreyfuss, R Stetler-Stevenson, M Rick, ME White, TA Wilson, WH Marti, GE AF Lunning, MA Zenger, VE Dreyfuss, R Stetler-Stevenson, M Rick, ME White, TA Wilson, WH Marti, GE TI Albumin enhanced morphometric image analysis in CLL SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE chronic lymphocytic leukemia; morphology; atypical morphology; atypical chronic lymphocytic leukemia; morphometric analysis ID CHRONIC LYMPHOCYTIC-LEUKEMIA; IN-SITU HYBRIDIZATION; B-CELL DISORDERS; PROLYMPHOCYTIC LEUKEMIA; PROGNOSTIC-SIGNIFICANCE; SCORING SYSTEM; NUCLEAR CLEFTS; LABORATORY FEATURES; LYMPHOID LEUKEMIAS; MORPHOLOGY AB Background: The heterogeneity of lymphocytes from patients with chronic lymphocytic leukemia (CLL) and blood film artifacts make morphologic subclassification of this disease difficult. Methods: We reviewed paired blood films prepared from ethylene-diamine-tetraacetic acid (ETDA) samples with and without bovine serum albumin (BSA) from 82 CLL patients. Group 1 adhered to NCCLS specifications for the preparations of EDTA blood films. Group 2 consisted of blood films containing EDTA and a 1:12 dilution of 22% BSA. Eight patients were selected for digital photomicroscopy and statistical analysis. Approximately 100 lymphocytes from each slide were digitally captured. Results: The mean cell area +/- standard error was 127.8 muM(2) +/- 1.42 for (n = 793) for group 1 versus 100.7 muM(2) +/- 1.39 (n = 831) for group 2. The nuclear area was 88.9 muM(2) +/- 0.85 for group 1 versus 76.4 muM(2) 0.83 for group 2. For the nuclear transmittance, the values were 97.6 +/- 0.85 for group 1 and 104.1 +/- 0.83 for group 2. The nuclear:cytoplasmic ratios were 0.71 +/- 0.003 for group 1 and 0.78 +/- 0.003 for group 2. All differences were statistically significant (P < 0.001). Conclusions: BSA addition results in the reduction of atypical lymphocytes and a decrease in smudge cells. BSA also decreases the lymphocyte area and nuclear area, whereas nuclear transmittance and nuclear:cytoplasmic ratio are increased. A standardized method of slide preparation would allow accurate interlaboratory comparison. The use of BSA may permit better implementation of the blood film-based subclassification of CLL and lead to a better correlation of morphology with cytogenetics and immunophenotyping. Published 2003 Wiley-Liss, Inc(dagger). C1 US FDA, Flow & Image Cytometry Sect, Lab Stem Biol, DCGT,CBER, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Med Oncol Clin Res Unit, NIH, Bethesda, MD 20892 USA. NIH, Hematol Serv, Ctr Clin, Bethesda, MD 20892 USA. NIH, Clin Flow Cytometry Sect, Pathol Lab, Div Clin Sci, Bethesda, MD 20892 USA. NIH, Med Arts Photog Branch, Bethesda, MD 20892 USA. RP Marti, GE (reprint author), US FDA, Flow & Image Cytometry Sect, Lab Stem Biol, DCGT,CBER, NIH Bldg 29B,Room 2NN08,8800 Rockville Pike, Bethesda, MD 20892 USA. EM gemarti@helix.nih.gov NR 40 TC 6 Z9 6 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD JAN PY 2004 VL 57B IS 1 BP 7 EP 14 DI 10.1002/cyto.b.10059 PG 8 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 760XQ UT WOS:000187860900002 PM 14696058 ER PT J AU Jackson, G AF Jackson, G TI Austria dances - Past and present SO DANCE CHRONICLE LA English DT Book Review C1 US FDA, Rockville, MD 20857 USA. Univ Chicago, Chicago, IL 60637 USA. Rockefeller Univ, New York, NY USA. RP Jackson, G (reprint author), US FDA, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0147-2526 J9 DANCE CHRONICLE JI Dance Chron. PY 2004 VL 27 IS 1 BP 143 EP 145 DI 10.1081/DNC-120029930 PG 3 WC Dance SC Dance GA 823HO UT WOS:000221601400006 ER PT J AU Alosh, M Wilkin, J AF Alosh, M Wilkin, J TI Assessing the relationship between investigator global evaluation and acne lesion counts SO DRUG INFORMATION JOURNAL LA English DT Article DE acne trials; lesion counts; logistic regression ID LOGISTIC-REGRESSION AB Efficacy evaluation for acne clinical trials is usually based on analysis of: (1) change (or relative change) in lesion counts from baseline and (2) the investigator global evaluation (IGE) at the final study endpoint, usually dichotomized to treatment success or failure. As lesion counts provide a quantitative assessment of the subject's acne condition and the IGE reflects the dermatologist's visual evaluation of the same condition, one would expect the two evaluations to be related. In this article we investigate the relationship between the two assessments by fitting logistic regression models to three data sets with different features. The results of the analysis show that final lesion counts explain very well the variability in the IGE treatment success. However, changes in lesion counts per se do not fully explain the variability in IGE treatment success, as baseline lesion counts are still a significant covariate in the model. Finally, inflammatory lesions consistently have a much greater impact than nonin-inflammatory lesions on explaining the variability in the IGE treatment success. The findings of this study emphasize the importance of having an initial estimate of treatment effect before embarking on phase 3 trials. Such an estimate would be very useful in guiding the decision on whether to seek a lesion-specific or general acne indication, which, in turn, impacts the sample size required for establishing efficacy. C1 US FDA, CDER, OB, Div Biometr 3, Rockville, MD 20850 USA. US FDA, CDER, Off Durg Evaluat 5, Div Dermatol & Dent Drug Prod, Rockville, MD 20850 USA. RP Alosh, M (reprint author), US FDA, CDER, OB, Div Biometr 3, HFD-725,S-128,9201 Corp Blvd, Rockville, MD 20850 USA. EM aloshm@cder.fda.gov NR 6 TC 2 Z9 2 U1 0 U2 0 PU DRUG INFORMATION ASSOCIATION PI FORT WASHINGTON PA 501 OFFICE CENTER DR, STE 450, FORT WASHINGTON, PA 19034-3212 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PY 2004 VL 38 IS 4 BP 343 EP 351 PG 9 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 869OL UT WOS:000224993800005 ER PT J AU Cui, YY Ang, CYW Beger, RD Heinze, TM Hu, LH Leakey, J AF Cui, YY Ang, CYW Beger, RD Heinze, TM Hu, LH Leakey, J TI In vitro metabolism of hyperforin in rat liver microsomal systems SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID ST-JOHNS-WORT; PERFORMANCE LIQUID-CHROMATOGRAPHY; PREGNANE X-RECEPTOR; HYPERICUM-PERFORATUM; PHENOBARBITAL-INDUCTION; DIETARY-SUPPLEMENTS; GENE; ANTIDEPRESSANT; STABILITY; MACROMOLECULES AB Hyperforin is an important active component of St. John's wort (Hypericum perforatum) that has been suggested to be responsible for the St. John's wort antidepressive effects and herbal-drug interactions. In this study, the in vitro metabolism profile of hyperforin was investigated using liver microsomes from male and female Sprague-Dawley rats, with or without induction by phenobarbital or dexamethasone. Four major Phase I metabolites, named 19-hydroxyhyperforin, 24-hydroxyhyperforin, 29-hydroxyhyperforin, and 34-hydroxyhyperforin, were isolated by high performance liquid chromatography and identified by mass spectrometry and NMR. Results suggest that hydroxylation is a major biotransformation of the hyperforin pathway in rat liver and that inducible cytochrome P450 3A (CYP450 3A) and/or CYP2B may be the major cytochrome P450 isoforms catalyzing these hydroxylation reactions. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Ang, CYW (reprint author), US FDA, Natl Ctr Toxicol Res, Div Chem, HFT-230,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 43 TC 22 Z9 24 U1 0 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JAN 1 PY 2004 VL 32 IS 1 BP 28 EP 34 DI 10.1124/dmd.32.1.28 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 760RJ UT WOS:000187847900005 PM 14709617 ER PT J AU Wiener, D Doerge, DR Fang, JL Upadhyaya, P Lazarus, P AF Wiener, D Doerge, DR Fang, JL Upadhyaya, P Lazarus, P TI Characterization of N-glucuronidation of the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (nnal) in human liver: Importance of UDP-glucuronosyltransferase 1A4 SO DRUG METABOLISM AND DISPOSITION LA English DT Article; Proceedings Paper CT 94th Annual Meeting of the American-Association-for-Cancer-Research CY JUL 11-14, 2003 CL WASHINGTON, D.C. SP Amer Assoc Canc Res ID TOBACCO-SPECIFIC NITROSAMINES; STABLE EXPRESSION; SMOKERS URINE; F344 RATS; METABOLITES; MICROSOMES; INDUCTION; BENZOPYRENE; QUANTITATION; XENOBIOTICS AB The nicotine-derived tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone (NNK), is one of the most potent and abundant procarcinogens found in tobacco and tobacco smoke and is considered to be a causative agent for several tobacco-related cancers. Glucuronidation of the major metabolite of NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), has been implicated as an important mechanism for NNK detoxification. To characterize NNAL metabolism by N-glucuronidation in humans, high-pressure liquid chromatography was used to detect glucuronide conjugates of NNAL formed in human liver microsomes in vitro. In addition to peaks corresponding to the O-glucuronides of NNAL (NNAL-O-Gluc), a second series of peaks were observed in human liver microsomes that were identified by liquid chromatography-mass spectrometry to be NNAL N-glucuronides (NNAL-N-Gluc). Microsomes prepared from liver specimens from individual subjects (n = 42) exhibited substantial variability in the levels of NNAL-N-Gluc (49-fold variability) and NNAL-O-Gluc (49-fold variability) formed in vitro. This variability was likely not due to differences in tissue quality, as substantial variability (5-fold) was also observed in the ratio of NNAL-N-Gluc/NNAL-O-Gluc formation, with a mean ratio of 1.7 in the 42 specimens. Liver microsomes from smokers (n = 14) exhibited no significant difference in the levels of either NNAL-N-Gluc or NNAL-O-Gluc formation, or in the ratio of NNAL-N-Gluc/NNAL-O-Gluc formation, as compared with liver microsomes from never smokers (n = 28). Overexpressed UDP-glucuronosyltransferase (UGT) 1A4 exhibited significant levels of N-glucuronidating activity (V-max/K-m = 3.11 mul . min(-1) . g(-1)) in vitro; no NNAL-N-glucuronide formation was detected for the 11 other overexpressed UGT enzymes tested in these studies. These results demonstrate the importance of N-glucuronidation in the metabolism of NNAL and the role of UGT1A4 in this pathway. C1 Univ S Florida, Canc Epidemiol & Prevent Program, H Lee Moffitt Canc Ctr, Dept Interdisciplinary Oncol, Tampa, FL USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN USA. RP Lazarus, P (reprint author), Penn State Coll, Dept Pharmacol, H078,500 Univ Dr, Hershey, PA 17033 USA. RI Wiener, Doris/A-8825-2013 FU NCI NIH HHS [CA68384]; NIDCR NIH HHS [DE13158] NR 38 TC 67 Z9 69 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JAN 1 PY 2004 VL 32 IS 1 BP 72 EP 79 DI 10.1124/dmd.32.1.72 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 760RJ UT WOS:000187847900011 PM 14709623 ER PT J AU Fu, PP Xia, QS Lin, G Chou, MW AF Fu, PP Xia, QS Lin, G Chou, MW TI Pyrrolizidine alkaloids - Genotoxicity, metabolism enzymes, metabolic activation, and mechanisms SO DRUG METABOLISM REVIEWS LA English DT Review DE genotoxicity; pyrrolizidine alkaloids; metabolism; enzymes; DNA adduct; mechanism; metabolic activation ID VENO-OCCLUSIVE DISEASE; PERFORMANCE LIQUID-CHROMATOGRAPHY; DNA ADDUCT FORMATION; PERFUSED-RAT-LIVER; FLAVIN-CONTAINING MONOOXYGENASE; ALCOHOL GLUTATHIONE CONJUGATE; HEPATIC-MICROSOMAL METABOLISM; RAGWORT SENECIO-JACOBAEA; AGE-DEPENDENT EXPRESSION; SOLID-PHASE EXTRACTION AB Pyrrolizidine alkaloid-containing plants are widely distributed in the world and are probably the most common poisonous plants affecting livestock, wildlife, and humans. Because of their abundance and potent toxicities, the mechanisms by which pyrrolizidine alkaloids induce genotoxicities, particularly carcinogenicity, were extensively studied for several decades but not exclusively elucidated until recently. To date, the pyrrolizidine alkaloid-induced genotoxicities were revealed to be elicited by the hepatic metabolism of these naturally occurring toxins. In this review, we present updated information on the metabolism, metabolizing enzymes, and the mechanisms by which pyrrolizidine alkaloids exert genotoxicity and tumorigenicity. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Chinese Univ Hong Kong, Dept Pharmacol, Shatin, Hong Kong, Peoples R China. RP Fu, PP (reprint author), 3900 NCTR Rd,HFT-110, Jefferson, AR 72079 USA. EM pfu@nctr.fda.gov NR 290 TC 223 Z9 230 U1 10 U2 58 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2004 VL 36 IS 1 BP 1 EP 55 DI 10.1081/DMR-120028426 PG 55 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 807RQ UT WOS:000220519000001 PM 15072438 ER PT J AU Kennedy, DL Uhl, K Kweder, SL AF Kennedy, DL Uhl, K Kweder, SL TI Pregnancy exposure registries SO DRUG SAFETY LA English DT Article ID SURVEILLANCE; DRUGS AB dScientifically valid data on the safety of drug use during pregnancy are a significant public: health need. Data are rarely available on the fetal effects of in utero exposure in human pregnancies, particularly when a drug is first marketed. Data from animal reproductive toxicology studies, which function as a screen for potential human teratogenicity, are usually all that is available in a product's labelling. For practising clinicians, translating known animal risks into an accurate assessment of teratogenic risks in their patients is very difficult, if not impossible. Without human data on the effects of in utero drug exposure, it is difficult for physicians and other healthcare providers (e.g. genetic counsellors) to adequately counsel patients about fetal risks. Therefore, a pregnant woman may decide to unnecessarily terminate a wanted pregnancy or forego needed drug therapy. In spite of the lack of data on the safety of drug use during human pregnancies, pregnant women are exposed to drugs either as prescribed therapy or inadvertently before pregnancy is known (over one-half of pregnancies are unplanned). Because little is known about the teratogenic potential of a drug in humans before marketing, post-marketing surveillance of drug use in pregnancy is critical to the detection of drug-induced fetal effects. The existing passive mechanism of spontaneous reporting of adverse drug effects is inadequate to routinely detect drug-induced fetal risks or lack of such risks. Therefore, post-marketing pregnancy exposure registries are being increasingly used to proactively monitor for major fetal effects and to describe margins of safety associated with drug exposure during pregnancy. However, differing methodological rigour has been applied to the development of pregnancy exposure registries. It is important that all pregnancy registries develop epidemiologically sound written study protocols a priori. It is only through the use of rigourous methodology and procedures that data from pregnancy exposure registries will withstand scientific scrutiny. Successful recruitment of an adequate number of exposed pregnancies, aggressive follow-up, and complete and accurate ascertainment of pregnancy outcome are critical attributes of a well-designed registry. C1 US FDA, Ctr Drug Evaluat & Res, Pregnancy Labeling Team, Pregnancy Labeling Task Force, Rockville, MD 20874 USA. RP Kennedy, DL (reprint author), US FDA, Ctr Drug Evaluat & Res, Pregnancy Labeling Team, Pregnancy Labeling Task Force, HFD-020,5600 Fishers Lane, Rockville, MD 20874 USA. EM kennedyd@cder.fda.gov NR 44 TC 30 Z9 31 U1 0 U2 3 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2004 VL 27 IS 4 BP 215 EP 228 DI 10.2165/00002018-200427040-00001 PG 14 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 805EU UT WOS:000220350400001 PM 15003034 ER PT J AU Brinker, A Goldkind, L Bonnel, R Beitz, J AF Brinker, A Goldkind, L Bonnel, R Beitz, J TI Spontaneous reports of hypertension leading to hospitalisation in association with rofecoxib, celecoxib, nabumetone and oxaprozin SO DRUGS & AGING LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; BLOOD-PRESSURE; RHEUMATOID-ARTHRITIS; METAANALYSIS; INHIBITORS; CYCLOOXYGENASE-2; OSTEOARTHRITIS; DICLOFENAC AB Background and objective: Data on file with the US FDA, and other published studies, suggest that the selective cyclo-oxygenase (COX)-2 inhibitor NSAID rofecoxib has a greater hypertensive adverse effect than other NSAIDs, including celecoxib. In this study we describe a pharmacoepidemiologic analysis of spontaneous adverse event reports of acute, clinically serious hypertension (as defined by hospitalisation) reported in association with rofecoxib, celecoxib, nabumetone and oxaprozin. The objective of this analysis is to assess whether postmarketing data are consistent with results of clinical trials. We also collapse cases into series for the identification of possible risk factors for clinically severe, NSAID-associated hypertension. Methods: Domestic (US) cases of apparently unconfounded, acute hypertension leading to hospitalisation were collected and reviewed from the spontaneous adverse events database of the FDA for rofecoxib, celecoxib, nabumetone and oxaprozin for the initial 3 years of marketing. Drug use data for the same intervals enabled calculation of reporting rates. Results: In an analysis of reporting rates, hospitalisation for acute blood pressure (BP) elevation was reported more frequently (3.8-fold) for rofecoxib compared with celecoxib. A total of 34 cases are collapsed into case series. No cases were identified for either nabumetone or oxaprozin. Inspection of reviewed cases for celecoxib and rofecoxib suggest that these patients (average age 72 years) were potentially high-risk candidates for NSAID therapy. Discussion and conclusion: During early marketing, hospitalisation for acute BP elevation appears to have been reported more frequently for rofecoxib compared with celecoxib. This is consistent with clinical trial data on file with the FDA, and other published studies that found rofecoxib to have a greater effect on BP than other NSAIDs, including celecoxib. This finding may be particularly relevant in older patients given the prevalence of hypertension and cardiovascular disease in this age group. C1 US FDA, Ctr Drug Evaluat & Res, Div Risk Evaluat, Off Drug Safety, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Div Anti Inflammatory, Off Drug Evaluat 5, Rockville, MD 20857 USA. RP Brinker, A (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Risk Evaluat, Off Drug Safety, 5600 Fishers Lane, Rockville, MD 20857 USA. EM brinkera@cder.fda.gov NR 23 TC 17 Z9 19 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PY 2004 VL 21 IS 7 BP 479 EP 484 DI 10.2165/00002512-200421070-00005 PG 6 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 826FJ UT WOS:000221814400005 PM 15132714 ER PT J AU Fraunfelder, FW AF Fraunfelder, FW TI Ocular side effects associated with isotretinoin SO DRUGS OF TODAY LA English DT Review ID THERAPY; ACNE AB Isotretinoin is used for severe recalcitrant nodular acne and has a variety of associated ocular side effects. This