FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Ross, SA McCaffery, PJ Drager, UC De Luca, LM AF Ross, SA McCaffery, PJ Drager, UC De Luca, LM TI Retinoids in embryonal development SO PHYSIOLOGICAL REVIEWS LA English DT Review ID ACID RESPONSE ELEMENT; PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE; FETAL ALCOHOL SYNDROME; CRANIAL NEURAL CREST; VITAMIN-A INTAKE; NORMAL CARDIOVASCULAR DEVELOPMENT; TERATOCARCINOMA STEM-CELLS; HOMEOBOX-CONTAINING GENES; BINDING-PROTEIN CRABP; EARLY MOUSE EMBRYO AB The key role of vitamin A in embryonal development is reviewed. Special emphasis is given to the physiological action of retinoids, as evident from the retinoid ligand knockout models. Retinoid metabolism in embryonic tissues and teratogenic consequences of retinoid administration at high doses are presented. Physiological and pharmacological actions of retinoids are outlined and explained on the basis of their interactions as ligands of the nuclear retinoid receptors. Immediate target genes and the retinoid response elements of their promoters are summarized. The fundamental role of homeobox genes in embryonal development and the actions of retinoids on their expression are discussed. The similarity of the effects of retinoid ligand knockouts to effects of compound retinoid receptor knockouts on embryogenesis is presented. Although much remains to be clarified, the emerging landscape offers exciting views for future research. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Nutr Prod Labeling & Dietary Supplements, Washington, DC 20204 USA. Eunice Kennedy Shriver Ctr Mental Retardat Inc, Waltham, MA 02154 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Ross, SA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Nutr Prod Labeling & Dietary Supplements, Washington, DC 20204 USA. OI Drager, Ursula C/0000-0003-1815-190X NR 321 TC 533 Z9 572 U1 3 U2 35 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0031-9333 J9 PHYSIOL REV JI Physiol. Rev. PD JUL PY 2000 VL 80 IS 3 BP 1021 EP 1054 PG 34 WC Physiology SC Physiology GA 332TE UT WOS:000088088900006 PM 10893430 ER PT J AU Walsh, SL Haberny, KA Bigelow, GE AF Walsh, SL Haberny, KA Bigelow, GE TI Modulation of intravenous cocaine effects by chronic oral cocaine in humans SO PSYCHOPHARMACOLOGY LA English DT Article DE cocaine; oral; human; agonist treatment; laboratory ID ADMINISTERED COCAINE; DEPRESSED-PATIENTS; SQUIRREL-MONKEYS; CROSS-TOLERANCE; RHESUS-MONKEYS; SENSITIZATION; BEHAVIOR; STRESS; PHARMACOTHERAPIES; METHYLPHENIDATE AB Rationale: Agonist therapies have proven effective for the treatment of substance dependence disorders; limited data is available on their feasibility for treating cocaine dependence. Objectives: This laboratory study was designed to test the safety and utility of employing an agonist substitution therapy for the treatment of cocaine dependence in humans. Methods: Oral cocaine served as the agonist treatment and was administered chronically over a range of doses to volunteers with cocaine abuse histories (n=8). Oral capsules were administered daily under blind conditions (q.i.d.) during this 5-week inpatient study using a dose-rising sequence (0 mg 10 days; 25 mg 3 days, 50 mg 3 days, 100 mg 10 days, 0 mg 7 days). During each of these oral dosing periods, an i.v, cocaine challenge (0, 25, and 50 mg, 1 h apart) was administered at least once. Physiological, subjective and pharmacokinetic measures were collected before and after i.v. drug administration; additional measures were collected daily. Results: Oral cocaine produced no subjective effects or signs of toxicity but produced dose-related physiological effects. Significant interactions between oral and i.v. cocaine were observed; cocaine (100 mg, p.o.) significantly decreased responses to the 25-mg but not the 50-mg dose of i.v. cocaine for heart rate, mydriasis, and some subjective measures. There was no evidence of significant additive effects, although heart rate responses to i.v. cocaine were exaggerated during the final wash-out period. Conclusions: These data indicate that treatment with a cocaine "agonist" - in this case oral cocaine - can modestly attenuate the subjective and physiological responses to cocaine in humans under conditions that are safely tolerated. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Behav Pharmacol Res Unit, Baltimore, MD 21224 USA. US FDA, DACCAP, HFD 170, Rockville, MD 20857 USA. RP Walsh, SL (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Behav Pharmacol Res Unit, 5510 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA 05196, DA 07209, N01-DA1-9205] NR 52 TC 38 Z9 38 U1 3 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 2000 VL 150 IS 4 BP 361 EP 373 DI 10.1007/s002130000439 PG 13 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 336WB UT WOS:000088325000002 PM 10958077 ER PT J AU O'Boyle, KP Chen, T Kozlowski, S AF O'Boyle, KP Chen, T Kozlowski, S TI Mucin inhibition of lymphocyte function does not require specific mucin-ligand interactions SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID WISKOTT-ALDRICH SYNDROME; INTERCELLULAR-ADHESION MOLECULE-1; BOVINE SUBMAXILLARY MUCIN; T-CELL ACTIVATION; ANTIGEN RECOGNITION; NEGATIVE REGULATION; CD43 MOLECULE; PROLIFERATION; LEUKOSIALIN; SIALOGLYCOPROTEIN AB Mucins are large highly glycosylated molecules that have been postulated to interfere with certain cell-cell interactions. Steric, charge and specific signalling effects have been postulated for the inhibition by cell-surface mucin molecules. In this report we evaluate the inhibitory effects of bovine submaxillary mucin (BSM), a mucin without specific lymphocyte interactions, on lymphocyte function. BSM inhibits the adhesion of lymphocytes when coimmobilized with intercellular adhesion molecule-1 (ICAM-1) and blocks the activation of T lymphocytes when coimmobilized with anti-CD3. These data demonstrate a general mucin effect on lymphocyte adhesion and activation that is primarily steric in nature and implicates mucins as general barriers to lymphocyte-tumour cell interactions. Mucin blockade of cell-cell interactions may explain why mucinous tumours are often associated with a poor prognosis. C1 US FDA, DMA, CBER, Bethesda, MD 20892 USA. RP Kozlowski, S (reprint author), US FDA, DMA, CBER, 880 Rockville Pike,Bldg 29B-3NN08,HFM-561, Bethesda, MD 20892 USA. NR 37 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD JUL PY 2000 VL 52 IS 1 BP 46 EP 52 PG 7 WC Immunology SC Immunology GA 328GL UT WOS:000087841200007 PM 10886783 ER PT J AU Antony, AC Hansen, DK AF Antony, AC Hansen, DK TI Hypothesis: Folate-responsive neural tube defects and neurocristopathies SO TERATOLOGY LA English DT Article ID METHYLENETETRAHYDROFOLATE REDUCTASE GENE; FOLIC-ACID SUPPLEMENTATION; PERICONCEPTIONAL MULTIVITAMIN SUPPLEMENTATION; CONOTRUNCAL HEART-DEFECTS; RED-BLOOD-CELLS; RISK FACTOR; SPINA-BIFIDA; OROFACIAL CLEFTS; 5,10-METHYLENETETRAHYDROFOLATE REDUCTASE; THERMOLABILE VARIANT AB Background: What accounts for the wide spectrum of folate-responsive dysmorphogeneses? Both embryonic and fetal cells are entirely dependent on maternal folate to support their requirement for precisely timed proliferative bursts during gestation. Folate receptors (FRs) mediate transport into cells and are central to transplacental maternal-to-fetal folate transport. FRs are also critical for neural tube and neural crest development because recent murine "knock-out" and "knock-down" of FRs results in a high percentage of folate-responsive neural tube defects (NTDs) and neurocristopathies. Hypothesis: Central to our hypothesis is the fact that folate deficiency is accompanied by a reduction in the proliferative capacity of highly mitotic neural tube or neural crest cells. Therefore, depending on when In pregnancy various cohorts of highly proliferative cells are deprived of folate, and the origin of the affected cells will determine the type of developmental dysmorphogenesis. Thus, selective folate deficiency in early pregnancy of only highly proliferative neural tube or neural crest cells predisposes to NTDs or gross dysmorphogenesis, respectively. Folate deficiency that compromises placental development will predispose to small-for-date babies due to an overall nutrient deficiency, and the development of folate insufficiency later in pregnancy could predispose to more subtle midline birth defects involving atresia of neural crest cell-derived structures. Finally, a congenital folate transport defect would only be corrected by supra-pharmacological doses of folate, which ensures passive diffusion. Conclusion: This hypothesis can explain the results of several earlier and more recent clinical trials on folate supplementation in pregnancy, but it also raises the possibility that there may be several as yet undiscovered neurocristopathies that are folate responsive. Published 2000 Wiley-Liss, Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Indiana Univ, Sch Med, Div Hematol Oncol, Dept Med, Indianapolis, IN 46202 USA. Richard L Roudebush Vet Affairs Med Ctr, Med Serv, Indianapolis, IN 46202 USA. RP Hansen, DK (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. FU NCI NIH HHS [R01CA58919]; NICHD NIH HHS [R01HD/DK39395] NR 71 TC 40 Z9 40 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0040-3709 J9 TERATOLOGY JI Teratology PD JUL PY 2000 VL 62 IS 1 BP 42 EP 50 DI 10.1002/1096-9926(200007)62:1<42::AID-TERA9>3.3.CO;2-L PG 9 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 330PG UT WOS:000087970000009 PM 10861632 ER PT J AU Wang, C Bammler, TK Guo, YY Kelly, EJ Eaton, DL AF Wang, C Bammler, TK Guo, YY Kelly, EJ Eaton, DL TI Mu-class GSTs are responsible for aflatoxin B-1-8,9-epoxide-conjugating activity in the nonhuman primate Macaca fascicularis liver SO TOXICOLOGICAL SCIENCES LA English DT Article DE aflatoxin; glutathione S-transferase; nonhuman primate; biotransformation; cDNA; mu-class; liver ID GLUTATHIONE-S-TRANSFERASE; HEPATOCELLULAR-CARCINOMA; B-1 EXO-8,9-EPOXIDE; HEPATIC GLUTATHIONE; ISOENZYME ACTIVITY; POLYMORPHIC FORMS; COVALENT BINDING; AZAARENE OXIDES; CHANNEL CATFISH; DIOL EPOXIDES AB Mice are resistant to the carcinogenic effects of the mycotoxin aflatoxin B-1 (AFB(1)) because they constitutively express an alpha-class glutathione S-transferase (mGSTA3-3) that has high (similar to 200,000 pmol/min/mg) activity toward aflatoxin B-1-8,9-epoxide (AFBO). Rats do not constitutively express a GST with high AFBO-conjugating activity and are sensitive to AFB(1)-induced hepatocarcinogenesis. Constitutively expressed human hepatic alpha-class GSTs (hGSTA1-1 and hGSTA2-2) possess little or no AFBO-detoxifying activity ( <2 pmol/min/mg). Recently, we found that the nonhuman primate, Macaca fascicularis (Mf), exhibits significant (similar to 300 pmol/min/mg) constitutive hepatic GST activity towards AFBO. To determine which specific GST isoenzyme(s) is (are) responsible for this activity, MfGSTs were purified from liver tissue and characterized and, Mf mil-class GST cDNAs were cloned by reverse transcriptase-coupled polymerase chain reaction (RT-PCR). Purification by glutathione agarose (GSHA) affinity chromatography yielded a protein, GSHA-GST, that exhibited relatively high AFBO-conjugating activity (239 pmol/min/mg) compared to other GST-containing peaks. Western blotting and enzymatic activity analyses revealed that GSHA-GST belongs to the mu class. Two distinct mu-class GST cDNAs, mfaGSTM1 (GenBank accession # AF200709) and mfaGSTM2 (GenBank: accession # AF200710), were generated by RT-PCR. CDNA-derived amino acid sequence analysis revealed that mfaGSTM1 and mfaGSTM2 share 97% and 96% homology with the human mu-class GSTs hGSM4 and hcSTM2, respectively. In contrast to recombinant mfaGSTM1-1, which had no detectable AFBO-conjugating activity, mfaGSTM2-2 exhibited this activity at 333 pmol/min/mg, Activity profiles for the stereoisomers exo- and endo-AFBO, and of 1-chloro-2,4-dinitrobenzene of the purified protein GSHA-GST and recombinant mfaGSTM2-2, suggested that they are two distinct enzymes. Our results indicate that, in contrast to rodents, mu-class GSTs are responsible for the majority of AFBO-conjugating activity in the liver of Macaca fascicularis. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Washington, Dept Environm Hlth, Seattle, WA 98105 USA. RP Eaton, DL (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Dr,HFT-100, Jefferson, AR 72079 USA. NR 52 TC 15 Z9 18 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUL PY 2000 VL 56 IS 1 BP 26 EP 36 DI 10.1093/toxsci/56.1.26 PG 11 WC Toxicology SC Toxicology GA 330BL UT WOS:000087942900007 PM 10869451 ER PT J AU Smith, GW Constable, PD Eppley, RM Tumbleson, ME Gumprecht, LA Haschek-Hock, WM AF Smith, GW Constable, PD Eppley, RM Tumbleson, ME Gumprecht, LA Haschek-Hock, WM TI Purified fumonisin B-1 decreases cardiovascular function but does not alter pulmonary capillary permeability in swine SO TOXICOLOGICAL SCIENCES LA English DT Article DE fumonisin; cardiovascular; heart failure; pulmonary edema; swine ID FUSARIUM-MONILIFORME; SPHINGOLIPID BIOSYNTHESIS; CORN SCREENINGS; DOSED SWINE; SPHINGOSINE; CELLS; CYTOTOXICITY; INHIBITION; EDEMA; ACID AB Fumonisins are mycotoxins produced by Fusarium verticillioides, which induce acute pulmonary edema in swine. We previously reported that ingestion of fumonisin-containing culture material decreases cardiovascular function in swine (1996,a,b; Fundam. Appl. Toxicol. 31, 169-172; 33, 140-148; 1999, Am. J Vet. Bes. 60, 1291-1300). The main purpose of this study was to confirm that fumonisin B-1 was responsible for the observed cardiovascular changes. Treated pigs (n = 6) were given daily intravenous injections of purified fumonisin B-1 at 1 mg/kg for 4 days, while controls (n = 6) were injected with equal volumes of saline. On day 5, pigs were anesthetized with butorphanol-chloralose and instrumented for hemodynamic studies. Terminally, bronchoalveolar lavage was performed on each pig to determine the relative permeability index of the pulmonary endothelium. Fumonisin B-1-treated pigs had marked decreases in the maximal rate of change of left ventricular pressure (dP/dt(max)), mean aortic pressure, cardiac output, and arterial pO(2), accompanied by increases in mean pulmonary artery pressure, oxygen extraction ratio, and blood hemoglobin concentration. Plasma and left ventricular sphingosine and sphinganine concentrations were markedly increased in treated pigs at day 5; however, there was no difference in the relative permeability index between groups. Serum cholesterol concentrations and activities of hepatic-derived enzymes were increased, and hepatocyte apoptosis and mitoses were present in the livers of fumonisin-treated pigs. In the lungs of treated pigs, there was proteinaceous edema and membranous accumulations in capillary endothelial cells. These results indicate that cardiovascular function is altered by fumonisin B-1, and that fumonisin-induced pulmonary edema is caused by left-sided heart failure and not by altered endothelial permeability. Because of the potential for contamination of human foodstuffs by fumonisins, the cardiovascular toxicity of these compounds must be taken into consideration. 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, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Smith, GW (reprint author), Univ Illinois, Coll Vet Med, Dept Vet Clin Med, 1008 W Hazelwood Dr, Urbana, IL 61802 USA. NR 59 TC 26 Z9 28 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUL PY 2000 VL 56 IS 1 BP 240 EP 249 DI 10.1093/toxsci/56.1.240 PG 10 WC Toxicology SC Toxicology GA 330BL UT WOS:000087942900029 PM 10869473 ER PT J AU Yourick, JJ Bronaugh, RL AF Yourick, JJ Bronaugh, RL TI Percutaneous penetration and metabolism of 2-nitro-p-phenylenediamine in human and fuzzy rat skin SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE 2-nitro-p-phenylenediamine; hair dye; skin absorption; skin metabolism; rat skin; human skin; dermal penetration; intestinal absorption ID NITRO-PARA-PHENYLENEDIAMINE; HAIRLESS GUINEA-PIG; CARCINOGENIC ARYLAMINES; N-HYDROXYARYLAMINE; AROMATIC AMINE; BENZOIC-ACID; BROWN-FK; ABSORPTION; INVITRO; LIVER AB 2-Nitro-p-phenylenediamine (2NPPD) is a dye used in semipermanent and permanent (tinting color) hair dye formulations. National Toxicology Program toxicology and carcinogenesis testing of 2NPPD has raised concerns about its safety. Therefore, we initiated in vitro studies to measure absorption and metabolism of 2NPPD in human and fuzzy rat skin and rat jejunal tissue. Intestinal tissue metabolism of 2NPPD was compared to skin metabolism since toxicology data from oral 2NPPD studies will be used for future safety assessment purposes. Absorption was measured over 24 h by using flow-through diffusion cells with a receptor fluid consisting of Hepes-buffered Hank's balanced salt solution, Dosing vehicles were applied to skin and intestine in the diffusion cells for 30 min. 2NPPD metabolites were determined by high-performance liquid chromatography methodology. In human skin, the percentages of total applied dose absorbed (receptor fluid + skin) over 24 h were 9.2 +/- 5.7 (mean +/- SD) and 9.5 +/- 3.2 for the ethanol and semipermanent vehicles, respectively, with approximately 3% remaining in skin. In rat skin, the percentages of total applied dose absorbed over 24 h were 9.3 +/- 1.2 (mean +/- SE), 6.9 +/- 1.2, and 4.2 +/- 0.1 for the ethanol, semipermanent, and permanent formulation vehicles, respectively, with approximately 3% remaining in skin. In rat intestinal tissue, the percentage of total applied dose absorbed over 24 h was 10.9 +/- 1.2, with approximately 5% remaining in the tissue. In human and rat skin, 2NPPD was metabolized to triaminobenzene and N4-acetyl-2NPPD. 2NPPD was also metabolized to a sulfated 2NPPD metabolite in rat skin, but not in human skin, 2NPPD was extensively metabolized in both human and rat skin with ethanol application; metabolism was not as extensive with a semipermanent formulation application. In rat intestinal tissue, 62% of 2NPPD was metabolized upon absorption to triaminobenzene and N4-acetyl-2NPPD. Differences in the metabolic profiles (proportion of each metabolite formed) were found between the skin and intestinal tissue. These results suggest that 2NPPD is rapidly absorbed and extensively metabolized in both skin and intestinal tissue. The extent of metabolism and the metabolic profile were found to be species-, tissue-, and dosing vehicle-dependent. Metabolism information will be useful in predicting the extent of 2NPPD and/or 2NPPD metabolite systemic absorption relative to a dermal exposure, which will improve the health hazard assessment of 2NPPD. C1 US FDA, Skin Absorpt & Metab Sect, Cosmet Toxicol Branch, Off Cosmet & Colors, Laurel, MD 20708 USA. RP Yourick, JJ (reprint author), US FDA, Skin Absorpt & Metab Sect, Cosmet Toxicol Branch, Off Cosmet & Colors, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM JJY@CFSAN.FDA.GOV NR 40 TC 18 Z9 19 U1 0 U2 7 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 JUL 1 PY 2000 VL 166 IS 1 BP 13 EP 23 DI 10.1006/taap.2000.8962 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 334RP UT WOS:000088199700002 PM 10873714 ER PT J AU Lucas, AD Tomazic-Jezic, VJ AF Lucas, AD Tomazic-Jezic, VJ TI Modification of the Lowry method for analysis of soluble latex proteins SO TOXICOLOGY METHODS LA English DT Article DE allergens; Lowry method; natural rubber latex proteins; protein quantitation ID NATURAL-RUBBER LATEX; SKIN PRICK TEST; ALLERGENS; GLOVES; IDENTIFICATION; ASSAY AB Proteins from natural rubber latex (NRL) can cause local and systemic reactions in people who are allergic to it. Reducing the total protein in NRL products to minimize the allergenic potential requires methods of accurately estimating the amount of protein. Previous work in this laboratory and others has indicated that, of the colorimetric assays, a modified Lowry method performs best. The American Society for Testing Materials (ASTM) has adopted the modified Lowry method for analysis of soluble NRL proteins. This method, although the best currently available, lacks sufficient reproducibility and sensitivity. In an attempt to improve the method, we address in, this article the importance of various extraction conditions and additional approaches to eliminate interfering substances that may cause the false-positive values in the test. Depending on the chemical composition of the accelerants added during manufacturing processes, different means may be employed to remove or to account for the presence of these small organic molecules. The best general way to remove these chemical compounds is the partitioning of the latex extracts with ethyl acetate followed by acid precipitation. Although there is no one perfect method for all NRL proteins and products, the data presented here indicate that changes in the standard protocol of the Lowry method may result in more reproducible and reliable results. C1 US FDA, CDER, Rockville, MD 20852 USA. RP Lucas, AD (reprint author), US FDA, CDER, HFZ 112,12709 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 22 TC 2 Z9 2 U1 3 U2 7 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 1051-7235 J9 TOXICOL METHOD JI Toxicol. Method. PD JUL-SEP PY 2000 VL 10 IS 3 BP 165 EP 179 PG 15 WC Toxicology SC Toxicology GA 350JV UT WOS:000089098300001 ER PT J AU Poli, MA Musser, SM Dickey, RW Eilers, PP Hall, S AF Poli, MA Musser, SM Dickey, RW Eilers, PP Hall, S TI Neurotoxic shellfish poisoning and brevetoxin metabolites: a case study from Florida SO TOXICON LA English DT Article ID ELIMINATION; PBTX-3; RATS AB In June of 1996, three family members were diagnosed as suffering From neurotoxic shellfish poisoning (NSP) as a result of eating shellfish harvested from Sarasota Bay, Florida. Urine from two of these patients and extracts of shellfish collected from the same location were analyzed by radioimmunoassay (RIA) and by receptor binding assay. Activity consistent with brevetoxins was present in both urine and shellfish extracts. High performance liquid chromatographic (HPLC) analysis of shellfish extracts demonstrated multiple fractions recognized by specific anti-brevetoxin antibodies, suggesting metabolic conversion of parent brevetoxins. Affinity-purification of these extracts yielded four major peaks of activity. One peak was identified by HPLC-mass spectroscopy (HPLC-MS) to be PbTx-3, which was likely produced metabolically from the dominant parent toxin PbTx-2. No PbTx-2, however, was detected. Other peaks of activity were determined to consist of compounds of apparent masses of [M + H](+) of 1018, 1034, and 1005. These higher masses are suggestive of conjugated metabolites, but their structures have yet to be determined. The material associated with these latter three peaks were recognized by both RIA and receptor binding assay, but they quantitated differently. This finding suggests that these metabolites react differently in the two assays, and this result may have important implications for seafood safety and regulation. We suggest these metabolites to be the true cause of NSP. and they should be taken into account Juring regulatory testing. Published by Elsevier Science Ltd. C1 USA, Med Res Inst Infect Dis, Toxinol Div, Ft Detrick, MD 21702 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. US FDA, Gulf Coast Res Lab, Dauphin Isl, AL 36528 USA. RP Poli, MA (reprint author), USA, Med Res Inst Infect Dis, Toxinol Div, Ft Detrick, MD 21702 USA. NR 10 TC 93 Z9 97 U1 4 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD JUL PY 2000 VL 38 IS 7 BP 981 EP 993 DI 10.1016/S0041-0101(99)00191-9 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 287UJ UT WOS:000085524600008 PM 10728835 ER PT J AU Hofmann, J Gerstenberger, S Lachmann, I Atreya, CD Liebert, UG AF Hofmann, J Gerstenberger, S Lachmann, I Atreya, CD Liebert, UG TI Rubella virus nonstructural protein 2 is a minor immunogen SO VIRUS RESEARCH LA English DT Article DE rubella; nonstructural protein; immunity; monoclonal antibodies ID MONOCLONAL-ANTIBODIES; STRUCTURAL PROTEINS; CELL EPITOPES; T-CELL; INFECTION; RNA; GENERATION AB The full-length nonstructural protein P90 of rubella virus (RV) was expressed as recombinant protein in Escherichia coli bacteria, as well as in Vero cells. Monoclonal antibodies raised against the protein specifically reacted with the protein in both P90-transfected and RV infected Vero cells. Ninety human sera obtained from reconvalescents, vaccinces and patients with acute RV infection were tested for reactivity against the P90 protein. A weak immune reaction was detected only in a small minority (8%), indicating that P90 is minor immunogen for RV and is not suitable for diagnostic purposes. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Leipzig, Inst Virol, D-04103 Leipzig, Germany. Univ Leipzig, Inst Zool, D-04103 Leipzig, Germany. US FDA, Bethesda, MD 20014 USA. RP Liebert, UG (reprint author), Univ Leipzig, Inst Virol, Johannisallee 30, D-04103 Leipzig, Germany. NR 19 TC 5 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD JUL PY 2000 VL 68 IS 2 BP 155 EP 160 DI 10.1016/S0168-1702(00)00170-2 PG 6 WC Virology SC Virology GA 346YA UT WOS:000088897600007 PM 10958987 ER PT J AU Kapley, A Lampel, K Purohit, HJ AF Kapley, A Lampel, K Purohit, HJ TI Development of duplex PCR for the detection of Salmonella and Vibrio in drinking water SO WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article DE Salmonella; Vibrio; PCR; waterborne pathogens AB We report here a rapid protocol for the detection of Vibrio and Salmonella in drinking water using a duplex PCR reaction. The developed protocol can detect as few as 500 cells in a single reaction, which has been achieved by optimizing the temperature steps and magnesium chloride concentration for the reactions. The described PCR protocol could detect Vibrio and Salmonella spiked in drinking water. C1 Natl Environm Engn Res Inst, Nagpur 440020, Maharashtra, India. US FDA, Washington, DC 20204 USA. RP Purohit, HJ (reprint author), Natl Environm Engn Res Inst, Nagpur 440020, Maharashtra, India. NR 6 TC 18 Z9 18 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0959-3993 J9 WORLD J MICROB BIOT JI World J. Microbiol. Biotechnol. PD JUL PY 2000 VL 16 IS 5 BP 457 EP 458 DI 10.1023/A:1008924119825 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 354YN UT WOS:000089359000010 ER PT J AU Unger, EF Goncalves, L Epstein, SE Chew, EY Trapnell, CB Cannon, RO Quyyumi, AA Stine, A Loscalzo, F Stiber, JA AF Unger, EF Goncalves, L Epstein, SE Chew, EY Trapnell, CB Cannon, RO Quyyumi, AA Stine, A Loscalzo, F Stiber, JA TI Effects at a single intracoronary injection of basic fibroblast growth factor in stable angina pectoris SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; COLLATERAL DEVELOPMENT; MYOCARDIAL-ISCHEMIA; GENE-THERAPY; ANGIOGENESIS; HEART AB We sought to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of basic fibroblast growth factor (bFGF), administered as a single intracoronary injection, to subjects with stable angina pectoris secondary to coronary artery disease. bFGF, on angiogenic growth factor, has been shown to enhance collateral development in animal models of progressive coronary occlusion. To our knowledge, this study represents the initial introduction of parenteral bFGF into humans. This was a phase 1, randomized, dose-escalation trial of bFGF in 25 subjects with coronary artery disease and stable angina. Subjects were randomized 2:1 to a single dose of bFGF or placebo, injected into the left main coronary artery. bFGF doses ranged from 3 to 100 mu g/kg, increasing in half-log increments. bFGF was generally well tolerated at doses of 3 to 30 mu g/kg. Plasma clearance was 20 +/- 2 ml/kg/min, with an elimination half-life of 85 +/- 11 minutes. bFGF caused acute hypotension (approximate to 10%) that did not appear to be dose-related through the dose range studied. Of the 9 subjects who received 30 to 100 mu g/kg bFGF, 2 had sustained hypotension, mild to moderate in severity, lasting 1 to 3 days, and 3 subjects developed bradycardia hours to days after bFGF administration. bFGF dilated epicardial coronary arteries (7.4 +/- 2.5% mean diameter increase, p < 0.02). Transient mild thrombocytopenia and proteinuria were observed in some subjects in the 30-mu g/kg cohort. No subject had signs suggesting systemic angiogenesis. Thus, intracoronary bFGF, at doses of 3 to 30 mu g/kg, was generally well tolerated in subjects with stable angina. (C) 2000 by Excerpta Medico, Inc. C1 US FDA, Ctr Biol Evaluat & Res, Pharmacol Toxicol Branch, Div Clin Trial Design & Anal, Rockville, MD 20852 USA. NEI, NHLBI, Cardiol Branch, NIH, Bethesda, MD USA. RP Unger, EF (reprint author), US FDA, Ctr Biol Evaluat & Res, Pharmacol Toxicol Branch, Div Clin Trial Design & Anal, 1401 Rockville Pike,HFM-576, Rockville, MD 20852 USA. OI Goncalves, Lino/0000-0001-9255-3064 NR 15 TC 93 Z9 99 U1 0 U2 4 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 15 PY 2000 VL 85 IS 12 BP 1414 EP 1419 DI 10.1016/S0002-9149(00)00787-6 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 322KB UT WOS:000087507800004 PM 10856385 ER PT J AU Booth, BP Tabrizi-Fard, MA Fung, HL AF Booth, BP Tabrizi-Fard, MA Fung, HL TI Calcitonin gene-related peptide-dependent vascular relaxation of rat aorta - An additional mechanism for nitroglycerin SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE nitroglycerin; CGRP; vasodilation; nitroxyl anion; hydroxylamine; NO donors ID WHOLE-BLOOD AGGREGATION; NITRIC-OXIDE; SODIUM-NITROPRUSSIDE; GLYCERYL TRINITRATE; ENDOTHELIAL-CELLS; GUANYLATE-CYCLASE; ORGANIC NITRATES; SMOOTH-MUSCLE; SUBSTANCE-P; IN-VIVO AB We investigated the involvement of calcitonin gene-related peptide (CGRP) in the vasodilatory mechanism of action of nitric oxide (NO) donors. The functional role of CGRP in NO donor-induced vasodilation of isolated rat aortic rings was determined by incubating these drugs with and without CGRP(8-37), a selective CGRP receptor antagonist. CGRP(8-37) (0.63 mu M) induced rightward shifts in the vasodilatory concentration-response curves for nitroglycerin (NTG), Piloty's acid (PA), and SIN-1 (linsidomine). The Ec(50) values for NTG, PA, and SIN-1 were increased by 8.3-, 5.2-, and 2.3-fold, respectively (P < 0.05). The release of CGRP from rat aorta in response to NTG and PA was measured specifically by radioimmunoassay. Thirty-minute incubations of NTG or PA with rat aorta induced 189.5 and 214.6% increases, respectively, in CGRP release when compared with the control (P ( 0.05). The concentration-response curves of sodium nitroprusside (SNP), S-nitroso-acetylpenicillamine (SNAP), tetranitromethane (TNM), diethylamine NO complex (DEA-NO), and diethylenetriamine/nitric oxide adduct (DETA NONOate) were not inhibited significantly by CGRP(8-37) co-incubation (P > 0.05). NO donors also were incubated with aortic strips, and NTG and PA alone induced significant formation of hydroxylamine, a NO- metabolite (232.4 and 364.9%, respectively, P < 0.05). These results indicate that only NTG and PA, and to a lesser extent SIN-1, stimulate the release of CGRP from the rat aorta, which subsequently contributes to the vasodilatory activity of these agents. The hydroxylamine formation suggests a possible link between NO- generation and CGRP release from the vascular wall. (C) 2000 Elsevier Science Inc. C1 SUNY Buffalo, Sch Pharm, Dept Pharmaceut, Buffalo, NY 14260 USA. RP Booth, BP (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, HFD-860,WOC II,Rm 2077,5600 Fishers Lane, Rockville, MD 20857 USA. RI fard, masoud/D-4652-2011 FU NHLBI NIH HHS [HL22273] NR 34 TC 50 Z9 58 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUN 15 PY 2000 VL 59 IS 12 BP 1603 EP 1609 DI 10.1016/S0006-2952(00)00290-2 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 314TN UT WOS:000087073800015 PM 10799659 ER PT J AU Hu, YZ Pan, Q Pardali, E Mills, FC Bernstein, RM Max, EE Sideras, P Hammarstrom, L AF Hu, YZ Pan, Q Pardali, E Mills, FC Bernstein, RM Max, EE Sideras, P Hammarstrom, L TI Regulation of germline promoters by the two human Ig heavy chain 3 ' alpha enhancers SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-SWITCH RECOMBINATION; B-CELLS; LOCATED DOWNSTREAM; INTRONIC ENHANCER; LINE TRANSCRIPTS; TRANSGENIC MICE; CONTROL REGION; MESSENGER-RNA; IMMUNOGLOBULIN; GENE AB The human IgH 3' enhancers, located downstream of each of the two Ca genes, modulate germline (GL) transcription of the IgH genes By influencing the activity of promoter-enhancer complexes upstream of the switch and intervening (I) regions, The regulation of GL alpha 1 and alpha 2 promoters by different human 3' enhancer fragments was investigated in cell lines representing various developmental stages. Both alpha 1HS1,2 and alpha 2HS1,2 fragments show equally strong enhancer activity on the GL alpha 1 and alpha 2 promoters in both orientations when transiently transfected into a number of mature B cell line (DG75, CL-01, and HS Sultan). However, there is no activity in a human pre-B cell line (NALM-6) nor a human T cell line (Jurkat), HS3 shows no enhancer activity by itself in any of the cell lines, whereas a modest effect is noted using HS4 in the three mature B cell lines. However, the combination of the alpha 2HS3-HS1,2-HS4 fragments, which together form a potential locus control region, displays a markedly stronger enhancer activity than the individual fragments with a differential effect on the alpha 1 and alpha 2 promoters as compared with the gamma 3 promoter. Our results suggest that the human GL alpha promoter may be regulated by two independent pathways. One pathway is induced by TGF-beta(1) which directs IgA isotype switch through activation of the GL alpha promoter and no TGB-beta(1)-responsive elements are present in the different 3' enhancer fragments. The other route is through the human 3' enhancer regions that cis-up-regulate the GL alpha promoter activity in mature B cells. C1 Huddinge Hosp, Karolinska Inst, Div Clin Immunol, SE-14186 Huddinge, Sweden. Novum, Ctr Oral Biol, Huddinge, Sweden. Umea Univ, Dept Cell & Mol Biol, Umea, Sweden. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Hammarstrom, L (reprint author), Huddinge Hosp, Karolinska Inst, Div Clin Immunol, SE-14186 Huddinge, Sweden. NR 52 TC 21 Z9 21 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2000 VL 164 IS 12 BP 6380 EP 6386 PG 7 WC Immunology SC Immunology GA 322KJ UT WOS:000087508500038 PM 10843693 ER PT J AU Bosio, CM Gardner, D Elkins, KL AF Bosio, CM Gardner, D Elkins, KL TI Infection of B cell-deficient mice with CDC 1551, a clinical isolate of Mycobacterium tuberculosis: Delay in dissemination and development of lung pathology SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PULMONARY TUBERCULOSIS; AVIUM COMPLEX; IFN-GAMMA; T-CELLS; INTERFERON; VIRULENT; GENE; VACCINATION; CHEMOKINES; MECHANISM AB Long-term survival of mice infected with Mycobacterium tuberculosis is dependent upon IFN-gamma and T cells, but events in early phases of the immune response are not well, understood, In this study, we describe a role for B cells during early immune responses to infection with a clinical isolate of M. tuberculosis (CDC 1551), Following a low-dose infection with M. tuberculosis CDC 1551, similar numbers of bacteria were detected in the lungs of both B cell knockout (IgH 6(-), BKO) and C57BL/6J (wild-type) mice. However, despite comparable bacterial loads in the lungs, less severe pulmonary granuloma formation and delayed dissemination of bacteria from lungs to peripheral organs were observed in BKO mice. BKO mice reconstituted with naive B cells, but not those given M, tuberculosis-specific Abs, before infection developed pulmonary granulomas and dissemination patterns similar to wildtype animals. Further analysis of lung cell populations revealed greater numbers of lymphocytes, especially CD8(+) T cells, macrophages, and neutrophils in wild-type and reconstituted mice than in BKO mice. Thus, less severe lesion formation and delayed dissemination of bacteria found in BKO mice were dependent on B cells, not Abs, and were associated with altered cellular infiltrate to the lungs. These observations demonstrate an important, previously unappreciated, role for B cells during early immune responses to M. tuberculosis infections. C1 US FDA, Lab Mycobacteria, Div Bacterial Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NIH, Vet Resource Branch, Comparat Pathol Sect, Rockville, MD 20852 USA. RP Elkins, KL (reprint author), US FDA, Lab Mycobacteria, Div Bacterial Prod, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM431, Rockville, MD 20852 USA. RI Bosio, Catharine/D-7456-2015 NR 30 TC 92 Z9 98 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2000 VL 164 IS 12 BP 6417 EP 6425 PG 9 WC Immunology SC Immunology GA 322KJ UT WOS:000087508500042 PM 10843697 ER PT J AU Bogusz, S Venable, RM Pastor, RW AF Bogusz, S Venable, RM Pastor, RW TI Molecular dynamics simulations of octyl glucoside micelles: Structural properties SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID SODIUM OCTANOATE MICELLE; TRIBLOCK-COPOLYMER MICELLES; BETA-D-GLUCOPYRANOSIDE; DIBLOCK COPOLYMERS; SELECTIVE SOLVENTS; AQUEOUS-SOLUTION; MONTE-CARLO; 3-DIMENSIONAL CRYSTALS; SURFACTANT MICELLES; MEMBRANE-PROTEINS AB Molecular dynamics simulations were used to explore the effect of aggregate size on structural properties of octyl glucoside (OG) micelles. Systems included micelles of 1, 5, 10, 20, 27, 34, 50, and 75 surfactant molecules in water, as well as an OCT bilayer, and neat octane. Micelles consisting of 5 lipids were unstable, while those of 10 or more remained intact (except for rare single lipid escapes) during the 4 ns simulations. Aggregate shape and internal properties (tail length, dihedral angle distributions, and isomerization rates) change little with size. In contrast, surface properties (hydrophobic accessible surface area and headgroup cluster size) vary with size, a consequence of the decreasing surface area-to-volume ratio in larger aggregates. Micelles in the studied size range are nonspherical with rough, uneven surfaces. Their tail lengths are comparable to those in the bilayer and neat octane, indicating that packing into a compact highly curved shape does not significantly distort the tails. Instead, the preference of the tails for an extended conformation may drive the micelle to exhibit a rough surface with large hydrophobic patches. C1 Ctr Biol Evaluat & Res, US FDA, Biophys Lab, Rockville, MD 20852 USA. RP Pastor, RW (reprint author), Ctr Biol Evaluat & Res, US FDA, Biophys Lab, Rockville, MD 20852 USA. NR 64 TC 98 Z9 100 U1 4 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5647 J9 J PHYS CHEM B JI J. Phys. Chem. B PD JUN 15 PY 2000 VL 104 IS 23 BP 5462 EP 5470 DI 10.1021/jp000159y PG 9 WC Chemistry, Physical SC Chemistry GA 327DZ UT WOS:000087779300010 ER PT J AU Maher, JP Worth, JA Arvay, J Raum, K Iampetro, L Welte, JR AF Maher, JP Worth, JA Arvay, J Raum, K Iampetro, L Welte, JR CA CDC TI Scombroid fish poisoning - Pennsylvania, 1998 (Reprinted from MMWR, vol 49, pg 398-400, 2000) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Chester Cty Hlth Dept, W Chester, PA USA. Penn Dept Hlth, Bur Labs, Harrisburg, PA 17108 USA. Natl Ctr Infect Dis, Div Bacterial & Mycot Dis, Atlanta, GA USA. US FDA, Rockville, MD 20857 USA. CDC, Atlanta, GA 30333 USA. RP Maher, JP (reprint author), Chester Cty Hlth Dept, W Chester, PA USA. NR 2 TC 1 Z9 1 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 14 PY 2000 VL 283 IS 22 BP 2927 EP 2927 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 321XL UT WOS:000087480600014 ER PT J AU Jinneman, KC Weagant, SD Johnson, JM Abbott, SL Hill, WE Tenge, BJ Dang, NL Ramsden, R Omiecinski, CJ AF Jinneman, KC Weagant, SD Johnson, JM Abbott, SL Hill, WE Tenge, BJ Dang, NL Ramsden, R Omiecinski, CJ TI A large insertion in the Shiga-like toxin 2 gene (stx(2)) of an Escherichia coli O157 : H7 clinical isolate SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE E. coli O157 : H7; IS 1203; Shiga-like toxin 2 ID FIELD GEL-ELECTROPHORESIS; HEMOLYTIC UREMIC SYNDROME; OUTBREAK; SEROTYPE; SEQUENCE; ASSAY; DNA; IDENTIFICATION; AMPLIFICATION; EPIDEMIOLOGY AB Six clinical Escherichia coli O157:H7 isolates were epidemiologically linked as part of an outbreak in which the most likely source was undercooked ground beef or cross-contamination from the ground beef to other food products at a Mexican-style restaurant. These cultures were analyzed using molecular genetic, immunological and cytotoxicity procedures. All six isolates were confirmed as E. coli O157:H7 and were indistinguishable by pulsed-field gel electrophoresis using XbaI. The results of polymerase chain reaction (PCR) tests, non-isotopic gene probing, reversed passive latex agglutination (RPLA) kit results and Vero cell assays were consistent for the presence of a functional Shiga-like toxin 1 (Stx 1) protein. All six strains produced a stx(2) PCR amplicon product; five strains produced a product which was consistent with the predicted amplicon size and one (SEA 6414) produced a much larger PCR product. The SEA 6414 isolate produced a protein reactive with the RPLA kit anti-Stx 2 antibody but was not cytotoxic to Vero cells. Sequencing of this region revealed that this 1310 bp insertion was very similar to a previously identified IS 1203 sequence and the insertion interrupted the carboxyl end of the coding region of the stx(2) gene 'A' subunit. Published by Elsevier Science B.V. C1 US FDA, Seafood Prod Res Ctr, Bothell, WA 98021 USA. US FDA, Seattle Dist Lab, Bothell, WA 98021 USA. Calif Dept Hlth Serv, Microbial Dis Lab, Div Communicable Dis Control, Berkeley, CA 94704 USA. Univ Washington, Dept Environm Hlth, Seattle, WA 98105 USA. RP Jinneman, KC (reprint author), US FDA, Seafood Prod Res Ctr, Bothell, WA 98021 USA. NR 34 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD JUN 10 PY 2000 VL 57 IS 1-2 BP 115 EP 124 DI 10.1016/S0168-1605(00)00237-3 PG 10 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 323EM UT WOS:000087552200012 ER PT J AU Lawrence, SM Huddleston, KA Pitts, LR Nguyen, N Lee, YC Vann, WF Coleman, TA Betenbaugh, MJ AF Lawrence, SM Huddleston, KA Pitts, LR Nguyen, N Lee, YC Vann, WF Coleman, TA Betenbaugh, MJ TI Cloning and expression of the human N-acetylneuraminic acid phosphate synthase gene with 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid biosynthetic ability SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-ADHESION MOLECULE; ESCHERICHIA-COLI; SIALIC ACIDS; 2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE; LIQUID-CHROMATOGRAPHY; ELEVATED EXPRESSION; INSECT CELLS; SYNTHETASE; GLYCOSYLATION; PURIFICATION AB Sialic acids participate in many important biological recognition events, yet eukaryotic sialic acid biosynthetic genes are not well characterized. In this study, we have identified a novel human gene based on homology to the Escherichia coli sialic acid synthase gene (neuB), The human gene is ubiquitously expressed and encodes a 40-kDa enzyme. The gene partially restores sialic acid synthase activity in a neuB-negative mutant of E. coli and results in N-acetylneuraminic acid (Neu5Ac) and 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN) production in insect cells upon recombinant baculovirus infection. In vitro the human enzyme uses N-acetylmannosamine 6-phosphate and mannose 6-phosphate as substrates to generate phosphorylated forms of Neu5Ac and KDN, respectively, but exhibits much higher activity toward the Neu5Ac phosphate product. C1 Johns Hopkins Univ, Dept Chem Engn, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. US FDA, Lab Bacterial Toxins, Bethesda, MD 20892 USA. US FDA, Lab Bacterial Polysaccharides, Bethesda, MD 20892 USA. Human Genome Sci, Prot Dev, Rockville, MD 20850 USA. RP Betenbaugh, MJ (reprint author), Johns Hopkins Univ, Dept Chem Engn, Baltimore, MD 21218 USA. EM beten@jhu.edu RI Betenbaugh, Michael J./A-3252-2010 OI Betenbaugh, Michael J./0000-0002-6336-4659 NR 34 TC 69 Z9 70 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 9 PY 2000 VL 275 IS 23 BP 17869 EP 17877 DI 10.1074/jbc.M000217200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 321ZJ UT WOS:000087485000091 PM 10749855 ER PT J AU Hay, A Gust, I Hampson, A Nerome, K Tashiro, M Canas, L Lavanchay, D Levandowski, R AF Hay, A Gust, I Hampson, A Nerome, K Tashiro, M Canas, L Lavanchay, D Levandowski, R CA CDC TI Update: Influenza activity - United States and worldwide, 1999-2000 season, and composition of the 2000-2001 influenza vaccine (Reprinted from MMWR, vol 49, pg 375-381, 2000) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Natl Med Inst Med Res, WHO, Collaborating Ctr Reference & Res Influenza, London, England. WHO, Collaborating Ctr Reference & Res Influenza, Parkville, Vic, Australia. Natl Inst Infect Dis, WHO, Collaborating Ctr Reference & Res Influenza, Tokyo, Japan. Armstrong Lab, Brooks AFB, TX 78235 USA. WHO, Natl Influenza Ctr, Div Emerging & Other Communicable Dis Surveillanc, Geneva, Switzerland. WHO, Natl Resp Enter Virus Surveillance Syst Collabora, Sentinel Phys Influenza Surveillance Syst, Geneva, Switzerland. US FDA, Div Virol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Natl Ctr Infect Dis, Div Viral & Rickettsial Dis, Influenza Br, WHO Collaborating Ctr Reference & Res Influenza, Atlanta, GA USA. CDC, Atlanta, GA 30333 USA. RP Hay, A (reprint author), Natl Med Inst Med Res, WHO, Collaborating Ctr Reference & Res Influenza, London, England. NR 3 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 7 PY 2000 VL 283 IS 21 BP 2781 EP 2782 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 320BQ UT WOS:000087381500013 ER PT J AU Do Luu, HM Hutter, JC AF Do Luu, HM Hutter, JC TI Pharmacokinetic modeling of 4,4 '-methylenedianiline released from reused polyurethane dialyzer potting materials SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article DE polyurethane; hemodialyzer; reuse; PBPK model; 4,4 '-methylenedianiline ID HEMOGLOBIN ADDUCTS; DIISOCYANATE; EXPOSURE; URINE; METABOLITES; INHALATION; PRODUCTS; RATS AB 4, 4'-Methylenedianiline (MDA) is a hydrolysis degradation product that can be released from polyurethanes commonly used in medical device applications. MDA is mutagenic and carcinogenic in animals. In humans, it is hepatotoxic, a known contact and respiratory allergen, and a suspected carcinogen. A physiologically based pharmacokinetic (PBPK) model was developed to estimate the absorption, distribution, metabolism, and excretion of MDA in patients exposed to MDA leached from the potting materials of hemodialyzers. A worst-case reuse situation and a single use case were investigated. The PBPK model included five tissue compartments: liver, kidney, gastrointestinal tract, slowly perfused tissues, and richly perfused tissues. Physiological and chemical parameters of a healthy individual used in the model were obtained from the literature. The model was calibrated using previously published kinetic studies of IV administered doses of(14) C-MDA to rats. The model was validated using independent data published for MDA-exposed workers. The PBPK results indicated that dialysis patients who are exposed to MDA released from dialyzers (new or reused) could accumulate low levels of MDA and metabolites (total MDA) over time. (C) 2000 John Wiley & Sons, Inc. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20852 USA. RP Do Luu, HM (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, HFZ-150,12725 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 24 TC 7 Z9 7 U1 1 U2 4 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD JUN 5 PY 2000 VL 53 IS 3 BP 276 EP 286 DI 10.1002/(SICI)1097-4636(2000)53:3<276::AID-JBM13>3.0.CO;2-E PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 318AF UT WOS:000087260600013 PM 10813768 ER PT J AU Leef, M Elkins, KL Barbic, J Shahin, RD AF Leef, M Elkins, KL Barbic, J Shahin, RD TI Protective immunity to Bordetella pertussis requires both B cells and CD4(+) T cells for key functions other than specific antibody production SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE pertussis; immunization; protective immunity; B cell; T cell ID RESPIRATORY-INFECTION; MEDIATED-IMMUNITY; MONOCLONAL-ANTIBODIES; GAMMA-INTERFERON; CONTROLLED TRIAL; VACCINE; MICE; LYMPHOCYTES; TOXIN; MOUSE AB To investigate the fundamental nature of protective immunity to Bordetella pertussis, we studied intranasal immunization of adult mice with formalin-fixed B. pertussis (FFBP), followed by aerosol B. pertussis challenge. Mice given two doses of FFBP intranasally completely cleared a subsequent pertussis aerosol challenge from tracheae and lungs (defined as protection), but there was no correlation between levels of specific antibody and clearance of bacteria. Further, transfer of immune serum before aerosol challenge had minimal effects on bacterial burdens. However, pertussis-specific T cells producing interferon gamma but not interleukin 4 or interleukin 10 were detected in draining lymph nodes of FFBP-immunized mice. Significantly, repeated immunization of B cell knockout (BKO) mice resulted in partial protection, and complete protect ion was reconstituted by transfer of pertussis-immune B cells; reconstituted BKO mice had little ii any detectable antipertussis antibodies. Immunization of mice lacking all T cells or lacking CD4(+) T cells did trot lead to protection; in contrast, CD8(-) mice were protected. Mice depleted of CD4(+) T cells after immunization but before aerosol challenge, which thus had normal amounts of specific antibodies, were not optimally protected. Taken together, these data indicate that protective immunity to pertussis is dependent on both CD4(+) T cells and B cells, and both cell types provide significant functions other than specific antibody production. C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, Lab Mycobacteria, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, Lab Pertussis, Rockville, MD 20852 USA. RP Elkins, KL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, Lab Mycobacteria, 1401 Rockville Pike,HFM 431, Rockville, MD 20852 USA. NR 37 TC 81 Z9 82 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 5 PY 2000 VL 191 IS 11 BP 1841 EP 1852 DI 10.1084/jem.191.11.1841 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 322UL UT WOS:000087527300004 PM 10839801 ER PT J AU Castellino, F Boucher, PE Eichelberg, K Mayhew, M Rothman, JE Houghton, AN Germain, RN AF Castellino, F Boucher, PE Eichelberg, K Mayhew, M Rothman, JE Houghton, AN Germain, RN TI Receptor-mediated uptake of antigen/heat shock protein complexes results in major histocompatibility complex class I antigen presentation via two distinct processing pathways SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE immunology; vaccines; macrophages; T cells; peptides ID MHC CLASS-I; EXOGENOUS ANTIGENS; PRESENTING CELLS; DENDRITIC CELLS; PEPTIDE-BINDING; B-CELLS; T-CELLS; MOLECULES; EXPRESSION; LYMPHOCYTES AB Heat shock proteins (HSPs) derived from tumors or virally infected cells carl stimulate antigen-specific CD8(+) T cell responses in vitro and in vivo. Although this antigenicity is known to arise from HSP-associated peptides presented to the immune system by major histocompatibility complex (MHC) class I molecules, the cell biology underlying this presentation process remains poorly understood. Here we show that HSP 70 binds to the surface of antigen presenting cells by a mechanism with the characteristics of a saturable receptor system. Alter this membrane interaction processing and MHC class I presentation of the HSP-associated antigen can occur via either a cytosolic (transporter associated with antigen processing [TAP] and proteasome-dependent) or an endosomal (TAP and proteasome-independent) route, with the preferred pathway determined by the sequence context of the optimal antigenic peptide within the HSP-associatsd material. These findings not only characterize two highly efficient, specific pathways leading to the conversion of HSP-associated antigens into ligands for CD8(+) T cells, they also imply the existence of a mechanism for receptor-facilitated transmembrane transport of HSP or HSP-associated ligands from the plasma membrane or lumen of endosomes into the cytosol. C1 NIAID, Lymphocyte Biol Sect, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10021 USA. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, NIH, Bldg 10,Rm 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. NR 49 TC 305 Z9 330 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 5 PY 2000 VL 191 IS 11 BP 1957 EP 1964 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 322UL UT WOS:000087527300013 PM 10839810 ER PT J AU Loveys, DA Kulkarni, S Atreya, PL AF Loveys, DA Kulkarni, S Atreya, PL TI Role of type IIFNs in the in vitro attenuation of live, temperature-sensitive vaccine strains of human respiratory syncytial virus SO VIROLOGY LA English DT Article ID MOUSE SPLEEN-CELLS; INTERFERON MESSENGER-RNA; SUBGROUP-B; ANTIGENIC RELATEDNESS; INTERLEUKIN-4 IL-4; INDUCE INTERFERON; GAMMA-INTERFERON; EPITHELIAL-CELLS; G-GLYCOPROTEIN; MEASLES-VIRUS AB The contributions of type I interferons (IFNs) to the in vitro attenuation of three temperature-sensitive (Ts) subgroup A and one subgroup B deletion mutant RSV strains were evaluated. The ability of these vaccine viruses to induce IFNs at their permissive and restrictive temperatures and their sensitivity to the antiviral effects of exogenous I IFNs were tested in human lung epithelial A549 cells. Our results show that the highly attenuated and immunogenic subgroup A vaccine strain Ts1C produced higher levels of IFN-beta than its parent RSS-2 or two related strains, Ts1A and Ts1B, at their permissive temperature. Growth of RSV-infected A549 cultures at restrictive temperatures or prior UV inactivation of the virus abolished the observed induction of IFN-beta, suggesting a strict requirement of viral replication for cellular IFN induction. The enhanced induction of IFN-beta by the highly immunogenic Ts1C at permissive temperature may be an advantageous characteristic of a live intranasal vaccine candidate. The subgroup B strain RSV B1 and its mutant cp-52 (with SH and G gene deletions) both Induced similar but low levels of IFN-beta. Hence the observed overattenuation of cp-52 in human infants is probably not due to enhanced IFN induction during its replication in the host. The ability of cp-52, which does not express the SH and G proteins, to induce IFN-beta levels similar to those of its parent strain suggests that these viral proteins may not have a role in the induction of IFN-beta in the host. In addition, both subgroup A and B mutants and their respective parent strains were similarly resistant to the antiviral effects of exogenous IFN-alpha or -beta. Therefore, increased sensitivity of the mutants to IFNs does not seem to contribute to their attenuation. (C) 2000 Academic Press. C1 US FDA, Lab Pediat & Resp Viral Dis, DVP, CBER, Bethesda, MD 20892 USA. RP Atreya, PL (reprint author), US FDA, Lab Pediat & Resp Viral Dis, DVP, CBER, HFM-445,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 52 TC 4 Z9 5 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 5 PY 2000 VL 271 IS 2 BP 390 EP 400 DI 10.1006/viro.2000.0290 PG 11 WC Virology SC Virology GA 323KR UT WOS:000087565000020 PM 10860892 ER PT J AU Schwartz, PJ Rosenthal, NE Kajimura, N Han, L Turner, EH Bender, C Wehr, TA AF Schwartz, PJ Rosenthal, NE Kajimura, N Han, L Turner, EH Bender, C Wehr, TA TI Ultradian oscillations in cranial thermoregulation and electroencephalographic slow-wave activity during sleep are abnormal in humans with annual winter depression SO BRAIN RESEARCH LA English DT Article DE seasonal affective disorder; body temperature; sleep; circadian rhythm; ultradian rhythm; EEG ID SEASONAL AFFECTIVE-DISORDER; EEG POWER-DENSITY; BLOOD-FLOW; BODY TEMPERATURES; LIGHT TREATMENT; REM-SLEEP; AMBIENT-TEMPERATURES; CIRCADIAN PACEMAKER; CORE TEMPERATURE; SYRIAN-HAMSTERS AB The level of core body, and presumably brain temperature during sleep varies with clinical state in patients with seasonal affective disorder (SAD), becoming elevated during winter depression and lowered during clinical remission induced by either light treatment or summer. During sleep, brain temperatures are in part determined by the level of brain cooling activity, which may be reflected by facial skin temperatures. In many animals, the level of brain cooling activity oscillates across the NREM-REM sleep cycle. Facial skin temperatures during sleep in patients with winter depression are abnormally low and uncorrelated with octal temperatures, although their relationship to EEG-defined sleep stages remains unknown. We therefore measured the sleep EEG, fore body and facial skin temperatures in 23 patients with winter depression and 23 healthy controls, and tested the hypothesis that ultradian oscillations in facial skin temperatures exist in humans and are abnormal in patients with winter depression. We found that facial skin temperatures oscillated significantly across the NREM-REM sleep cycle, and were again significantly lower and uncorrelated with rectal temperatures in patients with winter depression Mean slow-wave activity and NREM episode duration were significantly greater in patients with winter depression, whereas the intraepisodic dynamics of stow-wave activity were normal in patients with winter depression. These results suggest that brain cooling activity oscillates in an ultradian manner during sleep in humans and is reduced during winter depression, and provide additional support for the hypothesis that brain temperatures are elevated during winter depression. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH USA. Vet Affairs Med Ctr, Cincinnati, OH 45267 USA. NIMH, Sect Biol Rhythms, Bethesda, MD 20892 USA. Natl Ctr Hosp Mental Nervous & Muscular Disorders, Tokyo, Japan. McGill Univ, Montreal, PQ, Canada. US FDA, Rockville, MD 20857 USA. RP Schwartz, PJ (reprint author), 3429 Cornell Pl, Cincinnati, OH 45220 USA. EM pjs4@ix.netcom.com RI Turner, Erick/A-4848-2008 OI Turner, Erick/0000-0002-3522-3357 NR 87 TC 15 Z9 16 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 2 PY 2000 VL 866 IS 1-2 BP 152 EP 167 DI 10.1016/S0006-8993(00)02271-X PG 16 WC Neurosciences SC Neurosciences & Neurology GA 320JX UT WOS:000087399000017 PM 10825491 ER PT J AU Wilkes, JG Conte, ED Kim, Y Holcomb, M Sutherland, JB Miller, DW AF Wilkes, JG Conte, ED Kim, Y Holcomb, M Sutherland, JB Miller, DW TI Sample preparation for the analysis of flavors and off-flavors in foods SO JOURNAL OF CHROMATOGRAPHY A LA English DT Review DE sample preparation; food analysis; aroma compounds; off-flavor compounds; reviews ID LIQUID-CHROMATOGRAPHIC DETERMINATION; SOLID-PHASE MICROEXTRACTION; SUPERCRITICAL-FLUID EXTRACTION; CATFISH ICTALURUS-PUNCTATUS; CAPILLARY GAS-CHROMATOGRAPHY; BIOGENIC-AMINE CONTENT; LACTIC-ACID BACTERIA; ORANGE JUICE; CHANNEL CATFISH; QUANTITATIVE-ANALYSIS AB Off-flavors in foods may originate from environmental pollutants, the growth of microorganisms, oxidation of Lipids, or endogenous enzymatic decomposition in the foods. The chromatographic analysis of flavors and off-flavors in foods usually requires that the samples first be processed to remove as many interfering compounds as possible. For analysis of foods by gas chromatography (GC), sample preparation may include mincing, homogenation, centrifugation, distillation, simple solvent extraction, supercritical fluid extraction, pressurized-fluid extraction, microwave-assisted extraction, Soxhlet extraction, or methylation. For high-performance liquid chromatography of amines in fish, cheese, sausage and olive oil or aldehydes in fruit juice, sample preparation may include solvent extraction and derivatization. Headspace GC analysis of orange juice, fish, dehydrated potatoes, and milk requires almost no sample preparation. Purge-and-trap GC analysis of dairy products, seafoods, and garlic may require heating, microwave-mediated distillation, purging the sample with inert gases and trapping the analytes with Tenax or C(18), thermal desorption, cryofocusing, or elution with ethyl acetate. Solid-phase microextraction GC analysis of spices, milk and fish can involve microwave-mediated distillation, and usually requires adsorption on poly(dimethyl)siloxane or electrodeposition on fibers followed by thermal desorption. For short-path thermal desorption GC analysis of spices, herbs, coffee, peanuts, candy, mushrooms, beverages, olive oil, honey, and milk, samples are placed in a glass-lined stainless steel thermal desorption tube, which is purged with helium and then heated gradually to desorb the volatiles for analysis. Few of the methods that are available for analysis of food flavors and off-flavors can be described simultaneously as cheap, easy and good. (C) 2000 Published by Elsevier Science B.V. C1 US FDA, Natl Ctr Toxicol Res, Dept Hlth & Human Serv, Div Chem,Mass Spectrometry Branch, Jefferson, AR 72079 USA. RP Wilkes, JG (reprint author), US FDA, Natl Ctr Toxicol Res, Dept Hlth & Human Serv, Div Chem,Mass Spectrometry Branch, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 149 TC 113 Z9 118 U1 17 U2 146 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUN 2 PY 2000 VL 880 IS 1-2 BP 3 EP 33 DI 10.1016/S0021-9673(00)00318-6 PG 31 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 324ED UT WOS:000087608100002 PM 10890508 ER PT J AU Ross, S AF Ross, S TI Functional foods: the Food and Drug Administration perspective SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT 17th Ross Research Conference on Medical Issues CY FEB 22-24, 1998 CL SAN DIEGO, CALIFORNIA SP Ross Prod Div, Abbott Lab Inc DE functional food; Food and Drug Administration; FDA; dietary supplement; medical food; product labeling AB Because the Federal Food, Drug, and Cosmetic Act (FFDCA) does not provide a statutory definition of functional foods, the Food and Drug Administration has no authority to establish a formal regulatory category for such foods. The primary determinant of the regulatory status of a food is its intended use, which is determined largely by the label and labeling information accompanying the product. This information includes nutrient information, nutrient content claims, and various types of health claims. In marketing these foods, manufacturers may come under one of several existing regulatory options. The first decision manufacturers will make that will help determine their product's regulatory status is whether the product is a food or a drug. Thus, manufacturers and retailers have a range of legal and regulatory categories in which their products may be classified. This article describes the definitions provided in the FFDCA for a drug and a food, the safety and labeling requirements of various food categories, and types of possible claims for dietary supplements. C1 US FDA, CFSAN, Off Special Nutr, Washington, DC 20204 USA. RP Ross, S (reprint author), US FDA, CFSAN, Off Special Nutr, HFS 465,200 C St SW, Washington, DC 20204 USA. NR 11 TC 28 Z9 28 U1 1 U2 4 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 JUN PY 2000 VL 71 IS 6 SU S BP 1735S EP 1738S PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 321NW UT WOS:000087462400023 PM 10837331 ER PT J AU Weisburger, JH Roberfroid, MB Dwyer, J Harper Fernstrom, JD Hathcock, JN Ross, S Milner, JA AF Weisburger, JH Roberfroid, MB Dwyer, J Harper Fernstrom, JD Hathcock, JN Ross, S Milner, JA TI Physiologically active food components: Their role in optimizing health and aging - Discussion 8 SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material C1 Amer Hlth Fdn, New York, NY 10017 USA. Univ Catholique Louvain, Dept Pharmaceut Sci, B-1200 Brussels, Belgium. Tufts Univ, New England Med Ctr Hosp, Sch Med, Boston, MA 02111 USA. Tufts Univ, New England Med Ctr Hosp, Sch Nutr, Boston, MA 02111 USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Council Responsible Nutr, Washington, DC USA. Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Special Nutr, Washington, DC 20204 USA. RP Weisburger, JH (reprint author), Amer Hlth Fdn, New York, NY 10017 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2000 VL 71 IS 6 SU S BP 1739S EP 1740S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 321NW UT WOS:000087462400024 ER PT J AU Honda, K Kanegane, H Eguchi, M Kimura, H Morishima, T Masaki, K Tosato, G Miyawaki, T Ishii, E AF Honda, K Kanegane, H Eguchi, M Kimura, H Morishima, T Masaki, K Tosato, G Miyawaki, T Ishii, E TI Large deletion of the X-linked lymphoproliferative disease gene detected by fluorescence in situ hybridization SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE X-linked lymphoproliferative disease; SAP gene; gene deletion; fluorescence in situ hybridization ID BONE-MARROW TRANSPLANTATION; ENCODING GENE; FAMILIES; INFECTION; MUTATIONS; CELLS; XQ25; XLP AB The X-linked lymphoproliferative disease (XLP) is an inherited immunodeficiency characterized by an abnormal responses to infection with Epstein-Barr virus (EBV), resulting in fatal infectious mononucleosis, hypogammaglobulinemia, virus-associated hemophagocytic syndrome, and malignant lymphoma. Mutations in the gene coding for a T cell-specific SLAM-associated protein (SAP) have been recently identified in XLP patients. We report on a 1-year-old boy representing fulminant hemophagocytic syndrome. He developed high fever, lymphadenopathy, hepatosplenomegaly with liver dysfunction, and pancytopenia with marrow hemophagocytosis, EBV DNA was abnormally increased in the blood. Polymerase chain reaction failed to amplify SAP mRNA and genomic DNA products from the patient's peripheral blood. A large deletion of the SAP gene was confirmed by fluorescence in situ hybridization (FISH), FISH analysis also disclosed that the patient's mother was a carrier. We conclude that FISH can be useful in the diagnosis of XLP with large deletions of the SAP gene and its carrier state. Am. J, Hematol, 64: 128-132, 2000, (C) 2000 Wiley-Liss. Inc. C1 Hamanoumachi Hosp, Div Pediat, Chuo Ku, Fukuoka 8108539, Japan. Toyama Med & Pharmaceut Univ, Fac Med, Dept Pediat, Toyama, Japan. Hiroshima Univ, Res Inst Radiat Biol & Med, Hiroshima, Japan. Nagoya Univ, Sch Med, Dept Pediat, Nagoya, Aichi 466, Japan. Nagoya Univ, Sch Med, Dept Hlth Sci, Nagoya, Aichi 466, Japan. Chidoribashi Hosp, Div Pediat, Fukuoka, Japan. US FDA, Div Hematol Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Ishii, E (reprint author), Hamanoumachi Hosp, Div Pediat, Chuo Ku, 3-5-27 Maizuru, Fukuoka 8108539, Japan. RI Kimura, Hiroshi/I-2246-2012 NR 20 TC 9 Z9 9 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2000 VL 64 IS 2 BP 128 EP 132 DI 10.1002/(SICI)1096-8652(200006)64:2<128::AID-AJH11>3.0.CO;2-# PG 5 WC Hematology SC Hematology GA 315PW UT WOS:000087123000011 PM 10814994 ER PT J AU Caron, A Menu, P Faivre-Fiorina, B Labrude, P Alayash, A Vigneron, C AF Caron, A Menu, P Faivre-Fiorina, B Labrude, P Alayash, A Vigneron, C TI Systemic and renal hemodynamics after moderate hemodilution with HbOCs in anesthetized rabbits SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE blood substitutes; vascular resistance; blood flow; vascular hindrance; viscosity; exchange transfusion ID HEMOGLOBIN POLYOXYETHYLENE CONJUGATE; OXYGEN-CARRYING SOLUTIONS; CELL-FREE HEMOGLOBIN; NITRIC-OXIDE; IN-VIVO; BLOOD; SUBSTITUTES; MECHANISMS; RESPONSES; CARRIERS AB Hb-based O-2-carrying solutions (HbOCs) have been developed as red blood cell substitutes for use in patients undergoing hemodilution. Variously modified Hb with diverse solution properties have been shown to produce variable hemodynamic responses. We examined, through pulsed-Doppler velocimetry, the systemic and renal hemodynamic effects of dextran-benzene-tetracarboxylate-conjugated (Hb-Dex-BTC), bis(3,5-dibromosalicyl) fumarate cross-linked (alpha alpha-Hb), and o-raffinose-polymerized (o-raffinose-Hb) Hb perfused in rabbits after moderate hemodilution (30% hematocrit), and we compared the effects of these Hb solutions with the effects elicited by plasma volume expanders. In addition, vascular hindrance (resistance/blood viscosity at 128.5 s(-1)) was calculated to determine whether a moderate decrease in the viscosity of blood mixed with HbOCs may impair vasoconstriction as a result of autoregulation after infusion of cell-free Hb. No changes were observed in renal hemodynamics after hemodilution with reference or Hb solutions. Increase in blood pressure and vascular resistance was found with Hb-Dex-BTC and alpha alpha-Hb (for 180 min) and, to a lesser extent, with o-raffinose- Hb (for 120 min). Furthermore, Hb-Dex-BTC (high viscosity) and o-raffinose- Hb (medium viscosity) induced comparable increases in vascular hindrance (from 0.091 to 0.159 and from 0.092 to 0.162 cm(-1), respectively) but far less than that produced by alpha alpha-Hb (low viscosity, from 0.092 to 0.200 cm(-1)). These results suggest that maintaining the viscosity of blood by infusing solutions with high viscosity makes it possible to limit vasoconstriction due to autoregulation mechanisms and mainly caused by hemodilution per se. C1 US FDA, Ctr Biol Evaluat & Res, Lab Plasma Derivat, Bethesda, MD 20892 USA. Univ Nancy 1, Sch Pharm, Dept Hematol & Physiol, F-54001 Nancy, France. RP Caron, A (reprint author), Fac Pharm, Lab Hematol & Physiol, 5 Rue Albert Lebrun, F-54001 Nancy, France. RI FAIVRE , Beatrice/B-7535-2012 NR 41 TC 18 Z9 18 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUN PY 2000 VL 278 IS 6 BP H1974 EP H1983 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 323PE UT WOS:000087573500031 PM 10843896 ER PT J AU Landow, L AF Landow, L TI Current issues in clinical trial design - Superiority versus equivalency studies SO ANESTHESIOLOGY LA English DT Article DE active control; clinical trial; equivalency trial; FDA; non-inferiority trial; placebo; superiority trial C1 Harvard Univ, Sch Med, Boston, MA USA. US FDA, Anesthet & Crit Care Drugs, Rockville, MD USA. RP Landow, L (reprint author), 1600 Massachusetts Ave 304, Cambridge, MA 02138 USA. NR 14 TC 9 Z9 9 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 JUN PY 2000 VL 92 IS 6 BP 1814 EP 1820 DI 10.1097/00000542-200006000-00042 PG 7 WC Anesthesiology SC Anesthesiology GA 320ER UT WOS:000087389300038 PM 10839934 ER PT J AU Shahabuddin, M Khan, AS AF Shahabuddin, M Khan, AS TI Inhibition of human immunodeficiency virus type 1 by packageable, multigenic antisense RNA SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Article ID HIV-1 PACKAGING SIGNAL; HUMAN T-CELLS; GENE-TRANSFER; EXPRESSING ANTISENSE; RETROVIRAL VECTORS; INTRACELLULAR EXPRESSION; ANTIRETROVIRAL THERAPY; REVERSE-TRANSCRIPTASE; ANTI-TAT; REPLICATION AB Viral-based vectors can provide an efficient delivery mechanism for stable expression of antisense RNA. To enhance and propagate the antiviral effect of antisense RNA, two novel human immunodeficiency virus type 1 (HIV-1)-based vector DNAs, designated as pMAG7 and pMAG19, were constructed which contained HIV-1 cis-acting packaging elements and produced multigenic HIV-1 antisense RNA that could target the entire pal, env, vif, vpu, vpr, rev, and tat and portions of gag and nef. The two DNAs were identical except that pMAG19 had additional gag coding sequences, Cotransfection of pMAG DNA and infectious, cloned HIV-1 DNA in 293 cells inhibited virus production (81%-98% reduction in reverse transcriptase activity) of various T cell-tropic and macrophage-tropic clade B isolates, such as NL4-3, YU-2, and JR-CSF, In addition, virion-associated pMAG antisense RNA was detected in residual virus particles produced by pNL4-3 in the presence of pMAG7 DNA, and the antisense sequences were stably transferred by infection of 174 x CEM cells. The results suggest that pMAG DNA may confer broad protection against HIV-1 by reducing initial virus burden due to antisense RNA and subsequent virus spread by propagation of antisense sequences along with wild-type virus. C1 US FDA, Lab Retrovirus Res, Div Viral Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Khan, AS (reprint author), US FDA, Lab Retrovirus Res, Div Viral Prod, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-454, Rockville, MD 20852 USA. NR 66 TC 4 Z9 4 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD JUN PY 2000 VL 10 IS 3 BP 141 EP 151 DI 10.1089/oli.1.2000.10.141 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 330JJ UT WOS:000087958700001 PM 10905551 ER PT J AU Parshikov, IA Freeman, JP Lay, JO Beger, RD Williams, AJ Sutherland, JB AF Parshikov, IA Freeman, JP Lay, JO Beger, RD Williams, AJ Sutherland, JB TI Microbiological transformation of enrofloxacin by the fungus Mucor ramannianus SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID FLUOROQUINOLONE ENROFLOXACIN; METABOLITES; CIPROFLOXACIN; PHARMACOKINETICS; IDENTIFICATION; DERIVATIVES; DEGRADATION AB Enrofloxacin metabolism by Mucor ramannianus was investigated as a model for the biotransformation of veterinary fluoroquinolones. Cultures grown in sucrose-peptone broth were dosed with enrofloxacin. After 21 days, 22% of the enrofloxacin remained. Three metabolites were Identified: enrofloxacin N-oxide (62% of the total absorbance), N-acetylciprofloxacin (8.0%), and desethylene-enrofloxacin (3.5%). 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 Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RI Lay, Jackson/G-1007-2011; OI Lay, Jackson/0000-0003-3789-2527; Parshikov, Igor/0000-0003-1466-1128 NR 24 TC 47 Z9 50 U1 4 U2 19 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 JUN PY 2000 VL 66 IS 6 BP 2664 EP 2667 DI 10.1128/AEM.66.6.2664-2667.2000 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 319TP UT WOS:000087358700055 PM 10831454 ER PT J AU Faaland, RW Grossman, LW AF Faaland, RW Grossman, LW TI Design and evaluation of a null lens for testing the optical performance of silicone intraocular lenses SO APPLIED OPTICS LA English DT Article ID IMPLANTS; QUALITY AB A two-element null lens, optimized for a 20-diopter silicone intraocular lens (IOL), was designed and tested The performance of the null lens was examined for silicone IOL's with in situ powers from 16 to 24 diopters. Improvements in resolution, resolution efficiency, and modulation transfer function were obtained over the tested power range. (C) 2000 Optical Society of America OCIS codes: 110.4100, 170.4460, 220.3620, 350.4800. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20850 USA. RP Faaland, RW (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, HFZ-134,Corp Blvd, Rockville, MD 20850 USA. EM rwf@cdrh.fda.gov NR 11 TC 3 Z9 3 U1 0 U2 2 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 JUN 1 PY 2000 VL 39 IS 16 BP 2678 EP 2682 DI 10.1364/AO.39.002678 PG 5 WC Optics SC Optics GA 318XZ UT WOS:000087311100022 PM 18345188 ER PT J AU Proudnikov, D Kirillov, E Chumakov, K Donlon, J Rezapkin, G Mirzabekov, A AF Proudnikov, D Kirillov, E Chumakov, K Donlon, J Rezapkin, G Mirzabekov, A TI Analysis of mutations in oral poliovirus vaccine by hybridization with generic oligonucleotide microchips SO BIOLOGICALS LA English DT Article DE generic microchip; mutation analysis; hybridization; vaccine quality control ID FLUORESCENCE ANALYSIS; DNA; ARRAYS; VIRUS; IMMOBILIZATION; POLYMORPHISMS; POPULATIONS; DIAGNOSTICS; SEQUENCE AB This paper describes use of a new technology of hybridization with a micro-array of immobilized oligonucleotides for detection and quantification of neurovirulent mutants in Oral Poliovirus Vaccine (OPV). We used a micro-array consisting of three-dimensional gel-elements containing all possible hexamers (total of 4096 probes). Hybridization of fluorescently labelled viral cDNA samples with such microchips resulted in a pattern of spots that was registered and quantified by a computer-linked CCD camera, so that the sequence of the original cDNA could be deduced. The method could reliably identify single point mutations, since each of them affected fluorescence intensity of 12 micro-array elements. Micro-array hybridization of DNA mixtures with varying contents of point mutants demonstrated that the method can detect as little as 10% of revertants in a population of vaccine virus. This new technology should be useful for quality control of live viral vaccines, as well as for other applications requiring identification and quantification of point mutations. C1 Argonne Natl Lab, Ctr Mechanist Biol & Biotechnol, Argonne, IL 60439 USA. VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. Ctr Biol Evaluat & Res, US FDA, Rockville, MD 20852 USA. RP Mirzabekov, A (reprint author), Argonne Natl Lab, Ctr Mechanist Biol & Biotechnol, 9700 S Cass Ave, Argonne, IL 60439 USA. NR 23 TC 27 Z9 27 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD JUN PY 2000 VL 28 IS 2 BP 57 EP 66 DI 10.1006/biol.1999.0241 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 318GU UT WOS:000087276200001 PM 10885613 ER PT J AU Razzaghi, M Kodell, RL AF Razzaghi, M Kodell, RL TI Risk assessment for quantitative responses using a mixture model SO BIOMETRICS LA English DT Article DE dose-response; EM algorithm; nonquantal responses; susceptibility; upper confidence limit ID MAXIMUM-LIKELIHOOD; EM ALGORITHM; DOSE-RESPONSE; NONRESPONDERS AB A problem that frequently occurs in biological experiments with laboratory animals is that some subjects are less susceptible to the treatment than others. A mixture model has traditionally been proposed to describe the distribution of responses in treatment groups for such experiments. Using a mixture dose-response model, Re derive an upper confidence limit on additional risk, defined as the excess risk over the background risk due to an added dose. Our focus will be on experiments with continuous responses for which risk is the probability of an adverse effect defined as an event that is extremely rare in controls. The asymptotic distribution of the likelihood ratio statistic is used to obtain the upper confidence limit on additional risk. The method can also be used to derive a benchmark dose corresponding to a specified level of increased risk. The EM algorithm is utilized to find the maximum likelihood estimates of model parameters and an extension of the algorithm is proposed to derive the estimates when the model is subject to a specified level of added risk. An example is used to demonstrate the results, and it is shown that by using the mixture model a more accurate measure of added risk is obtained. C1 Bloomsburg Univ Penn, Dept Math, Bloomsburg, PA 17815 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Razzaghi, M (reprint author), Bloomsburg Univ Penn, Dept Math, Bloomsburg, PA 17815 USA. NR 26 TC 16 Z9 19 U1 1 U2 2 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2000 VL 56 IS 2 BP 519 EP 527 DI 10.1111/j.0006-341X.2000.00519.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 325LR UT WOS:000087677500027 PM 10877312 ER PT J AU Chen, JJ Lin, KK Huque, M Arani, RB AF Chen, JJ Lin, KK Huque, M Arani, RB TI Weighted p-value adjustments for animal carcinogenicity trend test SO BIOMETRICS LA English DT Article DE bootstrap resampling method; James approximation; multiple comparisons; poly-3 test; p-Value adjustment; weighted adjustment; weighted Bonferroni ID TUMOR; MORTALITY AB A typical animal carcinogenicity experiment routinely analyzes approximately 10-30 tumor sites. Comparisons of tumor responses between dosed and control groups and dose-related trend tests are often evaluated for each individual tumor site/type separately, p-Value adjustment approaches have been proposed for controlling the overall Type I error rate or familywise error rate (FWE). However, these adjustments often result in reducing the power to detect a dose effect. This paper proposes using weighted adjustments bg assuming that each tumor can be classified as either class A or class B based on Drier considerations. The tumors in class A, which are considered as more critical endpoints, are given less adjustment. Two weighted methods of adjustments are presented, the weighted p adjustment and weighted alpha adjustment. A Monte Carlo simulation shows that both weighted adjustments control the FWE well. Further more, the power increases if a treatment-dependent tumor is analyzed as in class A tumors and the power decreases if it is analyzed as in class B tumors. A data set front a National Toxicology Program (NTP), 2-year animal carcinogenicity experiment with 13 tumor types:sites observed in male mice was analyzed using the proposed methods. The modified poly-3 test was used to test for increased carcinogenicity since it has been adopted by the NTP as a standard test for a dose-related trend. The unweighted adjustment analysis concluded that there was no statistically significant dose-related trend. Using the Feed and Drug Administration classification scheme for the weighted adjustment analyses, two rare tumors (with background rates of 1% or less) were analyzed as class A tumors and 11 common tumors (with background rates higher than 1%) as class B. Both weighted analyses showed a significant dose-related trend for one rare tumor. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. US FDA, Ctr Drug Evaluat & Res, Off Biostat, Rockville, MD 20857 USA. Univ Alabama, Ctr Comprehens Canc, Biostat Unit, Birmingham, AL 35294 USA. RP Chen, JJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. NR 13 TC 7 Z9 9 U1 0 U2 3 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2000 VL 56 IS 2 BP 586 EP 592 DI 10.1111/j.0006-341X.2000.00586.x PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 325LR UT WOS:000087677500036 PM 10877321 ER PT J AU Husain, SR Puri, RK AF Husain, SR Puri, RK TI Interleukin-13 fusion cytotoxin as a potent targeted agent for AIDS-Kaposi's sarcoma xenograft SO BLOOD LA English DT Article ID PSEUDOMONAS EXOTOXIN; GROWTH-FACTOR; SIGNAL-TRANSDUCTION; CARCINOMA-CELLS; IL-13 RECEPTOR; IN-VITRO; PROTEIN; EXPRESSION; CYTOKINES; PATHOGENESIS AB Clinically advanced and rapidly progressive AIDS-associated Kaposi sarcoma (AIDS-KS) tumors require an aggressive tumor-directed therapy. We have observed that AIDS-KS cells express high levels of receptors for immune regulatory cytokine, interleukin-13 (IL-13). Two tumorigenic AIDS-KS cell lines, KS Y-1 and KS-imm, expressed 4560 and 9480 IL-13 binding sites per cell with an affinity (kd) of similar to 0.9 and 3.7 nmol/L, respectively. IL-13 cytotoxin IL13-PE38QQR, consisting of human IL-13 and a derivative of Pseudomonas exotoxin, is specifically cytotoxic to KS tumor cells. Systemic and loco regional administration of IL13-PE38QQR in immunodeficient mice with established human KS tumors produced remarkable antitumor activity. Three intratumoral (IT) injections of IL-13 toxin (250 mu g/kg per dose) on alternate days (qod) or 5 daily (qd) IT injections with lower doses (50 or 100 mu g/kg per dose) resulted in a complete regression of established subcutaneous tumors in most animals. Daily IT treatment with 250 mu g/kg of IL-13 toxin in another KS-derived cell line also produced complete responses. Twice daily intraperitoneal injections of IL13-PE38QQR (25 or 50 mu g/kg per dose) for 10 days (total injections = 20) also completely eradicated KS Y-1 tumors, Intravenous administration of IL13-PE38QQR also suppressed tumor growth; however, complete responses were not observed. All animals tolerated the therapeutic doses of IL-13 toxin without any visible signs of toxicity. The efficacy of receptor-directed IL13-PE38QQR therapy in mice warrants further exploration of this drug for AIDS-KS treatment. (Blood, 2000;95: 3506-3513) (C) 2000 by The American Society of Hematology. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, Bldg 29B,Rm 2NN10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. NR 38 TC 58 Z9 61 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 2000 VL 95 IS 11 BP 3506 EP 3513 PG 8 WC Hematology SC Hematology GA 319QA UT WOS:000087351600032 PM 10828036 ER PT J AU Tan, W Song, N Wang, GQ Liu, Q Tang, HJ Kadlubar, FF Lin, DX AF Tan, W Song, N Wang, GQ Liu, Q Tang, HJ Kadlubar, FF Lin, DX TI Impact of genetic polymorphisms in cytochrome P450 2E1 and glutathione S-transferases M1, T1, and P1 on susceptibility to esophageal cancer among high-risk individuals in China SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID METABOLIZING ENZYME POLYMORPHISMS; POLYCYCLIC AROMATIC-HYDROCARBONS; SQUAMOUS-CELL CARCINOMA; SURGICAL LIVER SAMPLES; HUMAN CYP2E1 GENE; LUNG-CANCER; HEPATOCELLULAR-CARCINOMA; CHLORZOXAZONE METABOLISM; MONOOXYGENASE ACTIVITIES; 5'-FLANKING REGION AB Esophageal cancer, which is prevalent in China, is believed to be induced by environmental carcinogens such as nitrosamines and other agents. The disproportionate geographical distribution of this cancer among individuals suggests a role for gene-environment interactions in developing the disease. We have shown in our preliminary study that a genetic polymorphism in cytochrome P450 2E1 (CYP2E1) that is known to activate nitrosamines mag be a susceptibility factor involved in the early events leading to the development of esophageal canter (Lin Et al,, Cancer Epidemiol, Biomark, Prev,, 7: 1013-1018, 1998), This relatively larger study was conducted to compare the results with our previous findings. One hundred and fifty cases with esophageal cancer, 146 cases with esophageal dysplasia, and 150 normal controls were residents of Linxian, China, a highrisk area. Genomic DNA samples were assayed for restriction fragment length polymorphisms in the CYP2E1 and GSTP1 loci by PCR amplification followed by digestion with RsaI and Alw26I, respectively. Deletion of the GSTM1 and GSTT1 genes was detected by multiples PCR, The distribution of CYP2E1 c1/c1 allele frequency was found to be significantly different between controls (44.0%) and cases with cancer (71.3%) or cases with dysplasia (70.6%; P < 0.0001), Individuals having the c1/c1 genotype were at a 3.1-fold [95% confidence interval (CI), 2.4-3.9] increased risk of developing dysplasia and a 3.2-fold (95% CI, 2.5-4.1) increased risk of developing squamous cell carcinoma of the esophagus, Although polymorphisms in the GSTT1 and GSTP1 were not significantly different between cases with cancer or cases with dysplasia and controls, the frequency of the GSTM1 non-null (+/+ and +/0) genotypes appeared to be overrepresented in cases with cancer compared with controls (odds ratio, 2.3; 95% CI, 1.8-3.0). Furthermore, a joint effect of the CYP2E1 c1/c1 genotype and GSTM1 non-null genotype on the cancer risk was observed, showing an odds ratio of 8.5 (95% CI, 3.7-19.9). These results demonstrate that CYP2E1 and perhaps GSTM1 are genetic determinants in the development of squamous cell carcinoma of the esophagus. C1 Chinese Acad Med Sci, Inst Canc, Dept Chem Etiol & Carcinogenesis, Beijing 100021, Peoples R China. Beijing Union Med Coll, Beijing 100021, Peoples R China. Sun Yat Sen Univ, Dept Med Stat, Guangzhou 510060, Peoples R China. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Lin, DX (reprint author), Chinese Acad Med Sci, Inst Canc, Dept Chem Etiol & Carcinogenesis, Beijing 100021, Peoples R China. EM dlin@public.bta.net.cn NR 82 TC 121 Z9 142 U1 1 U2 8 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2000 VL 9 IS 6 BP 551 EP 556 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 324RC UT WOS:000087634300003 PM 10868687 ER PT J AU Kawakami, K Leland, P Puri, RK AF Kawakami, K Leland, P Puri, RK TI Structure, function, and targeting of interleukin 4 receptors on human head and neck cancer cells SO CANCER RESEARCH LA English DT Article ID CIRCULARLY PERMUTED INTERLEUKIN-4; COMMON GAMMA-CHAIN; CARCINOMA-CELLS; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; SIGNAL-TRANSDUCTION; IL-4 RECEPTORS; SARCOMA-CELLS; GROWTH; EXPRESSION AB Despite advances in diagnosis and treatment, survival rates for patients with head and neck cancer have remained unchanged for the last 30 years. in an attempt to develop novel therapeutic agents, we have observed that a variety of murine and human carcinoma cells expresses high levels of receptors for interleukin 4 (IL-4) in vitro and irt vivo. Here, we demonstrate that 17 head and neck cancer cell, lines also express surface IL-4 receptors (IL-4R) and IL-4 binds to IL-4R on one cell line studied with low affinity (k(d) = 37.9 +/- 0.4 nM). The investigation of the subunit structure of IL-4R demonstrated that head and neck cancer cell lines expressed mRNA for IL-4R beta chain (also known as IL-4R alpha) and IL-13R alpha' chain (also known as IL-13R alpha(1)). However, no cell line expressed IL-2R common gamma-chain, which is known to be shared with IL-4R in immune cells. IL-4R is functional because IL-4 strongly induced activation of signal transducers and activators of transcription 6 (STAT-6) in these cell lines. A fusion protein, IL4(38-37)-PE38KDEL, containing translocation and enzymatic domains of Pseudomonas exotoxin and a circularly permuted human IL-4 was found to be highly and specifically cytotoxic to IL-4R-positive head and neck canter cells, as determined by protein synthesis inhibition assay and confirmed by clonogenic assay. IL4(38-37)-PE38KDEL induced DNA fragmentation and condensation of nuclei indicative of apoptotic cell death. These results establish uniform expression of IL-4R on head and neck cancer cell lines and IL-4 toxin IL4(38-37)-PE38KDEL as a novel therapeutic agent for the possible treatment of human head and neck cancers. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bldg 29B,Room 2NN10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. NR 40 TC 56 Z9 56 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2000 VL 60 IS 11 BP 2981 EP 2987 PG 7 WC Oncology SC Oncology GA 321BH UT WOS:000087434700041 PM 10850446 ER PT J AU Agus, C Ilett, KF Kadlubar, FF Minchin, RF AF Agus, C Ilett, KF Kadlubar, FF Minchin, RF TI Characterization of an ATP-dependent pathway of activation for the heterocyclic amine carcinogen N-hydroxy-2-amino-3-methylimidazo[4,5-f]quinoline SO CARCINOGENESIS LA English DT Article ID DNA ADDUCT FORMATION; FOOD MUTAGEN 2-AMINO-3-METHYLIMIDAZO<4,5-F>QUINOLINE; NONHUMAN-PRIMATES; COOKED BEEF; IN-VITRO; INHIBITION; RATS; IDENTIFICATION; METABOLITES; INDUCTION AB 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) is one of several mutagenic and carcinogenic heterocyclic amines formed during the cooking process of protein-rich foods, These compounds are highly mutagenic and have been shown to produce tumours in various tissues in rodents and non-human primates. Metabolic activation of IQ is a two-step process involving N-hydroxylation by CYP1A2 followed by esterification to a more reactive species capable of forming adducts with DNA, To date, acetylation and sulphation have been proposed as important pathways in the formation of N-hydroxy esters, In this study we have demonstrated the presence of an ATP-dependent activation pathway for N-hydroxy-IQ (N-OH-IQ) leading to DNA adduct formation measured by covalent binding of [H-3]N-OH-IQ to DNA, ATP-dependent DNA binding of N-OH-IQ was greatest in the cytosolic fraction of rat liver, although significant activity was also seen in colon, pancreas and lung. ATP was able to activate N-OH-IQ almost 10 times faster than N-hydroxy-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (7.7 +/- 0.3 and 0.9 +/- 0.1 pmol/mg protein/min, respectively). Using reported intracellular concentrations of cofactor, the ability of ATP to support DNA binding was similar to that seen with 3'-phosphoadenosine 5'-phosphosulphate and similar to 50% of that seen with acetyl coenzyme A (AcCoA), In addition to DNA binding, HPLC analysis of the reaction mixtures using ATP as co-factor showed the presence of two stable, polar metabolites, With AcCoA, only one metabolite was seen. The kinase inhibitors genistein, tyrphostin A25 and rottlerin significantly inhibited both DNA binding and metabolite formation with ATP. However, inhibition was unlikely to be due to effects on enzyme activity since the broad spectrum kinase inhibitor staurosporine had no effect and the inactive analogue of genistein, daidzein, was as potent as genistein, The effects of genistein and daidzein, which are naturally occurring isoflavones from soy and other food products, on DNA adduct formation may potentially be useful in the prevention of heterocyclic amine-induced carcinogenesis. C1 Royal Perth Hosp, Lab Canc Med, Perth, WA 6000, Australia. Univ Western Australia, Dept Pharmacol, Nedlands, WA 6907, Australia. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Western Australian Ctr Pathol & Med Res, Clin Pharmacol & Toxicol Lab, Nedlands, WA 6009, Australia. RP Minchin, RF (reprint author), Royal Perth Hosp, Lab Canc Med, Perth, WA 6000, Australia. NR 52 TC 9 Z9 9 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2000 VL 21 IS 6 BP 1213 EP 1219 DI 10.1093/carcin/21.6.1213 PG 7 WC Oncology SC Oncology GA 327XE UT WOS:000087819100020 PM 10837012 ER PT J AU Palom, Y Belcourt, MF Musser, SM Sartorelli, AC Rockwell, S Tomasz, M AF Palom, Y Belcourt, MF Musser, SM Sartorelli, AC Rockwell, S Tomasz, M TI Structure of adduct X, the last unknown of the six major DNA adducts of mitomycin C formed in EMT6 mouse mammary tumor cells SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID REDUCTIVE ACTIVATION; DT-DIAPHORASE; IN-VIVO; 2,7-DIAMINOMITOSENE; ALKYLATION; MODULATION; MECHANISM; AGENTS AB Treatment of EMT6 mouse mammary tumor cells with mitomycin C (MC) results in the formation of six major MC-DNA adducts. We identified the last unknown of these ("adduct X") as a guanine N-2 adduct of 2,7-diaminomitosene (2,7-DAM), in which the mitosene is linked at its C-10 position to guanine N-2. The assigned structure is based on UV and mass spectra of adduct X isolated directly from the cells, as well as on its difference UV, second-derivative UV, and circular dichroism spectra, synthesis from [8-H-3]deoxyguanosine, and observation of its heat stability. These tests were carried out using 17 mu g of synthetic material altogether. The mechanism of formation of adduct X involves reductive metabolism of MC to 2,7-DAM, which undergoes a second round of reductive activation to alkylate DNA, yielding adduct X and another 2,7-DAM-guanine adduct (adduct Y), which is linked at guanine N7 to the mitosene, Adduct Y has been described previously. Adduct X is formed preferentially at GpG, while adduct Y favors the GpG sequence. In contrast to MC-DNA adducts, the 2,7-DAM-DNA adducts are not cytotoxic. C1 CUNY Hunter Coll, Dept Chem, New York, NY 10021 USA. Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06520 USA. US FDA, Washington, DC 20204 USA. RP Tomasz, M (reprint author), CUNY Hunter Coll, Dept Chem, New York, NY 10021 USA. RI Rockwell, Sara/B-8458-2009 FU NCI NIH HHS [CA71961, CA80845]; NCRR NIH HHS [RR03037] NR 31 TC 31 Z9 31 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JUN PY 2000 VL 13 IS 6 BP 479 EP 488 DI 10.1021/tx000024j PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 326LX UT WOS:000087738000007 PM 10858321 ER PT J AU Rand, RW Kreitman, RJ Patronas, N Varricchio, F Pastan, I Puri, RK AF Rand, RW Kreitman, RJ Patronas, N Varricchio, F Pastan, I Puri, RK TI Intratumoral administration of recombinant circularly permuted interleukin-4-Pseudomonas exotoxin in patients with high-grade glioma SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL-CARCINOMA-CELLS; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; INTERLEUKIN 4-TOXIN; CANCER-CELLS; BRAIN-TUMORS; PHASE-I; IMMUNOTOXIN; THERAPY; TOXIN AB Human glioblastoma but not normal brain cells express numerous receptors for the cytokine interleukin (IL)-4. To target these receptors, we have investigated the safety and activity of directly infusing IL-4(38-37)-PE38KDEL, a chimeric protein composed of circularly permuted IL-4 and a truncated form of Pseudomonas exotoxin (PE), into recurrent malignant high-grade gliomas, IL-4(38-37)-PE38KDEL (IL-4-toxin) was infused over a 4-8-day period into gliomas of nine patients by one to three stereotactically placed catheters, No apparent systemic toxicity occurred in any patient. The infusion of IL-4-toxin in six of nine patients showed glioma necrosis as evidenced by diminished gadolinium enhancement on magnetic resonance imaging. Seven of nine patients underwent craniotomy because of increased intracranial pressure at 16-101 days after the beginning of infusion. In six of these seven patients, partial-to-extensive tumor necrosis with edema was confirmed pathologically. No histological evidence of neurotoxicity to normal brain was identified in any patient. Two patients were not operated on; by magnetic resonance imaging, one showed mottled gadolinium enhancement, and the other showed extensive necrosis of tumor leading to complete remission; this patient remains disease-free >18 months after the procedure. We conclude that direct glioma injection of IL-4(38-37)-PE38KDEL is safe without systemic toxicity. Local toxicity seemed attributable mainly to tumor necrosis or occasionally to the volume of infusion. Histological evidence of toxicity to normal brain was not observed and in many patients, could be pathologically excluded. Additional patients are being treated to determine the maximal tolerated concentration and volume of IL-4(38-37)-PE38KDEL. C1 NIH, Lab Mol Tumor Biol, Div Cellullar & Gene Therapies, Ctr Biol Evaluat & Res,UD FDA, Bethesda, MD 20892 USA. John Wayne Canc Inst, Dept Neurooncol, Santa Monica, CA 90404 USA. NCI, Mol Biol Lab, Div Basic Sci, NCI, Bethesda, MD 20892 USA. NIH, Dept Neuroradiol, Bethesda, MD 20892 USA. US FDA, Div Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20850 USA. RP Puri, RK (reprint author), NIH, Lab Mol Tumor Biol, Div Cellullar & Gene Therapies, Ctr Biol Evaluat & Res,UD FDA, Bldg 29B,Room 2NN10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. NR 36 TC 171 Z9 177 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN PY 2000 VL 6 IS 6 BP 2157 EP 2165 PG 9 WC Oncology SC Oncology GA 322ZR UT WOS:000087540300006 PM 10873064 ER PT J AU Brennan, MJ AF Brennan, MJ TI Moving new vaccines for tuberculosis through the regulatory process SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT International Symposium on Tuberculosis Vaccine Development and Evaluation CY AUG 26-28, 1998 CL SAN FRANCISCO, CALIFORNIA SP Ctr Dis Control & Prevent, Amer Lung Assoc, Amer Thoracic Soc, Natl Inst Allergy & Infect Dis, Int Union Against Tuberculosis & Lung Dis, WHO AB The development of novel vaccines for the prevention of tuberculosis is an area of intense interest for scientific researchers, public health agencies, and pharmaceutical manufacturers. Development of effective new vaccines directed against tuberculosis for use in target populations will require close cooperation among several different international organizations, including regulatory agencies responsible for evaluating the safety and effectiveness of new biologics for human use. C1 US FDA, Lab Mycobacteria, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Brennan, MJ (reprint author), US FDA, Lab Mycobacteria, Ctr Biol Evaluat & Res, 29 Lincoln Dr,HFM-431, Bethesda, MD 20892 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN PY 2000 VL 30 SU 3 BP S247 EP S249 DI 10.1086/313869 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 341DR UT WOS:000088576200011 PM 10875792 ER PT J AU Klinman, DM Ishii, KJ Gursel, M Gursel, I Takeshita, S Takeshita, F AF Klinman, DM Ishii, KJ Gursel, M Gursel, I Takeshita, S Takeshita, F TI Immunotherapeutic applications of CpG-containing oligodeoxynucleotides SO DRUG NEWS & PERSPECTIVES LA English DT Article ID IMMUNOSTIMULATORY DNA-SEQUENCES; NATURAL-KILLER ACTIVITY; B SURFACE-ANTIGEN; BACTERIAL-DNA; INTERFERON-GAMMA; DENDRITIC CELLS; CUTTING EDGE; MURINE LEISHMANIASIS; IMMUNE-RESPONSES; PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDES AB Bacterial DNA and synthetic oligodeoxynucleotides (ODN) expressing unmethylated CpG motifs stimulate the mammalian immune system to mount a rapid innate immune response. This response is characterized by the production of polyreactive IgM, immunomodulatory cytokines and chemokines. CpG ODN directly stimulate lymphocytes, natural killer cells and professional antigen-presenting cells (such as macrophages and dendritic cells). Owing to the strength and nature of this stimulation, CpG ODN are being harnessed for a variety of therapeutic uses. They are being tested for their ability to act as immune adjuvants, boosting the immune response elicited by conventional and DNA vaccines. As a result of their ability to activate a strong interferon gamma-dominated Th1 response while blocking the development of Th2-dependent allergies, CpG ODN are being examined for their antiallergic properties. Finally, CpG ODN are being used as "immunoprotective agents," since the innate immune response they elicit can protect the host from a variety of pathogenic bacteria, viruses and parasites. (C) 2000 Prous Science. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Res, Bethesda, MD 20892 USA. 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 68 TC 15 Z9 16 U1 0 U2 0 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0214-0934 J9 DRUG NEWS PERSPECT JI Drug News Perspect. PD JUN PY 2000 VL 13 IS 5 BP 289 EP 296 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 354FV UT WOS:000089319900005 PM 12937643 ER PT J AU Ornstein, DK Gillespie, JW Paweletz, CP Duray, PH Herring, J Vocke, CD Topalian, SL Bostwick, DG Linehan, WM Petricoin, EF Emmert-Buck, MR AF Ornstein, DK Gillespie, JW Paweletz, CP Duray, PH Herring, J Vocke, CD Topalian, SL Bostwick, DG Linehan, WM Petricoin, EF Emmert-Buck, MR TI Proteomic analysis of laser capture microdissected human prostate cancer and in vitro prostate cell lines SO ELECTROPHORESIS LA English DT Article DE pharmacoproteomics; prostate cancer; laser capture microdissection; cell culture; electrophoresis ID EXPRESSION; PROTEIN; ELECTROPHORESIS; PROGRESSION; CARCINOMAS; MEN AB Specific populations of normal and malignant epithelium from three radical prostatectomy tissue specimes were procured by laser capture microdissection (LCM) and analyzed by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). Six proteins that were only seen in malignant cells and two proteins that were only seen in benign epithelium were reproducibly observed in two of two cases examined. Furthermore, these proteins were not observed in the 2-D PAGE profiles from the patient-matched microdissected stromal cell populations, but were seen in the protein profiles from the undissected whole cryostat Sections. One of these proteins was determined to be prostate-specific antigen (PSA) by Western blot analysis, and intriguingly the remaining protein candidates were found to be at least as abundant as the PSA protein. Comparison of 2-D PAGE profiles of microdissected cell with matched in vitro cell lines from the same patient, and metastatic prostate cancer cell lines (LnCaP and PC3) showed striking differences between prostate cells in vivo and in vitro with less than 20% shared proteins. The data demonstrate that 2-D PAGE analysis of LCM-derived cells can reliably detect alterations in protein expression associated with prostate cancer, and that these differentially expressed proteins are produced in high enough levels which could allow for their clinical utility as new targets for therapeutic intervention, serum markers, and/or imaging markers. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prod, Tissue Proteom Unit, Bethesda, MD 20892 USA. NCI, Pathol Lab, Pathogenet Unit, Bethesda, MD USA. NCI, Off Director, Canc Genome Anat Project, Bethesda, MD USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. Mayo Clin, Dept Pathol, Rochester, MN USA. Georgetown Univ, Dept Chem, Washington, DC 20057 USA. RP Petricoin, EF (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prod, Tissue Proteom Unit, Bldg 29A Room 2B01,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 21 TC 201 Z9 215 U1 1 U2 13 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUN PY 2000 VL 21 IS 11 BP 2235 EP 2242 DI 10.1002/1522-2683(20000601)21:11<2235::AID-ELPS2235>3.3.CO;2-1 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 330RN UT WOS:000087975100016 PM 10892734 ER PT J AU Razzaghi, M Kodell, R AF Razzaghi, M Kodell, R TI Dose-response modeling for developmental neurotoxicity data SO ENVIRONMENTAL AND ECOLOGICAL STATISTICS LA English DT Article DE intralitter correlation; maximum likelihood; neurotoxic effect; nonquantal data ID RISK ASSESSMENT; EXPOSURE; HUMANS; COMPARABILITY; ANIMALS; MIXTURE; LEAD AB The fact that maternal exposures to some chemicals during pregnancy can adversely affect the structure and function of the nervous system in the offspring is well established. Government agencies have for a long time been concerned with regulation of developmental neurotoxicants and safe perinatal exposures. However, despite this concern, current guidelines provide only broad and nonspecific recommendations and lack clear directions for a model based approach to risk estimation. In this paper we propose a dose-response model for the nonquantal data obtained from developmental neurotoxicological experiments. To account for the critical issue of the correlation among responses from pups in the same litter, the so called intralitter correlation, a hierarchical distributional structure is used to derive the underlying unconditional distribution of responses. The maximum likelihood method is used to estimate model parameters and the covariance matrix of the estimates is derived. An example is used to illustrate the results. C1 Bloomsburg Univ, Bloomsburg, PA 17815 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Razzaghi, M (reprint author), Bloomsburg Univ, Bloomsburg, PA 17815 USA. NR 34 TC 3 Z9 3 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1352-8505 J9 ENVIRON ECOL STAT JI Environ. Ecol. Stat. PD JUN PY 2000 VL 7 IS 2 BP 191 EP 203 DI 10.1023/A:1009683114075 PG 13 WC Environmental Sciences; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Environmental Sciences & Ecology; Mathematics GA 324EL UT WOS:000087608800005 ER PT J AU Dietert, RR Etzel, RA Chen, D Halonen, M Holladay, SD Jarabek, AM Landreth, K Peden, DB Pinkerton, K Smialowicz, RJ Zoetis, T AF Dietert, RR Etzel, RA Chen, D Halonen, M Holladay, SD Jarabek, AM Landreth, K Peden, DB Pinkerton, K Smialowicz, RJ Zoetis, T TI Workshop to identify critical windows of exposure for children's health: Immune and respiratory systems work group summary SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE children's health; developmental exposure; developmental immunotoxicity; respiratory toxicity; risk assessment; windows of vulnerability ID DEVELOPMENTAL LEAD-EXPOSURE; STACHYBOTRYS-ATRA; MATERNAL SMOKING; PERINATAL EXPOSURE; PASSIVE SMOKING; NASAL PASSAGES; F344 RAT; T-CELL; RESPONSES; MICE AB Fetuses, infants, and juveniles (preadults) should not be considered simply "small adults" when it comes to toxicological risk. We present specific examples of developmental toxicants that are more toxic to children than to adults, focusing on effects on the immune and respiratory systems. We describe differences in both the pharmacokinetics of the developing immune and respiratory systems as well as changes in target organ sensitivities to toxicants. Differential windows of vulnerability during development are identified in the context of available animal models. We provide specific approaches to directly investigate differential windows of vulnerability. These approaches are based on fundamental developmental biology and the existence of discrete developmental processes within the immune and respiratory systems. The processes are likely to influence differential developmental susceptibility to toxicants, resulting in lifelong toxicological changes. We also provide a template for comparative research. Finally, we discuss the application of these data to risk assessment. C1 Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, Ithaca, NY 14853 USA. Cornell Univ, Inst Comparat & Environm Toxicol, Ithaca, NY 14853 USA. US Food Safety & Inspect Serv, Epidemiol & Risk Assessment Div, Washington, DC 20250 USA. US EPA, Off Childrens Hlth Protect, Washington, DC 20460 USA. Univ Arizona, Arizona Hlth Sci Ctr, Tucson, AZ USA. Virginia Polytech Inst & State Univ, Coll Vet Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 USA. US EPA, Natl Ctr Environm Assessment, Res Triangle Pk, NC 27711 USA. W Virginia Univ, Med Ctr, Dept Microbiol & Immunol, MBR Canc Ctr, Morgantown, WV 26506 USA. Univ N Carolina, Sch Med, Ctr Environm Med & Lung Biol, Chapel Hill, NC USA. Univ Calif Davis, Dept Anat Physiol & Cell Biol, Davis, CA 95616 USA. US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Dietert, RR (reprint author), Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, C5135 Vet Med Ctr,Tower Rd, Ithaca, NY 14853 USA. NR 67 TC 159 Z9 166 U1 2 U2 8 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 2000 VL 108 SU 3 BP 483 EP 490 DI 10.2307/3454540 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 326RK UT WOS:000087748400019 PM 10852848 ER PT J AU Altekruse, SF Bishop, RD Baldy, LM Thompson, SG Wilson, SA Ray, BJ Griffin, PM AF Altekruse, SF Bishop, RD Baldy, LM Thompson, SG Wilson, SA Ray, BJ Griffin, PM TI Vibrio gastroenteritis in the US Gulf of Mexico region: the role of raw oysters SO EPIDEMIOLOGY AND INFECTION LA English DT Article ID INFECTIONS; SURVEILLANCE; CONSUMPTION; VULNIFICUS; CONSUMER; COAST AB We examined clinical and epidemiological features of 575 laboratory-confirmed cases of vibrio gastroenteritis in Alabama, Florida, Louisiana, and Texas from 1988 to 1997 (the US Gulf of Mexico Regional Vibrio Surveillance System). Illnesses occurred year round, with peaks in spring and autumn, Illnesses lasted a median of 7 days and included fever in half of patients and bloody stools in 25 % of patients with relevant information. Seventy-two percent of patients reported no underlying illnesses. In the week before onset, 236 (53 %) of 445 patients for whom data were available ate raw oysters, generally at a restaurant or bar. Educational efforts should address the risk of vibrio gastroenteritis for raw oyster consumers, including healthy individuals. Further studies should examine environmental conditions affecting vibrio counts on seafood and processing technologies to enhance the safety of raw oysters. C1 Ctr Dis Control & Prevent, Foodborne & Diarrheal Dis Branch, Atlanta, GA 30333 USA. US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. TRW Co Inc, Atlanta, GA USA. Louisiana Dept Hlth & Hosp, Off Publ Hlth, Baton Rouge, LA 70821 USA. Texas Dept Hlth, Austin, TX 78756 USA. RP Griffin, PM (reprint author), Ctr Dis Control & Prevent, Foodborne & Diarrheal Dis Branch, 1600 Clifton Rd A38, Atlanta, GA 30333 USA. NR 21 TC 34 Z9 41 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD JUN PY 2000 VL 124 IS 3 BP 489 EP 495 DI 10.1017/S0950268899003714 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 349GQ UT WOS:000089037700017 PM 10982073 ER PT J AU Tortorello, ML Reineke, KF AF Tortorello, ML Reineke, KF TI Direct enumeration of Escherichia coli and enteric bacteria in water, beverages and sprouts by 16S rRNA in situ hybridization SO FOOD MICROBIOLOGY LA English DT Article ID EPIFLUORESCENT FILTER TECHNIQUE; TARGETED OLIGONUCLEOTIDE PROBES; IN-SITU; RIBOSOMAL-RNA; IDENTIFICATION; CELLS; PROTEOBACTERIA; POPULATIONS AB A fluorescent oligonucleotide probe complementary to a published 16S ribosomal RNA sequence of Escherichia coli was used for in situ hybridization on membrane filters for direct enumeration of cells. The direct epifluorescent filter technique (DEFT) was modified by performing a 2-h oligonucleotide hybridization on intact cells collected on a membrane filter surface ('oligo-DEFT'). instead of the traditional acridine orange staining. The filter was examined by epifluorescence microscopy, and digital image analysis was used for the cell enumeration. Oligo-DEFT counts were linear over the range of 10(3)-10(6) cells ml(-1) and correlated with DEFT counts (r = 0.99) The oligo-DEFT detection limit was approximately 1 cell ml(-1). Oligo-DEFT counts correlated with standard coliform counts by membrane filtration or plating on selective media for analysis of wafer and beverages artificially inoculated with E, coli. Heat inactivation of the cells did not destroy their reactivity in the oligo-DEFT Natural coliform populations in aquarium water were countable in the oligo-DEFT after a 90-min incubation of the filter on nutrient agar before the hybridization step, which allowed the dormant cells to increase their rRNA content. Natural populations in bean sprouts were countable directly without having to perform the incubation before hybridization. (C) 2000 Academic Press. C1 US FDA, Summit Argo, IL 60501 USA. IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Tortorello, ML (reprint author), US FDA, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM mlt@cfsan.fda.gov NR 23 TC 8 Z9 8 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 EI 1095-9998 J9 FOOD MICROBIOL JI Food Microbiol. PD JUN PY 2000 VL 17 IS 3 BP 305 EP 313 DI 10.1006/fmic.1999.0317 PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 318MB UT WOS:000087287000008 ER PT J AU Turturro, A Hass, BS Hart, RW AF Turturro, A Hass, BS Hart, RW TI Does caloric restriction induce hormesis? SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Article DE caloric restriction; diet restriction; body weight; hormesis ID DIETARY RESTRICTION; FOOD RESTRICTION; BODY-WEIGHT; MALE-RATS; ONCOGENE EXPRESSION; RISK ASSESSMENT; MORTALITY-RATE; LIFE-SPAN; LONGEVITY; EXERCISE AB The question of whether caloric restriction (CR) is hermetic is addressed in terms of two common definitions of the term. In terms of the older definition, i.e., a growth-stimulatory effect when lower doses of a compound which resulted in growth inhibition at higher doses, CR is better characterized as a co-hormetic (i.e., a paradigm which at relatively "low doses," in combination with some stimulus, will evince increased growth (proliferation) and at higher "doses" will inhibit this increased proliferation) rather than a hermetic agent. Mechanisms such as cellular selection of cellular subpopulations, increases in receptor efficiency, and preservation of cellular proliferative potential can interact with agents and produce increased growth as long as the CR is not too severe. In terms of a broader definition, i.e., nonmonotonic dose-response behavior of a compound for any adverse response, CR appears to be hermetic, both as a result of body weight (BW) loss and other potential mechanisms. The impact of changes in BW, or frank CR, can be considered a component of every test for hormesis, and is thus capable for interaction with any other agent. The changes that BW loss (or CR) induce are so profound that any aspect of an agent's action - metabolism, pharmacokinetics, pharmacodynamics - can modulate the response of an organism to an agent. Similarly, other effects of a chemical that induce BW loss, e.g., physical activity or temperature dysregulation, can also induce dose-response curves that appear hermetic. The interaction of the hermetic agents of BW loss and CR can influence agent tests. Controlling these factors may make it possible to dissect the key components of a hermetic response. In addition, the effects of CR or BW loss appear to extrapolate well across species [Colman R, Kemnitz JW. Aging experiments using nonhuman primates. In: Yu BP (Ed), Methods in Aging Research. CRC Press, Boca Raton, FL, 1999, pp. 249-267]. Thus there is some reason to believe that these hermetic factors may be important for humans, and may already be a factor for tests of adverse agents already conducted in humans. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Off Director, Jefferson, AR 72079 USA. RP Turturro, A (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. NR 72 TC 21 Z9 22 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0144-5952 J9 HUM EXP TOXICOL JI Hum. Exp. Toxicol. PD JUN PY 2000 VL 19 IS 6 BP 320 EP 329 DI 10.1191/096032700678815981 PG 10 WC Toxicology SC Toxicology GA 347RG UT WOS:000088942500002 PM 10962498 ER PT J AU Turturro, A Hass, BS Hart, RW AF Turturro, A Hass, BS Hart, RW TI Response to the commentaries on "Does caloric restriction induce hormesis?" SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Editorial Material ID ENERGY-METABOLISM; FISCHER-344 RATS; BODY-WEIGHT; DIETARY; TOXICITY C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Off Director, Jefferson, AR 72079 USA. RP Turturro, A (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. NR 25 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0144-5952 J9 HUM EXP TOXICOL JI Hum. Exp. Toxicol. PD JUN PY 2000 VL 19 IS 6 BP 355 EP 359 DI 10.1191/096032700678816098 PG 5 WC Toxicology SC Toxicology GA 347RG UT WOS:000088942500013 PM 10962509 ER PT J AU Love, PE Shores, EW AF Love, PE Shores, EW TI ITAM multiplicity and thymocyte selection: How low can you go? SO IMMUNITY LA English DT Review ID T-CELL DEVELOPMENT; TCR-ZETA-CHAIN; EPSILON-RI-GAMMA; RECEPTOR SIGNAL-TRANSDUCTION; NEGATIVE SELECTION; POSITIVE SELECTION; ANTIGEN-RECEPTOR; MICE LACKING; CD4(+)CD8(+) THYMOCYTES; INTRAEPITHELIAL LYMPHOCYTES C1 US FDA, Div Therapeut Prot, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Shores, EW (reprint author), US FDA, Div Therapeut Prot, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 76 TC 62 Z9 62 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUN PY 2000 VL 12 IS 6 BP 591 EP 597 DI 10.1016/S1074-7613(00)80210-1 PG 7 WC Immunology SC Immunology GA 329ZA UT WOS:000087937300001 PM 10894159 ER PT J AU Goering, PL Kuester, RK Neale, AR Chapekar, MS Zaremba, TG Gordon, EA Hitchins, VM AF Goering, PL Kuester, RK Neale, AR Chapekar, MS Zaremba, TG Gordon, EA Hitchins, VM TI Effects of particulate and soluble cadmium species on biochemical and functional parameters in cultured murine macrophages SO IN VITRO & MOLECULAR TOXICOLOGY-A JOURNAL OF BASIC AND APPLIED RESEARCH LA English DT Article ID TUMOR-NECROSIS-FACTOR; HEAT-SHOCK PROTEINS; MOUSE PERITONEAL-MACROPHAGES; NITRIC-OXIDE PRODUCTION; FACTOR-ALPHA; INDUCED HEPATOTOXICITY; LIPID-PEROXIDATION; SUPEROXIDE ANION; STRESS PROTEINS; CELL-LINE AB Cultured murine macrophages (RAW 264.7) were used to evaluate the temporal relationships between cytotoxicity, phagocytosis, tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO) production, and alterations in expression of stress proteins after exposure to cadmium oxide (CdO) or cadmium chloride (CdCl2), particulate and soluble forms of cadmium, respectively. Macrophages were exposed. in vitro to CdO (25 or 50 mu g) or CdCl2 (30 or 40 mu M) for 2 to 72 h. Cytotoxicity Tvas not evident until 18 h when exposed to 30 mu M CdCl2 or 25 mu g CdO, but occurred as early as 12 h after exposure to 40 mu M CdCl2 or 50 mu g CdO. Relative to untreated controls, phagocytic activity decreased progressively from 2 to 24 h after exposure to both forms of cadmium. TNF-alpha levels increased to 2- to 3-fold after 4 h and remained elevated until 24 h after exposure to 25 and 50 lug CdO and 30 mu M CdCl2, but decreased by 18-24 h at 40 mu M CdCl2. CdCl2 or CdO alone did not induce NO; however, both cadmium species reduced Lipopolysaccharide (LPS)-stimulated NO production in a dose-dependent manner. Enhanced de novo synthesis of 70- and 90-kD heat shock, or stress, proteins was observed 2 to 8 h after exposure to both CdCl2 and CdO; however, synthesis of these proteins returned to control levels by 24 h. Stress protein synthesis was enhanced by CdCl2 or CdO prior to cytotoxicity, but coincided with a decrease in phagocytic capacity and an increase in TNF-alpha levels. The data suggest that cultured macrophages respond similarly in vitro to a particulate form and a soluble form of cadmium in a cell type that plays a pivotal role in inflammatory and immune responses. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Div Life Sci, Rockville, MD 20857 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Goering, PL (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Div Life Sci, Rockville, MD 20857 USA. NR 48 TC 22 Z9 22 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1097-9336 J9 IN VITRO MOL TOXICOL JI In Vitro Mol. Toxicol.-J. Basic Appl. Res. PD SUM PY 2000 VL 13 IS 2 BP 125 EP 136 PG 12 WC Toxicology SC Toxicology GA 357DD UT WOS:000089482500005 ER PT J AU Delogu, G Howard, A Collins, FM Morris, SL AF Delogu, G Howard, A Collins, FM Morris, SL TI DNA vaccination against tuberculosis: Expression of a ubiquitin-conjugated tuberculosis protein enhances antimycobacterial immunity SO INFECTION AND IMMUNITY LA English DT Article ID COLONY-STIMULATING FACTOR; CYTOTOXIC T-LYMPHOCYTES; MYCOBACTERIUM-TUBERCULOSIS; PROTECTIVE EFFICACY; ANTIGEN TRANSFER; IN-VIVO; VACCINES; INDUCTION; IMMUNIZATION; IMMUNOGENICITY AB Genetic immunization is a promising new technology for developing vaccines against tuberculosis that are more effective. In the present study, we evaluated the effects of intracellular turnover of antigens expressed by DNA vaccines on the immune response induced by these vaccines in a mouse model of pulmonary tuberculosis. The mycobacterial culture filtrate protein MPT64 was expressed as a chimeric protein fused to one of three variants of the ubiquitin protein (UbG, UbA, and UbGR) known to differentially affect the intracellular processing of the coexpressed antigens, Immunoblot analysis of cell lysates of in vitro-transfected cells showed substantial differences in the degradation rate of ubiquinated MPT64 (i.e., UbG64 < UbA64 < UbGR64). The specific immune response generated in mice correlated with the stability of the ubiquitin-conjugated antigen. The UbA64 DNA vaccine induced a weak humoral response compared to UbG64, and a mixed population of interleukin-4 (IL-4)- and gamma interferon (IFN-gamma)-secreting tells, Vaccination with the UbGR64 plasmid generated a strong Th1 cell response (high IFN-gamma, low IL-4) in the absence of a detectable humoral response, Aerogenic challenge of vaccinated mice with Mycobacterium tuberculosis indicated that immunization with both the UbA64- and UbGR64-expressing plasmids evoked an enhanced protective response compared to the vector control. The expression of mycobacterial antigens from DNA vaccines as fusion proteins with a destabilizing ubiquitin molecule (UbA or UbGR) shifted the host response toward a stronger Th1-type immunity which was characterized by low specific antibody levels, high numbers of IFN-gamma-secreting cells, and significant resistance to a tuberculous challenge. C1 US FDA, CBER, OVRR, Lab Mycobacteria, Bethesda, MD 20892 USA. RP Morris, SL (reprint author), US FDA, CBER, OVRR, Lab Mycobacteria, HFM 431,Bldg 29,Rm 502,29 Lincoln Dr, Bethesda, MD 20892 USA. RI Delogu, Giovanni/I-3701-2012 OI Delogu, Giovanni/0000-0003-0182-8267 NR 34 TC 85 Z9 109 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 JUN PY 2000 VL 68 IS 6 BP 3097 EP 3102 DI 10.1128/IAI.68.6.3097-3102.2000 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 316LF UT WOS:000087167900005 PM 10816449 ER PT J AU Chatellier, S Ihendyane, N Kansal, RG Khambaty, F Basma, H Norrby-Teglund, A Low, DE McGeer, A Kotb, M AF Chatellier, S Ihendyane, N Kansal, RG Khambaty, F Basma, H Norrby-Teglund, A Low, DE McGeer, A Kotb, M TI Genetic relatedness and superantigen expression in group A streptococcus serotype MZ isolates from patients with severe and nonsevere invasive diseases SO INFECTION AND IMMUNITY LA English DT Article ID GROUP-A STREPTOCOCCI; COMPLEMENT-INHIBITING PROTEIN; POLYMERASE CHAIN-REACTION; PYROGENIC EXOTOXIN-A; TOXIC-SHOCK-SYNDROME; CYTOKINE PRODUCTION; CLINICAL-FEATURES; GENOMIC DNA; INFECTIONS; PYOGENES AB The relatedness of group A streptococcal (GAS) strains isolated from 35 Canadian patients with invasive disease of different severity was investigated by a variety of molecular methods. All patients were infected with M1T1 strains and, based on clinical criteria, were classified as severe (n = 21) and nonsevere (n = 11) invasive GAS infection cases. All the M1 strains studied had the emm1.0 allele and the same streptococcal pyrogenic exotoxin (Spe) genotype, speA(+) speB(+) speC speF(+) speG(+) speH smeZ(+) ssa. All isolates had the same speA allotype, speA2. The randomly amplified polymorphic DNA banding pattern with two different primers was identical for all strains, and pulsed field gel electrophoresis analysis showed that 33 and 30 isolates had identical banding patterns after DNA digestion with SfiI or SmaI, respectively; the nonidentical isolates differed from the main pattern by only one band. A relatively high degree of polymorphism in specific regions of the sic gene was observed among isolates; however, this polymorphism was not associated with disease severity. Likewise, although the phenotypic expression of SpeA, SpeB, and SpeF proteins varied among the M1T1 isolates, there was no correlation between the amount of Spe expressed and disease severity. Importantly, mitogenic and cytokine responses induced by partially purified bacterial culture supernatants containing a mixture of expressed superantigens mere very similar for isolates from severe and nonsevere cases (P > 0.1). Together, the data indicate that highly related invasive M1T1 isolates, some indistinguishable, can cause disease of varying severity in different individuals. These findings underscore the contribution of host factors to the outcome of invasive GAS infections. C1 Univ Tennessee, Dept Surg, Memphis, TN 38163 USA. Univ Tennessee, Dept Microbiol, Memphis, TN 38163 USA. Univ Tennessee, Dept Immunol, Memphis, TN 38163 USA. Vet Affairs Med Ctr, Res Serv, Memphis, TN 38104 USA. Huddinge Univ Hosp, Karolinska Inst, Div Infect Dis, S-14186 Huddinge, Sweden. US FDA, Washington, DC 20204 USA. Univ Toronto, Toronto, ON M5G 1X5, Canada. Mt Sinai Hosp, Dept Microbiol, Toronto, ON M5G 1X5, Canada. RP Kotb, M (reprint author), Univ Tennessee, Dept Surg, 956 Court Ave,Suite A-202, Memphis, TN 38163 USA. RI Low, Donald/B-1726-2012; mcgeer, allison /H-7747-2014 OI mcgeer, allison /0000-0001-5647-6137 FU NIAID NIH HHS [AI40198, R01 AI040198] NR 39 TC 161 Z9 167 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 2000 VL 68 IS 6 BP 3523 EP 3534 DI 10.1128/IAI.68.6.3523-3534.2000 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 316LF UT WOS:000087167900063 PM 10816507 ER PT J AU Fernandez-Prada, CM Hoover, DL Tall, BD Hartman, AB Kopelowitz, J Venkatesan, MM AF Fernandez-Prada, CM Hoover, DL Tall, BD Hartman, AB Kopelowitz, J Venkatesan, MM TI Shigella flexneri IpaH(7.8) facilitates escape of virulent bacteria from the endocytic vacuoles of mouse and human macrophages SO INFECTION AND IMMUNITY LA English DT Article ID MONOCYTE-DERIVED MACROPHAGES; EPITHELIAL-CELLS; INDUCED APOPTOSIS; ESCHERICHIA-COLI; MAMMALIAN-CELLS; PROMOTES ENTRY; IPA PROTEINS; ANTIGEN GENE; INVASION; PLASMID AB The behavior of Shigella flexneri ipaH mutants was studied in human monocyte-derived macrophages (HMDM), in I-day-old human monocytes, and in J774 mouse macrophage cell line. In HMDM, strain pWR700, an ipaH(7.8) deletion mutant of S. flexneri 2a strain 2457T, behaved like the wild-type strain 2457T. This strain caused rapid host cell death by oncosis, and few bacterial CFU were recovered after incubation in the presence of gentamicin as previously described for 2457T-infected HMDM. However, analysis of bacterial compartmentalization within endocytic vacuoles with gentamicin and chloroquine indicated that more pWR700 than 2457T was present within the endocytic vacuoles of HMDM, suggesting that ipaH(9.8) deletion mutant transited more slowly from the vacuoles to the cytoplasm. In contrast to findings with HMDM, CFU recovered from pVVR700infected mouse J774 cells were 2 to 3 logs higher than CFU from 2457T-infected J774 cells. These values exceeded CFU recovered after infection of J774 cells with plasmid-cured avirulent strain M4243A1. Incubation with gentamicin and chloroquine clearly showed that pWR700 within J774 cells was mostly present within the endocytic vacuoles. This distribution pattern was similar to that seen with M4243A1 and contrasted with the pattern seen with 2457T. Complementation of pWR700 with a recombinant clone expressing ipaH(7.8) restored the intracellular distribution of bacteria to that seen with the wild-type strain. Strains with deletions in ipaH(4.5) or ipaH(9.8), however, behaved like 2457T in both HMDM and J774 cells. The distribution profile of pWR700 in 1-day-old monocytes was similar to that seen in J774 cells. Like infected J774 cells, 1-day-old human monocytes demonstrated apoptosis upon infection with virulent Shigella. These results suggest that a role of the ipaH(9.8) gene product is to facilitate the escape of the virulent bacteria from the phagocytic vacuole of monocytes and macrophages. C1 Walter Reed Army Inst Res, Dept Enter Infect, Div Communicable Dis & Immunol, Washington, DC 20307 USA. Walter Reed Army Inst Res, Dept Bacterial Dis, Div Communicable Dis & Immunol, Washington, DC 20307 USA. US FDA, CFSAN, Microbial Ecol Branch, Washington, DC 20204 USA. RP Venkatesan, MM (reprint author), Walter Reed Army Inst Res, Dept Enter Infect, Div Communicable Dis & Immunol, 503 Robert Grant Ave,Room 3S12, Washington, DC 20307 USA. OI Tall, Ben/0000-0003-0399-3629 NR 46 TC 69 Z9 73 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 JUN PY 2000 VL 68 IS 6 BP 3608 EP 3619 DI 10.1128/IAI.68.6.3608-3619.2000 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 316LF UT WOS:000087167900075 PM 10816519 ER PT J AU Hausman, SZ Burns, DL AF Hausman, SZ Burns, DL TI Use of pertussis toxin encoded by ptx genes from Bordetella bronchiseptica to model the effects of antigenic drift of pertussis toxin on antibody neutralization SO INFECTION AND IMMUNITY LA English DT Article ID ISLET-ACTIVATING PROTEIN; MONOCLONAL-ANTIBODIES; ADENYLATE-CYCLASE; VIRULENCE FACTORS; ADP-RIBOSYLATION; B-OLIGOMER; VACCINE; CELLS; PARAPERTUSSIS; SUBUNITS AB Recently, concern has been voiced about the potential effect that antigenic divergence of circulating strains of Bordetella pertussis might have on the efficacy of pertussis vaccines. In order to model antigenic drift of pertussis toxin, a critical component of many pertussis vaccines, and to examine the effects of such drift on antibody neutralization, we engineered a strain of B. pertussis to produce a variant pertussis toxin molecule that contains many of the amino acid changes found in the toxin encoded by Bordetella bronchiseptica ptx genes. This altered form of the toxin, which is efficiently secreted by B. pertussis and which displays significant biological activity, was found to be neutralized by antibodies induced by vaccination as readily as toxin produced by wild-type B. pertussis. These findings suggest that significant amino acid changes in the pertussis toxin sequence can occur without drastically altering the ability of antibodies to recognize and neutralize the toxin molecule. C1 US FDA, Ctr Biol Evaluat & Res, Lab Resp & Special Pathogens, Bethesda, MD 20892 USA. RP Burns, DL (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Resp & Special Pathogens, HFM-434,Bldg 29,Room 418,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 26 TC 23 Z9 23 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 JUN PY 2000 VL 68 IS 6 BP 3763 EP 3767 DI 10.1128/IAI.68.6.3763-3767.2000 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 316LF UT WOS:000087167900100 PM 10816544 ER PT J AU Buchanan, RL AF Buchanan, RL TI The development of science-based food safety regulations in the United States SO IRISH JOURNAL OF AGRICULTURAL AND FOOD RESEARCH LA English DT Article; Proceedings Paper CT International Conference on Emerging Issues in Food Safety CY JUN, 2000 CL UNIV COLL CORK, CORK, IRELAND SP Univ Coll Cork, Us-Ireland Co-operat Agr Sci & Technol HO UNIV COLL CORK DE food law; inspection; liability AB The safe production, processing, distribution, and marketing of foods in the United States is overseen by several Federal regulatory agencies, as well as their counterparts in each of the individual states. While somewhat confusing at first glance, the responsibilities of each agency reflects its specific jurisdiction and mission. State agencies provide oversight for food products produced and consumed within that state, whereas Federal regulatory agencies have responsibility for the interstate and international commerce. At the Federal level, responsibilities are divided on the basis of commodity and/or activity lines. The USDA Food Safety and Inspection Service is responsible for the inspection of meat, poultry, and egg products, where as the DHHS Food and Drug Administration has jurisdiction of virtually all other products including fruits, vegetables, shell eggs, and seafood. The FDA also has primary responsibility for the pre-market approval of food additives and the development of the 'Food Code' for retail food operations. The EPA is responsible for the pre-market approval of pesticides and related antimicrobials for use with raw agricultural commodities. While there are differences in how each of these agencies approach their responsibilities, the goal of each is to ensure food manufacturers meet their responsibility for producing safe foods, and that the US consumer has confidence in the safety of the US food supply. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Buchanan, RL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU TEAGASC PI DUBLIN PA 19 SANDYMOUNT AVE, DUBLIN 4, IRELAND SN 0791-6833 J9 IRISH J AGR FOOD RES JI Irish J. Agr. Food Res. PD JUN PY 2000 VL 39 IS 2 BP 331 EP 342 PG 12 WC Agriculture, Multidisciplinary; Food Science & Technology SC Agriculture; Food Science & Technology GA 334BJ UT WOS:000088165000022 ER PT J AU Poley, GE Slater, JE AF Poley, GE Slater, JE TI Latex allergy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE latex; rubber; immediate hypersensitivity; allergen; immunotherapy; skin testing ID NATURAL-RUBBER LATEX; HEALTH-CARE WORKERS; DISPOSABLE MEDICAL GLOVES; HEVEA-BRASILIENSIS LATEX; AMINO-ACID-SEQUENCE; SPINA-BIFIDA; ELONGATION-FACTOR; RISK-FACTORS; CROSS-REACTIVITY; IGE ANTIBODIES AB Latex allergy continues to be an important medical problem. In this review we re-examine the definition of latex allergy, the offending allergens, the factors that enhance sensitization, the threshold levels that sensitize and elicit reactions in sensitized individuals, current diagnostic techniques, avoidance measures, the barrier properties of nonlatex alternatives, and the roles of premedication and immunotherapy. Twenty years after its resurgence, later allergy is a well-defined condition with established diagnostic criteria and rational treatment and prevention strategies. However, in spite of advances associated with molecular studies of latex allergens and improved understanding of immunotherapy, avoidance remains the only effective treatment. C1 US FDA, Ctr Biol Evaluat & Res, DFA,Lab Immunobiochem, Div Bacterial Parasit & Allergen Prod, Rockville, MD 20852 USA. Childrens Natl Med Ctr, Childrens Res Inst, Dept Allergy Immunol & Pulm Med, Washington, DC 20010 USA. RP Slater, JE (reprint author), US FDA, Ctr Biol Evaluat & Res, DFA,Lab Immunobiochem, Div Bacterial Parasit & Allergen Prod, 1401 Rockville Pike,HFM-422, Rockville, MD 20852 USA. NR 138 TC 94 Z9 98 U1 0 U2 2 PU MOSBY-YEAR BOOK 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 JUN PY 2000 VL 105 IS 6 BP 1054 EP 1062 DI 10.1067/mai.2000.106925 PN 1 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 327EX UT WOS:000087781800002 PM 10856135 ER PT J AU O'Hanlon, TP Lawless, OJ Katzin, WE Feng, LJ Miller, FW AF O'Hanlon, TP Lawless, OJ Katzin, WE Feng, LJ Miller, FW TI Restricted and shared patterns of TCR beta-chain gene expression in silicone breast implant capsules and remote sites of tissue inflammation SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE human; inflammation; silicone; T-cell receptors ID CELL-RECEPTOR REPERTOIRE; RHEUMATOID-ARTHRITIS; AUTOIMMUNE ENCEPHALOMYELITIS; MAMMARY PROSTHESES; NONSPECIFIC CELLS; T-CELLS; GEL; WOMEN; LYMPHOCYTES; PATHOGENESIS AB Silicone breast implants (SBI) induce formation of a periprosthetic, often inflammatory, fibrovascular neo-tissue called a capsule. Histopathology of explanted capsules varies from densely fibrotic, acellular specimens to those showing intense inflammation-with activated macrophages, multinucleated giant cells, and lymphocytic infiltrates. It has been proposed that capsule-infiltrating lymphocytes comprise a secondary, bystander component of an otherwise benign foreign body response in women with SBIs. In symptomatic women with SBIs, however, the relationship of capsular inflammation to inflammation in other remote tissues remains unclear. In the present study, we utilized a combination of TCR beta-chain CDR3 spectratyping and DNA sequence analysis to assess the clonal heterogeneity of T cells infiltrating SBI capsules and remote, inflammatory tissues. TCR CDR3 fragment analysis of 22 distinct beta variable (BV) gene families revealed heterogeneous patterns of T cell infiltration in patients' capsules. In some cases, however, TCR BV transcripts exhibiting restricted clonality with shared CDR3 lengths were detected in left and right SBI capsules and other inflammatory tissues. DNA sequence analysis of shared, size-restricted CDR3 fragments confirmed that certain TCR BV transcripts isolated from left and right SBI capsules and multiple, extracapsular tissues had identical amino acid sequences within the CDR3 antigen binding domain. These data suggest that shared, antigen-driven T cell responses may contribute to chronic inflammation in SBI capsules as well as systemic sites of tissue injury. (C) 2000 Academic Press. C1 US FDA, Ctr Biol Evaluat & Res, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. Ctr Arthritis Immunol & Environm Disorders, Olney, MD 20832 USA. Mt Sinai Med Ctr, Dept Pathol, Cleveland, OH 44106 USA. Mt Sinai Med Ctr, Div Plast Surg, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. RP O'Hanlon, TP (reprint author), US FDA, Ctr Biol Evaluat & Res, Mol & Dev Biol Lab, Bldg 29B,Rm 2G11,HFM 561,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 58 TC 2 Z9 2 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD JUN PY 2000 VL 14 IS 4 BP 283 EP 293 DI 10.1006/jaut.2000.0376 PG 11 WC Immunology SC Immunology GA 318YE UT WOS:000087311600003 PM 10882054 ER PT J AU Plikaytis, BD Goldblatt, D Frasch, CE Blondeau, C Bybel, MJ Giebink, GS Jonsdottir, I Kayhty, H Konradsen, HB Madore, DV Nahm, MH Schulman, CA Holder, PF Lezhava, T Elie, CM Carlone, GM AF Plikaytis, BD Goldblatt, D Frasch, CE Blondeau, C Bybel, MJ Giebink, GS Jonsdottir, I Kayhty, H Konradsen, HB Madore, DV Nahm, MH Schulman, CA Holder, PF Lezhava, T Elie, CM Carlone, GM TI An analytical model applied to a multicenter pneumococcal enzyme-linked immunosorbent assay study SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYSACCHARIDE ANTIBODY-LEVELS; REFERENCE SERUM AB Pneumococcal conjugate vaccines will eventually be licensed after favorable results from phase III efficacy trials. After licensure of a conjugate vaccine for invasive pneumococcal disease in infants, new conjugate vaccines will likely be licensed primarily on the basis of immunogenicity data rather than clinical efficacy. Analytical methods must therefore be developed, evaluated, and validated to compare immunogenicity results accurately within and between laboratories for different vaccines. At present no analytical technique is uniformly accepted and used in vaccine evaluation studies to determine the acceptable level of agreement between a laboratory result and the assigned value for a given serum sample. This multicenter study describes the magnitude of agreement among 12 laboratories quantifying an identical series of 48 pneumococcal serum specimens from 24 individuals (quality-control sera) by a consensus immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) developed For this study. After provisional or trial antibody concentrations were assigned to the quality-control serum samples for this study, four methods for comparison of a series of laboratory-determined values with the assigned concentrations were evaluated. The percent error between assigned values and laboratory-determined concentrations proved to be the most informative of the four methods. We present guidelines that a laboratory may follow to analyze a series of quality-control sera to determine if it can reproduce the assigned antibody concentrations within an acceptable level of tolerance. While this study focused on a pneumococcal IgG ELISA, the methods that we describe are easily generalizable to other immunological assays. C1 Ctr Dis Control & Prevent, NCID, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. UCL, Inst Child Hlth, Immunobiol Unit, London, England. US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, Bethesda, MD 20014 USA. Pasteur Merieux Connaught, Clin Seroimmunol Lab, Val De Reuil, France. Pasteur Merieux Connaught, Clin Serol, Swiftwater, PA USA. Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. Natl Univ Hosp Reykjavik, Dept Immunol, Reykjavik, Iceland. Natl Publ Hlth Inst, Helsinki, Finland. Statens Serum Inst, Div Microbiol, DK-2300 Copenhagen, Denmark. Wyeth Lederle Vaccines & Pediat, W Henrietta, NY USA. Univ Rochester, Sch Med, Rochester, NY USA. Merck Res Labs, Dev Human Vaccine Serol, West Point, PA USA. RP Plikaytis, BD (reprint author), Ctr Dis Control & Prevent, NCID, Div Bacterial & Mycot Dis, Mailstop C09, Atlanta, GA 30333 USA. EM bdp1@cdc.gov RI Goldblatt, David/C-5972-2008; OI Goldblatt, David/0000-0002-0769-5242; Nahm, Moon/0000-0002-6922-1042 NR 13 TC 66 Z9 67 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 JUN PY 2000 VL 38 IS 6 BP 2043 EP 2050 PG 8 WC Microbiology SC Microbiology GA 320YR UT WOS:000087428600004 PM 10834951 ER PT J AU Orlandi, PA Lampel, KA AF Orlandi, PA Lampel, KA TI Extraction-free, filter-based template preparation for rapid and sensitive PCR detection of pathogenic parasitic protozoa SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; SUBUNIT RIBOSOMAL-RNA; CRYPTOSPORIDIUM-PARVUM OOCYSTS; ENTEROCYTOZOON-BIENEUSI; INTESTINAL PATHOGEN; AIDS PATIENT; CYCLOSPORA; MICROSPORIDIA; WATER; IDENTIFICATION AB Within the last several years, the protozoan parasites Cyclospora cayetanensis, Cryptosporidium parvum, and microsporidia have become recognized as important, rapidly emerging human pathogens in immunocompromised and immunocompetent individuals. Since the early 1990s, many of the reported outbreaks of enteric illness caused by these microorganisms have been attributed to food- and water-borne contamination, Many inherent obstacles affect the success of current surveillance and detection methods used to monitor and control levels of contamination by these pathogens. Unlike methods that incorporate preenrichment for easier and unambiguous identification of bacterial pathogens, similar methods for the detection of parasitic protozoa either are not currently available or cannot be performed in a timely manner. We have developed an extraction-free, filter-based protocol to prepare DNA templates for use in PCR to identify C. cayetanensis and C. parvum oocysts and microsporidia spores, This method requires only minimal preparation to partially purify and concentrate isolates prior to filter application, DNA template preparation is rapid, efficient, and reproducible. As few as 3 to 10 parasites could be detected by PCR from direct application to the filters. In studies, as few 10 to 50 Encephalitozoon intestinalis spores could be detected when seeded in a 100-mu l stool sample and 10 to 30 C. cayetanensis oocysts could be detected per 100 g of fresh raspberries, This protocol can easily be adapted to detect parasites from a wide variety of food, clinical, and environmental samples and can be used in multiplex PCR applications. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Virulence Assessment, Washington, DC 20204 USA. RP Orlandi, PA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Virulence Assessment, HFS-327,200 C St SW, Washington, DC 20204 USA. NR 41 TC 101 Z9 107 U1 0 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 2000 VL 38 IS 6 BP 2271 EP 2277 PG 7 WC Microbiology SC Microbiology GA 320YR UT WOS:000087428600041 PM 10834988 ER PT J AU Flockhart, DA Drici, MD Kerbusch, T Soukhova, N Richard, E Pearle, PL Mahal, SK Babb, VJ AF Flockhart, DA Drici, MD Kerbusch, T Soukhova, N Richard, E Pearle, PL Mahal, SK Babb, VJ TI Studies on the mechanism of a fatal clarithromycin-pimozide interaction in a patient with Tourette syndrome SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 97th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 20-22, 1996 CL ORLANDO, FLORIDA SP Amer Soc Clin Pharmcol & Therapeut ID SYSTEMIC ANTIMYCOTICS KETOCONAZOLE; TORSADES-DE-POINTES; CYTOCHROME-P450 ISOFORMS; HYDROXYLATION PHENOTYPE; PLASMA-LEVELS; ERYTHROMYCIN; PHARMACOKINETICS; TERFENADINE; ITRACONAZOLE; HALOPERIDOL AB The authors report in detail the case of a 27-year-old man who experienced sudden cardiac death 2 days after coprescription of the neuroleptic pimozide and the macrolide antibiotic clarithromycin after the documentation of a prolonged QT interval. To determine the prevalence of this interaction, the authors referred to the Spontaneous Reporting System of the Food and Drug Administration and identified one similar case in which clarithromycin was coprescribed with pimozide and sudden cardiac death occurred shortly thereafter. In addition, the search identified 39 cases of cardiac arrhythmia associated with pimozide, 11 with pimozide alone, and 6 with clarithromycin alone, 1 of which had a positive rechallenge. The mechanism of the interaction between clarithromycin and pimozide seems to involve the inhibition of the hepatic metabolism of pimozide by the macrolide. The authors demonstrated that clarithromycin is able to inhibit the metabolism of pimozide in human liver microsomal preparations (K-i = 7.65 +/- 1.18 mu M) and that pimozide, but not clarithromycin or its primary metabolite, is able to prolong the electrocardiac QT interval in a dose-dependent manner in the isolated perfused rabbit heart. The increase was 9.6 +/- 1.1% in male hearts (N = 5) and 13.4 +/- 1.2% in female hearts (N = 4) (p < 0.05). C1 Georgetown Univ, Med Ctr, Div Clin Pharmacol, Dept Med, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA. Washington Hosp Ctr, Dept Neurol, Washington, DC 20010 USA. US FDA, Off Epidemiol & Biostat, Div Pharmacovigilance & Epidemiol, Rockville, MD 20857 USA. RP Flockhart, DA (reprint author), Georgetown Univ, Med Ctr, Div Clin Pharmacol, Dept Med, Room NE 403,Med Dent Bldg,3900 Reservoir Rd, Washington, DC 20007 USA. FU NIGMS NIH HHS [R55-GM56898, R01-GM56898-01, T32-GM08386] NR 49 TC 54 Z9 54 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD JUN PY 2000 VL 20 IS 3 BP 317 EP 324 DI 10.1097/00004714-200006000-00005 PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 313YT UT WOS:000087027900005 PM 10831018 ER PT J AU Wallace, DJ Van Gilder, T Shallow, S Fiorentino, T Segler, SD Smith, KE Shiferaw, B Etzel, R Garthright, WE Angulo, FJ AF Wallace, DJ Van Gilder, T Shallow, S Fiorentino, T Segler, SD Smith, KE Shiferaw, B Etzel, R Garthright, WE Angulo, FJ CA Foodnet Working Grp TI Incidence of foodborne illnesses reported by the Foodborne Diseases Active Surveillance Network (FoodNet)-1997 SO JOURNAL OF FOOD PROTECTION LA English DT Article AB In 1997, the Foodborne Diseases Active Surveillance Program (FoodNet) conducted active surveillance for culture-confirmed cases of Campylobacter, Escherichia coli O157, Listeria, Salmonella, Shigella, Vibrio, Yersinia, Cyclospora, and Cryptosporidium in five Emerging Infections Program sites. FoodNet is a collaborative effort of the Centers for Disease Control and Prevention's National Center for Infectious Diseases, the United States Department of Agriculture's Food Safety and Inspection Service, the Food and Drug Administration's Center for Food Safety and Applied Nutrition, and state health departments in California, Connecticut, Georgia, Minnesota, and Oregon. The population under active surveillance for foodborne infections was approximately 16.1 million persons or roughly 6% of the United States Population. Through weekly or monthly contact with all clinical laboratories in these sites, 8,576 total isolations were recorded: 2,205 cases of salmonellosis, 1,273 cases of shigellosis, 468 cases of cryptosporidiosis, 340 of E. coli O157:H7 infections, 139 of yersiniosis, 77 of listeriosis, 51 of Vibrio infections, and 49 of cyclosporiasis. Results from 1997 demonstrate that while there are regional and seasonal differences in reported incidence rates of certain bacterial and parasitic diseases, and that some pathogens showed a change in incidence from 1996, the overall incidence of illness caused by pathogens under surveillance was stable. More data over more years are needed to assess if observed variations in incidence reflect yearly fluctuations or true changes in the burden of foodborne illness. C1 Ctr Dis Control & Prevent, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, Foodborne & Diarrheal Dis Branch, Atlanta, GA 30333 USA. Calif Emerging Infect Program, San Francisco Off, San Francisco, CA 94103 USA. Yale Univ, Sch Publ Hlth, Connecticut Emerging Infect Program, New Haven, CT 06510 USA. Vet Affairs Med Ctr, Georgia Emerging Infect Program, Decatur, GA 30033 USA. Minnesota Dept Hlth, Minneapolis, MN 55414 USA. Oregon Hlth Div, Portland, OR 97232 USA. US Food Safety & Inspect Serv, USDA, Epidemiol & Risk Assessment Div, Washington, DC 20250 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Wallace, DJ (reprint author), Ctr Dis Control & Prevent, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, Foodborne & Diarrheal Dis Branch, 1600 Clifton Rd NE, Atlanta, GA 30333 USA. NR 4 TC 66 Z9 69 U1 1 U2 3 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUN PY 2000 VL 63 IS 6 BP 807 EP 809 PG 3 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 322ZD UT WOS:000087538900017 PM 10852576 ER PT J AU Kvenberg, JE Schwalm, DJ AF Kvenberg, JE Schwalm, DJ TI Use of microbial data for hazard analysis and critical control point verification - Food and drug administration perspective SO JOURNAL OF FOOD PROTECTION LA English DT Article AB This paper examines the role that the microbiologist and microbiological testing play in implementing hazard analysis and critical control point (HACCP) programs. HACCP offers a more comprehensive and science-based alternative for controlling food safety hazards compared with traditional sanitation programs based upon good manufacturing practices. Controlling hazards under an HACCP program requires a systematic assemblage of reliable data relating to the occurrence, elimination, prevention, and reduction of hazards. These data need to be developed in a transparent environment that will ensure that the best scientific methodologies have been employed in developing the needed data. The two mechanisms used in HACCP to assess the adequacy of the database are validation studies and the verification assessments. Microbiological testing is an important mechanism for collecting data used in developing and implementing an HACCP plan. Microbial sample data can help establish standard operating procedures (SOPs) for sanitation, assess the likelihood of the occurrence of hazards, establish critical limits, and assess the validity of the HACCP plan. The use of a performance standard to assess whether microbiological hazards have been reduced to an acceptable level creates an especially important use for microbial analysis. Microbial testing is also useful in implementing an HACCP plan by helping to monitor the effectiveness of sanitation SOPs, the compliance of incoming ingredients with safety criteria, the safety of product being held for corrective action, and the safety of the finished product. The verification audits demonstrate that all control measures have been applied as designed in the HACCP plan. Although auditing HACCP records is the primary means of verification, microbial sampling can play an important role as well. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Kvenberg, JE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-601,200 C St SW, Washington, DC 20204 USA. NR 4 TC 21 Z9 21 U1 0 U2 4 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUN PY 2000 VL 63 IS 6 BP 810 EP 814 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 322ZD UT WOS:000087538900018 PM 10852577 ER PT J AU Buchanan, RL AF Buchanan, RL TI Acquisition of microbiological data to enhance food safety SO JOURNAL OF FOOD PROTECTION LA English DT Article AB The routine acquisition and archiving of microbiological data is undertaken for two reasons. The first is the development of historical microbiological profiles of foods, ingredients, or processes in order to determine or verify that microorganisms of concern are being controlled to the level desired. The second reason is data concerning the pathogenicity or virulence of foodborne pathogens and their behavior in foods in order to develop strategies and criteria for assuring microbiological safety. Both types of microbiological data are essential to effective food safety programs. A firm understanding of the uses and limitations of both is essential to correct acquisition, interpretation, and use of such data. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Buchanan, RL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 4 TC 16 Z9 17 U1 0 U2 2 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUN PY 2000 VL 63 IS 6 BP 832 EP 838 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 322ZD UT WOS:000087538900023 PM 10852582 ER PT J AU Murdin, AD Gellin, B Brunham, RC Campbell, LA Christiansen, G Deal, CD Jenson, HB Metcalf, B Sankaran, B Stephens, RS Wilfert, C AF Murdin, AD Gellin, B Brunham, RC Campbell, LA Christiansen, G Deal, CD Jenson, HB Metcalf, B Sankaran, B Stephens, RS Wilfert, C TI Collaborative multidisciplinary workshop report: Progress toward a Chlamydia pneumoniae vaccine SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material C1 Aventis Pasteur, Toronto, ON M2R 3T4, Canada. Univ British Columbia, Fac Med, Ctr Dis Control, Vancouver, BC, Canada. Aarhus Univ, Dept Med Microbiol & Immunol, Aarhus, Denmark. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Pathobiol, Seattle, WA 98195 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Univ Texas, Hlth Sci Ctr, Dept Pediat & Microbiol, San Antonio, TX USA. Wyeth Lederle Vaccines, Mol Biol & Genet, W Henrietta, NY USA. Wyeth Lederle Vaccines, Prot Chem, W Henrietta, NY USA. Univ Calif Berkeley, Sch Publ Hlth, Div Infect Dis, Berkeley, CA 94720 USA. Duke Univ, Med Ctr, Dept Pediat, Chapel Hill, NC USA. Duke Univ, Med Ctr, Dept Microbiol, Chapel Hill, NC USA. RP Murdin, AD (reprint author), Aventis Pasteur, 1755 Steeles Ave W, Toronto, ON M2R 3T4, Canada. NR 13 TC 3 Z9 3 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 2000 VL 181 SU 3 BP S552 EP S557 DI 10.1086/315601 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 331MY UT WOS:000088023900036 PM 10839757 ER PT J AU Rosen, H Muhlestein, JB Bartlett, J Chen, S Chikami, G Corson, M Shah, PK Gurfinkel, E Handsfield, H Jackson, L Knirsch, C Kronmal, R McCutchan, JA Shea, S AF Rosen, H Muhlestein, JB Bartlett, J Chen, S Chikami, G Corson, M Shah, PK Gurfinkel, E Handsfield, H Jackson, L Knirsch, C Kronmal, R McCutchan, JA Shea, S TI Collaborative multidisciplinary workshop report: Clinical antimicrobial trials for primary and secondary prevention of atherosclerotic cardiovascular disease SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Multidisciplinary Meeting to Promote Collaborative Research CY SEP 22-25, 1999 CL SEATTLE, WASHINGTON SP Infect Dis Soc Amer, Ctr Dis Control & Prevent, Natl Heart, Lung, & Blood Inst, Natl Inst Allergy &Infect Dis ID AZITHROMYCIN AB The task assigned to the working group on Clinical Antimicrobial Trials for Primary and/or Secondary Prevention of Atherosclerotic Cardiovascular Disease was to evaluate the need for additional clinical antibiotic trials of a primary or secondary nature for the treatment of atherosclerotic heart disease and to suggest possible designs for future trials. In addition, the working group was to define the role of collaboration in answering research questions. C1 Univ Utah, Latter Day St Hosp, Div Cardiol, Salt Lake City, UT 84143 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Div Cardiol, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Med Infect Dis & Epidemiol, Harborview Med Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Seattle King Cty Dept Publ Hlth, Sexually Transmitted Dis Control Program, Seattle, WA USA. Johns Hopkins Univ, Div Infect Dis, Baltimore, MD USA. US FDA, Div Cardiorenal Drugs, Rockville, MD 20857 USA. US FDA, Div Antiinfect Drug Prod, Rockville, MD 20857 USA. Cedars Sinai Med Ctr, Div Cardiol, Los Angeles, CA 90048 USA. Cedars Sinai Med Ctr, Atherosclerosis Res Unit, Los Angeles, CA 90048 USA. Univ San Diego, Treatment Ctr, Div Infect Dis, San Diego, CA 92110 USA. Fundac Favaloro, Coronary Unit, Buenos Aires, DF, Argentina. Pfizer Inc, Med Directors Off, New York, NY USA. Columbia Univ, Div Gen Internal Med, New York, NY USA. RP Muhlestein, JB (reprint author), Univ Utah, Latter Day St Hosp, Div Cardiol, 8th Ave & C St, Salt Lake City, UT 84143 USA. NR 4 TC 2 Z9 2 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 2000 VL 181 SU 3 BP S582 EP S584 DI 10.1086/315597 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 331MY UT WOS:000088023900043 PM 10839764 ER PT J AU Lee, YH Fang, KM Yang, CM Hwang, SM Chiu, CT Tsai, WH AF Lee, YH Fang, KM Yang, CM Hwang, SM Chiu, CT Tsai, WH TI Kainic acid-induced neurotrophic activities in developing cortical neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE kainic acid; alpha-amino-3-hydroxy-5-methyl-4-isoxazole; propionate/kainic acid receptors; neuroprotection; phospholipase C; nerve growth factor; calcium ID NERVE GROWTH-FACTOR; GLUTAMATE-RECEPTOR SUBUNITS; AMPA RECEPTORS; RAT-BRAIN; CALCIUM; SURVIVAL; CELLS; CA2+; CHANNELS; RELEASE AB Using primary cultured cortical neurons from embryonic rat brains, we elucidated an alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainic acid (KA) receptor-mediated neuroprotective mechanism through actions of nerve growth factor (NGF) in developing neurons. Neurotoxicity of KA in early days in vitro neurons was quite low compared with the mature neurons. However, pretreatment with anti-NGF antibody or TrkA inhibitor AG-879 profoundly raised KA toxicity. Furthermore, KA stimulation resulted in an increase of Trk A expression and phosphorylation, which was blocked not only by the AMPA/KA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione and AG-879, but also by the phospholipase C inhibitor U73122 and the intracellular calcium chelator BAPTA. A study of polyphosphoinositide turnover showed that KA-stimulated phospholipase C (PLC) activity was directly triggered by the AMPA/KA receptor activity, but not by the activity of TrkA or other excitatory amino acid receptor subtypes. Sources of KA-increased intracellular calcium levels were contributed by both extracellular calcium influx and intracellular calcium release and were partially sensitive to guanosine 5'-O-(2-thiodiphosphate). These results indicate that in developing cortical neurons, activation of AMPA/KA receptors by KA may induce expression, followed by activation of TrkA via PLC signaling and intracellular calcium elevation and hence increase reception of NGF on KA-challenged neurons. A G protein-coupled AMPA/KA receptor may be involved in these metabotropic events for neuronal protection. C1 Taipei Med Coll, Dept Physiol, Taipei, Taiwan. Taipei Med Coll, Grad Inst Med, Taipei, Taiwan. Chang Gung Univ, Dept Pharmacol, Tao Yuan, Taiwan. Chang Gung Univ, Dept Anat, Tao Yuan, Taiwan. US FDA, Antiviral Res Lab, CDER, Rockville, MD 20857 USA. RP Lee, YH (reprint author), Taipei Med Coll, Dept Physiol, 250 Wu Hsing St, Taipei, Taiwan. NR 41 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2000 VL 74 IS 6 BP 2401 EP 2411 DI 10.1046/j.1471-4159.2000.0742401.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 312XG UT WOS:000086968800020 PM 10820201 ER PT J AU Johnson, K AF Johnson, K TI Cost effectiveness analysis - Assessing the assumptions behind the assumptions SO JOURNAL OF RHEUMATOLOGY LA English DT Letter ID QUALITY-OF-LIFE; HEALTH-CARE; ECONOMIC-EVALUATION; MEDICINE; ISSUES C1 US FDA, Rockville, MD 20857 USA. RP Johnson, K (reprint author), US FDA, Rockville, MD 20857 USA. NR 28 TC 4 Z9 4 U1 0 U2 1 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 JUN PY 2000 VL 27 IS 6 BP 1565 EP 1567 PG 3 WC Rheumatology SC Rheumatology GA 320BH UT WOS:000087380800051 PM 10852296 ER PT J AU Wear, KA AF Wear, KA TI Anisotropy of ultrasonic backscatter and attenuation from human calcaneus: Implications for relative roles of absorption and scattering in determining attenuation SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID HIP FRACTURE; MYOCARDIAL TISSUE; TRABECULAR BONE; VELOCITY; DENSITY; WOMEN; OSTEOPOROSIS; DIFFRACTION; DISPERSION; SIGNALS AB Although bone sonometry has been demonstrated to be useful in the diagnosis of osteoporosis, much remains to be learned about the processes governing the interactions between ultrasound and bone. In order to investigate these processes, ultrasonic attenuation and backscatter in two orientations were measured in 43 human calcaneal specimens in vitro at 500 kHz. In the mediolateral (ML) orientation, the ultrasound propagation direction is approximately perpendicular to the trabecular axes. In the anteroposterior (AP) orientation, a wide range of angles between the ultrasound propagation direction and trabecular axes is encountered. Average attenuation slope was 18% greater while average backscatter coefficient was 50% lower in the AP orientation compared with the ML orientation. Backscatter coefficient in both orientations approximately conformed to a cubic dependence on frequency, consistent with a previously reported model. These results support the idea that absorption is a greater component of attenuation than scattering in human calcaneal trabecular bone. (C) 2000 Acoustical Society of America. [S0001-4966(00)03806-6]. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP US FDA, Ctr Devices & Radiol Hlth, HFZ-142,12720 Twinbrook Pkwy, Rockville, MD 20852 USA. EM kaw@cdrh.fda.gov NR 38 TC 56 Z9 56 U1 1 U2 4 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JUN PY 2000 VL 107 IS 6 BP 3474 EP 3479 DI 10.1121/1.429417 PG 6 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 322KE UT WOS:000087508100051 PM 10875391 ER PT J AU Lee, S Lapham, CK Chen, H King, L Manischewitz, J Romantseva, T Mostowski, K Stantchev, TS Broder, CC Golding, H AF Lee, S Lapham, CK Chen, H King, L Manischewitz, J Romantseva, T Mostowski, K Stantchev, TS Broder, CC Golding, H TI Coreceptor competition for association with CD4 may change the susceptibility of human cells to infection with T-tropic and macrophagetropic isolates of human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID MONOCYTE-DERIVED MACROPHAGES; PROTEIN-COUPLED RECEPTOR; POST-ENTRY LEVEL; HIV-1 ENTRY; ENVELOPE GLYCOPROTEIN; SURFACE ASSOCIATION; CCR5 EXPRESSION; DENDRITIC CELLS; AMINO-TERMINUS; VIRAL ENTRY AB The chemokine receptors CCR5 and CXCR4 were found to function in vivo as the principal coreceptors for hi-tropic and T-tropic human immunodeficiency virus (HIV) strains, respectively. Since many primary cells express multiple chemokine receptors, it mas important to determine if the efficiency of virus-cell fusion is influenced not only by the presence of the appropriate coreceptor (CXCR4 or CCR5) but also by the levels of other coreceptors expressed by the same target cells, We found that in cells with low to medium surface CD4 density, coexpression of CCR5 and CXCR4 resulted in a significant reduction in the fusion with CXCR4 domain (X4) envelope-expressing cells and in their susceptibility to infection with X4 viruses. The inhibition could be reversed either by increasing the density of surface CD4 or by antibodies against the N terminus and second extracellular domains of CCRS, In addition, treatment of macrophages with a combination of anti-CCR5 antibodies or beta-chemokines increased their fusion with X4 envelope-expressing cells, Conversely, overexpression of CXCR4 compared with CCR5 inhibited CCR5-dependent HIV-dependent fusion in 3T3.CD4.401 cells, Thus, coreceptor competition for association with CD4 may occur in vivo and is likely to have important implications for the course of HIV type 1 infection, as well as for the outcome of coreceptor-targeted therapies. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cell & Gene Therapy, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Immunol & Microbiol, Bethesda, MD 20814 USA. RP Golding, H (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, HFM-454,Bldg 29B,Rm 4NN04,8800 Rockville Pike, Bethesda, MD 20892 USA. FU NIAID NIH HHS [R01 AI043885, R01AI43885] NR 40 TC 41 Z9 43 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 JUN PY 2000 VL 74 IS 11 BP 5016 EP 5023 DI 10.1128/JVI.74.11.5016-5023.2000 PG 8 WC Virology SC Virology GA 312MX UT WOS:000086948000009 PM 10799575 ER PT J AU Weng, YK Yang, ZN Weiss, CD AF Weng, YK Yang, ZN Weiss, CD TI Structure-function studies of the self-assembly domain of the human immunodeficiency virus type 1 transmembrane protein gp41 SO JOURNAL OF VIROLOGY LA English DT Article ID SIV GP41; ENVELOPE GLYCOPROTEIN; MUTATIONAL ANALYSIS; CRYSTAL-STRUCTURE; ATOMIC-STRUCTURE; LEUCINE ZIPPER; CORE STRUCTURE; COILED-COIL; HIV-1 GP41; ECTODOMAIN AB The coiled-coil region of the human immunodeficiency virus type 1 transmembrane protein (gp41) makes up the interior core of the six-helix bundle structure of the gp41 self-assembly domain. We extended our previous study of this domain (Y. Weng and C. D. Weiss, J. Virol. 72:9676-9682, 1998) by analyzing 23 additional mutants at positions that lie at the interface of the interior core and outer helices. We found nine new functional mutants. For most mutants, the activity could be explained by the ability of the modeled mutants to stabilize the six-helix bundle structure. The present study provides insights into the envelope glycoprotein fusion mechanism and information for rational drug and vaccine design. C1 US FDA, CBER, Bethesda, MD 20892 USA. NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. RP Weiss, CD (reprint author), US FDA, CBER, HFM 466,NIH Bldg 29,Room 532,29 Lincoln Dr, Bethesda, MD 20892 USA. RI Weiss, Carol/F-6438-2011 OI Weiss, Carol/0000-0002-9965-1289 NR 19 TC 36 Z9 36 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 JUN PY 2000 VL 74 IS 11 BP 5368 EP 5372 DI 10.1128/JVI.74.11.5368-5372.2000 PG 5 WC Virology SC Virology GA 312MX UT WOS:000086948000050 PM 10799616 ER PT J AU Rubin, SA Pletnikov, M Taffs, R Snoy, PJ Kobasa, D Brown, EG Wright, KE Carbone, KM AF Rubin, SA Pletnikov, M Taffs, R Snoy, PJ Kobasa, D Brown, EG Wright, KE Carbone, KM TI Evaluation of a neonatal rat model for prediction of mumps virus neurovirulence in humans SO JOURNAL OF VIROLOGY LA English DT Article ID RUBELLA VACCINE; ASEPTIC-MENINGITIS; MEASLES; HYDROCEPHALUS; INFECTION; HAMSTERS; STRAINS; BRAIN; CHILDREN; DISEASE AB Neurovirulence of several mumps virus strains was assessed in a prototype rat neurovirulence test and compared to results obtained in the monkey neurovirulence test. The relative human neurovirulence of these strains was proportional to the severity of hydrocephalus in rats but not to lesion scores in the monkeys. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Psychiat, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD 21218 USA. Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON K1H 8M5, Canada. RP Rubin, SA (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29A,Room 1A-21,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 34 TC 46 Z9 47 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 JUN PY 2000 VL 74 IS 11 BP 5382 EP 5384 DI 10.1128/JVI.74.11.5382-5384.2000 PG 3 WC Virology SC Virology GA 312MX UT WOS:000086948000053 PM 10799619 ER PT J AU Pazdur, R AF Pazdur, R TI The Damjanov/Meropol article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID 5-FLUOROURACIL; TOXICITY C1 US FDA, Div Oncol Drug Prod, Washington, DC 20204 USA. RP Pazdur, R (reprint author), US FDA, Div Oncol Drug Prod, Washington, DC 20204 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUN PY 2000 VL 14 IS 6 BP 819 EP 820 PG 2 WC Oncology SC Oncology GA 368QP UT WOS:000090129300008 ER PT J AU McLaughlin, SM Tall, BD Shaheen, A Elsayed, EE Faisal, M AF McLaughlin, SM Tall, BD Shaheen, A Elsayed, EE Faisal, M TI Zoosporulation of a new Perkinsus species isolated from the gills of the softshell clam Mya arenaria SO PARASITE-JOURNAL DE LA SOCIETE FRANCAISE DE PARASITOLOGIE LA English DT Article DE Perkinsus spp.; softshell clam (Mya arenaria]; zoosporulation; zoospores; ultrastructure ID RIBOSOMAL-RNA GENE; FINE-STRUCTURE; PATINOPECTEN-YESSOENSIS; ATLANTICUS APICOMPLEXA; RUDITAPES-DECUSSATUS; PHYLUM APICOMPLEXA; JAPANESE SCALLOPS; BRITISH-COLUMBIA; OYSTER PATHOGEN; PARASITE AB A gill-associated Perkinsus sp. isolated from the softshell clam (Myo arenaria) is described as a new species, P. chesapeaki sp. nov. Examination of the parasite in seawater cultures revealed life cycle stages and zoosporulation processes similar to those described for other species of the genus Perkinsus. Prezoosporangia developed thickened cell walls upon contraction of the cytoplasm and development of a distinctive clear area between the cell wall and the protoplast. Successive bipartition of the protoplast led to the formation of hundred's of zoospores within mature sporangia. Zoospores were released into seawater through one or more discharge tubes, Ultrastructural studies revealed an oblong zoospore possessing two flagella that arose from a concave side located in the upper third of the zoospore body. The anterior flagellum possessed a unilateral array of hair-like structures. A large anterior vacuole and basolateral nucleus dominated the cytoplasm of the zoospore body. The presence of a rudimentary apical complex including an open-sided conoid, rhoptries, micronemes, and subpellicular microtubules were also discerned. Differences in zoospore morphology, and sequence analyses of two genes previously reported, support the designation of the gill-associated Perkinsus from the softshell clam as a new species. C1 Coll William & Mary, Sch Marine Sci, Virginia Inst Marine Sci, Gloucester Point, VA 23062 USA. NOAA, Natl Ocean Serv, Ctr Coastal Environm Hlth & Biomol Res, Oxford, MD 21654 USA. US FDA, Microbial Ecol Branch, Washington, DC 20204 USA. Fac Vet Med Moshtohor, Benha, Egypt. Cairo Univ, Fac Vet Med, Giza, Egypt. RP Faisal, M (reprint author), Coll William & Mary, Sch Marine Sci, Virginia Inst Marine Sci, Gloucester Point, VA 23062 USA. OI Tall, Ben/0000-0003-0399-3629 NR 29 TC 41 Z9 42 U1 0 U2 4 PU PRINCEPS EDITIONS PI ISSY MOULINEAUX PA 64 AVENUE CHARLES DE GAULLE, 92130 ISSY MOULINEAUX, FRANCE SN 1252-607X J9 PARASITE JI Parasite-J. Soc. Fr. Parasitol. PD JUN PY 2000 VL 7 IS 2 BP 115 EP 122 PG 8 WC Parasitology SC Parasitology GA 324RY UT WOS:000087636200008 PM 10887658 ER PT J AU Andrews, CW Bennett, L Yu, LX AF Andrews, CW Bennett, L Yu, LX TI Predicting human oral bioavailability of a compound: Development of a novel quantitative structure-bioavailability relationship SO PHARMACEUTICAL RESEARCH LA English DT Article DE bioavailability; quantitative structure-bioavailability relationship; Lipinski's Rule of Five ID DRUGS AB Purpose. The purpose of this investigation was to develop a quantitative structure-bioavailability relationship (QSBR) model for drug discovery and development. Methods. A database of drugs with human oral bioavailability was assembled in electronic form with structure in SMILES format. Using that database, a stepwise regression procedure was used to link oral bioavailability in humans and substructural fragments in drugs. The regression model was compared with Lipinski's Rule of Five. Results. The human oral bioavailability database contains 591 compounds. A regression model employing 85 descriptors was built to predict the human oral bioavailability of a compound based on its molecular structure. Compared to Lipinski's Rule of Five, the false negative predictions were reduced from 5% to 3% while the false positive predictions decreased from 78% to 53%. A set of substructural descriptors was identified to show which fragments tend to increase/ decrease human oral bioavailability. Conclusions. A novel quantitative structure-bioavailability relationship (QSBR) was developed. Despite a large degree of experimental error, the model was reasonably predictive and stood up to crossvalidation. When compared to Lipinski's Rule of Five, the QSBR model was able to reduce false positive predictions. C1 Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Yu, LX (reprint author), US FDA, Div Prod Qual Res, 5600 Fishers Lane,HFD-941,NLRC 2400B, Rockville, MD 20857 USA. EM yul@cder.fda.gov NR 9 TC 94 Z9 99 U1 1 U2 15 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORDR JI Pharm. Res. PD JUN PY 2000 VL 17 IS 6 BP 639 EP 644 DI 10.1023/A:1007556711109 PG 6 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 342VF UT WOS:000088665300001 PM 10955834 ER PT J AU Sheehan, DM AF Sheehan, DM TI Activity of environmentally relevant low doses of endocrine disrupters and the bisphenol a controversy: Initial results confirmed SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Editorial Material ID REPRODUCTIVE-ORGANS; ESTRADIOL; MICE; DIETHYLSTILBESTROL; RAT; XENOESTROGENS; EXPOSURE; GROWTH; GLAND C1 US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Sheehan, DM (reprint author), US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 25 TC 37 Z9 37 U1 0 U2 5 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD JUN PY 2000 VL 224 IS 2 BP 57 EP 60 DI 10.1046/j.1525-1373.2000.22401.x PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 315HC UT WOS:000087106400001 PM 10806411 ER PT J AU Desaiah, D Reddy, SLN Imam, SZ Ali, SF AF Desaiah, D Reddy, SLN Imam, SZ Ali, SF TI Role of neuronal nitric oxide in methamphetamine neurotoxicity and protection by nNOS inhibitor SO PURE AND APPLIED CHEMISTRY LA English DT Article; Proceedings Paper CT 4th Congress of Toxicology in Developing Countries CY NOV 06-10, 1999 CL ANTALYA, TURKEY SP Int Union Toxicol, Int Union Pure & Appl Chem, Nat Inst Environm Hlth Sci, Dow Agrochem, SE Asia, Proctor & Gamble, US Soc Toxicol, European Soc Toxicol, IBRO, TUBITAK, EISAI, SANKYO, Glaxo Wellcome ID INDUCED DOPAMINERGIC NEUROTOXICITY; SYNTHASE; MICE; 7-NITROINDAZOLE; INCREASE AB Methamphetamine (METH) is a potent psychostimulant known to produce neurotoxicity. The dopaminergic pathway is particularly sensitive to METH. Recent studies showed that 7-nitroindazole (7-NI), a selective inhibitor of neuronal nitric oxide synthase (nNOS), provided protection against METH neurotoxicity both in vitro and in vivo. The present studies were conducted to determine the nNOS activity in various regions of the brain of young adult male Sprague-Dawley rats treated with different doses of METH. Rats were injected ip with 5, 10, 20, and 40 mg/kg and 24 h after the rats were sacrificed and the brain regions (hippocampus, frontal cortex, and cerebellum) were quickly dissected. The cytosolic fractions were prepared, and the nNOS activity was determined using the H-3-citrulline assay. The results showed that nNOS activity was significantly increased in all three brain regions of rats treated with METH. The increase was dose dependent reaching a maximum of 40-100% over the control values. Rats treated with 7-NI 30 min prior to METH injection provided protection against the toxicity and also showed a reduction of nNOS activity. The activation of nNOS is known to increase the synthesis of NO which is involved in the regulation of several neurotransmitter pathways including catecholaminergic system. Reducing the METH-induced production of NO by pretreatment with selective inhibitor of nNOS, 7-NI, provided protection against METH neurotoxicity. C1 Univ Mississippi, Med Ctr, Dept Neurol, Jackson, MS 39216 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Desaiah, D (reprint author), Univ Mississippi, Med Ctr, Dept Neurol, Jackson, MS 39216 USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU INT UNION PURE APPLIED CHEMISTRY PI RES TRIANGLE PK PA 104 TW ALEXANDER DR, PO BOX 13757, RES TRIANGLE PK, NC 27709-3757 USA SN 0033-4545 J9 PURE APPL CHEM JI Pure Appl. Chem. PD JUN PY 2000 VL 72 IS 6 BP 1001 EP 1006 DI 10.1351/pac200072061001 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 355YJ UT WOS:000089415900005 ER PT J AU Kaczmarek, RV Conway, BJ Slayton, RO Suleiman, OH AF Kaczmarek, RV Conway, BJ Slayton, RO Suleiman, OH TI Results of a nationwide survey of chest radiography: Comparison with results of a previous study SO RADIOLOGY LA English DT Article DE images, quality; quality assurance; radiations, exposure to patients and personnel; radiations, measurement; screens and films; thorax, radiography ID FILM RADIOGRAPHY; EXPOSURE AB PURPOSE: To provide public health information by means of measurement of the radiation exposures that patients undergoing chest radiography would receive and to compare the results with those of a similar previous survey. MATERIALS AND METHODS: Surveyed facilities,were randomly selected from each state. Patient exposure was evaluated along with film processing, half-value layer, and image quality. Additional information obtained concerned type of equipment, facility work load, radiographic technique, screen-film system, and grid type. RESULTS: Mean entrance air kerma in all facilities was 141 mu Gy (16.1 mR). Mean kilovoltage in all facilities was 101 kV. In 1994, 140 (90%) of 156 hospitals (vs 71% in 1984) and 92 (58%; nearly double the percentage in 1984) of 159 nonhospital sites were using grids. Scoring with the imaging test tool resulted in a mean spatial resolution of 2.3 cycles per millimeter, and a mean low-contrast sensitivity of about 3%. Two hundred fifty-three (80%) of 315 facilities surveyed were processing film at minimum acceptable performance levels. CONCLUSION: Mean entrance air kerma for ail facilities did not substantially change. Although increased grid usage would lead to the expectation of higher measured exposures, this was offset by an increase in the use of faster screen-film combinations. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Kaczmarek, RV (reprint author), US FDA, Ctr Devices & Radiol Hlth, 1350 Piccard Dr, Rockville, MD 20857 USA. NR 17 TC 13 Z9 13 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 2000 VL 215 IS 3 BP 891 EP 896 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 317VE UT WOS:000087247000042 PM 10831717 ER PT J AU Rulis, AM AF Rulis, AM TI International Society of Regulatory Toxicology and Pharmacology 1999 International Achievement Award SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID CARCINOGENIC POTENCY DATABASE; ANIMAL BIOASSAYS; CHRONOLOGICAL SUPPLEMENT C1 US FDA, Ctr Food Safety & Appl Nutr, Off Premarket Approval, Washington, DC 20204 USA. RP Rulis, AM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Premarket Approval, Washington, DC 20204 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD JUN PY 2000 VL 31 IS 3 BP 244 EP 247 DI 10.1006/rtph.2000.1388 PG 4 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 346DJ UT WOS:000088855200001 ER PT J AU Klinman, DM Kamstrup, S Verthelyi, D Gursel, I Ishii, KJ Takeshita, F Gursel, M AF Klinman, DM Kamstrup, S Verthelyi, D Gursel, I Ishii, KJ Takeshita, F Gursel, M TI Activation of the innate immune system by CpG oligodeoxynucleotides: immunoprotective activity and safety SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Article ID IMMUNOSTIMULATORY DNA-SEQUENCES; ALLERGIC LUNG INFLAMMATION; INDUCE AUTOIMMUNE-DISEASE; NECROSIS-FACTOR-ALPHA; BACTERIAL-DNA; INTERFERON-GAMMA; B-CELLS; MURINE LEISHMANIASIS; TH1 RESPONSES; NZB/NZW MICE C1 US FDA, Sect Retroviral Res, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Sect Retroviral Res, Ctr Biol Evaluat & Res, Bldg 29A,Rm 3 D 10, Bethesda, MD 20892 USA. 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 55 TC 32 Z9 32 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PD JUN PY 2000 VL 22 IS 1-2 BP 173 EP 183 DI 10.1007/s002810050027 PG 11 WC Immunology; Pathology SC Immunology; Pathology GA 334DL UT WOS:000088170400018 PM 10944812 ER PT J AU Flynn, KM Ferguson, SA Delclos, KB Newbold, RR AF Flynn, KM Ferguson, SA Delclos, KB Newbold, RR TI Effects of genistein exposure on sexually dimorphic behaviors in rats SO TOXICOLOGICAL SCIENCES LA English DT Article DE estrogen; phytoestrogen; isoflavone; endocrine disrupter; nutrition; chronic exposure ID SEX-DIFFERENCES; GONADAL-HORMONES; EARLY-LIFE; PLAY; PHYTOESTROGENS; ISOFLAVONES; DIFFERENTIATION; TESTOSTERONE; CHEMICALS; DAIDZEIN AB The phytoestrogen genistein, the principal isoflavone in soybeans, has adverse effects on animal reproduction. As adult physiology and behavior are sensitive to perturbation by developmental estrogens, exposure to genistein during development may produce behavioral alterations as well. Pregnant rats were fed soy-free diets containing 0, 25, 250, or 1250 ppm genistein (approximately 0, 2, 20, or 100 mg/kg/day) beginning on gestational day 7, and offspring continued on these diets through postnatal day (PND) 77. Male and female offspring were assessed for levels of sexually dimorphic behaviors: open field activity, play behavior, running wheel activity, and consumption of saccharin- and sodium chloride-flavored solutions. Consumption of the salt solution was affected by genistein, with animals in the 1250-ppm group drinking significantly more than controls; consumption of plain water was unaffected. Genistein treatment also significantly affected play behavior; although no treated group was significantly different from controls, and the effect was not sexually dimorphic. Running wheel activity and saccharin solution consumption showed significant sex differences, but no effects of genistein treatment. Gestational duration, total and live pups per litter, and total and live litter sex ratios were not significantly affected by genistein. However, average weight per live pup at birth and offspring body weights from PND 42-77 were significantly decreased in the 1250-ppm group. Body weight and food intake for the darns were also significantly decreased in the 1250-ppm group. These results indicate that developmental genistein treatment, at levels that decrease maternal and offspring body weight, causes subtle alterations in some sexually dimorphic behaviors. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NIEHS, Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Flynn, KM (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd,HFT-132, Jefferson, AR 72079 USA. NR 39 TC 74 Z9 75 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUN PY 2000 VL 55 IS 2 BP 311 EP 319 DI 10.1093/toxsci/55.2.311 PG 9 WC Toxicology SC Toxicology GA 319JT UT WOS:000087338300010 PM 10828262 ER PT J AU Kodell, RL Lin, KK Thorn, BT Chen, JJ AF Kodell, RL Lin, KK Thorn, BT Chen, JJ TI Bioassays of shortened duration for drugs: Statistical implications SO TOXICOLOGICAL SCIENCES LA English DT Article DE chronic; dose-response; food and drug administration (FDA); Monte Carlo; MVK model; power; survival; trend ID CARCINOGENICITY EXPERIMENTS; SURVIVAL FUNCTIONS; TUMOR-INCIDENCE; MODEL; MORTALITY; DISEASE; ONSET AB Declining survival rates in rodent carcinogenesis bioassays have raised a concern that continuing the practice of terminating such studies at 24 months could result in too few live animals at termination for adequate pathological evaluation. One option for ensuring sufficient numbers of animals at the terminal sacrifice is to shorten the duration of the bioassay, but this approach is accompanied by a reduction in statistical power for detecting carcinogenic potential. The present study was conducted to evaluate the loss of power associated with early termination. Data from drug studies in rats were used to formulate biologically based dose-response models of carcinogenesis using the 2-stage clonal expansion model as a context. These dose-response models, which were chosen to represent 6 variations of the initiation-promotion-completion cancer model, were employed to generate a large number of representative bioassay data sets using Monte Carlo simulation techniques. For a variety of tumor dose-response trends, tumor lethality, and competing risk-survival rates, the power of age-adjusted statistical tests to assess the significance of carcinogenic potential was evaluated at 18 and 21 months, and compared to the power at the normal 24-month stopping time. The results showed that stopping at 18 months would reduce power to an unacceptable level for all 6 submodels of the 2-stage clonal expansion model, with the pure-promoter and pure-completer models being most adversely affected. For the 21-month stopping time, the results showed that, unless pure promotion can be ruled out a priori as a potential carcinogenic mode of action, the loss of power is too great to warrant early stopping. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. US FDA, Ctr Drug Evaluat & Res, Div Biometr 2, Rockville, MD 20857 USA. ROW Sci Inc, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Kodell, RL (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. NR 27 TC 4 Z9 4 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 JUN PY 2000 VL 55 IS 2 BP 415 EP 432 DI 10.1093/toxsci/55.2.415 PG 18 WC Toxicology SC Toxicology GA 319JT UT WOS:000087338300023 PM 10828275 ER PT J AU Epstein, JS AF Epstein, JS TI Should the FDA mandate that autologous units drawn and transfused within a single institution be tested for markers of infectious disease? Reply SO TRANSFUSION LA English DT Letter C1 US FDA, OBRR, CBER, Rockville, MD 20857 USA. RP Epstein, JS (reprint author), US FDA, OBRR, CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 2000 VL 40 IS 6 BP 754 EP 754 PG 1 WC Hematology SC Hematology GA 325JE UT WOS:000087671800024 ER PT J AU Burkhardt, W Calci, KR Watkins, WD Rippey, SR Chirtel, SJ AF Burkhardt, W Calci, KR Watkins, WD Rippey, SR Chirtel, SJ TI Inactivation of indicator microorganisms in estuarine waters SO WATER RESEARCH LA English DT Article DE indicators; inactivation; sunlight; male-specific bacteriophage ID ESCHERICHIA-COLI; FECAL-COLIFORMS; SOLAR-RADIATION; SEAWATER; SURVIVAL; ENUMERATION; SUNLIGHT; BACTERIA; BACTERIOPHAGES; ENTEROVIRUSES AB In the United States, shellfish growing areas are classified, in part, using standards based on the densities of either the total or fecal coliform groups in surface waters. However, the standards currently employed may not reliably index the presence of certain enteric pathogens, particularly enteric viruses responsible for human illnesses, even though both the pathogens and indicators derive from the same fecal contamination. To some extent, this may be due to differences in the survival of these pathogens in the environment relative to that of the bacterial indicators. This investigation was conducted to assess the effects of temperature, salinity, dissolved oxygen, geographic location, season, and solar radiation on the survival of selected indicator microorganisms in estuarine waters. The indicators examined included fecal coliforms, Escherichia coli. Clostridium perfringens, and male-specific bacteriophage (MSB), a potential indicator of enteric viruses. In situ experiments were performed in estuarine waters of Alabama and Rhode Island. Among the parameters examined, sunlight and/or temperature most significantly affected indicator decay rates. In general. the effects from exposure to sunlight accounted for up to 83, 84, and 99% of the density reductions of MSB, C, perfringens and fecal coliforms, respectively. Thus, the effects from sunlight were greatest on fecal coliforms and much less pronounced on MSB and C. perfringens. For fecal coliforms. the effect of sunlight was more pronounced during the winter than the summer. In the absence of sunlight, the rate of MSB decline was strongly negatively correlated with estuarine water temperatures and dissolved oxygen. Overall. fecal coliform decay rates were dissimilar to those found for MSB. From this. it would appear that fecal coliforms may not be reliable indicators of viruses in estuarine waters. Published by Elsevier Science Ltd. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. US FDA, Div Programs & Enforcement Policy, Off Seafood, Bethesda, MD 20205 USA. US FDA, Div Math, Bethesda, MD 20205 USA. RP Burkhardt, W (reprint author), US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. NR 26 TC 63 Z9 64 U1 1 U2 24 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0043-1354 J9 WATER RES JI Water Res. PD JUN PY 2000 VL 34 IS 8 BP 2207 EP 2214 DI 10.1016/S0043-1354(99)00399-1 PG 8 WC Engineering, Environmental; Environmental Sciences; Water Resources SC Engineering; Environmental Sciences & Ecology; Water Resources GA 306UG UT WOS:000086614600004 ER PT J AU Bigger, CAH Ponten, I Page, JE Dipple, A AF Bigger, CAH Ponten, I Page, JE Dipple, A TI Mutational spectra for polycyclic aromatic hydrocarbons in the supF target gene SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE pS189; pSP189; supF; shuttle vector; sequence specificity; polymerase stop assay; site-specific mutagenesis; dihydrodiol epoxide; DNA adduct; benzo[c]phenanthrene; benzo[a]pyrene; 5-methychrysene; 5,6-dimethylchrysene; 7-methylbenz[a]anthracene; benzo[g]chrysene; 7-bromomethylbenz[a]anthracene; 7-bromomethyl-12-methylbenz[a]anthracene ID BENZOPHENANTHRENE DIHYDRODIOL EPOXIDES; (+)-ANTI-BENZOPYRENE DIOL EPOXIDE; SITE-SPECIFIC MUTAGENESIS; SINGLE-STRANDED VECTOR; EMBRYO CELL-CULTURES; ESCHERICHIA-COLI; SEQUENCE CONTEXT; SHUTTLE-VECTOR; DNA-ADDUCTS; 1,2-DIHYDRODIOL 3,4-EPOXIDE AB An SV40-based shuttle vector system was used to identify the types of mutational changes and the sites of mutation within the supF DNA sequence generated by the four stereoisomers of benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide (B[c]PhDE), by racemic mixtures of bay or fjord region dihydrodiol epoxides (DE) of 5-methylchrysene, of 5,6-dimethylchrysene, of benzo[g]chrysene and of 7-methylbenz[a]anthracene and by two direct acting polycyclic aromatic hydrocarbon carcinogens, 7-bromomethylbenz[a]anthracene (7-BrMeBA) and 7-bromomethyl-12-methylbenz[a]anthracene (7-BrMe-12- MeBA). The results of these studies demonstrated that the predominant type of mutation induced by these compounds is the base substitution. The chemical preference for reaction at deoxyadenosine (dAdo) or deoxyguanosine (dGuo) residues in DNA, which is in general correlated with the spatial structure (planar or non-planar) of the reactive polycyclic aromatic hydrocarbon, is reflected in the preference for mutation at A . T or G . C pairs. In addition, if the ability to react with DNA in vivo is taken into account, the relative mutagenic potencies of the B[c]PhDE stereoisomers are consistent with the higher tumorigenic activity associated with non-planar polycyclic aromatic hydrocarbons and their extensive reaction with dAdo residues in DNA. Comparison of the types of mutations generated by polycyclic aromatic hydrocarbons and other bulky carcinogens in this shuttle vector system suggests that all bulky lesions may be processed by a similar mechanism related to that involved in replication past apurinic sites. However, inspection of the distribution of mutations over the target gene induced by the different compounds' demonstrated that individual polycyclic aromatic hydrocarbons induce unique patterns of mutational hotspots within the target gene. A polymerase arrest assay was used to determine the sequence specificity of the interaction of reactive polycyclic aromatic hydrocarbons with the shuttle vector DNA. The results of these assays revealed a divergence between mutational hotspots and polymerase arrest sites for all compounds investigated, i.e., sites of mutational hotspots do not correspond to sites where high levels of adduct formation occur, and suggested that some association between specific adducts and sequence context may be required to constitute a premutagenic lesion. A site-specific mutagenesis system employing a single-stranded vector (M13mp7L2) was used to investigate the mutational events a single benzo[a]pyrene or benzo[c]phenanthrene dihydrodiol epoxide-DNA adduct elicits within specific sequence contexts. These studies showed that sequence context can cause striking differences in mutagenic frequencies for given adducts. In addition, these sequence context effects do not originate only from nucleotides immediately adjacent to the adduct, but are also modulated by more distal nucleotides. The implications of these results for mechanisms of polycyclic aromatic hydrocarbon-induced mutagenesis and carcinogenesis are discussed. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NCI, Chem Carcinogenesis Lab, Basic Res Program, Adv Biosci Labs,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Bigger, CAH (reprint author), US FDA, Ctr Drug Evaluat & Res HFD530, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 77 TC 24 Z9 25 U1 1 U2 4 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 30 PY 2000 VL 450 IS 1-2 SI SI BP 75 EP 93 DI 10.1016/S0027-5107(00)00017-8 PG 19 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 323DL UT WOS:000087549500006 PM 10838135 ER PT J AU Berger, VW AF Berger, VW TI Pros and cons of permutation tests in clinical trials SO STATISTICS IN MEDICINE LA English DT Article ID ENRICHMENT; DESIGN AB Hypothesis testing, in which the null hypothesis specifies no difference between treatment groups, is an important tool in the assessment of new medical interventions. For randomized clinical trials, permutation tests that reflect the actual randomization are design-based analyses for such hypotheses. This means that only such design-based permutation tests can ensure internal validity, without which external validity is irrelevant. However, because of the conservatism of permutation tests, the virtues of permutation tests continue to be debated in the literature, and conclusions are generally of the type that permutation tests should always be used or permutation tests should never be used. A better conclusion might be that there are situations in which permutation tests should be used, and other situations in which permutation tests should not be used. This approach opens the door to broader agreement, but begs the obvious question of when to use permutation tests. We consider this issue from a variety of perspectives, and conclude that permutation tests are ideal to study efficacy in a randomized clinical trial which compares, in a heterogeneous patient population, two or more treatments, each of which may be most effective in some patients, when the primary analysis does not adjust for covariates. We propose the p-value interval as a novel measure of the conservatism of a permutation test that can be defined independently of the significance level. This p-value interval can be used to ensure that the permutation test have both good global power and an acceptable degree of conservatism. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Berger, VW (reprint author), NCI, Biometry Res Grp, Div Canc Prevent, Execut Plaza N,Suite 344, Bethesda, MD 20892 USA. FU DRS NIH HHS [RSR-96-004A] NR 28 TC 68 Z9 72 U1 1 U2 6 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAY 30 PY 2000 VL 19 IS 10 BP 1319 EP 1328 DI 10.1002/(SICI)1097-0258(20000530)19:10<1319::AID-SIM490>3.3.CO;2-S 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 314NN UT WOS:000087062300005 PM 10814980 ER PT J AU Fang, JL Beland, FA AF Fang, JL Beland, FA TI Development of a novel P-32-postlabeling method for the analysis of 3 '-azido-3 '-deoxythymidine SO CANCER LETTERS LA English DT Article DE 3 '-azido-3 '-deoxythymidine; thymidine kinase; P-32-postlabeling ID PLACEBO-CONTROLLED TRIAL; VIRUS REVERSE-TRANSCRIPTASE; AIDS-RELATED COMPLEX; EXPOSED IN-UTERO; AZIDOTHYMIDINE AZT; DOUBLE-BLIND; CELL-LINE; 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE AZT; DNA INCORPORATION; ZIDOVUDINE AB 3'-Azido-3'-deoxythymidine (AZT) was the first anti-retroviral nucleoside analog to be used in the treatment and prevention of acquired immunodeficiency syndrome (AIDS). A novel P-32-postlabeling assay, based upon thymidine kinase (TK) instead of the conventional T-4 polynucleotide kinase, has been developed for the detection of the levels of AZT incorporated into DNA. After enzymatic digestion of DNA to deoxynucleoside 3'-monophosphates, AZT was isolated by ethyl acetate extraction. The ethyl acetate was evaporated and the AZT was postlabeled by 5'-phosphorylation with [gamma-P-32]ATP and TK. AZT was detected at a level of 51.5 +/- 6.3 (mean +/- SD; n = 4) AZT molecules/10(5) nucleotides following in vitro incorporation of the drug into high-molecular-weight rat-liver DNA. The P-32-postlabeling method was further validated by the detection of AZT in lung and liver DNA from neonatal mice treated with AZT. The levels of AZT in lung and liver DNA were proportional to the dose, with the levels in lung DNA being two-fold higher than those for liver DNA. The limit of detection for the assay was 8 AZT molecules/10(7) nucleotides using 10 mug of DNA. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Fang, JL (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 33 TC 2 Z9 2 U1 0 U2 0 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 MAY 29 PY 2000 VL 153 IS 1-2 BP 25 EP 33 DI 10.1016/S0304-3835(00)00346-3 PG 9 WC Oncology SC Oncology GA 396WV UT WOS:000166661600004 PM 10779626 ER PT J AU Markoff, L AF Markoff, L TI Points to consider in the development of a surrogate for efficacy of novel Japanese encephalitis virus vaccines SO VACCINE LA English DT Editorial Material ID ANTIBODIES AB Although an effective killed virus vaccine to prevent illness due to Japanese encephalitis virus (JEV) infection exists, many authorities recognize that a safe, effective live JEV vaccine is desirable in order to reduce the cost and the number of doses of vaccine required per immunization. A large-scale clinical efficacy trail for such a vaccine would be both unethical and impractical. Therefore, a surrogate for the efficacy of JE vaccines should be established. Detection of virus-neutralizing antibodies in sera of vaccinees could constitute such a surrogate for effacy. Field studies of vaccinees in endemic areas and studies done in mice already exist to support this concept. Also, titers of virus-neutralizing antibodies are already accepted as a surrogate for the efficacy of yellow fever virus vaccines and for the efficacy of other viral vaccines as well. In developing a correlation between N antibody titers and protection from JEV infection, standard procedures must be validated and adopted for both measuring N antibodies and for testing in animals. A novel live virus vaccine could be tested in the mouse and/or the monkey model of JEV infection to establish a correlation between virus-neutralizing antibodies elicited by the vaccines and protection from encephalitis. In addition, sera of subjects receiving the novel live JEV vaccine in early clinical trials could be passively transferred to mice or monkeys in order to establish the protective immunogenicity of the vaccine in humans. A monkey model for JEV infection was recently established by scientists at WRAIR in the US. From this group, pools of JEV of known infectivity for Rhesus macaques may be obtained for testing of immunity elicited by live JE vaccine virus. Published by Elsevier Science Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Lab Vestorborne Virus Dis, Rockville, MD 20852 USA. RP Markoff, L (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Vestorborne Virus Dis, Rockville, MD 20852 USA. NR 16 TC 39 Z9 42 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 MAY 26 PY 2000 VL 18 SU 2 BP 26 EP 32 DI 10.1016/S0264-410X(00)00038-4 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 322FD UT WOS:000087498800001 PM 10821970 ER PT J AU Heffelfinger, JD Dowell, SF Jorgensen, JH Klugman, KP Mabry, LR Musher, DM Plouffe, JF Rakowsky, A Schuchat, A Whitney, CG AF Heffelfinger, JD Dowell, SF Jorgensen, JH Klugman, KP Mabry, LR Musher, DM Plouffe, JF Rakowsky, A Schuchat, A Whitney, CG CA Drug Resistant Streptococcus Pneum TI Management of community-acquired pneumonia in the era of pneumococcal resistance - A report from the Drug-Resistant Streptococcus pneumoniae Therapeutic Working Group SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ANTIMICROBIAL SURVEILLANCE PROGRAM; ACUTE OTITIS-MEDIA; PENICILLIN-RESISTANT; UNITED-STATES; REQUIRING HOSPITALIZATION; STAPHYLOCOCCUS-AUREUS; BACTERIOLOGICAL RESPONSE; ORAL CEPHALOSPORINS; RISK-FACTORS; MENINGITIS AB Objective: To provide recommendations for the management of community-acquired pneumonia and the surveillance of drug-resistant Streptococcus pneumoniae (DRSP). Methods: We addressed the following questions: (1) Should pneumococcal resistance to beta-lactam antimicrobial agents influence pneumonia treatment? (2) What are suitable empirical antimicrobial regimens for outpatient treatment of community-acquired pneumonia in the DRSP era! (3) What are suitable empirical antimicrobial regimens for treatment of hospitalized patients with community-acquired pneumonia in the DRSP era! and (4) How should clinical laboratories report antibiotic susceptibility patterns for S pneumoniae, and what drugs should be included in surveillance if community-acquired pneumonia is the syndrome of interest? Experts in the management of pneumonia and the DRSP Therapeutic Working Group, which includes clinicians, academicians, and public health practitioners, met at the Centers for Disease Control and Prevention in March 1998 to discuss the management of pneumonia in the era of DRSP. Published and unpublished data were summarized from the scientific literature and experience of participants. After group presentations and review of background materials, subgroup, chairs prepared draft responses, which were discussed as a group. Conclusions: When implicated in cases of pneumonia, S pneumoniac should be considered susceptible if penicillin minimum inhibitory concentration (MIC) is no greater than 1 mu g/mL, of intermediate susceptibility if MIC is 2 mu g/ Int, and resistant if MIC is no less than 4 mu g/mL. For outpatient treatment of community-acquired pneumonia, suitable empirical oral antimicrobial agents include a macrolide leg, erythromycin, clarithromycin, azithromycin), doxycycline (or tetracycline) for children aged 8 years or older, or an oral beta-lactam with good activity against pneumococci (eg, cefuroxime axetil, amoxicillin, or a combination of amoxicillin and clavulanate potassium). Suitable empirical antimicrobial regimens for inpatient pneumonia include an intravenous beta-lactam, such as cefuroxime, ceftriaxone sodium, cefotaxime sodium, or a combination of ampicillin sodium and sulbactam sodium plus a macrolide. New fluoroquinolones with improved activity against 5 pneumoniae can also be used to treat adults with community-acquired pneumonia. To limit the emergence of fluoroquinolone-resistant strains, the neu fluoroquinolones should he limited to adults (1) for whom one of the above regimens has already failed, (2) who are allergic to alternative agents, or (3) who have a documented infection with highly drug-resistant pneumococci (eg, penicillin MIC greater than or equal to 4 mu g/mL). Vancomycin hydrochloride is not routinely indicated for the treatment of community-acquired pneumonia or pneumonia caused by DRSP. C1 Ctr Dis Control & Prevent, Resp Dis Branch, Atlanta, GA USA. Natl Comm Clin Lab Stand, Wayne, PA USA. S African Inst Med Res, Johannesburg, South Africa. Amer Acad Family Physicians, Leahwood, MO USA. Coll Amer Pathologists, Northfield, IL USA. Ohio State Univ, Med Ctr, Infect Dis Sect, Columbus, OH 43210 USA. US FDA, Rockville, MD 20857 USA. RP Heffelfinger, JD (reprint author), 2820 W Barrett St, Seattle, WA 98199 USA. NR 80 TC 413 Z9 445 U1 1 U2 24 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 22 PY 2000 VL 160 IS 10 BP 1399 EP 1408 DI 10.1001/archinte.160.10.1399 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 315PJ UT WOS:000087121900001 PM 10826451 ER PT J AU Galvin, TA Muller, J Khan, AS AF Galvin, TA Muller, J Khan, AS TI Effect of different promoters on immune response elicited by HIV-1 gag/nev multigenic DNA vaccine in Macaca mulatta and Macaca nemestrina SO VACCINE LA English DT Article DE plasmid DNA vaccine; human immunodeficiency virus type 1; promoter activity ID IMMUNODEFICIENCY-VIRUS TYPE-1; INTRADERMAL GENE IMMUNIZATION; ANTIBODY-RESPONSES; NONHUMAN-PRIMATES; TRANSGENIC MICE; INFECTION; CELLS; INDUCTION; PROTEIN; AIDS AB pCMV-NLDelta pol and pAKV-NLDelta pol expressed human immunodeficiency virus type 1 (HIV-1) gag and env under the regulation of the human cytomegalovirus (CMV) immediate-early (IE) promoter:enhancer and the endogenous AKV murine leukemia viral long terminal repeat (LTR), respectively. Analysis of the immune responses elicited by direct DNA injection of pCMV- NLDelta pol and pAKV-NLDelta pol in macaques indicated that generation of the humoral and T-cell proliferative responses correlated directly with the promoter strength of the vaccine DNAs. In Mucaca mulatta, pCMV-NLDelta pol generated stronger humoral responses and T-cell proliferative responses to Gag and Env using less DNA and fewer number of injections than pAKV-NLDelta pol Similarly, in Macaca nemestrina pCMV-NLDelta pol elicited high humoral responses, which persisted long-term and were boostable. Injection of large amounts of pAKV-NLDelta pol, in general, failed to produce antibody levels comparable to pCMV-NLDelta pol. However. injection of a control animal with large amounts of vector DNA produced a generalized enzyme-linked immunosorbent assay (ELISA) reactivity to HIV-1. The results indicated that generation of high immune responses to HIV-1 cannot be achieved by increasing the vaccine DNA dose and may require high protein expression from the DNA by including a strong promoter or by the use of other boosting agents. Furthermore, safety concerns may arise with increasing the DNA dose that could need additional investigation. Published by Elsevier Science Ltd. C1 US FDA, Lab Retrovirus Res, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Lab Vector Borne Viral Dis, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. George Washington Univ, Grad Program Genet, Washington, DC 20052 USA. RP Khan, AS (reprint author), 1401 Rockville Pike,HFM-454, Rockville, MD 20852 USA. NR 50 TC 32 Z9 35 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 22 PY 2000 VL 18 IS 23 BP 2566 EP 2583 DI 10.1016/S0264-410X(99)00569-1 PG 18 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 316DA UT WOS:000087151100012 PM 10775791 ER PT J AU Bernard, GR Sopko, G Cerra, F Demling, R Edmunds, H Kaplan, S Kessler, L Masur, H Parsons, P Shure, D Webb, C Weidemann, H Weinmann, G Williams, D AF Bernard, GR Sopko, G Cerra, F Demling, R Edmunds, H Kaplan, S Kessler, L Masur, H Parsons, P Shure, D Webb, C Weidemann, H Weinmann, G Williams, D TI Pulmonary artery catheterization and clinical outcomes - National Heart, Lung, and Blood Institute and Food and Drug Administration workshop report SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CRITICALLY ILL PATIENTS; CARE; KNOWLEDGE; TIME AB Objective The efficacy and safety of the pulmonary artery catheter are under scrutiny because of its association with increased morbidity and mortality in observational studies. In response, the National Heart, Lung, and Blood Institute (NHLBI) and the US Food and Drug Administration (FDA) conducted the Pulmonary Artery Catheterization and Clinical Outcomes workshop in Alexandria, Va, on August 25 and 26, 1997, to develop recommendations regarding actions to improve pulmonary artery catheter utility and safety. Participants The NHLBI and FDA planning task force selected a workshop chairperson, subcommittee chairs, and participants. Approximately 85 participants were selected for their collective expertise in critical care, pulmonary medicine, cardiovascular medicine and surgery, pediatrics, nursing, biostatistics,and medical economics. The meeting was open to industry representatives and other government and lay observers. This workshop was funded by the NHLBI an the FDA's Division of Devices. Evidence Published reports relating to the efficacy and safety of the pulmonary artery catheter, especially consensus documents developed by professional societies. Consensus Process The planning task force disseminated materials, held teleconferences, and developed draft position papers prior to the workshop. These were modified during the workshop and thereafter in the course of several teleconferences, and presented to the entire group for final modifications and approval. Conclusions A need exists for collaborative education of physicians and nurses in performing, obtaining, and interpreting information from the use of pulmonary artery catheters. This effort should be led by professional societies, in collaboration with federal agencies, with the purpose of developing and disseminating standardized educational programs. Areas given high priority for clinical trials were pulmonary artery catheter use in persistent/refractory congestive heart failure, acute respiratory distress syndrome, severe sepsis and septic shock, and low-risk coronary artery bypass graft surgery. C1 Vanderbilt Univ, Sch Med, Nashville, TN 37232 USA. NHLBI, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Calif Los Angeles, Los Angeles, CA USA. US FDA, Rockville, MD 20857 USA. NIH, Bethesda, MD 20892 USA. Univ Colorado, Denver, CO 80202 USA. Washington Univ, St Louis, MO USA. Cleveland Clin, Cleveland, OH 44106 USA. Brown Univ, Providence, RI 02912 USA. RP Bernard, GR (reprint author), Vanderbilt Univ, Sch Med, Room T-1219 Med Ctr N, Nashville, TN 37232 USA. OI Wiedemann, Herbert/0000-0002-4587-4401 NR 33 TC 106 Z9 114 U1 1 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 MAY 17 PY 2000 VL 283 IS 19 BP 2568 EP 2572 DI 10.1001/jama.283.19.2568 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 312VL UT WOS:000086964600038 PM 10815121 ER PT J AU Nagaraju, K Casciola-Rosen, L Rosen, A Thompson, C Loeffler, L Parker, T Danning, C Rochon, PJ Gillespie, J Plotz, P AF Nagaraju, K Casciola-Rosen, L Rosen, A Thompson, C Loeffler, L Parker, T Danning, C Rochon, PJ Gillespie, J Plotz, P TI The inhibition of apoptosis in myositis and in normal muscle cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFLAMMATORY MYOPATHIES; T-CELLS; MUSCULAR-DYSTROPHIES; DNA-FRAGMENTATION; FAS LIGAND; EXPRESSION; DEATH; COMPLEX; ANTIGEN; FIBERS AB The mechanism of injury and death of muscle cells in the inflammatory myopathies (dermatomyositis, polymyositis, and inclusion body myositis) remains obscure, We and others have not detected apoptosis in the muscle biopsies from patients with myositis despite clear evidence of cell damage and loss. We provide evidence in this study that Fas ligand (FasL) as well as Fas is present on muscle cells and inflammatory cells in myositis biopsies: Fas is present on most muscle cells and lymphocytes, and Fast is present on degenerating muscle cells and many infiltrating mononuclear cells, The expression of both Pas and Fast in the inflamed tissue makes the absence of apoptosis more striking. To address the mechanisms of this resistance to classical apoptosis in muscle cells, we have investigated the expression of the antiapoptotic molecule FLICE (Fas-associated death domain-like IL-1-converting enzyme)-inhibitory protein (FLIP) in muscle biopsies of myositis patients and in cultured human skeletal muscle cells. Using laser capture microscopy, we have shown that FLIP is expressed in the muscle fibers and on infiltrating lymphocytes of myositis biopsies. Furthermore, we have shown that FLIP, but not Bcl-2, is expressed in cultured human skeletal muscle cells stimulated with proinflammatory cytokines, and inhibition of FLIP with antisense oligonucleotides promotes significant cleavage of poly(ADP-ribose) polymerase autoantigen, a sensitive indicator of apoptosis. These studies strongly suggest that the resistance of muscle to Fas-mediated apoptosis is due to the expression of FLIP in muscle cells in the inflammatory environment in myositis. C1 NIAMSD, Arthritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Dermatol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Cell Biol & Anat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Plotz, P (reprint author), NIAMSD, Arthritis & Rheumatism Branch, NIH, Bldg 10,Room 9N-244, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [AR44684] NR 32 TC 59 Z9 63 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2000 VL 164 IS 10 BP 5459 EP 5465 PG 7 WC Immunology SC Immunology GA 312MW UT WOS:000086947900065 PM 10799913 ER PT J AU Scallet, AC Pothuluri, N Rountree, RL Matthews, JC AF Scallet, AC Pothuluri, N Rountree, RL Matthews, JC TI Quantitating silver-stained neurodegeneration: the neurotoxicity of trimethlytin (TMT) in aged rats SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE trimethyltin; hippocampus; Fink-Heimer; image analysis; aging; neurodegeneration ID MEMORY-DEFICIENT RATS; SUSTAINED ELECTRICAL-STIMULATION; SPATIAL-LEARNING DEFICITS; EPILEPTIC BRAIN-DAMAGE; NUTRITIONAL INFLUENCES; DIFFERENT REGIONS; FISCHER-344 RATS; PERFORANT PATH; AMINO-ACIDS; DOMOIC ACID AB This report describes the development of a histoanalytical procedure to measure the degree of neurodegeneration produced by the organometal toxicant trimethyltin (TMT). Based on a previous, non-quantitated experiment we hypothesized that the same dose of TMT would produce greater damage in animals of increasing age. Male rats aged 6, 12, 18, or 24 months at the time of dosing were given either 4.5 mg/kg TMT or saline (i.p.). One month after dosing, rats were perfused and their brains removed and processed to selectively silver-impregnate degenerating cell bodies as well as axon terminals and dendrites. Neurodegeneration was most prominent in the hippocampi (especially CAI stratum radiatum) of TMT-treated rats, but not in the controls. Computer-assisted counting of the silver grains marking damage indicated greater neurotoxicity from the same dose of TMT when given to the older animals. Thus the grain density in the 6-month-old TMT-treated rats was not significantly elevated from the 6-month-old controls (P > 0.10). The 12-month-old TMT-treated rats had significantly increased grain densities compared to their controls (P < 0.05), but still larger increases of grain counts were observed in the 18- and 24-month-old rats (both P-values < 0.01). Our findings with TMT are similar to previous, but nonquantitative, reports that the neurotoxic effects of kainic acid and methionine sulfoximine were also greater in older rats. An increased sensitivity to neurotoxicants might help explain the apparently spontaneous degeneration of cortical neurons in aging and in the neurological diseases of old age. The method we report here for quantitation of silver grains marking neurodegeneration should be adaptable to a wide range of histologically based neurotoxicology investigations. (C) 2000 Published by Elsevier Science B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Mississippi, Sch Pharm, Dept Pharmacol, University, MS 38677 USA. Univ Mississippi, Sch Pharm, Res Inst Pharmaceut Sci, University, MS 38677 USA. RP Scallet, AC (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132,3900 NCTR Dr, Jefferson, AR 72079 USA. NR 42 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD MAY 15 PY 2000 VL 98 IS 1 BP 69 EP 76 DI 10.1016/S0165-0270(00)00191-6 PG 8 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 320BR UT WOS:000087381600009 PM 10837873 ER PT J AU Oshima, Y Joshi, BH Puri, RK AF Oshima, Y Joshi, BH Puri, RK TI Conversion of interleukin-13 into a high affinity agonist by a single amino acid substitution SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CARCINOMA CELL-LINES; RECEPTOR-GAMMA CHAIN; HUMAN GLIOMA-CELLS; HUMAN B-CELLS; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; SIGNAL-TRANSDUCTION; IL-13 RECEPTOR; SARCOMA-CELLS; TUMOR-CELLS AB We created a novel mutated form of human interleukin-13 (IL-13) in which a positively charged arginine (R) at position 112 was substituted to a negatively charged aspartic acid (D). This mutant, termed IL-13R112D, was expressed in Escherichia coli and purified to near homogeneity. IL-13R112D was found to be a potent IL-13 agonist with 5-10-fold improved binding affinity to IL-13 receptors compared with wild-type IL-13 (wtIL-13). The conclusion of IL-13 agonist activity was drawn on the basis of approximately 10-fold improved activity over wtIL-13 in several assays: (a) inhibition of CD14 expression in primary monocytes; (b) proliferation of TF-1 and B9 cell lines; and (c) activation of STAT6 in Epstein-Barr virus-immortalized B cells, primary monocytes, and THP-1 monocytic cell line. Furthermore, mutant IL-13R112D neutralized the cytotoxic activity of a chimeric fusion protein composed of wtIL-13 and a Pseudomonas exotoxin A (IL-13-PE38) approximately 10 times better than wtIL-13. Based on these results, it was concluded that IL-13R112D interacts with much stronger affinity than wtIL-13 on all cell types tested and that Arg-112 plays an important role in the interaction with its receptors (IL-13R). Thus, these results suggest that IL-13R112D may be a useful ligand for the study of IL-13 interaction with its receptors or, alternatively, in designing specific targeted agents for IL-13R-positive malignancies. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, 29 Lincoln Dr,NIH Bldg 29B,Rm 2NN10, Bethesda, MD 20892 USA. NR 40 TC 34 Z9 38 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 12 PY 2000 VL 275 IS 19 BP 14375 EP 14380 DI 10.1074/jbc.275.19.14375 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 313NZ UT WOS:000087006900051 PM 10799519 ER PT J AU Dorsam, V Weimer, T Schmeel, A Hein, B Enssle, K Chumakov, KM Fibi, MR AF Dorsam, V Weimer, T Schmeel, A Hein, B Enssle, K Chumakov, KM Fibi, MR TI Increased safety level of serotype 3 sabin oral poliomyelitis vaccine lots by improved seed virus, and tissue culture and virus infection conditions SO VACCINE LA English DT Article DE MAPREC; oral poliovirus vaccine; mutational analysis; quality control ID POLIOVIRUS VACCINE; GENETIC STABILITY; STRAIN; NEUROVIRULENCE; ATTENUATION; SELECTION; MUTATIONS; FREQUENCY; SEQUENCE; REGION AB The content of 472U to 472C revertant virus in serotype 3 oral poliomyelitis monovalent bulk vaccines can be quantified by MAPREC (Mutant Analysis by PCR and Restriction Enzyme Cleavage). Besides other wildtype reversions identified in propagated type 3 Sabin strain populations, the 472U to 472C reversion correlates most prominently with neurovirulence in the monkey neurovirulence test. Therefore, the results can be used for the discrimination of 'good' and 'bad' vaccines on the molecular level. In international collaborative studies it has been well established that vaccine lots containing revertant genomes below a critical threshold pass the in vivo monkey neurovirulence test (MNVT), while vaccine lots containing more revertants fail the MNVT. In this communication we show that the MAPREC test is a sensitive tool for quality control and the demonstration of consistency in large scale production. Furthermore, MAPREC offers a possibility to assess the effect of changed production conditions on the rate of reversion and to find conditions for consistent production with low reversion rates. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Chiron Behring GMBH & Co, D-35041 Marburg, Germany. Centeon Pharma GMBH, D-35041 Marburg, Germany. Hoechst Marion Roussel Germany, D-35041 Marburg, Germany. Food & Drug Adm, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Fibi, MR (reprint author), Chiron Behring GMBH & Co, Emil von Behring Str 76, D-35041 Marburg, Germany. NR 16 TC 4 Z9 5 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 MAY 8 PY 2000 VL 18 IS 22 BP 2435 EP 2443 DI 10.1016/S0264-410X(99)00531-9 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 313BN UT WOS:000086978600017 PM 10738101 ER PT J AU Hopkins, KJ Wang, GJ Schmued, LC AF Hopkins, KJ Wang, GJ Schmued, LC TI Temporal progression of kainic acid induced neuronal and myelin degeneration in the rat forebrain SO BRAIN RESEARCH LA English DT Article DE kainic acid; excitotoxin; Fluoro-Jade; black-gold; brain pathology ID RECEPTOR; EXCITOTOXICITY; ANTAGONISTS; GLUTAMATE; BINDING; BRAIN AB The excitatory amino acid glutamate has been implicated in the neurodegeneration associated with several different central nervous system diseases. Treatment with kainic acid (KA), a glutamate analog known to activate the AMPA/KA subtype of glutamate receptor, has been widely used as a model of epilepsy. Long term temporal studies of its neuropathological effects, however, are lacking. In this study, two techniques were used to directly visualize and characterize the neuropathology that occurred over a 2-month period following KA-induced status epilepticus in adult. female Sprague-Dawley rats. Post-injection survival was 2, 4, 8 h, 2 days, 2 weeks, or 2 months. Labeling with Fluoro-Jade B (FJB), a fluorescent green dye that labels the cell body, dendrites, axons and axon terminals of degenerating neurons, was observed within the cortex, hippocampus, thalamus, basal ganglia, and amygdala by 4 h post-treatment. The highest level of labeling was seen in the piriform cortex, hippocampus, and thalamus. Myelin changes in the rat forebrain following KA treatment were also examined using the myelin-specific Black-Gold (BG) stain, Varicose myelinated fibers were observed in the same regions as FJB positive neurons, although these changes were evident by the 2-h survival time-point. Both stains showed a temporal progression of brain damage throughout the affected areas. By 2 months post-treatment, few degenerating neurons could be detected and abnormal myelin was absent in most regions. As myelin chan,aes can be seen prior to neuronal degeneration, and oligodendrocytes express functional AMPA/kainate-type glutamate receptors, the neurodegeneration and myelin pathologies may occur as independent events. Thus, researchers should consider the temporal and multiple effects of kainic acid to optimize conditions for their endpoint of interest when designing experiments. (C) 2000 Elsevier Science B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Hopkins, KJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 15 TC 100 Z9 104 U1 0 U2 3 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 2 PY 2000 VL 864 IS 1 BP 69 EP 80 DI 10.1016/S0006-8993(00)02137-5 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 313MF UT WOS:000087002900008 PM 10793188 ER PT J AU Beiden, SV Wagner, RF Campbell, G AF Beiden, SV Wagner, RF Campbell, G TI Components-of-variance models and multiple-bootstrap experiments: An alternative method for random-effects, receiver operating characteristic analysis SO ACADEMIC RADIOLOGY LA English DT Article DE receiver operating characteristic (ROC) analysis; random effects; components of variance; bootstrap ID MONTE-CARLO VALIDATION; DISCRETE RATING DATA; EXPERIMENTAL-DESIGN; MULTIREADER METHOD; ROC; CURVES; INDEX AB Rationale and Objectives. The purpose of this study was to develop an alternative approach to random-effects, receiver operating characteristic analysis inspired by a general formulation of components-of-variance models. The alternative approach is a higher-order generalization of the Dorfman, Berbaum, and Metz (DBM) approach that yields additional information on the variance structure of the problem. Materials and Methods. Six population experiments were designed to determine the six variance components in the DBM model. For practical problems, in which only a finite set of readers and patients are available, six analogous bootstrap experiments may be substituted for the population experiments to estimate the variance components. Monte Carlo simulations were performed on the population experiments, and those results were compared with the corresponding multiple-bootstrap estimates and those obtained with the DBM approach. Confidence intervals on the difference of ROC parameters for competing diagnostic modalities were estimated, and corresponding comparisons were made. Results. For mean values, the agreement of present estimates of variance structures with population results was excellent and, when suitably weighted and mixed, similar to or closer than that with the DBM method. For many variance structures, the confidence intervals in this study for the difference in ROC area between modalities were comparable to those with the DBM method. When reader variability was large, however, mean confidence intervals from this study were tighter than those with the DBM method and closer to population results. Conclusion. The jackknife approach of DBM provides a linear approximation to receiver-operating-characteristic statistics that are intrinsically nonlinear. The multiple-bootstrap technique of this study, however, provides a more general, nonparametric, maximum-likelihood approach. It also yields estimates of the variance structure previously unavailable. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. US FDA, Off Sci & Technol, Rockville, MD 20857 USA. US FDA, Off Surveillance & Biometr, Rockville, MD 20857 USA. RP Wagner, RF (reprint author), US FDA, Off Sci & Technol, HFZ-142, Rockville, MD 20857 USA. NR 24 TC 92 Z9 93 U1 1 U2 6 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 MAY PY 2000 VL 7 IS 5 BP 341 EP 349 DI 10.1016/S1076-6332(00)80008-2 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 309UW UT WOS:000086788500006 PM 10803614 ER PT J AU Park, YK Sempos, CT Barton, CN Vanderveen, JE Yetley, EA AF Park, YK Sempos, CT Barton, CN Vanderveen, JE Yetley, EA TI Effectiveness of food fortification in the United States: The case of pellagra SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article AB Objectives. We evaluated the possible role of niacin fortification of the US food supply and other concurrent influences in eliminating the nutritional deficiency disease pellagra. Methods. We traced chronological changes in pellagra mortality and morbidity and compared them with the development of federal regulations, state laws, and other national activities pertaining to the fortification of cereal-grain products with niacin and other B vitamins. We also compared these changes with other concurrent changes that would have affected pellagra mortality or morbidity. Results. The results show the difficulty of evaluating the effectiveness of a single public health initiative such as food fortification without controlled experimental trials. Nonetheless, the results provide support for the belief that food fortification played a significant role in the elimination of pellagra in the United States. Conclusions. Food fortification that is designed to restore amounts of nutrients lost through grain milling was an effective tool in preventing pellagra, a classical nutritional deficiency disease, during the 1930s and 1940s, when food availability and variety were considerably less than are currently found in the United States. C1 US FDA, Off Nutrit Prod Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. RP Park, YK (reprint author), US FDA, Off Nutrit Prod Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, 200 C St SW,HFS-832, Washington, DC 20204 USA. NR 44 TC 48 Z9 50 U1 0 U2 7 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 2000 VL 90 IS 5 BP 727 EP 738 DI 10.2105/AJPH.90.5.727 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 308VN UT WOS:000086733700012 PM 10800421 ER PT J AU Jackson, AJ Conner, DP Miller, R AF Jackson, AJ Conner, DP Miller, R TI First measured plasma concentration value as C-max; impact on the C-max confidence interval in bioequivalence studies SO BIOPHARMACEUTICS & DRUG DISPOSITION LA English DT Article DE bioequivalence; first C-max; Monte Carlo simulations ID ABSORPTION AB In bioequivalence studies, the first blood or plasma sample taken after dosing sometimes yields a higher assayed drug concentration than any samples drawn thereafter. This circumstance ('first C-max' or 'FCM'), is usually considered undesirable, since a 'true C-max' requires that the sampled concentrations immediately preceding and immediately after the 'true C-max' concentration should be lower than the 'true C-max' concentration. Therefore, a question arises whether the presence of FCM in a bioequivalence study affects the power and accuracy of the computed statistical confidence interval (CI) for C-max. This study examines what effect, if any, the inclusion or exclusion of FCM data has on the statistical power and accuracy of the 90% CI computed for C-max in the analysis of results for in vivo bioequivalence studies. Actual experimental study data as well as data from simulated studies were evaluated. In the simulated studies, up to half of the study subjects exhibited FCM, and various levels of intrasubject variability were incorporated into the absorption rate constant. The two one-sided tests procedure was used to assess equivalence of C-max for the test versus reference products when either a complete set of C-max data was analysed (designated 'CCmax'), which included subjects with FCM profiles; or a truncated set of data was analysed (designated 'TCmax'), that excluded all subjects with FCM. The results showed that the CCmax metric had greater statistical power and comparable or greater statistical accuracy compared to TCmax for both bioequivalent and non-bioequivalent drug product formulations. Even when up to 50% of the study subjects had FCM, the power and accuracy of the 90% CI for rate of absorption (i.e. C-max) was not significantly affected. Consequently, this study shows that, in the analysis of data from conventional in vivo bioequivalence studies, the inclusion of 50% of the subjects exhibiting FCM does not greatly impact the statistical results obtained for C-max. Published in 2000 by John Wiley & Sons, Ltd. C1 US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Div Bioequivalence, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. RP Jackson, AJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Div Bioequivalence, Rockville, MD 20857 USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0142-2782 J9 BIOPHARM DRUG DISPOS JI Biopharm. Drug Dispos. PD MAY PY 2000 VL 21 IS 4 BP 139 EP 146 DI 10.1002/1099-081X(200005)21:4<139::AID-BDD223>3.0.CO;2-H PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 395ZC UT WOS:000166611000003 PM 11180192 ER PT J AU Donoghue, DJ Hairston, H AF Donoghue, DJ Hairston, H TI Food safety implication: certain antibiotics may rapidly contaminate egg albumen during the process of its formation SO BRITISH POULTRY SCIENCE LA English DT Article ID DRUG RESIDUE UPTAKE; LAYING HENS; OXYTETRACYCLINE; MEDICATION; YOLKS; AMPICILLIN AB 1. Egg white formation occurs in 3 phases: synthesis and storage of albumen proteins prior to ovulation, secretion of proteins during passage of the ovum down the reproductive tract (preplumping) and addition of water (plumping phase). 2. This study was to determine if oxytetracycline would transfer into egg albumen during the latter 2 phases of albumen formation. 3. In 2 experiments 48 hens were injected with either 400 mg/kg oxytetracycline or physiological saline. Hens were dosed at 0.5 h (preplumping phase) or 5.5 h (plumping phase) after oviposition. 4. Five hours following injections, hens were euthanised and albumen was collected from the reproductive tract. 5. Oxytetracycline transferred into albumen during both phases of albumen formation. Concentrations (ppm) were greater in the preplump vs plump phase (3.2 vs 1.8 in experiment 1; or 2.8 vs 1.6 in experiment 2. However, when differences in albumen weights were accounted for, total mu g transfer did not differ between the 2 phases. 6. Drugs may transfer into egg whites during the latter phases of formation prior to oviposition. Therefore, poultry producers or veterinary practitioners dosing laying hens must consider that egg whites contained in the 1st egg laid after dosing may contain drug residues. C1 US FDA, Ctr Vet Med, Laurel, MD USA. RP Donoghue, DJ (reprint author), Univ Arkansas, Dept Poultry Sci, Fayetteville, AR 72701 USA. NR 19 TC 14 Z9 18 U1 0 U2 5 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0007-1668 J9 BRIT POULTRY SCI JI Br. Poult. Sci. PD MAY PY 2000 VL 41 IS 2 BP 174 EP 177 DI 10.1080/713654912 PG 4 WC Agriculture, Dairy & Animal Science SC Agriculture GA 324PH UT WOS:000087630200009 PM 10890213 ER PT J AU Pai-Scherf, LH Carrasquillo, JA Paik, C Gansow, O Whatley, M Pearson, D Webber, K Hamilton, M Allegra, C Brechbiel, M Willingham, MC Pastan, I AF Pai-Scherf, LH Carrasquillo, JA Paik, C Gansow, O Whatley, M Pearson, D Webber, K Hamilton, M Allegra, C Brechbiel, M Willingham, MC Pastan, I TI Imaging and phase I study of In-111- and Y-90-labeled anti-Lewis(Y) monoclonal antibody B3 SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL LYMPHOMA; COLORECTAL-CANCER; ANTI-CD20 ANTIBODY; BREAST-CANCER; RADIOIMMUNOTHERAPY; Y-90; BIODISTRIBUTION; DOSIMETRY; CARCINOMA; THERAPY AB B3 is a murine monoclonal antibody (mAb) that recognizes a Lewis(Y) carbohydrate antigen present on the surface of many carcinomas. An imaging and Phase I trial was performed to study the ability of In-111-mAb B3 to image known metastasis and determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), kinetics, and biodistribution of Y-90-mAb B3, Patients (n = 26) with advanced epithelial tumors that express the Lewis' antigen were entered. All patients received 5 mCi of In-111-mAb B3 for imaging. Y-90-mAb B3 doses were escalated from 5 to 25 mCi in 5-mCi increments. In-111-mAb BS and Y-90-mAb B3 were coadministered over a 1-h infusion. Definite tumor imaging was observed in 20 of 26 patients. Sites imaged included lung, liver, bone, and soft tissues. The MTD of Y-90-mAb B3 was determined to be 20 mCi, The DLTs were neutropenia and thrombocytopenia, Tumor doses ranged from 7.7 to 65.1 rad/mCi. In-111- and Y-90-mAb B3 serum pharmacokinetics (n = 23) were found to be similar, The amount of B3 administered (5, 10, and 50 mg) did not alter the pharmatokinetics, Bone marrow biopsies (n = 23) showed 0.0038 +/- 0.0016% of injected dose/gram for In-111-mAb B3 compared to 0.0046 +/- 0.0017% of injected dose/gram for Y-90-mAb B3 (P = 0.009). When given to patients with carcinomas that express the Lewis' antigen, In-111-mAb B3 demonstrated good tumor localization. The MTD of Y-90-mAb B3 is 20 mCi, with myelosuppression as the DLT. Higher doses of radioactivity need to be delivered to achieve an antitumor effect. Humanized mAb B3 is being developed for evaluation in radioimmunotherapy. A clinical trial to explore the use of higher doses of Y-90-mAb B3 with autologous stem cell support is planned. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20892 USA. Wake Forest Univ, Dept Pathol, Winston Salem, NC 27157 USA. NCI, Dept Nucl Med, Warren G Magnuson Clin Canc Ctr, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. NCI, Chem Sect, ROB, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,Room 4E16,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 55 TC 29 Z9 29 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 2000 VL 6 IS 5 BP 1720 EP 1730 PG 11 WC Oncology SC Oncology GA 312LY UT WOS:000086945800016 PM 10815890 ER PT J AU Baumann, MH Rothman, RB Ali, SF AF Baumann, MH Rothman, RB Ali, SF TI Comparative neurobiological effects of ibogaine and MK-801 in rats SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE ibogaine; MK-801; dopamine; corticosterone; prolactin; addiction ID NMDA RECEPTOR COMPLEX; ANTI-ADDICTIVE DRUG; RADIOLIGAND-BINDING; IN-VIVO; MORPHINE; DOPAMINE; COCAINE; MECHANISMS; METABOLITE; ANTAGONIST AB Ibogaine is a plant-derived alkaloid with putative 'anti-addictive' properties. Although ibogaine binds to multiple targets in the brain, recent evidence suggests the drug acts as an N-methyl-D-aspartate (NMDA) antagonist similar to MK-801. The purpose of the present study was to compare neurochemical and neuroendocrine effects of ibogaine and MK-801 in vivo. Male rats received either i.p. saline, ibogaine (10 and 100 mg/kg), or MK-801 (0.1 and 1 mg/kg). Groups of rats (N = 6-8/group) were decapitated 30 or 60 min after injection. Brains were harvested for analysis of dopamine (DA) and its metabolites, while trunk blood was collected for analysis of plasma corticosterone and prolactin. Ibogaine produced marked dose-dependent reductions in tissue DA with concurrent increases in the metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). This profile of ibogaine-induced effects on DA metabolism was consistently observed in the cortex, striatum: olfactory tubercle, and hypothalamus. MK-801, on the other hand, did not reduce DA levels in any brain region but did cause modest region-specific elevations in DA metabolites. Ibogaine and MK-801 caused comparable elevations in circulating corticosterone, but only ibogaine increased prolactin. The present findings show that the effects of ibogaine on DA neurotransmission and neuroendocrine secretion are not fully mimicked by MK-801. Thus, the wide spectrum of in vivo actions of ibogaine can probably not be explained simply on the basis of antagonism at NMDA receptors. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 NIDA, Intramural Res Program, Medicat Discovery Res Branch, NIH, Baltimore, MD 21224 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Baumann, MH (reprint author), NIDA, Intramural Res Program, Medicat Discovery Res Branch, NIH, POB 5180,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 41 TC 7 Z9 7 U1 1 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAY 1 PY 2000 VL 59 IS 2 BP 143 EP 151 DI 10.1016/S0376-8716(99)00113-1 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 308KH UT WOS:000086709700004 PM 10891627 ER PT J AU Wolf, NS Pendergrass, W Schmeider, C Turturro, A AF Wolf, NS Pendergrass, W Schmeider, C Turturro, A TI Normal mouse and rat strains as models for age-related cataract and the effect of caloric restriction on its development SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE age-related cataract; life span; caloric restriction; mouse; rat; model; eye pigment ID LONG-TERM; OXIDATIVE STRESS; LENS; EYE; MORTALITY; MICE; EXTRACTION; GLAUCOMA AB The purpose of this study was to determine: (1) which of the commonly used strains of laboratory rats and mice provide good models for human age-related cataract, and (2) whether long term caloric restriction, a regimen that prolongs both median and maximum life span in rodents. would also delay the time of appearance of this age-related pathology. Three strains of mice and two rat strains commonly used in laboratory work and maintained on either ad libitum (AL) or calorically restricted (CR) diets in the National Institutes of Aging and Diet Restriction colony were examined by slit lamp for age-related cataracts at four or more time points during their life spans. These strains were Brown Norway and Fischer 344 rats, and C57BL/6, (C57BL6 x DBA/2)F1 and (C57BL/6 x C3H)F1 mice. None of these strains develop congenital cataracts. Various stages of cataract were found in the great majority of these animals in old age. In both rat strains and one mouse strain the cataracts occurred after mid-life, were most advanced late in life, and were similar in locations and appearance to those in humans. In the two mouse strains in which some cataracts appeared as early as 10-14 months of age, previously identified genetic defects affecting the eye mere probably involved in the early appearances. CR extended life spain in all five rat and mouse strains and also delayed both the time of first appearances and the subsequent increase in cataract severity over time in the four dark-eyed strains. CR did not delay cataract formation in the single albino rat strain studied. In summation: (1) commonly used strains of laboratory rats and mice that ape free of congenital or early appearing cataracts due to genetic defects would appear to serve as appropriate models for human age-related cataract, (2) caloric restriction (CR) provides a protective effect, delaying development of cataracts in the dark-eyed mouse and rat strains, while also extending their life spans, (3) CR did not delay the development of lens damage in the nonpigmented eye of the single albino strain studied, although it extended life span. (C) 2000 Academic Press. C1 Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Wolf, NS (reprint author), Univ Washington, Dept Pathol, POB 357470, Seattle, WA 98195 USA. FU NEI NIH HHS [R01-EY11733]; NIA NIH HHS [R01-AG07724] NR 37 TC 46 Z9 46 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD MAY PY 2000 VL 70 IS 5 BP 683 EP 692 DI 10.1006/exer.2000.0835 PG 10 WC Ophthalmology SC Ophthalmology GA 319CA UT WOS:000087321200016 PM 10870527 ER PT J AU Williams, KM Bigley, EC Raybourne, RB AF Williams, KM Bigley, EC Raybourne, RB TI Identification of murine B-cell and T-cell epitopes of Escherichia coli outer membrane protein F with synthetic polypeptides SO INFECTION AND IMMUNITY LA English DT Article ID SALMONELLA-TYPHIMURIUM PORINS; MONOCLONAL-ANTIBODIES; ANTIGENIC DETERMINANTS; SOLUTION CONFORMATION; FUNCTIONAL-PROPERTIES; SHIGELLA-FLEXNERI; CROSS-REACTIVITY; STRUCTURAL BASIS; TYPHOID-FEVER; PEPTIDE AB The major pore-forming outer membrane proteins (Omps) of gram-negative bacteria demonstrate numerous immunomodulating properties and are involved in the virulence of pathogenic strains. Because Escherichia coli OmpF is the best-characterized porin in terms of structural and functional characteristics, in vitro B-cell and T-cell responses to this porin in six different strains of mice were analyzed. Mice were immunized with purified OmpF trimers or overlapping synthetic polypeptides (20-mers) spanning the entire 340-amino-acid sequence of the OmpF monomer. T-cell proliferative responses and immunoglobulin G antibody responses to native OmpF and the peptide analogues were determined. For each strain, patterns of T-cell proliferation were similar regardless of whether native OmpF or synthetic peptides were inoculated, although all strains recognized one or more cryptic determinants. Mice exhibited several haplotype-specific responses, but genetically permissive epitopes were also identified. Four peptides (75-94, 265-284, 295-314, and 305-324) elicited strong T-cell proliferative responses from all strains of mice when mice were presensitized with native OmpF or a homologous peptide. In general, 10 or fewer peptides were recognized by sera from mice immunized with native OmpF or synthetic peptides, and most sera from peptide-immunized mice reacted poorly with the native protein. Four peptides spanning amino acids 45 to 64, 95 to 114, 115 to 134, and 275 to 294 were recognized by sera from all strains immunized with native OmpF but not by sera from peptide-immunized mice, Peptides 245-264 and 305-324 were universally recognized by sera from peptide-immunized mice, but these sera reacted weakly or were negative when tested against the native protein. Based on the pattern of cytokine secretion by proliferating T cells, immunization with native OmpF polarizes T helper cells toward development of a TH1 response. T-cell and B-cell responses have been investigated based on the assumption that differences in epitope specificity could influence protective or pathologic host reactions. Because of the high level of structural homology of OmpF to porins isolated from other enteric pathogens, the identification of T- and B-cell-stimulatory determinants of E. coli OmpF may have broader application. C1 US FDA, Ctr Food Safety & Appl Nutr, Immunobiol Branch, Laurel, MD 20708 USA. RP Williams, KM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Immunobiol Branch, 8301 Muirkirk Rd, Laurel, MD 20708 USA. RI Gonzalez Bonilla, Cesar/B-4972-2015 NR 55 TC 13 Z9 16 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2000 VL 68 IS 5 BP 2535 EP 2545 DI 10.1128/IAI.68.5.2535-2545.2000 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 305ZX UT WOS:000086572600020 PM 10768941 ER PT J AU Freidag, BL Melton, GB Collins, F Klinman, DM Cheever, A Stobie, L Suen, W Seder, RA AF Freidag, BL Melton, GB Collins, F Klinman, DM Cheever, A Stobie, L Suen, W Seder, RA TI CpG oligodeoxynucleotides and interleukin-12 improve the efficacy of Mycobacterium bovis BCG vaccination in mice challenged with M-tuberculosis SO INFECTION AND IMMUNITY LA English DT Article ID DNA VACCINE; IMMUNE-RESPONSES; INTERFERON-GAMMA; CUTTING EDGE; IMMUNOGENICITY; IL-12; LEISHMANIASIS; PROTECTION; RESISTANCE; ANTIGEN-85 AB Mycobacterium bovis bacillus Calmette-Guerin (BCG) is the only vaccine approved for prevention of tuberculosis. It has been postulated that serial passage of BCG over the years may have resulted in attenuation of its effectiveness. Because interleukin-12 (IL-12) and oligodeoxynucleotides (ODN) containing cytidine phosphate guanosine (CpG) motifs have been shown to enhance Th1 responses in vivo, they were chosen as adjuvants to increase the effectiveness of BCG vaccination. in this report, mice were vaccinated with BCG with or without IL-12 or CpG ODN and then challenged 6 weeks later via the aerosol route with the Erdman strain of M. tuberculosis. Mice vaccinated with BCG alone showed a 1- to 2-log reduction in bacterial load compared with control mice that did not receive any vaccination prior to M.. tuberculosis challenge. Moreover, the bacterial loads of mice vaccinated with BCG plus IL-12 or CpG ODN were a Further two- to fivefold lower than those of mice vaccinated with BCG alone. As an immune correlate, the antigen-specific production IFN-gamma and mRNA expression in spleen cells prior to challenge were evaluated. Mice vaccinated with BCG plus IL-12 or CpG ODN showed enhanced production of IFN-gamma compared with mice vaccinated with BCG done. Finally, granulomas in BCG-vaccinated mice were smaller and more lymphocyte rich than those in unvaccinated mice; however, the addition of IL-12 or CpG ODN to BCG vaccination did not alter granuloma formation or result in added pulmonary damage. These observations support a role for immune adjuvants given with BCG vaccination to enhance its biologic efficacy. C1 NIAID, Clin Immunol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Mycobacteria, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD USA. RP Seder, RA (reprint author), NIAID, Clin Immunol Sect, Clin Invest Lab, NIH, 10 Ctr Dr,Room 10-11C215, Bethesda, MD 20892 USA. NR 23 TC 89 Z9 97 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2000 VL 68 IS 5 BP 2948 EP 2953 DI 10.1128/IAI.68.5.2948-2953.2000 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 305ZX UT WOS:000086572600072 PM 10768993 ER PT J AU Yuan, R Venitz, J AF Yuan, R Venitz, J TI Effect of chronic renal failure on the disposition of highly hepatically metabolized drugs SO INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE renal; impairment; metabolism; binding ID PHARMACOKINETICS; CLEARANCE; INSUFFICIENCY; HEMODIALYSIS; IMPAIRMENT; LIVER; BLOOD AB <(Objective)under bar>: The objective of this study was to investigate the effect of renal impairment on the disposition of an extensively metabolized drug, i.e., drug X. Drug X has a hepatic extraction ratio of less than 0.1 and free fraction in plasma of less than 1% in healthy volunteers. <(Methods)under bar>: Pharmacokinetic (PK) parameters of drug X were obtained from subjects with normal renal function (I, n = 6), as well as in subjects with mild (II, n = 5), moderate (III, n = 7) and severe renal impairment (IV, n = 5). Disease-PK models were developed to describe the changes of PK parameters with respect to renal function measured by creatinine clearance. While experimentally observed data are presented for drug X, additional simulations were performed for other drugs that are extensively metabolized (extensive metabolism is defined as metabolism that accounts for more than 90% of total drug elimination). The simulated scenarios included drugs that have a low extraction ratio (ER) and with high plasma protein binding (PPB), low ER and with low PPB, high ER and with high PPB, or high ER and with low PPB. <(Results)under bar>: Systemic clearance of drug X, a low ER and high PPB drug, in renal patients depended on the simultaneous effects of renal disease on protein binding and intrinsic metabolic clearance. Protein binding of drug X was related to creatinine clearance in an inverse hyperbolic relationship, while the unbound intrinsic metabolic clearance declined linearly with creatinine clearance. Because the disease effects on these two factors offset each other in terms of total systemic clearance, the lowest total systemic clearance was not observed in the severely renal impairment patients, but rather in the moderately impaired group. Additional simulations showed that for low ER drugs that are highly metabolized, the pattern and magnitude of systemic clearance change in renal patients depended on how the disease affected PPB and/or intrinsic metabolic clearance. But the systemic clearance of high ER drugs would not be as susceptible to the effect of renal disease as that of low ER drug. <(Conclusions)under bar>: Chronic renal disease should not be considered as an isolated event that affects only renally excreted drugs. Uremia may also modify the disposition of a highly metabolized drug by changes in plasma protein binding and/or hepatic metabolism. C1 US FDA, CDER, OPS OCPB DPE I, Rockville, MD 20857 USA. Virginia Commonwealth Univ, Dept Pharmaceut, Richmond, VA USA. RP Yuan, R (reprint author), Bldg 1-3C39,340 Kingsland St, Nutley, NJ 07110 USA. NR 15 TC 32 Z9 32 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI MUNCHEN-DEISENHOFEN PA BAHNHOFSTRABE 9 POSTFACH 49, W-8024 MUNCHEN-DEISENHOFEN, GERMANY SN 0946-1965 J9 INT J CLIN PHARM TH JI Int. J. Clin. Pharmacol. Ther. PD MAY PY 2000 VL 38 IS 5 BP 245 EP 253 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 314AE UT WOS:000087031300003 PM 10839468 ER PT J AU Pensabene, JW Fiddler, W Donoghue, DJ AF Pensabene, JW Fiddler, W Donoghue, DJ TI Supercritical fluid extraction of atrazine and other triazine herbicides from fortified and incurred eggs SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE triazine herbicides; eggs; supercritical fluid extraction; atrazine ID METABOLITES; PESTICIDES; PRODUCTS; SOIL AB Triazines are a class of important pre-emergent weed herbicides. Some members of this class of herbicides exhibit carcinogenic and immunotoxicity properties, which make their use controversial in areas where animal feed crops are grown. It is therefore important to determine if triazine residues are transported to animal food products in order to ascertain the extent of human exposure. Most of the current herbicide residue extraction methods are time-consuming and solvent intensive. Supercritical fluid extraction (SFE) using CO2 has been used as a alternative for other residue extraction methods as a replacement for hazardous organic solvents. In this study, 10 triazines were extracted from eggs fortified at 100 ppb using unmodified supercritical CO2 at a pressure of 10000 psi and a temperature of 50 degrees C with off-line collection on a solid phase extraction cartridge containing Florisil. Atrazine recovery averaged 90.4% with an RSD of 3.3%. The other triazines were recovered at mean levels >73%. In a separate feeding study, atrazine and two of its dealkyl metabolites were detected in the egg. The results indicate that SFE is a viable technique for isolating triazine residues from eggs, requiring only 8 mL of solvent for each analysis. C1 ARS, Eastern Reg Res Ctr, USDA, Wyndmoor, PA 19038 USA. US FDA, Ctr Vet Med, Div Anim Res, Laurel, MD 20708 USA. RP Pensabene, JW (reprint author), ARS, Eastern Reg Res Ctr, USDA, 600 E Mermaid Lane, Wyndmoor, PA 19038 USA. NR 15 TC 27 Z9 32 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY PY 2000 VL 48 IS 5 BP 1668 EP 1672 DI 10.1021/jf990841t PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 315LV UT WOS:000087116000040 PM 10820076 ER PT J AU Ang, CYW Liu, FF Lay, JO Luo, WH McKim, K Gehring, T Lochmann, R AF Ang, CYW Liu, FF Lay, JO Luo, WH McKim, K Gehring, T Lochmann, R TI Liquid chromatographic analysis of incurred amoxicillin residues in catfish muscle following oral administration of the drug SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE LC; amoxicillin; incurred residues; catfish; depletion ID SOLID-PHASE EXTRACTION; HUMAN-PLASMA; MILK; PENICILLINS; AMPICILLIN; TISSUES; ASSAY AB Improper application of antibiotic chemicals to livestock and aquaculture species may lead to the occurrence of residues in food supplies. An appropriate depletion period is needed after the administration of drugs to animals for ensuring that residues in edible tissues are below established tolerance levels. This study was conducted to determine incurred amoxicillin residues in catfish muscle following oral administration. Dosed fish were harvested after four depletion periods, and muscle fillets were analyzed for amoxicillin residues using an HPLC method with precolumn derivatization and fluorescence detection. The residue levels in fish after a 6-h depletion ranged from 40 to 64 ng/g with one exception at 297 ng/g. Average residue levels decreased to 5.4 and 2.8 ng/g after 24- and 48-h depletions, respectively. Residue levels after a 72-h depletion decreased to below the method's limit of quantitation (1.2 ng/g). An LC-MS/MS confirmatory method was developed. Confirmation of the presence of amoxicillin was demonstrated in incurred fish samples containing residues at -50-300 ng/g. C1 US FDA, Div Chem, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Arkansas, Dept Fisheries & Aquaculture, Pine Bluff, AR 71611 USA. RP Ang, CYW (reprint author), US FDA, Div Chem, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. RI Lay, Jackson/G-1007-2011 OI Lay, Jackson/0000-0003-3789-2527 NR 11 TC 16 Z9 20 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY PY 2000 VL 48 IS 5 BP 1673 EP 1677 DI 10.1021/jf990410a PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 315LV UT WOS:000087116000041 PM 10820077 ER PT J AU de Silva, HD Sutherland, MF Suphioglu, C McLellan, SC Slater, JE Rolland, JM O'Hehir, RE AF de Silva, HD Sutherland, MF Suphioglu, C McLellan, SC Slater, JE Rolland, JM O'Hehir, RE TI Human T-cell epitopes of the latex allergen Hev b 5 in health care workers SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE T cells; latex; Hev b 5; peptides; T-cell epitopes; allergen; allergy ID RUBBER ELONGATION-FACTOR; HOUSE-DUST MITE; SPINA-BIFIDA; IGE ANTIBODIES; IDENTIFICATION; CLONING; PREVALENCE; BINDING; PEPTIDES; HEV-B-5 AB Background: Latex allergy affects health care workers as a high-risk cohort. Hev b 5 is a major latex allergen reacting with serum IgE from 92% of later-allergic health care workers, Because CD4(+) T-cell recognition is central to the specific immune response to allergens, identification of dominant T-cell epitopes is important for the development of specific immunotherapy for latex allergy. Objective: Our purpose was to map T-cell epitopes of Hev b 5 in health care workers. Methods: Six later-allergic health care workers (grade 3 to 4 enzyme allergosorbent test score) were studied. Peripheral blood latex specific 3-week T-cell lines were generated and screened for proliferative response to overlapping 20-mer peptides of Hev b 5, Supernatants collected at 48 hours were analyzed by ELISA for IL-5 and IFN-gamma. Results: Dot immunoblotting with use of recombinant Hev b 5/maltose-binding protein indicated serum-specific IgE in 5 of 6 patients. T-cell reactivity to one or more Hev b 5 peptides was identified in these 5 donors, but not in the sixth. Hev b 5 (46-65) induced T-cell proliferation in all 5 donors. Hev b 5 (109-128) stimulated T cells from 3 of these patients. Proliferative responses were accompanied by substantial IL-5 secretion and minimal IFN-gamma, indicating a T(H)2-predominant cytokine profile. Conclusions: Five of 6 latex-allergic patients demonstrated T-cell responsiveness to Hev b 5 consistent with a major T-cell reactive latex allergen. Two T-cell immunodominant regions of Hev b 5 were identified, and reactivity to these sites was associated with strong IL-5 but minimal IFN-gamma production. C1 Alfred Hosp, Dept Allergy Asthma & Clin Immunol, Prahran, Vic 3181, Australia. Alfred Hosp, Dept Pathol & Immunol, Prahran, Vic 3181, Australia. Monash Univ, Clayton, Vic 3168, Australia. US FDA, Ctr Biol Evaluat & Res, Lab Immunobiochem, Rockville, MD 20857 USA. RP O'Hehir, RE (reprint author), Alfred Hosp, Dept Allergy Asthma & Clin Immunol, Commercial Rd, Prahran, Vic 3181, Australia. RI Rolland, Jennifer/E-7543-2011; O'Hehir, Robyn/H-3627-2011 OI O'Hehir, Robyn/0000-0002-3489-7595 NR 37 TC 24 Z9 24 U1 0 U2 1 PU MOSBY-YEAR BOOK 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 2000 VL 105 IS 5 BP 1017 EP 1024 DI 10.1067/mai.2000.105806 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 316TW UT WOS:000087185000023 PM 10808185 ER PT J AU Rupp, HS Turnipseed, SB AF Rupp, HS Turnipseed, SB TI Confirmation of patulin and 5-hydroxymethylfurfural in apple juice by gas chromatography/mass spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MYCOTOXINS AB A gas chromatographic/mass spectrometric (GC/MS) method was developed for the confirmation of patulin and 5-hydroxymethytfurfural (HMF) extracted from apple juice. The extraction is based on the official AOAC method for liquid chromatographic analysis. Juice extracts are quickly and easily derivatized with bis(trimethylsilyl)trifluoracetamide under mild conditions, and the trimethylsilyl ethers of the analytes are stable for at least several hours. The analytes are determined by GC/MS using an electron-impact source and selected ion monitoring of characteristic ions. For both analytes, the interassay differences between base-peak ratios for samples and standards were all <7.1% (absolute). The presence of patulin was confirmed at fortification levels of about 30-400 mu g/L and naturally occurring levels of about 80-400 mu g/L. The presence of HMF was also confirmed at levels less than or equal to 2 mg/L. The proposed mass spectral fragmentation pathways of the analytes are presented. C1 US FDA, Pacific Reg Lab NW, Bothell, WA 98021 USA. US FDA, Anim Drugs Res Ctr, Denver, CO 80225 USA. RP Rupp, HS (reprint author), US FDA, Pacific Reg Lab NW, Bothell, WA 98021 USA. NR 12 TC 34 Z9 36 U1 1 U2 6 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2000 VL 83 IS 3 BP 612 EP 620 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 322GF UT WOS:000087501300011 PM 10868584 ER PT J AU Blodgett, RJ AF Blodgett, RJ TI Averaging the closest two out of three observations SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB The average of 3 observations is the standard method of estimating the location of their distribution. The average of the closest 2 out of 3 observations, although often used, has more variability than the average of all 3 observations for a standard normal distribution. One statistic uses a threshold to decide when to use the average of all 3 observations rather than the closest 2. With the standard normal, this statistic still has more variability than the average of all 3 observations. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Blodgett, RJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-705,200 C St,SW, Washington, DC 20204 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2000 VL 83 IS 3 BP 661 EP 664 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 322GF UT WOS:000087501300016 PM 10868589 ER PT J AU Sahu, SC Chou, MW Sotomayor, RE Hinton, DM Barton, CN O'Donnell, MW AF Sahu, SC Chou, MW Sotomayor, RE Hinton, DM Barton, CN O'Donnell, MW TI Effects of intermittent exposures of aflatoxin B-1 on hepatic and testicular glutathione S-transferase in rats SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE aflatoxin B-1; glutathione S-transferase ID LIVER AB Glutathione S-transferase (GST) plays a major role in the detoxification of the potent hepatocarcinogen aflatoxin B-1 (AFB(1)). This study evaluated the effects of intermittent exposures to AFB(1) on hepatic and testicular GST in rats. Male Fischer 344 rats were fed diets containing APE, (0, 0.01, 0.04, 0.4 and 1.6 ppm) intermittently at 4-week intervals up to 20 weeks. The control animals were fed an AFB(1)-free NIH-31 diet. Rats consuming diets with 0.01 ppm AFB(1) did not show the induction of hepatic or testicular GST activity. Intermittent exposures to AFB(1) at concentrations of 0.04-1.6 ppm significantly increased the GST activities. The increase of the enzyme activity was proportional to the dose and length of AFB(1) exposure. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. US FDA, Natl Ctr Toxicol Res, Laurel, MD 20708 USA. RP US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. NR 11 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0260-437X EI 1099-1263 J9 J APPL TOXICOL JI J. Appl. Toxicol. PD MAY-JUN PY 2000 VL 20 IS 3 BP 215 EP 219 DI 10.1002/(SICI)1099-1263(200005/06)20:3<215::AID-JAT649>3.3.CO;2-U PG 5 WC Toxicology SC Toxicology GA 310RR UT WOS:000086841600008 PM 10797475 ER PT J AU Khan, SA Nawaz, MS Khan, AA Cerniglia, CE AF Khan, SA Nawaz, MS Khan, AA Cerniglia, CE TI Transfer of erythromycin resistance from poultry to human clinical strains of Staphylococcus aureus SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ANTIBIOTIC-RESISTANCE; CONJUGATIVE TRANSFER; PLASMID TRANSFER; GENE-TRANSFER; DETERMINANTS; EPIDERMIDIS; TRANSPOSON; INVITRO; ISOLATE; SPP. AB The transfer of ermA and ermC genes, the two most common resistance determinants of erythromycin resistance, was studied with Luria-Bertani broth in the absence of additional Ca2+ or Mg2+ ions, Fifteen human and five poultry isolates of Staphylococcus aureus, which were resistant to erythromycin but carried different genetic markers for erythromycin resistance, were used for conjugation, Since both the donors (Amp(s)-Tet(r)) and recipients (Amp(r)-Tet(s)) were resistant to erythromycin, the transconjugants were initially picked up as ampicillin- and tetracycline-resistant colonies. The resistance transfer mechanisms of the chromosomally located erythromycin rRNA methylase gene ermA and the plasmid-borne ermC gene were monitored by a multiplex PCR and gene-specific internal probing assay. Four groups of transconjugants, based upon the transfer of the ermA and/or ermC gene, were distinguished from each other by the use of this method, Selective antibiotic screening revealed only one type of transconjugant that was resistant to ampicillin and tetracycline, A high frequency of transfer (4.5 x 10(-3)) was observed in all of the 23 transconjugants obtained, and the direction of tetracycline and erythromycin resistance marker transfer was determined to be from poultry to clinical isolates. The transfers of the ermA and ermC genes were via transposition and transformation, respectively. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Nawaz, MS (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 39 TC 19 Z9 21 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2000 VL 38 IS 5 BP 1832 EP 1838 PG 7 WC Microbiology SC Microbiology GA 311TU UT WOS:000086902400025 PM 10790109 ER PT J AU Hudson, CR Quist, C Lee, MD Keyes, KI Dodson, SV Morales, C Sanchez, S White, DG Maurer, JJ AF Hudson, CR Quist, C Lee, MD Keyes, KI Dodson, SV Morales, C Sanchez, S White, DG Maurer, JJ TI Genetic relatedness of Salmonella isolates from nondomestic birds in southeastern united states SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID FIELD GEL-ELECTROPHORESIS; AVIAN ESCHERICHIA-COLI; TYPHIMURIUM DT104; PHAGE TYPES; WILD BIRDS; RESISTANCE; VIRULENCE; ENTERITIDIS; INFECTION; DNA AB Salmonella infections have been implicated in large-scale die-offs of wild birds in the United States. Although we know quite a bit about the epidemiology of Salmonella infection among domestic fowl, we know little about the incidence, epidemiology, and genetic relatedness of salmonellae in nondomestic birds. To gain further insight into salmonellae in these hosts, 22 Salmonella isolates from diseased nondomestic birds were screened for the presence of virulence and antibiotic resistance-associated genes and compared genetically using pulsed-field gel electrophoresis (PFGE) and random amplified polymorphic DNA analysis. Of the 22 Salmonella isolates examined, 15 were positive for the invasion gene invA and the virulence plasmid-associated genes spvC and pef. Most (15 of 22) were generally sensitive to antibiotics. However, two Salmonella isolates from pet birds were identified as Salmonella enterica serovar Typhimurium DT104. Despite the general susceptibility of these Salmonella isolates to most antimicrobial agents, antibiotic resistance-associated genes int11, merA, and aadA1 were identified in a number of these isolates. Five distinct XbaI and nine distinct BlnI DNA patterns were observed for the 22 Salmonella isolates typed by PFGE. PFGE analysis determined that Salmonella isolates from passerines in Georgia and Wyoming were genetically related. C1 Univ Georgia, Coll Vet Med, Dept Avian Med, Athens, GA 30602 USA. Univ Georgia, Coll Vet Med, Dept Med Microbiol & Parasitol, Athens, GA 30602 USA. Univ Georgia, Coll Vet Med, Athens Diagnost Lab, Athens, GA 30602 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Maurer, JJ (reprint author), Univ Georgia, Coll Vet Med, Dept Avian Med, 953 Coll Stn Rd, Athens, GA 30602 USA. NR 60 TC 67 Z9 71 U1 0 U2 6 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 2000 VL 38 IS 5 BP 1860 EP 1865 PG 6 WC Microbiology SC Microbiology GA 311TU UT WOS:000086902400029 PM 10790113 ER PT J AU Sen, K AF Sen, K TI Rapid identification of Yersinia enterocolitica in blood by the 5 ' nuclease PCR assay SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; RED-CELLS; DNA; AMPLIFICATION; RNA; OLIGONUCLEOTIDES; HYBRIDIZATION; TRANSFUSION; DISEASE; REMOVAL AB Yersinia enterocolitica accounts for 50% of the clinical sepsis episodes caused by the transfusion of contaminated red blood cells. A 5' nuclease TaqMan PCR assay was developed to detect Y. enterocolitica in blood. Primers and a probe based on the nucleotide sequence of the 16S rRNA gene from Y. enterocolitica were designed. Whole-blood samples were spiked with various numbers of Y. enterocolitica cells, and total chromosomal DNA was extracted. When the TaqMan PCR assay was performed, as few as six bacteria spiked in 200 pi of blood could be detected. The assay was specific and did not detect other Yersinia species. The TaqMan assay is easy to perform, takes 2 h, and has the potential for use in the rapid detection of Y. enterocolitica contamination in stored blood units. C1 US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Sen, K (reprint author), US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, HFM-320,1401 Rockville Pike, Rockville, MD 20852 USA. NR 33 TC 46 Z9 49 U1 1 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 MAY PY 2000 VL 38 IS 5 BP 1953 EP 1958 PG 6 WC Microbiology SC Microbiology GA 311TU UT WOS:000086902400043 PM 10790127 ER PT J AU Cohen, MH Johnson, JR AF Cohen, MH Johnson, JR TI Temozolomide for advanced, metastatic melanoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Cohen, MH (reprint author), US FDA, Rockville, MD 20857 USA. NR 1 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 2000 VL 18 IS 10 BP 2185 EP 2185 PG 1 WC Oncology SC Oncology GA 315YE UT WOS:000087139900022 PM 10811684 ER PT J AU Chakrabarti, K Thomas, JA Kaczmarek, RV Waynant, RW Loscocco, MF AF Chakrabarti, K Thomas, JA Kaczmarek, RV Waynant, RW Loscocco, MF TI Optimization of viewing conditions and phantom image quality evaluations on GE DMR and full-field digital mammography system SO JOURNAL OF DIGITAL IMAGING LA English DT Article; Proceedings Paper CT 17th Symposium for Computer Applications in Radiology held at the Annual Meeting of the Society-for-Computer-Applications-in-Radiology (SCAR 2000) CY JUN 03-06, 2000 CL PHILADELPHIA, PENNSYLVANIA SP Soc Comp Applicat Radiol C1 US FDA, CDRH, Div Mammog, Qual Program, Rockville, MD 20850 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Chakrabarti, K (reprint author), US FDA, CDRH, Div Mammog, Qual Program, HFZ-240,1350 Piccard Dr, Rockville, MD 20850 USA. NR 2 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD MAY PY 2000 VL 13 IS 2 SU 1 BP 226 EP 227 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 319KA UT WOS:000087339000062 PM 10847411 ER PT J AU Heinitz, ML Ruble, RD Wagner, DE Tatini, SR AF Heinitz, ML Ruble, RD Wagner, DE Tatini, SR TI Incidence of Salmonella in fish and seafood SO JOURNAL OF FOOD PROTECTION LA English DT Review ID KAUFFMANN-WHITE SCHEME; UNITED-STATES; TYPHIMURIUM OUTBREAK; NATIONAL OUTBREAK; FOOD; VIRCHOW; INFECTIONS; DISEASE; ENTERITIDIS; SENFTENBERG AB Field laboratories of the U.S. Food and Drug Administration collected and tested 11,312 import and 768 domestic seafood samples over a 9-year period (1990 to 1998) for the presence of Salmonella. The overall incidence of Salmonella was 7.2% for import and 1.3% for domestic seafood. Nearly 10% of import and 2.8% of domestic raw seafood were positive for Salmonella, The overall incidence of Salmonella in ready-to-eat seafood and shellfish eaten raw was 0.47% for domestic-one shucked oyster and one shark cartilage powder. The incidence in the 2,734 ready-to-eat import seafood was 2.6%-cooked shrimp, shellfish or fish paste, smoked fish, salted/dried fish, and caviar. The incidence in import shellfish consumed raw was 1% in oyster 3.4% in clams, and 0% in mussels. The incidence in raw, import fish was 12.2%. Distribution of Salmonella in seafood on a regional basis indicated the incidence to be highest in central Pacific and Africa and lowest in Europe/Russia and North America (12% versus 1.6%). I)ata on a country basis indicated Vietnam to have the highest (30%) and Republic of Korea the lowest (0.7%). While the most frequent serotypes in import seafood were Salmonella Weltevreden (Ist), Salmonella Senftenberg (2nd), Salmonella Lexington, and Salmonella Paratyphi-B (3rd, equal numbers for each serotype), the top 20 list included Salmonella Enteritidis (5th), Salmonella Newport (6th), Salmonella Thompson (7th), Salmonella Typhimurium (12th), and Salmonella Anatum (13th), commonly involved in foodborne illness in the United States. Because the incidence in the present study is based on only a small fraction of the seafood imported into the United States, efforts should be directed toward implementation of hazard analysis and critical control points to reduce the incidence of Salmonella in seafood without relying on resting for Salmonella. C1 US FDA, Minneapolis, MN 55401 USA. RP Tatini, SR (reprint author), Univ Minnesota, US FDA, Dept Nutr & Food Sci, 1334 Eckles Ave, St Paul, MN 55108 USA. NR 103 TC 127 Z9 132 U1 2 U2 15 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC 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 2000 VL 63 IS 5 BP 579 EP 592 PG 14 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 312CM UT WOS:000086925700004 PM 10826714 ER PT J AU Kutza, J Crim, L Feldman, S Hayes, MP Gruber, M Beeler, J Clouse, KA AF Kutza, J Crim, L Feldman, S Hayes, MP Gruber, M Beeler, J Clouse, KA TI Macrophage colony-stimulating factor antagonists inhibit replication of HIV-1 in human macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MEASLES-VIRUS; BLOOD MONOCYTES; CSF PRODUCTION; FACTOR-I; INFECTION; CELLS; PERSISTENCE; LEUKOCYTES; MECHANISM AB Macrophages infected with HIV-1 produce high levels of M-CSP and macrophage-inflammatory protein-1 alpha (MIP-1 alpha). M-CSF facilitates the growth and differentiation of macrophages, while the chemotactic properties of MIP-1 alpha attract both T lymphocytes and macrophages to the site of HIV infection. Studies described in this work indicate M-CSF may function in an autocrine/ paracrine manner to sustain HIV replication, and data suggest possible therapeutic strategies for decreasing viral load following HIV infection. We show that macrophage infection with measles virus or respiratory syncytial virus, in contrast to HIV-1, results in production of MIP-1 alpha, but not M-CSF. Thus, M-CSF appears to be specifically produced upon infection of macrophages with HIV-1. Furthermore, addition of M-CSP antagonists to HIV-1-infected macrophages, including anti-M-CSF monoclonal or polyclonal Abs or soluble M-CSP receptors, dramatically inhibited HIV-1 replication and reduced production of MIP-1 alpha. Our results suggest that biologic antagonists for M-CSF may represent novel strategies for inhibiting the spread of HIV-1 by 1) blocking virus replication in macrophages, 2) reducing recruitment of HIV-susceptible T cells and macrophages by MIP-1 alpha, and 3) preventing the establishment and maintenance of infected macrophages as a reservoir for HIV. C1 US FDA, Div Monoclonal Antibodies, Off Therapeut Res & Review, Bethesda, MD 20892 USA. US FDA, Div Viral Prod, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Genzyme Corp, Framingham, MA 01701 USA. RP Kutza, J (reprint author), US FDA, CBER, OTRR, DMA Bldg 29B,Room 3NN18,HFM-558,1401 Rockville Pi, Rockville, MD 20852 USA. NR 36 TC 32 Z9 33 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2000 VL 164 IS 9 BP 4955 EP 4960 PG 6 WC Immunology SC Immunology GA 306XQ UT WOS:000086624300066 PM 10779806 ER PT J AU Thompson, DK Deal, CD Ison, CA Zenilman, JM Bash, MC AF Thompson, DK Deal, CD Ison, CA Zenilman, JM Bash, MC TI A typing system for Neisseria gonorrhoeae based on biotinylated oligonucleotide probes to PIB gene variable regions SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 99th Annual Meeting of the American-Society-for-Microbiology CY MAY 30-JUN 03, 1999 CL CHICAGO, ILLINOIS SP Amer Soc Microbiol ID FIELD GEL-ELECTROPHORESIS; GONOCOCCAL PILUS VACCINE; MEMBRANE PROTEIN PIB; MONOCLONAL-ANTIBODIES; SEQUENCE-ANALYSIS; HYBRID PORINS; IB GENE; SEROVARS; MENINGITIDIS; EPIDEMIOLOGY AB The porin proteins PIA and PIE of Neisseria gonorrhoeae are serotyping antigens for the serovar classification system and leading candidates for gonococcal vaccine development. Although serotyping has been a useful tool, this method can be insensitive to critical sequence changes in the por gene, including those in surface-exposed variable regions (VRs), A sensitive and specific typing system for N. gonorrhoeae has been developed that uses biotin-labeled oligonucleotide probes with chemiluminescence detection to type PTB gene VRs, The PIE VR types of geographically and temporally diverse gonococcal strains and sexual contact isolates were determined. por VR typing discriminated between most unrelated isolates and provided information about individual VR type that was not apparent from serovar designations. PIB VR typing avoids limited monoclonal antibody availability, interlaboratory variation, and the requirement for culture-based surveillance associated with gonococcal serotyping, and provides useful information about the molecular epidemiology of individual por gene VRs. C1 Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allerg Prod, Rockville, MD 20852 USA. Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. Univ London Imperial Coll Sci Technol & Med, Div Infect Dis & Microbiol, London, England. RP Bash, MC (reprint author), Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allerg Prod, HFM-428,1401 Rockville Pike, Rockville, MD 20852 USA. NR 34 TC 23 Z9 28 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 2000 VL 181 IS 5 BP 1652 EP 1660 DI 10.1086/315464 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 319QV UT WOS:000087353700018 PM 10823765 ER PT J AU Daniels, NA MacKinnon, L Bishop, R Altekruse, S Ray, B Hammond, RM Thompson, S Wilson, S Bean, NH Griffin, PM Slutsker, L AF Daniels, NA MacKinnon, L Bishop, R Altekruse, S Ray, B Hammond, RM Thompson, S Wilson, S Bean, NH Griffin, PM Slutsker, L TI Vibrio parahaemolyticus infections in the United States, 1973-1998 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 39th Interdisciplinary Conference on Antimicrobial Agents and Chemotherapy (ICAAC) CY SEP 26-29, 1999 CL SAN FRANCISCO, CALIFORNIA ID GULF-COAST; OYSTERS; CHOLERA AB Vibrio parahaemolyticus infections are associated with consumption of raw or undercooked shellfish, contaminated food, and exposure of wounds to warm seawater. Foodborne outbreaks and sporadic infections from Vibrio species in 4 Gulf Coast states are reported routinely to the Centers for Disease Control and Prevention (CDC), Between 1988 and 1997, 345 sporadic V. parahaemolyticus infections were reported: 59% were gastroenteritis, 34% were wound infections, 5% were septicemia, and 2% were from other exposures. Forty-five percent of patients suffering from these conditions were hospitalized for their infections, and 88% of persons with acute gastroenteritis reported having eaten raw oysters during the week before their illness occurred. Between 1973 and 1998, 40 outbreaks of V. parahaemolyticus infections were reported to the CDC, and these outbreaks included >1000 illnesses. Most of these outbreaks occurred during the warmer months and were attributed to seafood, particularly shellfish, The median attack rate among persons who consumed the implicated seafood was 56%. To prevent V. parahaemolyticus infections, persons should avoid consumption of raw or undercooked shellfish and exposure of wounds to seawater. C1 Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94115 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Bacterial & Mycot Dis, Foodborne & Diarrheal Dis Branch, Atlanta, GA USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Bacterial & Mycot Dis, Biostat & Informat Management Branch, Atlanta, GA USA. Ctr Dis Control, Epidemiol Program Off, Epidem Intelligence Serv, Atlanta, GA 30333 USA. US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. Texas Dept Hlth, Austin, TX USA. Florida Dept Hlth & Rehabil Serv, Tallahassee, FL 32399 USA. Alabama Dept Publ Hlth, Montgomery, AL 36102 USA. Louisiana Dept Hlth, New Orleans, LA USA. RP Daniels, NA (reprint author), Univ Calif San Francisco, Dept Med, Div Gen Internal Med, 1701 Divisadero St,Ste 500, San Francisco, CA 94115 USA. NR 22 TC 302 Z9 327 U1 2 U2 16 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 2000 VL 181 IS 5 BP 1661 EP 1666 DI 10.1086/315459 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 319QV UT WOS:000087353700019 PM 10823766 ER PT J AU Shieh, YSC Monroe, SS Fankhauser, RL Langlois, GW Burkhardt, W Baric, RS AF Shieh, YSC Monroe, SS Fankhauser, RL Langlois, GW Burkhardt, W Baric, RS TI Detection of Norwalk-like virus in shellfish implicated in illness SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT International Workshop on Human Caliciviruses CY MAR 29-31, 1999 CL ATLANTA, GEORGIA SP Ctr Dis Control & Prevent, US EPA, US FDA, Natl Inst Infect Dis Japan, Natl Inst Publ Hlth & Environm Protect, NIAID, Publ Hlth Lab Serv, Task Force Child Survival & Dev, USA Med Res & Mat Command, WHO, Merck Res Labs, SmithKline Beecham Biol, Wyeth Lederle Vaccines & Pediat, Natl Ctr Infect Dis ID ROUND-STRUCTURED VIRUSES; HEPATITIS-A VIRUS; REVERSE TRANSCRIPTION PCR; HUMAN ENTERIC VIRUSES; ACUTE GASTROENTERITIS; MULTISTATE OUTBREAK; MOLLUSCAN SHELLFISH; RAW OYSTERS; HYBRIDIZATION; CONSUMPTION AB In the 1990s, Norwalk-like viruses (NLVs) were identified in patient specimens as the primary pathogen associated with shellfish-borne gastroenteritis in the United States. Identification of these viruses from implicated shellfish has been difficult due to inefficient recovery of viruses, natural polymerase chain reaction (PCR) inhibitors in shellfish, and low virus contamination. Recent improvements to the method of detecting NLVs in shellfish include enhanced processing of virus and shellfish samples, application of nested PCR and nucleotide sequencing, and increased knowledge of NLV genetic diversity. Using a newly developed and sensitive method, an NLV G2 strain was identified in 2 oyster samples implicated in a 1998 California outbreak involving 171 cases. NLV capsid primers demonstrated a greater specificity of PCR detection than did polymerase primers. The 175-base viral capsid nucleotide sequences derived from oysters were 100% identical to those derived from a patient stool sample. This finding supports the epidemiologic associations indicating that contaminated shellfish serve as the vehicle for NLV transmission. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. Atlanta VA Med Ctr, Atlanta, GA USA. Ctr Dis Control & Prevent, Viral Gastroenteritis Sect, Atlanta, GA USA. Calif Dept Hlth Serv, Berkeley, CA 94704 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. RP Shieh, YSC (reprint author), US FDA, Gulf Coast Seafood Lab, POB 158, Dauphin Island, AL 36528 USA. NR 47 TC 47 Z9 50 U1 1 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 2000 VL 181 SU 2 BP S360 EP S366 DI 10.1086/315578 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 321DH UT WOS:000087439400018 PM 10804149 ER PT J AU D'Agnillo, F Alayash, AI AF D'Agnillo, F Alayash, AI TI Oxyhemoglobin and apoptosis SO JOURNAL OF NEUROSURGERY LA English DT Letter ID HEMOGLOBIN C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20205 USA. RP D'Agnillo, F (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20205 USA. NR 7 TC 6 Z9 6 U1 0 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAY PY 2000 VL 92 IS 5 BP 899 EP 900 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 307VV UT WOS:000086675600032 PM 10794315 ER PT J AU Klecker, RW Eiseman, JL Getzenberg, RH Collins, JM AF Klecker, RW Eiseman, JL Getzenberg, RH Collins, JM TI Deoxyuridine (DURD) distribution in rat prostatic tumors: Rationale for a PET probe of thymidylate synthase (TS). SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh Canc Inst, Pittsburgh, PA USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 1160 BP 264P EP 264P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892401054 ER PT J AU Sun, H Collins, JM Mangner, TJ Muzik, O Shields, AF AF Sun, H Collins, JM Mangner, TJ Muzik, O Shields, AF TI Biodistribution and metabolism of F-18-FAU: A potential chemotherapeutic drug and PET imaging agent. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Detroit, MI USA. US FDA, Bethesda, MD 20014 USA. Wayne State Univ, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 1162 BP 264P EP 265P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892401056 ER PT J AU Adam, M Mossoba, MM Lee, T AF Adam, M Mossoba, MM Lee, T TI Rapid determination of total trans fat content by attenuated total reflection infrared spectroscopy: An International Collaborative Study SO JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY LA English DT Article DE attenuated total reflection; infrared spectroscopy; trans fatty acids ID GAS-CHROMATOGRAPHY; OILS AB Interest in trans fat labeling has prompted efforts to develop new, more efficient methods for rapidly and accurately determining trans fat content in foods. The lower limit of quantitation, 5% trans fat (as percent of total fat), of transmission infrared official methods, such as AOAC 944.14 and 965.34, for total isolated trans fatty acids is too high to be generally useful for the determination of low levels of trans fats in foods. A novel and rapid (5 min) attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopic procedure was recently developed and applied to food products. This procedure was voted official method AOCS Cd 14d-99. by the American Oil Chemists' Society in 1999 after testing in a 12-laboratory international collaborative study. The results of this study are described in this paper. Analytical ATR-FTIR results exhibited high accuracy in the range investigated, 1-40% trans; results tended to have <2% high bias relative to the gravimetrically determined values. The precision of this internal reflection method was found to he superior to those of transmission infrared official methods. It is recommended that the applicability of the ATR-FTIR method be limited to trans levels of >1% (as percent of total fat). C1 US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Washington, DC 20204 USA. Lipton, Baltimore, MD 21229 USA. Abbott Labs, Ross Prod Div, Columbus, OH 43216 USA. RP Mossoba, MM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Mail Stop HFS-717,200 C St SW, Washington, DC 20204 USA. NR 15 TC 31 Z9 33 U1 1 U2 6 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0003-021X J9 J AM OIL CHEM SOC JI J. Am. Oil Chem. Soc. PD MAY PY 2000 VL 77 IS 5 BP 457 EP 462 DI 10.1007/s11746-000-0074-9 PG 6 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 313NB UT WOS:000087004800001 ER PT J AU van den Hoven, R Wagenaar, JA Walker, RD AF van den Hoven, R Wagenaar, JA Walker, RD TI In vitro activity of difloxacin against canine bacterial isolates SO JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION LA English DT Article ID ARYL-FLUOROQUINOLONES; A-56619 DIFLOXACIN; INVITRO AB The in vitro activity of difloxacin against canine bacterial isolates from clinical cases was studied in the United States and The Netherlands. Minimal inhibitory concentrations (MIC), the postantibiotic effect, the effect of pH on antimicrobial activity, and the bacterial killing rate tests were determined according to standard techniques. The MICs of American and Dutch isolates agreed in general. The MICs of the American gram-negative isolates ranged from 0.06 to 2.0 mu g/ml, and the MICs of the Dutch gram-negative isolates ranged from 0.016 to 8.0 mu g/ml. A few European strains of Protests mirabilis and Klebsiella pneumoniae had relatively high MICs. Bordetella bronchiseptica also was less susceptible to difloxacin. The MICs of the American grampositive cocci ranged from 0.125 to 4.0 mu g/ml, and the MICs of Dutch isolates ranged from 0.125 to 2.0 mu 8/ml. Difloxacin induced a concentration-dependent postantibiotic effect that lasted 0.2-3 hours in cultures with Escherichia coli, Staphylococcus intermedius, Streptococcus canis, Proteus spp., and Klebsiella pneumoniae. There was no postantibiotic effect observed against canine Pseudomonas aeruginosa. Decreasing the pH of the medium increased the MIC of Proteus mirabilis for difloxacin. The MICs of Escherichia coli and Klebsiella pneumoniae were lowest at neutral pH and were slightly increased in acid or alkaline media. At a neutral pH, most tested bacterial species were killed at a difloxacin concentration of 4 times the MIG. Similar results were obtained when these same bacteria were tested against enrofloxacin. A Klebsiella pneumoniae strain in an acidic environment was readily killed at difloxacin or enrofloxacin MIG, but at neutral pH the drug concentration had to be raised to 4 times the MIC for a bactericidal effect. After 24 hours of incubation at pH 7.1, difloxacin and enrofloxacin had similar bactericidal activity for all bacteria tested except Staphylococcus intermedius. Against S. intermedius, difloxacin was more bactericidal than enrofloxacin. C1 FT Dodge Anim Hlth Holland, Dept Biol Res & Dev, NL-1381 AA Weesp, Netherlands. Inst Anim Sci & Hlth, NL-8200 AB Lelystad, Netherlands. Univ Utrecht, Fac Vet Med, Dept Infect Dis & Immunol, Vet Microbiol Diagnost Ctr, NL-3508 TD Utrecht, Netherlands. US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP van den Hoven, R (reprint author), FT Dodge Anim Hlth Holland, Dept Biol Res & Dev, POB 36, NL-1381 AA Weesp, Netherlands. NR 17 TC 8 Z9 8 U1 0 U2 0 PU AMER ASSOC VETERINARY LABORATORY DIAGNOSTICIANS INC PI TURLOCK PA PO BOX 1522, TURLOCK, CA 95381 USA SN 1040-6387 J9 J VET DIAGN INVEST JI J. Vet. Diagn. Invest. PD MAY PY 2000 VL 12 IS 3 BP 218 EP 223 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA 312MP UT WOS:000086947300004 PM 10826834 ER PT J AU West, MS Spelic, DC AF West, MS Spelic, DC TI Using light sensitometry to evaluate mammography film performance SO MEDICAL PHYSICS LA English DT Article DE sensitometry; gradient; image quality; mammography; contrast ID DENSITY AB The performance of commercially available light sensitometers was compared with two other methods of x-ray sensitometry to determine whether commercially available sensitometers are viable for evaluating clinical performance of mammography film. X-ray sensitometry was performed using mammography screens that were modified to accommodate a graded optical step tablet (screen sensitometry). Finally, a means for performing intensity-scale x-ray sensitometry was configured (inverse-square sensitometry). Clinical mammography x-ray exposure conditions were used and film processing quality was closely monitored during the study. Statistical results for chi-square probabilities on the resulting contrast curves yielded good agreement for most of the configurations investigated. Comparison of film gradient versus optical density curves showed good agreement for maximum contrast values and the corresponding optical density for maximum contrast for three of the four screen-film combinations used when comparing light sensitometry to screen sensitometry. A similar comparison of light sensitometers to inverse-square sensitometry showed good agreement for maximum contrast, but less agreement for the corresponding optical density of maximum contrast. Based on these results, the authors concluded that commercially available sensitometers could be used to estimate clinical film performance for the screen-film systems tested. In particular they can be used to determine the range of optical densities that provide optimal film contrast. (C) 2000 American Association of Physicists in Medicine. C1 Mentor Technol Inc, Lanham, MD 20706 USA. US FDA, Ctr Devices & Radiol Hlth, Div Mammog Qual, Rockville, MD 20850 USA. US FDA, Ctr Devices & Radiol Hlth, Radiat Program, Rockville, MD 20850 USA. RP West, MS (reprint author), Mentor Technol Inc, 7404 Execut Pl,Suite 100, Lanham, MD 20706 USA. NR 11 TC 8 Z9 8 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAY PY 2000 VL 27 IS 5 BP 854 EP 860 DI 10.1118/1.598996 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 317EA UT WOS:000087212200005 PM 10841387 ER PT J AU Cada, AM Gray, EP Ferguson, SA AF Cada, AM Gray, EP Ferguson, SA TI Minimal behavioral effects from developmental cerebellar stunting in young rats induced by postnatal treatment with alpha-difluoromethylornithine SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE DFMO; cerebellum; difluoromethylornithine; behavior ID RETINOIC ACID EXPOSURE; ORNITHINE DECARBOXYLASE; IRREVERSIBLE INHIBITOR; NEONATAL RAT; BRAIN; POLYAMINES; PERIODS; CORTEX AB Postnatal treatment with alpha-difluoromethylornithine (DFIWO), a potent inhibitor of ornithine decarboxylase, reduces polyamine levels in rats. Because polyamines are critically involved in growth and development, body and/or brain weights an often decreased by DFMO treatment. Here, rats were injected subcutaneously with 0, 250, 500, or 750 mg/kg of DFMO on postnatal days (PNDs) 5-10. Behavioral assessments included righting reflex, negative geotaxis, forelimb hanging, open field activity, and rotarod performance. Additionally, day of eye opening was recorded and on PND 28, whole and regional brain weights were measured. Cerebellar/whole-brain ratio was decreased in a dose-dependent manner whereas frontal cortex/whole-brain ratio was increased. Eye opening was delayed to a similar extent in all treated groups whereas body weight was unaffected. alpha-difluoromethylornithine treatment had no significant effects on the assessed behaviors. These results indicate that 6 days of DFMO treatment can substantially impact cerebellar development, but this appears to have few effects on these early assessed behaviors. However, potential behavioral alterations may not be apparent until adulthood. Published by Elsevier Science Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Cada, AM (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 27 TC 13 Z9 13 U1 0 U2 0 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 2000 VL 22 IS 3 BP 415 EP 420 DI 10.1016/S0892-0362(99)00085-9 PG 6 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 321RZ UT WOS:000087469600011 PM 10840185 ER PT J AU Patterson, TA Schmued, LC Sandberg, JA Slikker, W AF Patterson, TA Schmued, LC Sandberg, JA Slikker, W TI Temporal development of 2 ',3 '-dideoxyinosine (ddI)-induced peripheral myelinopathy SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE neuropathy; ddI; sciatic nerve; neuropathology ID AIDS-RELATED COMPLEX; PHASE-I TRIAL; MITOCHONDRIAL-DNA; 2',3'-DIDEOXYCYTIDINE; NEUROPATHY; PHARMACOKINETICS; TOXICITY; CELLS; RATS; DDI AB The anti-HIV therapeutic dideoxyinosine (ddI) has been reported to produce a painful, dose-limiting peripheral myelinopathy in HIV-infected patients after chronic administration. We have previously demonstrated ddI-induced myelinopathy in a non-HIV-infected rat model after 20 weeks of dosing, characterized by myelin splitting and intramyelin edema. The present study examined the time course needed to produce the ddI-induced neuropathy. Adult male Sprague-Dawley rats were gavaged with vehicle or 415 mg/kg ddI twice daily for up to 20 weeks. Groups of treated (n = 6-8) and control (n = 3-5) animals were killed after 5, 10, 15, and 20 weeks of dosing and the distal end of the sciatic nerve was removed. The nerve was postfixed by immersion in neutral phosphate-buffered formalin, dehydrated in graded alcohols, and embedded in plastic embedding media. One-micrometer-thick sections were cut and stained with toluidine blue and basic fuchsin. Plasma levels of ddI on the day the animals were killed were greater than 10 mu g/ml within the first hour after dosing and fell rapidly to less than 1 mu g/ml (clinical range 1-2 mu g/ml) within 3 h after dosing. The abnormalities observed in the sciatic nerve were few, if any, after 5 or 10 weeks, but very prominent after 15 weeks of dosing. Four of the six ddI-treated rats exhibited abnormal morphology as evidenced by myelin splitting and ballooned myelin sheaths. Although abnormal morphology was present at 20 weeks of dosing, the effect was not as robust as at 15 weeks. This suggests that the nerve may partially recover from the effects of ddI with time. Published by Elsevier Science Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Patterson, TA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. FU NIEHS NIH HHS [IAG Y01-ES-10187] NR 19 TC 9 Z9 10 U1 0 U2 0 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 2000 VL 22 IS 3 BP 429 EP 434 DI 10.1016/S0892-0362(99)00087-2 PG 6 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 321RZ UT WOS:000087469600013 PM 10840187 ER PT J AU Boorman, GA Owen, RD Lotz, WG Galvin, MJ AF Boorman, GA Owen, RD Lotz, WG Galvin, MJ TI Evaluation of in vitro effects of 50 and 60 Hz magnetic fields in regional EMF exposure facilities SO RADIATION RESEARCH LA English DT Article ID ANCHORAGE-INDEPENDENT GROWTH; INTRACELLULAR CALCIUM OSCILLATIONS; ORNITHINE DECARBOXYLASE ACTIVITY; T-CELL LINE; ELECTROMAGNETIC-FIELDS; TRANSCRIPT LEVELS; CHILDHOOD-CANCER; FLUX DENSITIES; JB6; ENHANCEMENT AB A weak association between magnetic-field exposure and increased incidences of cancer has been reported, While alterations in cellular processes after in vitro magnetic-field exposures have also been reported to provide plausibility for this association, other laboratories have been unable to repeat the findings. As part of an accelerated electric- and magnetic-field (EMF) research program, the National Institute of Environmental Health Sciences with the Department of Energy identified the replication of the published positive effects as a priority. Regional EMF exposure facilities were established to investigate major in vitro effects from the literature. These included effects on gene expression, intracellular calcium, colony growth in soft agar, and ornithine decarboxylase activity. The laboratories that first reported these effects provided experimental protocols, cell lines, and other relevant experiment details. Regional facility studies included sham/sham exposures (no applied field in either chamber) and were done in a blinded fashion to minimize investigator bias. In nearly all experiments, no effects of magnetic-field exposure were found. The effort provided insight into dealing with the difficulty of replication of subtle effects in complex biological systems. Experimental techniques provided some clues for the differences in experimental results between the regional facility and the original investigator. Studies of subtle effects require extraordinary efforts to confirm that the effect can be attributed to the applied exposure. (C) 2000 by Radiation Research Society. C1 NIEHS, Off Special Programs, Res Triangle Pk, NC 27709 USA. US FDA, Ctr Device & Radiol Hlth, Rockville, MD 20850 USA. NIOSH, Div Biomed & Behav Sci, Cincinnati, OH 45226 USA. NIOSH, Off Extramural Programs, Atlanta, GA USA. RP Boorman, GA (reprint author), NIEHS, Off Special Programs, POB 12233,MD B3-08, Res Triangle Pk, NC 27709 USA. NR 36 TC 17 Z9 18 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD MAY PY 2000 VL 153 IS 5 BP 648 EP 657 DI 10.1667/0033-7587(2000)153[0648:EOIVEO]2.0.CO;2 PN 2 PG 10 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 317BL UT WOS:000087204400006 PM 10790288 ER PT J AU Morehouse, CA Owen, RD AF Morehouse, CA Owen, RD TI Exposure to low-frequency electromagnetic fields does not alter HSP70 expression or HSF-HSE binding in HL60 cells SO RADIATION RESEARCH LA English DT Article ID SALIVARY-GLAND CELLS; HZ MAGNETIC-FIELDS; HEAT-SHOCK GENES; MYC; ACTIVATION; TRANSCRIPTION; STRESS AB Environmental exposure to extremely low-frequency electromagnetic fields (ELF EMFs) has been identified as a possible contributor to increased cancer incidence and other diseases. In vitro studies designed to probe for biological mechanisms that might explain such relationships have included several studies of gene expression. While gene expression studies have focused on MYC, effects of ELF EMFs on the expression of beta-actin, histone H2B, beta-tubulin, SRC, FOS and JUN have also been reported. In addition, some investigators have reported both an induction of HSP70 expression and an increase in HSF-HSE binding in HL60 (human promyelocytic leukemia) cells after exposure to a 60 Hz magnetic field. In this study, HL60 cells were exposed to a weak 60 Hz magnetic field (6.3 or 8.0 mu T) or to a positive control heat shock (42 or 44 degrees C), While heat shock led to reproducible induction of HSP70 expression and HSF-HSE binding, no significant effect of exposure to ELF EMFs on either of these end points was observed. (C) 2000 by Radiation Research Society. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Owen, RD (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-114,9200 Corp Blvd, Rockville, MD 20850 USA. FU NIEHS NIH HHS [Y1-ES-0006] NR 20 TC 28 Z9 29 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD MAY PY 2000 VL 153 IS 5 BP 658 EP 662 DI 10.1667/0033-7587(2000)153[0658:ETLFEF]2.0.CO;2 PN 2 PG 5 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 317BL UT WOS:000087204400007 PM 10790289 ER PT J AU Morehouse, CA Owen, RD AF Morehouse, CA Owen, RD TI Exposure of Daudi cells to low-frequency magnetic fields does not elevate MYC steady-state mRNA levels SO RADIATION RESEARCH LA English DT Article ID ELECTROMAGNETIC-FIELDS; HL-60 CELLS; C-MYC; TRANSCRIPTS; EXPRESSION AB effect of extremely low-frequency electromagnetic field (ELF EMF) exposures to human health has been widely debated. Epidemiological studies have found a possible correlation between increased cancer incidence and environmental ELF EMF exposures. Results from in vitro studies performed to examine the possible underlying bioeffects of ELF EMFs have varied greatly. Reported effects range from robust and reproducible effects to undetectable. In this study, Daudi cells were exposed to 60 Hz magnetic fields for 20, 40 or 60 min at flux densities of 12.5, 50, 100 or 500 mu T, Exposures were performed in the Regional ELF-EMF Exposure Facility (Rockville, MD) to minimize variables that might contribute to a false positive effect. Exposures included sham/sham, exposed/ sham or shant/exposed, and were performed with blinding with respect to type of exposure. 12-O-Tetradecanoylphorbol-13-acetate (TPA) treatment was used as a positive control. Total cellular RNA was isolated using a single-step technique. Human MYC expression was measured by northern blot hybridization as an indicator of the responsiveness of Daudi cells to experimental conditions. Beta-2-microglobulin (B2M) expression was measured simultaneously as an internal control. Exposure to a 60 Hz magnetic field did not significantly alter MYC expression in Daudi cells under any of the exposure conditions. (C) 2000 by Radiation Research Society. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Owen, RD (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-114,9200 Corp Blvd, Rockville, MD 20850 USA. FU NIEHS NIH HHS [Y1-ES-0006] NR 14 TC 12 Z9 13 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD MAY PY 2000 VL 153 IS 5 BP 663 EP 669 DI 10.1667/0033-7587(2000)153[0663:EODCTL]2.0.CO;2 PN 2 PG 7 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 317BL UT WOS:000087204400008 PM 10790290 ER PT J AU Schmidt, KA Deal, CD Kwan, M Thattassery, E Schneider, H AF Schmidt, KA Deal, CD Kwan, M Thattassery, E Schneider, H TI Neisseria gonorrhoeae MS11mkC opacity protein expression in vitro and during human volunteer infectivity studies SO SEXUALLY TRANSMITTED DISEASES LA English DT Article; Proceedings Paper CT 10th International Pathogenic Neisseria Conference CY SEP 08-13, 1996 CL BALTIMORE, MARYLAND ID OUTER-MEMBRANE PROTEINS; PHASE VARIATION; EPITHELIAL-CELLS; GONOCOCCAL OPACITY; HUMAN-NEUTROPHILS; MONOCLONAL-ANTIBODIES; ANTIGENIC VARIATION; ESCHERICHIA-COLI; GENE-EXPRESSION; COLONY OPACITY AB Background and Objectives: Neisseria gonorrhoeae Ms11mkC harbors 11 independently expressed opacity (Opa) protein genes with distinct in vitro expression frequencies. In experimental infections in which human male volunteers were inoculated with transparent (Opa(-)), piliated (P+) strains, the authors associate onset of symptoms with recovery of opaque (Opa(+)) gonococci, Goals: In vitro and recovered (Opa) protein expression rates were compared to determine if the human host influences Opa expression, Study Design: Opa expression was determined using Western immunoblot analysis; Opa sizes were determined using a scanning densitometer. Results: Seven of 10 Opa proteins were identified in gonococci recovered from all of the volunteers at frequencies consistent with in vitro results (Opa C, 29.5 kDa; Opa K, 30 kDa; Opa G, 31 kDa; Opa I, 32 kDa; Opa J, 33 kDa; Opa D, 34 kDa; and Opa H, 37 kDa) (P greater than or equal to 0.01, Fisher exact test). Opa B (30.5 kDa) was identified at lower than expected frequencies, whereas Opa E (31.2) and F (31.5) were identified at higher than expected frequencies. When recovered gonococci were reanalyzed for in vitro expression frequencies, they were consistent with preinfection frequencies. Conclusions: The host may influence the prevalence of some Opa proteins. C1 Walter Reed Army Inst Res, Dept Bacterial Dis, Washington, DC USA. US FDA, Ctr Biol Evauluat Res, Dept Enter & STDs, Rockville, MD 20857 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Schmidt, KA (reprint author), Dartmouth Coll, Sch Med, Dept Microbiol, 206 Vail, Hanover, NH 03755 USA. FU PHS HHS [P01A134582] NR 40 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD MAY PY 2000 VL 27 IS 5 BP 278 EP 283 DI 10.1097/00007435-200005000-00008 PG 6 WC Infectious Diseases SC Infectious Diseases GA 312HU UT WOS:000086938500008 PM 10821601 ER PT J AU Slikker, W Olivero, OA Patterson, TA Poirier, MC AF Slikker, W Olivero, OA Patterson, TA Poirier, MC TI Potential toxicities of HIV therapeutics in the developing infant SO TERATOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ZIDOVUDINE; MICE; 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE; PHARMACOKINETICS; TRANSMISSION C1 US FDA, Neurotox Div, NCTR, Jefferson, AR 72079 USA. NCI, Div Basic Sci, Bethesda, MD 20892 USA. RP Slikker, W (reprint author), US FDA, Neurotox Div, NCTR, 3900 NCTR Dr, Jefferson, AR 72079 USA. NR 9 TC 3 Z9 3 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 0040-3709 J9 TERATOLOGY JI Teratology PD MAY PY 2000 VL 61 IS 5 BP 397 EP 398 DI 10.1002/(SICI)1096-9926(200005)61:5<397::AID-TERA16>3.0.CO;2-8 PG 2 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 310FM UT WOS:000086815900015 PM 10777839 ER PT J AU Hinton, DM AF Hinton, DM TI USFDA "Redbook II" immunotoxicity testing guidelines and research in immunotoxicity evaluations of food chemicals and new food proteins SO TOXICOLOGIC PATHOLOGY LA English DT Article DE immunotoxicity guidelines; food additives; Redbook II; food proteins ID ADDITIVES; RAT AB The rapid advances in the field of immunology and an understanding of the potential adverse effects of xenobiotics on the immune system have resulted in the development of a discipline in toxicology now referred to as immunotoxicology. This discipline has evolved steadily over the last 2 decades as a result of research in the national and international communities. Various US, European, and Japanese regulatory agencies have recognized a need to promulgate resting guidelines for immunotoxicity in support of the approval process involving toxicological testing. The US Food and Drug Administration "Redbook II" guidelines and some of the research conducted in support of the concepts and testing strategies are presented here. Concerns raised with regard to these guidelines are included, as are on-going initiatives in development of experimental approaches for assessing allergic potential and/or hypersensitivity responses to new foods and food constituents. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Special Res Skills,Div Toxicol Studies, Biochem & Analyt Toxicol Branch, Washington, DC 20204 USA. RP Hinton, DM (reprint author), Module 1 Lab, HFS-509,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 37 TC 20 Z9 20 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI MT ROYAL PA 19 MANTUA RD, MT ROYAL, NJ 08061 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAY-JUN PY 2000 VL 28 IS 3 BP 467 EP 478 DI 10.1177/019262330002800318 PG 12 WC Pathology; Toxicology SC Pathology; Toxicology GA 321KT UT WOS:000087455200017 PM 10862567 ER PT J AU Bowyer, JF Newport, GD Slikker, W Gough, B Ferguson, SA Tor-Agbidye, J AF Bowyer, JF Newport, GD Slikker, W Gough, B Ferguson, SA Tor-Agbidye, J TI An evaluation of I-ephedrine neurotoxicity with respect to hyperthermia and caudate/putamen microdialysate levels of ephedrine, dopamine, serotonin, and glutamate SO TOXICOLOGICAL SCIENCES LA English DT Article DE neurotoxicity; microdialysis; ephedrine; striatum; dopamine; serotonin ID PERFORMANCE LIQUID-CHROMATOGRAPHY; METHAMPHETAMINE-INDUCED NEUROTOXICITY; TYROSINE-HYDROXYLASE ACTIVITY; STRIATAL DOPAMINE; CAUDATE-PUTAMEN; D-AMPHETAMINE; PRECOLUMN DERIVATIZATION; NEURONAL DEGENERATION; BRAIN MICRODIALYSATE; AMINO-ACIDS AB l-Ephedrine is an active ingredient in several herbal formulations with a mechanism of action similar to amphetamine and methamphetamine. However, its potential to damage dopaminergic terminals in the caudate/putamen (CPu) has yet to be fully evaluated. The studies here used in vivo brain microdialysis experiments to determine the systemic doses and extracellular brain levels of E-ephedrine necessary to produce similar increases in CPu extracellular dopamine and marked hyperthermia that were previously shown necessary for amphetamine-induced neurotoxicity in male Sprague-Dawley rats. At an environmental temperature of 23 degrees C, a single 40 mg/kg intraperitoneal (ip) dose of I-ephedrine produced marked hyperthermia (greater than or equal to 40 degrees C), peak microdialysate ephedrine levels of 7.3 +/- 1.2 mu M, and a 20-fold increase in microdialysate dopamine levels. Twenty-five mg/kg produced a lesser degree of hyperthermia, peak microdialysate ephedrine levels of 2.6 +/- 0.4 mu M, and a 10-fold increase in dopamine levels. Three doses: of 40 mg/kg given at 3-h intervals or 4 doses of 25 mg/kg I-ephedrine given at 2-h intervals were compared with 4 doses of 5 mg/kg d-amphetamine given at 2-h intervals. Multiple doses of either ephedrine or amphetamine caused severe hyperthermia (greater than or equal to 41.3 degrees C) but striatal tissue levels of dopamine 7 days after dosing were reduced only 25% or less by ephedrine compared to the 75% reductions produced by amphetamine. The increases in CPu microdialysate levels of serotonin produced by either 4 x 25 mg/kg E-ephedrine or 4 x 5 mg/kg d-amphetamine did not significantly differ, but elevation of dopamine levels by d-amphetamine were over 2-fold times the level caused by I-ephedrine. Microdialysate glutamate levels were elevated to the same extent by either 25 mg/kg E-ephedrine or 4 x 5 mg/kg d-amphetamine. E-Ephedrine may not be as neurotoxic to dopaminergic terminals as d-amphetamine, because non-lethal doses of I-ephedrine do not sufficiently increase the CPu dopamine levels within nerve terminals or the extracellular space to those necessary for a more pronounced long-term dopamine depletion. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Bowyer, JF (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132, Jefferson, AR 72079 USA. NR 52 TC 19 Z9 20 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2000 VL 55 IS 1 BP 133 EP 142 DI 10.1093/toxsci/55.1.133 PG 10 WC Toxicology SC Toxicology GA 310FH UT WOS:000086815500016 PM 10788568 ER PT J AU Wear, KA AF Wear, KA TI Measurements of phase velocity and group velocity in human calcaneus SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE calcaneus; trabecular bone; cancellous bone; velocity; dispersion; osteoporosis ID CANCELLOUS BONE; ULTRASONIC VELOCITY; TRABECULAR BONE; HIP FRACTURE; OS CALCIS; IN-VITRO; ATTENUATION; DENSITY; WOMEN; PREDICTION AB Ultrasonic velocity in calcaneus correlates highly with bone mineral density, which is a good predictor of osteoporotic fracture risk. Several commercial bone sonometers perform a velocity measurement based on the transit time of a broadband pulse to assess skeletal status. This approach is somewhat problematic, however, because several authors have reported ambiguities in measurements in calcaneus, Phase velocity is an alternative that may be less dependent on device spectral characteristics. In addition, dispersion (the frequency-dependence of phase velocity) is a fundamental property worth investigating to increase understanding of interaction between ultrasound and bone. To compare two group-velocity measurement methods and one phase-velocity measurement method, a polycarbonate sample (for method validation) and 24 human calcanei were investigated in vitro. Phase velocity in calcaneus at 500 kHz was 1511 m/s +/- 30 m/s (mean +/- standard deviation). Average phase velocity decreased approximately linearly with frequency (-18 m/s MHz). The two group velocity measurements were comparable and tended to be slightly lower than phase velocity, The magnitude of dispersion showed little correlation with bone mineral density. (C) 2000 World Federation for Ultrasound in Medicine & Biology. 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. NR 29 TC 92 Z9 94 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD MAY PY 2000 VL 26 IS 4 BP 641 EP 646 DI 10.1016/S0301-5629(99)00172-6 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 322EQ UT WOS:000087497600015 PM 10856627 ER PT J AU Tong, B Chang, SC Carpenter, EE O'Connor, CJ Lay, JO Norman, RE AF Tong, B Chang, SC Carpenter, EE O'Connor, CJ Lay, JO Norman, RE TI Di-mu-halo-bis{[tris(2-pyridylmethyl)amine-kappa N-4]nickel(II)} bis(triethylammonium) tetraperchlorate: Magnetostructural studies SO INORGANICA CHIMICA ACTA LA English DT Article DE crystal structures; nickel(II) complexes; magnetic susceptibility; ferromagnetic coupling ID CRYSTAL-STRUCTURE; MAGNETIC-PROPERTIES; COMPLEXES; DIFFRACTION; EXCHANGE; X=CL; CU; BR AB [{Ni(TPA)Br}(2)](Clo(4))(2).2HNEt(3)ClO(4), where TPA is tris-(2-pyridylmethyl)amine, crystallizes in the monoclinic space group P2(1)/c with Z = 2, a = 11.531(3) Angstrom, b = 22.141(3) Angstrom, c = 12.511(2) Angstrom and beta = 107.44(1)degrees. The structure was determined at ambient temperature from 5519 reflections (2937 observed) with R = 0.0426 and R-w = 0.0404. The [{Ni(TPA)Br}(2)](2+) core is centrosymmetric with unsymmetrical bridges (Ni-Br=2.504(1) and 2.662(1) Angstrom). Each Ni atom is pseudo-octahedral six-coordinate. Triethylammonium perchlorate cocrystallizes with the metal complex. Magnetic susceptibility studies (fit to the Ginsberg model) indicate the Ni centers are ferromagnetically coupled with J/k = 10.0(5) cm(-1). The chloro complex ([{Ni(TPA)Cl}(2)](Clo(4))(2).2HNEt(3)ClO(4)) is also ferromagnetically coupled with J/k = 7.6(1) cm(-1). (C) 2000 Elsevier Science S.A. All rights reserved. C1 Univ Louisiana Monroe, Dept Chem, Monroe, LA 71209 USA. Duquesne Univ, Dept Phys, Pittsburgh, PA 15282 USA. Univ New Orleans, Adv Mat Res Inst, New Orleans, LA 70148 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Norman, RE (reprint author), Univ Louisiana Monroe, Dept Chem, CNSB-210, Monroe, LA 71209 USA. RI Carpenter, Everett/A-2797-2010; Lay, Jackson/G-1007-2011 OI Carpenter, Everett/0000-0002-3497-0318; Lay, Jackson/0000-0003-3789-2527 NR 26 TC 17 Z9 17 U1 0 U2 3 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0020-1693 J9 INORG CHIM ACTA JI Inorg. Chim. Acta PD APR 30 PY 2000 VL 300 BP 855 EP 861 DI 10.1016/S0020-1693(99)00591-5 PG 7 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 320WA UT WOS:000087422800100 ER PT J AU Shuttleworth, KL Sung, JH Kim, E Cerniglia, CE AF Shuttleworth, KL Sung, JH Kim, E Cerniglia, CE TI Physiological and genetic comparison of two aromatic hydrocarbon-degrading Sphingomonas strains SO MOLECULES AND CELLS LA English DT Article DE aromatic hydrocarbon; biodegradation; Sphingomonas ID PSEUDOMONAS-PAUCIMOBILIS; DEEP-SUBSURFACE; YANOIKUYAE B1; DEGRADATION; DNA; BIPHENYL; BACTERIA; NAPHTHALENE; METABOLISM; CLONING AB Sphingomonas yanoikuyae strain B1 is able to degrade a wider range of aromatic hydrocarbons than S, paucimobilis strain TNE12 can degrade. Various culture techniques were used to corroborate that B1 used m-xylene, biphenyl, toluene, naphthalene. and phenanthrene as sole carbon and energy sources. In contrast, TNE12 could not mineralize m-xylene, biphenyl, toluene, or naphthalene. However, fluoranthene served as carbon and energy source for TNE12 but not B1. Southern blots were performed using the cloned genomic region (approximately 23 kb) containing the degradative genes for the upstream pathways for biphenyl and m-xylene and a TOL plasmid-type meta operon from B1 as a probe against the KpnI restriction-digested total DNA of TNE12, This 23 kb probe hybridized to three KpnI-digested fragments of TNE12 DNA; thus significant homology existed between the aromatic hydrocarbon-degrading genes of B1 and TNE12, Further work with smaller probes revealed, however, that TNE12 DNA fragments did not hybridize with the probe containing the genes encoding for xylene monooxygenase and part of an aromatic dioxygenase. A recombinant plasmid, which contains only the genes for xylene monooxygenase, is able to complement TNE12 on in-xylene, These genes are, therefore, probably missing from TNE12, Hence, TNE12 cannot use monocyclic aromatics whereas B1 can. Pulsed field gel electrophoresis coupled with Southern blotting revealed that the aromatic degradative genes were on an approximately 240 kb plasmid of TNE12; the same genes in B1 are known to be chromosomal. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Yonsei Univ, Dept Biol, Seoul 120749, South Korea. Yonsei Univ, Inst Life Sci, Seoul 120749, South Korea. RP Kim, E (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 26 TC 16 Z9 16 U1 1 U2 3 PU SPRINGER-VERLAG SINGAPORE PTE LTD PI SINGAPORE PA #04-01 CENCON I, 1 TANNERY RD, SINGAPORE 347719, SINGAPORE SN 1016-8478 J9 MOL CELLS JI Mol. Cells PD APR 30 PY 2000 VL 10 IS 2 BP 199 EP 205 DI 10.1007/s10059-000-0199-x PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 306RQ UT WOS:000086610400012 PM 10850662 ER PT J AU Chou, MW Mikhailova, MV Nichols, J Poirier, LA Warbritton, A Beland, FA AF Chou, MW Mikhailova, MV Nichols, J Poirier, LA Warbritton, A Beland, FA TI Interactive effects of methyl-deficiency and dietary restrictionon liver cell proliferation and telomerase activity in Fischer 344 rats pretreated with aflatoxin B-1 SO CANCER LETTERS LA English DT Article DE aflatoxin B-1; telomerase; hepatocarcinogenesis; dietary restriction; glutathione S-transferase ID CHOLINE-DEVOID DIET; ACID-DEFINED DIETS; CALORIC RESTRICTION; LIPID-PEROXIDATION; ADDUCT FORMATION; DNA METHYLATION; POSITIVE FOCI; CARCINOGENESIS; CANCER; HEPATOCARCINOGENESIS AB The effects of methyl-deficiency and dietary restriction (DR) on hepatic cell proliferation and telomerase activity was studied in male Fischer 344 rats pretreated with aflatoxin B-1 (AFB(1)). Five-week-old rats were gavaged 5 days per week for 3 weeks with AFB(1) (25 mug/rat per day) or solvent (100 mul 75% dimethylsulfoxide). Rats were then divided into four groups. Two groups were fed a methyl-sufficient (MS) diet either ab libitum (AL) or with DR. The other two groups were fed a methyl-deficient (MD) diet either AL or with DR. At 15, 20, and 32 weeks of age, hepatic cell proliferation, telomerase activity. and the number of glutathione S-transferase-P positive (GST-P+) foci were determined. DR reduced hepatic cell proliferation, while the MD diet and AFB(1) pretreatment increased cell proliferation. Telomerase activity was decreased by DR and increased by the MD diet and AFB(1) pretreatment. The same trend was observed with GST-P+ foci: in AFB(1)-pretreated rats, methyl deficiency increased the number of foci, while DR decreased the number. These results are consistent with a role of telomerase in hepatocarcinogenesis. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Pathol Associates Int, Jefferson, AR 72079 USA. RP Chou, MW (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 52 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD APR 28 PY 2000 VL 152 IS 1 BP 53 EP 61 DI 10.1016/S0304-3835(99)00436-X PG 9 WC Oncology SC Oncology GA 396WR UT WOS:000166661200008 PM 10754206 ER PT J AU Hutter, JC Kuehnert, MJ Wallis, RR Lucas, DD Sen, S Jarvis, WR AF Hutter, JC Kuehnert, MJ Wallis, RR Lucas, DD Sen, S Jarvis, WR TI Acute onset of decreased vision and hearing traced to hemodialysis treatment with aged dialyzers SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DIALYSIS CENTER; CELLULOSE; INTOXICATION; OXIDATION; MEMBRANES AB Context A recent event in which 7 patients at 1 hospital developed decreased vision and hearing, conjunctivitis, headache, and other severe neurologic symptoms 7 to 24 hours after hemodialysis drew attention to the issue of the long-term integrity of dialysis machines and materials. Objective To determine the cause of the adverse reactions that occurred during this event. Design, Patients, and Setting Retrospective cohort study of all 9 patients who received hemodialysis at hospital A on September 18, 1996, the day of the outbreak. A case-patient was defined as any hospital A patient with acute onset of decreased vision and hearing and conjunctivitis after dialysis on that day. Non-case-patients were all others who underwent dialysis at hospital A on that day but did not develop adverse reactions. in an attempt to reproduce the conditions of the event, cellulose acetate dialysis membranes of various ages were retrieved from other sources and tested for physical and chemical degradation, and degradation products were identified, characterized, and injected intravenously into rabbits. Main Outcome Measures Clinical signs and symptoms, time to resolution of symptoms, mortality, and dialyzer type and age, for case- vs non-case-patients. Results Seven of the 9 patients met the case definition. In addition to diminished vision and hearing, conjunctivitis, and headache, some case-patients had blood leak alarm activation (n=6), confusion/lethargy (n=5), corneal opacification (n=4), cardiac arrest (n=2), or other neurologic signs and symptoms. One case-patient died during hospitalization after the event; 5 of 7 case-patients died within 13 months. Resolution of signs and symptoms varied but persisted more than 3 years or until death in 3 of the 6 patients who survived hospitalization. All case-patients but no non-case-patients were exposed to 11.5-year-old cellulose acetate dialyzers (all of these dialyzers were discarded by the hospital before our investigation). Laboratory investigation of field-retrieved 0- to 13.6-year-old dialyzers of similar type indicated significant chemical degradation in the older membranes. In vivo injection of extracts of membrane degradation products produced iritis and hemorrhages in rabbits' eyes. Conclusions Severe patient injury was associated with exposure to aged cellulose acetate membranes of dialyzers, allowing cellulose acetate degradation products to enter the blood. Clinicians should be aware that aged cellulose acetate membranes may cause severe adverse reactions. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. Ctr Dis Control & Prevent, Hosp Infect Program, Natl Ctr Infect Dis, Atlanta, GA USA. RP Hutter, JC (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12725 Twinbrook Pkwy,HFZ 150, Rockville, MD 20852 USA. NR 27 TC 25 Z9 25 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 APR 26 PY 2000 VL 283 IS 16 BP 2128 EP 2134 DI 10.1001/jama.283.16.2128 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 305MA UT WOS:000086542800029 PM 10791505 ER PT J AU Dhar, S Weir, JP AF Dhar, S Weir, JP TI Herpes simplex virus 1 late gene expression is preferentially inhibited during infection of the TAF250 mutant ts13 cell line SO VIROLOGY LA English DT Article ID IMMEDIATE-EARLY PROTEINS; GLYCOPROTEIN-C GENE; RNA-POLYMERASE-II; TRANSCRIPTION FACTOR; CCG1/TAF(II)250 GENE; MUTATIONAL ANALYSIS; THYMIDINE KINASE; PROMOTER; CYCLE; ACTIVATION AB A key component of the polymerase II transcription machinery is the transcription factor TFIID, a complex that contains the TATA-box binding protein and several (10-12) associated factors designated as TAFs (TBP-associated factors), ts13 cells, which contain a temperature-sensitive mutant in TAF250, the largest subunit of TFIID, exhibit promoter-specific defects in gene expression at the nonpermissive temperature, suggesting that individual TAFs are required for transcription of specific subsets of eukaryotic genes. Herpes simplex virus 1 (HSV-1) does not replicate in ts13 cells at the nonpermissive temperature, but the point at which the replicative process is blocked is not known. We used the TAF250 defect in ts13 cells to investigate the role of TAF250 in the expression of HSV-1 genes of each temporal class. At a low m.o.i., expression of most immediate-early mRNAs is reduced at the nonpermissive temperature, and consequently, there is little expression of early genes and no viral DNA replication. In contrast, at high m.o.i., expression of immediate-early genes is unaffected by the TAF250 defect and is not dependent on de novo viral protein synthesis. Early genes and early proteins are produced under these conditions, and viral DNA replication ensues, albeit at somewhat reduced levels. In contrast, late gene expression and late protein synthesis are severely restricted, even in the presence of appreciable viral DNA replication. Thus the lack of late protein synthesis is responsible for the inability of HSV-I to replicate in ts13 cells at the nonpermissive temperature. Further, it appears that late viral gene expression may be preferentially inhibited by the TAF250 mutation in ts13 cells. (C) 2000 Academic Press. C1 US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Weir, JP (reprint author), HFM-457,1401 Rockville Pike, Rockville, MD 20852 USA. NR 46 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 25 PY 2000 VL 270 IS 1 BP 190 EP 200 DI 10.1006/viro.2000.0259 PG 11 WC Virology SC Virology GA 311NG UT WOS:000086889900019 PM 10772991 ER PT J AU Dietz, AC Tomazic-Jezic, VJ Merritt, K Umbreit, TH AF Dietz, AC Tomazic-Jezic, VJ Merritt, K Umbreit, TH TI Modulation of mouse immune responses by prosthetic biomaterial particles SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, CDRH, Div Life Sci, 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1156 EP A1156 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101438 ER PT J AU Difilippantonio, MJ Zhu, J Chen, HT Meffre, E Nussenzweig, MC Max, E Ried, T Nussenzweig, A AF Difilippantonio, MJ Zhu, J Chen, HT Meffre, E Nussenzweig, MC Max, E Ried, T Nussenzweig, A TI Ku80 is essential for maintaining genomic stability. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NIH, FDA, Bethesda, MD 20892 USA. Rockefeller Inst, 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1047 EP A1047 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100799 ER PT J AU Gilbert, KM Fecher, HB Freeman, JP Wahid, R Fifer, EK AF Gilbert, KM Fecher, HB Freeman, JP Wahid, R Fifer, EK TI Potential clinical use of butyric acid prodrugs to induce antigen-specific T cell inactivation. SO FASEB JOURNAL LA English DT Meeting Abstract 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1103 EP A1103 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101125 ER PT J AU Graham, LJ Debell, KE Veri, MC Frazier-Jessen, M Rawat, R Bonvini, E Rellahan, BL AF Graham, LJ Debell, KE Veri, MC Frazier-Jessen, M Rawat, R Bonvini, E Rellahan, BL TI 70Z/3 Cbl activates an alternate mechanism of PLCgamma1 phosphorylation in Jurkat T cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Immunobiol Lab, 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1176 EP A1176 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101557 ER PT J AU Muthukkumar, S Stein, KE AF Muthukkumar, S Stein, KE TI Characteristics of T cell clones derived from meningococcal polysaccharide-tetanus toroid (MCPS-TT) conjugate immunized mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A982 EP A982 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100413 ER PT J AU Vazquez, N Dickensheets, HL Shelburne, C Mirmonsef, P Ryan, JJ Donnelly, RP AF Vazquez, N Dickensheets, HL Shelburne, C Mirmonsef, P Ryan, JJ Donnelly, RP TI IL-4 suppresses IFN-gamma-induced Fc gamma RI (CD64) gene expression in human monocytes by inhibiting Stat1 alpha activation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, CBER, Div Therapeut Prot, Rockville, MD 20852 USA. Virginia Commonwealth Univ, Dept Biol, Richmond, VA 23284 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1064 EP A1064 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100896 ER PT J AU Williams, JA Lee, YJ Shacter, E AF Williams, JA Lee, YJ Shacter, E TI H2O2 inhibits phagocytosis of apoptotic cells. SO FASEB JOURNAL LA English DT Meeting Abstract 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1156 EP A1156 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101436 ER PT J AU Williams, K Babu, U Bigley, E Gaines, D Smith, M McClure, H Raybourne, R AF Williams, K Babu, U Bigley, E Gaines, D Smith, M McClure, H Raybourne, R TI Development of an animal model for human listeriosis using pregnant rhesus macaques orally dosed with Listeria monocytogenes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Laurel, MD 20708 USA. Univ Georgia, Athens, GA 30602 USA. Emory Univ, Atlanta, GA 30322 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1061 EP A1061 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100881 ER PT J AU Yu, CR Peden, KWC Zaitseva, MB Golding, H Farber, JM AF Yu, CR Peden, KWC Zaitseva, MB Golding, H Farber, JM TI CCR9 is a receptor for CCL25 with two forms that show differing sensitivities to ligand and that has SIV go-receptor. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. US FDA, 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1166 EP A1166 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101495 ER PT J AU McGinnis, TII AF McGinnis, TII TI Significant FDA approvals in 1999 SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material C1 US FDA, Pharm Affairs, Off Policy, Rockville, MD 20857 USA. RP McGinnis, TII (reprint author), US FDA, Pharm Affairs, Off Policy, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD APR 15 PY 2000 VL 61 IS 8 BP 2531 EP 2533 PG 3 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 307UW UT WOS:000086673400019 PM 10794586 ER PT J AU Gaines, AR AF Gaines, AR TI Acute onset hemoglobinemia and/or hemoglobinuria and sequelae following Rh-o(D) immune globulin intravenous administration in immune thrombocytopenic purpura patients SO BLOOD LA English DT Article ID ANTI-D TREATMENT; CHILDREN; WINRHO; EFFICACY; SAFETY AB Rh-o(D) immune globulin intravenous (anti-D IGIV) was licensed by the United States Food and Drug Administration (FDA) in March 1995 to treat patients with immune thrombocytopenic purpura (ITP). Anti-D IGIV induces extravascular hemolysis, an expected adverse reaction that is consistent with the presumed mechanism of action. Between licensure and April 1999, the FDA received 15 reports of hemoglobinemia and/or hemoglobinuria following anti-D IGIV administration that met the case definition for this review. The mechanism responsible for hemoglobinemia and/or hemoglobinuria is unexplained. Review of these reports was prompted by the seriousness and the unexpectedness of treatment-associated sequelae experienced by 11 patients, Of these patients, 7 developed sufficient onset or exacerbation of anemia that orders were written for packed red blood cell transfusions, although only 6 patients were transfused. Eight patients experienced the onset or exacerbation of renal insufficiency, and 2 patients underwent dialysis, One patient died due to complications of exacerbated anemia. Six patients experienced 2 to 3 sequelae, Absent validated incidence data, a 1.5% estimated incidence rate from published clinical trial data and a 0.1% estimated reporting rate from FDA and drug utilization data were calculated for reported cases of hemoglobinemia and/or hemoglobinuria, This review presents the first case series of anti-D-IGIV-associated hemoglobinemia and/or hemoglobinuria and provides pretreatment and posttreatment clinical and laboratory findings of the case series patients. The primary purpose of this review is to increase awareness of this potentially serious occurrence among physicians and health care professionals who manage ITP patients treated with anti-D IGIV, thereby enabling prompt recognition and treatment of sequelae. (Blood.2000;95:2523-2529) (C) 2000 by The American Society of Hematology. C1 US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Rockville, MD 20852 USA. RP Gaines, AR (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, HFM-220,1401 Rockville Pike, Rockville, MD 20852 USA. NR 35 TC 102 Z9 103 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2000 VL 95 IS 8 BP 2523 EP 2529 PG 7 WC Hematology SC Hematology GA 303KH UT WOS:000086420700011 PM 10753830 ER PT J AU Yoneda, O Imai, T Goda, S Inoue, H Yamauchi, A Okazaki, T Imai, H Yoshie, O Bloom, ET Domae, N Umehara, H AF Yoneda, O Imai, T Goda, S Inoue, H Yamauchi, A Okazaki, T Imai, H Yoshie, O Bloom, ET Domae, N Umehara, H TI Fractalkine-mediated endothelial cell injury by NK cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; IN-VIVO; RECOMBINANT INTERLEUKIN-2; SIGNAL-TRANSDUCTION; ALPHA-CHEMOKINE; CC-CHEMOKINES; CYTO-TOXICITY; ADHESION; LYMPHOCYTES; ACTIVATION AB Endothelial cells (ECs) are primary targets of immunological attack, and their injury can lead to vasculopathy and organ dysfunction in vascular leak syndrome and in rejection of allografts or xenografts, A newly identified CX3C-chemokine, fractalkine, expressed on activated ECs plays an important role in leukocyte adhesion and migration. In this study we examined the functional roles of fractalkine on NK cell activity and NK cell-mediated endothelial cell injury. Freshly separated NK cells expressed the fractalkine receptor (CX(3)CR1) determined by FAGS analysis and efficiently adhered to immobilized full-length fractalkine, but not to the truncated forms of the chemokine domain or mucin domain, suggesting that fractalkine functions as an adhesion molecule on the interaction between NK cells and ECs, Soluble fractalkine enhanced NK cell cytolytic activity against K562 target cells in a dose- and time-dependent manner, This enhancement correlated well with increased granular exocytosis from NK cells, which nas completely inhibited by the G protein inhibitor, pertussis toxin, Transfection of fractalkine cDNA into ECV304 cells or HUVECs resulted in increased adhesion of NK cells and susceptibility to NK cell-mediated cytolysis compared with control transfection, Moreover, both enhanced adhesion and susceptibility of fractalkine-transfected cells were markedly suppressed by soluble fractalkine or anti-CX(3)CR1 Ab, Our results suggest that fractalkine plays an important role not only in the binding of NK cells to endothelial cells, but also in NK cell-mediated endothelium damage, which may result in vascular injury. C1 Osaka Dent Univ, Dept Internal Med, Osaka, Japan. Osaka Dent Univ, Dept Periodontol, Osaka, Japan. Kinki Univ, Sch Med, Dept Microbiol, Osaka 589, Japan. Kyoto Univ, Grad Sch Med, Dept Surg Gastroenterol, Kyoto, Japan. Kyoto Univ, Grad Sch Med, Dept Hematol & Oncol, Kyoto, Japan. US FDA, Ctr Biol Evaluat Res, Div Cellular & Gene Therapies HFM 518, Bethesda, MD 20892 USA. RP Umehara, H (reprint author), 8-1 Kuzuha Hanazono Cho, Hirakata, Osaka 5731121, Japan. NR 54 TC 132 Z9 151 U1 2 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2000 VL 164 IS 8 BP 4055 EP 4062 PG 8 WC Immunology SC Immunology GA 303GZ UT WOS:000086415300017 PM 10754298 ER PT J AU Goda, S Imai, T Yoshie, O Yoneda, O Inoue, H Nagano, Y Okazaki, T Imai, H Bloom, ET Domae, N Umehara, H AF Goda, S Imai, T Yoshie, O Yoneda, O Inoue, H Nagano, Y Okazaki, T Imai, H Bloom, ET Domae, N Umehara, H TI CX3C-chemokine, fractalkine-enhanced adhesion of THP-1 cells to endothelial cells through integrin-dependent and -independent mechanisms SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TYROSINE KINASE P72(SYK); NATURAL-KILLER-CELLS; LYMPHOCYTE ADHESION; CHEMOKINE; CC; ACTIVATION; MONOCYTES; RECEPTORS; AVIDITY; INFLAMMATION AB Leukocyte adhesion and trafficking at the endothelium requires both cellular adhesion molecules and chemotactic factors. A newly identified CX3C chemokine, fractalkine, expressed on activated endothelial cells, plays an important role in leukocyte adhesion and migration. We examined the functional effects of fractalkine on beta(1) and beta(2) integrin-mediated adhesion using a macrophage-like cell line, THP-1 cells. In this study, we report that THP-1 cells express mRNA encoding a receptor for fractalkine, CX(3)CR1, determined by Northern blotting, Scatchard analysis using fractalkine-SEAP (secreted form of placental alkaline phosphatase) chimeric proteins revealed that THP-1 cells express a single class of CX(3)CR1 with a dissociation constant of 30 pM and a mean expression of 440 sites per cell. THP-1 cells efficiently adhered, in a fractalkine-dependent manner, to full-length of fractalkine immobilized onto plastic and to the membrane-bound form of fractalkine expressed on ECV304 cells or TNF-alpha-activated HUVECs. Moreover, soluble-fractalkine enhanced adhesion of THP-1 cells to fibronectin and ICAM-1 in a dose-dependent manner. Pertussis toxin, an inhibitor of G(i), inhibited the fractalkine-mediated enhancement of THP-1 cell adhesion to fibronectin and ICAM-1, Finally, we found that soluble-fractalkine also enhanced adhesion of freshly separated monocytes to fibronectin and ICAM-1, These results indicate that fractalkine may induce firm adhesion between monocytes and endothelial cells not only through an intrinsic adhesion function itself, but also through activation of integrin avidity for their ligands. C1 Osaka Dent Univ, Dept Internal Med, Hirakata, Osaka 5731121, Japan. Osaka Dent Univ, Dept Periodontol, Hirakata, Osaka 5731121, Japan. Kinki Univ, Sch Med, Dept Microbiol, Sayama, Osaka 589, Japan. Kyoto Univ, Grad Sch Med, Dept Hematol & Oncol, Sakyo Ku, Kyoto, Japan. US FDA, Ctr Biol Evaluat Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Umehara, H (reprint author), Osaka Dent Univ, Dept Internal Med, 8-1 Kuzuha Hanazono Cho, Hirakata, Osaka 5731121, Japan. NR 42 TC 142 Z9 148 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 APR 15 PY 2000 VL 164 IS 8 BP 4313 EP 4320 PG 8 WC Immunology SC Immunology GA 303GZ UT WOS:000086415300051 PM 10754331 ER PT J AU Morris, S Kelley, C Howard, A Li, ZM Collins, F AF Morris, S Kelley, C Howard, A Li, ZM Collins, F TI The immunogenicity of single and combination DNA vaccines against tuberculosis SO VACCINE LA English DT Article DE tuberculosis; DNA vaccines; combination vaccines ID MYCOBACTERIUM-TUBERCULOSIS; IMMUNE-RESPONSE; IMMUNODEFICIENCY-VIRUS; INTERFERON-GAMMA; MICE; VACCINATION; ANTIGENS; PROTECTION; MORTALITY; INFECTION AB DNA immunization is a promising new approach for the development of novel tuberculosis vaccines. In this study, the immune responses following the administration of single and combination tuberculosis DNA vaccines were evaluated. Single DNA vaccines encoding the MPT-63 and MPT-83 tuberculosis antigens evoked partial protection against an aerogenic challenge with M, tuberculosis Erdman in the mouse model of pulmonary tuberculosis. Immunization with a multivalent combination DNA vaccine (containing the ESAT-6, MPT-64, MPT-63, and KatG constructs) generated immune responses that indicated an absence of antigenic competition since antigen-specific cell-mediated and humoral responses were detected to each component of the mixture. More importantly, the combination vaccine elicited a strong protective response relative to the protection evoked by live BCG vaccine. (C) 2000 Published by Elsevier Science Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mycobacteria, Bethesda, MD 20892 USA. RP Morris, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mycobacteria, Bldg 29,Room 502,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 42 TC 110 Z9 146 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 14 PY 2000 VL 18 IS 20 BP 2155 EP 2163 DI 10.1016/S0264-410X(99)00540-X PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 303DE UT WOS:000086404900012 PM 10715531 ER PT J AU Colman, E Fossler, M AF Colman, E Fossler, M TI Reduction in blood cyclosporine concentrations by orlistat. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID TRANSPLANTATION C1 US FDA, Rockville, MD 20857 USA. RP Colman, E (reprint author), US FDA, Rockville, MD 20857 USA. NR 4 TC 20 Z9 20 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 13 PY 2000 VL 342 IS 15 BP 1141 EP 1142 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 303DZ UT WOS:000086406700031 PM 10766596 ER PT J AU Shallow, S Samuel, M McNees, A Rothrock, G Vugia, D Fiorentino, T Marcus, R Kazi, G Mshar, P Carter, M Hadler, J Farley, M Desai, S Segler, S Lance-Parker, S Blake, P Pass, M Karchmer, T Gregg, C Steiner, C Carter, M Henning, K Razeq, J Glenn, A Smith, K Bender, J Besser, J Soderlund, D Moore, K Morse, D Smith, P Cassidy, M McGivern, T Lorber, E Shiferaw, B Cieslak, P Fleming, D AF Shallow, S Samuel, M McNees, A Rothrock, G Vugia, D Fiorentino, T Marcus, R Kazi, G Mshar, P Carter, M Hadler, J Farley, M Desai, S Segler, S Lance-Parker, S Blake, P Pass, M Karchmer, T Gregg, C Steiner, C Carter, M Henning, K Razeq, J Glenn, A Smith, K Bender, J Besser, J Soderlund, D Moore, K Morse, D Smith, P Cassidy, M McGivern, T Lorber, E Shiferaw, B Cieslak, P Fleming, D CA CDC TI Preliminary FoodNet data on the incidence of foodborne illnesses - Selected sites, United States, 1999 (Reprinted from MMWR, vol 49, pg 201, 2000) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Calif Emerging Infect Program, Oakland, CA USA. Calif State Dept Hlth Serv, Sacramento, CA 95814 USA. Yale Univ, Sch Med, New Haven, CT USA. Connecticut State Dept Publ Hlth, Hartford, CT USA. Emory Univ, Sch Med, Atlanta, GA USA. Georgia Dept Human Resources, Atlanta, GA USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Maryland Dept Hlth & Mental Hyg, Baltimore, MD 21201 USA. Minnesota Dept Publ Hlth, St Paul, MN USA. New York State Dept Hlth, Albany, NY 12237 USA. US FDA, Ctr Food Safety & Appl Nutr, Food Safety & Inspect Serv, Off Publ Hlth & Sci, Rockville, MD 20857 USA. CDC, Foodborne & Diarrheal Dis Branch, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. CDC, Div Parasit Dis, Atlanta, GA 30333 USA. CDC, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. RP Shallow, S (reprint author), Calif Emerging Infect Program, Oakland, CA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 12 PY 2000 VL 283 IS 14 BP 1818 EP 1819 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 300HY UT WOS:000086248600011 ER PT J AU Clements, CJ Ball, LK Ball, R Pratt, D AF Clements, CJ Ball, LK Ball, R Pratt, D TI Thiomersal in vaccines SO LANCET LA English DT Letter C1 WHO, Dept Vaccines & Biol, CH-1211 Geneva 27, Switzerland. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Clements, CJ (reprint author), WHO, Dept Vaccines & Biol, CH-1211 Geneva 27, Switzerland. NR 4 TC 25 Z9 27 U1 1 U2 5 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 8 PY 2000 VL 355 IS 9211 BP 1279 EP 1280 DI 10.1016/S0140-6736(05)74714-0 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 303VX UT WOS:000086448000059 PM 10770336 ER PT J AU Zeng, GY Nystrom, FH Ravichandran, LV Cong, LN Kirby, M Mostowski, H Quon, MJ AF Zeng, GY Nystrom, FH Ravichandran, LV Cong, LN Kirby, M Mostowski, H Quon, MJ TI Roles for insulin receptor, PI3-kinase, and Akt in insulin-signaling pathways related to production of nitric oxide in human vascular endothelial cells SO CIRCULATION LA English DT Article DE insulin; endothelium; signal transduction; nitric oxide; receptors ID RAT ADIPOSE-CELLS; PROTEIN-KINASE-B; PHOSPHATIDYLINOSITOL 3-KINASE; GENE-TRANSFER; 1-PHOSPHATIDYLINOSITOL 3-KINASE; GLUCOSE-UPTAKE; GROWTH-FACTOR; TRANSLOCATION; GLUT4; ELECTROPORATION AB Background-Previously, we demonstrated that insulin stimulates production of nitric oxide (NO) in endothelial cells. However, specific insulin-signaling pathways mediating production of NO have not been elucidated. Methods and Results-We developed methods for transfection of human umbilical vein endothelial cells (HUVECs) and direct measurement of NO to begin defining insulin-signaling pathways related to NO production. HUVECs were cotransfected with enhanced Green Fluorescent Protein (eGFP) and another gene of interest. Transfection efficiencies >95% were obtained by selecting cells expressing eGFP. Overexpression of insulin receptors in HUVECs resulted in an approximate to 3-fold increase in production of NO in response to insulin. In contrast, HUVECs overexpressing a tyrosine kinase-deficient mutant insulin receptor had a dose-response curve similar to that of control cells. Overexpression of inhibitory mutants of either phosphatidylinositol 3-kinase (PI3K) or Akt resulted in nearly complete inhibition of insulin-stimulated production of NO. Overexpression of an inhibitory mutant of Rns had a much smaller effect. Conclusions-Receptor kinase activity is necessary to mediate production of NO through the insulin receptor. Both PI3K and Akt contribute importantly to this process, whereas the contribution of Ras is small. C1 NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Expt Res, Bethesda, MD 20014 USA. RP Quon, MJ (reprint author), NHLBI, Hypertens Endocrine Branch, NIH, Bldg 10,Room 8C-218,10 Ctr Dr,MSC 1755, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Nystrom, Fredrik/0000-0002-1680-1000; Quon , Michael /0000-0002-5289-3707 NR 39 TC 477 Z9 505 U1 1 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 4 PY 2000 VL 101 IS 13 BP 1539 EP 1545 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 300QE UT WOS:000086263000011 PM 10747347 ER PT J AU Ellenberg, SS AF Ellenberg, SS TI Select-drop designs in clinical trials SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT Symposium on How Should Phase II Trials in Cardiovascular Medicine be Conducted CY OCT 03-04, 1997 CL HILTON HEAD ISL, SOUTH CAROLINA C1 US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Ellenberg, SS (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-210, Rockville, MD 20852 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 2000 VL 139 IS 4 BP S158 EP S160 DI 10.1016/S0002-8703(00)90064-4 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 301RT UT WOS:000086324600033 PM 10740123 ER PT J AU Lipicky, R AF Lipicky, R TI An FDA perspective on antiarrhythmic drugs in Phase II trials SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT Symposium on How Should Phase II Trials in Cardiovascular Medicine be Conducted CY OCT 03-04, 1997 CL HILTON HEAD ISL, SOUTH CAROLINA C1 US FDA, Div Cardiorenal Drug Prod, Rockville, MD 20852 USA. RP Lipicky, R (reprint author), US FDA, Div Cardiorenal Drug Prod, HFD-110,1451 Rockville Pike,Room 5039, Rockville, MD 20852 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 2000 VL 139 IS 4 BP S197 EP S199 DI 10.1016/S0002-8703(00)90072-3 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 301RT UT WOS:000086324600041 PM 10740131 ER PT J AU Siegel, JP AF Siegel, JP TI Equivalence and noninferiority trials SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT Symposium on How Should Phase II Trials in Cardiovascular Medicine be Conducted CY OCT 03-04, 1997 CL HILTON HEAD ISL, SOUTH CAROLINA C1 US FDA, Off Therapeut Res & Review, Rockville, MD 20852 USA. RP Siegel, JP (reprint author), US FDA, Off Therapeut Res & Review, HFM-500,1451 Rockville Pike,Suite 2005, Rockville, MD 20852 USA. NR 4 TC 42 Z9 42 U1 1 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 2000 VL 139 IS 4 BP S166 EP S170 DI 10.1016/S0002-8703(00)90066-8 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 301RT UT WOS:000086324600035 PM 10740125 ER PT J AU Temple, R AF Temple, R TI Current definitions of phases of investigation and the role of the FDA in the conduct of clinical trials SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT Symposium on How Should Phase II Trials in Cardiovascular Medicine be Conducted CY OCT 03-04, 1997 CL HILTON HEAD ISL, SOUTH CAROLINA C1 US FDA, Ctr Drugs Evaluat & Res, Rockville, MD 20852 USA. RP Temple, R (reprint author), US FDA, Ctr Drugs Evaluat & Res, 5600 Fisher LN-HFD-100,Room 14B45, Rockville, MD 20852 USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 2000 VL 139 IS 4 BP S133 EP S135 DI 10.1016/S0002-8703(00)90060-7 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 301RT UT WOS:000086324600029 PM 10740119 ER PT J AU Villarino, ME Brennan, MJ Nolan, CM Catanzaro, A Lundergan, LL Bock, NN Jones, CL Wang, YC Burman, WJ AF Villarino, ME Brennan, MJ Nolan, CM Catanzaro, A Lundergan, LL Bock, NN Jones, CL Wang, YC Burman, WJ TI Comparison testing of current (PPD-SI) and proposed (PPD-S2) reference tuberculin standards SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID SKIN-TEST AB Since 1951, the tuberculin PPD-S1 has been used to standardize commercial PPD reagents and perform special tuberculin surveys. PPD-S1 is now in short supply and a new standard (PPD-S2) has been manufactured. To determine if PPD-S2 is equivalent and can replace PPD-S1, we conducted a double-blind clinical trial. between May 14 and October 28, 1997, 69 subjects with a history of culture-proven tuberculosis (TB patients) and 1,189 subjects with a very low risk for TB infection were enrolled, received four skin tests (with PPD-S1, PPD-S2, and one each of the commercially available PPDs), and had reactions measured by two trained observers. Among the TB patients, we found statistically indistinguishable immunogenicity (mean reaction size +/- standard deviation): 15.6 +/- 6.6 mm for PPD-S1 and 14.8 +/- 5.6 mm for PPD-S2. Among low-risk subjects, the tests had equally high specificities (PPD-S1, 98.7% and PPD-S2 98.5%), using a 10-mm cutoff. The number of discordant (negative versus positive) interpretations for PPD-S2, assuming that low-risk subjects who had a greater than or equal to 10 mm reaction to PPD-S1 were truly infected, was low (0.5%) and indistinguishable from the rate of discordant interpretations of the same test when read by two different observers (0.8%). The study results indicate that PPD-S2 is qualified to be used as the new U.S. reference standard for PPD tuberculin. C1 Ctr Dis Control & Prevent, Div TB Eliminat, Atlanta, GA 30333 USA. US FDA, Bethesda, MD 20014 USA. Seattle King Cty Dept Publ Hlth, Seattle, WA 98101 USA. Univ San Diego, San Diego, CA 92110 USA. Univ Arizona, Tucson, AZ 85712 USA. Emory Univ, Atlanta, GA 30322 USA. Marion Cty Hlth Dept, Marion, IN 46953 USA. Denver Publ Hlth Dept, Denver, CO 80201 USA. RP Villarino, ME (reprint author), 1600 Clifton Rd NE,MS E-10, Atlanta, GA 30333 USA. NR 19 TC 15 Z9 15 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR PY 2000 VL 161 IS 4 BP 1167 EP 1171 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 306AF UT WOS:000086573400018 PM 10764307 ER PT J AU Ussery, MA Zhang, H Wood, OL Pannecouque, C De Clercq, E Witvrouw, M AF Ussery, MA Zhang, H Wood, OL Pannecouque, C De Clercq, E Witvrouw, M TI Effects of ADA on intracellular nucleoside triphosphate pools and implications for use in combination therapy SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Innogenet Inc, Alpharetta, GA USA. Katholieke Univ Leuven, Rega Inst, B-3000 Louvain, Belgium. 