review classifies these ocular side effects according to World Health Organization (WHO) criteria and reviews the existing literature as well as 2449 spontaneous case reports collected from around the world. Ocular sicca, decreased dark adaptation and intracranial hypertension are identified as "certain" side effects from isotretinoin and clinicians are provided guidelines for care and follow-up. (C) 2004 Prous Science. All rights reserved. C1 Oregon Hlth Sci Univ, Casey Eye Inst, Natl Registry Drug Induces Ocular Side Effects, Portland, OR 97201 USA. WHO, Collaborating Ctr Int Drug Monitoring, Uppsala, Sweden. US FDA, Rockville, MD 20857 USA. RP Fraunfelder, FW (reprint author), Oregon Hlth Sci Univ, Casey Eye Inst, Natl Registry Drug Induces Ocular Side Effects, 3375 SW Terwilliger Blvd, Portland, OR 97201 USA. EM eyedrug@ohsu.edu NR 12 TC 17 Z9 17 U1 0 U2 5 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0025-7656 J9 DRUGS TODAY JI Drugs Today PD JAN PY 2004 VL 40 IS 1 BP 23 EP 27 DI 10.1358/dot.2004.40.1.799435 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 780MP UT WOS:000189385300003 PM 14988767 ER PT J AU Patrick, ME Adcock, PM Gomez, TM Altekruse, SF Holland, BH Tauxe, RV Swerdlow, DL AF Patrick, ME Adcock, PM Gomez, TM Altekruse, SF Holland, BH Tauxe, RV Swerdlow, DL TI Salmonella enteritidis infections, United States, 1985-1999 SO EMERGING INFECTIOUS DISEASES LA English DT Article ID PHAGE TYPE-4; EGGS; OUTBREAKS; FLOCKS; HENS AB Salmonella enterica serotype Enteritidis emerged as an important illness during the 1980s. Investigations showed that consumption of undercooked eggs was the major risk factor for disease, and a variety of prevention and control efforts were initiated during the 1990s. We describe sporadic infections and outbreaks of S. Enteritidis in the United States from 1985 through 1999 and discuss prevention and control efforts. After reaching a high of 3.9 per 100,000 population in 1995, S. Enteritidis infections declined to 1.98 per 100,000 in 1999. While the total number of outbreaks decreased by half, those in the western states tripled. Outbreaks of S. Enteritidis phage type 4 infections accounted for 49% of outbreaks in 1999. Outbreak-associated deaths in health facilities decreased from 14 in 1987 to 0 in 1999. Overall, rates of sporadic S. Enteritidis infection, outbreaks, and deaths have declined dramatically. For further reductions, control measures should continue to be applied along the entire farm-to-table continuum. C1 Ctr Dis Control & Prevent, Atlanta, GA USA. USDA, Atlanta, GA USA. US FDA, Rockville, MD 20857 USA. RP Patrick, ME (reprint author), Dekalb Cty Board Hlth, Div Hlth Assessment & Promot, Sakura, Ibaraki 30031, Japan. EM mcevans@gdph.state.ga.us NR 25 TC 163 Z9 171 U1 0 U2 7 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JAN PY 2004 VL 10 IS 1 BP 1 EP 7 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 762GD UT WOS:000187962800001 PM 15078589 ER PT J AU Raney, JL Delongchamp, RR Valentine, CR AF Raney, JL Delongchamp, RR Valentine, CR TI Spontaneous mutant frequency and mutation spectrum for gene A of Phi X174 grown in E-coli SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE single burst analysis; mutant spectra; spontaneous mutant frequency ID LACZ-TRANSGENIC MOUSE; IN-VIVO; MOLECULAR NATURE; MICE; SPECIFICITY; BACTERIOPHAGE-PHI-X174; SUPPRESSION; REVERTANTS; SEQUENCE; ORIGINS AB The use of transgenic targets for measuring mutant frequencies in mammalian tissue requires an estimate of the mutant frequency that results from recovery of the transgene in bacterial recovery systems. In this study, we have determined the spontaneous mutant frequency, estimated the mutation rate, and ascertained the mutation spectrum for gene A of (I)X 174 grown in E. coli strain CQ2 from 156 small independent cultures. The mutant frequency of 12 of the 156 cultures was 17 +/- 1.0 x 10(-6) and the estimated mutation rate per gene replication was 7.4 +/- 2.3 x 10(-6). The mutant frequency and spectrum from E. coli were not significantly different from that of solvent-treated embryonic mouse cells in culture, 19 +/- 0.5 x 10(-6) (Valentine CR et al. [2002]: Environ Mal Mutagen 39:55-68), indicating that those spontaneous mutants were primarily derived from E. coli. The E. coli spectrum was heavily weighted toward two major target sites (hot spots), 4225A-->G (56%) and 421 8G-->A or C (20%). Four new target sites and one new mutational event were recovered by the gene A forward assay. A mutant spectrum from an expanded phage stock was also determined to assess the effects of propagating the virus. This mutant frequency was higher (6 x 10(-4)), contained more double mutants (15% compared to 0.6%), and had a significantly different spectrum from the spectrum for independent cultures (fewer A:T-G:C and G:C C:G changes and more G:C-A:T; P < 0.002). The E. coli mutation spectrum will be useful for determining the origin of gene A mutation in tissues of PhiX174 transgenic mice. Published 2004 Wiley-Liss, Inc.(dagger) C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol, Div Biometry & Risk Assessment, Jefferson, AR USA. RP Valentine, CR (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd,HFT-120, Jefferson, AR 72079 USA. EM cvalentine@nctr.fda.gov NR 36 TC 23 Z9 23 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2004 VL 44 IS 2 BP 119 EP 127 DI 10.1002/em.20041 PG 9 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 845BS UT WOS:000223211300005 PM 15278916 ER PT J AU Valentine, CR Raney, JL Shaddock, JG Dobrovolsky, VN Delongchamp, RR AF Valentine, CR Raney, JL Shaddock, JG Dobrovolsky, VN Delongchamp, RR TI In vivo mutation in gene A of splenic lymphocytes from 4 Phi Chi 174 transgenic mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE Phi Chi 1 74; single-burst analysis; mutant spectra; ethylnitrosourea; clonality; spontaneous; mutant frequency; transgenic; forward mutational assay ID ESCHERICHIA-COLI; MOLECULAR CHARACTERISTICS; ETHYLATING AGENTS; MAMMALIAN-CELLS; GERM-CELLS; LACI GENE; BASE-PAIR; MUTAGENESIS; PHI-X174; REPAIR AB Single-burst analysis was applied to a forward assay for gene A mutation in splenic lymphocytes of PhiXI 74 transgenic mice for the purpose of optimizing analytical parameters for identifying in vivo mutations. The effect of varying the cutoff value for an in vivo burst on induced mutant frequency, fold increase, and the significance of the difference between control and N-ethyl-N-nitrosourea (ENU)treated mice was calculated by two different methods. The plating density was reduced to an average of less than 10 background mutant plaques per aliquot in order to separate in vitro bursts. The spectrum of mutations contributing < 60 plaques per aliquot from control animals was not significantly different from the control spectra from E. coli or transgenic PhiXI74 cells in culture. The mutant spectra from ENU-treated animals was highly different between mutant bursts of > 80 plaques per aliquot compared to mutations contributing < 60 plaques per aliquot (P < 0.000001), the former fitting the spectrum expected for ENU-induced mutations. The latter spectrum was also different from control animals and E. coli (P < 0.000001), suggesting the difference was caused by ex vivo mutation. With the mutations found in this study, the total number of reported target sites for gene A is now 33. The results support the interpretation that, in contrast to results for the lacl transgene, 100% of mutants isolated in gene A from control animals and cells were fixed in E. coli. We attribute the difference between the two genes to hot-spot sites for mutation in gene A and to a testable hypothesis that the mosaic plaque assay for the lacl transgene underestimates the frequency of ex vivo mutants. Published 2004 Wiley-Liss, Inc.(dagger) C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biometry, Jefferson, AR USA. RP Valentine, CR (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM cvalentine@nctr.fda.gov NR 47 TC 6 Z9 6 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2004 VL 44 IS 2 BP 128 EP 150 DI 10.1002/em.20043 PG 23 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 845BS UT WOS:000223211300006 PM 15278917 ER PT J AU Chen, L Mei, N Chen, T AF Chen, L Mei, N Chen, T TI Mutations induced by aristolochic acid in the kidney of big blue transgenic rat SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 35th Annual Meeting of the Environmental-Mutagen-Society CY OCT 02-06, 2004 CL Pittsburgh, PA SP Environm Mutagen Soc C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Shanghai Jiao Tong Univ, Coll Life Sci & Technol, Shanghai 200240, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2004 VL 44 IS 3 MA 26 BP 192 EP 192 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 852MF UT WOS:000223758700028 ER PT J AU Dobrovolsky, VN Heflich, RH McGarrity, LJ VonTungeln, LS Beland, FA AF Dobrovolsky, VN Heflich, RH McGarrity, LJ VonTungeln, LS Beland, FA TI Frequency of micronucleated erythroid cells in AZT-treated TK-proficient and TK-deficient mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 35th Annual Meeting of the Environmental-Mutagen-Society CY OCT 02-06, 2004 CL Pittsburgh, PA SP Environm Mutagen Soc C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2004 VL 44 IS 3 MA 40 BP 196 EP 196 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 852MF UT WOS:000223758700043 ER PT J AU Elespuru, RK Jenning, SM AF Elespuru, RK Jenning, SM TI Molecular epidemiology of human lung cancer: Analysis using the IARC tp53 database SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 35th Annual Meeting of the Environmental-Mutagen-Society CY OCT 02-06, 2004 CL Pittsburgh, PA SP Environm Mutagen Soc C1 US FDA, CDRH, OSEL, Div Biol, Silver Spring, MD 20903 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2004 VL 44 IS 3 MA 47 BP 197 EP 197 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 852MF UT WOS:000223758700049 ER PT J AU Jacobson-Kram, D AF Jacobson-Kram, D TI The role of the SHE cell transformation assay in drug development SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 35th Annual Meeting of the Environmental-Mutagen-Society CY OCT 02-06, 2004 CL Pittsburgh, PA SP Environm Mutagen Soc C1 US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2004 VL 44 IS 3 MA 85 BP 207 EP 207 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 852MF UT WOS:000223758700090 ER PT J AU Kovalchuk, OV Raiche, JN Slovack, MK Pogribny, IP AF Kovalchuk, OV Raiche, JN Slovack, MK Pogribny, IP TI Radiation-induced gemonic DNA methylation changes - The biological significance and possible mechanisms SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 35th Annual Meeting of the Environmental-Mutagen-Society CY OCT 02-06, 2004 CL Pittsburgh, PA SP Environm Mutagen Soc C1 Univ Lethbridge, Lethbridge, AB T1K 3M4, Canada. US FDA, NCTR, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2004 VL 44 IS 3 MA 99 BP 211 EP 211 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 852MF UT WOS:000223758700104 ER PT J AU MacGregor, J Bishop, ME Dertinger, S McNamee, J Harper, S Hotchkiss, C Hayashi, M AF MacGregor, J Bishop, ME Dertinger, S McNamee, J Harper, S Hotchkiss, C Hayashi, M TI Integration of chromosomal damage assessment with routine toxicity testing using a flow cytometric assay for micronucleated reticulocytes. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 35th Annual Meeting of the Environmental-Mutagen-Society CY OCT 02-06, 2004 CL Pittsburgh, PA SP Environm Mutagen Soc C1 US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. Toxicol Consulting Serv, Arnold, MD USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Hlth Canada, Ottawa, ON K1A 0L2, Canada. US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD USA. Natl Inst Hlth Sci, Tokyo 158, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2004 VL 44 IS 3 MA 107 BP 213 EP 213 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 852MF UT WOS:000223758700112 ER PT J AU Manjanatha, MG Aidoo, A Shelton, SD Bishop, ME McDaniel, LP Doerge, DR AF Manjanatha, MG Aidoo, A Shelton, SD Bishop, ME McDaniel, LP Doerge, DR TI Evaluation of mutagenicity in big blue (BB) mice administered acrylamide (AA) and glycidamide (GA) in drinking water for 4 weeks. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 35th Annual Meeting of the Environmental-Mutagen-Society CY OCT 02-06, 2004 CL Pittsburgh, PA SP Environm Mutagen Soc 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. NR 0 TC 2 Z9 3 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2004 VL 44 IS 3 MA 110 BP 214 EP 214 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 852MF UT WOS:000223758700115 ER PT J AU McKinzie, PB Chen, T Heflich, RH Parsons, BL AF McKinzie, PB Chen, T Heflich, RH Parsons, BL TI ACB-PCR measurement of rare K-ras codon 12 mutations in liver of N-hydroxy-2-acetylaminofluorene-treated Big Blue rats. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 35th Annual Meeting of the Environmental-Mutagen-Society CY OCT 02-06, 2004 CL Pittsburgh, PA SP Environm Mutagen Soc C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2004 VL 44 IS 3 MA 111 BP 214 EP 214 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 852MF UT WOS:000223758700116 ER PT J AU Mei, N Heflich, RH Chou, MW Fu, PP Chen, T AF Mei, N Heflich, RH Chou, MW Fu, PP Chen, T TI Riddelliine-induced mutations in the liver CII gene of transgenic Big Blue rats. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 35th Annual Meeting of the Environmental-Mutagen-Society CY OCT 02-06, 2004 CL Pittsburgh, PA SP Environm Mutagen Soc 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. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2004 VL 44 IS 3 MA 113 BP 214 EP 214 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 852MF UT WOS:000223758700118 ER PT J AU Mittelstaedt, RA Mei, N Shaddock, JG Dobrovolsky, VN McGarrity, LJ Greenlees, KJ Heflich, RH AF Mittelstaedt, RA Mei, N Shaddock, JG Dobrovolsky, VN McGarrity, LJ Greenlees, KJ Heflich, RH TI Liver CII mutant frequency correlates with tumorigenicity in female Big Blue mice and rats fed malachite green and leucomalachite green. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 35th Annual Meeting of the Environmental-Mutagen-Society CY OCT 02-06, 2004 CL Pittsburgh, PA SP Environm Mutagen Soc C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. US FDA, Ctr Vet Med, Rockville, MD 20855 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2004 VL 44 IS 3 MA 117 BP 215 EP 215 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 852MF UT WOS:000223758700122 ER PT J AU Torous, DK Dertinger, SD MacGregor, JT Bishop, ME Ponten, I Chen, Y Tometsko, CR AF Torous, DK Dertinger, SD MacGregor, JT Bishop, ME Ponten, I Chen, Y Tometsko, CR TI Flow cytometric analysis of micronuclei in rodent and human blood using a newly developed three-color labeling method SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 35th Annual Meeting of the Environmental-Mutagen-Society CY OCT 02-06, 2004 CL Pittsburgh, PA SP Environm Mutagen Soc C1 Litron Labs, Rochester, NY 14620 USA. US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. AstraZeneca R&D, Sodertalje, Sweden. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2004 VL 44 IS 3 MA 179 BP 232 EP 232 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 852MF UT WOS:000223758700188 ER PT J AU Valentine, CR Rainey, HF Delongchamp, RR AF Valentine, CR Rainey, HF Delongchamp, RR TI Comparison of in vivo mutation in gene A of PHIX174 to lacl and cll of lambda from splenic lymphocytes in transgenic mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 35th Annual Meeting of the Environmental-Mutagen-Society CY OCT 02-06, 2004 CL Pittsburgh, PA SP Environm Mutagen Soc C1 Natl Ctr Toxicol Res, Div Genet Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biometry, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2004 VL 44 IS 3 MA 183 BP 233 EP 233 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 852MF UT WOS:000223758700193 ER PT J AU Verkler, TL Delongchamp, RR Warbritton, A Couch, LH Miller, BJ Howard, PC Parsons, BL AF Verkler, TL Delongchamp, RR Warbritton, A Couch, LH Miller, BJ Howard, PC Parsons, BL TI Accumulation of simulated solar light-induced mouse p53 codon 270 CGT to TGT mutation during skin tumor development SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 35th Annual Meeting of the Environmental-Mutagen-Society CY OCT 02-06, 2004 CL Pittsburgh, PA SP Environm Mutagen Soc C1 US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Biometry, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Pathol Serv, Charles River Labs, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2004 VL 44 IS 3 MA 188 BP 234 EP 234 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 852MF UT WOS:000223758700198 ER PT J AU Huber, WW Teitel, CH Coles, BF King, RS Wiese, FW Kaderlik, KR Casciano, DA Shaddock, JG Mulder, GJ Ilett, KF Kadlubar, FF AF Huber, WW Teitel, CH Coles, BF King, RS Wiese, FW Kaderlik, KR Casciano, DA Shaddock, JG Mulder, GJ Ilett, KF Kadlubar, FF TI Potential chemoprotective effects of the coffee components kahweol and cafestol palmitates via modification of hepatic N-acetyltransferase and glutathione S-transferase activities SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE chemoprotection; coffee; 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (Ph IP); N-acetyltransferase; glutathione-5-transferase; rat ID DNA ADDUCT FORMATION; BORNE CARCINOGEN 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; GAMMA-GLUTAMYLCYSTEINE SYNTHETASE; HETEROCYCLIC AMINE CARCINOGENS; ACETYLATOR INBRED RATS; RATE-LIMITING ENZYME; ABERRANT CRYPT FOCI; COLON-TUMOR CELLS; COLORECTAL-CANCER; GENE-EXPRESSION AB Coffee drinking has been associated with reduced incidence of colorectal cancer, possibly via chemoprotection/modification of the metabolism of dietary heterocyclic amine carcinogens such as 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP) by kahweol and cafestol palmitates (K/C), two components of unfiltered coffee. Using the PhIP-exposed male Fisher F344 rat as a model, K/C have been shown to reduce colonic PhlP-DNA adducts by >50%. We have used the male F344 rat to investigate the effects of dietary K/C (0.02-0.2% as a 1:1 mixture) on the metabolism of PhIP by N-acetyltransferase- (NAT), sulfotransferose- (SULT), and glutathione-dependent pathways. K/C decreased hepatic NAT-dependent PhIP activation by up to 80% in a dose-dependent manner. Conversely, hepatic glutathione S-transferase (GST) activity/expression increased, e.g., 3-4 fold toward 1-chloro-2,4-dinitrobenzene (total activity), up to 23-fold toward 4-vinylpyridine (rGSTP1),Coffee drinking has been associated with reduced incidence of colorectal cancer, possibly via chemoprotection/modification of the metabolism of dietary heterocyclic amine carcinogens such as 2-amino-1-methyl-6 phenylimidazo-[4,5-b]pyridine (PhIP) by kahweol and cafestol palmitates (K/C), two components of unfiltered coffee. Using the PhIP-exposed male Fisher F344 rat as a model, K/C have been shown to reduce colonic PhIP-DNA adducts by > 50%. We have used the male F344 rat to investigate the effects of dietary K/C (0.02-0.2% as a 1:1 mixture) on the metabolism of PhIP by M-acetyltransferase- (NAT), sulfotransferose- (SULT), and glutathione-dependent pathways. K/C decreased hepatic NAT-dependent PhlP activation by up to 80% in a dose-dependent manner. Conversely, hepatic glutathione S-transferase (GST) activity/expression increased, e.g., 3-4 fold toward 1-chloro-2,4-dinitrobenzene (total activity), up to 23-fold toward 4-vinylpyridine (rGSTP1), and similar to7-fold for rGSTA2 protein. These effects had fully developed after 5 days of the test diet and persisted for at least 5 days after withdrawal of K/C. Hepatic glutathione increased two- to threefold and this increase was more short-lived than other changes. K/C did not modify hepatic SULT activity or colon NAT and GST activities. Benzylisothiocyanate and black tea, which have also been shown to reduce the formation of PhlP-DNA adducts in this model, had little effect on hepatic NAT, SULT, GST, or GSH. In primary culture of rat hepatocytes, both kahweol and cafestol palmitates reduced NAT activity by 80%. In summary, the unique potential of K/C to convert rapid acetylators to a slow acetylator phenotype, accompanied by GST induction, might contribute to chemoprevention against cancers associated with heterocyclic amines. (C) 2004 Wiley-Liss, Inc. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR USA. Natl Ctr Toxicol Res, Div Genet Toxicol, Jefferson, AR USA. Amsterdam Ctr Drug Res, Dept Toxicol, Leiden, Netherlands. Univ Western Australia, Sch Med & Pharmacol, Pharmacol Unit, Crawley, Australia. RP Huber, WW (reprint author), Med Univ Vienna, Dept Toxicol, Inst Krebsforsch, Borschkegasse 8A, A-1090 Vienna, Austria. EM wolfgang.huher@meduniwien.ac.at RI King, Roberta/A-1749-2010; yang, min/G-3030-2011 OI King, Roberta/0000-0002-3550-4255; NR 90 TC 25 Z9 28 U1 0 U2 6 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. PY 2004 VL 44 IS 4 BP 265 EP 276 DI 10.1002/em.20052 PG 12 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 867LY UT WOS:000224845300002 PM 15468054 ER PT J AU Dertinger, SD Camphausen, K MacGregor, JI Bishop, ME Torous, DK Avlasevich, S Cairns, S Tometsko, CR Menard, C Muanza, T Chen, YY Miller, RK Cederbrant, K Sandelin, K Ponten, I Bolcsfoldi, G AF Dertinger, SD Camphausen, K MacGregor, JI Bishop, ME Torous, DK Avlasevich, S Cairns, S Tometsko, CR Menard, C Muanza, T Chen, YY Miller, RK Cederbrant, K Sandelin, K Ponten, I Bolcsfoldi, G TI Three-color labeling method for flow cytometric measurement of cytogenetic damage in rodent and human blood SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE micronuclei; cytogenetic damage; DNA damage; reticulocytes; CD71 antigen ID RAT PERIPHERAL-BLOOD; MICRONUCLEUS ASSAY; BONE-MARROW; RETICULOCYTES; ERYTHROCYTES; ENUMERATION; CYCLOPHOSPHAMIDE; SUITABILITY AB Experiments described herein were designed to evaluate the performance characteristics of a flow cytometry-based system that scores the incidence of peripheral blood micronucleated reticulocytes IMN-RETs). These procedures represent the continued refinement of a previously reported anti-CD71-based method (Dertinger et al. [1996]: Mutat Res 371:283-292), with the following modifications: incorporation of a third fluorescent label to exclude platelets from the MN-RET region, and use of a CD71 -associated fluorescence thresholding technique to increase data acquisition rates. Mouse, rat, and human blood samples were analyzed using both the previously described two-color procedure (anti-CD71-FITC and propidium iodide) and a newly developed three-color technique (which adds an antiplatelet-PE antibody). The rodent specimens were also evaluated by standard microscopy procedures (acridine orange staining). Mouse blood was collected via heart puncture of vehicle- and 5-fluorouracil-treated CD-1 mice; blood samples from saline-treated Sprague-Dawley rats were collected from the tail vein and via heart puncture. Rodent blood samples were analyzed by both the two- and three-color methods. Human blood specimens, obtained via arm venipuncture from cancer patients undergoing radiation therapy, were analyzed for MNRETs using the two-color method. Subsequently, blood samples from a single chemotherapy patient were analyzed by both the two- and three-color methods. Finally, the chemotherapy patient blood samples and blood samples from 15 healthy volunteers were evaluated at very high densities in conjunction with a CD71-associated fluorescence thresholding technique. Results of these investigations showed that data from mouse blood analyzed by the two- and threecolor procedures correlated well with microscopy data (r values = 0.917 and 0.937 for the two- and three-color methods, respectively); all three methods confirmed the genotoxicity of 5-FU. Data from rat tail vein samples showed improved reproducibility with the three-color technique, but no significant difference between the two techniques was seen with the heart puncture specimens. Human blood analyzed according to the two-color procedure produced unreliable results, as platelets and platelet aggregates impacted the rare MN-RET scoring region. The three-color technique effectively overcome this problem and produced reproducible measurements that fell within expected ranges. For human blood analyses, the high cell density/CD71 -thresholding technique provided significant improvements over the low-density technique, as it allowed data acquisition to occur approximately six times faster with no loss of sensitivity. (C) 2004 Wiley-Liss, Inc. C1 Litron Labs, Rochester, NY 14620 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Rochester, Dept Radiat Oncol, James P Wilmot Canc Ctr, Rochester, NY USA. Univ Rochester, Med Ctr, Dept Obstet & Gynecol, Rochester, NY 14642 USA. AstraZeneca Res & Dev, Sodertalje, Sweden. RP Dertinger, SD (reprint author), Litron Labs, 1351 Mt Hope Ave, Rochester, NY 14620 USA. EM sdertinger@litronlabs.com OI Cederbrant, Karin/0000-0003-3341-5416 FU NIEHS NIH HHS [R44ES011244-03, R44ES010752-02] NR 21 TC 47 Z9 50 U1 0 U2 6 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. PY 2004 VL 44 IS 5 BP 427 EP 435 DI 10.1002/em.20075 PG 9 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 886MN UT WOS:000226231600009 PM 15517570 ER PT J AU Chapin, RE Robbins, WA Schieve, LA Sweeney, AM Tabacova, SA Tomashek, KM AF Chapin, RE Robbins, WA Schieve, LA Sweeney, AM Tabacova, SA Tomashek, KM TI Off to a good start: The influence of pre- and periconceptional exposures, parental fertility, and nutrition on children's health SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE birth defects; chemical exposure; conception; fertilization; review ID IN-VITRO FERTILIZATION; INTRACYTOPLASMIC SPERM INJECTION; NEURAL-TUBE DEFECTS; ASSISTED REPRODUCTIVE TECHNOLOGY; DIOXIN-LIKE CHEMICALS; GREAT-LAKES FISH; LOW-BIRTH-WEIGHT; FIRST CELL-CYCLE; POLYCHLORINATED-BIPHENYLS; SEMINAL PLASMA AB The scientific community is developing a compelling body of evidence that shows the importance of the in utero environment (including chemical and hormonal levels) to the ultimate health of the child and even of the aging adult. This article summarizes the evidence that shows this impact begins with conception. Only a full life-cycle evaluation will help us understand these impacts, and only such an understanding will produce logically prioritized mitigation strategies to address the greatest threats first. Clearly, the time for analysis begins when the next generation is but a twinkle in the eye. C1 Pfizer R&D, Groton, CT 06340 USA. Univ Calif Los Angeles, Ctr Environm & Occupat Hlth, Los Angeles, CA USA. Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA. Texas A&M Univ, Syst Hlth Sci Ctr, Dept Epidemiol & Biostat, Sch Publ Hlth, College Stn, TX 77843 USA. US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. Ctr Dis Control & Prevent, Maternal & Infant Hlth Branch, Atlanta, GA USA. RP Chapin, RE (reprint author), Pfizer R&D, Eastern Point Rd,MS8274-1336, Groton, CT 06340 USA. EM robert_e_chapin@groton.pfizer.com OI Chapin, Robert/0000-0002-5997-1261 NR 211 TC 44 Z9 46 U1 1 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 JAN PY 2004 VL 112 IS 1 BP 69 EP 78 DI 10.1289/ehp.6261 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 761NH UT WOS:000187914500043 PM 14698934 ER PT J AU Garber, EAE Erb, JL Magner, J Larsen, G AF Garber, EAE Erb, JL Magner, J Larsen, G TI Low levels of sodium and potassium in the water from wetlands in minnesota that contained malformed frogs affect the rate of Xenopus development SO ENVIRONMENTAL MONITORING AND ASSESSMENT LA English DT Article DE frog embryo teratogenesis assay : xenopus (FETAX); frog malformations; Minnesota; potassium; sodium ID EMBRYO TERATOGENESIS ASSAY; LIMB MALFORMATIONS; RANA-PIPIENS; POPULATION DECLINES; POND WATER; UV-B; LAEVIS; FETAX; METAMORPHOSIS; DEFORMITIES AB Water samples were collected between 1999 and 2000 from wetlands in Minnesota that contained malformed frogs. The water samples were analyzed for 14 minerals/ions and screened for the presence of biologically active compounds using Xenopus laevis. Results indicated that water from two sites, CWB and ROI2, induced severe retardation with embryo lengths reduced 20% after 96 hr of development. The developmental delay observed with water from ROI2 was alleviated by supplementation with sodium, while both sodium and potassium alleviated the developmental delay observed with water whose mineral content mimicked that of CWB. Seasonal fluctuations in the sodium and potassium content at ROI2 and NEY correlated with changes in the rates of Xenopus development. Xenopus embryos reared on water from ROI2 for 120 hr displayed gut malformations not present in embryos reared on a synthetic media designed to mimic the mineral content of the water from ROI2. Embryos reared on water from ROI2 supplemented with minerals at levels comparable to that routinely employed in the rearing of Xenopus were neither retarded nor malformed. It is proposed that climate driven hydrology may influence the mineral composition at selected wetlands and delay development which may alter window(s) of susceptibility towards biologically active agents and the occurrence of malformed frogs. C1 ARS, USDA, Biosci Res Lab, Fargo, ND USA. ThreeFold Sensors, Ann Arbor, MI USA. Minnesota Pollut Control Agcy, St Paul, MN USA. RP Garber, EAE (reprint author), US FDA, Div Nat Prod, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS-315, College Pk, MD 20740 USA. NR 41 TC 5 Z9 5 U1 1 U2 6 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6369 J9 ENVIRON MONIT ASSESS JI Environ. Monit. Assess. PD JAN PY 2004 VL 90 IS 1-3 BP 45 EP 64 DI 10.1023/B:EMAS.0000003565.25474.8f PG 20 WC Environmental Sciences SC Environmental Sciences & Ecology GA 744CP UT WOS:000186610600003 PM 15887362 ER PT J AU Buzatu, DA Beger, RD Wilkes, JG Lay, JO AF Buzatu, DA Beger, RD Wilkes, JG Lay, JO TI Predicting toxic equivalence factors from C-13 nuclear magnetic resonance spectra for dioxins, furans, and polychlorinated biphenyls using linear and nonlinear pattern recognition methods SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY LA English DT Article DE dioxin; spectroscopic data-activity relationship ID NMR; BINDING; MODELS; PCBS; DIBENZOFURANS; MIXTURES; SVALBARD AB Two quantitative spectrometric data-activity relationships (QSDAR) models have been developed relating 29 dioxin or dioxin-like molecules to their toxic equivalence factors (TEFs). These models were based on patterns in simulated C-13 nuclear magnetic resonance (NMR) data with the patterns defined by comparative spectral analysis (CoSA). Two versions of CoSA multiple linear regression (MLR) models using 7 or 10 spectral bins had, respectively, explained variances (r(2)) of 0.88 and 0.95, and leave-one-out (LOO) cross-validated variances (q(2)) of 0.78 and 0.88. A third, artificial neural network model-using a feed forward, back propagating, three-layer neural network-produced an r(2) of 0.99, a LOO q(2) of 0.82, and a leave-three-out q(2) of 0.81. A postulated reason that the results of these QSDAR models are better than traditional quantitative structure-activity relationship QSAR) models is based on the difference in descriptors rather than on any differences in pattern recognition approach. Results suggest that the C-13 NMR spectral data contain molecular quantum mechanical information more reflective of each molecule's biochemical properties than do the calculated electrostatic potentials and molecular alignment assumptions used in developing QSAR models. The QSDAR models provide a rapid, simple way to model the toxicity of dioxin and dioxin-like compounds. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Buzatu, DA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. EM dbuzatu@nctr.fda.gov RI Lay, Jackson/G-1007-2011 OI Lay, Jackson/0000-0003-3789-2527 NR 37 TC 4 Z9 4 U1 0 U2 9 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 JAN PY 2004 VL 23 IS 1 BP 24 EP 31 DI 10.1897/02-516 PG 8 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 761JF UT WOS:000187897200005 PM 14768863 ER PT J AU Roecklein, BA Kupferburg, HJ Mortko, H Hartman, N Strong, J AF Roecklein, BA Kupferburg, HJ Mortko, H Hartman, N Strong, J TI Metabolism of fluorofelbamate differs from that of felbamate SO EPILEPSIA LA English DT Meeting Abstract CT Annual Meeting of the American-Epilepsy-Society CY DEC 03-07, 2004 CL New Orlands, LA SP Amer Epilepsy Soc C1 MedPointe Pharmaceut, Med Marketing, Somerset, NJ USA. US FDA, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2004 VL 45 SU 7 BP 135 EP 136 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 861MG UT WOS:000224420100398 ER PT J AU Zhang, W Wang, TG Qin, LY Gao, HM Wilson, B Ali, SF Zhang, WQ Hong, JS Liu, B AF Zhang, W Wang, TG Qin, LY Gao, HM Wilson, B Ali, SF Zhang, WQ Hong, JS Liu, B TI Neuroprotective effect of dextromethorphan in the MPTP Parkinson's disease model: role of NADPH oxidase SO FASEB JOURNAL LA English DT Article DE reactive oxygen species; microglia; dopamine; substantia nigra; morphinan ID INJURY FOLLOWING TRANSIENT; DOPAMINERGIC-NEURONS; FOCAL ISCHEMIA; NITRIC-OXIDE; MICROGLIAL ACTIVATION; SUPEROXIDE PRODUCTION; GLUTAMATE TOXICITY; TETRAZOLIUM SALT; MOUSE MODEL; PROTECTS AB Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by a progressive loss of dopaminergic neurons in the substantia nigra and depletion of the neurotransmitter dopamine in the striatum. Progress in the search for effective therapeutic strategies that can halt this degenerative process remains limited. Mechanistic studies using animal systems such as the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rodent PD model have revealed the involvement of the brain's immune cells and free radical-generating processes. We recently reported that dextromethorphan (DM), a widely used anti-tussive agent, attenuated endotoxin-induced dopaminergic neurodegeneration in vitro. In the current study, we investigated the potential neuroprotective effect of DM and the underlying mechanism of action in the MPTP rodent PD model. Mice (C57BL/6J) that received daily MPTP injections (15 mg free base/kg body weight, s.c.) for 6 consecutive days exhibited significant degeneration of the nigrostriatal dopaminergic pathway. However, the MPTP-induced loss of nigral dopaminergic neurons was significantly attenuated in those mice receiving DM (10 mg/kg body weight, s.c.). In mesencephalic neuron-glia cultures, DM significantly reduced the MPTP-induced production of both extracellular superoxide free radicals and intracellular reactive oxygen species (ROS). Because NADPH oxidase is the primary source of extracellular superoxide and intracellular ROS, we investigated the involvement of NADPH oxidase in the neuroprotective effect of DM. Indeed, the neuroprotective effect of DM was only observed in the wild-type but not in the NADPH oxidase-deficient mice, indicating that NADPH oxidase is a critical mediator of the neuroprotective activity of DM. More importantly, due to its proven safety record of long-term clinical use in humans, DM may be a promising agent for the treatment of degenerative neurological disorders such as PD. C1 Univ Florida, Coll Pharm, Dept Pharmacodynam, Gainesville, FL 32610 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. First Clin Hosp, Dept Neurol, Dalian, Peoples R China. Dalian Med Univ, Dept Physiol, Dalian, Peoples R China. US FDA, Neurochem Lab, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Liu, B (reprint author), Univ Florida, Coll Pharm, Dept Pharmacodynam, Box 100487 HSC, Gainesville, FL 32610 USA. EM liu@cop.ufl.edu RI gao, huiming/C-8454-2012; liu, Bin/A-7695-2009 NR 47 TC 116 Z9 120 U1 0 U2 8 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD JAN PY 2004 VL 18 IS 1 BP 589 EP + DI 10.0983/fj.03-0983fje PG 21 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 772EX UT WOS:000188829300001 PM 14734632 ER PT J AU Kroes, R Renwick, AG Cheeseman, M Kleiner, J Mangelsdorf, I Piersma, A Schilter, B Schlatter, J van Schothorst, F Vos, JG Wurtzen, G AF Kroes, R Renwick, AG Cheeseman, M Kleiner, J Mangelsdorf, I Piersma, A Schilter, B Schlatter, J van Schothorst, F Vos, JG Wurtzen, G TI Structure-based thresholds of toxicological concern (TTC): guidance for application to substances present at low levels in the diet SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE risk assessment; threshold of toxicological concern (TTC); carcinogenicity; neurotoxicity; teratogenicity; exposure; de Minimis Risk; toxicity; food safety ID CARCINOGENIC POTENCY DATABASE; DEVELOPMENTAL TOXICITY; PRENATAL TOXICITY; BORIC-ACID; CHOLINESTERASE INHIBITION; GENERAL LITERATURE; LITHIUM-CARBONATE; WISTAR RAT; CD-1 MOUSE; TERATOGENICITY AB The threshold of toxicological concern (TTC) is a pragmatic risk assessment tool that is based on the principle of establishing a human exposure threshold value for all chemicals, below which there is a very low probability of an appreciable risk to human health. The concept that there are levels of exposure that do not cause adverse effects is inherent in setting acceptable daily intakes (ADIs) for chemicals with known toxicological profiles. The TTC principle extends this concept by proposing that a de minimis value can be identified for many chemicals, in the absence of a full toxicity database, based on their chemical structures and the known toxicity of chemicals which share similar structural characteristics. The establishment and application of widely accepted TTC values would benefit consumers, industry and regulators. By avoiding unnecessary toxicity testing and safety evaluations when human intakes are below such a threshold, application of the TTC approach would focus limited resources of time, cost, animal use and expertise on the testing and evaluation of substances with the greatest potential to pose risks to human health and thereby contribute to a reduction in the use of animals. An Expert Group of the European branch of the International Life Sciences Institute-ILSI Europe-has examined the TTC principle for its wider applicability in food safety evaluation. The Expert Group examined metabolism and accumulation, structural alerts, endocrine disrupting chemicals and specific endpoints, such as neurotoxicity, teratogenicity, developmental toxicity, allergenicity and immunotoxicity, and determined whether such properties or endpoints had to be taken into consideration specifically in a step-wise approach. The Expert Group concluded that the TTC principle can be applied for low concentrations in food of chemicals that lack toxicity data, provided that there is a sound intake estimate. The use of a decision tree to apply the TTC principle is proposed, and this paper describes the step-wise process in detail. Proteins, heavy metals and polyhalogenated-dibenzodioxins and related compounds were excluded from this approach. When assessing a chemical, a review of prior knowledge and context of use should always precede the use of the TTC decision tree. The initial step is the identification and evaluation of possible genotoxic and/or high potency carcinogens. Following this step, non-genotoxic substances are evaluated in a sequence of steps related to the concerns that would be associated with increasing intakes. For organophosphates a TTC of 18mug per person per day (0.3 mug/kg bw/day) is proposed, and when the compound is not an OP, the TTC values for the Cramer structural classes III, II and I, with their respective TTC levels (e.g. 1800, 540 and 90 mug per person per day; or 30, 9 and 1.5 mug/kg bw /day), would be applied sequentially. All other endpoints or properties were shown to have a distribution of no observed effect levels (NOELs) similar to the distribution of NOELs for general toxicity endpoints in Cramer classes I, II and III. The document was discussed with a wider audience during a workshop held in March 2003 (see list of workshop participants). (C) 2003 Published by Elsevier Ltd. C1 ILSI Europe, B-1200 Brussels, Belgium. Univ Utrecht, Inst Risk Assessment Sci, Fac Med Vet, NL-3508 TD Utrecht, Netherlands. Univ Southampton, Clin Pharmacol Grp, Sch Med, Southampton SO16 7PX, Hants, England. Food & Drug Adm, Food Contact Div, Washington, DC 20204 USA. Fraunhofer Inst Toxicol & Aerosol Res, Dept Chem Risk Assessment, D-30625 Hannover, Germany. Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. Nestle Res Ctr, CH-1000 Lausanne 26, Switzerland. Swiss Fed Off Publ Hlth, Food Toxicol Sect, CH-8004 Zurich, Switzerland. Coca Cola Nord & Balt Div, DK-2900 Hellerup, Denmark. RP Kleiner, J (reprint author), ILSI Europe, Ave E Mounier 83,Box 6, B-1200 Brussels, Belgium. EM publications@ilsieurope.be NR 85 TC 290 Z9 304 U1 10 U2 58 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 JAN PY 2004 VL 42 IS 1 BP 65 EP 83 DI 10.1016/j.fct.2003.08.006 PG 19 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 763XU UT WOS:000188126400008 PM 14630131 ER PT J AU Basile, EM Gross, M AF Basile, EM Gross, M TI The First Amendment and federal court deference to the Food and Drug Administration: The times they are a-changin SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 King & Spalding LLP, Washington, DC USA. FDA Practice Grp, Washington, DC USA. Howard Univ, Sch Law, Washington, DC USA. RP Basile, EM (reprint author), King & Spalding LLP, Washington, DC USA. NR 6 TC 1 Z9 1 U1 1 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 2004 VL 59 IS 1 BP 31 EP 44 PG 14 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 826EH UT WOS:000221811600002 PM 15190924 ER PT J AU Crawford, LM AF Crawford, LM TI Remarks of the acting FDA commissioner: FDLI's 47th Annual Conference SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 US FDA, Rockville, MD 20857 USA. RP Crawford, LM (reprint author), US FDA, Rockville, MD 20857 USA. NR 2 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 2004 VL 59 IS 2 BP 201 EP 208 PG 8 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 843CF UT WOS:000223052400001 PM 15318391 ER PT J AU Pape, SM Rubin, PD Kim, H AF Pape, SM Rubin, PD Kim, H TI Food security would be compromised by combining the food and drug administration and the US department of agriculture into a single food agency SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 Patton Boggs LLP, FDA Practice Grp, Washington, DC USA. RP Pape, SM (reprint author), Patton Boggs LLP, FDA Practice Grp, Washington, DC USA. NR 13 TC 1 Z9 2 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 2004 VL 59 IS 3 BP 405 EP 416 PG 12 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 862UL UT WOS:000224516500005 PM 15586990 ER PT J AU Klamt, F Shacter, E AF Klamt, F Shacter, E TI Taurine chloramine treatment activates mitochondria-dependent programmed cell death in human B lymphoma cells SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 37 SU 1 BP S126 EP S126 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900388 ER PT J AU Shabalina, SA Spiridonov, NA AF Shabalina, SA Spiridonov, NA TI The mammalian transcriptome and the function of non-coding DNA sequences SO GENOME BIOLOGY LA English DT Editorial Material ID MATRIX-ATTACHMENT REGIONS; RNA UNTRANSLATED REGIONS; PRE-MESSENGER-RNA; INTERGENIC REGIONS; HUMAN GENOME; TRANSLATION INITIATION; SELECTIVE CONSTRAINT; CONSERVED SEQUENCES; POLYADENYLATED RNA; EXPRESSED GENES AB For decades, researchers have focused most of their attention on protein-coding genes and proteins. With the completion of the human and mouse genomes and the accumulation of data on the mammalian transcriptome, the focus now shifts to non-coding DNA sequences, RNA-coding genes and their transcripts. Many non-coding transcribed sequences are proving to have important regulatory roles, but the functions of the majority remain mysterious. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Shabalina, SA (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 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; NR 73 TC 76 Z9 86 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2004 VL 5 IS 4 AR 105 DI 10.1186/gb-2004-5-4-105 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 808QX UT WOS:000220584700002 PM 15059247 ER PT J AU Kessler, L Ramsey, SD Tunis, S Sullivan, SD AF Kessler, L Ramsey, SD Tunis, S Sullivan, SD TI From the field - Clinical use of medical devices in the 'Bermuda Triangle' SO HEALTH AFFAIRS LA English DT Article ID PULMONARY-ARTERY CATHETERIZATION; VOLUME-REDUCTION SURGERY; CRITICALLY-ILL PATIENTS; LUNG-VOLUME; RANDOMIZED-TRIAL; SEVERE EMPHYSEMA; CANCER; HEART; CARE AB The pace of medical technological development shows no sign of abating. Analyzing the effect of major federal health agencies on the availability of such technology is critical. This paper describes functions of three government health agencies: the Centers for Medicare and Medicaid Services (CMS), the Food and Drug Administration (FDA), and the National Institutes of Health (NIH). Certain medical technologies fall into gaps between these agencies, which pose challenges in today's era of demand for evidence-based medicine. We suggest new policy and pragmatic strategies that can close the gaps and move decision making relevant to technology forward more rapidly than is now the case. C1 US FDA, Off Sci & Technol, Rockville, MD 20857 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Ctr Medicare & Medicaid Serv, Baltimore, MD USA. Washington Univ, Pharm & Hlth Serv, Seattle, WA USA. Washington Univ, Pharm Outcomes Res & Policy Program, Seattle, WA USA. RP Kessler, L (reprint author), US FDA, Off Sci & Technol, Rockville, MD 20857 USA. NR 34 TC 18 Z9 19 U1 1 U2 3 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JAN-FEB PY 2004 VL 23 IS 1 BP 200 EP 207 DI 10.1377/hlthaff.23.1.200 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 761KH UT WOS:000187907600025 PM 15002643 ER PT S AU Brackett, RE AF Brackett, RE BE Looney, NE TI Safety of fresh produce: Why is this such an issue today? SO HORTICULTURE: ART AND SCIENCE FOR LIFE SE ACTA HORTICULTURAE LA English DT Proceedings Paper CT 26th International Horticultural Congress CY AUG 11-17, 2002 CL TORONTO, CANADA SP Canadian Soc Hort Sci, Int Soc Hort Sci, Univ Guelph DE good agricultural practices; food-borne disease; sources of contamination; and factors associated with product source; distribution and storage; life style and population demographics; pathogen virulence; disease monitoring and reporting; and consumer awareness AB Although some of the apparent increase in food-borne illnesses associated with fresh produce is likely a result of better surveillance and reporting, there does appear to be a real increase in the number of cases. However, this does not necessarily mean that there is an absolute increase in the likelihood of any individual fresh produce item causing illness. Rather, increased consumption of fresh produce, diverse sources and complex distribution systems, the sources and types of food-borne pathogens. and demographic and societal changes we are experiencing combine to increase the risk of encountering a food-borne disease. However, solutions do exist and fresh produce can be made safer with appropriate research, technology, and education. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Brackett, RE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS-001, College Pk, MD 20740 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU INTERNATIONAL SOCIETY HORTICULTURAL SCIENCE PI LEUVEN 1 PA PO BOX 500, 3001 LEUVEN 1, BELGIUM SN 0567-7572 BN 90-6605-217-1 J9 ACTA HORTIC PY 2004 IS 642 BP 137 EP 144 PG 8 WC Horticulture SC Agriculture GA BBM82 UT WOS:000226246800015 ER PT J AU Lee, SJ Badano, A Kanicki, J AF Lee, SJ Badano, A Kanicki, J TI Monte Carlo modeling of the light transport in polymer light-emitting devices on plastic substrates SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article DE Monte Carlo simulation; out-coupling efficiency; plastic substrate; polymer light-emitting devices ID QUANTUM EFFICIENCY; EMISSION; DIODES AB A Monte Carlo method for modeling the light transport phenomena organic polymer light-emitting devices (PLEDs) has been reported previously (Badano and Kanicki, 2001). The advantage of this simulation method is its ability to model bulk absorption, thin-film coatings, and uneven or irregular surfaces by tracking the photon polarization in realistic device structures. We have applied this method to analyze the PLEDs spectral outputs and out-coupling efficiencies. We have established that the calculated out-coupling efficiencies are approximately the same (eta(coup) similar to 0.2) for the red and green PLEDs. Using a description of uneven surfaces with Fresnel analysis, we showed that the nonsmooth interfaces (as modeled by the algorithm for uneven surfaces) between light-emitting polymer and hole transporting layer increase the probabilities of out-coupling and wave-guiding of the internally generated light. In this paper, we use this method to calculate the angular distribution of the PLED light-emission. We found that the Monte Carlo simulated PLED light-emission angular distribution shows better agreement with the experimental data than previously used models relying on standard refraction theory at one interface [2]. C1 Univ Michigan, Macromol Sci & Engn & Solid State Elect Lab, Coll Engn, Dept Elect Engn & Comp Sci, Ann Arbor, MI 48109 USA. US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Univ Calif Santa Barbara, Ctr Polymers & Organ Solids, Santa Barbara, CA 93106 USA. RP Lee, SJ (reprint author), Univ Michigan, Macromol Sci & Engn & Solid State Elect Lab, Coll Engn, Dept Elect Engn & Comp Sci, Ann Arbor, MI 48109 USA. EM kanicki@eecs.umich.edu RI Kanicki, Jerzy/E-2753-2016; OI Kanicki, Jerzy/0000-0002-3649-8360; badano, aldo/0000-0003-3712-6670 NR 25 TC 10 Z9 10 U1 1 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD JAN-FEB PY 2004 VL 10 IS 1 BP 37 EP 44 DI 10.1109/JSTQE.2004.824073 PG 8 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 813KI UT WOS:000220905600007 ER PT J AU Jakubzick, C Kunkel, SL Puri, RK Hogaboam, CM AF Jakubzick, C Kunkel, SL Puri, RK Hogaboam, CM TI Therapeutic targeting of IL-4- and IL-13-responsive cells in pulmonary fibrosis SO IMMUNOLOGIC RESEARCH LA English DT Article DE idiopathic pulmonary fibrosis; IL-13; IL-4; IL-13 receptor; IL-4 receptor ID NONSPECIFIC INTERSTITIAL PNEUMONIA; MONOCYTE CHEMOATTRACTANT PROTEIN-1; HUMAN LUNG FIBROBLASTS; INTERFERON GAMMA-1B; SIGNAL-TRANSDUCTION; SKIN FIBROBLASTS; IMMUNE-RESPONSE; GENE-EXPRESSION; NECK-CANCER; IL-13 AB Severe forms of idiopathic interstitial pneumonia (IIP), such as usual interstitial pneumonia (UIP), can be impervious to modern steroid and immunosuppressive treatment regimens, thereby emphasizing the need for novel effective therapies. Understanding the cytokine networks that may affect immune and structural cell activation and, hence, the progression of these fatal fibrotic diseases, has been a focus in our research. In this regard, we have examined the role of interleukin (IL)-4 and IL-13 and their respective receptor subunits in this process. Examination of clinical surgical lung biopsies (SLBs) showed that IIP is characterized by the abnormal, heightened expression of the receptor subunits that bind IL-4 and IL-13. Specifically, IL-4Ralpha and IL-13Ralpha2 (the high-affinity IL-13 receptor subunit) was present in greater abundance in SLBs and fibroblasts from IIP patients compared with normal patients, who exhibited no evidence of pulmonary fibrosis. These clinical findings prompted us to investigate whether the targeting Of Pulmonary cell types that were highly responsive to IL-4 and IL-13 was a viable therapeutic option in IIP. Using a chimeric protein comprised of human IL-13 and a truncated version of an exotoxin from Pseudomonas (abbreviated IL13-PE), we observed that IL13-PE selectively targeted human pulmonary fibroblasts grown from IIP SLBs, whereas it had a minimal effect on fibroblasts grown from biopsies from normal patients. In murine models characterized by abnormal airway or interstitial fibrotic responses, the intranasal administration of IL13-PE significantly attenuated the fibrotic response through the targeting of IL-4Ralpha- and IL-13Ralpha2-expressing pulmonary cells, including monocytes, macrophages, and pulmonary fibroblasts. Together, these data demonstrate that IL-4 and IL-13 are required for the initiation and maintenance of pulmonary fibrosis, and highlight the importance of further investigation of anti-fibrotic therapeutics that prevent the action of both cytokines during clinical pulmonary fibrosis. C1 Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Hogaboam, CM (reprint author), Univ Michigan, Sch Med, Dept Pathol, Rm 5216B,Med Sci 1,1303 Catherine Rd, Ann Arbor, MI 48109 USA. EM Hogaboam@med.umich.edu RI hogaboam, cory /M-3578-2014 FU NIAID NIH HHS [T32 AI007413] NR 65 TC 48 Z9 53 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 2004 VL 30 IS 3 BP 339 EP 349 DI 10.1385/IR:30:3:339 PG 11 WC Immunology SC Immunology GA 870TR UT WOS:000225081700006 PM 15531774 ER PT J AU Coban, C Ishii, KJ Stowers, AW Keister, DB Klinman, DM Kumar, N AF Coban, C Ishii, KJ Stowers, AW Keister, DB Klinman, DM Kumar, N TI Effect of CpG oligodeoxynucleotides on the immunogenicity of Pfs25, a Plasmodium falciparum transmission-blocking vaccine antigen SO INFECTION AND IMMUNITY LA English DT Article ID MEROZOITE SURFACE PROTEIN-1; IMMUNE-RESPONSES; SYNTHETIC OLIGODEOXYNUCLEOTIDES; MALARIA VACCINE; BACTERIAL-DNA; CUTTING EDGE; ANTIBODIES; ADJUVANTS; MOTIFS; MICE AB Antibodies directed against Pfs25, a protein present on the surface of zygotes and ookinetes of Plasmodium falciparum, completely block pathogen transmission. We evaluated the immunomodulatory effect of CpG oligodeoxynucleotides (ODN) on the immunogenicity of recombinant Pfs25 (rPfs25) formulated in alum (A1). Immunization of mice with rPfs25 plus CpG ODN improved both the antibody titer (a 30-fold-higher antibody response than that with rPfs25-A1 alone) and avidity. Coadministration of CpG ODN dramatically enhanced the titer of immunoglobulin G2A (IgG2a) compared to the titer of the IgG1-dominant response caused by rPfs25-A1 alone, and the sera from the CpG ODN-coadministered group completely blocked the transmission of P. falciparum parasites to mosquitoes, as determined by membrane feeding assays. However, transmission-blocking experiments revealed that blocking efficacy was dependent on high-titer antibody levels, independent of isotypes. These results suggest that CpG ODN can be used as an adjuvant to enhance the immunogenicity of rPfs25 as a malaria transmission-blocking vaccine. C1 Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Bloomberg Sch Publ Hlth, Malaria Res Inst, Baltimore, MD 21205 USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NIAID, Malaria Vaccine Dev Unit, Parasit Dis Lab, NIH, Rockville, MD USA. RP Kumar, N (reprint author), Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Bloomberg Sch Publ Hlth, Malaria Res Inst, 615 N Wolfe St, Baltimore, MD 21205 USA. RI Coban, Cevayir/B-2129-2012; Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 FU NCRR NIH HHS [M01 RR000722]; NIAID NIH HHS [AI47089, R01 AI047089] NR 37 TC 21 Z9 24 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 2004 VL 72 IS 1 BP 584 EP 588 DI 10.1128/IAI.72.1.584-588.2004 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 758JR UT WOS:000187631600067 PM 14688140 ER PT J AU Fang, GC Wu, YS Fu, PPC Chang, CN Ho, TT Chen, MH AF Fang, GC Wu, YS Fu, PPC Chang, CN Ho, TT Chen, MH TI The study of temple and pastureland particle-bound polycyclic aromatic hydrocarbons concentrations in central Taiwan SO INTERNATIONAL JOURNAL OF ENVIRONMENT AND POLLUTION LA English DT Article DE PAH; pastureland; PM2.5; PM2.5-10; PM10; temple ID PARTICULATE; ATMOSPHERE; AEROSOLS; INDOOR; AIR AB The concentrations of polycyclic aromatic hydrocarbons in the atmosphere were measured simultaneously at Tzu Yun Yen temple and Tung Hai University pastureland in Taichung, central Taiwan. At both sites, 24 h samplings were performed between August 2001 and December 2001. The results indicated that high molecular mass polycyclic aromatic hydrocarbons are predominant at the Tzu Yun Yen temple sampling site. Moreover, the PM2.5 (fine particulate) fraction of total polycyclic aromatic hydrocarbons was higher than that of the PM2.5-10 (coarse particulate) fraction by a factor of about 1.48 at the temple sampling site. This ratio was 1.24 for the pastureland environment. C1 Hungkuang Univ, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Tunghai Univ, Dept Environm Sci, Taichung 407, Taiwan. RP Fang, GC (reprint author), Hungkuang Univ, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. EM gcfang@sunrise.hk.edu.tw NR 12 TC 2 Z9 2 U1 0 U2 1 PU INDERSCIENCE ENTERPRISES LTD PI GENEVA PA WORLD TRADE CENTER BLDG, 29 ROUTE DE PRE-BOIS, CASE POSTALE 896, CH-1215 GENEVA, SWITZERLAND SN 0957-4352 J9 INT J ENVIRON POLLUT JI Int. J. Environ. Pollut. PY 2004 VL 22 IS 6 BP 688 EP 700 DI 10.1504/IJEP.2004.006049 PG 13 WC Environmental Sciences SC Environmental Sciences & Ecology GA 893CF UT WOS:000226696200004 ER PT J AU Fang, GC Wu, YS Huang, WJ Lu, HC Fu, PPC Chen, YS AF Fang, GC Wu, YS Huang, WJ Lu, HC Fu, PPC Chen, YS TI Short-term variations in ambient particulates and their sources in Taichung, Taiwan SO INTERNATIONAL JOURNAL OF ENVIRONMENT AND POLLUTION LA English DT Article DE diurnal variation; fine and coarse particulates; PCA; short-term variation; TSP ID ATMOSPHERIC AEROSOL; SUSPENDED PARTICLES; SIZE DISTRIBUTION; COARSE PARTICLES; COASTAL SITE; PM10; URBAN; CALIFORNIA; SUBURBAN; ELEMENTS AB Ambient particulate measurements were carried out using TE-PUF sampling and a Universal Air Sampler between 8 March and 25 April 2001 at Taichung. Samples were collected every 6 hours beginning at 0100 LST (Local Standard Time) each day at two sites, one at a university campus and the other at a roadside. Chemical species (Cl-, NO3-, SO42-, Na+, NH4+, K+, MgZ(+), Ca2+, Fe, Zn, Pb, Ni) were analysed simultaneously. The main sources at the campus sampling site were identified as soil dust re-suspension, sea salt spray, secondary aerosols and zinc-related industry, and those at the traffic sampling site as soil dust re-suspension, sea salt spray, secondary aerosol and fuel combustion. The diurnal variation of all the chemical species' concentrations were also measured. The meteorological conditions and the pollutant emission sources near the sampling sites are likely impact factors. These results also showed that the short-term diurnal variation of the concentrations of chemical species in the ambient suspended particulates is useful to identify the sources and modes of formation of the particulates. C1 Hungkuang Univ, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Hungkuang Univ, Dept Food Nutr, Taichung 433, Taiwan. RP Fang, GC (reprint author), Hungkuang Univ, Air Tox & Environm Anal Lab, Sha Lu, Taichung 433, Taiwan. EM gcfang@sunrise.hk.edu.tw NR 23 TC 1 Z9 1 U1 3 U2 5 PU INDERSCIENCE ENTERPRISES LTD PI GENEVA PA WORLD TRADE CENTER BLDG, 29 ROUTE DE PRE-BOIS, CASE POSTALE 896, CH-1215 GENEVA, SWITZERLAND SN 0957-4352 J9 INT J ENVIRON POLLUT JI Int. J. Environ. Pollut. PY 2004 VL 21 IS 4 BP 383 EP 399 DI 10.1504/IJEP.2004.005115 PG 17 WC Environmental Sciences SC Environmental Sciences & Ecology GA 823NA UT WOS:000221618500006 ER PT J AU Wu, YS Fang, GC Chu, CC Fu, PPC Ji, DY Chen, MH Yang, IL AF Wu, YS Fang, GC Chu, CC Fu, PPC Ji, DY Chen, MH Yang, IL TI A study of polycyclic aromatic hydrocarbons in airborne particulate matter in central Taiwan SO INTERNATIONAL JOURNAL OF ENVIRONMENT AND POLLUTION LA English DT Article DE coal combustion; PAH; TSP; vehicular emissions ID CARBONYL-COMPOUNDS; PAHS; URBAN; DEPOSITION; SITES; KOREA; AIR AB Two sampling sites in central Taiwan, at Hungkuang University (HKU) and Tunghai University (THU), were chosen to contrast the content of polycyclic aromatic hydrocarbons (PAHs) in the atmosphere from November 2000 to April 2001. PAHs that arise from incomplete combustion of organic materials, especially fossil fuels, are the major toxic pollutants in central Taiwan. This study aimed to analyse PAHs, by using a PS-1 sampler and a gas chromatograph/mass selective detector (GC/MSD), and to identify the major sources of PAHs. At the HKU sampling site, the primary emission sources are probably vehicles and coal burning, and vehicular emissions are the primary contributor at the THU sampling site. C1 Hungkuang Univ, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. Chien Yu Reg Teaching Hosp, Dept Internal Med, Intens Care Unit, Kaohsiung 832, Taiwan. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Fang, GC (reprint author), Hungkuang Univ, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. EM gcfang@sunrise.hk.edu.tw NR 15 TC 0 Z9 0 U1 0 U2 2 PU INDERSCIENCE ENTERPRISES LTD PI GENEVA PA WORLD TRADE CENTER BLDG, 29 ROUTE DE PRE-BOIS, CASE POSTALE 896, CH-1215 GENEVA, SWITZERLAND SN 0957-4352 J9 INT J ENVIRON POLLUT JI Int. J. Environ. Pollut. PY 2004 VL 21 IS 5 BP 471 EP 480 DI 10.1504/IJEP.2004.005121 PG 10 WC Environmental Sciences SC Environmental Sciences & Ecology GA 837BS UT WOS:000222602000005 ER PT J AU Fang, GC Wu, YS Fu, PPC AF Fang, GC Wu, YS Fu, PPC TI Sampling errors in the study of acid gases and anion species in atmospheric aerosols SO INTERNATIONAL JOURNAL OF ENVIRONMENT AND POLLUTION LA English DT Article DE acid aerosols; annular denuder; MOUDI; ions; size distribution ID ANNULAR DENUDER SYSTEM; AIRBORNE PARTICLES; AIR-POLLUTION; SIZE; TAIWAN AB Atmospheric acid aerosols were sampled by two annular denuder systems (ADS) and a micro-orifice uniform deposit impactor (MOUDI) at a traffic site in central Taiwan. Theoretical analysis showed that the relative artifact for HNO3 gas sampling was about 0.53 when the initial HNO3 concentration was under 0.2 mug/m(3) and should be considered carefully. The concentrations of gaseous acid at the traffic sampling site were higher than those in the other study. The size distributions of acid aerosols were unimodal for Cl-, NO2- and NO3-, and bimodal for SO42-. The dominant acid ions in particles less than 18 mum were SO42-, NO3-, NO2- and Cl-. C1 Hungkuang Univ, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. Chien Yu Reg Teaching Hosp, Dept Internal Med, Kaohsiung 832, Taiwan. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Fang, GC (reprint author), Hungkuang Univ, Air Tox & Environm Anal Lab, Sha Lu, Taichung 433, Taiwan. NR 14 TC 0 Z9 0 U1 0 U2 1 PU INDERSCIENCE ENTERPRISES LTD PI GENEVA PA WORLD TRADE CENTER BLDG, 29 ROUTE DE PRE-BOIS, CASE POSTALE 896, CH-1215 GENEVA, SWITZERLAND SN 0957-4352 J9 INT J ENVIRON POLLUT JI Int. J. Environ. Pollut. PY 2004 VL 21 IS 6 BP 566 EP 578 PG 13 WC Environmental Sciences SC Environmental Sciences & Ecology GA 841YZ UT WOS:000222970100004 ER PT J AU Tonidandel, S Overall, JE Smith, F AF Tonidandel, S Overall, JE Smith, F TI Use of resampling to select among alternative error structure specifications for GLMM analyses of repeated measurements SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH LA English DT Article DE clinical trials; repeated measures; mixed models; goodness of fit; significance testing; type I errors; power ID MODELS AB Autocorrelated error and missing, data due to dropouts have fostered interest in the flexible general linear mixed model (GLMM) procedures for analysis of data from controlled clinical trials. The user of these adaptable statistical tools must, however, choose among, alternative structural models to represent the correlated repeated measurements. The fit of the error structure model specification is important for validity of tests for differences in patterns of treatment effects across time, particularly when maximum likelihood procedures are relied upon. Results can he affected significantly by the error specification that is selected, so a principled basis for selecting the specification is important. As no theoretical grounds are usually available to guide this decision, empirical criteria have been developed that focus on model fit. The current report proposes alternative empirical criteria that focus on bootstrap estimates of actual type I error and power of tests for treatment effects. Results for model selection before and after the blind is broken are compared. Goodness-of-fit statistics also compare favourably for models fitted to the blinded or unblinded data, although the correspondence to actual type I error and power depends on the particular fit statistic that is considered. C1 Davidson Coll, Dept Psychol, Davidson, NC 28035 USA. US FDA, Rockville, MD 20857 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, Houston, TX USA. RP Tonidandel, S (reprint author), Davidson Coll, Dept Psychol, Box 7061, Davidson, NC 28035 USA. EM sctonidandel@davidson.edu FU NIMH NIH HHS [MH32457] NR 21 TC 1 Z9 1 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1049-8931 J9 INT J METH PSYCH RES JI Int. J. Methods Psychiatr. Res. PY 2004 VL 13 IS 1 BP 24 EP 33 DI 10.1002/mpr.161 PG 10 WC Psychiatry SC Psychiatry GA 826VE UT WOS:000221856800003 PM 15181484 ER PT J AU Royce, ME Rowinsky, EK Hoff, PM Coyle, J DeJager, R Pazdur, R Saltz, LB AF Royce, ME Rowinsky, EK Hoff, PM Coyle, J DeJager, R Pazdur, R Saltz, LB TI A Phase II study of intravenous exatecan mesylate (DX-8951f) administered daily for five days every three weeks to patients with metastatic adenocarcinoma of the colon or rectum SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE camptothecin; clinical trial; DX-8951f; exatecan mesylate; topoisomerase-1 inhibitor ID ADVANCED COLORECTAL-CANCER; POTENT ANTITUMOR-ACTIVITY; CAMPTOTHECIN ANALOG; RANDOMIZED-TRIAL; CONTINUOUS-INFUSION; FLUOROURACIL FAILURE; 1ST-LINE TREATMENT; TOPOISOMERASE-I; HUMAN PLASMA; TUMOR-CELLS AB Background: To evaluate the antitumor activity, toxicities, and pharmacokinetics (PK) of DX-895 If administered as a 30-min infusion daily for 5 days every 3 weeks in patients with fluorouracil-resistant metastatic colorectal carcinoma. Patients and methods: Sixteen patients were enrolled. All had metastatic colorectal carcinoma resistant to or progressing after chemotherapy containing 5-fluorouracil and no prior chemotherapy with camptothecin derivatives. DX-8951f was administered until disease progression or unacceptable toxicity. Responses were assessed after every two courses. Results: Fifteen patients were evaluable. Fifty-one courses of therapy were delivered (median 2). Responses were one minor response, six stable disease, and eight progressive disease. The principal adverse event was neutropenia, with grade 3 and 4 toxicities in three and eight patients, respectively. Non-hematologic toxicities were mild to moderate; the most common were fatigue, nausea, and diarrhea. Plasma concentrations of DX-8951 were well described using a linear two-compartment PK model. There was no evidence of nonlinearity in the elimination of PK or auto-inhibition or induction of DX-8951 clearance over the 5 days of administration. Conclusions: DX-8951f at this dose and schedule had no significant activity in this patient population. The toxicity profile, mainly hematologic, was consistent with previous reports. The clearance and volume of distribution were not different from those previously reported. C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Canc Therapy & Res Ctr S Texas, Inst Drug Dev, San Antonio, TX 78229 USA. Albert Einstein Hosp, Ctr Clin Studies Canc, Sao Paulo, Brazil. Daiichi Pharmaceut Corp, Montvale, NJ USA. US FDA, Div Oncol Drug Prod, Rockville, MD 20857 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Royce, ME (reprint author), Univ Texas, MD Anderson Canc Ctr, 1515 Holcombe Blvd,Box 424, Houston, TX 77030 USA. OI Saltz, Leonard/0000-0001-8353-4670 NR 39 TC 7 Z9 7 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD JAN PY 2004 VL 22 IS 1 BP 53 EP 61 DI 10.1023/B:DRUG.0000006174.87869.6b PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 749AC UT WOS:000186895600005 PM 14707494 ER PT S AU Morehouse, KM Komolprasert, V AF Morehouse, KM Komolprasert, V BE Komolprasert, V Morehouse, KM TI Irradiation of food and packaging: An overview SO IRRADIATION OF FOOD AND PACKAGING: RECENT DEVELOPMENTS SE ACS SYMPOSIUM SERIES LA English DT Article; Proceedings Paper CT Symposium on Food Irradiation and Packing for Irradiated Food CY AUG 18-22, 2002 CL Boston, MA SP Amer Chem Soc, Div Agr & Food Chem ID DNA COMET ASSAY; UNITED-STATES; EUROPEAN-UNION; IDENTIFICATION; ACCEPTANCE; RADIATION; CONSUMER AB Ionizing radiation can extend shelf life and improve the quality and safety of foods. National and international organizations and regulatory agencies have concluded that irradiated food is safe and wholesome. A brief background of the food irradiation issues leading to these conclusions is given. Despite its limited use in the past, use of food irradiation is increasing as consumers are beginning to appreciate the benefits of irradiated food. Interest in the use of food irradiation increased following the 1997 US Food and Drug Administration approval of irradiation for pathogen control in unprocessed red meat and meat products. This approval led to numerous studies on a variety of food irradiation applications. Since food is usually prepackaged prior to irradiation, the possibility of radiolytic products being released from packaging materials into food requires a safety evaluation. Therefore, the use of these packaging materials is subject to regulatory review and approval prior to their use. U.S. government work. Published 2004 American Chemical Society. C1 US FDA, Off Food Addit Safety, Div Chem Res & Environm Review, College Pk, MD 20740 USA. US FDA, Off Plant Dairy Foods & Beverages, Div Food Proc & Packaging, Summit Argo, IL 60501 USA. RP Morehouse, KM (reprint author), US FDA, Off Food Addit Safety, Div Chem Res & Environm Review, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 45 TC 19 Z9 19 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 0-8412-3869-3 J9 ACS SYM SER PY 2004 VL 875 BP 1 EP 11 PG 11 WC Chemistry, Multidisciplinary; Food Science & Technology; Nuclear Science & Technology; Polymer Science SC Chemistry; Food Science & Technology; Nuclear Science & Technology; Polymer Science GA BY69K UT WOS:000189440600001 ER PT S AU Paquette, KE AF Paquette, KE BE Komolprasert, V Morehouse, KM TI Irradiation of prepackaged food: Evolution of the US food and drug administration's regulation of the packaging materials SO IRRADIATION OF FOOD AND PACKAGING: RECENT DEVELOPMENTS SE ACS SYMPOSIUM SERIES LA English DT Article; Proceedings Paper CT Symposium on Food Irradiation and Packing for Irradiated Food CY AUG 18-22, 2002 CL Boston, MA SP Amer Chem Soc, Div Agr & Food Chem ID CHROMATOGRAPHY-MASS SPECTROMETRY; VOLATILE RADIOLYSIS PRODUCTS; ELECTRON-BEAM IRRADIATION; POLYETHYLENE FILM; RADIATION; POLYMERS; POLYPROPYLENE; MIGRATION AB The FDA approved the first materials intended for use as packaging for irradiated foods (polyolefin films, polystyrene, cellophane, vinylidene chloride copolymers, and others) in 1964. Several other materials were approved for this use during the next four years. Since then, only one material, ethylene vinyl acetate copolymer, was added to Title 21 of the Code of Federal Regulations, in 1989. The recent interest in irradiating meat to eliminate pathogens such as E. coli O157:H7 has resulted in several industry submissions to the Agency regarding new packaging materials, as well as the radiation sources, intended for use during the irradiation of prepackaged food. A brief history of FDA regulation of packaging materials irradiated in contact with food, including a discussion of human exposures to radiolysis products formed in irradiated polymers, will be presented. The evaluation of new packaging materials for irradiated foods will be discussed within the context of FDA's Food Contact Substance Notification Program. U.S. government work. Published 2004 American Chemical Society. C1 US FDA, Off Food Addit Safety, College Pk, MD 20740 USA. RP Paquette, KE (reprint author), US FDA, Off Food Addit Safety, 5100 Paint Branch Pkwy,MS HFS-275, College Pk, MD 20740 USA. NR 37 TC 7 Z9 7 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 0-8412-3869-3 J9 ACS SYM SER PY 2004 VL 875 BP 182 EP 202 PG 21 WC Chemistry, Multidisciplinary; Food Science & Technology; Nuclear Science & Technology; Polymer Science SC Chemistry; Food Science & Technology; Nuclear Science & Technology; Polymer Science GA BY69K UT WOS:000189440600012 ER PT S AU Sadler, GD AF Sadler, GD BE Komolprasert, V Morehouse, KM TI Fate of energy absorbed by polymers during irradiation treatment SO IRRADIATION OF FOOD AND PACKAGING: RECENT DEVELOPMENTS SE ACS SYMPOSIUM SERIES LA English DT Article; Proceedings Paper CT Symposium on Food Irradiation and Packing for Irradiated Food CY AUG 18-22, 2002 CL Boston, MA SP Amer Chem Soc, Div Agr & Food Chem C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Sadler, GD (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 0-8412-3869-3 J9 ACS SYM SER PY 2004 VL 875 BP 203 EP 213 PG 11 WC Chemistry, Multidisciplinary; Food Science & Technology; Nuclear Science & Technology; Polymer Science SC Chemistry; Food Science & Technology; Nuclear Science & Technology; Polymer Science GA BY69K UT WOS:000189440600013 ER PT S AU McNeal, TP Komolprasert, V Buchalla, R Olivo, C Begley, TH AF McNeal, TP Komolprasert, V Buchalla, R Olivo, C Begley, TH BE Komolprasert, V Morehouse, KM TI Effects of ionizing radiation on food contact materials SO IRRADIATION OF FOOD AND PACKAGING: RECENT DEVELOPMENTS SE ACS SYMPOSIUM SERIES LA English DT Article; Proceedings Paper CT Symposium on Food Irradiation and Packing for Irradiated Food CY AUG 18-22, 2002 CL Boston, MA SP Amer Chem Soc, Div Agr & Food Chem ID PRODUCTS; POLYMERS AB FDA's Office of Food Additive Safety is responsible for the evaluation of food additive petitions and pre-market notifications requesting approval of new food contact materials for irradiation. Our lab supports that review process by conducting research to identify and quantify the products formed in food contact polymers after exposure to ionizing radiation and then determining whether any of these compounds migrate into food. A major objective of this research is to assist in the development of guidance to manufacturers seeking FDA approval to irradiate their products. Different polyesters, polyamides, a high-density polyethylene, and an ethylene vinyl alcohol copolymer were evaluated before and after exposure to different levels of gamma and electron-beam radiation. Volatile chemicals were isolated from the test materials using static headspace sampling and analyzed by gas chromatography with mass selective detection. Semi-volatile and non-volatile chemicals were extracted from the test materials using a variety of solvents including n-heptane, a fatty food simulating solvent, and the extracts were analyzed using high performance liquid chromatography with mass selective detection, The extracts containing semi-volatiles were also analyzed by gas chromatography with mass selective detection. Most of the chemicals found are thought to be products of the polymerization process or conversion of the polymer(s) into a finished package, and breakdown products of polymer additives. Although exposure to ionizing radiation increases the concentration of some of these chemicals and decreases the concentration of other chemicals, few of the chemicals determined are thought to be chemicals specifically formed by ionizing radiation. Results of these analyses and data on the migration of some of the chemicals are presented. C1 US FDA, Div Chem Res & Environm Review, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. US FDA, Natl Ctr Food Safety & Technol, Div Food Proc & Packaging, Summit Argo, IL 60501 USA. Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA. RP McNeal, TP (reprint author), US FDA, Div Chem Res & Environm Review, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 20 TC 3 Z9 3 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 0-8412-3869-3 J9 ACS SYM SER PY 2004 VL 875 BP 214 EP 235 PG 22 WC Chemistry, Multidisciplinary; Food Science & Technology; Nuclear Science & Technology; Polymer Science SC Chemistry; Food Science & Technology; Nuclear Science & Technology; Polymer Science GA BY69K UT WOS:000189440600014 ER PT J AU Pergantis, SA Miguens-Rodriguez, M Vela, NP Heitkemper, DT AF Pergantis, SA Miguens-Rodriguez, M Vela, NP Heitkemper, DT TI Investigating the non-enzymatic methylation of arsenite by methylcobalamin B-12 using high-performance liquid chromatography on-line with inductively coupled plasma-mass spectrometry SO JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY LA English DT Article ID MONOMETHYLARSONOUS ACID; HUMAN URINE; IN-VITRO; SPECIATION; GLUTATHIONE; WATER; IDENTIFICATION; SEPARATION; TRIVALENT; ARSENATE AB In this study, we have demonstrated the use of HPLC-ICP-MS as a powerful toot for studying the reaction of arsenite with methylcobalamin in the presence of glutathione. Even though this reaction has previously been investigated using radioactive As-73, HPLC-ICP-MS provides considerable advantages relating to sample throughput, sensitivity, and separation efficiency of the arsenic-containing reaction products. As a result of these advantages, kinetic studies were easily conducted, potentially providing valuable insight into the reaction itself. In addition, the HPLC-ICP-MS approach allowed for the tentative identification of methylarsonous acid, an arsenic species that had escaped detection in previous studies of the same reaction. Overall, this study confirmed that methylcobalamin acts as a methylating agent for arsenite in the presence of glutathione in an abiotic environment. A series of methylated arsenic species, identified as methylarsonic acid, dimethylarsinic acid and methylarsonous acid were detected. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. Univ London, Birkbeck Coll, Sch Biol & Chem Sci, London WC1H 0PP, England. RP Heitkemper, DT (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. EM spergantis@chemistry.uoc.gr RI Pergantis, Spiros/D-4022-2009; OI Pergantis, Spiros A./0000-0002-9077-7870 NR 40 TC 10 Z9 10 U1 0 U2 1 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. PD JAN PY 2004 VL 19 IS 1 BP 178 EP 182 DI 10.1039/b306947h PG 5 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 803TN UT WOS:000220253500028 ER PT J AU Schlesser, J AF Schlesser, J. TI Survival of a five strain cocktail of Escherichia coli O157 : H7 during thermalization and the 60 day aging period of hard cheese made from unpasteurized milk SO JOURNAL OF ANIMAL SCIENCE LA English DT Meeting Abstract DE thermalization; Escherichia coli O157 : H7; raw milk cheese C1 [Schlesser, J.] US FDA, NCFST, Summit Argo, IL USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 2004 VL 82 SU 1 BP 122 EP 123 PG 2 WC Agriculture, Dairy & Animal Science SC Agriculture GA V45UM UT WOS:000203095200491 ER PT J AU Perfield, JW Delmonte, P Lock, AL Yurawecz, MP Baumani, DE AF Perfield, J. W., II Delmonte, P. Lock, A. L. Yurawecz, M. P. Baumani, D. E. TI Trans-10, trans-12 conjugated linoleic acid (CLA) reduces the Delta(9)-desaturase index without affecting milk fat yield in lactating dairy cows SO JOURNAL OF ANIMAL SCIENCE LA English DT Meeting Abstract DE conjugated linoleic acid; milk fat depression; StearoylCoA desaturase C1 [Perfield, J. W., II; Lock, A. L.; Baumani, D. E.] Cornell Univ, Ithaca, NY 14853 USA. [Delmonte, P.; Yurawecz, M. P.] Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 U1 0 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 2004 VL 82 SU 1 BP 128 EP 128 PG 1 WC Agriculture, Dairy & Animal Science SC Agriculture GA V45UM UT WOS:000203095200513 ER PT J AU Schlesser, J Gerdes, R AF Schlesser, J. Gerdes, R. TI Incidence of Escherichia coli O157 : H7 in raw milk and survival of a five strain cocktail of E. coli O157 : H7 during the 60 days aging period of hard cheese made from unpasteurized milk SO JOURNAL OF ANIMAL SCIENCE LA English DT Meeting Abstract DE raw milk cheese; Escherichia coli O157 : H7; E. coli O157 : H7 in raw milk C1 [Schlesser, J.] NCFST, US FDA, Summit Argo, IL USA. [Gerdes, R.] IIT, Summit Argo, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 2004 VL 82 SU 1 BP 383 EP 384 PG 2 WC Agriculture, Dairy & Animal Science SC Agriculture GA V45UM UT WOS:000203095201577 ER PT J AU Baumgard, LH Sanders, SR Mendivil, OB Kay, JK Marchello, JA Delmonte, P Griinari, JM Yurawecz, MP AF Baumgard, L. H. Sanders, S. R. Mendivil, O. B. Kay, J. K. Marchello, J. A. Delmonte, P. Griinari, J. M. Yurawecz, M. P. TI Subcutaneous and abdominal fatty acid composition and CLA profiles in grain finished steers SO JOURNAL OF ANIMAL SCIENCE LA English DT Meeting Abstract DE beef; CLA; adipose depot C1 [Baumgard, L. H.; Sanders, S. R.; Mendivil, O. B.; Kay, J. K.; Marchello, J. A.] Univ Arizona, Tucson, AZ USA. [Delmonte, P.; Yurawecz, M. P.] US FDA, Washington, DC 20204 USA. [Griinari, J. M.] Univ Helsinki, FIN-00014 Helsinki, Finland. NR 0 TC 0 Z9 0 U1 0 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 2004 VL 82 SU 1 BP 422 EP 422 PG 1 WC Agriculture, Dairy & Animal Science SC Agriculture GA V45UM UT WOS:000203095201731 ER PT J AU Vela, NP Heitkemper, DT AF Vela, NP Heitkemper, DT TI Total arsenic determination and speciation in infant food products by ion chromatography-inductively coupled plasma-mass spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ATOMIC-ABSORPTION-SPECTROMETRY; MICROWAVE DIGESTION; UNITED-STATES; BABY FOODS; TOTAL DIET; ICP-MS; EXTRACTION; SAMPLES; RICE AB Health risk associated with dietary arsenic intake may be different for infants and adults. Seafood is the main contributor to arsenic intake for adults while terrestrial-based food is the primary source for infants. Processed infant food products such as rice-based cereals, mixed rice/formula cereals, milk-based infant formula, applesauce and puree of peaches, pears, carrots, sweet potatoes, green beans, and squash were evaluated for total and speciated arsenic content. Arsenic concentrations found in rice-based cereals (63-320 ng/g dry weight) were similar to those reported for raw rice. Results for the analysis of powdered infant formula by inductively coupled plasma-mass spectrometry (ICP-MS) indicated a narrow and low arsenic concentration range (12 to 17 ng/g). Arsenic content in puree infant food products, including rice cereals, fruits, and vegetables, varies from <1 to 24 ng/g wet weight. Sample treatment with trifluoroacetic acid at 100degreesC were an efficient and mild method for extraction of arsenic species present in different food matrixes as compared to alternative methods that included sonication and accelerated solvent extraction. Extraction recoveries from 94 to 128% were obtained when the summation of species was compared to total arsenic. The ion chromatography (IC)-ICP-MS method selected for arsenic speciation allowed for the quantitative determination of inorganic arsenic [As(III) + As(V)], dimethylarsinic acid (DMA), and methylarsonic acid (MMA). Inorganic arsenic and DMA are the main species found in rice-based and mixed rice/formula cereals, although traces of MMA were also detected. Inorganic arsenic was present in freeze-dried sweet potatoes, carrots, green beans, and peaches. MMA and DMA were not detected in these samples. Arsenic species in squash, pears, and applesauce were not detected above the method detection limit [5 ng/g dry weight for As(III), MMA, and DMA and 10 ng/g dry weight for As(V)]. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Vela, NP (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. EM nohora.vela@fda.hhs.gov NR 28 TC 32 Z9 36 U1 2 U2 28 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 2004 VL 87 IS 1 BP 244 EP 252 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 805KA UT WOS:000220364000038 PM 15084107 ER PT J AU Hungerford, JM AF Hungerford, JM TI Committee on natural toxins and food allergens SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID SHELLFISH POISONING TOXINS; LIQUID-CHROMATOGRAPHIC DETERMINATION; RECEPTOR-BINDING ASSAY; CAPILLARY-ELECTROPHORESIS; DOMOIC ACID; CYANOBACTERIAL TOXINS; MIST ALERT(TM); ALGAL TOXINS; AQUATIC ENVIRONMENT; MASS-SPECTROMETRY 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 52 TC 1 Z9 1 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2004 VL 87 IS 1 BP 270 EP 275 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 805KA UT WOS:000220364000042 PM 15084110 ER PT J AU Trucksess, MW AF Trucksess, MW TI Mycotoxins SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID OCHRATOXIN-A; PENICILLIUM-EXPANSUM; AFLATOXIN B-1; LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; FUMONISIN B-1; DEOXYNIVALENOL VOMITOXIN; NATURAL COOCCURRENCE; CITRININ PRODUCTION; ASPERGILLUS-FLAVUS 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 85 TC 3 Z9 3 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2004 VL 87 IS 1 BP 275 EP 284 PG 10 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 805KA UT WOS:000220364000043 ER PT J AU Andrews, WH AF Andrews, WH TI Food microbiology, non-dairy 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 NR 7 TC 1 Z9 1 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2004 VL 87 IS 1 BP 296 EP 302 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 805KA UT WOS:000220364000049 PM 15084113 ER PT J AU Kim, PI Bai, H Bai, D Chae, H Chung, S Kim, Y Park, R Chi, YT AF Kim, PI Bai, H Bai, D Chae, H Chung, S Kim, Y Park, R Chi, YT TI Purification and characterization of a lipopeptide produced by Bacillus thuringiensis CMB26 SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article DE Bacillus thuringiensis CMB26; biocontrol agent; Colletotrichum gloeosporioides; fengycin; lipopeptide ID BACILLUS-SUBTILIS; RHIZOCTONIA-SOLANI; ITURIN-A; STRUCTURAL-CHARACTERIZATION; MASS-SPECTROMETRY; SURFACTANT; BIOSURFACTANTS; PEPTIDE AB Aims: To isolate an antagonist for use in the biological control of phytopathogenic fungi including Colletotrichum gloeosporioides, then to purify and characterize the biocontrol agent produced by the antagonist. Methods and Results: Bacteria that exhibited antifungal activity against the causative agent pepper anthracnose were isolated from soil, with Bacillus thuringiensis CMB26 showing the strongest activity. A lipopeptide produced by B. thuringiensis CMB26 was precipitated by adjusting the pH 2 with 3 n HCl and extracted using chloroform/methanol (2 : 1, v/v) and reversed-phase HPLC. The molecular weight was estimated as 1447 Da by MALDI-TOF mass spectrometry. Scanning electron and optical microscopies showed that the lipopeptide has activity against Escherichia coli O157:ac88, larvae of the cabbage white butterfly (Pieris rapae crucivora) and phytopathogenic fungi. The lipopeptide had cyclic structure and the amino acid composition was l-Glu, d-Orn, l-Tyr, d-allo-Thr, d-Ala, d-Val, l-Pro, and l-Ile in a molar ratio of 3 : 1 : 2 : 1 : 1 : 2 : 1 : 1. The purified lipopeptide showed the same amino acid composition as fengycin, but differed slightly in fatty acid composition, in which the double bond was at carbons 13-14 (m/z 303, 316) and there was no methyl group. Conclusion: A lipopeptide was purified and characterized from B. thuringiensis CMB26 and found to be similar to the lipopeptide fengycin. This lipopeptide can function as a biocontrol agent, and exhibits fungicidal, bactericidal, and insecticidal activity. Significance and Impact of the Study: Compared with surfactin and iturin, the lipopeptide from B. thuringiensis CMB26 showed stronger antifungal activity against phytopathogenic fungi. This lipopeptide is a candidate for the biocontrol of pathogens in agriculture. C1 Chonnam Natl Univ, Sch Biol Sci & Technol, Kwangju 500757, South Korea. Chonnam Natl Univ, Biotechnol Res Inst, Kwangju 500757, South Korea. Chonnam Natl Univ, Div Appl Plant Sci, Kwangju 500757, South Korea. Korea Basic Sci Inst, Proteome Anal Team, Taejon, South Korea. US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Chonnam Natl Univ, Div Appl Biosci & Biotechnol, Kwangju 500757, South Korea. RP Chi, YT (reprint author), Chonnam Natl Univ, Sch Biol Sci & Technol, Kwangju 500757, South Korea. EM ytchi@chonnam.chonnam.ac.kr NR 39 TC 96 Z9 122 U1 4 U2 23 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1364-5072 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PY 2004 VL 97 IS 5 BP 942 EP 949 DI 10.1111/j.1365-2672.2004.02356.x PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 861EN UT WOS:000224399000008 PM 15479409 ER PT J AU Ge, H Chuang, YYE Zhao, SP Tong, M Tsai, MH Temenak, JJ Richards, AL Ching, WM AF Ge, H Chuang, YYE Zhao, SP Tong, M Tsai, MH Temenak, JJ Richards, AL Ching, WM TI Comparative genomics of Rickettsia prowazekii Madrid E and Breinl strains SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; CELL-DIVISION; SACCHAROMYCES-CEREVISIAE; EPIDEMIC TYPHUS; CYTOCHROME-C; AGROBACTERIUM-TUMEFACIENS; TRANSCRIPTIONAL ANALYSIS; SEQUENCE-ANALYSIS; SPOTTED-FEVER; ATP SYNTHASE AB Rickeusia prowazekii, the causative agent of epidemic typhus, has been responsible for millions of human deaths. Madrid E is an attenuated strain of R. prowazekii, while Breinl is a virulent strain. The genomic DNA sequence of Madrid E has recently been published. To study the genomic variations between Madrid E (reference) and Breinl (test) DNAs, cohybridization experiments were performed on a DNA microarray containing all 834 protein-coding genes of Madrid E. Of the 834 genes assessed, 24 genes showed 1.5- to 2.0-fold increases in hybridization signals in Breinl DNA compared to Madrid E DNA, indicating the presence of genomic variations in similar to3% of the total genes. Eighteen of these 24 genes are predicted to be involved in different functions. Southern blot analysis of five genes, virB4,ftsK, rfbE, lpx,4, and rpoH, suggested the presence of an additional paralog(s) in BreinI, which might be related to the observed increase in hybridization signals. Studies by real-time reverse transcription-PCR revealed an increase in expression of the above-mentioned five genes and five other genes. In addition to the elevated hybridization signals of 24 genes observed in the Breinl strain, one gene (rp084) showed only 1/10 the hybridization signal of Madrid E. Further analysis of this gene by PCR and sequencing revealed a large deletion flanking the whole rp084 gene and part of the rp083 gene in the virulent Breinl strain. The results of this first rickettsial DNA microarray may provide some important information for the elucidation of pathogenic mechanisms of R. prowazekii. C1 USN, Med Res Ctr, Infect Dis Directorate, Rickettsial Dis Dept, Silver Spring, MD 20910 USA. Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. NCI, NIH, Radiat Oncol Sci Program, Microarray Lab, Gaithersburg, MD 20877 USA. Ctr Biol Evaluat & Res, Food & Drug Adm, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Review, Rockville, MD 20852 USA. RP Ching, WM (reprint author), USN, Med Res Ctr, Infect Dis Directorate, Rickettsial Dis Dept, Silver Spring, MD 20910 USA. EM chingw@nmrc.navy.mil NR 52 TC 26 Z9 27 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JAN PY 2004 VL 186 IS 2 BP 556 EP 565 DI 10.1128/JB.186.2.556-565.2004 PG 10 WC Microbiology SC Microbiology GA 763GP UT WOS:000188066800032 PM 14702324 ER PT J AU Choudhuri, S AF Choudhuri, S TI Microarrays in biology and medicine SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Review DE microarray; genomics; proteomics; glycomics; molecular pathology; RNAi ID LINKED IMMUNOSORBENT ASSAY; GENE-EXPRESSION PATTERNS; CARBOHYDRATE MICROARRAYS; TISSUE MICROARRAYS; QUANTITATIVE ASSAY; PROTEIN; HYBRIDIZATION; VARIANCE; OLIGONUCLEOTIDE; IMMUNOGLOBULIN AB The remarkable speed with which biotechnology has become critical to the practice of life sciences owes much to a series of technological revolutions. Microarray is the latest invention in this ongoing technological revolution. This technology holds the promise to revolutionize the future of biology and medicine unlike any other technology that preceded it. Development of microarray technology has significantly changed the way questions about diseases and/or biological phenomena are addressed. This is because microarrays facilitate monitoring the expression of thousands of genes or proteins in a single experiment. This enormous power of microarrays has enabled scientists to monitor thousands of genes and their products in a given living organism in one experiment, and to understand how these genes function in an orchestrated manner. Obtaining such a global view of life at the molecular level was impossible using conventional molecular biological techniques. However, despite all the progress made in developing this technology, microarray is yet to reach a point where all data are obtained, analyzed, and shared in a standardized fashion. The present article is a brief overview of microarray technologies and their applications with an emphasis on DNA microarray. (c) 2004 Wiley Periodicals, Inc. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Biotechnol, College Pk, MD 20740 USA. US FDA, Ctr Food Safety & Appl Nutr, GRAS Notice Review, College Pk, MD 20740 USA. RP Choudhuri, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Biotechnol, College Pk, MD 20740 USA. EM Supratim.Choudhuri@cfsan.fda.gov NR 42 TC 29 Z9 30 U1 0 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PY 2004 VL 18 IS 4 BP 171 EP 179 DI 10.1002/jbt.20023 PG 9 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 912JR UT WOS:000228074500001 PM 15452887 ER PT J AU Lange, BJ Dinndorf, P Smith, FO Arndt, C Barnard, D Feig, S Feusner, J Seibel, N Weiman, M Aplenc, R Gerbing, R Alonzo, TA AF Lange, BJ Dinndorf, P Smith, FO Arndt, C Barnard, D Feig, S Feusner, J Seibel, N Weiman, M Aplenc, R Gerbing, R Alonzo, TA TI Pilot study of idarubicin-based intensive-timing induction therapy for children with previously untreated acute myeloid leukemia: Children's Cancer Group Study 2941 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; TRIAL COMPARING IDARUBICIN; CANCER-STUDY-GROUP; BONE-MARROW TRANSPLANTATION; BRITISH COOPERATIVE GROUP; CONSOLIDATION CHEMOTHERAPY; RANDOMIZED-TRIAL; ADULT PATIENTS; DAUNORUBICIN; CYTARABINE AB Purpose Randomized comparisons of idarubicin (IDA) with daunorubicin (DNR) show that in adults with acute myeloid leukemia (AML), IDA achieves higher remission rates and longer remission durations. In Children's Cancer Group Pilot Study CCG-2941, we assessed toxicity and feasibility of substituting 4 mg of DNR with 1 mg of IDA in intensive-timing daunorubicin-based induction therapy (DNR/DNR) used in CCG-2891. Patients and Methods On days 1 through 3 and 10 through 14, patients received two courses of dexamethasone, cytarabine, 6-thioguanine, etoposide, and IDA (IDA/IDA). After enrollment of 65 patients, toxicity prompted replacement of IDA with DNR (IDA/DNR) on days 10 through 14 for the remaining 28 patients. Outcomes were compared with those of intensive timing in CCG-2891. Results Treatment-related mortality after two courses of induction was not significantly different among the three regimens: 14% with IDA/IDA, 7% with IDA/DNR, and 9% with DNR/DNR. In course I of CCG-2941 IDA/IDA, 11% of patients withdrew compared with 1.5% in CCG-2891 (P <.001) and 5% in CCG-2941 IDA/DNR (P = not significant). Compared with CCG-2891 DNR/DRN, CCG-2941 IDA/IDA increased days in hospital (43 v36 days; P =.007), mean duration of course I by a week (P =.002), and risk of grade 3 or 4 hyperbilirubinemia (18% v 5%; P =.02). Toxicity of IDA/DNR was not different from that of DNR/DNR in CCG-2891. The mean day 7 marrow blast percentage was 11.4% in CCG-2941 versus 21.1% in CCG-2891 (P =.004). Remission induction, survival, and event-free survival rates were not significantly different from those of CCG-2891. Conclusion In CCG-2941, excessive toxicity and withdrawals outweighed potential benefits of early response with IDA. C1 Childrens Oncol Grp, Arcadia, CA 91066 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. US FDA, Cincinnati, OH USA. Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. Mayo Clin, Rochester, MN USA. Univ Calif Los Angeles, Izaak Walton Killam Hosp Children, Sch Med, Los Angeles, CA USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Childrens Hosp Oakland, Oakland, CA USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Lange, BJ (reprint author), Childrens Oncol Grp, POB 60012, Arcadia, CA 91066 USA. NR 29 TC 23 Z9 24 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 JAN 1 PY 2004 VL 22 IS 1 BP 150 EP 156 DI 10.1200/JCO.2004.04.016 PG 7 WC Oncology SC Oncology GA 760DL UT WOS:000187796300023 PM 14701777 ER PT J AU Wang, SJ Chen, JJ AF Wang, SJ Chen, JJ TI Sample size for identifying differentially expressed genes in microarray experiments SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE standardized effect size; number of arrays; one- and two-sample t-tests; power; replicate ID STATISTICAL-METHODS; REPLICATION; ARRAYS AB Microarray technology allows simultaneous comparison of expression levels of thousands of genes under each condition. This paper concerns sample size calculation in the identification of differentially expressed genes between a control and a treated sample. In a typical experiment, only a fraction of genes (altered genes) is expected to be differentially expressed between two samples. Sample size determination depends on a number of factors including the specified significance level (alpha), the desired statistical power (1 - beta), the fraction (eta) of truly altered genes out of the total g genes studied, and the effect sizes (A) for the altered genes. This paper proposes a method to calculate the number of arrays required to detect at least 100lambda % (where 0 < lambda <= 1) of the truly altered genes under the model of an equal effect size for all altered genes. The required numbers of arrays are tabulated for various values of alpha, beta, Delta, eta, and lambda for the one-sample and two-sample t-tests for g = 10,000. Based on the proposed approach, to identify up to 90% of truly altered genes among the unknown number of truly altered genes, the estimated numbers of arrays needed appear to be manageable. For instance, when the standardized effect size is at least 2.0, the number of arrays needed is less than or equal to 14 for the two-sample t-test and is less than or equal to 10 for the one-sample t-test. As the cost per array declines, such array numbers become practical. The proposed method offers a simple, intuitive, and practical way to determine the number of arrays needed in microarray experiments in which the true correlation structure among the genes under investigation cannot be reasonably assumed. An example dataset is used to illustrate the use of the proposed approach to plan microarray experiments. C1 US FDA, Div Biometr 2, Off Biostat, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Wang, SJ (reprint author), US FDA, Div Biometr 2, Off Biostat, Ctr Drug Evaluat & Res, HFD-715,5600 Fishers Lane, Rockville, MD 20857 USA. EM wangs@cder.fda.gov NR 18 TC 24 Z9 24 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PY 2004 VL 11 IS 4 BP 714 EP 726 PG 13 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 855LL UT WOS:000223974700011 PM 15579240 ER PT J AU Schlesser, J AF Schlesser, J. TI Survival of a five strain cocktail of Escherichia coli O157 : H7 during thermalization and the 60 day aging period of hard cheese made from unpasteurized milk SO JOURNAL OF DAIRY SCIENCE LA English DT Meeting Abstract DE thermalization; Escherichia coli O157 : H7; raw milk cheese C1 [Schlesser, J.] US FDA, NCFST, Summit Argo, IL USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER DAIRY SCIENCE ASSOC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PY 2004 VL 87 SU 1 BP 122 EP 123 PG 2 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA V45UN UT WOS:000203095300491 ER PT J AU Schlesser, J Gerdes, R AF Schlesser, J. Gerdes, R. TI Incidence of Escherichia coli O157 : H7 in raw milk and survival of a five strain cocktail of E. coli O157 : H7 during the 60 days aging period of hard cheese made from unpasteurized milk SO JOURNAL OF DAIRY SCIENCE LA English DT Meeting Abstract DE raw milk cheese; Escherichia coli O157 : 117; E. coli O157 : H7 in raw C1 [Schlesser, J.] NCFST, Food & Drug Adm, Summit Argo, IL USA. [Gerdes, R.] IIT, Chicago, IL 60616 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER DAIRY SCIENCE ASSOC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PY 2004 VL 87 SU 1 BP 383 EP 384 PG 2 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA V45UN UT WOS:000203095301577 ER PT J AU Baumgard, LH Sanders, SR Mendivill, OB Kay, JK Marchello, JA Delmonte, P Griinari, JM Yurawecz, MP AF Baumgard, L. H. Sanders, S. R. Mendivill, O. B. Kay, J. K. Marchello, J. A. Delmonte, P. Griinari, J. M. Yurawecz, M. P. TI Subcutaneous and abdominal fatty acid composition and CLA profiles in grain finished steers SO JOURNAL OF DAIRY SCIENCE LA English DT Meeting Abstract DE beef; CLA; adipose depot C1 [Baumgard, L. H.; Sanders, S. R.; Mendivill, O. B.; Kay, J. K.; Marchello, J. A.] Univ Arizona, Tucson, AZ USA. [Delmonte, P.; Yurawecz, M. P.] US FDA, Washington, DC 20204 USA. [Griinari, J. M.] Univ Helsinki, FIN-00014 Helsinki, Finland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER DAIRY SCIENCE ASSOC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PY 2004 VL 87 SU 1 BP 422 EP 422 PG 1 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA V45UN UT WOS:000203095301731 ER PT J AU Akhtar, S Lee, VH Florence, AT Cho, MJ Yokoyama, M Wickstrom, E Shoji, Y Hughes, J Mrsny, R Akhtar, S AF Akhtar, S Lee, VH Florence, AT Cho, MJ Yokoyama, M Wickstrom, E Shoji, Y Hughes, J Mrsny, R Akhtar, S TI In honour of Professor Rudy Juliano, winner of the 2004 life-time achievement award from the Journal of Drug Targeting SO JOURNAL OF DRUG TARGETING LA English DT Biographical-Item C1 Cardiff Univ, Welsh Sch Pharm, Ctr Genome Based Therapeut, Cardiff CF10 3XF, S Glam, Wales. US FDA, Rockville, MD 20857 USA. Univ London, Sch Pharm, London WC1E 7HU, England. Univ N Carolina, Sch Pharm, Chapel Hill, NC USA. Tokyo Womens Med Univ, Tokyo, Japan. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. St Marianna Univ, Kawasaki, Kanagawa, Japan. Univ Florida, Gainesville, FL 32611 USA. Cardiff Univ, Cardiff, S Glam, Wales. RP Akhtar, S (reprint author), Cardiff Univ, Welsh Sch Pharm, Ctr Genome Based Therapeut, Redwood Bldg,King Edward VII Ave, Cardiff CF10 3XF, S Glam, Wales. EM saghirakhtar@cf.ac.uk RI Lee, Vincent/A-9439-2008 OI Lee, Vincent/0000-0001-7708-6269 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 1061-186X J9 J DRUG TARGET JI J. Drug Target. PY 2004 VL 12 IS 6 BP 309 EP 311 DI 10.1080/10611860400005697 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 858BE UT WOS:000224164300001 PM 15545080 ER PT J AU Stockbridge, N Throckmorton, DC AF Stockbridge, N Throckmorton, DC TI Regulatory advice on evaluation of the proarrhythmic potential of drugs SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article; Proceedings Paper CT 29th Annual ISCE Conference on Research and Technology Transfer in Computerized Elecrocardiology CY APR 27-MAY 02, 2004 CL Hutchinson Isl, FL SP ISCE, Datex-Ohmeda Gems-It, Draeger-Siemens Med Syst, GE Med Syst Inc, Inovise Med Inc, Medtron, Mortara Instrument Inc, NE Montoring Inc, Philips Med Syst, Quinton Instrument Inc, Rozinn Elect Inc, Shiller AG, Welch Allyn - Cardio Control NV, Welch Allyn Inc C1 US FDA, Rockville, MD 20857 USA. RP Stockbridge, N (reprint author), US FDA, 5600 Fishers Lane, Rockville, MD 20857 USA. EM stockbridgen@cder.fda.gov NR 0 TC 9 Z9 9 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PY 2004 VL 37 SU S BP 40 EP 41 DI 10.1016/j.jelectrocard.2003.08.007 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 875XR UT WOS:000225456400006 PM 15534791 ER PT J AU Stockbridge, N Brown, BD AF Stockbridge, N Brown, BD TI Annotated ECG waveform data at FDA SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article; Proceedings Paper CT 29th Annual ISCE Conference on Research and Technology Transfer in Computerized Elecrocardiology CY APR 27-MAY 02, 2004 CL Hutchinson Isl, FL SP ISCE, Datex-Ohmeda Gems-It, Draeger-Siemens Med Syst, GE Med Syst Inc, Inovise Med Inc, Medtron, Mortara Instrument Inc, NE Montoring Inc, Philips Med Syst, Quinton Instrument Inc, Rozinn Elect Inc, Shiller AG, Welch Allyn - Cardio Control NV, Welch Allyn Inc C1 US FDA, Rockville, MD 20857 USA. RP Stockbridge, N (reprint author), US FDA, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PY 2004 VL 37 SU S BP 63 EP 64 DI 10.1016/j.jelectrocard.2004.08.018 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 875XR UT WOS:000225456400012 PM 15534802 ER PT J AU Buckles, D Aguel, F Brockman, R Cheng, J Demian, C Ho, C Jensen, D Mallis, E AF Buckles, D Aguel, F Brockman, R Cheng, J Demian, C Ho, C Jensen, D Mallis, E TI Advances in ambulatory monitoring: Regulatory considerations SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article; Proceedings Paper CT 29th Annual ISCE Conference on Research and Technology Transfer in Computerized Elecrocardiology CY APR 27-MAY 02, 2004 CL Hutchinson Isl, FL SP ISCE, Datex-Ohmeda Gems-It, Draeger-Siemens Med Syst, GE Med Syst Inc, Inovise Med Inc, Medtron, Mortara Instrument Inc, NE Montoring Inc, Philips Med Syst, Quinton Instrument Inc, Rozinn Elect Inc, Shiller AG, Welch Allyn - Cardio Control NV, Welch Allyn Inc DE Holter; ambulatory monitoring; 12-lead ECG; S-T segment analysis; regulatory AB Conventional ambulatory electrocardiogram (ECG) (Holter) monitoring involves 2 or 3 surface leads recorded with electrode positions and signal characteristics that are different from diagnostic quality 12-lead ECGs due to the limitations imposed by technology on the ambulatory recorders. The rapid pace of technological development for medical devices, particularly electrocardiography, has now enabled the recording of diagnostic quality 12-lead ECG waveforms for extended time periods. This capability allows Holter recording to become another source for diagnostic 12-lead ECG records on a par with other modalities Such as resting ECG and exercise stress testing. Additionally, other diagnostic techniques such as S-T segment analysis and Q-T interval analysis that rely on diagnostic quality waveforms can now be applied. All of these enhancements to the traditional Holter modality have altered the regulatory perspective of these devices, since the enhancements may represent a new intended use for the device. C1 US FDA, Cardiac Electrophysiol & Monitoring Branh, Ctr Devices & Radiol Hlth, Dept Hlth & Human Serv, Rockville, MD 20850 USA. RP Mallis, E (reprint author), US FDA, Cardiac Electrophysiol & Monitoring Branh, Ctr Devices & Radiol Hlth, Dept Hlth & Human Serv, HFZ-450,9200 Corp Blvd, Rockville, MD 20850 USA. EM eym@cdrh.fda.gov NR 0 TC 8 Z9 9 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PY 2004 VL 37 SU S BP 65 EP 67 DI 10.1016/j.jelectrocard.2004.08.048 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 875XR UT WOS:000225456400013 PM 15534803 ER PT J AU Muni, NI Ho, C Mallis, E AF Muni, NI Ho, C Mallis, E TI Regulatory issues for computerized electrocardiographic devices SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article; Proceedings Paper CT 29th Annual ISCE Conference on Research and Technology Transfer in Computerized Elecrocardiology CY APR 27-MAY 02, 2004 CL Hutchinson Isl, FL SP ISCE, Datex-Ohmeda Gems-It, Draeger-Siemens Med Syst, GE Med Syst Inc, Inovise Med Inc, Medtron, Mortara Instrument Inc, NE Montoring Inc, Philips Med Syst, Quinton Instrument Inc, Rozinn Elect Inc, Shiller AG, Welch Allyn - Cardio Control NV, Welch Allyn Inc DE FDA; 510(k); ECG; regulation; classification; tool; clinical; claim ID T-WAVE ALTERNANS; RISK STRATIFICATION AB Computerized electrocardiogram (ECG) devices are regulated in the U.S. by the FDA Center for Devices and Radiological Health (CDRH). This article aims to highlight the salient points of the FDA regulatory review process, including the important distinction between a "tool" claim and a clinical" claim in the intended use of a computerized ECG device. Specifically, a tool claim relates to the ability of the device to accurately measure a certain ECG parameter, such as T-wave alternans (TWA), while a clinical claim imputes a particular health hazard associated with the identified parameter, such as increased risk of ventricular tachyarrhythmia or sudden death. Given that both types of claims are equally important and receive the same regulatory scrutiny, the manufacturer of a new ECG diagnostic device should consider the distinction and regulatory pathways for approval between the two types of claims discussed in this paper. C1 US FDA, Dept Hlth & Human Serv, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Muni, NI (reprint author), US FDA, Dept Hlth & Human Serv, Ctr Devices & Radiol Hlth, HFZ-450,9200 Corp Blvd, Rockville, MD 20850 USA. EM neal.muni@fda.hhs.gov NR 3 TC 2 Z9 2 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PY 2004 VL 37 SU S BP 74 EP 77 DI 10.1016/j.jelectrocard.2004.08.021 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 875XR UT WOS:000225456400016 PM 15534806 ER PT J AU Kim, YH Heinze, TM Kim, SJ Cerniglia, CE AF Kim, YH Heinze, TM Kim, SJ Cerniglia, CE TI Adsorption and clay-catalyzed degradation of erythromycin A on homoionic clays SO JOURNAL OF ENVIRONMENTAL QUALITY LA English DT Article ID ANTIBIOTIC-RESISTANCE; ACID DEGRADATION; PHARMACEUTICALS; DECOMPOSITION; MECHANISMS; SORPTION; SOILS AB Erythromycin has been widely used in food-producing animals and in humans, and is frequently detected as an organic pollutant in U.S. streams. In batch experiments with homoionic clays, the Freundlich isotherms were determined at 10 and 25degreesC. The adsorption of erythromycin A was strongly influenced by clay type, exchanged cations, the pH of the bulk solutions, and the acidity of clay surfaces. The formation of clay-erythromycin A complexes was thermodynamically favorable except for K+- and Fe3+-exchanged montmorillonites, since the reactions were exothermic (DeltaHdegrees > 0) and the systems became stable (DeltaSdegrees > 0). Clays catalyzed the erythromycin A degradation by the hydrolysis of the neutral sugar and the multiple dehydrations. The surface acidity of clay surface enhanced the rate of clay-catalyzed degradation of erythromycin A. In addition, the Fe3+-exchanged clay minerals seemed to have an electrostatic interaction with the erythromycin A molecule, by which the hydrolysis of the neutral sugar was influenced. 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 27 TC 25 Z9 28 U1 5 U2 39 PU AMER SOC AGRONOMY PI MADISON PA 677 S SEGOE RD, MADISON, WI 53711 USA SN 0047-2425 J9 J ENVIRON QUAL JI J. Environ. Qual. PD JAN-FEB PY 2004 VL 33 IS 1 BP 257 EP 264 PG 8 WC Environmental Sciences SC Environmental Sciences & Ecology GA 767WP UT WOS:000188497100028 PM 14964380 ER PT J AU Chen, JJZ Kadlubar, FF AF Chen, JJZ Kadlubar, FF TI Mitochondrial mutagenesis and oxidative stress in human prostate cancer SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE mitochondrial DNA; mutation; prostate cancer; oxidative stress ID LASER CAPTURE MICRODISSECTION; DNA MUTATIONS; CARCINOMA-CELLS; HIGH-FREQUENCY; TUMORS; PROGRESSION; POLYMERASE; SEQUENCE; DAMAGE; ADENOCARCINOMA AB Prostate cancer is the most common cancer diagnosed in men in the United States, but the primary cause and the molecular events leading to prostate carcinogenesis are poorly understood. Using the approach of laser capture microdissection, we revealed extensive somatic mitochondrial DNA (mtDNA) mutations in prostatic neoplastic lesions. Inspection of the lesion associated Mutations not only provided new insights into the genetics of prostate cancer, but also revealed new patterns of mtDNA mutation in prostate carcinogenesis. Further analysis on a high frequency of multiple mutational events observed in the same neoplastic lesion revealed an unusually rapid process in mitochondrial mutagenesis, suggesting a new process of mitochondrial hyper-mutagenesis in cancer cells, likely mediated by cellular oxidative stress. Thus, active mitochondrial mutagenesis in prostate cancer suggests a prominent role of increased cellular oxidative stress in neoplastic transformation and the increased susceptibility of neoplastic cells to oxidative damage. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Chen, JJZ (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM jjchen@nctr.fda.gov FU PHS HHS [E07113.01] NR 40 TC 53 Z9 54 U1 0 U2 5 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1059-0501 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PY 2004 VL 22 IS 1 BP 1 EP 12 DI 10.1081/GNC-120037931 PG 12 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 832MA UT WOS:000222270400001 PM 15845219 ER PT J AU Edelson-Mammel, SG Buchanan, RL AF Edelson-Mammel, SG Buchanan, RL TI Thermal inactivation of Enterobacter sakazakii in rehydrated infant formula SO JOURNAL OF FOOD PROTECTION LA English DT Article ID NEONATAL MENINGITIS; POWDERED MILK; BACTEREMIA; CONTAMINATION; INFECTIONS; RESISTANCE; OUTBREAK AB The presence of low levels of Enterobacter sakazakii in dried infant formula have been linked to outbreaks of meningitis, septicemia, and necrotizing enterocolitis in neonates, particularly those who are premature or immunocompromised. In the current study, the ability of 12 strains of E. sakazakii to survive heating in rehydrated infant formula was determined at 58degreesC with a submerged coil apparatus. The observed D-58-values ranged from 30.5 to 591.9 s, with the strains appearing to fall into two distinct heat resistance phenotypes. The z-value of the most heat-resistant strain was 5.6degreesC. When dried infant formula containing this strain was rehydrated with water preequilibrated to various temperatures, a more than 4-log reduction in E sakazakii levels was achieved by preparing the formula with water at 70degreesC or greater. C1 US FDA, Dept Hlth & Human Serv, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Buchanan, RL (reprint author), US FDA, Dept Hlth & Human Serv, Ctr Food Safety & Appl Nutr, 510 Paint Branch Pkwy, College Pk, MD 20740 USA. EM robert.buchanan@cfsan.fda.gov NR 27 TC 80 Z9 84 U1 0 U2 6 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JAN PY 2004 VL 67 IS 1 BP 60 EP 63 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 761XB UT WOS:000187939800009 PM 14717352 ER PT J AU Benner, RA Staruszkiewicz, WF Otwell, WS AF Benner, RA Staruszkiewicz, WF Otwell, WS TI Putrescine, cadaverine, and indole production by bacteria isolated from wild and aquacultured penaeid shrimp stored at 0, 12, 24, and 36 degrees C SO JOURNAL OF FOOD PROTECTION LA English DT Article ID POND-REARED SHRIMP; SHELF-LIFE; CHEMICAL CHARACTERISTICS; DIFFERENT TEMPERATURES; MICROBIAL-FLORA; STORAGE AB Putrescine, cadaverine, and indole production capabilities of bacteria isolated from wild domestic and aquacultured Nicaraguan penaeid shrimp in progressive decomposition states were evaluated. The numbers and types of microorganisms responsible for the production of putrescine, cadaverine, and indole in wild and aquacultured shrimp increased with increasing decomposition temperature and time. Throughout the storage experiments, mean aerobic plate counts (log/g) ranged from 4.5 to 9.7 and 4.5 to 9.0 for domestic and Nicaraguan shrimp, respectively. Vibrio spp. were more prominent in Nicaraguan shrimp (Litopenaeus vannamei) than in domestic shrimp (Litopenaeus setiferus and Litopenaeus brasiliensis). The only amine-producing (putrescine) microorganism isolated from wild and aquacultured shrimp at all temperatures of decomposition (0, 12, 24, and 36degreesC) was Shewanella putrefaciens. On the basis of putrescine production by S. putrefaciens at 0 and 12degreesC and putrescine production by S. putrefaciens, Vibrio spp., and Morganella morganii at 24 and 36degreesC, putrescine should be considered a potential chemical indicator of decomposition in shrimp. C1 US FDA, Off Seafood, Washington Seafood Lab, Laurel, MD 20708 USA. Univ Florida, Dept Food Sci & Human Nutr, Aquat Food Prod Lab, Gainesville, FL 32611 USA. RP Benner, RA (reprint author), US FDA, Off Seafood, Washington Seafood Lab, HFS-426,8501 Muirkirk Rd, Laurel, MD 20708 USA. EM rbenner@cfsan.fda.gov NR 21 TC 11 Z9 12 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 2004 VL 67 IS 1 BP 124 EP 133 PG 10 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 761XB UT WOS:000187939800019 PM 14717362 ER PT J AU Staruszkiewicz, WF Barnett, JD Rogers, PL Benner, RA Wong, LL Cook, J AF Staruszkiewicz, WF Barnett, JD Rogers, PL Benner, RA Wong, LL Cook, J TI Effects of on-board and dockside handling on the formation of biogenic amines in mahimahi (Coryphaena hippurus), skipjack tuna (Katsuwonus pelamis), and yellowfin tuna (Thunnus albacares) SO JOURNAL OF FOOD PROTECTION LA English DT Article ID HISTAMINE FORMATION; ELEVATED-TEMPERATURES; DECOMPOSITION; CADAVERINE; QUALITY; PUTRESCINE; FISH AB Consumer illnesses by scombroid poisonings have been a continuing problem for many years. The intoxications follow the ingestion of fish such as tuna and mahimahi that have undergone bacterial decomposition, leading to the formation of biogenic amines. Research studies have concluded that histamine is one of the indicators of scombrotoxic fish and that other amines, such as cadaverine, could be involved in the illnesses. Guidance for the handling of fish on board fishing vessels to prevent the production of scombrotoxic fish has been limited by a lack of data addressing changes that occur in fish from the water to delivery at dockside. In this study, the changes in selected biogenic amines were determined in mahimahi and tuna, which were captured and held in seawater at 25 to 35degreesC for incubation times up to 18 h. The fillets from the treated fish were sectioned by transverse cuts and analyzed for histamine, cadaverine, and putrescine. Results showed that at 26degreesC, more than 12 h of incubation were required before a histamine concentration of 50 ppm was reached in mahimahi. At 35degreesC, 50 ppm histamine formed within 9 h. Similar results were found for skipjack and yellowfin tuna. Histamine concentrations exceeded 500 ppm within an additional 3 h of incubation in mahimahi. At both temperatures, an increase in the concentration of cadaverine preceded an increase in histamine levels. Changes in putrescine concentrations in the fish were less pronounced. The study also demonstrated that histidine decarboxylase activity was retained in some frozen samples of fish and could result in further increases in histamine on thawing. C1 US FDA, Washington Seafood Lab, Laurel, MD 20708 USA. US FDA, Seattle Reg Lab, Bothell, WA 98021 USA. US FDA, Honolulu, HI 96850 USA. RP Staruszkiewicz, WF (reprint author), US FDA, Washington Seafood Lab, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM wstarusz@cfsan.fda.gov NR 20 TC 25 Z9 26 U1 1 U2 6 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JAN PY 2004 VL 67 IS 1 BP 134 EP 141 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 761XB UT WOS:000187939800020 PM 14717363 ER PT J AU Penteado, AL Eblen, BS Miller, AJ AF Penteado, AL Eblen, BS Miller, AJ TI Evidence of Salmonella internalization into fresh mangos during simulated postharvest insect disinfestation procedures SO JOURNAL OF FOOD PROTECTION LA English DT Article AB A recent U.S. salmonellosis outbreak was epidemiologically associated with consumption of imported fresh mangos. Studies were conducted to simulate the commercial heat disinfestation method used to eliminate tephritid fly larvae from mangos, as well as subsequent product cooling procedures, to assess whether this process promotes internalization of Salmonella into mangos. The experimental parameters were chosen to mimic the disinfestation method used by the South American producer/packer implicated in the recent outbreak. Untreated domestically grown immature and ripened Tommy Atkins variety mangos were immersed in water at 47degreesC for 90 min and then immersed in 21degreesC water containing brilliant blue FD&C no. 1 dye for 10 min. After dye internalization potential was established (67%), the same experiment was performed using 21degreesC water containing 10(7) CFU/ml Salmonella Enteritidis expressing constitutive green fluorescent protein. Fruit was then stored at 10, 20, or 30degreesC for up to 1 week. Immature and ripened mangos were positive for Salmonella internalization at a frequency of 80 and 87%, respectively. Internalization frequency into the stem-end segment (83%) was significantly higher (P < 0.05) than internalization into the middle-side (19%) or blossom-end (9%) segments of the fruit. Salmonella was detected in the mango pulp after 1 week of incubation. The degree of fruit ripeness, posttreatment holding temperature, or duration of storage had no significant effect (P > 0.05) on internalization frequency or survival of Salmonella inside mangos. This study illustrates the high potential for pathogen internalization if heat-disinfested mangos are cooled using contaminated water. C1 Univ Estadual Campinas, Fac Engn Alimentos, Dept Tecnol Alimentos, Sao Paulo, Brazil. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Miller, AJ (reprint author), Univ Estadual Campinas, Fac Engn Alimentos, Dept Tecnol Alimentos, Cidade Univ,Zeferino Vaz Caixa Postal 6121, Sao Paulo, Brazil. EM amiller@cfsan.fda.gov NR 6 TC 47 Z9 50 U1 1 U2 6 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JAN PY 2004 VL 67 IS 1 BP 181 EP 184 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 761XB UT WOS:000187939800028 PM 14717371 ER PT J AU Ferreira, JL Eliasberg, SJ Edmonds, P Harrison, MA AF Ferreira, JL Eliasberg, SJ Edmonds, P Harrison, MA TI Comparison of the mouse bioassay and enzyme-linked immunosorbent assay procedures for the detection of type A botulinal toxin in food SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ELISA AB Samples of chili linked to a foodborne illness outbreak of type A botulism were examined for preformed type A botulinal toxin using two enzyme-linked immunosorbent assay (ELISA) procedures and the mouse bioassay. One of the samples was positive for type A botulinal toxin and three of the samples were negative for type A, B, E, and F botulinal toxins using the three methods. The mouse bioassay indicated that type A toxin was present at the 10,000 minimal lethal dose per gram (MLD per g) of product. The ELISA tests indicated a toxicity of 7,650 MLD per g with one method and 8,350 MLD per g with the other method. The sample toxicity determined by the ELISA was estimated by comparing samples to a standard curve generated with standard type A neurotoxin in casein buffer. The ELISA methods are more rapid than the mouse bioassay, since the toxin type can be determined in I day. The mouse bioassay is more sensitive than the ELISA but usually requires multiple assays to obtain the toxin type and toxicity. Type A culture isolates from the sample were also verified using one ELISA method. C1 US FDA, Atlanta, GA 30309 USA. Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. Univ Georgia, Dept Food Sci & Technol, Athens, GA 30602 USA. RP Ferreira, JL (reprint author), US FDA, 60 8th St NE, Atlanta, GA 30309 USA. EM jfeffeir@ora.fda.gov NR 8 TC 40 Z9 42 U1 1 U2 7 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JAN PY 2004 VL 67 IS 1 BP 203 EP 206 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 761XB UT WOS:000187939800033 PM 14717376 ER PT J AU Lineback, DR AF Lineback, DR TI Globalization and food security - Plenary discussion session 1 SO JOURNAL OF FOOD SCIENCE LA English DT Editorial Material C1 Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Lineback, DR (reprint author), Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA 525 WEST VAN BUREN, STE 1000, CHICAGO, IL 60607-3814 USA SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD JAN-FEB PY 2004 VL 69 IS 1 BP R2 EP R3 PG 2 WC Food Science & Technology SC Food Science & Technology GA 802CR UT WOS:000220142100004 ER PT J AU Argaw, T Colon-Moran, W Wilson, CA AF Argaw, T Colon-Moran, W Wilson, CA TI Limited infection without evidence of replication by porcine endogenous retrovirus in guinea pigs SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID ANTIBODY-DEPENDENT ENHANCEMENT; IN-VIVO; CLINICAL XENOTRANSPLANTATION; VIRUS-INFECTION; GENE-TRANSFER; HUMAN-CELLS; HOST-RANGE; LIVER; TRANSMISSION; TISSUE AB Porcine endogenous retrovirus (PERV) may potentially be transmitted through porcine xenotransplantation products administered to humans. This study examined the feasibility of using guinea pigs as a model to characterize the in vivo infectivity of PERV. To enhance the susceptibility of guinea pigs to retroviral infection or genomic integration, moderate physiological or immunological changes were induced prior to exposing the animals to PERV. Quantitative PERV-specific PCR performed on all tested samples resulted in either undetectable or very low copy numbers of proviruses, even in animals possessing PERV-specific antibody responses. The low copy number of viral DNA detected suggests that PERV infected a limited number of cells. However, PERV DNA levels did not increase over time, suggesting no virus replication occurred. These results in the guinea pig are similar to previous observations of non-human primate cells that allow PERV infection but do not support PERV replication in vitro. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Immunol & Virol, Bethesda, MD 20892 USA. RP Wilson, CA (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Immunol & Virol, 8800 Rockville Pike,HFM-725, Bethesda, MD 20892 USA. EM wilsonc@cber.fda.gov NR 30 TC 16 Z9 18 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD JAN PY 2004 VL 85 BP 15 EP 19 DI 10.1099/vir.0.19495-0 PN 1 PG 5 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 770BT UT WOS:000188703900002 PM 14718614 ER PT J AU Xu, LL Heinze, T Pogge, A Slikker, W Schmued, L AF Xu, LL Heinze, T Pogge, A Slikker, W Schmued, L TI Isolation and characterization of Fluoro-Jade B, a selective histochemical stain for neuronal degeneration SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE fluorescent dye; Fluoro-Jade B components; neuronal degeneration; derivatives of carboxyfluorescein ID LOCALIZATION; FLUORESCEIN; CELLS; PH AB Fluoro-Jade B is a novel fluorescent dye, and since its introduction in 1999 it has been widely used in neuroscience research for selectively staining degenerating neurons in brain tissue sections. However, the chemical composition of Fluoro-Jade B has not been previously resolved. We here report successful separation and identification of eight isomers and structural analogues of Fluoro-Jade B. Two analytical HPLC methods, consisting of a reversed-phase C18 column and a mobile phase with either a pH gradient or an acetonitrile gradient, were developed. A quantitative separation was performed by a semi-preparative reversed phase C-18 HPLC column. Each individual component was characterized by LC/ESI mass spectrometry and NMR spectroscopy. The compounds 5-(6'-hydroxy-3'-oxo-3H-xanthen-9'-yl)benzene-1,2,4-tricarboxylic acid, 2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)-5-(2,4-dihydroxybenzoyl)terephthalic acid, and 4-(6-hydroxy-3-oxo-3H-xanthen-9-yl)-6-(2,4-dihydroxybenzoyl)isophthalic acid represent three new fluorescent compounds discovered in Fluoro-Jade B. They are, presumably, responsible for the dye's ability to detect degenerating neurons. C1 US FDA, Natl Ctr Toxicol Res, USA, Div Neurotoxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, USA, Div Chem, Jefferson, AR 72079 USA. RP Schmued, L (reprint author), US FDA, Natl Ctr Toxicol Res, USA, Div Neurotoxicol, HFT132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM lschmued@nctr.fda.gov NR 22 TC 5 Z9 5 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2004 VL 27 IS 10 BP 1627 EP 1640 DI 10.1081/JLC-120034096 PG 14 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 827WR UT WOS:000221934900012 ER PT J AU Mahmood, I AF Mahmood, I TI Interspecies scaling of protein drugs: Prediction of clearance from animals to humans SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE interspecies scaling; protein drugs; clearance; two versus three species ID ATRIAL-NATRIURETIC-PEPTIDE; ENDOTHELIAL GROWTH-FACTOR; RECOMBINANT FACTOR-IX; DIGOXIN-SPECIFIC FAB; METABOLIC-CLEARANCE; EPOETIN-BETA; FACTOR-VIII; PHARMACOKINETICS; DOGS; ERYTHROPOIETIN AB The objective of this study was to evaluate the interspecies scaling for therapeutic protein drugs to predict the systemic clearance in humans from animal data. This study was undertaken to examine whether the rule of exponents of Mahmood and Balian for the prediction of clearance of nonprotein drugs can also be extended to macromolecules. Three different methods were used to predict clearance in humans: (1) clearance versus body weight (simple allometry), (2) the product of clearance and maximum life-span potential (MLP) versus body weight, and (3) the product of clearance and brain weight versus body weight. Data from 15 therapeutic proteins were analyzed, and the results indicated that the clearance of protein drugs can be predicted accurately using simple allometry or brain weight depending on the exponents of the simple allometry. Furthermore, these 15 drugs were scaled up using two species and the predicted clearance was compared with the predicted clearance obtained from more than two species. It was found that more than two species are needed for a reliable prediction of clearance. (C) 2004 Wiley-Liss, Inc. C1 US FDA, Div Clin Trial Design & Anal, Off Therapeut Res & Review,Ctr Biol Evaluat & Res, Clin Pharmacol & Toxicol Branch HFD579, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Div Clin Trial Design & Anal, Off Therapeut Res & Review,Ctr Biol Evaluat & Res, Clin Pharmacol & Toxicol Branch HFD579, Woodmont Off Ctr 1,Suite 200N,1401 Rockville Pike, Rockville, MD 20852 USA. NR 36 TC 43 Z9 43 U1 0 U2 3 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 2004 VL 93 IS 1 BP 177 EP 185 DI 10.1002/jps.10531 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 758UH UT WOS:000187668400019 PM 14648647 ER PT J AU Wear, KA AF Wear, KA TI Measurement of dependence of backscatter coefficient from cylinders on frequency and diameter using focused transducers - with applications in trabecular bone SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID ULTRASONIC BACKSCATTER; SCATTERING; TISSUES; ECHOES AB A theory for the elastic scattering response from a cylinder insonified by a plane wave was previously derived by Faran. In the present paper, the empirical relationship between Faran's theory and measurements of backscatter coefficient from cylindrical targets using focused transducers is investigated. Experimental measurements of dependence of backscatter coefficient on frequency and diameter for nylon wires are reported. It is found that, under certain conditions (including weak, incoherent scattering), backscatter coefficient measurements from collections of cylindrical scatterers may be meaningfully compared with Faran's model predictions. At low frequencies, the theory and experimental measurements exhibit similar dependences on frequency and diameter, provided that the scatterers are not too densely packed. At higher frequencies, the fine structure of Faran's predictions becomes difficult to reproduce experimentally with a focused transducer. Implications regarding applications to characterization of trabecular bone are discussed. (C) 2004 Acoustical Society of America. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-142,12720 Twinbrook Pkwy, Rockville, MD 20852 USA. EM kaw@cdrh.fda.gov NR 25 TC 30 Z9 30 U1 0 U2 0 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JAN PY 2004 VL 115 IS 1 BP 66 EP 72 DI 10.1121/1.1631943 PG 7 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 765CJ UT WOS:000188249300006 PM 14758996 ER EF