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 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD APR PY 2000 VL 46 IS 1 MA 38 BP A46 EP A46 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 305EZ UT WOS:000086527600039 ER PT J AU Burkhardt, W Calci, KR AF Burkhardt, W Calci, KR TI Selective accumulation may account for shellfish-associated viral illness SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; CLOSTRIDIUM-PERFRINGENS; MYA-ARENARIA; WASTE-WATER; ENUMERATION; BACTERIOPHAGES; ENTEROVIRUSES; INDICATORS; DEPURATION; BACTERIA AB From 1991 through 1998, 1,266 cases of shellfish-related illnesses were attributed to Norwalk-like viruses. Seventy-eight percent of these illnesses occurred following consumption of oysters harvested from the Gulf Coast during the months of November through January. This study investigated the ability of eastern oysters (Crassostrea virginica) to accumulate indicator microorganisms (i.e., fecal coliforms, Escherichia call, Clostridium perfringens, and F+ coliphage) from estuarine water. One-week trials over a 1-year period were used to determine if these indicator organisms could provide insight into the seasonal occurrence of these gastrointestinal illnesses, The results demonstrate that oysters preferentially accumulated F+ coliphage, an enteric viral surrogate, to their greatest levels from late November through January, with a concentration factor of up to 99-fold. However, similar increases in accumulation of the other indicator microorganisms,were not observed, These findings suggest that the seasonal occurrence of shellfish-related illnesses by enteric viruses is, in part, the result of seasonal physiological changes undergone by the oysters that affect their ability to accumulate viral particles from estuarine waters. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Burkhardt, W (reprint author), US FDA, Gulf Coast Seafood Lab, 1 Iberville Dr,POB 158, Dauphin Isl, AL 36528 USA. EM Wburkhar@cfsan.fda.gov NR 27 TC 118 Z9 126 U1 0 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 EI 1098-5336 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD APR PY 2000 VL 66 IS 4 BP 1375 EP 1378 DI 10.1128/AEM.66.4.1375-1378.2000 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 300ZY UT WOS:000086284700019 PM 10742214 ER PT J AU Mayorga, AJ Popke, EJ Fogle, CM Paule, MG AF Mayorga, AJ Popke, EJ Fogle, CM Paule, MG TI Similar effects of amphetamine and methylphenidate on the performance of complex operant tasks in rats SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE dopamine; norepinephrine; catecholamine; cognitive; behavior; timing ID DEFICIT-HYPERACTIVITY DISORDER; BEHAVIORAL-TEST BATTERY; RHESUS-MONKEYS; TIME-ESTIMATION; MODEL; METHAMPHETAMINE; SEROTONIN; DOPAMINE; CHILDREN; DIAZEPAM AB Methylphenidate and D-amphetamine are central nervous system stimulants that have been suggested to share certain behavioral and neurochemical effects. The current study was undertaken to determine whether methylphenidate and D-amphetamine have similar effects on the performance of a battery of complex operant tasks in rats. Thus, the effects of amphetamine (0.1-6.0 mg/kg, i.p.) and methylphenidate (1.12-18.0 mg/kg, i.p) on the performance of rats in three complex food-reinforced operant tasks were examined. The tasks land the brain functions they are intended to model) included: (1) conditioned position responding (auditory/visual/position discrimination); (2) incremental repeated acquisition (learning); and (3) temporal response differentiation (time estimation). In addition, each of these tasks was paired with a progressive ratio task to assess drug effects on the rats' motivation to lever press for the food reinforcers used. Consistent with their effects in other behavioral paradigms, methylphenidate and D-amphetamine produced very similar patterns of disruption of the four tasks. Drug-induced changes in the endpoints of the progressive ratio task generally paralleled changes in the other three tasks, suggesting a major role for appetitive motivation in the effects of these agents. Several effects of these agents seen in the current study are consistent with their effects in children with attention-deficit-hyperactivity disorder. These data further validate the use of this battery of operant tasks for the characterization of pharmacological agents, and suggest that findings using these tasks may be predictive of what is seen in humans. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Food & Drug Adm, Jefferson, AR 72079 USA. RP Mayorga, AJ (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, Food & Drug Adm, HFT-132, Jefferson, AR 72079 USA. NR 48 TC 33 Z9 33 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD APR PY 2000 VL 109 IS 1 BP 59 EP 68 DI 10.1016/S0166-4328(99)00165-5 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 298GF UT WOS:000086130400007 PM 10699658 ER PT J AU Ferguson, SA Frisby, NB Ali, SF AF Ferguson, SA Frisby, NB Ali, SF TI Acute effects of cocaine on play behaviour of rats SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE cocaine; play behaviour; gender effects; rat ID JUVENILE RATS; AMPHETAMINE; RESPONSIVITY AB Play behaviours are exhibited by many mammalian species. The similarity of such behaviour across children, non-human primates and rats makes it an especially appropriate target for the investigation of drug- or toxicant-induced disruption. In this study the acute effects of cocaine on play behaviour in male and female Sprague-Dawley rats was assessed. Same-sex dyads of rats (postnatal day 35-36) were separated 24 h prior to testing. On the following day, one or both rats of the dyad were Injected with the same dose of cocaine (0, 2.5, 5.0 or 20.00 mg/kg). Thirty minutes later the rats were placed together and, after 5 min of habituation, the frequency of pins and crawl-overs were measured for each subject. In dyads in which both rats were treated, crawl-overs and pinning behaviour were decreased by 20 mg/kg cocaine. In dyads in which only one rat was treated, there was marginal effect of cocaine treatment on pinning frequency, while crawl-overs were unaffected. Pinning frequency was not sexually dimorphic in either type of dyad; however, crawl-overs were more frequently exhibited by females in dyads in which only one rat was treated. Thus, pinning behaviour in juvenile rats appears somewhat more sensitive to cocaine-induced disruption than crawl-over behaviours. Additionally, the presence of an untreated rat appears to attenuate the play-disrupting effects of cocaine on pinning frequency. (C) 2000 Lippincott Williams & Wilkins. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 22 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD APR PY 2000 VL 11 IS 2 BP 175 EP 179 PG 5 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 316VE UT WOS:000087188100010 PM 10877123 ER PT J AU Herman, EH Zhang, J Chadwick, DP Ferrans, VJ AF Herman, EH Zhang, J Chadwick, DP Ferrans, VJ TI Comparison of the protective effects of amifostine and dexrazoxane against the toxicity of doxorubicin in spontaneously hypertensive rats SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE doxorubicin; cardiomyopathy; nephrotoxicity; amifostine; dexrazoxane ID PARATHYROID-HORMONE SECRETION; ADRIAMYCIN CARDIOTOXICITY; INDUCED CARDIOMYOPATHY; NORMAL-TISSUES; WR-2721; INHIBITION; ICRF-187; RADIOPROTECTOR; CHEMOTHERAPY; WR-1065 AB Purpose: To compare the protective effects of amifostine and dexrazoxane against the chronic toxicity induced by doxorubicin in spontaneously hypertensive rats (SHR). Methods: The animals were pretreated with amifostine (200 mg/kg, i.p.), dexrazoxane (25 mg/kg, i.p.) or saline 30 min before the administration of doxorubicin (1 mg/kg, i.v.), once-weekly for 12 weeks. Control animals received similar amounts of amifostine or saline. The SHR underwent necropsy examination 1 week after the last dosing, and cardiac, renal, and gastrointestinal lesions were graded semiquantitatively. Results: Amifostine and dexrazoxane provided equal degrees of protection against the renal toxicity of doxorubicin. However, dexrazoxane was more cardioprotective than amifostine, and prevented the mortality induced by doxorubicin. This mortality was not decreased by pretreatment with amifostine. The loss of body weight caused by doxorubicin was actually worsened by coadministration of amifostine. Conclusions: Compared to dexrazoxane, amifostine provided a comparable degree of protection against the nephrotoxicity of doxorubicin, but was less cardioprotective and did not prevent the mortality and loss of body weight produced by doxorubicin. These differences may be related to the fact that amifostine may act as a scavenger of reactive oxygen species, whereas dexrazoxane may prevent their formation. C1 US FDA, Div Appl Pharmacol Res HFD910, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Herman, EH (reprint author), US FDA, Div Appl Pharmacol Res HFD910, Ctr Drug Evaluat & Res, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 39 TC 66 Z9 66 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD APR PY 2000 VL 45 IS 4 BP 329 EP 334 DI 10.1007/s002800050048 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 298VE UT WOS:000086159200010 PM 10755322 ER PT J AU Troxell, T Buckner, R AF Troxell, T Buckner, R TI Food safety in the new millennium: The past is the prologue SO CEREAL FOODS WORLD LA English DT Editorial Material C1 US FDA, Off Plant & Dairy Foods & Beverages, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Troxell, T (reprint author), US FDA, Off Plant & Dairy Foods & Beverages, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CEREAL CHEMISTS PI ST PAUL PA 3340 PILOT KNOB RD, ST PAUL, MN 55121-2097 USA SN 0146-6283 J9 CEREAL FOOD WORLD JI Cereal Foods World PD APR PY 2000 VL 45 IS 4 BP 169 EP 172 PG 4 WC Food Science & Technology SC Food Science & Technology GA 308YY UT WOS:000086741500005 ER PT J AU Collins, JM AF Collins, JM TI Cytochrome P-450 and other determinants of pharmacokinetics, toxicity, and efficacy in humans SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID IMPAIRED RENAL-FUNCTION; LEUKEMIA C1 US FDA, Lab Clin Pharmcol, Rockville, MD 20850 USA. RP Collins, JM (reprint author), US FDA, Lab Clin Pharmcol, Room 314,4 Res Court, Rockville, MD 20850 USA. NR 16 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR PY 2000 VL 6 IS 4 BP 1203 EP 1204 PG 2 WC Oncology SC Oncology GA 307BL UT WOS:000086633500001 PM 10778942 ER PT J AU Lao, CS AF Lao, CS TI Statistical issues involved in medical device postmarketing surveillance SO DRUG INFORMATION JOURNAL LA English DT Article DE medical device reports; model fitting; trend analysis; monitoring; threshold cutoff point AB This paper describes several statistical methods for analyzing medical device reports received by the Food and Drug Administration. The nonparametric regressions (polynomial, loess, kernel smooth, and cubic spline smoothing) are used as exploratory tools to evaluate trends in adverse event reports. Several statistical models, including simple Poisson, mixed binomial/Poisson, zero-truncated Poisson, and the negative binomial (compound Poisson), are used to monitor and to determine the upper 95% threshold values for reported adverse events during the study period. The hip implant injury data and the intravenous tube total (sum of death, device malfunction, and injury) data are used to illustrate our model fitting procedures. in this paper only the numerator data (medical device adverse events), not the denominator data (medical device usage), are available in our statistical analysis. The possible effects of marketing time and other factors, which may be available in adverse drug reactions, are not available and are not considered for medical device adverse events in this paper. C1 US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Div Biostat, Rockville, MD 20850 USA. RP Lao, CS (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Div Biostat, HFZ-542,1350 Piccard Dr, Rockville, MD 20850 USA. NR 18 TC 3 Z9 3 U1 1 U2 2 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. PD APR-JUN PY 2000 VL 34 IS 2 BP 483 EP 493 PG 11 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 317HP UT WOS:000087220200017 ER PT J AU Chen, JJ Tsong, Y Kang, SH AF Chen, JJ Tsong, Y Kang, SH TI Tests for equivalence or noninferiority between two proportions SO DRUG INFORMATION JOURNAL LA English DT Article DE asymptotic test; bioequivalence; binomial; conditional exact test; difference; odds ratio; ratio ID ESTABLISH EQUIVALENCE; NULL HYPOTHESIS; TRIALS AB Bioequivalence between two treatments or two drugs is often assessed by comparing the two proportions (success rate or eradication rate) of binomial outcomes when the conventional pharmacokinetic parameters are inadequate for the assessment. Setting the equivalence limits can be based on one of the three measures: difference, ratio, or odds ratio between the two binomial probabilities. This paper reviews the existing asymptotic rest statistics for comparing two independent binomial probabilities in terms of the three measures in the context of equivalence or noninferiority testing. The actual type I error and power of the asymptotic tests are evaluated by enumerating the exact probabilities in the rejection region. The results show that to establish an equivalence between two treatments with an equivalence limit of 20% in difference, a sample size of at least 50 per treatment is needed. When the sample size is sufficient, the actual type I error rate is close to the nominal level (slightly above the nominal level in several cases)for a test in terms of difference for equivalence limits, and it tends to exceed the nominal level for tests in terms of ratio or odds ratio. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, HFT20, Jefferson, AR 72079 USA. US FDA, Ctr Drug Evaluat & Res, Quantitat Methods & Res Staff, Off Biostat, Rockville, MD 20857 USA. RP Chen, JJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, HFT20, Jefferson, AR 72079 USA. NR 18 TC 35 Z9 36 U1 0 U2 1 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. PD APR-JUN PY 2000 VL 34 IS 2 BP 569 EP 578 PG 10 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 317HP UT WOS:000087220200025 ER PT J AU Sprando, RL Collins, TFX Black, TN Olejnik, N Rorie, JI Scott, M Wiesenfeld, P Babu, US O'Donnell, M AF Sprando, RL Collins, TFX Black, TN Olejnik, N Rorie, JI Scott, M Wiesenfeld, P Babu, US O'Donnell, M TI The effect of maternal exposure to flaxseed on spermatogenesis in F-1 generation rats SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE rat; spermatogenesis; testis; flaxseed; flaxmeal ID SPERM COUNTS; ESTROGENS; PHYTOESTROGENS; PRECURSOR; PITUITARY; PROSTATE AB Pregnant Sprague-Dawley rats were exposed to a flaxseed (20 or 40%), flaxmeal (13 or 26%) or standard NlH AlN-93 (0% flaxseed control) diet throughout gestation and until their offspring were weaned. After weaning, Fl generation males were placed in the same diet treatment groups as their mothers for 70 days. Statistically significant differences were not observed between either low-dose or high-dose flaxsced and flaxmeal-treated animals and the 0% flaxseed control animals for testis weights, homogenization resistant spermatid counts, daily sperm production rates, epididymal weights, seminal vesicle weights, seminiferous tubule fluid testosterone! concentrations and the percentage of sperm abnormalities. The following statistically significant differences were observed when treated groups and the 0% flaxseed control groups were compared: (1) increases in serum LH in the 20% and 40% flaxseed treatment groups and in serum LH and testosterone in the 26% flaxmeal treatment group; (2) increases in the cauda epididymal weight from the 20% and 40% flaxseed groups; (3) increases in cauda epididymal sperm numbers/g epididymis from the 20% and 40% flaxspeed and the 13% and 26% flaxmeal treatment groups; (4) a decrease in prostatic a weight from the 20% flaxseed and 13% and 26% flaxmeal treatment groups. Prostate weight in the 40% flaxseed treatment group was lower but not statistically significantly different than the 0% flaxseed control group. Histological effects on spermatogenesis sere not observed in either the control group, flaxseed or the flaxseed treated groups. Published by Elsevier Science Ltd. C1 US FDA, Div Toxicol Res, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Sprando, RL (reprint author), US FDA, Div Toxicol Res, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 37 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD APR PY 2000 VL 38 IS 4 BP 325 EP 334 DI 10.1016/S0278-6915(99)00165-9 PG 10 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 310EP UT WOS:000086813800003 PM 10722886 ER PT J AU Hopkins, RJ Dixon, CA Meyer, JM AF Hopkins, RJ Dixon, CA Meyer, JM TI Duodenal ulcer healing associated with Helicobacter pylori clearance at the end of treatment using ranitidine bismuth citrate-based regimens. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 5708 BP A1247 EP A1247 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RY UT WOS:000086784100782 ER PT J AU Meyer, JM Higgins, KM Wang, WJ Siepman, NY Sugg, JE Morris, D Zhang, J Bhattacharya, H King, EC Hopkins, RJ AF Meyer, JM Higgins, KM Wang, WJ Siepman, NY Sugg, JE Morris, D Zhang, J Bhattacharya, H King, EC Hopkins, RJ TI Evaluation of risk factors in the surveillance of Helicobacter pylori antimicrobial resistance partnership (SHARP) in the United States from 1993-1999. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Wyeth Ayerst Res, Philadelphia, PA USA. TAP Holdings Inc, Deerfield, IL USA. AstraZeneca LP, Wayne, PA USA. Abbott Labs, Abbott Pk, IL 60064 USA. Pfizer Pharmaceut, New York, NY USA. Procter & Gamble Co, Mason, OH USA. NR 0 TC 5 Z9 5 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3702 BP A677 EP A677 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702772 ER PT J AU Carrington, CD Bolger, PM AF Carrington, CD Bolger, PM TI A pooled analysis of the Iraqi and Seychelles methylmercury studies SO HUMAN AND ECOLOGICAL RISK ASSESSMENT LA English DT Article DE methylmercury; dose-response; childhood development ID FETAL METHYLMERCURY; CHILD-DEVELOPMENT; METHYL MERCURY; EXPOSURE; HAIR AB Several epidemiology studies have investigated the impact of maternal exposure to methylmercury (MeHg) on childhood development of the central nervous system (CNS). In the present report, data from the Iraqi episode that occurred in 1970 from contaminated grain are integrated with those from a more recent study of a population with a high fish intake in the Seychelles Islands. The latter study had many more subjects whose mercury hair levels that were much lower and more representative of levels typically found in consumers whose MeHg exposure is from fish. The age of onset of talking (AOT), the age of onset of walking (AOW) and a combined measure (CM) that integrated the two were used as common scales of MeHg effect for the two studies. The first step of the analyses involved the construction of separate two-dimensional cumulative frequency tables for each study for different groups spanning the range of hair levels and observed effect for each measure. Models were then fit to the values in the tables that were constructed from four components: (1) A dose-effect function that related hair MeHg to the effect measure; (2) a frequency distribution describing population variability; (3) parameters to represent dose-independent influences on effect; and (4) parameters to represent study dependent influences on effect. When the four submodels were assembled, a series of 1092 candidate models resulted which contained 3 to 7 parameters (e.g., slope, standard-deviation, dose-independent age of talking) whose value could be adjusted to improve the fit. After optimizing the fit of each model, a weighting algorithm that rewards for fit and penalizes for the number of parameters in the model was used to identify the best 200 models. The same algorithm was then used to assign a probability to each model in a probability tree. A two-dimensional Monte-Carlo simulation using the resulting function in combination with exposure values typical of U.S. consumers yielded predicted delays in AOT, AOW, and CM attributable to fish consumption in a variable and uncertain range of 0.000 to 1 day. C1 US FDA, Washington, DC 20204 USA. RP Carrington, CD (reprint author), US FDA, 200 C St SW HFS-308, Washington, DC 20204 USA. NR 13 TC 8 Z9 9 U1 1 U2 2 PU CRC PRESS INC PI BOCA RATON PA 2000 CORPORATE BLVD NW, JOURNALS CUSTOMER SERVICE, BOCA RATON, FL 33431 USA SN 1080-7039 J9 HUM ECOL RISK ASSESS JI Hum. Ecol. Risk Assess. PD APR PY 2000 VL 6 IS 2 BP 323 EP 340 PG 18 WC Biodiversity Conservation; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 315HW UT WOS:000087108300011 ER PT J AU Black, LE Green, JD Rener, J Dayan, A Cavagnaro, JA Spindler, P Bussiere, JL Bouchard, P Inoue, T Thomas, PT Essayan, DM Gillett, NA Hart, TK Hastings, K House, RV Latta, D Liminga, U Treacy, G Wierda, D AF Black, LE Green, JD Rener, J Dayan, A Cavagnaro, JA Spindler, P Bussiere, JL Bouchard, P Inoue, T Thomas, PT Essayan, DM Gillett, NA Hart, TK Hastings, K House, RV Latta, D Liminga, U Treacy, G Wierda, D TI Safety evaluation of immunomodulatory biopharmaceuticals: can we improve the predictive value of preclinical studies? SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Editorial Material C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Biogen Inc, Cambridge, MA 02142 USA. Covance Labs Inc, Vienna, VA 22182 USA. Access BIO, Leesburg, VA 20177 USA. Novo Nordisk AS, DK-2820 Gentofte, Denmark. Genentech Inc, S San Francisco, CA 94080 USA. Genet Inst, Andover, MA 01810 USA. Natl Inst Hlth Sci, Setagaya Ku, Tokyo 158, Japan. Sierra Biomed Inc, Sparks, NV 89431 USA. SmithKline Beecham Pharmaceut, King Of Prussia, PA 19406 USA. Ctr Drug Educ & Res, Rockville, MD 20852 USA. Wyeth Ayerst Res, Chazy, NY 12921 USA. Med Prod Agcy, S-75103 Uppsala, Sweden. Centocor Inc, Malvern, PA 19355 USA. Lilly Res Labs, Greenfield, IN 46140 USA. RP Black, LE (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0144-5952 J9 HUM EXP TOXICOL JI Hum. Exp. Toxicol. PD APR PY 2000 VL 19 IS 4 BP 205 EP 206 DI 10.1191/096032700678815855 PG 2 WC Toxicology SC Toxicology GA 329XL UT WOS:000087933700001 PM 10918508 ER PT J AU Green, JD Black, LE AF Green, JD Black, LE TI Status of preclinical safety assessment for immunomodulatory biopharmaceuticals SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Editorial Material AB Scientists from academia, industry, FDA, European and Japanese regulatory groups met to discuss key considerations that are central to the safe and expeditious development of novel biologic agents that are thought to act by modulation of the host immune system. In the presentations and case studies, particular attention was given to the current clinical experience with immunosuppressant agents. Many new biologic agents (such as humanized monoclonal antibodies) have been developed to interact in a highly specific manner with their target. However, their pharmacologic properties may be more complex than originally appreciated, impacting on clinical trial designs. The goal of preclinical safety assessment should be to provide some assurance that patients will be protected from any unacceptable risks by defining "safe" and "active" doses. For immunomodulatory molecules, particular attention is paid to defining potential for increased risks of lymphoproliferative disorders, opportunistic infections, and immune impairment. To address these issues, a wide variety of preclinical studies, mainly in non-human primates, have been performed for the purpose of assessing the potential risk of drug-induced, human immunotoxicity. Case studies presented at this symposium showed the feasibility of assessing humoral and cell-mediated aspects of the immune system, using antigen and neoantigen challenges, immunohistochemical, and flow cytometric (FACS) methods. In some cases, homologous forms of the biologic agent and "humanized" transgenic models have been used to assess potential clinical risks. These data have been useful in providing some assurance that severe adverse effects would not be induced in patients. Despite these limitations, it is important that industry sponsors provide information to regulatory authorities, the clinical investigator, and patients that provides the best feasible basis for risk assessment, safe clinical trial design, informed consent, and eventually, appropriate labeling. It is recognized that existing preclinical models often have significant limitations. Consequently, the sponsor's and regulatory authority's experienced judgement has determined whether or not the purported benefits of the novel therapeutic agent are balanced by the potential short- and long-term risks. In this field of development, preclinical models often need to reflect recent. technology innovations; therefore, these models are not always "validated" in a conventional sense. Experience to date suggests that improved methods and approaches are needed as these agents are developed for use in lower or moderate risk patient populations. Consequently, there is an increased need for an industry/regulatory partnership in order to achieve progress in these risk assessment areas. C1 Biogen Inc, Cambridge, MA 02142 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Green, JD (reprint author), Biogen Inc, 14 Cambridge Ctr, Cambridge, MA 02142 USA. NR 0 TC 8 Z9 10 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0144-5952 J9 HUM EXP TOXICOL JI Hum. Exp. Toxicol. PD APR PY 2000 VL 19 IS 4 BP 208 EP 212 DI 10.1191/096032700678815864 PG 5 WC Toxicology SC Toxicology GA 329XL UT WOS:000087933700003 PM 10918509 ER PT J AU Bussiere, JL Black, LE AF Bussiere, JL Black, LE TI In vivo methods for assessing immunocompetence SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Editorial Material C1 Genentech Inc, S San Francisco, CA 94080 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Bussiere, JL (reprint author), Immunex Res & Dev Corp, 51 Univ St, Seattle, WA 98101 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0144-5952 J9 HUM EXP TOXICOL JI Hum. Exp. Toxicol. PD APR PY 2000 VL 19 IS 4 BP 215 EP 216 PG 2 WC Toxicology SC Toxicology GA 329XL UT WOS:000087933700005 ER PT J AU Essayan, DM AF Essayan, DM TI Clinical trial design for immunomodulatory biologics SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Article; Proceedings Paper CT Conference on Safety Evaluation of Immunomodulatory Biopharmaceuticals: Can We Improve the Predictive Value of Preclinical Studies? CY SEP 23-24, 1999 CL BETHESDA, MARYLAND DE clinical trial; immunomodulatory; biologics; preclinical; pharmacokinetics; pharmacodynamics C1 US FDA, Div Clin Trial Design & Anal, Off Therapeut Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Essayan, DM (reprint author), US FDA, Div Clin Trial Design & Anal, Off Therapeut Res & Review, Ctr Biol Evaluat & Res, HFM-579,1401 Rockville Pike, Rockville, MD 20852 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0144-5952 J9 HUM EXP TOXICOL JI Hum. Exp. Toxicol. PD APR PY 2000 VL 19 IS 4 BP 255 EP 256 DI 10.1191/096032700678815846 PG 2 WC Toxicology SC Toxicology GA 329XL UT WOS:000087933700015 PM 10918518 ER PT J AU Hastings, KL AF Hastings, KL TI Assessment of immunosuppressant drug carcinogenicity: standard and alternative animal models SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Article; Proceedings Paper CT Conference on Safety Evaluation of Immunomodulatory Biopharmaceuticals: Can We Improve the Predictive Value of Preclinical Studies? CY SEP 23-24, 1999 CL BETHESDA, MARYLAND DE immunosuppressants; carcinogenicity; alternative models ID CYCLOSPORINE-A; HEPATOCELLULAR-CARCINOMA; LIVER-TRANSPLANTATION; RATS; INDUCTION; EXPRESSION; MECHANISM; CANCERS; TUMORS; RISK AB Drugs intended for use in preventing allograft rejection in transplant patients are likely to be administered chronically; thus, it is normally expected that sponsors would conduct nonclinical studies to determine the carcinogenic potential of candidate compounds. For pharmaceuticals other than biologic agents, this would mean that rodent carcinogenicity bioassays would be performed under most circumstances. Immunosuppressant drugs have presented unique challenges with respect to the issue of carcinogenicity bioassays. The pharmacological activity of therapeutic immunosuppressants is thought to make them highly likely to act as promoters/cocarcinogens, even in the absence of genotoxic activity. Thus, it is assumed that this class of drug would represent a carcinogenic hazard in the absence of confirmatory standard rodent bioassay data. In addition, rodents typically have been sensitive to the pharmacological/toxicological effects of immunosuppressants, It has proven to be difficult, therefore, to conduct life-time bioassays at doses reasonably equivalent to those that would be used clinically. For this and other reasons, alternative models might be more appropriate for risk assessment with this class of drugs. C1 US FDA, Div Special Pathogen & Immunol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Hastings, KL (reprint author), US FDA, Div Special Pathogen & Immunol Drug Prod, Ctr Drug Evaluat & Res, HFD-590,5600 Fishers Lane, Rockville, MD 20857 USA. NR 46 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0144-5952 J9 HUM EXP TOXICOL JI Hum. Exp. Toxicol. PD APR PY 2000 VL 19 IS 4 BP 261 EP 265 DI 10.1191/096032700678815837 PG 5 WC Toxicology SC Toxicology GA 329XL UT WOS:000087933700017 PM 10918520 ER PT J AU Dreisbach, VC Cowley, S Elkins, KL AF Dreisbach, VC Cowley, S Elkins, KL TI Purified lipopolysaccharide from Francisella tularensis live vaccine strain (LVS) induces protective immunity against LVS infection that requires B cells and gamma interferon SO INFECTION AND IMMUNITY LA English DT Article ID INTRACELLULAR PATHOGEN; T-CELLS; PSEUDOMONAS-AERUGINOSA; MONOCLONAL-ANTIBODY; MICE; TULAREMIA; INDUCTION; IMMUNOGLOBULIN; ACTIVATION; RESISTANCE AB Previous results have demonstrated that nonspecific protective immunity against lethal Francisella tularensis live vaccine strain (LVS) or Listeria monocytogenes infection can be stimulated either by sublethal infection dth bacteria or by treatment with bacterial DNA given 3 days before lethal challenge. Here we characterize the ability of purified lipopolysaccharide (LPS) from F. tularensis LVS to stimulate similar early protective immunity. Treatment of mice with surprisingly small amounts of LVS LPS resulted in very strong and long-lived protection against lethal LVS challenge within 2 to 3 days. Despite this strong protective response, LPS purified from F. tularensis LVS did not activate murine B cells for proliferation or polyclonal immunoglobulin secretion, nor did it activate marine splenocytes for secretion of interleukin-4 (IL-4), IL-6, IL-12, or gamma interferon (IFN-gamma). Immunization of mice with purified LVS LPS induced a weak specific anti-LPS immunoglobulin M (IgM) response and very little IgG; however, infection of mice with LVS bacteria resulted in vigorous IgM and IgG, particularly IgG2a, anti-LPS antibody responses. Studies using various immunodeficient mouse strains, including LPS-hyporesponsive C3H/HeJ mice, mu MT- (B-cell-deficient) knockout mice, and IFN-gamma-deficient mice, demonstrated that the mechanism of protection does not involve recognition through the Lps(n) gene product; nonetheless, protection was dependent on B cells as well as IFN-gamma. C1 US FDA, Lab Mycobacteria, Div Bacterial Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Univ Victoria, Dept Biochem & Microbiol, Victoria, BC V8W 3P6, Canada. RP Elkins, KL (reprint author), US FDA, Lab Mycobacteria, Div Bacterial Prod, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 431, Rockville, MD 20852 USA. NR 46 TC 79 Z9 83 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2000 VL 68 IS 4 BP 1988 EP 1996 DI 10.1128/IAI.68.4.1988-1996.2000 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 296EP UT WOS:000086010300034 PM 10722593 ER PT J AU Frasch, CE Concepcion, NF AF Frasch, CE Concepcion, NF TI Specificity of human antibodies reactive with pneumococcal C polysaccharide SO INFECTION AND IMMUNITY LA English DT Article ID STREPTOCOCCUS-PNEUMONIAE; CELL-WALL; PHOSPHOCHOLINE; SERUM AB Antibodies reactive with C polysaccharide (PS) were found in healthy adults, pneumococcal patients, and vaccinees. These antibodies were not directed to the phosphocholine determinant of the C PS, as they appear to be in mice, since the human antibodies were inhibitable only with C PS. We found another population of phosphocholine-specific antibodies inhibitable only by phosphocholine and related compounds. C1 US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Bethesda, MD USA. RP Frasch, CE (reprint author), CBER, Div Bacterial Prod, 1401 Rockville Pike,HFM-428, Rockville, MD 20852 USA. NR 17 TC 9 Z9 10 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2000 VL 68 IS 4 BP 2333 EP 2337 DI 10.1128/IAI.68.4.2333-2337.2000 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 296EP UT WOS:000086010300079 PM 10722638 ER PT J AU Yip, L Hickey, V Wagner, B Liss, G Slater, J Breiteneder, H Sussman, G Beezhold, D AF Yip, L Hickey, V Wagner, B Liss, G Slater, J Breiteneder, H Sussman, G Beezhold, D TI Skin prick test reactivity to recombinant latex allergens SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article DE latex allergy; antigens; IgE antibodies; recombinant allergens ID RUBBER ELONGATION-FACTOR; HEVEA-BRASILIENSIS; SPINA-BIFIDA; IGE; IDENTIFICATION; CLONING; WORKERS; BETA-1,3-GLUCANASE; PROTEINS; HEV-B-5 AB Background: Allergy to latex has become a serious and increasingly common health problem, particularly for healthcare workers and patients who undergo frequent surgical procedures. Testing for latex allergy currently involves in vitro tests and skin prick testing using crude preparations of natural rubber latex (NRL). To date, 10 latex proteins have received designation as allergens (Hev b 1 to Hev b 10) and, except for Hev b 4, have been cloned as recombinant proteins. Our aim was to compare the skin prick test (SPT) reactivity of six recombinant latex allergens with SPT reactivity to natural rubber latex proteins in known latex-allergic individuals. Methods: Six recombinant proteins were expressed in Escherichia coli, and tested as the intact fusion proteins (Hev b 2, 5, 6, 8) or as purified proteins (Hev b 3 and 7). SPT with the six recombinant latex allergens was performed using 10-fold serial dilutions on 31 latex-allergic subjects to determine the level of reactivity to each recombinant allergen. Latex-specific IgE was determined using the AlaSTAT assay. Results All six recombinant allergens were reactive by SPT in at least 1 latex-allergic patient but not in any of the control patients. The frequency of sensitization to the various recombinant allergens was similar to previous studies using the native proteins isolated from NRL. The minimal level of protein for a positive skin test was 70 pg/ml for NRL and 1 ng/ml for one recombinant allergen (Hev b 7). In our patients, the use of a combination of recombinant latex allergens Hev b 5, 6 and 7 diagnosed latex allergy with 93% sensitivity and 100% specificity. Conclusion: Recombinant latex allergens are clinically reactive, can be produced in a standardized manner, and could potentially provide safe, sensitive and specific reagents for the diagnosis of latex allergy. Copyright (C) 2000 S. Karger AG, Basel. C1 Guthrie Res Inst, Immunobiol Lab, Sayre, PA 18840 USA. Univ Toronto, Toronto, ON, Canada. Univ Vienna, Dept Gen & Expt Pathol, A-1010 Vienna, Austria. US FDA, Lab Immunobiochem, Washington, DC USA. RP Beezhold, D (reprint author), Guthrie Res Inst, Immunobiol Lab, 1 Guthrie Sq, Sayre, PA 18840 USA. NR 25 TC 60 Z9 61 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PD APR PY 2000 VL 121 IS 4 BP 292 EP 299 DI 10.1159/000024342 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 312AJ UT WOS:000086919800004 PM 10828719 ER PT J AU Portillo-Gomez, L Morris, SL Panduro, A AF Portillo-Gomez, L Morris, SL Panduro, A TI Rapid and efficient detection of extra-pulmonary Mycobacterium tuberculosis by PCR analysis SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE extra-pulmonary tuberculosis; PCR; M-tuberculosis ID POLYMERASE CHAIN-REACTION; CLINICAL-SAMPLES; DNA FRAGMENT; DIAGNOSIS; AMPLIFICATION; MENINGITIS; SPECIMENS; COMPLEX; SPUTUM; IS6110 AB SETTING: The diagnosis of extra-pulmonary tuberculosis (EPTB) remains an important clinical problem, primarily because of the inadequate sensitivity of conventional bacteriologic methods for detecting Mycobacterium tuberculosis in extra-pulmonary specimens. OBJECTIVE: TO evaluate whether a IS6110-based polymerase chain reaction (PCR) method can be utilized to detect M. tuberculosis in non-pulmonary specimens. DESIGN: Specimens from 286 Mexican patients with a presumptive clinical diagnosis of EPTB were prospectively examined by Ziehl-Neelsen staining, mycobacterial culture on Lowenstein-Jensen slants, and by PCR. The DNA for PCR was extracted by the buffer lysis method and phenol-guanidine thiocyanate-chloroform. Primers that amplify a 200 bp fragment from the insertion-like M. tuberculosis sequence element IS6110 were utilized. RESULTS: Our results demonstrate that this PCR method is highly specific (100%) for identifying M. tuberculosis from a variety of specimens including cerebrospinal fluid (CSF), pleural fluid, ascitic fluid, pericardial fluid, urine, and lymph node exudate. Moreover, the sensitivity of PCR for detecting M. tuberculosis in CSF (94%), pleural fluid (94%), ascitic fluid and other extrapulmonary specimens (93%) greatly exceeds the sensitivity of conventional smear and culture methods. CONCLUSION: These results demonstrate that PCR can be a highly specific and sensitive aid in the detection of M. tuberculosis from extra-pulmonary specimens. C1 Univ Guadalajara, Hosp Civil Belen, CUCS, Guadalajara 44280, Jalisco, Mexico. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Portillo-Gomez, L (reprint author), Univ Guadalajara, Hosp Civil Belen, CUCS, POB 2-500, Guadalajara 44280, Jalisco, Mexico. NR 36 TC 55 Z9 57 U1 0 U2 2 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD APR PY 2000 VL 4 IS 4 BP 361 EP 370 PG 10 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 301MJ UT WOS:000086313700014 PM 10777087 ER PT J AU Merritt, K Hitchins, VM Brown, SA AF Merritt, K Hitchins, VM Brown, SA TI Safety and cleaning of medical materials and devices SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article ID ADHERENCE AB A study was undertaken to evaluate different procedures to safely remove microorganisms, protein, and mammalian cells from materials and provide a suitable method for cleaning and assessing effectiveness of cleaning medical devices for reuse or for analysis of failure. Safety considerations for the personnel performing the cleaning or handling the device after cleaning are important issues, Polystyrene plates (96 well) were used to simulate device surfaces not amenable to manual scrubbing, Staphylococcus epidermidis, Candida albicans, Escherichia coli, Pseudomonas aeruginosa and oral flora were grown in the plates. The plates were stained with crystal violet and the optical densities recorded. The results indicated that E. coli did not adhere well and Pseudomonas formed clumps that mere easily detached from the surface of the plates. However, S. epi, C. albicans, and the oral organisms formed adherent biofilms that were difficult to remove from the plates, Detergents with enzymes and sodium hypochlorite (NaOCl) bleach mere both effective in removing the biofilm, Other detergents and surfactants were not effective. The aldehyde agents did not remove the organisms and made further cleaning difficult. Allowing the biofilm to dry first made cleaning very difficult, Only the NaOCl bleach could subsequently remove the dried or aldehyde fixed organisms from the wells. The same 96-well polystyrene plate format was used to measure the amount of protein and cell adherence as well as the effectiveness of subsequent cleaning. Bradford reagent was used to detect protein as a measure of the cleaning efficacy. As with the bacteria, NaOCl bleach was effective at removing the protein and cells that had been dried or fixed by formalin or alcohol, whereas detergent with enzymes was not very effective. This study confirmed that used medical devices, contaminated with microorganisms, protein, and/or mammalian cells, should not be allowed to dry before cleaning and that a thorough cleaning procedure should precede sterilization or disinfection (with the exception of NaOCl bleach which also cleans). (C) 2000 John Wiley & Sons, Inc. C1 US FDA, Ctr Devices & Radiol Hlth, Div Life Sci, HFZ 112, Rockville, MD 20852 USA. RP Merritt, K (reprint author), 17704 Stoneridge Dr, Gaithersburg, MD 20878 USA. NR 8 TC 53 Z9 55 U1 0 U2 13 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD APR PY 2000 VL 53 IS 2 BP 131 EP 136 DI 10.1002/(SICI)1097-4636(2000)53:2<131::AID-JBM1>3.0.CO;2-I PG 6 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 298RK UT WOS:000086152800001 PM 10713558 ER PT J AU Mahmood, I AF Mahmood, I TI Prospective allometric scaling: Does the emperor have clothes? SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Editorial Material ID PHARMACOKINETIC PARAMETERS; DRUGS; CLEARANCE; HUMANS; INTEGRATION; METABOLISM C1 US FDA, Div Pharmaceut Evaluat 1 HFD 860, Off Clin Pharmacol & Biopharmceut, Woodmont Off Ctr 2, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Div Pharmaceut Evaluat 1 HFD 860, Off Clin Pharmacol & Biopharmceut, Woodmont Off Ctr 2, Room 4079,1451 Rockville Pike, Rockville, MD 20852 USA. NR 17 TC 5 Z9 5 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD APR PY 2000 VL 40 IS 4 BP 341 EP 344 DI 10.1177/00912700022009026 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 298TB UT WOS:000086154300002 PM 10761159 ER PT J AU Bowen, RL Farahani, M Dickens, SH Guttman, CM AF Bowen, RL Farahani, M Dickens, SH Guttman, CM TI MALDI-TOF MS analysis of a library of polymerizable cyclodextrin derivatives SO JOURNAL OF DENTAL RESEARCH LA English DT Article; Proceedings Paper CT 77th General Session of the International-Association-for-Dental-Research CY MAR 10-13, 1999 CL VANCOUVER, CANADA SP Int Ass Dent Res DE dental; resins; cyclodextrins; MALDI-TOF; spectrometry ID FLIGHT MASS-SPECTROMETRY AB Polymerizable cyclodextrin derivatives (PCDs) have been proposed as candidates for use in dental therapeutics (Bowen, 1996; Bowen and Reed, 1997). Here, PCD "libraries" were synthesized by quasi-random reactions of 6 moles of methacrylic anhydride plus 6 moles of cyclic glutaric anhydride per mole of beta-cyclodextrin (BCD) in solution. BCD has 21 reactive sites on each of its molecules. These proportions were based on probability calculations, which predicted that the products should have a minimum of 2 polymerizable substituents and acidic ligand groups on practically every one of the diverse product molecules. Matrix-assisted laser desorption/ionization (MALDI) time of flight (TOF) mass spectrometry (MS) gave valuable information regarding the masses of molecular ions representing the molecules that made up the PCD libraries. For the MALDI-TOF MS analyses, small samples were analyzed by the successive application of 3 solutions to the sample holder: the matrix in acetone, the products in water, and sodium trifluoroacetate in water. The resulting spectra had > 40 envelopes of mass peaks above background. The ionic-abundance peak heights had quasi-Gaussian configurations, with central peaks having masses in the neighborhood of 2000 g/mol (Daltons). Regardless of structural permutations within each peak, the range of these peaks was between about 1500 g/mol and 2900 g/mol. This range of masses was in accord with, but perhaps somewhat more narrow than, that predicted by the statistical method, which was based on equal reactivity of all hydroxyl groups. Analysis by MALDI-TOF MS gave valuable data regarding the masses, structures, and characteristics of the products formed and provided unanticipated information to facilitate improvements in future PCD syntheses. C1 Natl Inst Stand & Technol, ADA Hlth Fdn, Paffenbarger Res Ctr, Gaithersburg, MD 20899 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20855 USA. NIST, Div Polymers, Rockville, MD 20850 USA. RP Bowen, RL (reprint author), Natl Inst Stand & Technol, ADA Hlth Fdn, Paffenbarger Res Ctr, Gaithersburg, MD 20899 USA. FU NIDCR NIH HHS [P50 DE09322, R37 DE05129] NR 21 TC 7 Z9 7 U1 2 U2 5 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD APR PY 2000 VL 79 IS 4 BP 905 EP 911 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 312BA UT WOS:000086921800003 PM 10831091 ER PT J AU Anderson, DL AF Anderson, DL TI Neutron capture prompt gamma-ray activation analysis of meat homogenates SO JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY LA English DT Article; Proceedings Paper CT 10th International Conference on Modern Trends in Activation Analysis (MTAA-10) CY APR 19-23, 1999 CL NIH, BETHESDA, MARYLAND SP Natl Inst Stand & Technol HO NIH ID SCATTERING AB Thermal neutron capture prompt gamma-ray activation analysis (PGAA) was used to determine mass fractions of H, B, C, N, Na, Cl, K, and S in 2 meat homogenates. Twelve units of candidate Standard Reference Material (SRM) 1546 Meat Homogenate produced by the National Institute of Standards and Technology (NIST) were analyzed to provide NIST with certification data. This SRM is a realistic processed food matrix, ideal for food analysis programs such as the Food and Drug Administration's Total Diet Study. Another meat homogenate, Certified Reference Material LGC 7002 Pork/Chicken (along with NIST SRMs 1549 Non-Fat Milk Powder and 1571 Orchard Leaves) was analyzed for quality control. Candidate SRM 1546 unit-to-unit heterogeneity was <2% for H, Na, Cl, and K, and 3.5% for N and within-unit heterogeneity was <2% for H, N, Cl, and K, and 2.9% for Na,similar to LGC 7002 homogeneity results. Control material mass fractions agreed well with certificate and consensus values. Protein mass fractions, calculated from N results, were 15.2% and 11.9% for candidate SRM 1546 and LGC 7002, respectively. Protein content calculated for SRM 1549 (36.0%) agreed well with known values for dried non-fat milk powder. C1 US FDA, Elemental Res Branch HFS 338, Washington, DC USA. RP Anderson, DL (reprint author), US FDA, Elemental Res Branch HFS 338, 200 C St SW, Washington, DC USA. NR 11 TC 8 Z9 9 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0236-5731 J9 J RADIOANAL NUCL CH JI J. Radioanal. Nucl. Chem. PD APR PY 2000 VL 244 IS 1 BP 225 EP 229 DI 10.1023/A:1006761525590 PG 5 WC Chemistry, Analytical; Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA 338GH UT WOS:000088410400039 ER PT J AU Feuers, RJ Desai, VG Chen, FX Hunter, JD Duffy, PH Oriaku, ET AF Feuers, RJ Desai, VG Chen, FX Hunter, JD Duffy, PH Oriaku, ET TI Effects of dietary restriction on insulin resistance in obese mice SO JOURNAL OF THE AMERICAN AGING ASSOCIATION LA English DT Article ID CHRONIC CALORIC RESTRICTION; MALE FISCHER-344 RAT; DIABETES-MELLITUS; METABOLISM; VARIABLES; ENZYMES AB In many cases, development of insulin resistance has been linked to obesity and may contribute to mechanism of aging. The role of diet, irrespective of degree of obesity, in modulating insulin resistance and development of age degeneration disease remains uncertain. Lowered blood glucose levels are commonly associated with diet restriction (DR), which is an intervention shown to successfully retard aging and age associated disease. The effects of DR on blood glucose and insulin resistance were measured in yellow obese (A(vy)/A), lean black(a/a) mice and in another common inbred strain (B6C3F1) (at three different ages). The yellow obese mice become diabetic as a result of an insulin receptor defect which is not clearly understood. Insulin responses and radioinsulin binding were assayed in yellow obese and lean black mice fed either ad libitum (AL) or DR diets (YAL, BAL, YDR and YAL, respectively) at four different circadian intervals. The B6C3F1 controls were fed either AL (CAL) or DR (CDR) and measures were made at six circadian stages and three different ages. Within 23 days, DR produced a significant loss in body weight and a time-dependent 22-55% reduction in basal blood glucose levels in the yellow obese mice. Additionally, exogenous insulin produced circadian stage dependent (at the time of food intake) reductions in blood glucose in the YDR animals that were not present in YAL animals. I-125-insulin binding in liver was increased nearly 2-fold in YDR and BDR mice during the time of day that animals were active and eating. I-125-insulin binding was two-fold-higher in CDR mice at 4, 12 and >24 months of age. Binding decreased as a function of age in both the CAL and CDR animals. However, even in the >24 month group the CDR animals were found to have levels of binding that were as high as those found in younger CAL liver. The mechanism of action appears to be through resolution of insulin resistance by modulating an insulin receptor defect. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Anat, Little Rock, AR 72205 USA. Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Tallahassee, FL 32307 USA. Guangzhou Univ, Dept Pediat, Guangzhou 510235, Peoples R China. Univ Texas, Dept Biol, El Paso, TX 79968 USA. RP Feuers, RJ (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 38 TC 0 Z9 0 U1 0 U2 4 PU AMER AGING ASSOC PI MEDIA PA SALLY BALIN MEDICAL CENTER, 110 CHESLEY DR, MEDIA, PA 19063 USA SN 0161-9152 J9 J AM AGING ASSOC JI J. Am. Aging Assoc. PD APR PY 2000 VL 23 IS 2 BP 95 EP 101 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 362TZ UT WOS:000089795500005 PM 23604843 ER PT J AU Duffy, R Tomashek, K Spangenberg, M Spry, L Dwyer, D Safranek, TJ Ying, C Portesi, D Divan, H Kobrenski, J Arduino, M Tokars, J Jarvis, W AF Duffy, R Tomashek, K Spangenberg, M Spry, L Dwyer, D Safranek, TJ Ying, C Portesi, D Divan, H Kobrenski, J Arduino, M Tokars, J Jarvis, W TI Multistate outbreak of hemolysis in hemodialysis patients traced to faulty blood tubing sets SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Conference on Forefronts in Nephrology - News in Aldosterone Action CY AUG 15-18, 1999 CL CHANTILLY, FRANCE SP Int Soc Nephrol DE hemodialysis tubing; hemolysis; dialyzer blood lines; epidemic AB Background. Hemolysis associated with hemodialysis is rare. The most frequent causes of hemodialysis-associated hemolysis are chemical contamination, heat, or mechanical injury of erythrocytes from occluded or kinked hemodialysis blood lines. When patients in three states developed hemolysis while undergoing hemodialysis between May 13 and 23, 1998, an investigation was initiated. Methods. A case-patient was defined as any patient at healthcare facilities A (Nebraska), B (Maryland), or C (Massachusetts) during May 13 through 23, 1998 (epidemic period), who had hemolysis diagnosed greater than or equal to 48 hours after undergoing hemodialysis. To identify case-patients and to determine background rates, the medical records of patients from facilities A, B, and C who were undergoing hemodialysis during the epidemic and pre-epidemic (that is, May 5 through 19, 1998) periods were reviewed. Experiments simulating hemodialysis with the same lot numbers of hemodialysis blood tubing cartridge sets used on case- and control-patients were conducted. Results. The rates of hemolysis among patients at facilities A, B, and C were significantly higher during the epidemic than the pre-epidemic period (13 out of 118 vs. 0 out of 118. Pt 0.001: 12 out of 298 vs. 0 out of 298, P = 0.001: and 5 out of 62 vs. 0/65, P = 0.03, respectively). All case-patients had hemolysis. Twenty (66%) had hypertension. Eighteen (60%) had abdominal pain, and 10 (36%) were admitted to an intensive care unit. There were two deaths. The only commonality among the three outbreaks was the use of the same lot of disposable hemodialysis blood tubing from one manufacturer. Examination of the implicated hemodialysis blood tubing cartridge sets revealed narrowing of an aperture through which blood was pumped before entering the dialyzers. In vitro experiments with the hemodialysis blood tubing revealed that hemolysis was caused by increased pressure on erythrocytes as they passed through the partially occluded hemodialysis blood tubing. Conclusions. Our investigation traced the multiple hemolysis outbreaks to partially occluded hemodialysis blood tubing produced by a single manufacturer. On May 25, 1998, the manufacturer issued a voluntary nationwide recall of the implicated lots of hemodialysis blood tubing cartridge sets. C1 Ctr Dis Control & Prevent, Hosp Infect Program, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, US Dept HHS, Publ Hlth Serv, Natl Ctr Environm Hlth,Int Emergency & Refugee Hl, Atlanta, GA 30333 USA. US FDA, Off Regulatory Affairs, Omaha, NE USA. Dialysis Ctr, Lincoln, NE USA. Nebraska Hlth & Human Serv Syst, Lincoln, NE USA. Maryland Dept Hlth & Mental Hyg, Baltimore, MD USA. Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA USA. RP Jarvis, W (reprint author), Ctr Dis Control & Prevent, Hosp Infect Program, 1600 Clifton Rd NE,Mail Stop-E69, Atlanta, GA 30333 USA. RI Arduino, Matthew/C-1461-2012 OI Arduino, Matthew/0000-0001-7072-538X NR 9 TC 15 Z9 15 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD APR PY 2000 VL 57 IS 4 BP 1668 EP 1674 DI 10.1046/j.1523-1755.2000.00011.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 300TU UT WOS:000086269300055 PM 10760102 ER PT J AU Marmillot, P Rao, MN Liu, QH Chirtel, SJ Lakshman, MR AF Marmillot, P Rao, MN Liu, QH Chirtel, SJ Lakshman, MR TI Effect of dietary omega-3 fatty acids and chronic ethanol consumption on reverse cholesterol transport in rats SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID DENSITY LIPOPROTEINS; LIPOGENIC ENZYMES; PLASMA-LIPIDS; APOPROTEIN-E; FISH-OIL; LIVER; FIBROSIS; HYPERTRIGLYCERIDEMIA; MACROPHAGES; HEPATOCYTES AB We previously showed that chronic ethanol feeding reads to a decrease of apolipoprotein E (apoE) in high-density lipoprotein (HDL), whereas supplementing this diet with 2.8% of total dietary calories as omega 3-fatty acids (omega 3FAs) restores HDL-apoE to the control values. Since HDL containing apoE plays a major role in reverse cholesterol transport (RCT), we measured the effects chronic ethanol intake and omega 3-FAs -FAs on RCT in the present study. Four groups of rats, control normal fat (CN), alcohol-normal fat (AN), control omega 3FA fat (CF), and alcohol-omega 3FA fat (AF), were fed their respective diets for 8 weeks, after which hepatocytes and HDLs from each group were evaluated for RCT capacity (cholesterol efflux from macrophages end uptake by liver cells). Compared with the control diet (CN), chronic ethanol (AN) feeding inhibited the cholesterol efflux capacity of HDL by 21% (P <.01), whereas w3FA feeding (2.8% of total dietary calories) stimulated this capacity by 79% (P <.01) and 25% (P <.01) in CF and AF rats, respectively. With respect to cholesterol uptake by the liver, there were no significant 3-way or 4-way interactions between the 4 factors, HDL-alcohol, MDL-fish oil, hepatocyte-alcohol, and hepatocyte-fish oil. The main effects for HDL-alcohol, HDL-fish oil, and hepatocyte-alcohol were all highly significant (P =.0001,.0001, and .007, respectively). There was a significant HDL-alcohol and HDL-fish oil interaction (P =.0001). Hepatocyte-alcohol was not a factor in any 2-way interactions. Our study indicates no evidence of an interaction between the effects of omega 3FAs end the effects of alcohol on hepatocytes in terms of RCT function. Thus, feeding as little as 2.8% of the total dietary calories as w3FA not only restored the impaired RCT function of HDL caused by chronic ethanol intake, but also enhanced by severalfold the ability of HDL to promote RCT even in normal animals. Copyright (C) 2000 by W.B. Saunders Company. C1 George Washington Univ, Dept Med, Vet Affairs Med Ctr, Lipid Res Lab, Washington, DC USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Lakshman, MR (reprint author), DVA Med Ctr, Lipid Res Lab, 50 Irving St NW, Washington, DC 20422 USA. NR 33 TC 19 Z9 19 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD APR PY 2000 VL 49 IS 4 BP 508 EP 512 DI 10.1016/S0026-0495(00)80017-7 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 303VD UT WOS:000086444800017 PM 10778877 ER PT J AU Drazek, ES Hammack, CA Schmitt, MP AF Drazek, ES Hammack, CA Schmitt, MP TI Corynebacterium diphtheriae genes required for acquisition of iron from haemin and haemoglobin are homologous to ABC haemin transporters SO MOLECULAR MICROBIOLOGY LA English DT Article ID TOXIN REPRESSOR DTXR; OUTER-MEMBRANE PROTEIN; INFLUENZAE TYPE-B; ESCHERICHIA-COLI O157-H7; HAEMOPHILUS-INFLUENZAE; CYTOPLASMIC MEMBRANE; BINDING PROTEINS; VIBRIO-CHOLERAE; SHIGELLA-DYSENTERIAE; MOLECULAR-CLONING AB Corynebacterium diphtheriae and Corynebacterium ulcerans use haemin and haemoglobin as essential sources of iron during growth in iron-depleted medium. C. diphtheriae and C. ulcerans mutants defective in haemin iron utilization were isolated and characterized. Four clones from a C. diphtheriae genomic library complemented several of the Corynebacteria haemin utilization mutants. The complementing plasmids shared an approximate to 3 kb region, and the nucleotide sequence of one of the plasmids revealed five open reading frames that appeared to be organized in a single operon. The first three genes, which we have termed hmuT, hmuU and hmuV, shared striking homology with genes that are known to be required for haemin transport in Gram-negative bacteria and are proposed to be part of an ABC (ATP-binding cassette) transport system. The hmuT gene encodes a 37 kDa lipoprotein that is associated with the cytoplasmic membrane when expressed in Escherichi coli and C. diphtheriae. HmuT binds in vitro to haemin- and haemoglobin-agarose, suggesting that it is capable of binding both haemin and haemoglobin and may function as the haemin receptor in C. diphtheriae. This study reports the first genetic characterization of a transport system that is involved in the utilization of haemin and haemoglobin as iron sources by a Gram-positive bacterium. C1 US FDA, Ctr Biol Evaluat & Res, LBT, Div Bacterial Prod, Bethesda, MD 20892 USA. RP Schmitt, MP (reprint author), US FDA, Ctr Biol Evaluat & Res, LBT, Div Bacterial Prod, Bldg 29,Rm 108,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 55 TC 82 Z9 84 U1 0 U2 12 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD APR PY 2000 VL 36 IS 1 BP 68 EP 84 DI 10.1046/j.1365-2958.2000.01818.x PG 17 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 301YM UT WOS:000086338200007 PM 10760164 ER PT J AU Krause, PR Klinman, DM AF Krause, PR Klinman, DM TI Varicella vaccination: Evidence for frequent reactivation of the vaccine strain in healthy children SO NATURE MEDICINE LA English DT Article ID ZOSTER VIRUS-INFECTIONS; FOLLOW-UP; EFFICACY; IMMUNIZATION; EPIDEMIOLOGY; CHICKENPOX; IMMUNITY AB Wild-type varicella tester virus (VZV) causes chickenpox, a common childhood illness characterized by fever and a vesicular rash(1) and rare serious complications'. Wild-type VZV persists in a latent form in the sensory ganglia, and can re-activate to cause herpes zoster(3). More than 10 million American children have received the live attenuated Oka strain VZV vaccine (OkaVZV) since its licensure in 1995. Pre-licensure clinical studies showed that mean serum anti-VZV levels among vaccinees continued to increase with time after vaccination. This was attributed to immunologic boosting caused by exposure to wild-type VZV in the community(4,5). Here, we examine the alternative, that large-scale asymptomatic reactivation of OkaVZV might occur in vaccinees. We analyzed serum antibody levels and infection rates for 4 years of follow-up in 4,631 children immunized with OkaVZV. Anti-VZV titers decreased over time in high-responder subjects, but rose in vaccinees with low titers. Among subjects with low anti-VZV titers, the frequency of clinical infection and immunological boosting substantially exceeded the 13%-per-year rate of exposure to wild-type varicella. These findings indicate that OkaVZV persisted in vivo and reactivated as serum antibody titers decreased after vaccination. This has salient consequences for individuals immunized with OkaVZV. C1 US FDA, Lab DNA Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Sect Retroviral Res, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Krause, PR (reprint author), US FDA, Lab DNA Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 24 TC 55 Z9 58 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2000 VL 6 IS 4 BP 451 EP 454 DI 10.1038/74715 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 376UA UT WOS:000165474100041 PM 10742154 ER PT J AU Murphy, D Roberts, R AF Murphy, D Roberts, R TI Pediatric clinical trials: How they are different SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 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 2000 VL 47 IS 4 SU S MA 1252 BP 212A EP 212A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301252 ER PT J AU Anziano, P Quan, R Mize, C AF Anziano, P Quan, R Mize, C TI Expression of an isoform of manganese superoxide dismutase in a child with multiple deletions of the human mitochondrial DNA SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 CHOP, Philadelphia, PA USA. US FDA, GI, UNR, NV,CFSAN, Washington, DC 20204 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 2000 VL 47 IS 4 SU S MA 1401 BP 238A EP 238A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301400 ER PT J AU Cote, CJ Notterman, DA Karl, HW Weinberg, JA McCloskey, C AF Cote, CJ Notterman, DA Karl, HW Weinberg, JA McCloskey, C TI Adverse sedation events in pediatrics: A critical incident analysis of contributing factors SO PEDIATRICS LA English DT Review DE sedation; adverse events; critical incident; medication errors; monitoring; guidelines ID CLOSED CLAIMS ANALYSIS; PULSE OXIMETRY; ORTHOPEDIC EMERGENCIES; ANESTHESIA ACCIDENTS; GENERAL-ANESTHESIA; SINGLE-BLIND; DRUG EVENTS; CHILDREN; LIMITATIONS; MORTALITY AB Objective. Factors that contribute to adverse sedation events in children undergoing procedures were examined using the technique of critical incident analysis. Methodology. We developed a database that consists of descriptions of adverse sedation events derived from the Food and Drug Administration's adverse drug event reporting system, from the US Pharmacopeia, and from a survey of pediatric specialists. One hundred eighteen reports were reviewed for factors that may have contributed to the adverse sedation event. The outcome, ranging in severity from death to no harm, was noted. Individual reports were first examined separately by 4 physicians trained in pediatric anesthesiology, pediatric critical care medicine, or pediatric emergency medicine. Only reports for which all 4 reviewers agreed on the contributing factors and outcome were included in the final analysis. Results. Of the 95 incidents with consensus agreement on the contributing factors, 51 resulted in death, 9 in permanent neurologic injury, 21 in prolonged hospitalization without injury, and in 14 there was no harm. Patients receiving sedation in nonhospital-based settings compared with hospital-based settings were older and healthier. The venue of sedation was not associated with the incidence of presenting respiratory events leg, desaturation, apnea, laryngospasm, similar to 80% in each venue) but more cardiac arrests occurred as the second (53.6% vs 14%) and third events (25% vs 7%) in nonhospital-based facilities. Inadequate resuscitation was rated as being a determinant of adverse outcome more frequently in nonhospital-based events (57.1% vs 2.3%). Death and permanent neurologic injury occurred more frequently in nonhospital-based facilities (92.8% vs 37.2%). Successful outcome (prolonged hospitalization without injury or no harm) was associated with the use of pulse oximetry compared with a lack of any documented monitoring that was associated with unsuccessful outcome (death or permanent neurologic injury). In addition, pulse oximetry monitoring of patients sedated in hospitals was uniformly associated with successful outcomes whereas in the nonhospital-based venue, 4 out of 5 suffered adverse outcomes. Adverse outcomes despite the benefit of an early warning regarding oxygenation likely reflect lack of skill in assessment and in the use of appropriate interventions, ie, a failure to rescue the patient. Conclusions. This study-a critical incident analysis-identifies several features associated with adverse sedation events and poor outcome. There were differences in outcomes for venue: adverse outcomes (permanent neurologic injury or death) occurred more frequently in a nonhospital-based facility, whereas successful outcomes (prolonged hospitalization or no harm) occurred more frequently in a hospital-based setting. Inadequate resuscitation was more often associated with a nonhospital-based setting. Inadequate and inconsistent physiologic monitoring (particularly failure to use or respond appropriately to pulse oximetry) was another major factor contributing to poor outcome in all venues. Other issues rated by the reviewers were: inadequate presedation medical evaluation, lack of an independent observer, medication errors, and inadequate recovery procedures. Uniform, specialty-independent guidelines for monitoring children during and after sedation are essential. Age and size-appropriate equipment and medications for resuscitation should be immediately available regardless of the location where the child is sedated. All health care providers who sedate children, regardless of practice venue, should have advanced airway assessment and management training and be skilled in the resuscitation of infants and children so that they can successfully rescue their patient should an adverse sedation event occur. C1 Northwestern Univ, Childrens Mem Hosp, Sch Med, Dept Pediat Anesthesiol, Chicago, IL 60614 USA. Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. New York Presbyterian Hosp, Div Crit Care Med, New York, NY USA. Univ Washington, Sch Med, Childrens Hosp, Dept Pediat Anesthesiol, Seattle, WA 98195 USA. Univ Tennessee, Coll Med, Dept Pediat,Dept Emergency Serv, Lebonheur Childrens Med Ctr, Memphis, TN USA. US FDA, Ctr Drug Evaluat & Res, Off Post Mkt Drug Risk Assessment, Div Drug Evaluat 2, Washington, DC 20204 USA. RP Cote, CJ (reprint author), Northwestern Univ, Childrens Mem Hosp, Sch Med, Dept Pediat Anesthesiol, Chicago, IL 60614 USA. NR 102 TC 257 Z9 260 U1 3 U2 14 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2000 VL 105 IS 4 BP 805 EP 814 DI 10.1542/peds.105.4.805 PG 10 WC Pediatrics SC Pediatrics GA 299GC UT WOS:000086189400028 PM 10742324 ER PT J AU Hauck, WW Hyslop, T Chen, ML Patnaik, R Williams, RL AF Hauck, WW Hyslop, T Chen, ML Patnaik, R Williams, RL CA FDA Population Individual Bioequiv TI Subject-by-formulation interaction in bioequivalence: Conceptual and statistical issues SO PHARMACEUTICAL RESEARCH LA English DT Article DE individual bioequivalence; within-subject variability; subject-by-formulation interaction; subgroups ID INDIVIDUAL BIOEQUIVALENCE; CONFIDENCE-INTERVALS; CLINICAL-TRIALS; DRUGS; BIAS AB Purpose. The FDA has proposed replacing the current average bioequivalence criterion with population and individual bioequivalence criteria that consider variances in addition to the difference of averages. One of these variances in the individual bioequivalence criterion measures subject-by-formulation interaction, the extent to which the test-reference difference varies from person to person. This paper discusses conceptual acid statistical issues raised in various publications and presentations with respect to the presence and estimation of such an interaction. Methods. We focus on the importance of subject-by-formulation interaction, an understanding of what is a large interaction, and the assessment of the magnitude of this interaction in bioequivalence studies. Simulation studies, examples from the literature, and data from FDA files are used to demonstrate the magnitude of the interaction and its distribution under various conditions. Results. The concept of a large interaction is tied to the concept of a large mean difference. We suggest that an interaction greater than 0.15 is a conservative criterion for a large interaction. Magnitudes of estimated interaction are affected by variability, sample size, and the selection of data sets that pass average bioequivalence. Conclusions. Examples of substantial interactions are beginning to appear. More data is needed before reaching definitive conclusions regarding the frequency and importance of observed interactions. C1 Thomas Jefferson Univ, Biostat Sect, Div Clin Pharmacol, Philadelphia, PA 19107 USA. US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Div Bioequivalence, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Hauck, WW (reprint author), Thomas Jefferson Univ, Biostat Sect, Div Clin Pharmacol, Philadelphia, PA 19107 USA. NR 28 TC 27 Z9 30 U1 1 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD APR PY 2000 VL 17 IS 4 BP 375 EP 380 PG 6 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 322NT UT WOS:000087516200001 PM 10870978 ER PT J AU Meyer, MC Straughn, AB Jarvi, EJ Patrick, KS Pelsor, FR Williams, RL Patnaik, R Chen, ML Shah, VP AF Meyer, MC Straughn, AB Jarvi, EJ Patrick, KS Pelsor, FR Williams, RL Patnaik, R Chen, ML Shah, VP TI Bioequivalence of methylphenidate immediate-release tablets using a replicated study design to characterize intrasubject variability SO PHARMACEUTICAL RESEARCH LA English DT Article DE methylphenidate; average bioequivalence; individual bioequivalence; human; pharmacokinetics; replicated design ID MASS-SPECTROMETRIC ANALYSIS AB Purpose. To determine the relative bioavailability of two marketed, immediate-release methylphenidate tablets. The study used a replicated study design to characterize intrasubject variability, and determine bioequivalence using both average and individual bioequivalence criteria. Methods. A replicated crossover design was employed using 20 subjects. Each subject received a single 20 mg dose of the reference tablet on two occasions and two doses of the test tablet on two occasions. Blood samples were obtained for 10 hr after dosing, and plasma was assayed for methylphenidate by GC/MS. Results. The test product was more rapidly dissolved in vitro and more rapidly absorbed in vivo than the reference product. The mean Cmax and AUC(0 - infinity) differed by 11% and 9%, respectively Using an average bioequivalence criterion, the 90% confidence limits for the Ln-transformed Cmax and AUC(0 - infinity), comparing the two replicates of the test to the reference product, fell within the acceptable range of 80-125%. Using an individual bioequivalence criterion the test product failed to demonstrate equivalence in Cmax to the reference product. Conclusions. The test and reference tablets were bioequivalent using an average bioequivalence criterion. The intrasubject variability of the generic product was greater and the subject-by-formulation interaction variance was borderline high. For these reasons, the test tablets were not individually bioequivalent to the reference tablets. C1 Univ Tennessee, Dept Pharmaceut Sci, Coll Pharm, Memphis, TN 38163 USA. Idaho State Univ, Coll Pharm, Dept Pharmaceut Sci, Pocatello, ID 83209 USA. Med Univ S Carolina, Coll Pharm, Dept Pharmaceut Sci, Charleston, SC 29425 USA. US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. RP Meyer, MC (reprint author), Univ Tennessee, Dept Pharmaceut Sci, Coll Pharm, Memphis, TN 38163 USA. FU PHS HHS [223-87-1802] NR 13 TC 16 Z9 17 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD APR PY 2000 VL 17 IS 4 BP 381 EP 384 DI 10.1023/A:1007560500301 PG 4 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 322NT UT WOS:000087516200002 PM 10870979 ER PT J AU Lobenberg, R Kramer, J Shah, VP Amidon, GL Dressman, JB AF Lobenberg, R Kramer, J Shah, VP Amidon, GL Dressman, JB TI Dissolution testing as a prognostic tool for oral drug absorption: Dissolution behavior of glibenclamide SO PHARMACEUTICAL RESEARCH LA English DT Article DE dissolution test; glibenclamide; bioequivalence ID IN-VIVO PERFORMANCE; DOSAGE FORMS; PREDICTION; SYSTEMS AB Purpose. The dissolution behavior of two commercially available glibenclamide formulations was tested in various media. The aim of the study was to investigate whether the use of biorelevant dissolution media (BDM) would be advantageous over the use of standard media for predicting the in vivo performance of the two formulations. Methods. The dissolution tests were performed using USP 23 apparatus 2. Conventional buffers and USP media were compared with two BDM containing different amounts of lecithin and sodium taurocholate. Results. The dissolution of two drug powders was highly dependent on wetting, particle size, pH, and the composition of the medium used. In addition, the dissolution behavior of the two glibenclamide formulations showed differences in all media tested. The dissolution results of the two formulations were compared with those from an in vivo bioequivalence study undertaken by the central quality control laboratory of the German pharmacists (ZL). The bioequivalence criterion set by the ZL requires mon than 80% drug release within 10 minutes. Results in FaSSIF one of the BDMs, met the ZL criterion and this medium was also able to discriminate between the two formulations. This was not the case for the other media tested. Conclusions. The study indicates that BDM are better able to discriminate between glibenclamide formulations than standard dissolution media. C1 Univ Frankfurt, Inst Pharmazeut Technol, D-6000 Frankfurt, Germany. Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. LQS GmbH, Eschborn, Germany. US FDA, Rockville, MD 20857 USA. RP Dressman, JB (reprint author), Univ Frankfurt, Inst Pharmazeut Technol, D-6000 Frankfurt, Germany. RI Fachbereich14, Dekanat/C-8553-2015; OI Lobenberg, Raimar/0000-0002-0919-0213 FU PHS HHS [24 3816 00 95 TD 00] NR 24 TC 51 Z9 56 U1 1 U2 19 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD APR PY 2000 VL 17 IS 4 BP 439 EP 444 DI 10.1023/A:1007529020774 PG 6 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 322NT UT WOS:000087516200011 PM 10870988 ER PT J AU Yang, M Katoh, T Delongchamp, R Ozawa, S Kohshi, K Kawamoto, T AF Yang, M Katoh, T Delongchamp, R Ozawa, S Kohshi, K Kawamoto, T TI Relationship between NAT1 genotype and phenotype in a Japanese population SO PHARMACOGENETICS LA English DT Article DE NAT1; genotype; phenotype; Japanese ID N-ACETYLTRANSFERASE NAT1; POLYADENYLATION POLYMORPHISM; COLORECTAL ADENOMAS; ACETYLATION; GENE; N-ACETYLTRANSFERASE-1; ASSOCIATION; BLADDER; MUTATIONS; CANCER AB NAT1, which biotransforms many carcinogens, is genetically polymorphic. This polymorphism has been postulated as a mechanism for susceptibility differences in cancer, possibly due to NAT1 activity differences. However, the relationship between NAT1 genotype and phenotype is not clear. In our study of 110 Japanese, the frequency of the NAT1*10 allele (0.53, 95% confidence interval 0.46-0.59) was higher than others have observed in Caucasians (0,16). From genotype frequency studies, 26.4% of the subjects belonged to the NAT1*10/*10 genotype, 53.6% to the NAT1*4/*10 genotype and 20% to the NAT1*4/*4 genotype. Neither NAT1*3 nor NAT1*11 genotype was seen in these subjects. In female subjects, we found higher NAT1 activity in NAT1*4/*10 subjects than in NAT1*4/*4 subjects (n = 49; 2.63 versus 2.16 nmol/min/mg protein). NAT1 activity-difference between NAT1*4/*10 and NAT1*10/*10 was not statistically significant, Thus, not only the presence of NAT1*10 allele, but also other factors are suspected of increasing NAT1 activities. After full sequencing of 10 subjects, five individuals having the highest activities and five individuals having the lowest activities, we found NAT1*18A and NAT1*18B to be in the high activity group and the low activity group, respectively. The genotypes containing these variants were heterozygous, i.e. NAT1*4/*18A and NAT1*4/*18B. Due to rare frequencies of these variants, they cannot be considered as other effective, genetic factors on NAT1 activity. Age and tobacco smoking did not affect the relationship between NAT1 genotype and phenotype. Pharmacogenetics 10:225-252 (C) 2000 Lippincott Williams & Wilkins. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Univ Occupat & Environm Hlth, Sch Med, Dept Environm Hlth, Kitakyushu, Fukuoka 807, Japan. Univ Occupat & Environm Hlth, Sch Hlth Sci, Dept Hlth Informat Sci, Kitakyushu, Fukuoka 807, Japan. Natl Inst Hlth Sci, Biol Safety Res Ctr, Div Pharmacol, Jefferson, AR USA. Univ Occupat & Environm Hlth, Sch Med, Div Hyperbar Med, Kitakyushu, Fukuoka 807, Japan. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Yang, M (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 21 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD APR PY 2000 VL 10 IS 3 BP 225 EP 232 DI 10.1097/00008571-200004000-00003 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 309BW UT WOS:000086748500003 PM 10803678 ER PT J AU Gaylor, DW Kodell, RL AF Gaylor, DW Kodell, RL TI Percentiles of the product of uncertainty factors for establishing probabilistic reference doses SO RISK ANALYSIS LA English DT Article DE uncertainty factors; probabilistic reference dose ID NONCANCER RISK ASSESSMENT; RFD AB Exposure guidelines for potentially toxic substances are often based on a reference dose (RfD) that is determined by dividing a no-observed-adverse-effect-level (NOAEL), lowest-observed-adverse-effect-level (LOAEL), or benchmark dose (BD) corresponding to a low level of risk, by a product of uncertainty factors. The uncertainty factors for animal to human extrapolation, variable sensitivities among humans, extrapolation from measured subchronic effects to unknown results for chronic exposures, and extrapolation from a LOAEL to a NOAEL can be thought of as random variables that vary from chemical to chemical. Selected databases are examined that provide distributions across chemicals of inter- and intraspecies effects, ratios of LOAELs to NOAELs, and differences in acute and chronic effects, to illustrate the determination of percentiles for uncertainty factors. The distributions of uncertainty factors tend to be approximately lognormally distributed. The logarithm of the product of independent uncertainty factors is approximately distributed as the sum of normally distributed variables, making it possible to estimate percentiles for the product. Hence, the size of the products of uncertainty factors can be selected to provide adequate safety for a large percentage (e.g., approximately 95%) of RfDs. For the databases used to describe the distributions of uncertainty factors, using values of 10 appear to be reasonable and conservative. For the databases examined the following simple "Rule of 3s" is suggested that exceeds the estimated 95th percentile of the product of uncertainty factors: If only a single uncertainty factor is required use 33, for any two uncertainty Factors use 3 x 33 approximate to 100, for any three uncertainty factors use a combined factor of 3 x 100 = 300, and if all four uncertainty factors are needed use a total factor of 3 x 300 = 900. If near the 99th percentile is desired use another factor of 3. An additional factor may be needed for inadequate data or a modifying factor for other uncertainties (e.g., different routes of exposure) not covered above. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Gaylor, DW (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 22 TC 28 Z9 29 U1 0 U2 2 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD APR PY 2000 VL 20 IS 2 BP 245 EP 250 DI 10.1111/0272-4332.202023 PG 6 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 414LH UT WOS:000167667800009 PM 10859783 ER PT J AU Hedeker, D Siddiqui, O Hu, FB AF Hedeker, D Siddiqui, O Hu, FB TI Random-effects regression analysis of correlated grouped-time survival data SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Article ID PROPORTIONAL HAZARDS MODEL; GENERALIZED LINEAR-MODELS; ORDINAL DATA; SMOKING PREVENTION; LOGISTIC-REGRESSION; LONGITUDINAL DATA; CLUSTERED DATA; EM ALGORITHM; ODDS MODELS; DURATION AB Random-effects regression modelling is proposed for analysis of correlated grouped-time survival data. Two analysis approaches are considered. The first treats survival time as an ordinal outcome, which is either right-censored or not. The second approach treats survival time as a set of dichotomous indicators of whether the event occurred for time periods up to the period of the event or censor. For either approach both proportional hazards and proportional odds versions of the random-effects model are developed, while partial proportional hazards and odds generalizations are described for the latter approach. For estimation, a full-information maximum marginal likelihood solution is implemented using numerical quadrature to integrate over the distribution of multiple random effects. The quadrature solution allows some flexibility in the choice of distributions for the random effects; both normal and rectangular distributions are considered in this article. An analysis of a dataset where students are clustered within schools is used to illustrate features of random-effects analysis of clustered grouped-time survival data. C1 Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat MC 922, Ctr Hlth Policy Res, Chicago, IL 60612 USA. US FDA, Rockville, MD 20857 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. RP Hedeker, D (reprint author), Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat MC 922, Ctr Hlth Policy Res, 2121 W Taylor St,Room 525, Chicago, IL 60612 USA. EM hedeker@uic.edu FU NIDA NIH HHS [DA06307]; NIMH NIH HHS [MH56146] NR 58 TC 58 Z9 58 U1 2 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0962-2802 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PD APR PY 2000 VL 9 IS 2 BP 161 EP 179 DI 10.1191/096228000667253473 PG 19 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 333RL UT WOS:000088144500006 PM 10946432 ER PT J AU Harvath, L AF Harvath, L TI Food and Drug Administration's Proposed Approach to Regulation of Hematopoietic Stem/Progenitor Cell Products for Therapeutic use SO TRANSFUSION MEDICINE REVIEWS LA English DT Review C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Harvath, L (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 12 TC 6 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD APR PY 2000 VL 14 IS 2 BP 104 EP 111 DI 10.1016/S0887-7963(00)80002-4 PG 8 WC Hematology SC Hematology GA 302GL UT WOS:000086357300002 PM 10782496 ER PT J AU Graham, LJ DeBell, KE Veri, MC Stoica, B Mostowski, H Bonvini, E Rellahan, B AF Graham, LJ DeBell, KE Veri, MC Stoica, B Mostowski, H Bonvini, E Rellahan, B TI Differential effects of Cbl and 70Z/3 Cbl on T cell receptor-induced phospholipase C gamma-1 activity SO FEBS LETTERS LA English DT Article DE Cbl; 70Z/3 Cbl; phospholipase C gamma-1; Ca2+; T cell receptor signaling; NF-AT ID PROTOONCOGENE C-CBL; PHOSPHOTYROSINE-BINDING DOMAIN; GROWTH-FACTOR RECEPTOR; TYROSINE PHOSPHORYLATION; ANTIGEN RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; PROTEIN PRODUCT; V-CBL; SIGNAL-TRANSDUCTION; JURKAT CELLS AB We demonstrate that the differential effects Cbl and oncogenic 70Z/3 Cbl have on Ca2+/Ras-sensitive NF-AT reporters is partially due to their opposing ability to regulate phospholipase C gamma 1 (PLC gamma 1) activation as demonstrated by analysis of the activation of an NF-AT reporter construct and PLC gamma 1-mediated inositol phospholipid (PI) hydrolysis. Cbl overexpression resulted in reduced T cell receptor-induced Pf hydrolysis, in the absence of any effect on PLC gamma 1 tyrosine phosphorylation, In contrast, expression of 70Z/3 Cbl led to an increase in basal and OKT3-induced PLC gamma 1 phosphorylation and PI hydrolysis, These data indicate that Cbl and 70Z/3 Cbl differentially regulate PLC gamma 1 phosphorylation and activation, The implications of these data on the mechanism of Chi-mediated signaling regulation are discussed. (C) 2000 Federation of European Biochemical Societies. C1 US FDA, Ctr Biol Evaluat & Res, Immunobiol Lab, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Bonvini, E (reprint author), US FDA, Ctr Biol Evaluat & Res, Immunobiol Lab, Div Monoclonal Antibodies, HFM-564,Bldg 29B,Room 3NN10,29 Lincoln Dr MSC, Bethesda, MD 20892 USA. RI STOICA, BOGDAN/H-9782-2013 OI STOICA, BOGDAN/0000-0002-2501-6434 NR 58 TC 14 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAR 31 PY 2000 VL 470 IS 3 BP 273 EP 280 DI 10.1016/S0014-5793(00)01341-7 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 302FL UT WOS:000086355000009 PM 10745081 ER PT J AU Difilippantonio, MJ Zhu, J Chen, HT Meffre, E Nussenzweig, MC Max, EE Ried, T Nussenzweig, A AF Difilippantonio, MJ Zhu, J Chen, HT Meffre, E Nussenzweig, MC Max, EE Ried, T Nussenzweig, A TI DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation SO NATURE LA English DT Article ID V(D)J RECOMBINATION; MICE; P53; TRANSPOSITION; GROWTH; RAG1; GENE AB Cancer susceptibility genes have been classified into two groups: gatekeepers and caretakers(1). Gatekeepers are genes that control cell proliferation and death, whereas caretakers are DNA repair genes whose inactivation leads to genetic instability. Abrogation of both caretaker and gatekeeper function markedly increases cancer susceptibility. Although the importance of Ku80 in DNA double-strand break repair is well established, neither Ku80 nor other components of the non-homologous end-joining pathway are known to have a caretaker role in maintaining genomic stability. Here we show that mouse cells deficient for Ku80 display a marked increase in chromosomal aberrations, including breakage, translocations and aneuploidy. Despite the observed chromosome instabilities, Ku80(-/-) mice have only a slightly earlier onset of cancer(2,3). Loss of p53 synergizes with Ku80 to promote tumorigenesis such that all Ku80(-/-) p53(-/-) mice succumb to disseminated pro-B-cell lymphoma before three months of age. Tumours result from a specific set of chromosomal translocations and gene amplications involving IgH and c-Myc, reminiscent of Burkitt's lymphoma. We conclude that Ku80 is a caretaker gene that maintains the integrity of the genome by a mechanism involving the suppression of chromosomal rearrangements. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Dept Genet, NIH, Bethesda, MD 20892 USA. Rockefeller Inst, Lab Mol Immunol, New York, NY 10021 USA. Rockefeller Inst, Howard Hughes Med Inst, New York, NY 10021 USA. US FDA, Lab Cell Regulat, Ctr Biol Evaluat & Res, NIH, Bethesda, MD 20892 USA. RP Nussenzweig, A (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CA999999] NR 30 TC 383 Z9 391 U1 1 U2 8 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 30 PY 2000 VL 404 IS 6777 BP 510 EP 514 DI 10.1038/35006670 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 300MX UT WOS:000086257700052 PM 10761921 ER PT J AU O'Neill, RT AF O'Neill, RT TI Commentary on 'Alpha calculus in clinical trials: considerations and commentary for the new millennium' SO STATISTICS IN MEDICINE LA English DT Editorial Material ID MULTIPLE END-POINTS C1 US FDA, Ctr Drug Evaluat & Review, Off Biostat, Rockville, MD 20857 USA. RP O'Neill, RT (reprint author), US FDA, Ctr Drug Evaluat & Review, Off Biostat, 5600 Fishers Lane,Parklawn Bldg,Room 15B-45, Rockville, MD 20857 USA. NR 16 TC 10 Z9 10 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR 30 PY 2000 VL 19 IS 6 BP 785 EP 793 DI 10.1002/(SICI)1097-0258(20000330)19:6<785::AID-SIM520>3.3.CO;2-B PG 9 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 301UP UT WOS:000086328900004 PM 10734282 ER PT J AU Kang, SH Park, SM AF Kang, SH Park, SM TI Exact likelihood ratio test of independence of binary responses within clusters SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE correlated binary data; exchangeability; exact test; otolaryngology; ophthalmology; longitudinal study ID TRIAL AB We consider the exact likelihood ratio test of independence of binary responses within clusters developed by George and Kodell (J. Amer. Statist. Assoc., 1996, 91, 1602-1611) conditional on the sufficient statistics for the nuisance parameter under the null hypothesis. Only an exchangeability of responses within clusters is assumed for the distribution of the observed vector. Two formulas for the exact P-values are obtained. An algorithm is proposed to avoid unnecessary enumeration when the cluster size is two. We compare the exact and asymptotic P-values in several cases. (C) 2000 Elsevier Science B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Univ Wisconsin, Dept Stat, Madison, WI 53706 USA. NR 16 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD MAR 28 PY 2000 VL 33 IS 1 BP 15 EP 23 DI 10.1016/S0167-9473(99)00044-4 PG 9 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 294XE UT WOS:000085935100002 ER PT J AU Ang, CYW Liu, FF Rankin, JD AF Ang, CYW Liu, FF Rankin, JD TI Comparison of sample extraction methods for HPLC analyses of Hypericum perforatum leaves. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 91-AGFD BP U39 EP U39 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246100092 ER PT J AU Armstrong, DJ AF Armstrong, DJ TI Chemistry and food safety in 2025. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, NCFST, Summit, IL 60501 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 78-AGFD BP U37 EP U37 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246100079 ER PT J AU Beaucage, SL Wilk, A Grajkowski, A AF Beaucage, SL Wilk, A Grajkowski, A TI Deoxyribonucleoside cyclic N-acylphosphoramidites in the stereocontrolled synthesis of oligonucleoside phosphorothioates and their potential application to oligonucleotide synthesis on arrays. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 8-CARB BP U238 EP U238 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246101120 ER PT J AU Chou, MW Yang, YC Yan, J Churchwell, M Beger, R Doerge, DR Fu, PP AF Chou, MW Yang, YC Yan, J Churchwell, M Beger, R Doerge, DR Fu, PP TI Development of a P-32-postlabeling/HPLC method for detection of dehydroretonecine-modified DNA adducts in vitro and in vivo. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 182-ENVR BP U647 EP U647 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246103516 ER PT J AU Diachenko, GW Warner, CR AF Diachenko, GW Warner, CR TI Overview of potassium bromate in bakery products. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, Div Prod Manufacture & Use HFS245, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 205-AGFD BP U57 EP U57 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246100203 ER PT J AU Jackson, LS Reynolds, BH Keller, SE AF Jackson, LS Reynolds, BH Keller, SE TI Effect of apple quality and sanitation on patulin levels in apple cider. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 IIT, NCFST, Summit Argo, IL 60501 USA. US FDA, NCFST, Summit Argo, IL 60501 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 84-AGFD BP U38 EP U38 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246100085 ER PT J AU Lawrence, S Pitts, L Coleman, T Vann, W Lee, YC Betenbaugh, MJ AF Lawrence, S Pitts, L Coleman, T Vann, W Lee, YC Betenbaugh, MJ TI Metabolic engineering of glycosylation pathways in insect cells. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Dept Chem Engn, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. Human Genome Sci Inc, Rockville, MD 20850 USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 92-BIOT BP U173 EP U174 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246100821 ER PT J AU Liu, FF Ang, CYW Rankin, J Beger, R Heinze, T Freeman, P Lay, J AF Liu, FF Ang, CYW Rankin, J Beger, R Heinze, T Freeman, P Lay, J TI Determination of major biologically active components in St. John's Wort dietary supplements by high-performance liquid chromatography with photodiode-array detection and mass-spectrometry comfirmation. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RI Lay, Jackson/G-1007-2011 OI Lay, Jackson/0000-0003-3789-2527 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 35-ANYL BP U90 EP U90 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246100360 ER PT J AU Luu, HMD Hutter, JC AF Luu, HMD Hutter, JC TI Physiologically based pharmacokinetic (PBPK) model for octamethylcyclotetrasiloxane (D4). SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Div Mech & Mat Sci, Chem Grp, Ctr Devices & Radiol Hlth,Off Sci & Technol, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 55-TOXI BP U481 EP U481 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246102598 ER PT J AU Nowak, RM Pogribna, M Wilson, VL James, SJ Stanton, D Boehm, J Swenson, DH AF Nowak, RM Pogribna, M Wilson, VL James, SJ Stanton, D Boehm, J Swenson, DH TI MTHFR variants in Alzheimer's disease and control cells. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Saginaw Valley State Univ, Dept Chem, University Ctr, MI 48710 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Louisiana State Univ, Inst Mutagenesis, Baton Rouge, LA 70803 USA. Saginaw Valley State Univ, Dept Biol, University Ctr, MI 48710 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 605-CHED BP U386 EP U386 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246101996 ER PT J AU Tong, WD Perkins, R Fang, H Blair, R Branham, W Sheehan, D AF Tong, WD Perkins, R Fang, H Blair, R Branham, W Sheehan, D TI Computer-based priority setting of xenoestrogens. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 ROW Sci Inc, N Little Rock, AR 72079 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 90-ENVR BP U632 EP U632 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246103426 ER PT J AU Yu, SJ Welsh, WJ Tong, W Perkins, R Chen, Y Sheehan, D AF Yu, SJ Welsh, WJ Tong, W Perkins, R Chen, Y Sheehan, D TI Quantitative structure-activity relationship (QSAR) models for predicting the estrogenic activity of xenoestrogens to estrogen receptor alpha and beta subtypes. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Missouri, Dept Chem, St Louis, MO 63121 USA. Univ Missouri, Ctr Mol Elect, St Louis, MO 63121 USA. ROW Sci Inc, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 201-ENVR BP U650 EP U650 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246103535 ER PT J AU Dowell, JA Sancho, AR Anand, D Wolf, W AF Dowell, JA Sancho, AR Anand, D Wolf, W TI Noninvasive measurements for studying the tumoral pharmacokinetics of platinum anticancer drugs in solid tumors SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE anticancer drugs; pharmacokinetics; imaging; noninvasive measurements; cisplatin; carboplatin ID IN-VIVO; CISPLATIN; CHEMOTHERAPY; KINETICS; TISSUES; PT-195M AB An effective methodology to determine the amount of cisplatin or carboplatin at the solid tumor site in a noninvasive manner may enable clinicians to design drug regimens based on an individual's in situ pharmacokinetics. Such noninvasive methods may allow optimization of an individual's drug exposure at the target site, as well as provide a screening measure to determine individual efficacy based on exposure to these platinated drugs. Pt-195m appears to be the radionuclide of platinum most suitable for radiolabeling cisplatin or carboplatin, and an analysis is presented of the methods available for preparing such radiolabeled drugs. The use of this methodology is illustrated in detail in studies in animals, as well as some preliminary studies in humans. The animals used were Sprague Dawley rats bearing the Walker 256 carcinoma, and drug biodistribution was studied following administration of cisplatin or carboplatin radiolabeled with Pt-195m. This radionuclide permitted noninvasive imaging of the drug and its metabolites at the tumor site and at selected organs. The results obtained show an ability to estimate the amount of platinated drug species in the tumor environment using a noninvasive methodology. Various compartmental models were tested, some of which could be validated experimentally. This noninvasive method is able to provide individual estimates of the active component of the drug at the target site, and is therefore a method that can be implemented in human studies. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ So Calif, Sch Pharm, Dept Pharmaceut Sci, Los Angeles, CA 90089 USA. Skilled Care Pharm, IV Infus Serv, Monrovia, CA 91016 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Wyeth Ayerst Res, Radnor, PA 19087 USA. RP Wolf, W (reprint author), Univ So Calif, Sch Pharm, Dept Pharmaceut Sci, 1985 Zonal Ave, Los Angeles, CA 90089 USA. NR 38 TC 20 Z9 20 U1 0 U2 2 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 MAR 15 PY 2000 VL 41 IS 1 BP 111 EP 126 DI 10.1016/S0169-409X(99)00059-9 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 294WH UT WOS:000085933100008 PM 10699308 ER PT J AU Xing, L Tjarnlund, K Lindqvist, B Kaplan, GG Feigelstock, D Cheng, RH Casasnovas, JM AF Xing, L Tjarnlund, K Lindqvist, B Kaplan, GG Feigelstock, D Cheng, RH Casasnovas, JM TI Distinct cellular receptor interactions in poliovirus and rhinoviruses SO EMBO JOURNAL LA English DT Article DE cryo-EM and image reconstruction; picornavirus entry; poliovirus; rhinovirus; virus-receptor interaction ID ADHESION MOLECULE-1 ICAM-1; 3-DIMENSIONAL RECONSTRUCTION; CONFORMATIONAL ALTERATION; CRYOELECTRON MICROSCOPY; VIRUS; BINDING; DOMAINS; SURFACE; MACROMOLECULES; NEUTRALIZATION AB Receptor binding to human poliovirus type 1 (PV1/M) and the major group of human rhinoviruses (HRV) was studied comparatively to uncover the evolution of receptor recognition in picornaviruses. Surface plasmon resonance showed receptor binding to PV1/M with faster association and dissociation rates than to HRV3 and HRV16, two serotypes that have similar binding kinetics. The faster rate for receptor association to PV1/M suggested a relatively more accessible binding site. Thermodynamics for receptor binding to the viruses and assays for receptor-mediated virus uncoating showed a more disruptive receptor interaction with PV1/M than with HRV3 or HRV16. Cryoelectron microscopy and image reconstruction of receptor-PV1/M complexes revealed receptor binding to the 'wall' of surface protrusions surrounding the 'canyon', a depressive surface in the capsid where the rhinovirus receptor binds. These data reveal more exposed receptor-binding sites in poliovirus than rhinoviruses, which are less protected from immune surveillance but more suited for receptor-mediated virus uncoating and entry at the cell surface. C1 Karolinska Inst, Novum, Dept Biosci, Ctr Biotechnol, S-14157 Huddinge, Sweden. US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis Viruses, Bethesda, MD 20892 USA. RP Cheng, RH (reprint author), Karolinska Inst, Novum, Dept Biosci, Ctr Biotechnol, S-14157 Huddinge, Sweden. RI Cheng, Holland/A-8973-2008; Casasnovas, Jose/L-6299-2014 OI Casasnovas, Jose/0000-0002-2873-6410 NR 46 TC 85 Z9 86 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 15 PY 2000 VL 19 IS 6 BP 1207 EP 1216 DI 10.1093/emboj/19.6.1207 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 296NU UT WOS:000086031100006 PM 10716921 ER PT J AU Blakely, SR Jenkins, MY Mitchell, GV AF Blakely, SR Jenkins, MY Mitchell, GV TI Lutein enhances hepatic vitamin C levels in Zucker lean but not obese female rats SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Washington, DC 20204 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 15 PY 2000 VL 14 IS 4 BP A235 EP A235 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101363 ER PT J AU Brown, AT Moursi, MM Williams, K Wise, CK Poirier, LA AF Brown, AT Moursi, MM Williams, K Wise, CK Poirier, LA TI Intimal hyperplasia (IH) correlates with plasma homocysteine (HCys), methylenetetrahydrofolate reductase (MTHFR) and hepatic S-adenosylmethionine (SAM) in a rat carotid endarterectomy (CEA) model. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Arkansas Med Sci, Dept Surg, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Biometry, Little Rock, AR 72205 USA. US FDA, Div Mol Epidemiol, NCTR, Jefferson, AR 72709 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 15 PY 2000 VL 14 IS 4 BP A496 EP A496 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102868 ER PT J AU Chanmugam, P Guthrie, J Cecelio, S Morton, J Basiotis, P Anand, R AF Chanmugam, P Guthrie, J Cecelio, S Morton, J Basiotis, P Anand, R TI Food group sources of increased fat and energy intakes in adults. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Louisiana State Univ, Sch Human Ecol, Baton Rouge, LA 70803 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. USDA, Ctr Nutr Policy & Promot, Washington, DC 20036 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 15 PY 2000 VL 14 IS 4 BP A222 EP A222 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101285 ER PT J AU Collins, M Blakely, SR Grundel, E Khachik, F AF Collins, M Blakely, SR Grundel, E Khachik, F TI Vitamin E enhances lutein bioavailability in Zucker lean but not obese female ra SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Washington, DC 20204 USA. RI Khachik, Frederick/C-5055-2009 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 15 PY 2000 VL 14 IS 4 BP A235 EP A235 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101359 ER PT J AU Herbert, A Blakely, SR Mitchell, GV Jenkins, MY AF Herbert, A Blakely, SR Mitchell, GV Jenkins, MY TI Vitamin C and lutein interact to increase glutathione peroxidase (GSHPx) and superoxide dismutase (SOD) in Zucker lean but not obese female SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Washington, DC 20204 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 15 PY 2000 VL 14 IS 4 BP A235 EP A235 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101360 ER PT J AU James, SJ Yi, P Melnyk, S Hine, RJ Pogribny, IP AF James, SJ Yi, P Melnyk, S Hine, RJ Pogribny, IP TI Plasma levels of S-adenosylhomocysteine increase linearly with homocysteine levels and lymphocyte DNA hypomethylation SO FASEB JOURNAL LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Little Rock, AR 72202 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 15 PY 2000 VL 14 IS 4 BP A202 EP A202 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101169 ER PT J AU Lester, DS Pine, PS Davis, HD Hanig, JP AF Lester, DS Pine, PS Davis, HD Hanig, JP TI Innovative imaging approaches for detecting brain neurotoxicity SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Ctr Drug Evaluat Res, Div Appl Pharmac Res, Laurel, MD 20708 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 15 PY 2000 VL 14 IS 4 BP A568 EP A568 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918103288 ER PT J AU Melnyk, S Pogribny, IP Pogribna, M James, SJ AF Melnyk, S Pogribny, IP Pogribna, M James, SJ TI A new HPLC method for the measurement of S-adenosylmethionine and S-adenosylhomocysteine using coulometric electrochemical detection SO FASEB JOURNAL LA English DT Meeting Abstract C1 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 15 PY 2000 VL 14 IS 4 BP A230 EP A230 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101333 ER PT J AU Park, YK Yetley, EA AF Park, YK Yetley, EA TI Estimation of nutrient intakes from dietary supplements in NHANES III(1988-94): Impact of assumptions used to assign default potency. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Washington, DC 20204 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 15 PY 2000 VL 14 IS 4 BP A559 EP A559 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918103234 ER PT J AU Park, YK McDowell, MA Barton, CN Calvo, MS AF Park, YK McDowell, MA Barton, CN Calvo, MS TI Phylloquinone intakes of the US population: Estimates from NHANES III (1988-94). SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Washington, DC 20204 USA. NCHS, Hyattsville, 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 15 PY 2000 VL 14 IS 4 BP A221 EP A221 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101282 ER PT J AU Pogribna, M Pogribny, IP Melnyk, S James, SJ AF Pogribna, M Pogribny, IP Melnyk, S James, SJ TI Exogenous S-adenosylhomocysteine independently induces DNA hypomethylation and increases DNA methyltransferase activity in cultured rat and human fibroblasts SO FASEB JOURNAL LA English DT Meeting Abstract C1 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 15 PY 2000 VL 14 IS 4 BP A769 EP A769 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918104447 ER PT J AU Whittaker, P Dunkel, VC AF Whittaker, P Dunkel, VC TI Effects of increasing iron supplementation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Washington, DC 20204 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 15 PY 2000 VL 14 IS 4 BP A753 EP A753 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918104357 ER PT J AU Yi, P Hobbs, C Melnyk, S Sherman, S Gravel, R Wu, Q Rozen, R James, SJ AF Yi, P Hobbs, C Melnyk, S Sherman, S Gravel, R Wu, Q Rozen, R James, SJ TI Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) and in the methionine synthase reductase (MTRR) genes increase maternal risk of Down syndrome SO FASEB JOURNAL LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Arkansas Childrens Hosp, Little Rock, AR 72202 USA. Emory Univ, Atlanta, GA 30322 USA. McGill Univ, Montreal, PQ, Canada. 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 15 PY 2000 VL 14 IS 4 BP A231 EP A231 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101339 ER PT J AU Byrnes, GA Miller, SA Mazur, DO Grossman, LW AF Byrnes, GA Miller, SA Mazur, DO Grossman, LW TI Laser characteristics through fundus contact treatment lenses: Risk potential for anterior segment complications. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Natl Naval Med Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 20B20 BP S4 EP S4 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700021 ER PT J AU DiCarlo, CD Chenault, MV Borst, DE AF DiCarlo, CD Chenault, MV Borst, DE TI The unique lens crystallin composition of the Fat Sand Rat, Psammomys obesus. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3109B207 BP S585 EP S585 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703179 ER PT J AU King, JF Chenault, VM Ansari, RR AF King, JF Chenault, VM Ansari, RR TI Detection of diabetic cataracts in psammomys obesus (sand rat) using Dynamic Light Scattering. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NASA, Glenn Res Ctr, NCMR, Cleveland, OH 44135 USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1120B495 BP S214 EP S214 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701119 ER PT J AU Kusakabe, K Xin, KQ Katoh, H Sumino, K Hagiwara, E Kawamoto, S Okuda, K Miyagi, Y Aoki, I Nishioka, K Klinman, D Okuda, K AF Kusakabe, K Xin, KQ Katoh, H Sumino, K Hagiwara, E Kawamoto, S Okuda, K Miyagi, Y Aoki, I Nishioka, K Klinman, D Okuda, K TI The timing of GM-CSF expression plasmid administration influences the Th1/Th2 response induced by an HIV-1-specific DNA vaccine SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING-FACTOR; IMMUNODEFICIENCY-VIRUS TYPE-1; CELL-MEDIATED-IMMUNITY; PERIPHERAL LYMPHOID ORGANS; FACTOR PLUS INTERLEUKIN-4; CYTOTOXIC-T-LYMPHOCYTES; DENDRITIC CELLS; IN-VIVO; RT-PCR; IMMUNIZATION AB The mechanism of immune activation induced by a plasmid-encoding GM-CSF (pGM-CSF), administered in combination with a DNA vaccine encoding the envelope of HIV, was studied. Injecting pGM-CSF i.m. into mice 3 days before DNA vaccination primarily induced a Th2 response. Simultaneous administration of the DNA vaccine plus pGM-CSF activated both a Th1 and a Th2 response. When the plasmid was injected 3 days after DNA vaccination, enhancement of Th1 immunity predominated. These results suggest that the timing of cytokine expression determines the phenotype of the resultant Th response. After 3 days of pGM-CSF injection, the increased percentages of CD11c(+), CD8(+) cells were observed in the regional lymph nodes. In addition, many infiltrated cells, including S-100 protein-positive cells, were found in the pGM-CSF-injected tissue. The importance of these S-100(+) cells or both CD8(+) and CD11c(+) cells, especially that of dendritic cells (DCs), was also studied. DCs derived from bone marrow and cultured in RPMI 1640 medium containing IL-4 and GM-CSF were incubated with DNA vaccine and then transferred into naive mice. Mice receiving DCs showed strong HIV-1-specific Th2 immune responses. Our results suggest that DCs play important roles in the activation or modification of the Th2-type immune response induced by DNA vaccination. C1 Yokohama City Univ, Sch Med, Dept Bacteriol, Kanazawa Ku, Yokohama, Kanagawa 236004, Japan. Yokohama City Univ, Sch Med, Dept Internal Med, Kanazawa Ku, Yokohama, Kanagawa 236004, Japan. Yokohama City Univ, Sch Med, Dept Pathol, Kanazawa Ku, Yokohama, Kanagawa 236004, Japan. Tokyo Dent Coll, Dept Microbiol, Chiba, Japan. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Okuda, K (reprint author), Yokohama City Univ, Sch Med, Dept Bacteriol, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 236004, Japan. NR 57 TC 105 Z9 116 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2000 VL 164 IS 6 BP 3102 EP 3111 PG 10 WC Immunology SC Immunology GA 291YF UT WOS:000085766800033 PM 10706700 ER PT J AU Wilk, A Grajkowski, A Phillips, LR Beaucage, SL AF Wilk, A Grajkowski, A Phillips, LR Beaucage, SL TI Deoxyribonucleoside cyclic N-acylphosphoramidites as a new class of monomers for the stereocontrolled synthesis of oligothymidylyl- and oligodeoxycytidylyl- phosphorothioates SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NUCLEOSIDE BICYCLIC OXAZAPHOSPHOLIDINES; PHASE STEREOSELECTIVE SYNTHESIS; SULFUR-TRANSFER REAGENT; 3H-1,2-BENZODITHIOL-3-ONE 1,1-DIOXIDE; OLIGO(NUCLEOSIDE PHOSPHOROTHIOATE)S; DINUCLEOTIDE PHOSPHOROTHIOATES; NONBONDED INTERACTIONS; OLIGODEOXYRIBONUCLEOTIDES; OLIGONUCLEOTIDES; CLEAVAGE AB A simple and straightforward synthesis of the pyrimidine 2'-deoxyribonucleoside cyclic N-acylphosphoramidites R-P-1 and S-P-1 is described. Specifically, (+/-)-2-amino-1-phenylethanol 2 was chemoselectively N-acylated to 4 by treatment with ethyl fluoroacetate 3 followed by reaction with hexaethylphosphorus triamide to afford the cyclic N-acylphosphoramidite 5 as a mixture of diastereomeric rotamers (5a and 5b). Condensation of N-4-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2-deoxycytidine 8 with 5 in the presence of 1H-tetrazole gave, after silica gel chromatography, pure R-P-1 and S-P-1. P-31 NMR studies indicated that when Rp-l or Sp-l is reacted with 3'-O-acetylthymidine and N,N,N',N'-tetramethylguanidine in CD3CN, the dinucleoside phosphotriester S-P-9 or R-P-9 is formed in near quantitative yield with total P-stereospecificity (delta(P) 144.2 or 143.9 ppm, respectively). Sulfurization of Sp-9 or R-P-9 generated the P-stereodefined dinucleoside phosphorothioate R-P-11 or S-P-11 (delta(P) 71.0 or 71.2 ppm, respectively). The 2'-deoxycytidine cyclic N-acylphosphoramidite derivatives R-P-1 and S-P-1 were subsequently applied to the solid-phase synthesis of [R-P,R-P]- and [S-P,S-P] -trideoxycytidilyl diphosphorothioate d(CPSCPSC), and [R-P,S-P,R-P]-tetradeoxycytidilyl triphosphorothioate d(CPSCPSCPSC) Following deprotection, reversed-phase (RP) HPLC analysis of these oligonucleotide analogues showed a single peak for each oligomer. By comparison, RP-HPLC analysis of purified P-diastereomeric d(CPSCPSC) and d(CPSCPSCPSC) prepared from standard 2-cyanoethyl deoxyribonucleoside phosphoramidites exhibited 4 and 8 peaks, respectively, each peak corresponding to a specific P-diastereomer (see Figure 3A). The thymidine cyclic N-acylphosphoramidite derivatives R-P-14 and S-P-14 were also prepared, purified, and used successfully in the solid-phase synthesis of [R-P](11)-d[(T-PS)(11)T]. Thus, the application of deoxyribonucleoside cyclic N-acyl phosphoramidites to P-stereocontrolled synthesis of oligodeoxyribonucleoside phosphorothioates may offer a compelling alternative to the methods currently used for such syntheses. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Frederick, MD 21701 USA. RP Beaucage, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 51 TC 60 Z9 60 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAR 15 PY 2000 VL 122 IS 10 BP 2149 EP 2156 DI 10.1021/ja991773u PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 296WZ UT WOS:000086050900002 ER PT J AU Henney, JE Shuren, JE AF Henney, JE Shuren, JE TI Direct sale of sildenafil (Viagra) to consumers over the Internet. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Henney, JE (reprint author), US FDA, Rockville, MD 20857 USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 9 PY 2000 VL 342 IS 10 BP 740 EP + PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 290ZW UT WOS:000085708800023 PM 10712127 ER PT J AU Venable, RM Brooks, BR Pastor, RW AF Venable, RM Brooks, BR Pastor, RW TI Molecular dynamics simulations of gel (L-beta I) phase lipid bilayers in constant pressure and constant surface area ensembles SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID COMPUTER-SIMULATION; DIPALMITOYLPHOSPHATIDYLCHOLINE BILAYER; LIQUID/LIQUID INTERFACES; PHOSPHOLIPID-BILAYER; BOUNDARY-CONDITIONS; FLUID MEMBRANES; TENSION; PHOSPHATIDYLCHOLINE; TRANSITION; DISORDER AB The results of a series of molecular dynamics simulations of the gel state of a dipalmitoylphosphatidylcholine bilayer at 293 K are described. The simulations, ranging from 40 ps to 2.5 ns, show clearly that: a flexible cell geometry is essential during equilibration; Ewald summation of electrostatics is superior to spherical cutoff methods; water exchange with the carbonyl group of chain 2 takes place on the ns time scale, while there is almost no hydration of chain 1. There is overall good agreement (D-spacing, chain tilt, fraction gauche, and area compressibility modulus) with experiment, though the surface area per lipid is slightly underestimated. The randomization of torsion 1 of chain 2 from exclusively gauche minus (as specified in the initial condition modeled from the crystal structure of a related lipid) to a mixture of g+/g- over the course of approximately 2 ns is a critical feature of the study. The torsional equilibration proceeded steadily when simulating at constant surface tension, but was effectively quenched by simulation at constant area. The associated presence of conformational degeneracy of this torsion, and conformational disorder in the upper region of chain 2, is most likely associated with the seemingly anomalous infrared (IR) results for gauche bonds in the upper region of the chains. It may also be a characteristic of the gel phase, and be related to the long time required for the gel to subgel transition. [S0021-9606(00)50210-4]. C1 US FDA, Phys Lab, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NHLBI, Computat Biophys Sect, Biophys Chem Lab, Bethesda, MD 20892 USA. RP Venable, RM (reprint author), US FDA, Phys Lab, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NR 44 TC 76 Z9 76 U1 0 U2 9 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD MAR 8 PY 2000 VL 112 IS 10 BP 4822 EP 4832 DI 10.1063/1.481085 PG 11 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 288LG UT WOS:000085563800043 ER PT J AU Kaczmarek, RG Beaulieu, MD Kessler, LG AF Kaczmarek, RG Beaulieu, MD Kessler, LG TI Medical device tracking: Results of a case study of the implantable cardioverter defibrillator SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID OUTLET STRUT FRACTURE; PROSTHESIS AB Case reports were received of a fatal tachycardia caused by a malfunction of an implantable cardioverter defibrillator (ICD), a device that is subject to the tracking regulations of the Food and Drug Administration's Center for Devices and Radiological Health. The case reports led to a decision to notify 5,604 patients of the need for reprogramming of their ICDs to prevent the tachycardia. In the first 60 days, a total of 98.7% of the patients were successfully located and their devices reprogrammed. Multiple logistic regression analysis wets conducted to examine an extensive array of factors that might have been related to the time to reprogramming. Patient-specific factors such as age, sex, and ejection fraction did not serve as a barrier to reprogramming in the first week (p = NS). patients whose regular physician had >5 patients with the ICD subject to the recall were significantly more likely to have their ICDs reprogrammed in the first week (odds ratio [OR] 2.11, 95% confidence interval [CI] 1.85 to 2.43, p <0.001). Patients who changed physicians were significantly less likely to undergo reprogramming in the first week (OR 0.73, 95% CI 0.63 to 0.86, p <0.001). The experience of the recall of this tracked device is highly encouraging because it demonstrates that most tracked device recipients can be successfully located and receive medical intervention. Although tracking devices is a manufacturer's responsibility, the clinical community plays a critical role in its success. This report highlights the importance of understanding that role among physicians. (C)2000 by Excerpta Medico, Inc. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. St Jude Med Cardiac Rhythm Management Div, Sylmar, CA USA. RP Kaczmarek, RG (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-541,1350 Piccard Dr, Rockville, MD 20850 USA. NR 6 TC 4 Z9 4 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 2000 VL 85 IS 5 BP 588 EP 592 DI 10.1016/S0002-9149(99)00816-4 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 289ZB UT WOS:000085650900013 PM 11078272 ER PT J AU Casamassimi, A De Luca, A Agrawal, S Stromberg, K Salomon, DS Normanno, N AF Casamassimi, A De Luca, A Agrawal, S Stromberg, K Salomon, DS Normanno, N TI EGF-related antisense oligonucleotides inhibit the proliferation of human ovarian carcinoma cells SO ANNALS OF ONCOLOGY LA English DT Article DE antisense oligonucleotides; EGF-related peptides; ovarian carcinoma ID GROWTH-FACTOR RECEPTOR; DIFFERENTIAL IMMUNOHISTOCHEMICAL DETECTION; MAMMARY EPITHELIAL-CELLS; FACTOR-RELATED PROTEINS; FACTOR-ALPHA; COLORECTAL TUMORS; SUPERGENE FAMILY; MESSENGER-RNA; CANCER CELLS; AMPHIREGULIN AB Background: The epidermal growth factor (EGF)-like peptides CRIPTO (CR), amphiregulin (AR) and transforming growth factor alpha (TGF alpha) are expressed in human ovarian carcinomas. Materials and methods: The expression of AR, CR and TGF alpha in ovarian carcinoma cell lines was assessed by immunocytochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). The antiproliferative effects of antisense phosphorothioate oligodeoxynucleotides (AS S-Oligos) directed against either AR, CR or TGF alpha was evaluated by using a clonogenic assay. Results: A majority of the ovarian carcinoma cell lines was found to express TGF alpha, AR and CR mRNAs and proteins. AS S-Oligos directed against either AR, CR or TGF alpha were able to inhibit the anchorage-independent growth of NIH:OVCAR3 and NIH:OVCAR8 cells in a dose dependent manner. A 30%-50% growth inhibition was observed at a 2 mu M concentration of the AS S-Oligos. Treatment of these cells with combinations of EGF-related AS S-Oligos resulted in a more significant growth inhibition when compared to treatment with a single AS S-oligo. A 60%-75% growth inhibition was observed using combinations of AR, CR and TGF alpha AS S-oligos at a total concentration of 2 mu M. An additive growth-inhibitory effect occurred when ovarian carcinoma cells were exposed to the AS S-Oligos after treatment with either paclitaxel or cis-platinum. Conclusions: These data suggest that EGF-related peptides function as autocrine growth factors in ovarian carcinoma cells, and that they might represent targets for experimental therapy of ovarian carcinoma. C1 ITN Fdn Pascale, Novel Therapeut Approaches Sect, I-80131 Naples, Italy. Hybridon Inc, Cambridge, MA USA. NCI, Tumor Growth Factor Sect, LTIB, NIH, Bethesda, MD 20892 USA. US FDA, DCB, CBER, Bethesda, MD 20014 USA. RP Normanno, N (reprint author), ITN Fdn Pascale, Novel Therapeut Approaches Sect, I-80131 Naples, Italy. RI De Luca, Antonella/J-8737-2016 OI De Luca, Antonella/0000-0001-5762-447X NR 29 TC 23 Z9 24 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 2000 VL 11 IS 3 BP 319 EP 325 DI 10.1023/A:1008350811639 PG 7 WC Oncology SC Oncology GA 297UE UT WOS:000086100400018 PM 10811499 ER PT J AU Landry, ML Stanat, S Biron, K Brambilla, D Britt, W Jokela, J Chou, SW Drew, WL Erice, A Gilliam, B Lurain, N Manischewitz, J Miner, R Nokta, M Reichelderfer, P Spector, S Weinberg, A Yen-Lieberman, B Crumpacker, C AF Landry, ML Stanat, S Biron, K Brambilla, D Britt, W Jokela, J Chou, SW Drew, WL Erice, A Gilliam, B Lurain, N Manischewitz, J Miner, R Nokta, M Reichelderfer, P Spector, S Weinberg, A Yen-Lieberman, B Crumpacker, C CA AIDS Clin Trials Grp CMV Resistance Working Grp TI A standardized plaque reduction assay for determination of drug susceptibilities of cytomegalovirus clinical isolates SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IMMUNOCOMPROMISED PATIENTS; GANCICLOVIR; RESISTANT; FOSCARNET; VIRUS; UL97; AIDS AB Twelve laboratories collaborated in formulating and testing a standardized plaque reduction assay for cyto megalovirus (CMV) cell-associated clinical isolates, Four characterized and plaque-purified CMV strains, as well as six coded clinical isolates obtained after antiviral therapy, were distributed and tested. Good agreement was obtained for four of the clinical isolates, but a broad distribution of results was obtained for two Isolates. Analysis of these results indicates the problems associated,vith clinical isolates, including the large genetic variability and the highly cell-associated phenotype. This collaborative effort, by addressing these problems, represents a significant step toward the development of a standardized assay. C1 Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06520 USA. Glaxo Wellcome, Res Triangle Pk, NC USA. New England Res Inst, Watertown, MA 02172 USA. Univ Alabama, Birmingham, AL USA. Univ Oregon, Portland, OR USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Minnesota, Minneapolis, MN USA. Univ N Carolina, Chapel Hill, NC USA. Rush Med Coll, Chicago, IL 60612 USA. US FDA, Bethesda, MD 20014 USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. Univ Texas, Galveston, TX 77555 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Harvard Univ, Boston, MA 02115 USA. RP Landry, ML (reprint author), Yale Univ, Sch Med, Dept Lab Med, 333 Cedar St, New Haven, CT 06520 USA. FU NIAID NIH HHS [U01 AI038858, AI32766, AI38858, AI41690] NR 13 TC 77 Z9 80 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 2000 VL 44 IS 3 BP 688 EP 692 DI 10.1128/AAC.44.3.688-692.2000 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 285QF UT WOS:000085399200034 PM 10681339 ER PT J AU Hammer, SM Pedneault, L AF Hammer, SM Pedneault, L TI Antiretroviral resistance testing comes of age SO ANTIVIRAL THERAPY LA English DT Editorial Material ID DRUG-RESISTANCE; INFECTION C1 US FDA, AVAC Meeting Chair, Rockville, MD 20857 USA. RP Hammer, SM (reprint author), US FDA, AVAC Meeting Chair, Rockville, MD 20857 USA. NR 14 TC 9 Z9 9 U1 0 U2 0 PU INT MEDICAL PRESS PI LONDON PA 125 HIGH HOLBORN, LONDON WC1V 6QA, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PD MAR PY 2000 VL 5 IS 1 BP 23 EP 26 PG 4 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 316RZ UT WOS:000087183000006 PM 10846589 ER PT J AU DeGruttola, V Dix, L D'Aquila, R Holder, D Phillips, A Ait-Khaled, M Baxter, J Clevenbergh, P Hammer, S Harrigan, R Katzenstein, D Lanier, R Miller, M Para, M Yerly, S Zolopa, A Murray, J Patick, A Miller, V Castillo, S Pedneault, L Mellors, J AF DeGruttola, V Dix, L D'Aquila, R Holder, D Phillips, A Ait-Khaled, M Baxter, J Clevenbergh, P Hammer, S Harrigan, R Katzenstein, D Lanier, R Miller, M Para, M Yerly, S Zolopa, A Murray, J Patick, A Miller, V Castillo, S Pedneault, L Mellors, J TI The relation between baseline HIV drug resistance and response to antiretroviral therapy: re-analysis of retrospective and prospective studies using a standardized data analysis plan SO ANTIVIRAL THERAPY LA English DT Article ID REVERSE-TRANSCRIPTASE; PROTEASE; MUTATIONS; FAILURE AB To assess the relation between resistance to antiretroviral drugs for treatment of HIV-1 infection and virological response to therapy, results from 12 different studies were re-analysed according to a standard data analysis plan. These studies included nine clinical trials and three observational cohorts. The primary end-point in our analyses was virological failure by week 24. Baseline factors that were investigated as predictors of virological failure were plasma HIV-1 RNA, the number and type of new antiretroviral drugs in the regimen, and viral susceptibility to the drugs in the regimen, determined by genotyping or phenotyping methods. These analyses confirmed the importance of both genotypic and phenotypic drug resistance as predictors of virological failure, whether these factors were analysed separately or adjusted for other baseline confounding factors. In most of the re-analysed studies, the odds of virological failure were reduced by about twofold for each additional drug in the regimen to which the patient's virus was sensitive by genotyping methods, and by about two- to threefold for each additional drug that was sensitive by phenotyping. C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. Pittsburgh VA HealthCare Syst, Pittsburgh, PA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Merck Co Inc, W Point, PA USA. Royal Free Hosp & Univ Coll Med Sch, London, England. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA. Hop Archet, Nice, France. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. Gilead Sci, Foster City, CA USA. Ohio State Univ, Sch Med, Columbus, OH 43210 USA. Univ Hosp Geneva, Geneva, Switzerland. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Agouron Pharmaceut, La Jolla, CA USA. Univ Frankfurt, D-6000 Frankfurt, Germany. RP Mellors, J (reprint author), Univ Pittsburgh, Pittsburgh, PA 15260 USA. RI Phillips, Andrew/B-4427-2008 OI Phillips, Andrew/0000-0003-2384-4807 FU NIAID NIH HHS [AI28076-09] NR 20 TC 252 Z9 259 U1 0 U2 7 PU INT MEDICAL PRESS PI LONDON PA 125 HIGH HOLBORN, LONDON WC1V 6QA, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PD MAR PY 2000 VL 5 IS 1 BP 41 EP 48 PG 8 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 316RZ UT WOS:000087183000009 PM 10846592 ER PT J AU Laessig, KA Murray, JS Chikami, G AF Laessig, KA Murray, JS Chikami, G TI The role of resistance testing in clinical trial design and product labelling: a regulatory perspective SO ANTIVIRAL THERAPY LA English DT Article ID HIV-INFECTION; THERAPY AB Assays that attempt to characterize HIV susceptibility or resistance are among the latest technologies that are likely to impact HIV clinical trial design, antiretroviral drug development and patient management. However, at present the Food and Drug Administration (FDA) have yet to approve any phenotypic or genotypic HIV resistance assay and the role of resistance testing in clinical management of patients and in drug development is ill defined. In November 1999, the Division of Antiviral Drug Products at the FDA convened a meeting of its advisory committee to consider the available information about HIV resistance testing, and to generate some recommendations about how these assays could be utilized in antiretroviral drug development. In addition, the committee was presented with several hypothetical regulatory scenarios in order to illustrate how HIV resistance testing might be incorporated in antiretroviral drug development and drug labelling. In this article, we discuss the regulatory history of resistance testing in antimicrobial drug development, the current use of resistance testing for antiretrovirals, as well as a summary of the hypothetical scenarios that were presented to the committee and the discussion of the committee members regarding those scenarios. C1 US FDA, Ctr Drug Evaluat & Res, Div Antiviral Drug Prod, Rockville, MD 20857 USA. RP Murray, JS (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Antiviral Drug Prod, 5600 Fishers Lane,HFD-530, Rockville, MD 20857 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU INT MEDICAL PRESS PI LONDON PA 125 HIGH HOLBORN, LONDON WC1V 6QA, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PD MAR PY 2000 VL 5 IS 1 BP 77 EP 83 PG 7 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 316RZ UT WOS:000087183000014 PM 10846597 ER PT J AU Moody, JD Heinze, TM Hansen, EB Cerniglia, CE AF Moody, JD Heinze, TM Hansen, EB Cerniglia, CE TI Metabolism of the ethanolamine-type antihistamine diphenhydramine (Benadryl)(TM) by the fungus Cunninghamella elegans SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID IONIZATION MASS-SPECTROMETRY; CHEMICAL IONIZATION; N-OXIDE; TRANSFORMATIONS; TRIPELENNAMINE; METHAPYRILENE; THENYLDIAMINE; HYDROGEN AB Two strains of the filamentous fungus Cunninghamella elegans (ATCC 9245 and ATCC 36112) were grown in Sabouraud dextrose broth and screened for the ability to metabolize the ethanolamine-type antihistamine diphenhydramine. Based on the amount of parent drug recovered after 7 days incubation, both C, elegans strains metabolized approximately 74% of the diphenhydramine, 58% of this being identified as organic extractable metabolites. The organic extractable metabolites were isolated by reversed-phase high-performance liquid chromatography and identified by analyzing their mass and nuclear magnetic resonance spectra. Desorption chemical ionization mass spectrometry (DCIMS) with deuterated ammonia was used to differentiate possible isobaric diphenhydramine metabolites and to probe the mechanisms of ion formation under ammonia DCIMS conditions. C. elegans transformed diphenhydramine by demethylation, oxidation, and N-acetylation. The major metabolites observed were diphenhydramine-N-oxide (3%), N-desmethyldiphenhydramine (30%), N-acetyldidesmethyldiphenhydramine (13%), and N-acetyl-N-desmethyldiphenhydramine (12%). These compounds are known mammalian metabolites of diphenhydramine and may be useful for further toxicological studies. 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. NR 15 TC 12 Z9 12 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD MAR PY 2000 VL 53 IS 3 BP 310 EP 315 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 298ZX UT WOS:000086172300010 PM 10772471 ER PT J AU Rider, LG Miller, FW AF Rider, LG Miller, FW TI Idiopathic inflammatory muscle disease: clinical aspects SO BEST PRACTICE & RESEARCH IN CLINICAL RHEUMATOLOGY LA English DT Article DE myositis; classification; prognosis; autoantibody ID MYOSITIS-SPECIFIC AUTOANTIBODIES; DERMATOMYOSITIS SINE MYOSITIS; INTERSTITIAL LUNG-DISEASE; VON-WILLEBRAND-FACTOR; TERM FOLLOW-UP; JUVENILE DERMATOMYOSITIS; POLYMYOSITIS-DERMATOMYOSITIS; IMMUNOGENETIC FEATURES; CUTANEOUS CHANGES; MYOPATHIES AB Although much remains to be learned about the immune-mediated myositis syndromes, information generated from recent studies in a number of areas may assist physicians in patient management. Topics reviewed here include: data supporting the association of myositis with cancer and the appropriate evaluations for malignancy in a myositis patient; an approach to the assessment of patients with dermatomyositis sine myositis; the usefulness of the clinicopathological and serological classifications; a discussion of whether childhood and adult myositis are the same or different entities; a review of those prognostic factors to consider in the clinical management of myositis patients; current approaches and their limitations for assessing disease activity and damage. To improve our limited understanding of the myositis syndromes, national and international collaborations are needed to obtain the necessary numbers of subjects, given the rarity and heterogeneity of these disorders. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mol & Dev Immunol, Bethesda, MD 20892 USA. RP Rider, LG (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mol & Dev Immunol, Bldg 29B,Room 2G11,HFM-561,8800 Rockville Pike, Bethesda, MD 20892 USA. OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 NR 55 TC 29 Z9 30 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-6942 J9 BEST PRACT RES CL RH JI Best Pract. Res. Clin. Rheumatol. PD MAR PY 2000 VL 14 IS 1 BP 37 EP 54 DI 10.1053/berh.1999.0076 PG 18 WC Rheumatology SC Rheumatology GA 321XV UT WOS:000087481400003 PM 10882213 ER PT J AU Sierra-Honigmann, A Krause, PR AF Sierra-Honigmann, A Krause, PR TI Live oral poliovirus vaccines do not contain detectable simian virus 40 (SV40) DNA SO BIOLOGICALS LA English DT Article ID CHOROID-PLEXUS; SEQUENCES; TUMORS AB Prior to 1962, poliovirus vaccines produced in rhesus monkey kidney cells were contaminated with SV40. Recent studies reporting the detection of SV40 in human tumours raised concern that SV40 may be oncogenic in humans. To provide further assurance that currently used poliovirus vaccines are not contaminated with SV40, we used the polymerase chain reaction (PCR) to search for SV40 DNA in live oral poliovirus vaccines manufactured in the United States between 1972 and 1996. SV40 DNA sequences were not found in any of the vaccine lots tested. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Krause, PR (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29A,Rm 1C16,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 16 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD MAR PY 2000 VL 28 IS 1 BP 1 EP 4 DI 10.1006/biol.1999.0233 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 304UL UT WOS:000086502500001 PM 10799049 ER PT J AU Audet, SA Crim, RL Beeler, J AF Audet, SA Crim, RL Beeler, J TI Evaluation of vaccines, interferons and cell substrates for pestivirus contamination SO BIOLOGICALS LA English DT Article ID POLYMERASE CHAIN-REACTION; VIRUS-VACCINES; BOVINE; RNA; DIFFERENTIATION; ASSAY; PCR AB Pestiviruses are potential contaminants of biological products produced in bovine or porcine cells or manufactured via processes using animal-derived raw materials such as bovine serum. In order to investigate possible contamination of products including those manufactured and/or licensed in the US, 38 lots of viral vaccines and five lots of interferon alpha (IFN alpha) were tested by reverse transcriptase polymerase chain reaction (RT-PCR) for the presence of bovine viral diarrhoea virus (BVDV). All vaccines and interferons were negative for contaminating BVDV RNA when tested by RT-PCR, with the exception of an experimental live viral vaccine that had been produced in BVDV contaminated rabbit kidney cells. Cell lines commonly used to produce biological products and vaccines were experimentally infected with the NADL strain of BVDV to determine ii they were permissive for virus replication. MRC-5 and WI-38 cells were not infected. In contrast, Vero, CHO and CEF cells showed evidence of pestivirus infection. Taken together these data suggested that currently licensed viral vaccines were unlikely to be contaminated with pestiviruses. However, cell banks derived from non-human primate, hamster or rabbit kidney cell lines, or cultures of primary chick embryo fibroblasts, may be infected with BVDV if exposed to pestivirus contaminated raw materials during manufacture. C1 US FDA, CBER, Lab Pediat & Resp Viral Dis, Rockville, MD 20852 USA. RP Beeler, J (reprint author), US FDA, CBER, Lab Pediat & Resp Viral Dis, 1401 Rockville Pke,HFM-463, Rockville, MD 20852 USA. NR 20 TC 29 Z9 30 U1 0 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD MAR PY 2000 VL 28 IS 1 BP 41 EP 46 DI 10.1006/biol.1999.0240 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 304UL UT WOS:000086502500007 PM 10799055 ER PT J AU Junod, SW AF Junod, SW TI The politics of purity: Harvey Washington Wiley and the origins of federal food policy. SO BUSINESS HISTORY REVIEW LA English DT Book Review C1 US FDA, Rockville, MD 20857 USA. RP Junod, SW (reprint author), US FDA, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU HARVARD BUSINESS SCHOOL PI BOSTON PA BUSINESS HISTORY REVIEW, 60 HARVARD WAY, BOSTON, MA 02163 USA SN 0007-6805 J9 BUS HIST REV JI Bus. Hist. Rev. PD SPR PY 2000 VL 74 IS 1 BP 151 EP 155 DI 10.2307/3116367 PG 5 WC Business; History Of Social Sciences SC Business & Economics; Social Sciences - Other Topics GA 355MF UT WOS:000089388900016 ER PT J AU Pennello, G Devesa, S Gail, M AF Pennello, G Devesa, S Gail, M TI Association of surface ultraviolet B radiation levels with melanoma and nonmelanoma skin cancer in United States blacks SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; SUN EXPOSURE; CARCINOMA; WHITES AB Ultraviolet B (UVB) radiation exposure increases the risk of skin cancer in whites. Motivated by indications that United States geographic variation of relative skin cancer risk in blacks approaches that in whites, we used Poisson regression to estimate the risk of skin cancer in blacks as a function of average annual surface-levels of UVB radiation, measured by Robertson-Berger meters. United States data were used on deaths in 506 state economic areas, 1970-1994, and on incident cases in the nine areas of the Surveillance, Epidemiology, and End Results Program, 1973-1994, For black males, the age-adjusted relative risk of mortality for a 50% increase in UVB radiation was significantly above one for malignant melanoma, 1970-1994 (1.16; 95% confidence interval, 1.02-1.32) and nearly so for nonmelanoma skin cancer, 1970-1981 (1.18; 95% confidence interval, 1.00-1.39), for which the time period was chosen to avoid AIDS-related deaths from Kaposi's sarcoma. However, for black females, the relative risk of mortality was not significantly elevated for either skin cancer, and, for both black males and females, the relative risk of incidence was not significantly elevated for melanoma in the period 1973-1994. Incidence data on nonmelanoma skin cancer were not available. Although the public health implication is uncertain because of the much lower absolute risk of skin cancer in blacks compared with whites, the findings suggest that sunlight exposure increases skin cancer risk in blacks. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Pennello, G (reprint author), US FDA, Ctr Devices & Radiol Hlth, OSB DBS HFZ-542,1350 Piccard Dr, Rockville, MD 20850 USA. NR 36 TC 26 Z9 26 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2000 VL 9 IS 3 BP 291 EP 297 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 295TG UT WOS:000085983500008 PM 10750668 ER PT J AU Joshi, BH Plautz, GE Puri, RK AF Joshi, BH Plautz, GE Puri, RK TI Interleukin-13 receptor alpha chain: A novel tumor-associated transmembrane protein in primary explants of human malignant gliomas SO CANCER RESEARCH LA English DT Article ID PSEUDOMONAS EXOTOXIN; SIGNAL-TRANSDUCTION; CHIMERIC PROTEIN; IL-13 RECEPTOR; CARCINOMA-CELLS; CANCER-CELLS; EGF RECEPTOR; BRAIN-TUMORS; TOXIN; LINES AB Human malignant glioma cell lines express high levels of interleukin-13 receptor (IL-13R), However, the subunit structure of this receptor in primary brain tumor cells is not known. Herein, we examined the subunit composition of IL-13R by analyzing the expression of four different putative subunits of IL-13R complex in 25 primary explants of malignant brain tumors. Reverse transcription-PCR (RT-PCR) of RNA from these tumor cells, normal astrocytes, and normal brain tissue showed that transcripts of IL-13R alpha chain were present in greater abundance in malignant glioma cells compared with normal astrocytes or normal brain tissues. The transcripts for two other chains (e.g., IL-13R alpha' and IL-4R beta), on the other hand, yielded similar PCR positivity in brain tumors as well as in normal samples, whereas transcripts for gamma c chain were absent in all brain tumor cells and normal tissues. The specificity of RT-PCR products for these genes was confirmed by oligo liquid hybridization analysis using a radiolabeled sequence-specific internal probe. Indirect immunofluorescence studies for different receptor chains confirmed the RT-PCR results and demonstrated a striking difference in the level of expression of IL-13R alpha protein between normal astrocytes and malignant astrocytoma cells. These studies establish the IL-13R alpha subunit as a novel tumor-specific protein that may be useful as a tumor marker, a target for cytotoxin/immunotoxin, or alternatively, a tumor-associated antigen for active, specific immunotherapy. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Surg Res Ctr, Cleveland, OH 44195 USA. RP Puri, RK (reprint author), NIH Bldg 29B,Room 2NN10,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 26 TC 131 Z9 145 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2000 VL 60 IS 5 BP 1168 EP 1172 PG 5 WC Oncology SC Oncology GA 293RA UT WOS:000085865700005 PM 10728667 ER PT J AU Zhou, YF Shou, M Harrell, RF Yu, ZX Unger, EF Epstein, SE AF Zhou, YF Shou, M Harrell, RF Yu, ZX Unger, EF Epstein, SE TI Chronic non-vascular cytomegalovirus infection: effects on the neointimal response to experimental vascular injury SO CARDIOVASCULAR RESEARCH LA English DT Article DE arteries; angioplasty; cytokines; infection/inflammation; restenosis ID SCAVENGER RECEPTOR; ATHEROSCLEROSIS; PROLIFERATION; EXPRESSION; RESTENOSIS; KINETICS; GROWTH; CELLS AB Objective: Epidemiologic and mechanistic evidence implicates a role for cytomegalovirus (CMV) in atherogenesis. Recently, we demonstrated that CMV has the capacity to causally contribute to atherogenesis; acute infection of rats with rat CMV(RCMV) 1 day after carotid artery injury increased neointimal accumulation. Importantly, in the injured vessel infectious virus could not be detected and viral genome was present only transiently, suggesting that additional mechanisms play a role in the virus-induced exacerbation of the vascular injury response other than the changes caused by direct infection of vessel wall cells. The present investigation was designed to determine whether chronic persistent RCMV infection, more relevant to the clinical situation, also exacerbates the response to injury and, if so, whether similar mechanisms are operative. Methods: Sixty 3-week-old male Spraque-Dawley rats received an i.p. injection of either 10(6) TCID50 RCMV (Priscott strain) or normal saline. The left carotid artery was balloon-injured 3 months after infection. Rats were killed 6 weeks later. This model produces persistent infection, as demonstrated by presence of infectious virus in the salivary glands at time of sacrifice. Results: The neointima to media (N/M) ratio of the injured vessel was 41% greater in the RCMV-infected than in control rats (1.40+/-0.48 vs. 0.99+/-0.45; P=0.003). The aorta never contained infectious RCMV, and exhibited RCMV DNA, detected by PCR, only transiently. The persistent infection of non-vascular tissues was associated with increased serum levels of IL-2, IL-4 and IFN-gamma. Conclusions: CMV infection of young rats causes persistent infection of non-vascular tissues and increased cytokine levels. The neointimal response to subsequent vascular injury is increased, despite absence of virus from the vessel wall. These findings, as in acute infection following vascular injury, suggest that inflammatory and immune responses to chronic persistent CMV infection contribute to an exaggerated response to vascular injury. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Washington Hosp Ctr, Vasc Biol Lab, Cardiovasc Res Inst, Washington, DC 20010 USA. Univ Calif Los Angeles, Sch Med, Dept Cardiovasc Surg, Los Angeles, CA 90024 USA. NHLBI, Pathol Branch, NIH, Bethesda, MD 20895 USA. US FDA, Rockville, MD 20852 USA. RP Zhou, YF (reprint author), Washington Hosp Ctr, Vasc Biol Lab, Cardiovasc Res Inst, GHRB-217,108 Irving St, Washington, DC 20010 USA. NR 24 TC 15 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD MAR PY 2000 VL 45 IS 4 BP 1019 EP 1025 DI 10.1016/S0008-6363(99)00394-6 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 288MN UT WOS:000085566800025 PM 10728428 ER PT J AU da Costa, GG Hamilton, LP Beland, FA Marques, MM AF da Costa, GG Hamilton, LP Beland, FA Marques, MM TI Characterization of the major DNA adduct formed by alpha-hydroxy-N-desmethyltamoxifen in vitro and in vivo SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID BREAST-CANCER PATIENTS; REDUCED GENOTOXICITY; ENDOMETRIAL SAMPLES; LIVER CARCINOGEN; RAT HEPATOCYTES; GENE-MUTATIONS; F344 RATS; TAMOXIFEN; METABOLITES; HYDROXYTAMOXIFEN AB Tamoxifen is hepatocarcinogenic in rats and has been associated with an increased risk of endometrial cancer in women. Recent reports suggest that it may be genotoxic in humans. N-Desmethyltamoxifen is a major tamoxifen metabolite that has been proposed to be responsible for one of the major adducts detected in liver DNA of rats treated with tamoxifen. The metabolic activation of N-desmethyltamoxifen to DNA binding products may involve oxidation to alpha-hydroxy-N-desmethyltamoxifen followed by esterification. in the study presented here, we report the synthesis of alpha-hydroxy-N-desmethyltamoxifen and the characterization of the major adduct obtained from alpha-sulfoxy-N-desmethyltamoxifen in vitro as (E)-alpha-(deoxyguanosin-N-2)-N-desmethyltamoxifen. In addition, we use P-32-postlabeling in combination with HPLC to compare the adducts formed in the livers of female Sprague-Dawley rats treated by gavage with tamoxifen or equimolar doses of alpha-hydroxy-N-desmethyltamoxifen. We conclude that one of the major adducts formed in vivo and previously suggested to derive from N-desmethyloxifen is chromatographically identical to alpha-(deoxyguanosin-N-2-yl)-N-desmethyloxifen. C1 Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-1049001 Lisbon, Portugal. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Beland, FA (reprint author), Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, Complexo I,Ave Rovisco Pais, P-1049001 Lisbon, Portugal. EM qmdmar@beta.ist.utl.pt RI Marques, M. Matilde/E-2535-2012 OI Marques, M. Matilde/0000-0002-7526-4962 NR 62 TC 25 Z9 25 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR PY 2000 VL 13 IS 3 BP 200 EP 207 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 297KV UT WOS:000086082800008 ER PT J AU Yu, XH Sun, Y Frasch, C Concepcion, N Nahm, MH AF Yu, XH Sun, Y Frasch, C Concepcion, N Nahm, MH TI Towards a synthetic pneumococcal vaccine: Synthetic oligosaccharides as tools for improving the specificity of enzyme-linked immunosorbent assays - Reply SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Letter C1 Univ Rochester, Sch Med, Dept Pediat, Rochester, NY 14642 USA. US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, Bethesda, MD 20853 USA. Univ Rochester, Sch Med, Dept Pathol, Rochester, NY 14642 USA. Univ Rochester, Sch Med, Dept Med, Rochester, NY 14642 USA. RP Yu, XH (reprint author), Univ Rochester, Sch Med, Dept Pediat, Rochester, NY 14642 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD MAR PY 2000 VL 7 IS 2 BP 325 EP 325 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 290VT UT WOS:000085699100035 ER PT J AU Spyker, DA Harvey, ED Harvey, BE Harvey, AM Rumack, BH Peck, CC Atkinson, AJ Woosley, RL Abernethy, DR Cantilena, LR AF Spyker, DA Harvey, ED Harvey, BE Harvey, AM Rumack, BH Peck, CC Atkinson, AJ Woosley, RL Abernethy, DR Cantilena, LR TI Assessment and reporting of clinical pharmacology information in drug labeling - Commentary SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material C1 Purdue Pharma LP, Norwalk, CT 06850 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Rocky Mt Poison & Drug Ctr, Denver, CO USA. Georgetown Univ, Washington, DC USA. NIH, Ctr Clin, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Spyker, DA (reprint author), Purdue Pharma LP, 100 Connecticut Ave, Norwalk, CT 06850 USA. NR 3 TC 16 Z9 16 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 MAR PY 2000 VL 67 IS 3 BP 196 EP 200 DI 10.1067/mcp.2000.104737 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 296LT UT WOS:000086026400002 PM 10741621 ER PT J AU Doerge, DR Chang, HC Churchwell, MI Holder, CL AF Doerge, DR Chang, HC Churchwell, MI Holder, CL TI Analysis of soy isoflavone conjugation in vitro and in human blood using liquid chromatography-mass spectrometry SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID SOYBEAN ISOFLAVONES; BILIARY METABOLITES; GENISTEIN; DAIDZEIN; PLASMA; RATS; URINARY; WOMEN; CANCER; FOODS AB Soybean products containing isoflavones are widely consumed in Western and Asian diets for putative health benefits, but adverse effects are also possible. The conjugated forms of isoflavones present in a soy nutritional supplement (predominately acetyl glucosides) and in blood from two human volunteers after consuming the supplement (7- and 4'-glucuronides and sulfates) were identified using liquid chromatography coupled with electrospray/tandem mass spectrometry. Circulating conjugates of genistein and daidzein were quantified using selective enzymatic hydrolysis and deuterated internal standards for liquid chromatography-electrospray/mass spectrometry. The levels of isoflavone glucuronides were much greater than the corresponding sulfates or aglycones. The substrate activities of genistein and daidzein were evaluated with recombinant human UDP glucuronosyl transferase (UGT) and sulfotransferase (SULT) by using enzyme kinetics. The SULTs 1A1*2, 1E, and 2A1 catalyzed formation of a single genistein sulfate; however, SULTs 1A2*1 and 1A3 had no observed activity. None of the SULTs showed activity with daidzein. Although several UGTs (1A1, 1A4, 1A6, 1A7, 1A9, and 1A10) catalyzed 7- and 4'-glucuronidation of genistein or daidzein, the UGT 1A10 isoform, which is found in human colon but not liver, was found to be specific for genistein. Glucuronidation of only genistein was observed in human colon microsomes, although nearly equal activity was observed for daidzein in human liver and kidney microsomes. These findings suggest a prominent role for glucuronidation of genistein in the intestine concomitant with absorption, although hepatic glucuronidation of absorbed genistein and daidzein aglycones is also likely. C1 Natl Ctr Toxicol Res, Dept Hlth & Human Serv, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Dept Hlth & Human Serv, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 28 TC 161 Z9 165 U1 4 U2 15 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 MAR PY 2000 VL 28 IS 3 BP 298 EP 307 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 285PA UT WOS:000085396400009 PM 10681374 ER PT J AU Buchholz, U Mouzin, E Dickey, R Moolenaar, R Sass, N Mascola, L AF Buchholz, U Mouzin, E Dickey, R Moolenaar, R Sass, N Mascola, L TI Haff disease: From the Baltic Sea to the US shore SO EMERGING INFECTIOUS DISEASES LA English DT Article ID TOXINS AB Haff disease, identified in Europe in 1924, is unexplained rhabdomyolysis in a person who ate fish in the 24 hours before onset of illness. We describe a series of six U.S. patients from 1997 and report new epidemiologic and etiologic aspects. Although Haff disease is traditionally an epidemic foodborne illness, these six cases occurred in two clusters and as one sporadic case. C1 Los Angeles Cty Dept Hlth Serv, Los Angeles, CA 90012 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. US FDA, Dauphin Island, AL 36528 USA. US FDA, Laurel, MD USA. RP Buchholz, U (reprint author), Los Angeles Cty Dept Hlth Serv, 313 N Figueroa St,Room 212, Los Angeles, CA 90012 USA. NR 14 TC 18 Z9 24 U1 0 U2 3 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD MAR-APR PY 2000 VL 6 IS 2 BP 192 EP 195 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 308AZ UT WOS:000086687500015 PM 10756156 ER PT J AU Owen, RD AF Owen, RD TI Possible health risks of radiofrequency exposure from mobile telephones SO EPIDEMIOLOGY LA English DT Editorial Material ID LOW-LEVEL EXPOSURE; ELECTROMAGNETIC-FIELDS; LONG-TERM C1 US FDA, Radiat Biol Branch, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Owen, RD (reprint author), US FDA, Radiat Biol Branch, Ctr Devices & Radiol Hlth, HFZ-114,9200 Corp Blvd, Rockville, MD 20850 USA. NR 11 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 2000 VL 11 IS 2 BP 99 EP 100 DI 10.1097/00001648-200003000-00002 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 286WW UT WOS:000085472700002 PM 11021602 ER PT J AU Ilyukhin, SV Haley, TA Larkin, JW AF Ilyukhin, SV Haley, TA Larkin, JW TI Control system validation: Key to automated food processing SO FOOD TECHNOLOGY LA English DT Article C1 Purdue Univ, Comp Integrated Food Mfg Ctr, W Lafayette, IN 47906 USA. US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Haley, TA (reprint author), Purdue Univ, Comp Integrated Food Mfg Ctr, 1160 Food Sci Bldg, W Lafayette, IN 47906 USA. NR 24 TC 0 Z9 0 U1 1 U2 2 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA SUITE 300 221 N LASALLE ST, CHICAGO, IL 60601-1291 USA SN 0015-6639 J9 FOOD TECHNOL-CHICAGO JI Food Technol. PD MAR PY 2000 VL 54 IS 3 BP 66 EP 72 PG 7 WC Food Science & Technology SC Food Science & Technology GA 296QW UT WOS:000086036500010 ER PT J AU Goldkind, L AF Goldkind, L TI Rofecoxib versus placebo ulcer rates SO GASTROENTEROLOGY LA English DT Letter C1 US FDA, Div Gastrointestinal & Coagulat Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Goldkind, L (reprint author), US FDA, Div Gastrointestinal & Coagulat Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 3 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2000 VL 118 IS 3 BP 638 EP 639 DI 10.1016/S0016-5085(00)70279-4 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 291AM UT WOS:000085710500029 PM 10755870 ER PT J AU Tiffany, LJ Garcia-Ojeda, PA Stein, KE AF Tiffany, LJ Garcia-Ojeda, PA Stein, KE TI Determination of the IgG2a allotype of CXB recombinant inbred mouse strains by a PCR-based method (vol 50, pg 71, 1999) SO IMMUNOGENETICS LA English DT Correction C1 US FDA, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Stein, KE (reprint author), US FDA, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, 29 Lincoln Dr, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD MAR PY 2000 VL 51 IS 3 BP 252 EP 252 PG 1 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 298VB UT WOS:000086158900015 ER PT J AU Schwan, WR Huang, XZ Hu, L Kopecko, DJ AF Schwan, WR Huang, XZ Hu, L Kopecko, DJ TI Differential bacterial survival, replication, and apoptosis-inducing ability of Salmonella serovars within human and murine macrophages SO INFECTION AND IMMUNITY LA English DT Article ID INTRACELLULAR SURVIVAL; MOUSE MACROPHAGES; INNATE RESISTANCE; TYPHIMURIUM; STRAINS; TYPHI; MICE; PATHOGENICITY; PHAGOSOMES; EXPRESSION AB Salmonella serovars are associated with human diseases that range from mild gastroenteritis to host-disseminated enteric fever. Human infections by Salmonella enterica serovar Typhi can lead to typhoid fever, but this serovar does not typically cause disease in mice or other animals. In contrast, S. enterica serovar Typhimurium and S. enterica serovar Enteritidis, which are usually linked to localized gastroenteritis in humans and some animal species, elicit a systemic infection in mice. To better understand these observations, multiple strains of each of several chosen serovars of Salmonella were tested for the ability in the nonopsonized state to enter, survive. and replicate within human macrophage cells (U937 and elutriated primary cells) compared with murine macrophage cells (J774A.1 and primary peritoneal cells); in addition, death of the infected macrophages was monitored. The serovar Typhimurium strains all demonstrated enhanced survival within J774A.1 cells and murine peritoneal macrophages, compared with the significant, almost 100-fold declines in viable counts noted for serovar Typhi strains. Viable counts for serovar Enteritidis either matched the level of serovar Typhia (J774A.1 macrophages) or were comparable to counts for serovar Typhimurium (murine peritoneal macrophages), Apoptosis was significantly higher in J774A.1 cells infected with serovar Typhimurium strain LT2 compared to serovar Typhi strain Ty2, On the other hand, serovar Typhi survived at a level up to 100-fold higher in elutriated human macrophages and 2- to 3-fold higher in U937 cells compared to the serovar Typhimurium and Enteritidis strains tested, Despite the differential multiplication of serovar Typhi during infection of U937 cells, serovar Typhi caused significantly less apoptosis than infections with serovar Typhimurium. These observations indicate variability in intramacrophage survival and host cytotoxicity among the various serovars and are the first to show differences in the apoptotic response of distinct Salmonella serovars residing in human macrophage cells. These studies suggest that nonopsonized serovar Typhimurium enters, multiplies within, and causes considerable, acute death of macrophages, leading to a highly virulent infection in mice (resulting in death within 14 days). In striking contrast, nonopsonized serovar Typhi survives silently and chronically within human macrophages, causing little cell death, which allows for intrahost dissemination and typhoid fever (low host mortality). The type of disease associated with any particular serovar of Salmonella is linked to the ability of that serovar both to persist within and to elicit damage in a specific host's macrophage cells. C1 US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Biol & Microbiol, La Crosse, WI 54601 USA. RP Kopecko, DJ (reprint author), US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, HFM440,NIH Campus,Bldg 29-420, Bethesda, MD 20892 USA. NR 33 TC 87 Z9 88 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 2000 VL 68 IS 3 BP 1005 EP 1013 DI 10.1128/IAI.68.3.1005-1013.2000 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 285UW UT WOS:000085407400001 PM 10678900 ER PT J AU Babu, US Mitchell, GV Wiesenfeld, P Jenkins, MY Gowda, H AF Babu, US Mitchell, GV Wiesenfeld, P Jenkins, MY Gowda, H TI Nutritional and hematological impact of dietary flaxseed and defatted flaxseed meal in rats SO INTERNATIONAL JOURNAL OF FOOD SCIENCES AND NUTRITION LA English DT Article ID ALPHA-LINOLENIC-ACID; N-3 FATTY-ACIDS; VITAMIN-E; IRON-ABSORPTION; LIPID-PEROXIDATION; BLOOD-LIPIDS; PHYTIC ACID; HUMANS; OIL; METABOLISM AB An X-week study was conducted to determine the impact of dietary ground flaxseed (FS) or defatted flaxseed meal (FLM) on plasma lipids, minerals, hematological parameters and vitamin E status of weanling female Sprague-Dawley rats. These rats were fed isocaloric modified AIN-76 diets supplemented with 0.0, 5.0, 10.0% (w/w) FS or 6.2% (w/w) FLM for 56 days. Total and HDL cholesterol were not influenced by any of the dietary treatments. Plasma triglyceride was significantly increased by FLM, but not affected by FS. Total RBC counts and hematocrit were significantly higher in FS groups than in the control group; however, hemoglobin was not affected by FS. Dietary FLM had no effect on any of the above hematological parameters. Plasma alkaline phosphatase, an indicator of Zn status and a marker of bone formation, was significantly lower in the FS and FLM groups than in the control group. Plasma vitamin E content was not influenced by dietary treatment. Liver vitamin E was significantly higher in groups fed 10% FS and 6.2% FLM. In summary, moderate amounts of dietary FS may have the potential to increase liver vitamin E level and improve iron status. However, FS/FLM consumption may have a negative effect on zinc status, as indicated by decreased alkaline phosphatase levels. C1 US FDA, Div Sci & Appl Technol, Off Special Nutrit, Laurel, MD 20708 USA. US FDA, Div Sci & Appl Technol, Off Food Labeling, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Babu, US (reprint author), US FDA, Div Sci & Appl Technol, Off Special Nutrit, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 48 TC 23 Z9 24 U1 0 U2 1 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0963-7486 J9 INT J FOOD SCI NUTR JI Int. J. Food Sci. Nutr. PD MAR PY 2000 VL 51 IS 2 BP 109 EP 117 PG 9 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 293RX UT WOS:000085868000003 PM 10953754 ER PT J AU Blank, JA Luster, MI Langone, JJ Wilson, SD AF Blank, JA Luster, MI Langone, JJ Wilson, SD TI Immunotoxicology - Regulatory and risk assessment concepts SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE autoimmunity; chemical pharmaceutic; immunotoxicology; medical device; regulatory; risk assessment ID LYMPH-NODE ASSAY; AUTOIMMUNE-DISEASE; CYCLOSPORINE-A; IMMUNE-SYSTEM; CHEMICALS; BATTERY; MICE; SEX AB This article provides a review of presentations given at the symposium on Immunotoxicology: Regulatory and Risk Assessment Concepts held at the American College of Toxicology meeting in Orlando, Florida, in November, 1998, Immune system alterations have typically been assessed by histopathology of select lymphoid tissue, clinical pathology, clinical chemistry, plaque forming cell assay for humoral immunity, and allergic contact hypersensitivity. Advances in immunology and molecular biology have led to various activities to optimize hazard identification and risk assessment processes and strategies for immunotoxicants, With such advances, regulatory agencies have been either implementing immunotoxicology guidance as part of the safety of medical devices, evaluating environmental chemicals, or considering immunotoxicologic criteria for nonclinical assessments. Reviews of the guidance document provided by the Food and Drug Administration (FDA)/Center for Device and Radiological Health and concepts being considered by the FDA/Center for Drug Evaluation and Research are presented. In addition, a review of the process for evaluation of the murine local lymph node assay by the Interagency Coordinating Committee on the Validation of Alternative Methods and the state of risk assessment for chemical-induced autoimmunity are presented. C1 Pfizer Inc, Cent Res, Groton, CT 06340 USA. NIOSH, Toxicol & Mol Biol Branch, Morgantown, WV USA. US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Blank, JA (reprint author), Pfizer Inc, Cent Res, Mailbox 8014,Eastern Point Rd, Groton, CT 06340 USA. NR 39 TC 1 Z9 3 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD MAR-APR PY 2000 VL 19 IS 2 BP 95 EP 106 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 309FN UT WOS:000086757800003 ER PT J AU Slater, JE Pastor, RW AF Slater, JE Pastor, RW TI The determination of equivalent doses of standardized allergen vaccines SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE allergen; allergen extract; immunotherapy; standardization; allergy ID RAGWEED IMMUNOTHERAPY; HAY-FEVER; EXTRACTS; POTENCY; INJECTION; EFFICACY AB Background: Standardized allergen vaccines are tested for potency by manufacturers by using assays proposed in their license applications and approved by the Center for Biologics Evaluation and Research, which reviews and verifies the test results before lot release, The current lot-release limits for mite and grass pollen allergen vaccines impose statistical equivalence to the national reference extract; thus the limits are primarily based on assay variability, Objective: We sought to establish a clinical basis for lot-release limits for the relative potency of allergen vaccines and to evaluate alternative specifications. Methods: We performed literature selection and review, linear and logistic regression analyses of selected studies, and analysis of lots submitted to the Food and Drug Administration for approval since 1995, Results: Therapeutic equivalence is achieved over a 10-fold range of allergen concentration. Safety equivalence is more difficult to assign, but on the basis of injection data, a 4-fold increase in allergen concentration is associated with a 5% to 10% increase in adverse reaction rates. The SD in log relative potency for the submitted allergenic products was determined to be 0.090 for grasses and 0.061 for mites, compared with 0.079 for competition ELISA, Conclusions: Current lot-release limits are well within literature-based estimates of therapeutic, diagnostic, and safety equivalence ranges for the clinical use of allergen vaccines. In addition, the aggregate consistency of the submitted products is comparable with the precision of the assay that is used to assess the products. These results support expanded release limits for verification of relative potency, provided the submitted lots of material remain at their present level of consistency. C1 US FDA, CBER, DBPAP,Div Allergen Prod & Parasitol, Lab Immunobiochem, Rockville, MD 20852 USA. US FDA, CBER, Div Allergen Prod & Parasitol, Biophys Lab, Rockville, MD 20852 USA. RP Slater, JE (reprint author), US FDA, CBER, DBPAP,Div Allergen Prod & Parasitol, Lab Immunobiochem, 1401 Rockville Pike,HFM-422, Rockville, MD 20852 USA. NR 24 TC 12 Z9 12 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAR PY 2000 VL 105 IS 3 BP 468 EP 474 DI 10.1067/mai.2000.104551 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 347UC UT WOS:000088946700011 PM 10719295 ER PT J AU Soldatova, LN Paupore, EJ Burk, SH Pastor, RW Slater, JE AF Soldatova, LN Paupore, EJ Burk, SH Pastor, RW Slater, JE TI The stability of house dust mite allergens in glycerinated extracts SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE dust mite; monoclonal antibody; allergen; ELISA; immunoblot; stability; allergy; allergen extract ID SITE-DIRECTED MUTAGENESIS; DILUTION; DER-P-2 AB Background: Mite allergen vaccines are important diagnostic and immunotherapeutic reagents. Previous studies on mite allergen stability under different storage conditions have yielded contradictory results, Objective: We sought to compare, over a 12-month period, the stability of mite allergens reconstituted in 50% glycerol and stored at different temperatures and to examine the role of protease inhibitors in enhancing allergen stability. Methods: Lyophilized allergen extracts were reconstituted in 50% glycerol, with and without protease inhibitors, and stored at -70 degrees C, -20 degrees C, 4 degrees C, or 37 degrees C for 12 months. At 6 and 12 months, the extracts were compared with freshly dissolved extracts by competition ELISA with pooled allergic sera, 2-site ELISA with mite-specific mAbs, and immunoblot analyses, Results: The overall potencies of the stored extracts measured by competition ELISA were stable at -20 degrees C and 4 degrees C. As determined by means of the immunoblot and 2-site ELISA, Der fl levels decreased at 4 degrees C. Levels of Der f 2, Der p 1, and Der p 2 decreased in at least one of the allergen-specific assays. Storage at 37 degrees C led to overall loss of potency and allergen content, whereas storage at -70 degrees C was associated with a moderate loss of potency that increased with multiple freeze-thaw cycles, Protease inhibitors had no effect on allergen stability. Conclusion: Although overall potency of the extracts, as measured by competition ELISA, was preserved at -20 degrees C and 4 degrees C, allergen-specific assays indicated loss of allergens. These findings suggest that the competition ELISA is insensitive to decreases in the concentrations of individual allergens. C1 US FDA, CBER, DBPAP,Div Allergen Prod & Parasitol, Lab Immunobiochem, Rockville, MD 20852 USA. US FDA, CBER, Div Allergen Prod & Parasitol, Biophys Lab, Rockville, MD 20852 USA. RP Soldatova, LN (reprint author), US FDA, CBER, DBPAP,Div Allergen Prod & Parasitol, Lab Immunobiochem, 1401 Rockville Pike,HFM-422, Rockville, MD 20852 USA. NR 20 TC 19 Z9 20 U1 0 U2 6 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 2000 VL 105 IS 3 BP 482 EP 488 DI 10.1067/mai.2000.104549 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 347UC UT WOS:000088946700013 PM 10719297 ER PT J AU Tollefson, L Miller, MA AF Tollefson, L Miller, MA TI Antibiotic use in food animals: Controlling the human health impact SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID RESISTANT ENTEROCOCCUS-FAECIUM; SALMONELLA-TYPHIMURIUM DT104; QUINOLONE RESISTANCE; ANTIMICROBIAL AGENTS; VETERINARY-MEDICINE; UNITED-STATES; VANCOMYCIN; CAMPYLOBACTER; POULTRY; FARMS AB Resistance to antimicrobial drugs has compromised control of many bacterial pathogens, For foodborne pathogens, the most likely source of resistance is use of antimicrobials in food-producing animals, To control the human health impact from use of antimicrobials in animals, the U.S. Food and Drug Administration (FDA) recently announced plans to assess the microbial safety of all antimicrobials intended for use in food-producing animals. This paper describes the history of antimicrobial use and regulation in animals, the public health concern, the current animal drug approval process in the United States, the international perspective, and FDA's proposed procedures to evaluate the human health impact of the antimicrobial effects associated with animal drugs intended for use in food-producing animals. The primary public health goal of the improved regulatory paradigm is to ensure that significant human antimicrobial therapies are not lost due to use of antimicrobials in food animals. C1 US FDA, Ctr Vet Med, Off Surveillance & Compliance, Rockville, MD 20855 USA. US FDA, Off Womens Hlth, Rockville, MD 20857 USA. RP Tollefson, L (reprint author), US FDA, Ctr Vet Med, Off Surveillance & Compliance, 7500 Standish Pl, Rockville, MD 20855 USA. NR 56 TC 62 Z9 64 U1 3 U2 12 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2000 VL 83 IS 2 BP 245 EP 254 PG 10 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 299TU UT WOS:000086214600001 PM 10772160 ER PT J AU LeDoux, M Hall, S AF LeDoux, M Hall, S TI Proficiency testing of eight french laboratories in using the AOAC mouse bioassay for paralytic shellfish poisoning: Interlaboratory collaborative study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB In an interlaboratory study, 8 French laboratories were tested for their proficiency in using the AOAC mouse bioassay for paralytic shellfish poisoning (PSP). Each laboratory received 1 saxitoxin (STX) standard solution, 1 STX acidified water solution for determination of the titer, 1 noncontaminated shellfish sample, 1 naturally contaminated shellfish sample, and 2 shellfish samples spiked, respectively, at low (152.8 mu g STW100 g meat) and moderate (334.7 mu g STW100 g meat) levels. All samples were analyzed in duplicate. Mean recoveries were 35.1% for the low level and 46.6% for the moderate level. Relative standard deviations (RSD) for within-laboratory variations (repeatability) ranged from 5.4 to 9.8%; RSD for between-laboratory variations (reproducibility) varied from 7.8 to 39.6%, depending on STX level. On the basis of overall performance, all 8 participating laboratories were proficient in their use of the AOAC mouse bioassay. C1 CNEVA Paris, Ctr Natl Etud Vet & Alimentaires, F-94704 Maisons Alfort, France. US FDA, Div Res, Off Seafood, Washington, DC 20204 USA. RP LeDoux, M (reprint author), CNEVA Paris, Ctr Natl Etud Vet & Alimentaires, 10 Rue Pierre Curie, F-94704 Maisons Alfort, France. NR 13 TC 32 Z9 36 U1 0 U2 3 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 2000 VL 83 IS 2 BP 305 EP 310 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 299TU UT WOS:000086214600009 PM 10772168 ER PT J AU Horwitz, W Wood, R AF Horwitz, W Wood, R TI Relationship of (known) control values to (unknown) test values in proficiency studies of pesticide residues SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID HORWITZ AB Proficiency studies have been suggested as an alternative source of information for evaluating method performance characteristics when results from interlaboratory method performance studies conforming to internationally recognized protocols are not available. To explore this possibility, results were examined from ongoing proficiency studies of pesticide residue analyses in celery, carrot, and grape purees, and in wine. Statistical performance parameters were calculated from 18 data sets analyzed as unknowns by about 60 analysts for 12 analytes in the 25-1000 mu g/kg range, and from presumably parallel control (spike) analyses conducted by about half of the participants. A surprising finding was that recovery of known, independent control additions by the participant did not correlate with the recoveries determined as unknowns in the exercise. The data suggest that censoring or truncating of control data has occurred. The question of substitution of proficiency data for method performance data cannot be answered until the problem of unbiased reporting of control data is resolved. C1 US FDA, Washington, DC 20204 USA. MAFF, Norwich NR4 7UQ, Norfolk, England. RP Horwitz, W (reprint author), US FDA, HFS-500, Washington, DC 20204 USA. NR 11 TC 8 Z9 8 U1 1 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2000 VL 83 IS 2 BP 399 EP 406 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 299TU UT WOS:000086214600019 PM 10772178 ER PT J AU Chase, GW Thompson, B AF Chase, GW Thompson, B TI Accelerated solvent extraction of vitamin K-1 in medical foods in conjunction with matrix solid-phase dispersion SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB An extraction technique is described for vitamin K-1 in medical foods, using accelerated solvent extraction (ASE) in conjunction with matrix solid-phase dispersion (MSPD). The medical food sample is treated as it would be with MSPD extraction, followed by ASE for a hands-free automated extraction. The vitamin K-1 in the ASE extract is then quantitated by reversed-phase liquid chromatography with fluorescence detection. The chromatography specifications are identical to those in previous work that used MSPD only, with a limit of detection of 6.6 pg and a limit of quantitation of 22 pg on column. Recoveries, which were determined for an analyte-fortified zero control reference material for medical foods, averaged 97.6% (n = 25) for vitamin K-1. The method provides a rapid, automatic, specific, and easily controlled assay for vitamin K-1 in fortified medical foods with minimal solvent usage. C1 US FDA, SE Reg Lab, Atlanta, GA 30309 USA. Dionex Corp, Atlanta, GA 30339 USA. RP Chase, GW (reprint author), US FDA, SE Reg Lab, 60 8th St, Atlanta, GA 30309 USA. NR 15 TC 13 Z9 13 U1 1 U2 5 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2000 VL 83 IS 2 BP 407 EP 410 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 299TU UT WOS:000086214600020 PM 10772179 ER PT J AU Johannessen, JN AF Johannessen, JN TI Stability of domoic acid in saline dosing solutions SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Studies designed to assess the effects of repeated low doses of domoic acid require an assessment of its stability in solution under the conditions used for in vivo studies. The stability of 1 mg/mL solutions of domoic acid in saline, with or without ascorbic acid, was determined for 15 weeks. Solutions were refrigerated, but warmed to room temperature for several hours each working day to simulate conditions of actual use. The solutions of domoic acid showed no evidence of decomposition as evidenced by stability of UV absorbance spectrum, concentration of domoic acid as determined by a liquid chromatographic method, and the chromatographic elution pattern. The addition of ascorbate to the domoic acid/saline solution did not alter the stability, but was deemed unnecessary because of the firm stability of the domoic acid/saline solution. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Toxicol Res, Laurel, MD 20708 USA. RP Johannessen, JN (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Toxicol Res, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 3 TC 7 Z9 9 U1 1 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2000 VL 83 IS 2 BP 411 EP 412 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 299TU UT WOS:000086214600021 PM 10772180 ER PT J AU Bunch, EA AF Bunch, EA TI Drugs I SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US FDA, Bothell, WA 98021 USA. RP Bunch, EA (reprint author), US FDA, 22201 23rd Dr SE, Bothell, WA 98021 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2000 VL 83 IS 2 BP 436 EP 437 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 299TU UT WOS:000086214600026 ER PT J AU Linda, L AF Linda, L TI Drugs II SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Linda, L (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2000 VL 83 IS 2 BP 437 EP 437 PG 1 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 299TU UT WOS:000086214600027 ER PT J AU Long, AR AF Long, AR TI Color additives SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US FDA Pacific Reg, Pacific Reg Lab NW, Bothell, WA 98021 USA. RP Long, AR (reprint author), US FDA Pacific Reg, Pacific Reg Lab NW, 22201 23rd Dr SE, Bothell, WA 98021 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2000 VL 83 IS 2 BP 439 EP 439 PG 1 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 299TU UT WOS:000086214600030 ER PT J AU Warner, CR AF Warner, CR TI Food additives SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PRODUCTS C1 US FDA, Washington, DC 20204 USA. RP Warner, CR (reprint author), US FDA, HFS-245,200 C St SW, Washington, DC 20204 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2000 VL 83 IS 2 BP 439 EP 440 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 299TU UT WOS:000086214600031 ER PT J AU Trucksess, MW AF Trucksess, MW TI Mycotoxins SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; PERFORMANCE LIQUID-CHROMATOGRAPHY; SOLID-PHASE EXTRACTION; WHOLE WHEAT-FLOUR; OCHRATOXIN-A; MASS-SPECTROMETRY; IMMUNOAFFINITY COLUMN; FUSARIUM MYCOTOXINS; GAS-CHROMATOGRAPHY; CYCLOPIAZONIC ACID C1 US FDA, Div Nat Prod, Washington, DC 20204 USA. RP Trucksess, MW (reprint author), US FDA, Div Nat Prod, 200 C St SW, Washington, DC 20204 USA. NR 98 TC 5 Z9 5 U1 1 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2000 VL 83 IS 2 BP 442 EP 448 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 299TU UT WOS:000086214600033 ER PT J AU Firestone, D AF Firestone, D TI Fats and oils SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID REFLECTION INFRARED-SPECTROSCOPY; LIQUID-CHROMATOGRAPHY; GAS-CHROMATOGRAPHY; TRANS; SQUALENE; ACIDS C1 US FDA, Washington, DC 20204 USA. RP Firestone, D (reprint author), US FDA, 200 C St SW, Washington, DC 20204 USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2000 VL 83 IS 2 BP 467 EP 470 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 299TU UT WOS:000086214600038 ER PT J AU Chase, GW AF Chase, GW TI Infant formula and medical diets SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US FDA, Atlantic Ctr Nutrient Anal, Atlanta, GA 30309 USA. RP Chase, GW (reprint author), US FDA, Atlantic Ctr Nutrient Anal, 60 8th St, Atlanta, GA 30309 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2000 VL 83 IS 2 BP 470 EP 471 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 299TU UT WOS:000086214600040 ER PT J AU Long, AR AF Long, AR TI Fat-soluble vitamins SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US FDA Pacific Reg, Pacific Reg Lab NW, Bothell, WA 98021 USA. RP Long, AR (reprint author), US FDA Pacific Reg, Pacific Reg Lab NW, 22201 23rd Dr SE, Bothell, WA 98021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2000 VL 83 IS 2 BP 470 EP 470 PG 1 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 299TU UT WOS:000086214600039 ER PT J AU Parfitt, CH AF Parfitt, CH TI Multiresidue methods SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US FDA, Div Field Sci, Rockville, MD 20857 USA. RP Parfitt, CH (reprint author), US FDA, Div Field Sci, HFC-140,5600 Fishers Lane, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2000 VL 83 IS 2 BP 488 EP 489 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 299TU UT WOS:000086214600050 ER PT J AU Baratta, EJ AF Baratta, EJ TI Radioactivity SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. RP Baratta, EJ (reprint author), US FDA, Winchester Engn & Analyt Ctr, 109 Holton St, Winchester, MA 01890 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2000 VL 83 IS 2 BP 490 EP 490 PG 1 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 299TU UT WOS:000086214600052 ER PT J AU Hitchins, AD AF Hitchins, AD TI Cosmetic microbiology SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US FDA, Washington, DC 20204 USA. RP Hitchins, AD (reprint author), US FDA, HFS-516,200 C St SW, Washington, DC 20204 USA. NR 8 TC 0 Z9 0 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2000 VL 83 IS 2 BP 491 EP 492 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 299TU UT WOS:000086214600053 ER PT J AU Placencia, AM AF Placencia, AM TI Drug- and device-related microbiology SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US FDA, Steril Res Ctr, Minneapolis, MN 55401 USA. RP Placencia, AM (reprint author), US FDA, Steril Res Ctr, 240 Hennepin Ave, Minneapolis, MN 55401 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2000 VL 83 IS 2 BP 492 EP 494 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 299TU UT WOS:000086214600054 ER PT J AU Singleton, ER AF Singleton, ER TI Microbiological efficacy testing of disinfectants SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US FDA, DFC, Denver, CO 80225 USA. RP Singleton, ER (reprint author), US FDA, DFC, Bldg 20,POB 25087, Denver, CO 80225 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2000 VL 83 IS 2 BP 494 EP 495 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 299TU UT WOS:000086214600055 ER PT J AU Andrews, WH AF Andrews, WH TI Food microbiology-nondairy SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID RAPPAPORT-VASSILIADIS MEDIUM; HIGHLY CONTAMINATED FOODS; SELENITE CYSTINE BROTH; RELATIVE EFFECTIVENESS; TETRATHIONATE BROTH; ENRICHMENT MEDIUM; RAW FLESH; SALMONELLAE; RECOVERY C1 US FDA, Div Microbiol Studies, Washington, DC 20204 USA. RP Andrews, WH (reprint author), US FDA, Div Microbiol Studies, HFS-516,200 C St SW, Washington, DC 20204 USA. NR 15 TC 0 Z9 0 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2000 VL 83 IS 2 BP 495 EP 502 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 299TU UT WOS:000086214600056 ER PT J AU Corbin, NS Teichman, JMH Nguyen, T Glickman, RD Rihbany, L Pearle, MS Bishoff, JT AF Corbin, NS Teichman, JMH Nguyen, T Glickman, RD Rihbany, L Pearle, MS Bishoff, JT TI Laser lithotripsy and cyanide SO JOURNAL OF ENDOUROLOGY LA English DT Article ID HOLMIUM-YAG LITHOTRIPSY; URIC-ACID CALCULI; FRAGMENTATION PROCESS AB Background and Purpose: Holmium:YAG lithotripsy of uric acid calculi produces cyanide. The laser and stone parameters required to produce cyanide are poorly defined. In this study, we tested the hypotheses that cyanide production: (1) varies with holmium:YAG power settings; (2) varies among holmium:YAG, pulsed-dye, and alexandrite lasers; and (3) occurs during holmium:YAG lithotripsy of all purine calculi. Materials and Methods: Holmium:YAG lithotripsy of uric acid calculi was done using various optical fiber diameters (272-940 mu m) and pulse energies (0.5-1.5 J) for constant irradiation (0.25 kJ). Fragmentation and cyanide were quantified. Cyanide values were divided by fragmentation values, and fragment sizes were characterized. To test the second hypothesis, uric acid calculi were irradiated with Ho:YAG, pulsed-dye, and alexandrite lasers. Fragmentation and cyanide were measured, and cyanide per fragmentation was calculated. Fragment sizes were characterized. Finally, Ho:YAG lithotripsy (0.25 kJ) of purine and nonpurine calculi was done, and cyanide production was measured. Results: Fragmentation increased as pulse energy increased for the 550- and 940-mu m optical fibers (P < 0.05). Cyanide increased as pulse energy increased for all optical fibers (P < 0.002). Cyanide per fragmentation increased as pulse energy increased for the 272-mu m optical fiber (P = 0.03). Fragment size increased as pulse energy increased for the 272-mu m, 550-mu m, and 940-mu m optical fibers (P < 0.001). The mean cyanide production from 0.25 kJ of optical energy was Ho:YAG laser 106 mu g, pulsed-dye 55 mu m, and alexandrite 1 mu g (P < 0.001). The mean cyanide normalized for fragmentation (mu g/mg) was 1.18, 0.85, and 0.02, respectively (P < 0.001). The mean fragment size was 0.6, 1.1, and 1.9 mm, respectively (P < 0.001). After 0.25 kJ, the mean amount of cyanide produced was monosodium urate stones 85 mu g, uric acid 78 mu g, xanthine 17 mu g, ammonium acid urate 16 mu g, calcium phosphate 8 mu g, cystine 7 mu g, and struvite 4 mu g (P < 0.001). Conclusions: Cyanide production varies with Ho:YAG pulse energy. To minimize cyanide and fragment size, Ho:YAG lasertripsy is best done at a pulse energy less than or equal to 1.0 J. Cyanide production from laser lithotripsy of uric acid calculi varies among Ho:YAG, pulsed-dye, and alexandrite lasers and is related to pulse duration. Cyanide is produced by Ho:YAG lasertripsy of all purine calculi. C1 Univ Texas, Hlth Sci Ctr, Div Urol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Ophthalmol, San Antonio, TX 78284 USA. US FDA, Winchester, MA USA. Univ Texas, SW Med Ctr, Div Urol, Dallas, TX USA. Wilford Hall USAF Med Ctr, Div Urol, Lackland AFB, TX 78236 USA. RP Teichman, JMH (reprint author), Univ Texas, Hlth Sci Ctr, Div Urol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. OI Bush, Nicol/0000-0002-9887-3680 NR 16 TC 8 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD MAR PY 2000 VL 14 IS 2 BP 169 EP 173 DI 10.1089/end.2000.14.169 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 299YG UT WOS:000086225600010 PM 10772510 ER PT J AU Thunberg, RL Tran, TT Walderhaug, MO AF Thunberg, RL Tran, TT Walderhaug, MO TI Detection of thermophilic Campylobacter spp. in blood-free enriched samples of inoculated foods by the polymerase chain reaction SO JOURNAL OF FOOD PROTECTION LA English DT Article ID JEJUNI; COLI; CENTRIFUGATION; PRODUCTS; LARIDIS; PROBES; ASSAY AB The detection of thermophilic Campylobacter spp., as represented by Campylobacter jejuni, by the polymerase chain reaction (PCR) was investigated and compared with the selective agar isolation (SAI) method. Stationary-phase cultures of C. jejuni were inoculated into either blood-free enrichment broth (BFEB) or BFEB that contained 10% broccoli, crabmeat, mushroom, raw milk, and raw oyster rinses. Following a 48-h enrichment period, aliquots of food test portions were removed for simultaneous analysis by PCR and SAI. It was determined that the presence of charcoal and iron in the enrichment broth interfered with the PCR assay. Therefore, three DNA extraction techniques were developed and evaluated using a 168 rRNA primer pair in the PCR assay. The 50% end point (DL50) values (determined upon six initial C. jejuni spiking levels) were used to assess the frequency of isolation utilizing PCR versus SAI for the detection of this organism in the enrichment matrices. There were virtually no differences in detection of C. jejuni among enriched samples analyzed by PCR and SAI. Mean DL50 values (n = 3) for plain BFEB, broccoli, crabmeat, mushroom, raw milk, and raw oyster were, respectively, 0.02 (PCR) versus 0.01 (SAI), 0.01 versus 0.06, 0.07 versus 0.04, 0.03 versus 0.08, 0.01 versus 0.01, and 0.01 versus 0.01 CFU/5 g food. Significant variability in the detection limit of C. jejuni by PCR in the food enrichments was observed among DNA extraction techniques. Using 48-h enrichment cultures followed by PCR analysis could save 1 day of the time required for the presumptive identification of C. jejuni in suspected foods. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Thunberg, RL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 31 TC 12 Z9 13 U1 0 U2 1 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC 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 2000 VL 63 IS 3 BP 299 EP 303 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 290VL UT WOS:000085698500001 PM 10716555 ER PT J AU Ray, M Gam, AA Boykins, RA Kenney, RT AF Ray, M Gam, AA Boykins, RA Kenney, RT TI Inhibition of interferon-gamma signaling by Leishmania donovani SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY OCT, 1998 CL SAN JUAN, PUERTO RICO SP Amer Soc Trop Med & Hygiene ID NECROSIS-FACTOR-ALPHA; LYMPHOMA CELL-LINE; IFN-GAMMA; TYROSINE PHOSPHORYLATION; VISCERAL LEISHMANIASIS; INFECTED MACROPHAGES; MURINE MACROPHAGES; GENE-EXPRESSION; IMMUNE-RESPONSE; HUMAN MONOCYTES AB Leishmania infection causes marked down-regulation of interferon (IFN)-gamma-induced gene activity in macrophages, but the mechanism of the blockade has not been fully defined. The IFN-gamma signal transduction pathway was analyzed in Leishmania donovani-infected phorbol-differentiated U937 human promonocytic cells. IFN-gamma stimulation induced marked phosphorylation of its own receptor (IFN-gamma R)-alpha chain. Phosphorylation of the receptor subunit was significantly inhibited after 24 h of infection with the parasite, apparently because of decreased amounts of the receptor subunit, Formation of the IFN-gamma R complex, as assessed by tyrosine phosphorylation and association of Jak2, was strongly inhibited in cells infected for 24 h, Inhibition of the IFN-gamma R complex formation correlated with inhibition of STAT1 alpha binding to the IFN-gamma response region. Pretreatment with purified parasite lipophosphoglycan before IFN-gamma stimulation had no effect on tyrosine phosphorylation. Thus, inhibition of tyrosine phosphorylation of the IFN-gamma R-alpha chain and subsequent signal transduction are most likely due to the decreased amount of IFN-gamma R-alpha protein after infection. C1 US FDA, Ctr Biol Evaluat & Res, Lab Parasit Biol & Biochem, Bethesda, MD USA. RP Kenney, RT (reprint author), 1401 Rockville Pike,HFM-416, Rockville, MD 20852 USA. NR 47 TC 55 Z9 58 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR PY 2000 VL 181 IS 3 BP 1121 EP 1128 DI 10.1086/315330 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 302BE UT WOS:000086344400041 PM 10720539 ER PT J AU Argaw, T Cohen, JI Klutch, M Lekstrom, K Yoshikawa, T Asano, Y Krause, PR AF Argaw, T Cohen, JI Klutch, M Lekstrom, K Yoshikawa, T Asano, Y Krause, PR TI Nucleotide sequences that distinguish Oka vaccine from parental Oka and other varicella-zoster virus isolates SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID POLYMERASE-CHAIN-REACTION; FRAGMENT-LENGTH-POLYMORPHISM; TRANSMISSION; STRAIN; IDENTIFICATION; CHILDREN; LEUKEMIA; VZV AB The sequences of similar to 34 Icb from the 3' end of the varicella-zoster virus (VZV) Oka vaccine strain and the previously sequenced Dumas strain were compared. Sequence differences were noted in the coding sequences of several VZV open reading frames (ORFs), including ORFs 48, 51, 52, 55, 56, 58, 59, 60, 62, 64, and 68, Tests based on differences in the ORF62 gene and in the ORF64 poly-A region successfully distinguished the Oka vaccine strain from its wild-type parent and from other Japanese and US clinical isolates. These changes remained stable after passage of the virus in humans. C1 US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod, Bethesda, MD USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Fujita Hlth Univ, Dept Pediat, Aichi, Japan. RP Krause, PR (reprint author), 29A-1C16,29 Lincoln Dr, Bethesda, MD 20892 USA. RI Asano, Yoshizo/F-6870-2012 NR 18 TC 47 Z9 66 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR PY 2000 VL 181 IS 3 BP 1153 EP 1157 DI 10.1086/315335 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 302BE UT WOS:000086344400047 PM 10720545 ER PT J AU Williams, JA Pontzer, CH Shacter, E AF Williams, JA Pontzer, CH Shacter, E TI Regulation of macrophage interleukin-6 (IL-6) and IL-10 expression by prostaglandin E-2: The role of p38 mitogen-activated protein kinase SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID TUMOR-NECROSIS-FACTOR; MURINE PERITONEAL-MACROPHAGES; FACTOR-ALPHA; CYTOKINE PRODUCTION; GENE-EXPRESSION; SYNTHASE CYCLOOXYGENASE; ENDOPEROXIDE SYNTHASE-2; SELECTIVE INHIBITOR; HUMAN MONOCYTES; MESSENGER-RNA AB Prostaglandin E-2 (PGE(2)) regulates production of a wide array of cytokines, We have found that PGE(2) can upregulate the levels of both interleukin-10 (IL-10) and IL-6 produced by activated murine macrophages, but the molecular pathways leading to their augmentation differ. Synthesis of IL-10 in response to PGE(2) is dependent on p38 MAP kinase activity, whereas synthesis of IL-6 is not. Evidence to support this derives from two experimental approaches. First, me established that PGE(2) is effective in elevating IL-10 levels only when it is added to cells in which p38 kinase has been activated. In contrast, PGE(2) can augment IL-6 levels regardless of whether or not p38 kinase is active. Second, we showed that inhibitors that are selective for p38 kinase prevent the IL-10 response to PGE(2) but not the IL-6 response, We found that p38 kinase inhibitors are able to inhibit IL-6 production in activated macrophages, but this occurs primarily as a result of their concurrent inhibition of cyclooxygenase-2 and endogenous PGE(2) synthesis. These results indicate that macrophage IL-10 and IL-6 expression is differentially regulated by PGE(2) and p38 MAP kinase in murine inflammatory macrophages. C1 US FDA, Ctr Biol Evaluat & Res, Immunol Lab, Bethesda, MD 20892 USA. Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA. RP Shacter, E (reprint author), US FDA, Ctr Biol Evaluat & Res, Immunol Lab, HFM-538,Bldg 29A,Room 2A-11, Bethesda, MD 20892 USA. NR 39 TC 45 Z9 47 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD MAR PY 2000 VL 20 IS 3 BP 291 EP 298 DI 10.1089/107999000312423 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 297EY UT WOS:000086070000004 PM 10762076 ER PT J AU Anziano, P Quan, R Mize, C AF Anziano, P Quan, R Mize, C TI Mitochondrial DNA deletions associated with a novel, isoform of human manganese superoxide dismutase. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Nevada, Reno, NV 89557 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2000 VL 48 IS 2 MA 167 BP 212A EP 212A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CE UT WOS:000086346700180 ER PT J AU Stein, E Handelsman, E Matthews, R AF Stein, E Handelsman, E Matthews, R TI Reducing perinatal transmission of HIV: Early diagnosis and interventions during pregnancy SO JOURNAL OF MIDWIFERY & WOMENS HEALTH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ZIDOVUDINE PROPHYLAXIS; RISK-FACTORS; TYPE-1; WOMEN AB This article reviews the New York State regulations regarding expedited testing of newborns for exposure to HIV. Included is a review of statistics as well as the medical and obstetric management of HIV positive pregnant women, including route of delivery. The professional responsibility of midwives, physicians, and other clinicians regarding maternal and neonatal health care is emphasized, especially in states without expedited testing. (C) 2000 by the American College of Nurse-Midwives. C1 SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. Kings Cty Hosp Ctr, Brooklyn, NY 11203 USA. US FDA, Rockville, MD 20857 USA. RP Stein, E (reprint author), 345 E 73rd St, New York, NY 10021 USA. NR 21 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1526-9523 J9 J MIDWIFERY WOM HEAL JI J. Midwifery Women Health PD MAR-APR PY 2000 VL 45 IS 2 BP 122 EP 129 DI 10.1016/S1526-9523(00)00005-2 PG 8 WC Nursing SC Nursing GA 312JW UT WOS:000086941000006 PM 10812857 ER PT J AU Kisielewski, RW Routson, LB Chaput, MP Lytle, CD AF Kisielewski, RW Routson, LB Chaput, MP Lytle, CD TI Modification of ASTM F 1671-97a, resistance of materials to penetration by blood-borne pathogens, for use with elastomeric materials SO JOURNAL OF TESTING AND EVALUATION LA English DT Article DE viral penetration; barrier test; protective clothing; biological hazard; ASTM F 1670; ASTM F 1671; elastic; support screen AB A modification to ASTM F 1671-97a, Test Method for Resistance of Materials Used in Protective Clothing to Penetration by Blood-Borne Pathogens Using Phi-X174 Bacteriophage Penetration as a Test System, was developed to allow evaluation of elastomeric materials having small tears. The original method provides for a flat, open-mesh support screen to prevent expansion of such materials. While natural latex rubber specimens with open, laser-drilled holes (greater than or equal to 1 mu m) fail this test by allowing virus penetration , nitrile-butadiene rubber specimens with small tears (20 to 45 pm) pass. A stainless steel wire cloth support screen with a hemispherical-like dome, in lieu of the flat screen, provided controlled expansion and allowed detection of defective specimens with tears. The data also suggest a similar modification to enhance ASTM F 1670-97, Test Method for Resistance of Materials Used in Protective Clothing to Penetration by Synthetic Blood. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. RP Kisielewski, RW (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NR 4 TC 2 Z9 2 U1 0 U2 2 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 MAR PY 2000 VL 28 IS 2 BP 136 EP 138 PG 3 WC Materials Science, Characterization & Testing SC Materials Science GA 295QR UT WOS:000085979800011 ER PT J AU Jonnalagadda, SS Mitchell, DC Smiciklas-Wright, H Meaker, KB Van Heel, N Karmally, W Ershow, AG Kris-Etherton, PM AF Jonnalagadda, SS Mitchell, DC Smiciklas-Wright, H Meaker, KB Van Heel, N Karmally, W Ershow, AG Kris-Etherton, PM TI Accuracy of energy intake data estimated by a multiple-pass, 24-hour dietary recall technique SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID DOUBLY LABELED WATER; MAINTAIN BODY-WEIGHT; FOOD-INTAKE; FUNDAMENTAL PRINCIPLES; WOMEN; RECORDS; EXPENDITURE; OBESE; ADULTS; INTERVENTION AB Objective This study examined the accuracy of a multiple-pass, 24-hour dietary recall method for estimating energy intakes of men and women by comparing it with energy intake required for weight maintenance. Design Three-day, multiple-pass, 24-hour recalls were obtained on randomly selected days during a self-selected diet period when subjects were preparing their own meals and during a controlled diet period when all meals were provided by the study. During the dietary intervention, weight was maintained; body weight and dietary intake were monitored closely, thereby allowing estimation of the energy intake required for weight maintenance. Subjects/setting Seventy-eight men and women (22 to 67 years old) from the Dietary Effects on Lipoprotein and Thrombogenic Activity (DELTA) study participated in this study. All 24-hour recalls were collected using a computer-assisted, interactive, multiple-pass telephone interview technique. Energy requirements for each individual were determined by the energy content of the DELTA study foods provided to maintain weight. Statistical analysis Paired and independent t tests were conducted to examine differences among study variables. Agreement between recalled energy intake and weight maintenance energy intake was analyzed using the Bland-Altman technique, Results Compared with weight maintenance energy intake, during the self-selected diet period men and women underestimated energy intake by 11% and 13%, respectively. During the controlled diet period, men underestimated energy intake by 13%, whereas women overestimated energy by 1.3%. Applications/conclusions Men had a tendency to underestimate energy intake irrespective of the recording period. The accuracy of the recalled energy intake of women may be influenced by recording circumstances. Researchers should examine the factors influencing underreporting and overreporting by individuals and their impact on macronutrient and micronutrient intakes. Also, strategies need to be developed to minimize underreporting and overreporting. C1 Georgia State Univ, Dept Nutr, Atlanta, GA 30303 USA. Penn State Nutr Ctr, Diet Assessment Serv, University Pk, PA USA. Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. US FDA, Div Reprod & Urol Prod, Rockville, MD 20857 USA. Penn State Univ, Dept Stat, University Pk, PA 16802 USA. Univ Minnesota, Div Epidemiol, Nutr Coordinating Ctr, Minneapolis, MN 55455 USA. Columbia Univ, Irving Ctr Clin Res, New York, NY USA. NHLBI, Div Heart & Vasc Dis, NIH, Bethesda, MD 20892 USA. RP Jonnalagadda, SS (reprint author), Georgia State Univ, Dept Nutr, Univ Plaza, Atlanta, GA 30303 USA. FU NHLBI NIH HHS [U01-HL49659] NR 51 TC 121 Z9 121 U1 0 U2 8 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAR PY 2000 VL 100 IS 3 BP 303 EP 311 DI 10.1016/S0002-8223(00)00095-X PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 460MD UT WOS:000170310600010 PM 10719403 ER PT J AU Vesper, S Dearborn, DG Yike, I Allan, T Sobolewski, J Hinkley, SF Jarvis, BB Haugland, RA AF Vesper, S Dearborn, DG Yike, I Allan, T Sobolewski, J Hinkley, SF Jarvis, BB Haugland, RA TI Evaluation of Stachybotrys chartarum in the house of an infant with pulmonary hemorrhage: Quantitative assessment before, during, and after remediation SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article DE mold; pulmonary hemorrhage; remediation; Stachybotrys ID FUNGI; EXPOSURE; ATRA AB Stachybotrys chartarum is an indoor mold that has been associated with pulmonary hemorrhage cases in the Cleveland, Ohio, area. This study applied two new quantitative measurements to air samples from a home in which an infant developed PH. Quantitative polymerase chain reaction and a protein synthesis inhibition assay were used to determine the level of S. chartarum spores and their toxicity in air samples taken before, during, and after a remediation program was implemented to remove the fungus. Initial spore concentrations were between 0.1 and 9.3 spores/m(3) of air, and the toxicity of air particulates was correspondingly low. However, the dust in the house contained between 0.4 and 2.1 x 10(3) spores/mg (as determined by hemocytometer counts). The remediation program removed all contaminated wallboard, paneling, and carpeting in the water-damaged areas of the home, In addition, a sodium hypochlorite solution was used to spray all surfaces during remediation. Although spore counts and toxicity were high during remediation, air samples taken postremediation showed no detectable levels of S. chartarum or related toxicity. Nine isolates of S. chartarum obtained from the home were analyzed for spore toxicity, hemolytic activity, and random amplified polymorphic DNA banding patterns. None of the isolates produced highly toxic spores (>90 mu g T2 toxin equivalents per gram wet weight spores) after growth for 10 and 30 days on wet wallboard, but three isolates were hemolytic consistently. DNA banding patterns suggested that at least one of these isolates was related to isolates from homes of infants with previously investigated cases. C1 US EPA, Natl Exposure Res Lab, Cincinnati, OH 45268 USA. Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA. Cuyahoga Cty Board Hlth, Cleveland, OH USA. Univ Maryland, Dept Chem & Biochem, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Vesper, S (reprint author), US EPA, Natl Exposure Res Lab, 26 W Martin Luther King Dr,ML 314, Cincinnati, OH 45268 USA. EM Vesper.Stephan@EPA.gov OI Hinkley, Simon F.R./0000-0002-1831-8389 NR 22 TC 57 Z9 60 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1099-3460 J9 J URBAN HEALTH JI J. Urban Health PD MAR PY 2000 VL 77 IS 1 BP 68 EP 85 DI 10.1007/BF02350963 PG 18 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 287KM UT WOS:000085505100005 PM 10741843 ER PT J AU Dyer, NW Krogh, DF DeVold, R Wilson, SL White, DG AF Dyer, NW Krogh, DF DeVold, R Wilson, SL White, DG TI Chromobacteriosis in a Chinese red panda (Ailurus fulgens styani) SO JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION LA English DT Article ID ACUTE PLEUROPNEUMONIA; VIOLACEUM SEPTICEMIA; INFECTIONS AB An adult Chinese red panda (Ailurus fulgens styani) transported by airplane from Florida to a North Dakota zoo died 1 week after arrival. Grossly, an interscapular abscess, subcutaneous inflammation, lymphadenitis, and pulmonary abscesses were observed. Microscopic findings included necrotizing inflammation in liver, lung, lymph node, and spleen. Chromobacterium violaceum was cultured from the interscapular abscess, liver, lung, and spleen and was injected into Swiss Webster mice. These mice died 18 hours postinoculation, and C. violaceum was cultured from liver, lung, and spleen. Chromobacterium violaceum is a sporadically reported but highly virulent pathogenic bacterium of both animals and humans typically found as a soil and water inhabitant of tropical and subtropical regions. C1 N Dakota State Univ, Dept Vet & Microbiol Sci, Fargo, ND 58105 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Dyer, NW (reprint author), N Dakota State Univ, Dept Vet & Microbiol Sci, Fargo, ND 58105 USA. NR 22 TC 10 Z9 11 U1 1 U2 3 PU AMER ASSOC VETERINARY LABORATORY DIAGNOSTICIANS INC PI TURLOCK PA PO BOX 1522, TURLOCK, CA 95381 USA SN 1040-6387 J9 J VET DIAGN INVEST JI J. Vet. Diagn. Invest. PD MAR PY 2000 VL 12 IS 2 BP 177 EP 179 PG 3 WC Veterinary Sciences SC Veterinary Sciences GA 297YH UT WOS:000086110300017 PM 10730953 ER PT J AU Vernozy-Rozand, C Feng, P Montet, MP Ray-Gueniot, S Villard, L Bavai, C Meyrand, A Mazuy, C Atrache, V AF Vernozy-Rozand, C Feng, P Montet, MP Ray-Gueniot, S Villard, L Bavai, C Meyrand, A Mazuy, C Atrache, V TI Detection of Escherichia coli O157 : H7 in heifers' faecal samples using an automated immunoconcentration system SO LETTERS IN APPLIED MICROBIOLOGY LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; IMMUNOMAGNETIC SEPARATION; SEROTYPE O157-H7; MULTIPLEX PCR; FOOD SAMPLES; CATTLE; IDENTIFICATION; INFECTIONS; DAIRY; GENE AB Pre-treatment of a 5-h enrichment culture with an automated immunoconcentration (ICE) system greatly improved the isolation of Escherichia call O157:H7 from spiked heifer faecal samples. Enrichment samples plated directly onto sorbitol MacConkey agar (SMAC) and SMAC agar supplemented with cefixime and potassium tellurite (CT-SMAC) showed recovery rates of 8% and 56%, respectively. However, after ICE treatment, E. coli O157:H7 was recovered from 92% of the samples on SMAC and 100% on CT-SMAC. Immunoconcentration analysis of heifers' faecal samples collected from a slaughterhouse in France, during March to June 1998, showed that 1% (three of 300) was positive for E. coli O157:H7. Phenotypic and genotypic analysis showed that all three isolates carried both the O157 and H7 antigens, did not ferment sorbitol or had beta-glucuronidase activity and carried trait virulence factors for E. coli O157:H7 (uidA allele, eaeA and pO157 plasmid). However, only one strain was toxigenic and this strain produced a single toxin, namely verotoxin 2. C1 Ecole Natl Vet Lyon, Unite Microbiol Alimentaire & Microbiol Prevision, F-69280 Marcy Letoile, France. US FDA, Washington, DC 20204 USA. BioMerlieux, Marcy Letoile, France. RP Vernozy-Rozand, C (reprint author), Ecole Natl Vet Lyon, Unite Microbiol Alimentaire & Microbiol Prevision, 1 Ave Bourgelat,BP 83, F-69280 Marcy Letoile, France. NR 24 TC 20 Z9 21 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0266-8254 J9 LETT APPL MICROBIOL JI Lett. Appl. Microbiol. PD MAR PY 2000 VL 30 IS 3 BP 217 EP 222 DI 10.1046/j.1472-765x.2000.00702.x PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 300VA UT WOS:000086272800010 PM 10747254 ER PT J AU Wojnowski, L Stancato, LF Larner, AC Rapp, UR Zimmer, A AF Wojnowski, L Stancato, LF Larner, AC Rapp, UR Zimmer, A TI Overlapping and specific functions of Braf and Craf-1 proto-oncogenes during mouse embryogenesis SO MECHANISMS OF DEVELOPMENT LA English DT Article DE Braf; Craf-1; proto-oncogenes; embryogenesis ID SIGNAL-TRANSDUCTION PATHWAY; B-RAF; DIFFERENTIAL REGULATION; A-RAF; GENE-EXPRESSION; KINASE CASCADE; GROWTH-FACTOR; CELLS; ACTIVATION; MICE AB The three mammalian Raf serine/threonine protein kinases mediate the transduction of proliferative and differentiative signals from cell surface receptors to the nucleus. In vertebrates, Raf signaling has been implicated in the progression of mouse embryos through the two-cell stage and in the induction of posterior mesoderm. However, mouse embryos mutant for each of the Raf genes exhibit no developmental defects before mid-gestation. Here we describe the phenotype of mouse mutants with different combinations of mutant Craf-1 and Braf alleles. Our results show that Raf signaling is indeed indispensable for normal development beyond the blastocyst stage. However, due to a significant redundancy between Craf-1 and Braf, either gene is sufficient for normal development until mid-gestation. The molecular and developmental mechanisms for this redundancy were investigated by monitoring the expression of Raf genes throughout embryogenesis and by biochemical studies in mutant cell lines. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Epidauros Biotechnol Ag, D-82347 Bernried, Germany. NIMH, Genet Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. Univ Wurzburg, Inst Med Strahlenkunde & Zellforsch, Wurzburg, Germany. RP Wojnowski, L (reprint author), Epidauros Biotechnol Ag, Neuland 1, D-82347 Bernried, Germany. RI Zimmer, Andreas/B-8357-2009 NR 33 TC 78 Z9 81 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD MAR 1 PY 2000 VL 91 IS 1-2 BP 97 EP 104 DI 10.1016/S0925-4773(99)00276-2 PG 8 WC Developmental Biology SC Developmental Biology GA 298NR UT WOS:000086146500010 PM 10704835 ER PT J AU Emmert-Buck, MR Gillespie, JW Paweletz, CP Ornstein, DK Basrur, V Appella, E Wang, QH Huang, J Hu, N Taylor, P Petricoin, EF AF Emmert-Buck, MR Gillespie, JW Paweletz, CP Ornstein, DK Basrur, V Appella, E Wang, QH Huang, J Hu, N Taylor, P Petricoin, EF TI An approach to proteomic analysis of human tumors SO MOLECULAR CARCINOGENESIS LA English DT Article DE esophagus; neoplasia; microdissection; proteomics; two-dimensional electrophoresis ID MASS-SPECTROMETRIC IDENTIFICATION; LASER CAPTURE MICRODISSECTION; ANNEXIN-I; DIFFERENTIAL EXPRESSION; GEL-ELECTROPHORESIS; SAMPLE PREPARATION; COLORECTAL-CANCER; EPITHELIAL-CELLS; CARCINOMA; PROTEINS AB A strategy for proteomic analysis of microdissected cells derived from human tumor specimens is described and demonstrated by using esophageal cancer as an example. Normal squamous epithelium and corresponding tumor cells from two patients were procured by laser-capture microdissection and studied by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Fifty thousand cells resolved approximately 675 distinct proteins (or isoforms) with molecular weights ranging between 10 and 200 kDa and isoelectric points of pH 3-10. Comparison of the microdissected protein profiles showed a high degree of similarity between the matched normal-tumor samples (98% identical). However, 17 proteins showed tumor-specific alterations, including 10 that were uniquely present in the tumors and seven that were observed only in the normal epithelium. Two of the altered proteins were characterized by mass spectrometry and immunoblot analysis and were identified as cytokeratin 1 and annexin I. Acquisition of 2D-PAGE protein profiles, visualization of disregulated proteins, and subsequent determination of the identity of selected proteins through high-sensitivity MS-MS microsequencing are possible from microdissected cell populations. These separation and analytical techniques are uniquely capable of detecting tumor-specific alterations. Continued refinement of techniques and methodologies to determine the abundance and status of proteins in vivo holds great promise for future study of normal cells and associated neoplasms. Mol. Carcinog. 27:158-165, 2000. Published by Wiley-Liss Inc. C1 US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Tissue Proteom Unit, Bethesda, MD 20892 USA. NCI, Pathogenet Unit, Pathol Lab, Bethesda, MD 20892 USA. NCI, Canc Genome Anat Project, Off Director, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, Bethesda, MD 20892 USA. Shanxi Canc Hosp, Pathol Lab, Taiyuan, Peoples R China. NCI, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. Georgetown Univ, Dept Chem, Washington, DC 20057 USA. RP Petricoin, EF (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Tissue Proteom Unit, Bethesda, MD 20892 USA. NR 36 TC 157 Z9 175 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAR PY 2000 VL 27 IS 3 BP 158 EP 165 DI 10.1002/(SICI)1098-2744(200003)27:3<158::AID-MC2>3.0.CO;2-2 PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 289WL UT WOS:000085644900002 PM 10708477 ER PT J AU Leland, P Taguchi, J Husain, SR Kreitman, RJ Pastan, I Puri, RK AF Leland, P Taguchi, J Husain, SR Kreitman, RJ Pastan, I Puri, RK TI Human breast carcinoma cells express type IIIL-4 receptors and are sensitive to antitumor activity of a chimeric IL-4-Pseudomonas exotoxin fusion protein in vitro and in vivo SO MOLECULAR MEDICINE LA English DT Article ID CIRCULARLY PERMUTED INTERLEUKIN-4; TUMOR-NECROSIS-FACTOR; COMMON GAMMA-CHAIN; PSEUDOMONAS EXOTOXIN; CANCER-CELLS; FUNCTIONAL COMPONENT; IL-2 RECEPTOR; IN-VIVO; KAPOSIS-SARCOMA; HUMAN-MELANOMA AB Background: Human breast carcinoma cell lines express high-affinity interleukin-4 receptors (IL-4R). We examined the expression and structure of these receptors on primary and cultured breast carcinoma cell lines and normal breast epithelial cells. We also tested the antitumor activity in vitro and in vivo of a fusion protein comprised of circular permuted IL-4 and truncated Pseudomonas exotoxin, termed IL-4(38-37)-PE38KDEL. Materials and Methods: Eight different primary cell cultures and cell lines of human breast carcinomas were examined for the expression of IL-4R by radiolabeled binding, reverse transcription polymerase chain reaction (RT-PCR) and Northern analyses, and subunit structure by crosslinking studies. The antitumor activity of IL-4 toxin was tested in vitro by cytotoxicity assays and in vivo in a xenograft model in immunodeficient animals. Results: I-125-IL-4 specifically bound to primary cell cultures and cell lines with a Iid ranging between 0.2 and 1 nM. Breast tumor cells were found to express IL-4R beta and IL-13R alpha' chains, but not IL-2R gamma(c) chain. These cells were highly sensitive to the cytotoxic effect of IL-4(38-37)-PE38KDEL. The IC,, (concentration inhibiting protein synthesis by 50%) ranged between approximately 0.005-1.5 nM. A normal breast epithelial cell culture was not sensitive to the cytotoxic activity of IL-4(38-37)PE38KDEL. MDA-MB231 human breast carcinoma cell line formed a rapidly growing tumor in nude mice. Intratumor and intraperitoneal administration of IL-4(38-37)-PE38KDEL caused a dose dependent regression of established tumors. A control toxin, anti-Tac(Fv)-PE38KDEL, targeted to the IL-2 receptor a chain did not cause regression of these tumors. Conclusions: These results suggest that IL-4(38-37)-PE38KDEL may be a useful agent for targeting of IL-4 receptor positive human breast carcinomas and further studies should be performed to explore fully its potential. C1 NIH, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,Food & Drug Adm, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Div Canc Biol Diag & Ctr, NIH, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), NIH, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,Food & Drug Adm, Bethesda, MD 20892 USA. NR 50 TC 37 Z9 38 U1 0 U2 1 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD MAR PY 2000 VL 6 IS 3 BP 165 EP 178 PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 327MD UT WOS:000087796900003 PM 10965493 ER PT J AU Cada, A de la Torre, JC Gonzalez-Lima, F AF Cada, A de la Torre, JC Gonzalez-Lima, F TI Chronic cerebrovascular ischemia in aged rats: effects on brain metabolic capacity and behavior SO NEUROBIOLOGY OF AGING LA English DT Article DE cytochrome oxidase; cerebral blood flow; metabolic dysfunction; visuospatial learning; Alzheimer's disease ID CEREBRAL BLOOD-FLOW; CYTOCHROME-OXIDASE ACTIVITY; MULTI-INFARCT DEMENTIA; ALZHEIMERS-DISEASE; MEMORY DYSFUNCTION; GLUCOSE-METABOLISM; CAROTID ARTERIES; SENILE DEMENTIA; WISTAR RATS; HYPOPERFUSION AB The objective of this study was to model one of the risk factors for the development of late-onset Alzheimer's disease, decreased cerebral blood flow. Aging rats were tested for visuospatial behavioral deficits after permanent surgical occlusion of both carotid arteries. This was followed after 4 weeks by quantitative cytochrome oxidase histochemical mapping of metabolic capacity throughout the brain. The brain regions affected were related to observed deficits in spatial memory (CAI and posterior parietal cortex), visually guided movements (superior colliculus and secondary visual cortex), motor coordination (red nucleus), and escape behavior (central gray). The results suggest that deficits in visuospatial learning are not exclusively the result of hippocampal dysfunction, but may be directly correlated with altered oxidative energy metabolism in other integrative visuomotor regions identified in this study. It was concluded that chronic cerebrovascular ischemia in this aged rat model produces neurometabolic and behavioral alterations that may be relevant for an increased risk for the development of Alzheimer's disease. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Univ Texas, Inst Neurosci, Austin, TX 78712 USA. Univ Texas, Dept Psychol, Austin, TX 78712 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72029 USA. Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 USA. RP Gonzalez-Lima, F (reprint author), Univ Texas, Inst Neurosci, Mezes Hall 330, Austin, TX 78712 USA. NR 60 TC 23 Z9 33 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR-APR PY 2000 VL 21 IS 2 BP 225 EP 233 DI 10.1016/S0197-4580(00)00116-0 PG 9 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 328BY UT WOS:000087830000009 PM 10867207 ER PT J AU Hsia, CC Nakashima, Y Thorgeirsson, SS Harris, CC Minemura, M Momosaki, S Wang, NJ Tabor, E AF Hsia, CC Nakashima, Y Thorgeirsson, SS Harris, CC Minemura, M Momosaki, S Wang, NJ Tabor, E TI Correlation of immunohistochemical staining and mutations of p53 in human hepatocellular carcinoma SO ONCOLOGY REPORTS LA English DT Article DE hepatocellular carcinoma; immunohistochemistry; mutation; p53; tumor suppressor gene ID GENE MUTATION; CANCER; OVEREXPRESSION; MARKER AB Mutations of the p53 tumor suppressor gene are common in hepatocellular carcinomas (HCCs). Detection of mutations by sequencing provides more information than immunohistochemical staining, but the equipment needed and the time required make it less practical for use in large-scale studies or in studies in developing countries. The degree of correlation between results obtained with these two methods has been studied in various tumors but has not been well-established in human HCCs. Paraffin sections of HCCs of 28 patients from Qidong, China were immunohistochemically stained using monoclonal antibody to p53. In addition, exons 5-8 of the p53 gene were sequenced in these HCCs. Of the 28 HCCs, nine had 0-9% of nuclei stained for p53, and 19 had 50-95% stained. Mutations in p53 exons 5-8 were found in 17/28 (61%) HCCs, including 15 at codon 249 (exon 7), one at codon 198 (exon 6), and one at codon 175 (exon 5). Among these 17 cases with p53 mutations, 16 cases (94%) had 50-95% of nuclei stained. Among 11 HCCs with no mutations by sequencing, 8 were also negative by immunohistochemistry (0-9% of nuclei stained) (73%) (the five HCCs with no staining whatsoever all had wild-type p53). Immunohistochemical staining to detect p53 mutations in human HCCs detected most mutations that were detected by sequencing (94% sensitivity, 73% specificity), and this method is therefore suitable when sequencing cannot be performed. C1 US FDA, CBER, Div Transfus Transmitted Dis, Rockville, MD 20852 USA. NCI, NIH, Bethesda, MD 20892 USA. Toyama Med & Pharmaceut Univ, Toyama, Japan. Qidong Liver Canc Inst, Qidong, Peoples R China. RP Tabor, E (reprint author), US FDA, CBER, Div Transfus Transmitted Dis, HFM-300,1401 Rockville Pike,Suite 400N, Rockville, MD 20852 USA. NR 15 TC 28 Z9 30 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD MAR-APR PY 2000 VL 7 IS 2 BP 353 EP 356 PG 4 WC Oncology SC Oncology GA 282AV UT WOS:000085194400025 PM 10671685 ER PT J AU Pflug, IJ Evans, KD AF Pflug, IJ Evans, KD TI Carrying out biological qualification, the control operation of moist-heat (steam sterilization) processes for producing sterile pharmaceuticals and medical devices SO PDA JOURNAL OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY LA English DT Article AB In this report we will first discuss the principles behind the practices that are used today in the design and qualification of moist-heat (steam sterilization) microbial-control processes used to produce sterile pharmaceutical products and medical devices. Secondly, we will work through example applications of how to design and quality processes of three levels of complexity which we call Empirical Over-kill, Empirical, and Product Specific. Empirical Overkill is specifically for the microbial-control processes for indirect items, such as tanks, pipes, pumps and other hardware. Empirical is for pharmaceutical and medical-device products that are produced under good manufacturing conditions and therefore, there is control of the level of the microbial bioburden. Product Specific is for microbial-control processes designed and qualified for a specific product on the basis of the numbers and resistance of the bioburden of that product. We will treat design in this report; however; the major thrust is in setting up and carrying out the biological qualification of the process, which is the mode of control used to assure the adequacy of these microbial-control processes. C1 Univ Minnesota, St Paul, MN 55108 USA. US FDA, Off Regulatory Affairs, Rockville, MD 20857 USA. RP Pflug, IJ (reprint author), Univ Minnesota, Dept Food Sci & Nutr, Sheperd Lab 585, 100 Union St SE, Minneapolis, MN 55455 USA. NR 17 TC 5 Z9 5 U1 1 U2 4 PU PARENTERAL DRUG ASSOC INC PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 620, BETHESDA, MD 20814 USA SN 1076-397X J9 PDA J PHARM SCI TECH JI PDA J. Pharm. Sci. Technol. PD MAR-APR PY 2000 VL 54 IS 2 BP 117 EP 135 PG 19 WC Engineering, Biomedical; Pharmacology & Pharmacy SC Engineering; Pharmacology & Pharmacy GA 348KH UT WOS:000088983700006 PM 10822983 ER PT J AU Brinton, LA Brown, SL Colton, T Burich, MC Lubin, J AF Brinton, LA Brown, SL Colton, T Burich, MC Lubin, J TI Characteristics of a population of women with breast implants compared with women seeking other types of plastic surgery SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID RHEUMATOID-ARTHRITIS; AUGMENTATION MAMMAPLASTY; ORAL-CONTRACEPTIVES; LOS-ANGELES; FOLLOW-UP; CANCER; RISK AB Several previous studies have shown that breast implant patients demonstrate a number of differences compared with the general population. However, studies have not compared patients with breast implants with women receiving other types of plastic surgery, of interest because this latter group has been proposed as a comparison group for assessing the long-term health effects experienced by breast implant patients. Questionnaire data obtained from 7447 breast implant patients and 2203 patients with Other types plastic surgery were collected during the course of a retrospective cohort study, to determine whether implant patients demonstrate different characteristics compared with a more restricted group of patients. In contrast to previous investigations that compared implant patients with the general population, distinctive differences with respect to family income, number of pregnancies, alcohol consumption, cigarette smoking, or histories of previous gynecologic operations or operations for benign breast disease were not found. However, implant patients were significantly more likely than other plastic surgery patients to be white, have low levels of education, have early ages at first birth, be thin, and be screened frequently for breast disease. Furthermore, implant patients reported somewhat greater use of exogenous hormones and familial histories of rheumatoid arthritis. These results support the notion that other plastic surgery patients are a more appropriate comparison group than women in the general population for studies of the health effects of breast implants; however, there continue to be distinctive characteristics possessed by breast implant patients, which need to be taken into account in an assessment of what disease effects can be uniquely attributed to silicone breast implants. C1 NCI, Environm Epidemiol Branch, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20857 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. ABT Associates Inc, Cambridge, MA 02138 USA. NCI, Biostat Branch, Bethesda, MD 20892 USA. RP Brinton, LA (reprint author), NCI, Environm Epidemiol Branch, Execut Plaza S,Room 7068,6120 Execut Blvd,MSC 723, Bethesda, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 29 TC 43 Z9 44 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAR PY 2000 VL 105 IS 3 BP 919 EP 927 DI 10.1097/00006534-200003000-00014 PG 9 WC Surgery SC Surgery GA 292HB UT WOS:000085787600014 PM 10724251 ER PT J AU Junod, SW AF Junod, SW TI The history of the U.S. Army Medical Service Corps SO PUBLIC HISTORIAN LA English DT Book Review C1 US FDA, Washington, DC 20204 USA. RP Junod, SW (reprint author), US FDA, Washington, DC 20204 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU UNIV CALIF PRESS PI BERKELEY PA C/O JOURNALS DIVISION, 2000 CENTER ST, STE 303, BERKELEY, CA 94704-1223 USA SN 0272-3433 J9 PUBL HISTORIAN JI Public Hist. PD SPR PY 2000 VL 22 IS 2 BP 105 EP 106 PG 2 WC History SC History GA 322VD UT WOS:000087528900022 ER PT J AU Blair, RM Fang, H Branham, WS Hass, BS Dial, SL Moland, CL Tong, WD Shi, LM Perkins, R Sheehan, DM AF Blair, RM Fang, H Branham, WS Hass, BS Dial, SL Moland, CL Tong, WD Shi, LM Perkins, R Sheehan, DM TI The estrogen receptor relative binding affinities of 188 natural and xenochemicals: Structural diversity of ligands SO TOXICOLOGICAL SCIENCES LA English DT Article DE estrogen receptor competitive-binding assay; relative binding affinity; estrogens; antiestrogens; alkylphenols; organochlorines; pesticides; parabens; phthalates ID METHYL-P-HYDROXYBENZOATES; ENVIRONMENTAL ESTROGENS; POLYCHLORINATED-BIPHENYLS; RAT HEPATOCYTES; BISPHENOL-A; CHEMICALS; PRESERVATIVES; ESTRADIOL; PHTHALATE; MODEL AB We have utilized a validated (standardized) estrogen receptor (ER) competitive-binding assay to determine the ER affinity for a large, structurally diverse group of chemicals. Uteri from ovariectomized Sprague-Dawley rats were the ER source for the competitive-binding assay. Initially, test chemicals were screened at high concentrations to determine whether a chemical competed with [H-3]-estradiol for the ER. Test chemicals that exhibited affinity for the ER in the first tier were subsequently assayed using a wide range of concentrations to characterize the binding curve and to determine each chemical's IC50 and relative binding affinity (RBA) values. Overall, we assayed 188 chemicals, covering a 1 x 10(6)-fold range of RBAs from several different chemical or use categories, including steroidal estrogens, synthetic estrogens, antiestrogens, other miscellaneous steroids, alkylphenols, diphenyl derivatives, organochlorines, pesticides, alkylhydroxybenzoate preservatives (parabens), phthalates, benzophenone compounds, and a number of other miscellaneous chemicals. Of the 188 chemicals tested, 100 bound to the ER while 88 were non-binders. Included in the 100 chemicals that bound to the ER were 4-benzyloxyphenol, 2,4-dihydroxybenzophenone, and 2,2'-methylenebis(4-chlorophenol), compounds that have not been shown previously to bind the ER. It was also evident that certain structural features, such as an overall ring structure, were important for ER binding. The current study provides the most structurally diverse ER RBA data set with the widest range of RBA values published to date. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. ROW Sci, Jefferson, AR 72079 USA. RP Blair, RM (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 74 TC 459 Z9 473 U1 4 U2 62 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2000 VL 54 IS 1 BP 138 EP 153 DI 10.1093/toxsci/54.1.138 PG 16 WC Toxicology SC Toxicology GA 292MU UT WOS:000085799400016 PM 10746941 ER PT J AU McQuiston, JH Childs, JE Chamberland, ME Tabor, E AF McQuiston, JH Childs, JE Chamberland, ME Tabor, E TI Transmission of tick-borne agents of disease by blood transfusion: a review of known and potential risks in the United States SO TRANSFUSION LA English DT Review ID HUMAN GRANULOCYTIC EHRLICHIOSIS; POLYMERASE CHAIN-REACTION; MOUNTAIN-SPOTTED-FEVER; NEW-YORK-STATE; BORRELIA-BURGDORFERI; LYME-DISEASE; BABESIA-MICROTI; TRANSMITTED BABESIOSIS; RICKETTSIA-RICKETTSII; INFECTIOUS-DISEASES C1 Ctr Dis Control & Prevent, Viral & Rickettsial Zoonoses Branch, Epidemiol Program Off, Atlanta, GA 30333 USA. Ctr Dis Control, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. US FDA, Rockville, MD 20857 USA. RP Childs, JE (reprint author), Ctr Dis Control & Prevent, Viral & Rickettsial Zoonoses Branch, Epidemiol Program Off, 1600 Clifton Rd Mailstop G-13, Atlanta, GA 30333 USA. RI Childs, James/B-4002-2012 NR 107 TC 89 Z9 92 U1 0 U2 5 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAR PY 2000 VL 40 IS 3 BP 274 EP 284 DI 10.1046/j.1537-2995.2000.40030274.x PG 11 WC Hematology SC Hematology GA 296QT UT WOS:000086036200004 PM 10738026 ER PT J AU Wear, KA AF Wear, KA TI Temperature dependence of ultrasonic attenuation in human calcaneus SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE attenuation; calcaneus; bone; osteoporosis; temperature; ultrasound ID HIP FRACTURE; BONE; VELOCITY; DENSITY; WOMEN AB Ultrasonic attenuation in calcaneus has been shown to be a useful measurement for the diagnosis of osteoporosis. Several studies indicate that this measurement is affected by temperature fluctuations, although the fundamental causes for this are currently not well understood. To investigate this phenomenon, six defatted human calcanei were interrogated in vitro at six temperatures ranging from 10 degrees C to 40 degrees C. The temperature-related variation was -0.18 dB/cmMHz degrees C (95% confidence interval: -0.27 dB/cmMHz degrees C, -0.10 dB/ cmMHz degrees C), This study reinforces the notion, advanced by other investigators, that temperature-related effects need to be taken into account when performing diagnostic measurements that require high precision (such as monitoring responses to drug intervention), will aid in the interpretation of in vivo experiments designed to investigate temperature-dependent precision limitations, will facilitate comparisons between in vitro studies normally carried out at room temperature with in vivo studies carried out at body temperature, and fills a gap in the compendium of measurements of temperature-dependences of acoustic properties of biologic tissues. (C) 2000 World Federation for Ultrasound in Medicine & Biology. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP US FDA, Ctr Devices & Radiol Hlth, HFZ-142,12720 Twinbrook Pkwy, Rockville, MD 20852 USA. EM kaw@cdrh.fda.gov NR 18 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-5629 EI 1879-291X J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD MAR PY 2000 VL 26 IS 3 BP 469 EP 472 DI 10.1016/S0301-5629(99)00135-0 PG 4 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 306UK UT WOS:000086614900014 PM 10773378 ER PT J AU Puri, B Polo, S Hayes, CG Falgout, B AF Puri, B Polo, S Hayes, CG Falgout, B TI Construction of a full length infectious clone for dengue-1 virus Western Pacific,74 strain SO VIRUS GENES LA English DT Article DE dengue-1 virus; molecular cloning; Sp6 RNA polymerase; in vitro transcription; RNA transfection; nucleotide sequence ID MOLECULAR-BIOLOGY; VACCINE CANDIDATE; SERIAL PASSAGE; KIDNEY-CELLS; CDNA CLONES; TYPE-2; IDENTIFICATION; IMMUNIZATION; ATTENUATION; VOLUNTEERS AB The flavivirus dengue 1 Western Pacific,74 (DEN1 WP) virus has a positive-stranded RNA genome of 10,735 nucleotides. DEN1 WP genomic RNA was amplified into three overlapping fragments by RT-PCR. These fragments were assembled into a full-length cDNA clone in the yeast-E. coli shuttle vector pRS424, using homologous recombination in yeast. RNA produced by in vitro transcription of this clone was infectious upon electroporation into LLCMK2 cells, as shown by cytopathic effects and detection of viral antigens by indirect immunofluorescence, and by propagation of the virus released into the culture media. Biological properties of the transcript-derived virus, such as the pattern of dengue-specific protein synthesis and growth rate in LLCMK2 or C6/36 cells, resembled those of the parent DEN1 WP virus. C1 USN, Med Res Inst, Dept Infect Dis, Viral & Rickettsial Dis Program, Bethesda, MD 20889 USA. US FDA, Ctr Biol Evaluat & Res, Lab Vector Borne Viral Dis, Rockville, MD 20852 USA. RP Puri, B (reprint author), USN, Med Res Ctr, Dept Infect Dis, Code 41,8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 24 TC 43 Z9 49 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-8569 J9 VIRUS GENES JI Virus Genes PD MAR PY 2000 VL 20 IS 1 BP 57 EP 63 PG 7 WC Genetics & Heredity; Virology SC Genetics & Heredity; Virology GA 282BT UT WOS:000085196600007 PM 10766307 ER PT J AU Sahi, J Hamilton, G Sinz, M Barros, S Huang, SM Lesko, LJ LeCluyse, EL AF Sahi, J Hamilton, G Sinz, M Barros, S Huang, SM Lesko, LJ LeCluyse, EL TI Effect of troglitazone on cytochrome P450 enzymes in primary cultures of human and rat hepatocytes SO XENOBIOTICA LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; GENE-EXPRESSION; THIAZOLIDINEDIONE; INDUCTION; CYP3A4 AB 1. Troglitazone was the first thiazolidinedione approved for clinical use in the treatment of non-insulin-dependent diabetes mellitus. During clinical investigations of drug-drug interactions with therapeutics (terfenadine and cyclosporine) known to be metabolized by CYP3A4, pharmacokinetic interactions were noted upon troglitazone multiple-dose treatments. The nature of the interactions suggested induction of CYP3A enzymes. 2. Primary cultures of human hepatocytes were used to investigate the induction potential of troglitazone with respect to CYP3A4, CYP2B6 and CYP1A1/2. In human hepatocytes, troglitazone induced both immunoreactive CYP3A4 protein and testosterone OP-hydroxylase activity in a dose-dependent fashion (EC50 = 5-10 mu M), accompanied by an increase in CYP3A4 mRNA. The capacity of troglitazone to induce CYP3A4 was between that of rifampin (EC50 = similar to 0.8 mu M) and dexamethasone (40-50 mu M). Troglitazone increased CYP2B6 immunoreactive: protein but did not significantly effect CYP1A1/2 activity, immunoreactive protein or mRNA. 3. Troglitazone produced significant increases in CYP3A message, protein and activity in primary rat hepatocytes, a slight increase in CYP2B1/2 activity and no change in CYP1A1/2 message or activity. 4. These results provide evidence that troglitazone can induce CYP3A and CYP2B enzymes while apparently not altering CYP1A. This provides a rationale for the clinically observed interactions of troglitazone with selected CYP3A4 substrates. C1 Univ N Carolina, Sch Pharm, Div Pharmaceut, Chapel Hill, NC 27599 USA. Parke Davis Pharmaceut Res, Ann Arbor, MI USA. US FDA, CDER, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. RP LeCluyse, EL (reprint author), Univ N Carolina, Sch Pharm, Div Pharmaceut, CB 7360,Beard Hall, Chapel Hill, NC 27599 USA. OI LeCluyse, Edward/0000-0002-2149-8990 FU PHS HHS [223-97-3004] NR 31 TC 77 Z9 78 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD MAR PY 2000 VL 30 IS 3 BP 273 EP 284 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 294DN UT WOS:000085896200005 PM 10752642 ER PT J AU D'Agnillo, F Alayash, AI AF D'Agnillo, F Alayash, AI TI Site-specific modifications and toxicity of blood substitutes - The case of diaspirin cross-linked hemoglobin SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE hemoglobin; hydrogen peroxide; diaspirin; nitric oxide; blood substitutes ID CELL-FREE HEMOGLOBIN; NITRIC-OXIDE; BIS(3,5-DIBROMOSALICYL) FUMARATE; BACTERIAL-ENDOTOXIN; ENDOTHELIAL-CELLS; HYDROGEN-PEROXIDE; ALPHA-CHAINS; INJURY; RATS; HEME AB Safe and effective hemoglobin-based blood substitutes may be advantageous over conventional therapies for certain clinical settings requiring short term blood replacement such as emergency resuscitation and hemodilution in surgery. Many advances have been made in developing these oxygen therapeutics, however safety concerns continue to slow their clinical progress. An important and often overlooked consideration in evaluating the safety of modified hemoglobins is the impact of chemical and/or genetic modifications on the redox chemistry of these proteins. Diaspirin cross-linked hemoglobin (DBBF-Hb) has been extensively evaluated in vitro and in animal models, and thus represents a useful model to explore possible correlations between structural-functional alterations and toxicity of hemoglobin-based blood substitutes. (C) 2000 Published by Elsevier Science BN. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Plasma Derivatives, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Plasma Derivatives, Bethesda, MD 20892 USA. NR 74 TC 40 Z9 41 U1 2 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 28 PY 2000 VL 40 IS 3 BP 199 EP 212 DI 10.1016/S0169-409X(99)00050-2 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 284MJ UT WOS:000085335900007 PM 10837790 ER PT J AU Yang, ZP Frey, W Oliver, T Chilkoti, A AF Yang, ZP Frey, W Oliver, T Chilkoti, A TI Light-activated affinity micropatterning of proteins on self-assembled monolayers on gold SO LANGMUIR LA English DT Article ID LASER-ABLATION; SURFACES; STREPTAVIDIN; THIOLS; BIOTIN; IMMOBILIZATION; COADSORPTION; ANTIBODIES; ESTERS; SCALE AB We describe a method to pattern proteins onto a photolabile "caged" biotin-derivatized self-assembled monolayer (SAM) on gold, which we term light-activated affinity micropatterning of proteins (LAMP). LAMP is a multistep patterning process with considerable flexibility in its implementation. First, a reactive SAM on gold is formed from a mixture of 11-mercaptolandecanol and 16-mercaptohexadecanoic acid. Next, the carboxylic acid end groups in the SAM are coupled to methyl alpha-nitropiperonyloxycarbonyl biotin succinimidyl ester (caged biotin ester) through a diamine linker. The caged biotin is then deprotected in regions irradiated by masked UV light, and subsequent incubation with streptavidin results in selective binding of streptavidin to the irradiated regions. Micropatterning of various proteins has been demonstrated with a spatial resolution of similar to 6 mu m by confocal microscopic imaging of fluorophore-labeled proteins, and a contrast ratio of similar to 4:1 was determined by direct ellipsometric imaging of streptavidin. Immobilization of biotinylated antibodies on the streptavidin pattern indicates that LAMP can enable spatially resolved micropatterning of different biomolecules by repeated cycles of spatially defined photodeprotection of biotin, streptavidin incubation, followed by immobilization of the biotinylated moiety of interest. C1 Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. US FDA, Rockville, MD 20857 USA. RP Chilkoti, A (reprint author), Duke Univ, Dept Biomed Engn, Box 90281, Durham, NC 27708 USA. NR 31 TC 67 Z9 68 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD FEB 22 PY 2000 VL 16 IS 4 BP 1751 EP 1758 DI 10.1021/la9908079 PG 8 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 285XA UT WOS:000085412600040 ER PT J AU Barton, CC Bucci, TJ Lomax, LG Warbritton, AG Mehendale, HM AF Barton, CC Bucci, TJ Lomax, LG Warbritton, AG Mehendale, HM TI Stimulated pulmonary cell hyperplasia underlies resistance to alpha-naphthylthiourea SO TOXICOLOGY LA English DT Article DE ANTU; ARDS; colchicine; epidermal growth factor receptor; hyperplasia; keratinocyte growth factor; lung; paraquat; permeability; resistance transforming growth factor-alpha transforming growth factor-beta ID RESPIRATORY-DISTRESS-SYNDROME; KERATINOCYTE GROWTH-FACTOR; EUROPEAN CONSENSUS CONFERENCE; CLINICAL-TRIAL COORDINATION; INDUCED LUNG INJURY; VASCULAR-PERMEABILITY; RELEVANT OUTCOMES; ANTIMITOTIC AGENT; RAT-LIVER; COLCHICINE AB The rodenticide alpha-naphthylthiourea (ANTU) causes pulmonary edema and pleural effusion that leads to death via pulmonary insufficiency. Rats become resistant to the lethal effect of ANTU if they are first exposed to a small, nonlethal dose of ANTU. Young rats are also resistant to ANTU. The mechanism by which rats develop resistance by a prior, small dose exposure has yet to be determined. Growth factor induced-pulmonary hyperplasia has been demonstrated to attenuate ANTU-induced lung leak. We hypothesized that a small dose of ANTU protects against a large dose through pulmonary cell hyperplasia induced by the protective dose. Furthermore, we hypothesized that this hyperplasia is associated with altered transcription of growth factors. Male Sprague-Dawley rats (175-225 g) were treated with a low dose of ANTU (5 mg ANTU/kg; ANTU(L)) 24 h before challenge with a 100% lethal dose of ANTU (70 mg ANTU/kg; ANTU(H)) resulting in 100% protection against the lethal effect of ANTU(H). ANTU(L) protection against ANTU(H) lasted for 5 days, slowly phased out, all being lost by day 20. Injury was assessed by estimating pulmonary vascular permeability and through histopathological examination. ANTU(H) alone resulted in an increase in pulmonary edema leading to animal death. However, injury was prevented if the rats were first treated with ANTU(L). There was a stimulation of pulmonary cell hyperplasia in the lungs of ANTU(L) treated rats as measured by [H-3]-thymidine and bromodeoxyuridine incorporation. Treatment with the antimitotic agent colchicine abolished ANTU(L)-induced resistance to ANTU(H). ANTU resistant rats were also resistant to the lethal effect of paraquat. Paraquat is not taken up by pneumocytes if they are undergoing hyperplasia. ANTU(L) administration resulted in an up regulation of gene transcription for keratinocyte growth factor, transforming growth factor-beta, keratinocyte growth factor receptor and epidermal growth factor receptor as determined through reverse transcription-polymerase chain reaction. A significant increase in transforming growth factor-alpha was not observed. These findings collectively suggest that ANTU(L)-induced pulmonary cell hyperplasia underlies resistance to ANTU(H). Furthermore. the stimulation of hyperplasia may be due to altered growth factor and growth factor receptor expressions. (C) 2000 Elsevier Science ireland Ltd. All rights reserved. C1 Univ Louisiana, Coll Pharm & Hlth Sci, Div Toxicol, Monroe, LA 71209 USA. Univ Louisiana, Coll Pharm & Hlth Sci, Louisiana Inst Toxicol, Monroe, LA 71209 USA. Natl Ctr Toxicol Res, Pathol Associates Int, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), Univ Louisiana, Coll Pharm & Hlth Sci, Div Toxicol, Monroe, LA 71209 USA. NR 52 TC 14 Z9 14 U1 1 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 FEB 21 PY 2000 VL 143 IS 2 BP 167 EP 181 DI 10.1016/S0300-483X(99)00171-7 PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 291DK UT WOS:000085718700004 PM 10755703 ER PT J AU Sakai, A Marti, GE Caporaso, N Pittaluga, S Touchman, JW Fend, F Raffeld, M AF Sakai, A Marti, GE Caporaso, N Pittaluga, S Touchman, JW Fend, F Raffeld, M TI Analysis of expressed immunoglobulin heavy chain genes in familial B-CLL SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CHRONIC LYMPHATIC-LEUKEMIA; V-H GENES; SOMATIC HYPERMUTATION; CHROMOSOMAL-ABNORMALITIES; INSITU HYBRIDIZATION; CELLS; REPERTOIRE; SELECTION; DELETIONS AB In this study, we wished to determine whether familial chronic lymphocytic leukemia of B-cell phenotype (CLL) shares with sporadic B-CLL the same immunoglobulin (Ig) heavy chain variable region (VH) gene usage and occurrence of somatic mutation, to gain insight into the pathogenetic relatedness of these epidemiologically distinct forms of CLL. We therefore analyzed the expressed Ig heavy chain genes in 23 cases (11 families) of familial CLL, and compared these results with data previously reported for sporadic CLL, In addition, we assessed the relationship of the occurrence of somatic mutation to several clinical and phenotypic features. The distribution of V genes among these cases was similar to that observed in sporadic CLL: VH3 > VH1 > VH4. Thirteen of the 23 cases (57%) showed germ line VH gene sequences, whereas somatic mutations were detected in 10 cases (43%), The average mutation frequency of these latter 10 cases of was 6.7% (ranging from 1.7% to 8.8%), and evidence of antigen selection was noted in 6. Intraclonal variation, followed by clonal evolution and the appearance of a second clone over a 20 year period was observed in 1 case, suggesting that mutations can continue to accumulate after neoplastic transformation. The presence of somatic mutations correlated with age at presentation, low white blood cell (WBC) count, and low fluorescence intensity of surface CD5, and the potential significance of these relationships is discussed. Our data indicate that familial end sporadic B-CLL display a similar pattern of immunoglobulin gene usage and frequency of somatic mutation, and are consistent with a common ontogeny and immunogenetic origin for these 2 epidemiologically distinct forms of CLL. (C) 2000 by The American Society of Hematology. C1 NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Flow & Image Cytometry Sect, Lab Med & Mol Genet,Div Cell & Gene Therapies, Bethesda, MD USA. NCI, Genet Epidemiol Branch, NIH, Rockville, MD USA. NIH, Intramural Sequencing Ctr, Gaithersburg, MD USA. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. RP Raffeld, M (reprint author), NCI, Hematopathol Sect, Pathol Lab, NIH, Bldg 10,Room 2N110,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 42 TC 49 Z9 51 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 2000 VL 95 IS 4 BP 1413 EP 1419 PG 7 WC Hematology SC Hematology GA 283DV UT WOS:000085261600044 PM 10666219 ER PT J AU Ma, XJ Sun, JW Papasavvas, E Riemann, H Robertson, S Marshall, J Bailer, RT Moore, A Donnelly, RP Trinchieri, G Montaner, LJ AF Ma, XJ Sun, JW Papasavvas, E Riemann, H Robertson, S Marshall, J Bailer, RT Moore, A Donnelly, RP Trinchieri, G Montaner, LJ TI Inhibition of IL-12 production in human monocyte-derived macrophages by TNF SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; BLOOD MONONUCLEAR-CELLS; MICE LACKING; FACTOR-ALPHA; INTERFERON-GAMMA; IMMUNE-RESPONSES; IN-VITRO; P40 GENE AB IL-12 is a pivotal cytokine that links the innate and adaptive immune responses. TNF-alpha also plays a key role in orchestrating inflammation and immunity. The reciprocal influence of these two inflammatory mediators on each other may have significant impact on the cytokine balance that shapes the type and extent of immune responses. To investigate the relationship between TNF-alpha and IL-12 production, we analyzed the effects of exposure of human monocyte-derived macrophages to TNF-alpha on LPS- or Staphylococcus aureus-induced IL-12 production in the presence or absence of IFN-gamma, TNF-alpha is a potent inhibitor of IL-12 p40 and p70 secretion from human macrophages induced by LPS or S. aureus, IL-10 is not responsible for the TNF-alpha-mediated inhibition of IL-12. TNF-alpha selectively inhibits IL-12 p40 steady-state mRNA, but not those of IL-12 p35, IL-1 alpha, IL-1 beta, or IL-6. Nuclear run-on analysis identified this specific inhibitory effect at the transcriptional level for IL-12 p40 without down-regulation of the IL-12 p35 gene. The major transcriptional factors identified to be involved in the regulation of IL-12 p40 gene expression by LPS and IFN-gamma, i.e., c-Rel, NF-kappa B p50 and p65, IFN regulatory factor-1, and ets-2, were not affected by TNF-alpha when examined by nuclear translocation and DNA binding. These data demonstrate a selective negative regulation on IL-12 by TNF-alpha, identifying a direct negative feedback mechanism for inflammation-induced suppression of IL-12 gene expression. C1 Wistar Inst, Philadelphia, PA 19104 USA. US FDA, Div Cytokine Biol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Montaner, LJ (reprint author), Wistar Inst, 3601 Spruce St, Philadelphia, PA 19104 USA. FU NIAID NIH HHS [AI40379, AI43206, AI44304] NR 51 TC 82 Z9 82 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 2000 VL 164 IS 4 BP 1722 EP 1729 PG 8 WC Immunology SC Immunology GA 283VK UT WOS:000085296600013 PM 10657616 ER PT J AU Bi, DQ Anderson, LW Shapiro, J Shapiro, A Grem, JL Takimoto, CH AF Bi, DQ Anderson, LW Shapiro, J Shapiro, A Grem, JL Takimoto, CH TI Measurement of plasma uracil using gas chromatography-mass spectrometry in normal individuals and in patients receiving inhibitors of dihydropyrimidine dehydrogenase SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE uracil; eniluracil; dihydropyrimidine dehydrogenase ID ORAL 5-FLUOROURACIL PRODRUGS; BLOOD MONONUCLEAR-CELLS; 5-ETHYNYLURACIL 776C85; ANTITUMOR-ACTIVITY; ANTIVIRAL DRUG; SORIVUDINE; FLUOROURACIL; TEGAFUR; PHARMACOKINETICS; BIOAVAILABILITY AB A sensitive gas chromatographic-mass spectrometric method is described for reliably measuring endogenous uracil in 100 mu l of human plasma. Validation of this assay over a wide concentration range, 0.025 mu M to 250 mu M (0.0028 mu g/ml to 28 mu g/ml), allowed for the determination of plasma uracil in patients treated with agents such as eniluracil, an inhibitor of the pyrimidine catabolic enzyme, dihydropyrimidine dehydrogenase. Calibration standards were prepared in human plasma using the stable isotope, [N-15(2)]uracil, to avoid interference from endogenous uracil and 10 mu M 5-chlorouracil was added as the internal standard. Published by Elsevier Science B.V. C1 NCI, Dev Therapeut Dept, Med Branch, Div Clin Sci,Natl Naval Med Ctr, Bethesda, MD 20889 USA. US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, Rockville, MD 20850 USA. RP Takimoto, CH (reprint author), NCI, Dev Therapeut Dept, Med Branch, Div Clin Sci,Natl Naval Med Ctr, Bldg 8,Room 5101, Bethesda, MD 20889 USA. NR 25 TC 24 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD FEB 11 PY 2000 VL 738 IS 2 BP 249 EP 258 DI 10.1016/S0378-4347(99)00528-9 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 286ZU UT WOS:000085479400007 PM 10718643 ER PT J AU Imam, SZ Ali, SF AF Imam, SZ Ali, SF TI Selenium, an antioxidant, attenuates methamphetamine-induced dopaminergic toxicity and peroxynitrite generation SO BRAIN RESEARCH LA English DT Article DE methamphetamine; peroxynitrite; selenium; caudate nucleus; neurotoxicity; oxidative stress ID NITRIC-OXIDE SYNTHASE; GLUTATHIONE-PEROXIDASE; INDUCED NEUROTOXICITY; SUPEROXIDE; MICE; 7-NITROINDAZOLE; PROTECTION; OXIDATION; INHIBITOR AB Methamphetamine (METH) has been known to produce neurotoxicity via generation of reactive oxygen and nitrogen species. Selenium, an antioxidant, was reported to protect against METH-induced dopaminergic neurotoxicity in mouse caudate nucleus. In the present study, the in vitro and in vivo efficacy of the supplementation of selenium was studied in METH-induced generation of peroxynitrite. PC12 cell cultures were exposed to 200 mu M METH either with or without 10 mu M and 20 mu M selenium (30 min prior to METH exposure). After 24 h, METH exposure resulted in the significant depletion of dopamine, and its metabolites DOPAC and HVA, as well as the significant formation of 3-nitrotyrosine (3-NT), a marker of peroxynitrite generation, in PC12 cell cultures. Selenium supplementation attenuated the depletion of dopamine and its metabolites, DOPAC and HVA and the formation of 3-NT in PC12 cells. For in vivo studies, adult male mice were supplemented with selenium in drinking water, 1 week before and 1 week after the multiple injections of METH (4 X 10 mg/kg, i.p. at 2-h interval) or an equivalent volume of saline. The supplementation of Se attenuated the formation of 3-NT in the striatum resulting from METH treatment. These data suggest that METH-induced neurotoxicity is mediated by the production of peroxynitrite, and selenium plays a protective role in METH-induced neurotoxicity. (C) 2000 Published by Elsevier Science B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. Hamdard Univ, Dept Toxicol, Neurotoxicol Lab, New Delhi 110062, India. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 28 TC 90 Z9 92 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD FEB 7 PY 2000 VL 855 IS 1 BP 186 EP 191 DI 10.1016/S0006-8993(99)02249-0 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 282AT UT WOS:000085194200026 PM 10650149 ER PT J AU Pletnikov, MV Rubin, SA Schwartz, GJ Carbone, KM Moran, TH AF Pletnikov, MV Rubin, SA Schwartz, GJ Carbone, KM Moran, TH TI Effects of neonatal rat Borna disease virus (BDV) infection on the postnatal development of the brain monoaminergic systems SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE Borna; development; monoamine; rat ID METHYLAZOXYMETHANOL ACETATE; ELECTROCHEMICAL DETECTION; FRONTAL-CORTEX; NEUROCHEMISTRY; ABNORMALITIES; MALNUTRITION; RECEPTORS; NEOCORTEX; ONTOGENY; MARKERS AB Effects of neonatal Borna disease virus infection (BDV) on the postnatal development of brain monoaminergic systems in rats were studied. Tissue content of norepinephrine (NE), dopamine (DA) and its metabolite, 3,4-dihydroxyphenol acetic acid (DOPAC), and serotonin (5-HT) and its metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA) were assayed by means of HPLC-EC in frontal cortex, cerebellum, hippocampus, hypothalamus and striatum of neonatally BDV-infected and sham-inoculated male Lewis rats of 8, 14, 21, 60 and 90 days of age. Both NE and 5-HT concentrations were significantly affected by neonatal BDV infection. The cortical and cerebellar levels of NE and 5-HT were significantly greater in BDV-infected rats than control animals at postnatal days (PND) 60 and 90. Tissue content of NE in hippocampus was unaffected. In hippocampus, neonatally BDV-infected rats had lower 5-HT levels at PND 8 and significantly elevated levels at PND 21 and onwards. Neither striatal levels of 5-HT nor hypothalamic levels of 5-HT and NE were affected by neonatal BDV infection, suggesting that the monoamine systems in the prenatally maturing brain regions are less sensitive to effects of neonatal viral infection. 5-HIAA/5-HT ratio was not altered in BDV-infected rats indicating no changes in the 5-HT turnover in the brain regions damaged by the virus. Neither DA nor DOPAC/DA ratio was affected by neonatal BDV infection in any of the brain regions examined. The present data demonstrate significant and specific alterations in monoaminergic systems in neonatally BDV-infected rats. This pattern of changes is consistent with the previously reported behavioral abnormalities resulting from neonatal BDV infection. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. US FDA, CBER, Lab Pediat & Resp Viral Dis, Bethesda, MD 20892 USA. RP Pletnikov, MV (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Ross 618,720 Rutland Ave, Baltimore, MD 21205 USA. NR 39 TC 38 Z9 39 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD FEB 7 PY 2000 VL 119 IS 2 BP 179 EP 185 DI 10.1016/S0165-3806(99)00168-6 PG 7 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 284WD UT WOS:000085355100003 ER PT J AU Alizadeh, AA Eisen, MB Davis, RE Ma, C Lossos, IS Rosenwald, A Boldrick, JG Sabet, H Tran, T Yu, X Powell, JI Yang, LM Marti, GE Moore, T Hudson, J Lu, LS Lewis, DB Tibshirani, R Sherlock, G Chan, WC Greiner, TC Weisenburger, DD Armitage, JO Warnke, R Levy, R Wilson, W Grever, MR Byrd, JC Botstein, D Brown, PO Staudt, LM AF Alizadeh, AA Eisen, MB Davis, RE Ma, C Lossos, IS Rosenwald, A Boldrick, JG Sabet, H Tran, T Yu, X Powell, JI Yang, LM Marti, GE Moore, T Hudson, J Lu, LS Lewis, DB Tibshirani, R Sherlock, G Chan, WC Greiner, TC Weisenburger, DD Armitage, JO Warnke, R Levy, R Wilson, W Grever, MR Byrd, JC Botstein, D Brown, PO Staudt, LM TI Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling SO NATURE LA English DT Article ID NON-HODGKINS-LYMPHOMA; GERMINAL-CENTER FORMATION; CHROMOSOMAL TRANSLOCATION; PROGNOSTIC-SIGNIFICANCE; PROTEIN EXPRESSION; MOLECULAR-CLONING; BCL-6 EXPRESSION; ANTIGEN; CLASSIFICATION; TRANSCRIPTION AB Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease. We proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumours, Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumours of DLBCL patients, apparently reflecting the variation in tumour proliferation rate, host response and differentiation state of the tumour. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal centre B cells ('germinal centre B-like DLBCL'); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells ('activated B-like DLBCL'), Patients with germinal centre B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL, The molecular classification of tumours on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer. C1 NCI, Metab Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy Stat, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA. NIH, Bioinformat & Mol Anal Sect, CBEL, CIT, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Res Genet Inc, Huntsville, AL 35801 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Internal Med, Omaha, NE 68198 USA. NCI, Med Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21287 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RI Sherlock, Gavin/B-1831-2009; Sherlock, Gavin/E-9110-2012; OI Alizadeh, Arash Ash/0000-0002-5153-5625; Sherlock, Gavin/0000-0002-1692-4983 NR 50 TC 5435 Z9 5722 U1 32 U2 308 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 3 PY 2000 VL 403 IS 6769 BP 503 EP 511 DI 10.1038/35000501 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 282PM UT WOS:000085227300039 PM 10676951 ER PT J AU D'Agnillo, F Wood, F Porras, C Macdonald, VW Alayash, AI AF D'Agnillo, F Wood, F Porras, C Macdonald, VW Alayash, AI TI Effects of hypoxia and glutathione depletion on hemoglobin- and myoglobin-mediated oxidative stress toward endothelium SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE hemoglobin; myoglobin; hypoxia; oxidative stress; glutathione; endothelium ID RENAL-FAILURE; NITRIC-OXIDE; INJURY; FERRYLHEMOGLOBIN; FERRYLMYOGLOBIN; DERIVATIVES; BLOOD AB We investigated the toxicity of hemoglobin/myoglobin on endothelial cells under oxidative stress conditions that include cellular hypoxia and reduced antioxidant capacity. Bovine aorta endothelial cells (BAECs), grown on microcarrier beads, were subjected to cycles of hypoxia and reoxygenation in a small volume of medium, and endothelial cell monolayers were depleted of their intracellular glutathione (GSH) by treatment with buthionine sulfoximine. Incubation of diaspirin crosslinked hemoglobin (DBBF-Hb) or horse skeletal myoglobin (Mb) with BAECs subjected to 3 h of hypoxia caused transient oxidation of the hemoproteins to the ferryl form (Fe4+). Formation of the ferryl intermediate was decreased in a concentration-dependent manner by the addition of L-arginine, a substrate of NO synthase, after 3 h of hypoxia. Optimal inhibition of ferryl formation, possibly due to the antioxidant action of NO, was achieved with. 900 mu M L-arginine. Addition of hydrogen peroxide to GSH-depleted cells in the presence of DBBF-Hb or Mb significantly decreased cell viability. Ferryl Mb, but not ferryl DBBF-Hb, was observed in samples analyzed at the end of treatment, which may explain the greater toxicity observed with Mb as opposed to DBBF-Hb. This model may be utilized to identify causative agent(s) associated with hemoprotein cytotoxicity and in designing strategies to suppress or control hems-mediated injury under physiologically relevant conditions. (C) 2000 Elsevier Science B.V. All rights reserved. C1 US FDA, Lab Plasma Derivat, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Blood Res Detachment, Washington, DC 20307 USA. RP Alayash, AI (reprint author), US FDA, Lab Plasma Derivat, Div Hematol, Ctr Biol Evaluat & Res, 8800 Rockville Pike,Bldg 29,Rm 112, Bethesda, MD 20892 USA. NR 44 TC 29 Z9 30 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD FEB 2 PY 2000 VL 1495 IS 2 BP 150 EP 159 DI 10.1016/S0167-4889(99)00163-9 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 283UZ UT WOS:000085295600004 PM 10656972 ER PT J AU Powrie, R Kweder, S Rosene-Montella, K AF Powrie, R Kweder, S Rosene-Montella, K TI Teaching internal medicine residents about medical problems in pregnancy SO ACADEMIC MEDICINE LA English DT Article AB When they became aware that many of their internal medicine residents were not being routinely exposed to a representative range of medical illnesses in pregnancy, the authors set out to develop and implement a brief practical curriculum on the medical problems of pregnancy. They began with a retrospective chart review of 562 consultations with pregnant women and used their findings to develop nine 15-minute lectures that covered a majority of the concepts essential to the care of the medically compromised pregnant woman. Topics included hypertension in pregnancy, the febrile pregnant woman, and renal disease in pregnancy. The authors also created a learner handout, a teaching script, teaching cases, and a bibliography for each lecture. Residents have responded well to the curriculum, and their mean pre- and posttext scores have shown that the lectures improved their knowledge of obstetric medicine. This brief-lecture format may be adapted to other special topics in residency training and readily integrated into already-crowded training schedules. C1 Brown Univ, Dept Med, Div Obstet & Consultat Med, Sch Med, Providence, RI 02912 USA. Women & Infants Hosp Rhode Isl, Dept Med, Providence, RI 02908 USA. US FDA, CDER, Off Drug Evaluat 4, Rockville, MD 20857 USA. RP Powrie, R (reprint author), Brown Univ, Women & Infants Hosp, Dept Med, 101 Dudley St, Providence, RI 02905 USA. NR 1 TC 4 Z9 4 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD FEB PY 2000 VL 75 IS 2 BP 191 EP 193 DI 10.1097/00001888-200002000-00021 PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 286CH UT WOS:000085425700017 PM 10693855 ER PT J AU Popke, EJ Allen, SR Paule, MG AF Popke, EJ Allen, SR Paule, MG TI Effects of acute ethanol on indices of cognitive-behavioral performance in rats SO ALCOHOL LA English DT Article DE ethanol; operant behavior; time estimation; response inhibition; repeated acquisition; position discrimination; motivation ID PROGRESSIVE RATIO; TIME PERCEPTION; MARIJUANA SMOKE; RHESUS-MONKEYS; COCAINE; ALCOHOL; REINFORCEMENT; COMBINATION; SCHEDULES; HUMANS AB The present experiment examined the effects of ethanol on several complex operant behaviors in rats. Tasks included: temporal response differentiation (TRD) to assess timing behavior; differential reinforcement of low response rates (DRL) to assess timing and response inhibition; incremental repeated acquisition (IRA) to assess learning; conditioned position responding (CPR) to assess auditory, visual, and position discrimination; and progressive ratio (PR) to assess motivation. Ethanol (0.0, 0.5, 1.0, 1.5, 2.0, and 3.0 g/kg via orogastric gavage) reduced accuracy and/or percent task completed for the TRD, DRL, and CPR tasks. For CPR, this reduction was accompanied by a reduction in response rates. Ethanol also reduced response rates on the PR task. There were no effects of ethanol on IRA performance. These data suggest that ethanol can selectively impair performance on cognitive-behavioral tasks and that these effects can occur at doses that do not affect the subjects' ability to respond. Published by Elsevier Science Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Popke, EJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 27 TC 24 Z9 25 U1 3 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0741-8329 J9 ALCOHOL JI Alcohol PD FEB PY 2000 VL 20 IS 2 BP 187 EP 192 DI 10.1016/S0741-8329(99)00081-6 PG 6 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 289ZC UT WOS:000085651000011 PM 10719798 ER PT J AU Simone, NL Remaley, AT Charboneau, L Petricoin, EF Glickman, JW Emmert-Buck, MR Fleisher, TA Liotta, LA AF Simone, NL Remaley, AT Charboneau, L Petricoin, EF Glickman, JW Emmert-Buck, MR Fleisher, TA Liotta, LA TI Sensitive immunoassay of tissue cell proteins procured by laser capture microdissection SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PROSTATE-SPECIFIC ANTIGEN; RESOLVED IMMUNOFLUOROMETRIC ASSAY; MOLECULAR ANALYSIS; MESSENGER-RNA; LOCALIZATION; SERUM AB Coupling laser capture microdissection (LCM) with sensitive quantitative chemiluminescent immunoassays has broad applicability in the field of proteomics applied to normal, diseased, or genetically modified tissue. Quantitation of the number of prostate-specific antigen (PSA) molecules/cell was conducted on human prostate tissue cells procured by LCM from fixed and stained frozen sections. Under direct microscopic visualization, laser shots 30 mu m in diameter captured specific cells from the heterogeneous tissue section onto a polymer transfer surface. The cellular macromolecules from the captured cells were solubilized in a microvolume of extraction buffer and directly assayed using an automated (1.5 hour) sandwich chemiluminescent immunoassay, Calibration of the chemiluminescent assay was conducted by developing a standard curve using known concentrations of PSA, After the sensitivity, precision, and linearity of the chemiluminescent assay was verified for known numbers of solubilized microdissected tissue cells, it was then possible to calculate the number of PSA molecules per microdissected tissue cell for case samples, In a study set of 20 cases, using 10 replicate samples of 100 laser shots per sample, the within-run (intraassay) SD was approximately 10% of the mean or less for all cases. In this series the number of PSA molecules per microdissected tissue cell ranged from 2 x 10(4) to 6.3 x 10(6) in normal epithelium, prostate intraepithelial neoplasia (PIN), and invasive carcinoma, Immunohistochemical staining of human prostate for PSA was compared with the results of the soluble immunoassay for the same prostate tissue section. Independent qualitative scoring of anti-PSA immunohistochemical staining intensity paralleled the LCM quantitative immunoassay for each tissue subpopulation and verified the heterogeneity of PSA content between tissue subpopulations in the same case. Extraction buffers were successfully adapted for both secreted and membrane-bound proteins. This technology has broad applicability for the quantitation of protein molecules in pure populations of tissue cells. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Ctr Clin, Dept Clin Pathol, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Washington, DC 20204 USA. RP Liotta, LA (reprint author), NCI, Pathol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 16 TC 96 Z9 105 U1 1 U2 5 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 2000 VL 156 IS 2 BP 445 EP 452 DI 10.1016/S0002-9440(10)64749-9 PG 8 WC Pathology SC Pathology GA 283VJ UT WOS:000085296500012 PM 10666374 ER PT J AU Higgins, JA Hubalek, Z Halouzka, J Elkins, KL Sjostedt, A Shipley, M Ibrahim, MS AF Higgins, JA Hubalek, Z Halouzka, J Elkins, KL Sjostedt, A Shipley, M Ibrahim, MS TI Detection of Francisella tularensis in infected mammals and vectors using a probe-based polymerase chain reaction SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID FORMERLY YERSINIA-PHILOMIRAGIA; FLUOROGENIC PROBE; MEMBRANE-PROTEIN; PCR; DNA; TICKS; ASSAY; TULAREMIA; TAQMAN; IDENTIFICATION AB We investigated the use of a TaqMan 5' nuclease assay (5NA) directed against the Francisella tularensis outer membrane protein (Fop) gene and a polymerase chain reaction-enzyme immunoassay (PCR-EIA) directed against the tul 4 gene for detection of this organism in experimentally infected mice and in field-collected tick vectors. We also evaluated the use of specially formulated filter paper (FTA(TM)) for rapid sample preparation. The 5NA had a detection limit of 1 pg of genomic DNA (< 100 colony-forming units) and could be completed within several hours. The PCR-EIA could detect 1 pg of genomic DNA and 10 attograms (ag) (22 copies) of cloned insert, but takes longer to perform. Both assays were genus-specific, and successfully detected F. tularensis in mouse tissues (5NA) and in tick extracts (PCR-EIA). The FTA paper provided inexpensive, rapid, template preparation for the tick extracts, mouse tissues, and DNA obtained from clinical specimens. These probe-based assays have the potential to provide rapid, real-time/high-throughput molecular diagnostics in field situations. C1 ARS, USDA, Beltsville, MD 20705 USA. Acad Sci Czech Republ, Inst Vertebrate Biol, Lab Med Zool, CZ-69142 Valtice, Czech Republic. US FDA, Div Bacterial Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Umea Univ, Dept Clin Microbiol, Div Clin Bacteriol, Umea, Sweden. Def Res Estab, Umea, Sweden. GEO CENTERS Inc, Frederick, MD USA. USA, Med Res Inst Infect Dis, Diagnost Syst Div, Frederick, MD 21702 USA. RP Higgins, JA (reprint author), ARS, USDA, Room 202,Bldg 1040,10400 Baltimore Blvd, Beltsville, MD 20705 USA. RI Hubalek, Zdenek/G-1111-2014 OI Hubalek, Zdenek/0000-0003-4732-0987 NR 31 TC 51 Z9 53 U1 0 U2 3 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD FEB PY 2000 VL 62 IS 2 BP 310 EP 318 PG 9 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 311BN UT WOS:000086864800024 PM 10813490 ER PT J AU Irony, TZ Pereira, CAD Tiwari, RC AF Irony, TZ Pereira, CAD Tiwari, RC TI Analysis of opinion swing: Comparison of two correlated proportions SO AMERICAN STATISTICIAN LA English DT Article DE Bayes factor; credible interval; McNemar test; partial likelihood ID CONFIDENCE-INTERVALS AB An important problem that arises in introductory courses of applied statistics and categorical data analysis is the evaluation of opinion swing. Suppose that a group of individuals is surveyed on their support for the President. After the State of the Union Address the individuals are consulted again. The objective is to analyze whether or not there has been a change-a swing-in their opinion. Due to the longitudinal nature of data, only tests of hypothesis are presented to the students-for instance the McNemar test. The estimation of the parameters of interest is left to the advanced literature. In this article we suggest simple solutions for the estimation problem, to be presented in introductory courses of applied statistics. C1 US FDA, Ctr Devices & Radiol Hlth, Div Biostat, Rockville, MD 20850 USA. Univ N Carolina, Dept Math, Charlotte, NC 28223 USA. Univ Sao Paulo, Dept Stat, Sao Paulo, Brazil. RP Irony, TZ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Biostat, 1350 Piccard Dr, Rockville, MD 20850 USA. NR 17 TC 13 Z9 14 U1 3 U2 3 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0003-1305 J9 AM STAT JI Am. Stat. PD FEB PY 2000 VL 54 IS 1 BP 57 EP 62 DI 10.2307/2685613 PG 6 WC Statistics & Probability SC Mathematics GA 333JE UT WOS:000088126500012 ER PT J AU Keyes, K Hudson, C Maurer, JJ Thayer, S White, DG Lee, MD AF Keyes, K Hudson, C Maurer, JJ Thayer, S White, DG Lee, MD TI Detection of florfenicol resistance genes in Escherichia coli isolated from sick chickens SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID FLUORINATED ANALOGS; CHLORAMPHENICOL; PHARMACOKINETICS; THIAMPHENICOL; INTEGRON; DNA AB Florfenicol is an antibiotic approved for veterinary use in cattle in the United States in 1996. Although this drug is not used in poultry, we have detected resistance to florfenicol in clinical isolates of avian Escherichia coli. Molecular typing demonstrated that the florfenicol resistance gene, flo, was independently acquired and is plasmid encoded. C1 Univ Georgia, Coll Vet Med, Dept Microbiol & Parasitol, Athens, GA 30602 USA. Univ Georgia, Coll Vet Med, Dept Avian Med, Athens, GA 30602 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Lee, MD (reprint author), Univ Georgia, Dept Med Microbiol & Parasitol, Athens, GA 30602 USA. NR 22 TC 75 Z9 83 U1 4 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 2000 VL 44 IS 2 BP 421 EP 424 DI 10.1128/AAC.44.2.421-424.2000 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 276WZ UT WOS:000084902500034 PM 10639375 ER PT J AU Miller, FW Hess, EV Clauw, DJ Hertzman, PA Pincus, T Silver, RM Mayes, MD Varga, J Medsger, TA Love, LA AF Miller, FW Hess, EV Clauw, DJ Hertzman, PA Pincus, T Silver, RM Mayes, MD Varga, J Medsger, TA Love, LA TI Approaches for identifying and defining environmentally associated rheumatic disorders SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material ID EOSINOPHILIA-MYALGIA-SYNDROME; L-TRYPTOPHAN; CLASSIFICATION CRITERIA; AUTOIMMUNE-DISEASES; PEAK-E; EPIDEMIOLOGY; DIAGNOSIS; 1,1'-ETHYLIDENEBIS(L-TRYPTOPHAN); SCLERODERMA; VASCULITIS C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Lab Mol & Dev Immunol, Bethesda, MD 20892 USA. Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. Georgetown Univ Hosp, Washington, DC 20007 USA. Los Alamos Med Ctr, Los Alamos, NM USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Med Univ S Carolina, Charleston, SC 29425 USA. Wayne State Univ, Hutzel Hosp, Detroit, MI USA. Univ Illinois, Chicago, IL USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Miller, FW (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Lab Mol & Dev Immunol, Bldg 29B,Room 2G11,HFM-561,8800 Rockville Pike, Bethesda, MD 20892 USA. OI Miller, Frederick/0000-0003-2831-9593 NR 44 TC 55 Z9 55 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD FEB PY 2000 VL 43 IS 2 BP 243 EP 249 DI 10.1002/1529-0131(200002)43:2<243::AID-ANR2>3.0.CO;2-K PG 7 WC Rheumatology SC Rheumatology GA 284ZM UT WOS:000085362800002 PM 10693862 ER PT J AU Ball, R Parker, EC AF Ball, R Parker, EC TI A trial to determine the risk of decompression sickness after a 40 feet of sea water for 200 minute no-stop air dive SO AVIATION SPACE AND ENVIRONMENTAL MEDICINE LA English DT Article DE decompression sickness; risk estimation; probabilistic modeling; clinical trial AB Background: The USN93 probabilistic model of decompression sickness (DCS) predicts a DCS risk of 3.9% after a 40 ft of seawater (fsw) for 200 min no-stop air dive, although little data is available to evaluate the accuracy of this prediction. Based on an analysis of Navy Safety Center data from diving on U.S. Navy standard air decompression tables, the observed incidence of DCS for this type of dive is 0.11%. Knowing the true incidence of the dive is important for deciding whether or not to adopt proposed probability based decompression procedures for U.S. Navy diving. Hypothesis: The risk of DCS after a 40 fsw for 200 min no-stop air dive is 3.9%. Methods: We conducted a closed sequential trial to determine the DCS incidence on this dive. Results: Of 30 military divers who completed 91 dives, there were 2 cases of DCS (2.2%, 95% Cl: 0.27-7.7%). The study was terminated early after the second DCS case because of the presence of neurological symptoms and signs. Conclusions: This study demonstrates that the incidence of DCS in a laboratory setting is higher than observed in fleet diving. Use of the 40 fsw for 200 min schedule in a decompression computer is likely to result in DCS incidence 2.5- to 70-fold greater than that observed in U.S. Navy diving using table-based procedures. C1 USN, Med Res Inst, Bethesda, MD USA. RP Ball, R (reprint author), CBER, Div Biostat & Epidemiol, HFM-220,1401 Rockville Pike, Rockville, MD 20852 USA. NR 18 TC 4 Z9 4 U1 0 U2 1 PU AEROSPACE MEDICAL ASSOC PI ALEXANDRIA PA 320 S HENRY ST, ALEXANDRIA, VA 22314-3579 USA SN 0095-6562 J9 AVIAT SPACE ENVIR MD JI Aviat. Space Environ. Med. PD FEB PY 2000 VL 71 IS 2 BP 102 EP 108 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Sport Sciences SC Public, Environmental & Occupational Health; General & Internal Medicine; Sport Sciences GA 278LU UT WOS:000084991900002 PM 10685581 ER PT J AU Aokl, Y Tosato, G Nambu, Y Iwamoto, A Yarchoan, R AF Aokl, Y Tosato, G Nambu, Y Iwamoto, A Yarchoan, R TI Detection of vascular endothelial growth factor in AIDS-related primary effusion lymphomas SO BLOOD LA English DT Letter C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Univ Tokyo, Inst Med Sci, Tokyo, Japan. NCI, HIV & AIDS Malignancy Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Aokl, Y (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 2000 VL 95 IS 3 BP 1109 EP 1110 PG 2 WC Hematology SC Hematology GA 278MN UT WOS:000084993700054 ER PT J AU Coles, BF Anderson, KE Doerge, DR Churchwell, MI Lang, NP Kadlubar, FF AF Coles, BF Anderson, KE Doerge, DR Churchwell, MI Lang, NP Kadlubar, FF TI Quantitative analysis of interindividual variation of glutathione S-transferase expression in human pancreas and the ambiguity of correlating genotype with phenotype SO CANCER RESEARCH LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; DIOL EPOXIDES; CANCER SUSCEPTIBILITY; METABOLIC-ACTIVATION; HUMAN-LIVER; ALPHA; GENE; PI; IDENTIFICATION; LUNG AB Analysis of glutathione S-transferases (GSTs) of the alpha, mu, and pi classes by reverse-phase high-performance liquid chromatography and electrospray-ionization mass spectrometry in 43 samples of normal human pancreas demonstrated a wide variation in expression of subunits PI, A1, A2, A4, M1, M2, and M3 and the presence of a novel form designated GST "A5." GSTA2 consisted of three forms that were differentially expressed between individuals in a manner consistent with allelic polymorphism at the hGSTA2 locus. Expression, in terms of mu g GST subunit/mg cytosolic protein, varied by 6-15-fold for subunits P1, A2, and M3 and 17-30-fold in the case of GSTs Al and M2. Less consistently expressed were GSTs M1a, M1b, A4, and A5. Among these, GSTM1 expression (excluding M1-null samples) varied 12-fold between samples, whereas GST Al and A5 expression varied similar to 50-100-fold between samples, well beyond the range of other subunits, suggesting that their expression is highly inducible. Linear correlations (P < 0.001-0.003) existed between levels of the most:consistently expressed GST, GSTP1, and total GSTs, GSTA2 and M3, and in GSTM1-positive samples, between GSTM1, M3, and P1. The correlation between GST subunits P1 and M3 was bimodal according to M1 genotype, reflecting the presence of the regulatory element in hGSTM3*B that is linked with the hGSTM1*A genotype. It is concluded that although a degree of regulation of expression of GSTs occurs in human pancreas, the variability of phenotype is high and might obscure the effects of genetic polymorphisms on individual cancer susceptibility. Interindividual variation of GST expression is, therefore, a factor that should be taken account of in epidemiological studies. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55454 USA. Univ Arkansas Med Sci, Dept Surg, Little Rock, AR 72205 USA. Arkansas Canc Res Ctr, Little Rock, AR 72205 USA. Cent Arkansas Vet Hlth Care Syst, Surg Serv, Little Rock, AR 72205 USA. RP Coles, BF (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, HFT 100, Jefferson, AR 72079 USA. FU NCI NIH HHS [R01-CA58697] NR 51 TC 42 Z9 44 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2000 VL 60 IS 3 BP 573 EP 579 PG 7 WC Oncology SC Oncology GA 282TU UT WOS:000085235600016 PM 10676639 ER PT J AU Pogribny, IP Pogribna, M Christman, JK James, SJ AF Pogribny, IP Pogribna, M Christman, JK James, SJ TI Single-site methylation within the p53 promoter region reduces gene expression in a reporter gene construct: Possible in vivo relevance during tumorigenesis SO CANCER RESEARCH LA English DT Article ID FOLATE/METHYL-DEFICIENT RATS; TUMOR-SUPPRESSOR GENE; WILD-TYPE P53; DNA METHYLATION; CPG ISLAND; REPRESS TRANSCRIPTION; HISTONE DEACETYLASE; PROTEIN MECP2; BINDING-SITES; CANCER AB It is not known whether transcriptional suppression by de novo methylation occurs within the promoter region of the p53 gene during multistage tumorigenesis, To address this question, in vivo alterations in the CpG methylation within the rat p53 promoter region were evaluated in control, preneoplastic, and tumor tissue during tumor progression using the folate/methyl-deficient model of hepatocarcinogenesis. Alterations in CpG methylation were found to be site-specific and to vary depending on the stage of carcinogenesis. To further explore the effect of site-specific methylation on p53 promoter activity, reporter gene constructs were prepared containing specifically methylated sites within the p53 promoter region, and the transcriptional activity in cultured mammalian cells was determined in a transient transfection assay. Relative to the unmethylated construct as a positive control, single-site methylation at nucleotide (nt) -450, which occurs 216 nt upstream from the 85-nt minimal promoter region, suppressed promoter activity hy 85%. In contrast, single-site methylation at nt -179, which occurs within the minimal essential promoter region, suppressed activity by only 20%. The p53 promoter constructs containing the singly methylated CpG site at nt -450 were then reevaluated for processive changes in methylation status 48 h after transfection, during maximum suppression of promoter activity. Restriction analysis with methylation-sensitive enzymes revealed that de novo methylation had occurred after transfection at previously unmethylated sites. These findings suggest that nt -450 may constitute a critical site for initiation of de novo methylation and processive spreading of methylation associated with transcriptional inactivation of the p53 gene. Furthermore, the results suggest a possible alternative mechanism for the silencing of the p53 gene in tumors that do not have p53 mutations. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA. RP James, SJ (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 67 TC 82 Z9 84 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2000 VL 60 IS 3 BP 588 EP 594 PG 7 WC Oncology SC Oncology GA 282TU UT WOS:000085235600018 PM 10676641 ER PT J AU Manjanatha, MG Shelton, SD Culp, SJ Blankenship, LR Casciano, DA AF Manjanatha, MG Shelton, SD Culp, SJ Blankenship, LR Casciano, DA TI DNA adduct formation and molecular analysis of in vivo lacI mutations in the mammary tissue of Big Blue (R) rats treated with 7,12-dimethylbenz[a]anthracene SO CARCINOGENESIS LA English DT Article ID N-RAS MUTATION; TRANSGENIC MICE; HA-RAS; MUTANT FREQUENCY; GENE; CELLS; CARCINOGENESIS; ONCOGENES; SEQUENCE; SPECTRA AB Recently we compared the lad and Hprt mutant frequencies (MFs) and types of mutations in lymphocytes of Big Blue(R) (BB) rats exposed to 7,12-dimethylbenz[a]anthracene (DMBA) under conditions that result in mammary gland tumors. In this study, we have examined the target mammary tissue for DMBA-induced DNA adducts, lad MF and types of lad mutations. seven-week-old female BE rats were given single doses of 0, 20 or 130 mg/kg DMBA by gavage and the DNA adducts and lad MFs in the mammary tissue were measured over a period of 14 days and 18 weeks, respectively, following treatment, The lacI MF in the mammary tissue increased for 10 weeks and then remained relatively constant; 130 mg/kg DMBA produced a 14-fold increase in the MF (255 +/- 50 x 10(-6) p.f.u.) over control MF (18.3 +/- 4 x 10(-6) p.f.u.). P-32-post-labeling analysis of DNA from mammary tissue and splenic lymphocytes of treated rats revealed two major adducts, Comparison of these adducts with DMBA standards indicated that the adducts formed by DMBA involved both G:C and A:T base pairs. DNA sequencing revealed that the majority of DMBA-induced lad mutations were base pair sutbstitutions and that A:T-->T:A (44% of the independent mutations) and G:C-->T:A (24% of the independent mutations:) transversions were the predominant types. Furthermore, the mutational results revealed a 'hotspot' for a G-->T mutation in codon 95 (GTG-->TTG) of the lad gene in mammary tissue. These results suggest that DMBA is highly mutagenic to lad in mammary tissue and that adducts with bath G:C and A:T base pairs participate in forming mutations in DMBA-treated BB rats. C1 US FDA, Natl Ctr Toxicol Res, Dept Hlth & Human Serv, Div Genet, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Dept Hlth & Human Serv, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Manjanatha, MG (reprint author), US FDA, Natl Ctr Toxicol Res, Dept Hlth & Human Serv, Div Genet, Jefferson, AR 72079 USA. NR 39 TC 33 Z9 34 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 2000 VL 21 IS 2 BP 265 EP 273 DI 10.1093/carcin/21.2.265 PG 9 WC Oncology SC Oncology GA 287JU UT WOS:000085503400021 PM 10657967 ER PT J AU Ornstein, DK Englert, C Gillespie, JW Paweletz, CP Linehan, WM Emmert-Buck, MR Petricoin, EF AF Ornstein, DK Englert, C Gillespie, JW Paweletz, CP Linehan, WM Emmert-Buck, MR Petricoin, EF TI Characterization of intracellular prostate-specific antigen from laser capture microdissected benign and malignant prostatic epithelium SO CLINICAL CANCER RESEARCH LA English DT Article ID MULTICENTER CLINICAL-TRIAL; CANCER; ALPHA-1-ANTICHYMOTRYPSIN; SERUM; COMPLEX; TISSUE; CELLS AB The proportion of unbound serum prostate-specific antigen (PSA; percent-free PSA) is reported to be lower in men with prostate cancer compared to men with benign prostates (U. H. Stenman et al,, Cancer Res., 51: 222-226, 1991; H, Lilja et at, Clin, Chem,, 37: 1618-1625, 1991; D. L. Woodrum ed at, J. Urol., 159: 5-12, 1998; W. J. Catalona et al., J. Am. Med. Assoc., 279: 1542-1547, 1998), The majority of immunoreactive PSA in serum is complexed to alpha-1-antichymotrypsin (ACT), Two major mechanistic questions have previously been unknown: (a) Does PSA in human prostate cancer cells in tissue exist in a free or bound form? and (b) Is PSA produced by malignant cells in the free form because it has lost the ability to form a complex with ACT? Laser capture microdissection (LCM) enables the acquisition of pure populations of defined cell types from tissue (M. R. Emmert-Buck et al., Science, 274: 998-1001, 1996; R. F. Bonner et al,, Science, 278: 1481-1483, 1997), This technology provides a unique opportunity to study intracellular protein composition and structure from human cells, In this study, we used LCM to assess the bound versus free form of intracellular PSA in both benign and malignant epithelium procured from prostate tissue, One-dimensional and two-dimensional PAGE were performed on cellular lysates from LCM-procured benign and malignant prostate epithelium from frozen tissue specimens. Western blotting analysis of one-dimensional PAGE gels revealed a strong band at nl, 30,000 (expected molecular weight of unbound PSA) in ail cases demonstrating that the vast majority of intracellular tumor and normal PSA exists within cells in the "free" form. Binding studies showed that PSA recovered from LCM-procured cells retained the full ability to bind ACT, and two-dimensional PAGE Western analysis demonstrated that the PSA/ACT complex was stable under strong reducing conditions. We conclude that intracellular PSA exists in the "free" form and that binding to ACT occurs exclusively outside of the cell. C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Canc Genome Anat Project, Off Director, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. Georgetown Univ, Dept Chem, Washington, DC 20057 USA. NCI, Pathol Lab, Pathogenet Unit, NIH, Bethesda, MD 20892 USA. RP Ornstein, DK (reprint author), NCI, Urol Oncol Branch, NIH, Bldg 10,Room 2B47, Bethesda, MD 20892 USA. NR 11 TC 65 Z9 73 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB PY 2000 VL 6 IS 2 BP 353 EP 356 PG 4 WC Oncology SC Oncology GA 287JK UT WOS:000085502600006 PM 10690510 ER PT J AU Melnyk, S Pogribna, M Pogribny, IP Yi, P James, SJ AF Melnyk, S Pogribna, M Pogribny, IP Yi, P James, SJ TI Measurement of plasma and intracellular S-adenosylmethionine and S-adenosylhomocysteine utilizing coulometric electrochemical detection: Alterations with plasma homocysteine and pyridoxal 5 '-phosphate concentrations SO CLINICAL CHEMISTRY LA English DT Article ID ADENOSYL-L-HOMOCYSTEINE; NEURAL-TUBE DEFECTS; METHYLENETETRAHYDROFOLATE REDUCTASE; METHIONINE METABOLISM; HEALTHY-SUBJECTS; DNA METHYLATION; TISSUE-LEVELS; WHOLE-BLOOD; FOLATE; DEFICIENCY AB Background: The relative changes in plasma and intracellular concentrations of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAM) may be important predictors of cellular methylation potential and metabolic alterations associated with specific genetic polymorphisms and/or nutritional deficiencies. Because these metabolites are present in nanomolar concentrations in plasma, methods of detection generally require time-consuming precolumn processing or metabolite derivatization. Methods: We used HPLC with coulometric electrochemical detection for the simultaneous measurement of SAM and SAH in 200 mu L of plasma, 10(6) lymphocytes, or 10 mg of tissue. Filtered trichloroacetic acid extracts were injected directly into the HPLC system without additional processing and were eluted isocratically. Results: The limits of detection were 200 fmol/L for SAM and 40 fmol/L SAH. In plasma extracts, the interassay CV was 3.4-5.5% and the intraassay CV was 2.8-5.6%. The analytical recoveries were 96.8% and 97.3%. for SAM and SAH, respectively. In a cohort of healthy adult women with mean total homocysteine concentrations of 7.3 mu mol/L, the mean plasma value was 156 nmol/L for SAM and 20 nmol/L for SAH. In women with increased homocysteine concentrations (mean, 12.1 mu mol/L), plasma SAH, but not SAM, was increased (P <0.001), and plasma pyridoxal 5'-phosphate concentrations were reduced (P <0.001). Plasma SAM/SAH ratios were inversely correlated with homocysteine concentrations (r = 0.73; P < 0.01), and the SAM/SAH ratio in plasma was directly correlated with the:intracellular SAM/SAH ratio in lymphocytes (r 0.70; P <0.01). Conclusions: Increased homocysteine in serum is associated with an increase in SAH and a decrease in the SAM/SAH ratio that could negatively affect cellular methylation potential. Accurate and sensitive detection of these essential metabolites in plasma and in specific tissues should provide new insights into the regulation of:one-carbon metabolism under different nutritional and pathologic conditions. (C) 2000 American Association for Clinical Chemistry. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP James, SJ (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 51 TC 138 Z9 146 U1 0 U2 12 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 FEB PY 2000 VL 46 IS 2 BP 265 EP 272 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 283RF UT WOS:000085288500018 PM 10657384 ER PT J AU Honig, PK Graham, DJ Jenkins, JK AF Honig, PK Graham, DJ Jenkins, JK TI Identification and risk management of upper gastrointestinal (UGI) obstruction caused by an antihistamine-decongestant product. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 2000 VL 67 IS 2 MA PI2 BP 89 EP 89 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 288CA UT WOS:000085543200003 ER PT J AU Cantilena, LR Katki, AG Klecker, RW Collins, JM AF Cantilena, LR Katki, AG Klecker, RW Collins, JM TI Targeted inhibition of N-acetyltransferase, type I (NATI) in healthy volunteers. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Lab Clin Pharmacol, Rockville, MD 20857 USA. Uniformed Serv Univ Hlth Sci, Div Clin Pharmacol & Med Toxicol, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 2000 VL 67 IS 2 MA PI36 BP 98 EP 98 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 288CA UT WOS:000085543200036 ER PT J AU Kavanagh, R Kushmerick, P Smith, AL Unadkat, J AF Kavanagh, R Kushmerick, P Smith, AL Unadkat, J TI Sulfation in cystic fibrosis platelets. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. US FDA, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 2000 VL 67 IS 2 MA PI46 BP 100 EP 100 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 288CA UT WOS:000085543200046 ER PT J AU Kavanagh, R Unadkat, J AF Kavanagh, R Unadkat, J TI Sulfation in cystic fibrosis livers. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. US FDA, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 2000 VL 67 IS 2 MA PI47 BP 101 EP 101 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 288CA UT WOS:000085543200047 ER PT J AU Aszalos, A Ibrahim, S Knapton, A Licht, T AF Aszalos, A Ibrahim, S Knapton, A Licht, T TI Reversal of P-glycoprotein-mediated multidrug resistance in vitro by antihistamines and diuretics. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Laurenceville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 2000 VL 67 IS 2 MA PI70 BP 106 EP 106 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 288CA UT WOS:000085543200070 ER PT J AU Bies, R Ko, H Desjardins, R Gobburu, J Peck, C AF Bies, R Ko, H Desjardins, R Gobburu, J Peck, C TI Effective incorporation of preclinical information in the decision-making process for new drug development: An anonymous case study. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Georgetown Univ, Med Ctr, Ctr Drug Dev Sci, Washington, DC 20007 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 2000 VL 67 IS 2 MA PI73 BP 107 EP 107 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 288CA UT WOS:000085543200073 ER PT J AU Frye, RF Tracy, TS Hutzler, JM Korzekwa, KR Cannon, Y Pauli, M Huang, SM Branch, RA AF Frye, RF Tracy, TS Hutzler, JM Korzekwa, KR Cannon, Y Pauli, M Huang, SM Branch, RA TI Flurbiprofen as a selective in vivo probe of CYP2C9 activity. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. W Virginia Univ, Sch Pharm, Morgantown, WV 26506 USA. Univ Pittsburgh, Ctr Clin Pharmacol, Pittsburgh, PA USA. NR 0 TC 16 Z9 16 U1 0 U2 1 PU MOSBY-YEAR BOOK 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 2000 VL 67 IS 2 MA PI81 BP 109 EP 109 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 288CA UT WOS:000085543200081 ER PT J AU Wilson, JW Frye, RF Huang, HM Branch, RA AF Wilson, JW Frye, RF Huang, HM Branch, RA TI Sample size effects in assessing gender population bioequivalence (GPB) in a Pittsburgh cocktail SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Univ Pittsburgh, Dept Biostat, Ctr Clin Pharmacol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 2000 VL 67 IS 2 MA PII8 BP 116 EP 116 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 288CA UT WOS:000085543200110 ER PT J AU Lima, JJ Nguyen, BN Parker, RB Johnson, JA AF Lima, JJ Nguyen, BN Parker, RB Johnson, JA TI Chronopharmacodynamic model of S-verapamil-evoked antihypertensive effects. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 Univ Florida, Coll Pharm, Gainesville, FL USA. Univ Tennessee, Ctr Hlth Sci, Coll Pharm, Memphis, TN 38163 USA. US FDA, Rockville, MD 20857 USA. Nemours Childrens Clin, Ctr Clin Pediat Pharmacol, Jacksonville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 2000 VL 67 IS 2 MA PII42 BP 125 EP 125 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 288CA UT WOS:000085543200144 ER PT J AU Hutzler, JM Frye, RF Korzekwa, KR Branch, RA Huang, SM Tracy, TS AF Hutzler, JM Frye, RF Korzekwa, KR Branch, RA Huang, SM Tracy, TS TI Does dapsone-mediated activation of flurbiprofen metabolism by CYP2C9 occur in vivo? SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Univ Pittsburgh, Ctr Clin Pharmacol, Pittsburgh, PA USA. W Virginia Univ, Sch Pharm, Morgantown, WV 26506 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 2000 VL 67 IS 2 MA PII78 BP 134 EP 134 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 288CA UT WOS:000085543200180 ER PT J AU Ibrahim, S Knapton, A Licht, T Aszalos, A AF Ibrahim, S Knapton, A Licht, T Aszalos, A TI Modulation of the function of P-glycoprotein in NIH3T3 and human capillary endothelial cells by Ca2+ channel blockers. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 2000 VL 67 IS 2 MA PII79 BP 134 EP 134 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 288CA UT WOS:000085543200181 ER PT J AU Gobburu, JVS Holford, NHG Ko, HC Peck, CC AF Gobburu, JVS Holford, NHG Ko, HC Peck, CC TI Two-step model evaluation (TSME) for model qualification. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Georgetown Univ, Ctr Drug Dev Sci, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 2000 VL 67 IS 2 MA PII97 BP 139 EP 139 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 288CA UT WOS:000085543200199 ER PT J AU Katzper, M Averbuch, M AF Katzper, M Averbuch, M TI Gender and response to analgesia. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Ctr Drug Evaluat & Res, Div Analges Drugs, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 2000 VL 67 IS 2 MA PIII3 BP 142 EP 142 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 288CA UT WOS:000085543200214 ER PT J AU Al-Habet, S Bashaw, ED Lesko, L Williams, R Balian, J AF Al-Habet, S Bashaw, ED Lesko, L Williams, R Balian, J TI Narrow therapeutic index (NTI) drugs: Preliminary definition and criteria. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 1 U2 3 PU MOSBY-YEAR BOOK 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 2000 VL 67 IS 2 MA PIII23 BP 147 EP 147 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 288CA UT WOS:000085543200234 ER PT J AU Chatterjee, DJ Madani, S Parekh, A Hunt, J Chen, ML AF Chatterjee, DJ Madani, S Parekh, A Hunt, J Chen, ML TI Role of exposure-response relationship in drug development: Case studies. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 2000 VL 67 IS 2 MA PIII25 BP 148 EP 148 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 288CA UT WOS:000085543200236 ER PT J AU Huang, SM Booth, B Fadiran, E Uppoor, RS Doddapaneni, S Chen, M Ajayi, F Martin, T Lesko, L AF Huang, SM Booth, B Fadiran, E Uppoor, RS Doddapaneni, S Chen, M Ajayi, F Martin, T Lesko, L TI What lessons have we learned from the recent market withdrawal of terfenadine and mibefradil? SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 2000 VL 67 IS 2 MA PIII26 BP 148 EP 148 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 288CA UT WOS:000085543200237 ER PT J AU Venitz, J Yuan, R AF Venitz, J Yuan, R TI Effect of chronic renal failure (CRF) on the systemic PK of hepatically metabolized drugs. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Rockville, MD 20857 USA. Virginia Commonwealth Univ, Dept Pharmaceut, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 2000 VL 67 IS 2 MA PIII36 BP 151 EP 151 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 288CA UT WOS:000085543200247 ER PT J AU Sun, H Capparelli, E Lazor, J Connor, J AF Sun, H Capparelli, E Lazor, J Connor, J TI Identifying covariates (C) in pediatric population pharmacokinetic (PPK) studies using method of partial resampling (PR) and bootstrapping (BT). SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 Univ Calif San Diego, Pediat Patients Res Unit, San Diego, CA 92103 USA. US FDA, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 2000 VL 67 IS 2 MA PIII85 BP 163 EP 163 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 288CA UT WOS:000085543200296 ER PT J AU Sun, H Pelsor, F Lazor, J Selen, A Lesko, L AF Sun, H Pelsor, F Lazor, J Selen, A Lesko, L TI The reliability of population pharmacokinetic (PPK) approach in pediatric exclusivety claims (PEC). SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 2000 VL 67 IS 2 MA PIII86 BP 163 EP 163 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 288CA UT WOS:000085543200297 ER PT J AU Cunningham, WC Warner, CR AF Cunningham, WC Warner, CR TI Br concentration as an indication of pre-baking bromation of bread products SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE Br; bromine; bromate; bromide; bread products; INAA; HPLC ID PERFORMANCE LIQUID-CHROMATOGRAPHY; FLOW REACTOR DETECTION; POTASSIUM BROMATE; IMPROVER; MS AB Br concentration in bread for baked bread products was shown to be linearly proportional to the amount of Br added per kg of flour used to make the product. By concentration in bread can be used to help identify those bread products with the greatest likelihood of containing bromate residues. Instrumental neutron activation analysis was used to determine Br in test portions of bread products from commercial bakeries, homemade bread flour, and unbaked dough. High performance liquid chromatography was used to determine the bromate residue in selected test portions. C1 US FDA, Ctr Food Safety & Appl Nutr, Elemental Res Branch HFS338, Washington, DC 20204 USA. US FDA, Div Prod Manufacture & Use HFS245, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Cunningham, WC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Elemental Res Branch HFS338, Washington, DC 20204 USA. NR 13 TC 4 Z9 4 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD FEB PY 2000 VL 17 IS 2 BP 143 EP 148 PG 6 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 299CK UT WOS:000086178100002 PM 10793845 ER PT J AU Trucksess, MW Cho, TH Ready, DE AF Trucksess, MW Cho, TH Ready, DE TI Liquid chromatographic method for fumonisin B-1 in sorghum syrup and corn-based breakfast cereals SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE fumonisin; sorghum syrup; breakfast cereal ID FUSARIUM-MONILIFORME; ESOPHAGEAL CANCER; MYCOTOXINS; MAIZE; MOLDS AB The fungus Fusarium verticillioides has been found on corn and sorghum, so it is possible that one or move of these toxins may be found in corn products such as breakfast cereals and syrup prepared from sorghum. Published methods when applied to syrups spiked with fumonisins gave low recoveries, less than 50%. A method was therefore developed which would be applicable to the syrup and breakfast cereals as well. Test samples were extracted with methanol-0.1 M sodium phosphate buffer (pH3)(1 + 1). The extract was diluted with water and applied to a 1 g C-18 column. The column was washed with acetonitrile-water (2 + 8). Fumonisin B-I (FB1) was eluted with acetonitrile-trifluoroacetic acid (1000 + 1). The purified extract was evaporated and the toxin was derivatized with o-phthaldialdehyde mercaptoethanol. The reaction mixture was resolved on a C-18 liquid chromatographic column using acetonitrile-water-acetic acid (500 + 550 + 10.5) as the mobile phase at 37 degrees C, and FB1 measured with a fluorescence detector (excitation 335 nm, emission 440 nm). Recoveries of FB1 added to samples of sorghum syrup at levels ranging from 0.1 to 1.0 mu g/g were 94-132%. Recoveries of FB1 added to samples of breakfast cereal (corn flakes) at levels ranging from 0.2 to 1.6 mu g/g were 96-100%. The method was applied to the analysis of 35 samples of sorghum syrup collected from 15 states in the US. One sample was found to contain FB1 at 0.12 mu g/g. A total of 32 samples of breakfast cereals collected by the Food and Drug Administration inspectors from grocery stores around the Kansas City area were analysed; no FB1 was found in the breakfast cereals (< 0.01 mu g/g). Results of this study indicated that FB1 possibly is not a problem in sorghum syrup and corn-based breakfast cereals in the US. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Seoul Publ Hlth & Environm Inst, Seoul, South Korea. US FDA, Kansas City Dist Lab, Lenexa, KS USA. RP Trucksess, MW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 20 TC 16 Z9 17 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD FEB PY 2000 VL 17 IS 2 BP 161 EP 166 PG 6 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 299CK UT WOS:000086178100004 PM 10793847 ER PT J AU Moruzzi, G Garthright, WE Floros, JD AF Moruzzi, G Garthright, WE Floros, JD TI Aseptic packaging machine pre-sterilisation and package sterilisation: statistical aspects of microbiological validation SO FOOD CONTROL LA English DT Article DE aseptic packaging; validation; microbiological challenge; MPN; pre-sterilisation; package sterilisation; statistical AB Validation of the pre-sterilisation of an aseptic packaging machine and validation of the machine's sterilisation of the packages require many evaluations, including a microbiological challenge. This paper describes the statistical considerations supporting the microbiological challenge, focusing especially upon the use of the most probable number (MPN) technique. The uniformity of the log count reduction (LCR) must be demonstrated for the standard sterilisation technique to be applied to the machine and to the packages. The sites in the machine expected to receive the least sterilisation effect must be identified, and all sites in the machine must be verified independently of each other. If the uniformity of sterilisation can be shown for the packages, these can be evaluated as large sets of replicates, achieving considerable precision of the LCR. The MPN technique requires evaluation of the improbability of the results and must use credible estimates of the confidence interval. These techniques are thoroughly discussed, and a spreadsheet routine is demonstrated that incorporates the techniques. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Tetra Brik Packaging Syst SPA, I-41100 Modena, Italy. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Purdue Univ, Dept Food Sci, W Lafayette, IN 47907 USA. RP Moruzzi, G (reprint author), Tetra Brik Packaging Syst SPA, Via Delfini 1, I-41100 Modena, Italy. NR 14 TC 13 Z9 13 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-7135 J9 FOOD CONTROL JI Food Control PD FEB PY 2000 VL 11 IS 1 BP 57 EP 66 DI 10.1016/S0956-7135(99)00084-5 PG 10 WC Food Science & Technology SC Food Science & Technology GA 265VG UT WOS:000084266100009 ER PT J AU Lytle, CD Thomas, BM Gordon, EA Krauthamer, V AF Lytle, CD Thomas, BM Gordon, EA Krauthamer, V TI Electrostimulators for acupuncture: Safety issues SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID ELECTRICAL-STIMULATION; ELECTROACUPUNCTURE AB Three representative electrostimulators were evaluated to determine whether they meet the manufacturers' labeled nominal output parameters and how the measured parameters compare with a safety standard written for implanted peripheral nerve stimulators. The pulsed outputs (pulse width, frequency, and voltage) of three devices were measured with an oscilloscope across a 500-ohm resistance, meant to simulate subdermal tissue stimulated during electroacupuncture. For each device, at least two measured parameters were not within 25% of the manufacturer's claimed values. The measured values were compared with the American National Standard ANSI/AAMI NS15 safety standard for implantable peripheral nerve stimulators. Although for two stimulators the pulse voltage at maximum intensity was above that specified by the standard, short-term clinical use may still be safe because the standard was written for long-term stimulation. Similarly, the net unbalanced DC current, which could lead to tissue damage, electrolysis, and electrolytic degradation of the acupuncture needle, was within the limits of the standard at 30 pulses per second, but not at higher frequencies. The primary conclusions are (1) that the outputs of electrostimulators must be calibrated and (2) that practitioners must be adequately trained to use these electrostimulators safely. C1 US FDA, Off Sci & Technol, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Marquette Univ, Dept Biomed Engn, Milwaukee, WI 53233 USA. RP Lytle, CD (reprint author), POB 396, Arroyo Seco, NM 87514 USA. NR 25 TC 4 Z9 4 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD FEB PY 2000 VL 6 IS 1 BP 37 EP 44 DI 10.1089/acm.2000.6.37 PG 8 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 285PN UT WOS:000085397600006 PM 10706234 ER PT J AU Carlson, M Thompson, RD AF Carlson, M Thompson, RD TI Analyte loss due to membrane filter adsorption as determined by high-performance liquid chromatography SO JOURNAL OF CHROMATOGRAPHIC SCIENCE LA English DT Article C1 US FDA, Dept Hlth & Human Serv, Minneapolis, MN 55401 USA. RP Carlson, M (reprint author), US FDA, Dept Hlth & Human Serv, 240 Hennepin Ave, Minneapolis, MN 55401 USA. NR 12 TC 8 Z9 8 U1 0 U2 0 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0021-9665 J9 J CHROMATOGR SCI JI J. Chromatogr. Sci. PD FEB PY 2000 VL 38 IS 2 BP 77 EP 83 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 280XX UT WOS:000085130000006 PM 10677837 ER PT J AU Koller, EA Green, L Malozowski, S AF Koller, EA Green, L Malozowski, S TI Comment on growth hormone therapy and retinal changes mimicking diabetic retinopathy SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Letter C1 US FDA, CDER, Div Metab & Endocrine Drug Prod, Rockville, MD 20857 USA. US FDA, CDER, Div Drug Risk Evaluat, Rockville, MD 20857 USA. RP Koller, EA (reprint author), US FDA, CDER, Div Metab & Endocrine Drug Prod, Rockville, MD 20857 USA. NR 4 TC 2 Z9 2 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 2000 VL 85 IS 2 BP 923 EP 923 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 285EX UT WOS:000085377700076 ER PT J AU Matsumoto, C Okuda, J Ishibashi, M Iwanaga, M Garg, P Rammamurthy, T Wong, HC Depaola, A Kim, YB Albert, MJ Nishibuchi, M AF Matsumoto, C Okuda, J Ishibashi, M Iwanaga, M Garg, P Rammamurthy, T Wong, HC Depaola, A Kim, YB Albert, MJ Nishibuchi, M TI Pandemic spread of an O3 : K6 clone of Vibrio parahaemolyticus and emergence of related strains evidenced by arbitrarily primed PCR and toxRS sequence analyses SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID THERMOSTABLE DIRECT HEMOLYSIN; TDH-RELATED HEMOLYSIN; KANAGAWA PHENOMENON; TRH GENE; CHOLERAE; HOMOLOG; DNA AB Vibrio parahaemolyticus O3:K6 strains responsible for the increase in the number of cases of diarrhea in Calcutta, India, beginning in February 1996 and those isolated from Southeast Asian travelers beginning in 1995 were shown to belong to a unique clone characterized by possession of the tdh gene but not the trh gene and by unique arbitrarily primed PCR (AP-PCR) profiles (J. Okuda, M. Ishibashi, E. Hayakawa, T. Nishino, Y. Takeda, A. K. Mukhopadhyay, S. Garg S. K. Bhattacharya, G. B. Nair, and M. Nishibuchi, J. Clin. Microbiol. 35:3150-3155, 1997), Evidence supporting a hypothesis that this clone emerged only recently and is spreading to many countries was obtained in this study. Of 227 strains isolated in a hospital in Bangladesh between 1977 and 1998, only 22 strains isolated between 1996 and 1998 belonged to the new O3:K6 clone (defined by the serovar, the tdh and trh typing, and AP-PCR profiles). The O3:K6 strains isolated from clinical sources in Taiwan, Laos, Japan, Thailand, Korea, and the United States between 1997 and 1998 were also shown to belong to the new O3:K6 clone. The clonality of the new O3:K6 strains was also confirmed by analysis of the toxRS sequence, which has been shown to be useful for phylogenetic analysis of the members of the genus Vibrio. The toxRS sequences of the representative strains of the new O3:K6 clone differed from those of the O3:K6 strains isolated before 1995 at least at 7 base positions within a 1,346-bp region. A new PCR method targeted to 2 of the base positions unique to the new O3:K6 clone was developed. This PCR method could clearly differentiate all 172 strains belonging to the new O3:K6 clone from other O3:K6 strains isolated earlier. One hundred sixty-six strains belonging to 28 serovars other than O3:K6 were also examined by the new PCR method. The tdh-positive and trh-lacking strains that belonged to the O4:K68 and O1:K untypeable serovars and were isolated in three countries and from international travelers beginning in 1997 gave positive results. The AP-PCR profiles of these strains were nearly identical to those of the new O3:K6 clone, and their toxRS sequences were 100% identical to that of the new O3:K6 clone. The results suggest that these strains may have diverged from the new O3:K6 clone by alteration of the O:K antigens. In conclusion, this study presents strong evidence for the first pandemicity in the history of V. parahaemolyticus and reports a novel toxRS-targeted PCR method that will be useful in epidemiological investigation of the cases associated with the current pandemic spread. C1 Kyoto Univ, Ctr SE Asian Studies, Sakyo Ku, Kyoto 6068501, Japan. Osaka Prefectural Inst Publ Hlth, Higashinari Ku, Osaka 537, Japan. Univ Ryukyus, Dept Bacteriol, Sch Med, Nishihara, Okinawa 90301, Japan. Natl Inst Cholera & Enter Dis, Dept Microbiol, Calcutta 700010, W Bengal, India. Soochow Univ, Dept Microbiol, Taipei 11102, Taiwan. US FDA, Dauphin Island, AL 36528 USA. Pusan Natl Univ, Coll Med, Dept Microbiol, Pusan 602739, South Korea. Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. RP Nishibuchi, M (reprint author), Kyoto Univ, Ctr SE Asian Studies, Sakyo Ku, 46 Shimoadachi Cho, Kyoto 6068501, Japan. NR 24 TC 244 Z9 268 U1 2 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD FEB PY 2000 VL 38 IS 2 BP 578 EP 585 PG 8 WC Microbiology SC Microbiology GA 281XR UT WOS:000085187200019 PM 10655349 ER PT J AU Averbuch, M Katzper, M AF Averbuch, M Katzper, M TI Baseline pain and response to analgesic medications in the postsurgery dental pain model SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID LINE PAIN AB In designing clinical trials for the treatment of acute pain, enrollment of patients with moderate to severe pain is recommended even when the desired indication is treatment of mild pain. To test this approach, the authors explored the results of two studies that had the same standard placebo-controlled, parallel-group design and that compared the study medication to a single dose of ibuprofen 400 mg. One study had 25 subjects, the other 50 in its ibuprofen arm. Subjects indicating moderate or severe pain (on a scale ranging from 0 = none, 1 = mild, 2 = moderate, 3 = severe) following a surgical extraction of two or more third molars were enrolled. There was a difference between the ibuprofen groups in these two studies in average baseline pain intensity (PI) (2.88 +/- 0.33 vs. 2.26 +/- 0.44). In the higher baseline group, PI decreased faster, achieving lower levels of PI that were maintained for the rest of the study period. The results of pain relief measurements paralleled those of PI. The authors conclude that including patients with a higher degree of baseline pain in the postoperative dental pain model has the potential to increase discrimination of analgesic properties of new drugs. Journal of Clinical Pharmacology, 2000;40:133-137 (C)2000 the American College of Clinical Pharmacology. C1 US FDA, Ctr Drug Evaluat & Res, Div Analges Antiinflammatory & Ophthalm Drug Prod, Rockville, MD 20857 USA. RP Katzper, M (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Analges Antiinflammatory & Ophthalm Drug Prod, HFD-550,5600 Fishers Lane, Rockville, MD 20857 USA. NR 6 TC 22 Z9 24 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD FEB PY 2000 VL 40 IS 2 BP 133 EP 137 DI 10.1177/00912700022008775 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 276NM UT WOS:000084884400003 PM 10664918 ER PT J AU Kiesewetter, DO Sassaman, MB Robbins, J Jagoda, EM Carson, RE Appel, NM Sutkowski, E Herscovitch, P Braun, A Eckelman, WC AF Kiesewetter, DO Sassaman, MB Robbins, J Jagoda, EM Carson, RE Appel, NM Sutkowski, E Herscovitch, P Braun, A Eckelman, WC TI Synthesis and evaluation of an F-18 analog of forskolin for imaging adenylyl cyclase SO JOURNAL OF FLUORINE CHEMISTRY LA English DT Article; Proceedings Paper CT 16th International Conference on Fluorine Chemistry (ICFC 99) CY MAY 09-11, 1999 CL TOKYO, JAPAN SP Japan Soc Promot Sci DE adenylyl cyclase; forskolin; F-18 ID 7-DESACETYLFORSKOLIN; DERIVATIVES AB We prepared two fluorine containing carbamate analogs of forskolin as potential agents for imaging adenylyl cyclase in the Living brain with positron emission tomography. Both compounds display high in vitro affinity for adenylyl cyclase. The radiosynthesis of 7-(2-[F-18] fluoroethyl) carbamoyl forskolin from an imidazolyl carbamate utilizes [F-18] fluoroethyl amine, prepared by a novel method employing rapid deprotection and requiring no distillation. The brain uptake in rats and monkeys of 7-(2-[F-18] fluoroethyl) carbamoyl forskolin is too low to be an effective imaging agent for this second messenger system. (C) 2000 Elsevier Science S.A. All rights reserved. C1 NIH, Warren Grant Magnuson Clin Ctr, Posit Emiss Tomog Dept, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Mol Pharmacol Lab, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Communicat Disorders, Voice Speech & Language Branch, NIH, Bethesda, MD 20892 USA. RP Kiesewetter, DO (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Posit Emiss Tomog Dept, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 11 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0022-1139 J9 J FLUORINE CHEM JI J. Fluor. Chem. PD FEB PY 2000 VL 101 IS 2 BP 297 EP 304 DI 10.1016/S0022-1139(99)00174-8 PG 8 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA 269QH UT WOS:000084488700025 ER PT J AU Gendel, SM Ulaszek, J AF Gendel, SM Ulaszek, J TI Ribotype analysis of strain distribution in Listeria monocytogenes SO JOURNAL OF FOOD PROTECTION LA English DT Article ID DIVERSITY AB Changes in the temporal and spatial patterns of strain distribution for the foodborne pathogen Listeria monocytogenes were studied by ribotyping using the Qualicon Riboprinter system. Ribotype patterns were obtained by using the restriction enzymes EcoRI and PvuII for 72 isolates of L. monocytogenes recovered from smoked salmon samples over a period of 3 years. Each pattern was classified both by comparison to a pattern library and by comparison among the 72 isolate patterns. Eleven EcoRI-based ribogroups and 16 PvuII groups were identified. Eight of the 11 EcoRI ribogroups were found in isolates obtained over a period of >12 months, and 75% of the EcoRI ribogroups that were found in more than one food sample were distributed nationally. Within the set of isolates, there were 26 instances where more than one isolate was obtained from a single food sample. In 35% of these instances, the co-isolates produced different ribotype patterns, indicating that multiple strains of L. monocytogenes commonly coexist in the same environment. Overall, these data indicate that the population of L. monocytogenes consists of a number of widely dispersed strains with little geographic or temporal stratification. C1 Natl Ctr Food Safety & Technol, Food & Drug Adm, Summit Argo, IL 60501 USA. Natl Ctr Food Safety & Technol, IIT, Summit Argo, IL 60501 USA. RP Gendel, SM (reprint author), Natl Ctr Food Safety & Technol, Food & Drug Adm, 6502 S Archer, Summit Argo, IL 60501 USA. EM smg@cfsan.fda.gov FU FDA HHS [FD-000431] NR 20 TC 38 Z9 41 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 FEB PY 2000 VL 63 IS 2 BP 179 EP 185 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 282GU UT WOS:000085210500005 PM 10678421 ER PT J AU Yu, CR Peden, KWC Zaitseva, MB Golding, H Farber, JM AF Yu, CR Peden, KWC Zaitseva, MB Golding, H Farber, JM TI CCR9A and CCR9B: Two receptors for the chemokine CCL25/TECK/Ck beta-15 that differ in their sensitivities to ligand SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; IMMUNODEFICIENCY-VIRUS TYPE-1; MOLECULAR-CLONING; FUNCTIONAL-CHARACTERIZATION; CELL-LINES; IN-VIVO; EXPRESSION; LYMPHOCYTES; CXCR4; GENE AB We isolated cDNAs for a chemokine receptor-related protein having the database designation GPR-9-6. Two classes of cDNAs were identified from mRNAs that arose by alternative splicing and that encode receptors that we refer to as CCR9A and CCR9B, CCR9A is predicted to contain 12 additional amino acids at its N terminus as compared with CCR9B, Cells transfected with cDNAs for CCR9A and CCR9B responded to the chemokine CC chemokine ligand 25 (CCL25)/thymus-expressed chemokine (TECK)/chemokine beta-15 (CK beta-15) in assays for both calcium flux and chemotaxis. No other chemokines tested produced responses specific for the cDNA-transfected cells. mRNA for CCR9A/B is expressed predominantly in the thymus, coincident with the expression of CCL25, and highest expression for CCR9A/B among thymocyte subsets was found in CD4(+)CD8(+) cells. mRNAs encoding the A and B forms of the receptor were expressed at a ratio of similar to 10:1 in immortalized T cell lines, in PBMC, and in diverse populations of thymocytes, The EC50 of CCL25 for CCR9A was lower than that for CCR9B, and CCR9A was desensitized by doses of CCL25 that failed to silence CCR9B, CCR9 is the first example of a chemokine receptor in which alternative mRNA splicing leads to proteins of differing activities, providing a mechanism for extending the range of concentrations over which a cell can respond to increments in the concentration of ligand, The study of CCR9A and CCR9B should enhance our understanding of the role of the chemokine system in T cell biology, particularly during the stages of thymocyte development. C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Retrovirus Res, Bethesda, MD 20892 USA. RP Farber, JM (reprint author), NIAID, Clin Invest Lab, NIH, Bldg 10,Room 11N-228,MSC 1888, Bethesda, MD 20892 USA. NR 58 TC 39 Z9 40 U1 0 U2 4 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 1 PY 2000 VL 164 IS 3 BP 1293 EP 1305 PG 13 WC Immunology SC Immunology GA 277AJ UT WOS:000084910300021 PM 10640743 ER PT J AU Koehler, KM Cunningham-Sabo, L Lambert, LC McCalman, R Skipper, BJ Davis, SM AF Koehler, KM Cunningham-Sabo, L Lambert, LC McCalman, R Skipper, BJ Davis, SM TI Assessing food selection in a health promotion program: Validation of a brief instrument for American Indian children in the Southwest United States SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID SCHOOL-CHILDREN; OBESITY; NAVAJO; GUIDELINES; NUTRITION; FREQUENCY; ACCURACY; VALIDITY; PROJECT; ISSUES AB Objective Brief dietary assessment instruments are needed to evaluate behavior changes of participants in dietary intervention programs. The purpose of this project was to design and validate an instrument for children participating in Pathways to Health, a culturally appropriate, cancer prevention curriculum. Design Validation of a brief food selection instrument, Yesterday's Food Choices (YFC), which contained 33 questions about foods eaten the previous day with response choices of yes, no, or not sure. Reference data for validation were 24-hour dietary recalls administered individually to 120 students selected randomly. Subjects The YFC and 24-hour dietary recalls were administered to American Indian children in fifth- and seventh-grade classes in the Southwest United States. Statistical analyses performed Dietary recalls were coded for food items in the YFC and results were compared for each item using percentage agreement and the kappa statistic. Results Percentage agreement for all items was greater than 60%; for most items it was greater than 70%, and for several items it was greater than 80%. The amount of agreement beyond that explained by chance (kappa statistic) was generally small. Three items showed substantial agreement beyond chance (kappa greater than or equal to 0.6); 2 items showed moderate agreement (kappa = 0.40 to 0.59); most items showed fair agreement (kappa = 0.20 to 0.39). The food items showing substantial agreement were hot or cold cereal, low-fat milk, and mutton or chile stew. Fried or scrambled eggs and deep-fried foods showed moderate agreement beyond chance. Conclusions Previous development and validation of brief food selection instruments for children participating in health promotion programs has had limited success. In this study, instrument-related factors that apparently contributed to poor agreement between data from the YFC and 24-hour dietary recall were inclusion of categories of foods vs specific foods; food knowledge, preparation, and vocabulary; item length; and overreporting of attractive foods. Collecting and scoring the 24-hour recall data may also have contributed to poor agreement. Further development of brief instruments for evaluating changes in children's behavior in dietary intervention programs is necessary. Factors related to the YFC that need further development may be issues that are also important in the development of effective, brief dietary assessments for children as individual clients or patients. C1 Univ New Mexico, Sch Med, Dept Pediat, Albuquerque, NM 87131 USA. Univ New Mexico, Sch Med, Dept Family & Community Med, Albuquerque, NM 87131 USA. Univ Mexico, Sch Med, Mexico City, DF, Mexico. RP Koehler, KM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-728,200 C St SW, Washington, DC 20204 USA. FU NCI NIH HHS [1 UO1 CA52283] NR 43 TC 12 Z9 14 U1 3 U2 4 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 2000 VL 100 IS 2 BP 205 EP 211 DI 10.1016/S0002-8223(00)00064-X PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 460MC UT WOS:000170310500019 PM 10670393 ER PT J AU Martinez, M Friedlander, L Condon, R Meneses, J O'Rangers, J Weber, N Miller, M AF Martinez, M Friedlander, L Condon, R Meneses, J O'Rangers, J Weber, N Miller, M TI Response to criticisms of the USFDA parametric approach for withdrawal time estimation: rebuttal and comparison to the nonparametric method proposed by Concordet and Toutain SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID VETERINARY DRUGS AB The benefits and drawbacks of using nonparametric methods for estimating product withdrawal times have been debated for many years. This issue was recently revived by Concordet & Toutain (1997a, b) when they described a nonparametric method for withdrawal time estimation. The authors urged the international adoption of this approach, basing their recommendation on three fundamental concerns: (1) the lack of a consistent official procedure for determining a withdrawal time within the European Union (EU); (2) the need to identify a statistical method for improving the international harmonization of withdrawal times for new chemical entities; and (3) a lack of confidence in the robustness of the US Food and Drug Administration/Center for Veterinary Medicine (US FDA) procedure, particularly with respect to minor violations in the underlying parametric assumptions. Due to the critical nature of these issues, the US FDA considers it vital to respond to these concerns. This paper provides a description of the US FDA parametric procedure. We also examine the statistical concerns expressed by Concordet and Toutain, identifying the reasons for our confidence in the US FDA parametric approach. Finally, using their Monte Carlo simulation models, we generate additional datasets to explore the behaviour of their nonparametric procedure and evaluate its ability to support US FDA regulatory activities. C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. US FDA, Off Womens Hlth, Rockville, MD 20855 USA. RP Martinez, M (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20855 USA. NR 9 TC 8 Z9 10 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD FEB PY 2000 VL 23 IS 1 BP 21 EP 35 PG 15 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 299DK UT WOS:000086180400004 PM 10747240 ER PT J AU Kolykhalov, AA Mihalik, K Feinstone, SM Rice, CM AF Kolykhalov, AA Mihalik, K Feinstone, SM Rice, CM TI Hepatitis C virus-encoded enzymatic activities and conserved RNA elements in the 3 ' nontranslated region are essential for virus replication in vivo SO JOURNAL OF VIROLOGY LA English DT Article ID YELLOW-FEVER VIRUS; 3'-UNTRANSLATED REGION; SECONDARY STRUCTURE; SERINE PROTEINASE; CLEAVAGE SITES; E2-NS2 REGION; GENOME RNA; CDNA CLONE; IDENTIFICATION; POLYPROTEIN AB Hepatitis C virus (HCV) infection is a widespread major human health concern, Significant obstacles in the study of this virus include the absence of a reliable tissue culture system and a small-animal model. Recently, we constructed full-length HCV cDNA clones and successfully initiated HCV infection in two chimpanzees by intrahepatic injection of in vitro-transcribed RNA (A, A, Kolykhalov et al., Science 277:570-574, 1997). In order to validate potential targets for development of anti-HCV therapeutics, we constructed six mutant derivatives of this prototype infectious clone. Four clones contained point mutations ablating the activity of the NS2-3 protease, the NS3-4A serine protease, the NS3 NTPase/helicase, and the NS5B polymerase. Two additional clones contained deletions encompassing all or part of the highly conserved 98-base sequence at the 3' terminus of the HCV genome RNA. The RNA transcript from each of the six clones was injected intrahepatically into a chimpanzee. No signs of HCV infection were detected in the 8 months following the injection. Inoculation of the same animal with nonmutant RNA transcripts resulted in productive HCV infection, as evidenced by viremia, elevated serum alanine aminotransferase, and HCV-specific seroconversion, These data suggest that these four HCV-encoded enzymatic activities and the conserved 3' terminal RNA element are essential for productive replication in vivo. C1 Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. US FDA, Ctr Biol Evaluat & Res, Div Virol, Bethesda, MD 20892 USA. RP Rice, CM (reprint author), Washington Univ, Sch Med, Dept Mol Microbiol, Campus Box 8230,660 S Euclid Ave, St Louis, MO 63110 USA. FU NCI NIH HHS [R01 CA057973, CA57973]; NIAID NIH HHS [N01AI40034] NR 58 TC 477 Z9 489 U1 3 U2 14 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2000 VL 74 IS 4 BP 2046 EP 2051 DI 10.1128/JVI.74.4.2046-2051.2000 PG 6 WC Virology SC Virology GA 277XC UT WOS:000084958000052 PM 10644379 ER PT J AU Wang, RF Myers, MJ Campbell, W Cao, WW Paine, D Cerniglia, CE AF Wang, RF Myers, MJ Campbell, W Cao, WW Paine, D Cerniglia, CE TI A rapid method for PCR detection of bovine materials in animal feedstuffs SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE PCR; detection; bovine spongiform encephalopathy AB Rapid identification of bovine materials in animal feedstuffs is essential for effective control of a potential source of bovine spongiform encephalopathy. We have developed a rapid method for the detection of the presence of bovine materials in animal feeds. Animal feed samples were prepared by a Chelex-100 treatment method, then subjected to polymerase chain reaction (PCR) detection. The assay can be completed in 2 h including 30 min for sample preparation, 35-65 min for PCR cycling and 30 min for gel electrophoresis. This method is not only rapid, simple and consistent, beet also avoids a hazardous waste disposal issue associated with a previously described guanidine thiocyanate (GuSCN) extraction-PCR method. (C) 2000 Academic Press. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Ctr Vet Med, Div Anim Res, Laurel, MD 20708 USA. RP Wang, RF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 7 TC 65 Z9 77 U1 0 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD FEB PY 2000 VL 14 IS 1 BP 1 EP 5 DI 10.1006/mcpr.1999.0273 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 296XY UT WOS:000086053100001 PM 10722787 ER PT J AU Whitman, MC Strohmaier, J O'Boyle, K Tingem, JM Wilkinson, Y Goldstein, J Chen, T Brorson, K Brunswick, M Kozlowski, S AF Whitman, MC Strohmaier, J O'Boyle, K Tingem, JM Wilkinson, Y Goldstein, J Chen, T Brorson, K Brunswick, M Kozlowski, S TI The isolated major histocompatibility complex class I alpha 3 domain binds beta 2m and CD8 alpha alpha dimers SO MOLECULAR IMMUNOLOGY LA English DT Article DE MHC; CD8; beta 2-microglobulin; biochemistry ID MHC CLASS-I; T-CELL RECEPTOR; SURFACE-PLASMON RESONANCE; HEAVY-CHAINS; ANTIGENIC PEPTIDE; CD8 CORECEPTOR; MOLECULES; BETA-2-MICROGLOBULIN; RECOGNITION; ASSOCIATION AB The MHC class I molecule plays a crucial role in cytotoxic lymphocyte function. The heavy chain of the MHC class I molecule can form many non-covalent interactions with other molecules on multiple domains and surfaces. We have generated an isolated alpha 3 domain of a murine MHC class I molecule and evaluated the contribution of this domain to binding with the MHC class I light chain, beta 2m, and CD8. The alpha 3 domain binds beta 2m at a thousand-fold higher concentration than the whole MHC, and binds CD8 alpha alpha with a dependence on the alpha 3 CD loop. Our results are relevant for models of MHC folding and CD8-MHC function. The study of individual domains of complex molecules is an important strategy for understanding their dynamic structure and function. Published by Elsevier Science Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Ab, Bethesda, MD 20892 USA. RP Kozlowski, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Ab, Bethesda, MD 20892 USA. NR 50 TC 8 Z9 8 U1 0 U2 1 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 FEB-MAR PY 2000 VL 37 IS 3-4 BP 141 EP 149 DI 10.1016/S0161-5890(00)00034-1 PG 9 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 329JK UT WOS:000087903700006 PM 10865113 ER PT J AU Tu, M Tong, W Perkins, R Valentine, CR AF Tu, M Tong, W Perkins, R Valentine, CR TI Predicted changes in pre-mRNA secondary structure vary in their association with exon skipping for mutations in exons 2, 4, and 8 of the Hprt gene and exon 51 of the fibrillin gene SO MUTATION RESEARCH-GENOMICS LA English DT Article DE exon skipping; RNA secondary structure; exonic splicing enhancers ID HUMAN LYMPHOBLASTOID-CELLS; DIPLOID HUMAN FIBROBLASTS; SPLICE-SITE SELECTION; HAMSTER OVARY CELLS; MESSENGER-RNA; IN-VIVO; COMPUTER-SIMULATION; NONSENSE MUTATIONS; MOLECULAR ANALYSIS; N-NITROSOUREA AB Exon skipping that accompanies exonic mutation might be caused by an effect of the mutation on pre-mRNA secondary structure. Previous attempts to associate predicted secondary structure of pre-mRNA with exon skipping have been hindered by either a small number of available mutations, sub-optimal structures, or weak effects on exon skipping. This report identifies more extensive sets of mutations from the human and hamster Hprt gene whose association with exon skipping is clear. Optimal secondary structures of the wild-type and mutant pre-mRNA surrounding each exon were predicted by energy minimization and were compared by energy dot plots. A significant association was found between the occurrence of exon skipping and the disruption of a stem containing the acceptor site consensus sequences of exon 8 of the human Hprt gene. However, no change in secondary structure was associated with skipping of exon 4 of the hamster Hprt gene. Using updated energy parameters we found a different structure than that previously reported for exon 2 of the hamster Hl,rt gene. In contrast to the previously reported structure, no significant association was found between predicted structural changes and skipping of exon 2. For all three Hprt exons studied, there was a significantly greater number of deoxythymidine substitutions among mutations accompanied by exon skipping than among mutations without exon skipping. For exon 8, deoxythymidine substitution was also associated with structural changes in the stem containing the acceptor site consensus sequences. For exon 51 of the human fibrillin gene, structural differences from wild type were predicted for all four mutations accompanied by exon skipping that were: not were predicted for a single mutation without exon skipping. Our results suggest that both primary and secondary pre-mRNA structure contribute to definition of Hprt exons, which may involve exonic splicing enhancers. (C) 2000 Elsevier Science B,V. All rights reserved. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, ROW Sci, Jefferson, AR 72079 USA. RP Valentine, CR (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 53 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5726 J9 MUTAT RES-GENOMICS JI Mutat. Res.-Genomics PD FEB PY 2000 VL 432 IS 1-2 BP 15 EP 32 DI 10.1016/S1383-5726(99)00011-4 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 408AA UT WOS:000167303300004 PM 10729708 ER PT J AU Wang, RF Khan, AA Cao, WW Cerniglia, CE AF Wang, RF Khan, AA Cao, WW Cerniglia, CE TI Cloning, sequencing, and expression of the gene encoding enolase from Cunninghamella elegans SO MYCOLOGICAL RESEARCH LA English DT Article ID NEURON-SPECIFIC ENOLASE; FILAMENTOUS FUNGUS; METABOLISM; BIOTRANSFORMATION; BACTERIA; MARKER AB A polyclonal antibody was raised against microsomes prepared from Cunninghamella elegans and used to screen a C. elegans cDNA library. A cDNA clone from this screen was obtained, which corresponds to the C. elegans enolase gene. A single open reading frame (ORF) of 1311 bases was found, which encodes a protein of mel. wt 46882.9. The gene was found to start with an unusual initiation codon TCG, not a Standard ATG codon. This was demonstrated first by ORF analysis of the determined sequence and was further confirmed by alignment of the protein with other published enolase sequences. The enolase gene was sub-cloned and over-expressed in Escherichia coli using the expression vector pQE30. Purified recombinant protein from this sub-clone showed the predicted molecular size in SDS-PAGE gel separations. Enolase enzyme activity was also detected that indicating the TCG initiation codon was correct. The C. elegans enolase was found to cluster with other fungal enolases in a phylogenetic analysis. Bacterial enolases and those of animals were separated in different clusters. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Wang, RF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 19 TC 2 Z9 3 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0953-7562 J9 MYCOL RES JI Mycol. Res. PD FEB PY 2000 VL 104 BP 175 EP 179 DI 10.1017/S0953756299001112 PN 2 PG 5 WC Mycology SC Mycology GA 297GQ UT WOS:000086074500009 ER PT J AU Popke, EJ Mayorga, AJ Fogle, CM Paule, MG AF Popke, EJ Mayorga, AJ Fogle, CM Paule, MG TI Effects of acute nicotine on several operant behaviors in rats SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE nicotine; rats; operant behavior; cognitive function ID INFORMATION-PROCESSING PERFORMANCE; DEFICIT HYPERACTIVITY DISORDER; SHORT-TERM-MEMORY; PROGRESSIVE RATIO; AGED RATS; COGNITIVE PERFORMANCE; SUBCUTANEOUS NICOTINE; ALZHEIMERS-DISEASE; TOURETTES-SYNDROME; CIGARETTE-SMOKING AB The present experiment assessed nicotine's effects on complex cognitive processes using a variety of operant tasks in rats, including incremental repeated acquisition (IRA) to assess learning; conditioned position responding (CPR) to assess auditory, visual, and position discrimination; progressive ratio (PR) to assess motivation; temporal response differentiation (TRD) to assess timing; and differential reinforcement of low response rates (DRL) to assess timing and response inhibition. Acute nicotine administration (0.0, 0.3, 0.42, 0.56, 0.75, and 1.0 mg/kg, IP) increased IRA and CPR response rate without significantly altering accuracy. Nicotine had similar effects on response rate for PR. For TRD, nicotine had a U-shaped dose effect on accuracy, but failed to shift the mode of the TRD response distribution. For DRL, nicotine reduced accuracy and also shifted the mode of the DRL response initiation time distribution to the left. Nicotine produced an inverted U-shaped dose-effect curve for the overall number of "bursting" responses under both of these schedules. The results of this experiment suggest that nicotine can impair performance on some aspects of cognitive-behavioral performance, while simultaneously improving performance on others. (C) 2000 Elsevier Science Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Popke, EJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 44 TC 42 Z9 42 U1 1 U2 2 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 FEB PY 2000 VL 65 IS 2 BP 247 EP 254 DI 10.1016/S0091-3057(99)00205-1 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 275WE UT WOS:000084842500008 PM 10672976 ER PT J AU Gaylor, DW Culp, SJ Goldstein, LS Beland, FA AF Gaylor, DW Culp, SJ Goldstein, LS Beland, FA TI Cancer risk estimation for mixtures of coal tars and benzo(a)pyrene SO RISK ANALYSIS LA English DT Article DE cancer; risk estimation; coal tar mixtures; benzo(a)pyrene ID BIOASSAY AB Two-year chronic bioassays were conducted by using B6C3F1 female mice fed several concentrations of two different mixtures of coal tars from manufactured gas waste sites or benzo(a)pyrene (BaP). The purpose of the study was to obtain estimates of cancer potency of coal tar mixtures, by using conventional regulatory methods, for use in manufactured gas waste site remediation. A secondary purpose was to investigate the validity of using the concentration of a single potent carcinogen, in this case benzo(a)pyrene, to estimate the relative risk for a coal tar mixture. The study has shown that BaP dominates the cancer risk when its concentration is greater than 6,300 ppm in the coal tar mixture. In this case the most sensitive tissue site is the forestomach. Using low-dose linear extrapolation, the lifetime cancer risk for humans is estimated to be: Risk < 1.03 x 10(-4) (ppm coal tar in total diet) + 240 x 10(-4) (ppm BaP in total diet), based on forestomach tumors. If the BaP concentration in the coal tar mixture is less than 6,300 ppm, the more likely case, then lung tumors provide the largest estimated upper limit of risk, Risk < 2.55 x 10(-4) (ppm coal tar in total diet), with no contribution of BaP to lung tumors. The upper limit of the cancer potency (slope factor) for lifetime oral exposure to benzo(a)pyrene is 1.2 x 10(-3) per mu g per kg body weight per day from this Good Laboratory Practice (GLP) study compared with the current value of 7.3 x 10(-3) per mu g per kg body weight per day listed in the U.S. EPA Integrated Risk Information System. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Elect Power Res Inst, Palo Alto, CA USA. RP Gaylor, DW (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 12 TC 22 Z9 22 U1 0 U2 2 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD FEB PY 2000 VL 20 IS 1 BP 81 EP 85 DI 10.1111/0272-4332.00008 PG 5 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 361YF UT WOS:000089751300008 PM 10795341 ER PT J AU Clark, KJ Monser, M Stein, KE Shapiro, MA AF Clark, KJ Monser, M Stein, KE Shapiro, MA TI A novel activation induced lymphocyte surface antigen, 90.12, is also expressed on apoptotic cells SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID CALCIUM-BINDING PROTEINS; MOUSE BONE-MARROW; HUMAN NEUTROPHIL ACTIVATION; MURINE-B-LYMPHOPOIESIS; S100 PROTEIN; T-CELL; HUMAN-MONOCYTES; DIFFERENTIATION; MRP14; LIGAND AB We describe a monoclonal antibody, mAb 90.12, which recognizes a novel activation induced lymphocyte surface antigen. Flow cytometric analysis of normal tissues shows the antigen to be expressed on higher percentages of B lymphocytes in the bone marrow than in the spleen and the lymph node. Similarly, the 90.12 antigen is expressed on higher percentages of thymocytes than peripheral T cells. MAb 90.12 immunoprecipitates three proteins with a molecular weight of 12-18 kDa which are not linked to the membrane by phosphotidylinositol. Expression of the 90.12 antigen is increased on activated B cells and the extent of upregulation varies with the stimulus. Lipopolysaccharide (LPS) stimulation results in expression on most B cells, while expression is upregulated on only a subset of B cells stimulated with anti-immunoglobulin M (IgM), interleukin(IL)4 and IL5. Finally, we show that 90.12 antigen expression is also increased on apoptotic cells. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Rockville, MD 20852 USA. RP Shapiro, MA (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, HFM 561,1401 Rockville Pike, Rockville, MD 20852 USA. NR 50 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD FEB PY 2000 VL 51 IS 2 BP 155 EP 163 PG 9 WC Immunology SC Immunology GA 289FC UT WOS:000085609000007 PM 10652162 ER PT J AU Goering, PL Fisher, BR Noren, BT Papaconstantinou, A Rojko, JL Marler, RJ AF Goering, PL Fisher, BR Noren, BT Papaconstantinou, A Rojko, JL Marler, RJ TI Mercury induces regional and cell-specific stress protein expression in rat kidney SO TOXICOLOGICAL SCIENCES LA English DT Article DE mercury; kidney; acute renal injury; heat-shock proteins; hsp72; glucose-regulated proteins; grp94; stress proteins; immunohistochemistry ID HEAT-SHOCK PROTEINS; DEVELOPMENT INVITRO; GENE-EXPRESSION; ISCHEMIC-INJURY; MESSENGER-RNA; INDUCTION; HSP70; NEPHROTOXICITY; EMBRYOS; HSP-70 AB Cells respond to physiologic stress by enhancing the expression of specific stress proteins. Heat-shock proteins (hsps) and glucose-regulated proteins (grps) are members of a large superfamily of proteins collectively referred to as stress proteins. This particular stress-protein response has evolved as a cellular strategy to protect, repair, and chaperone other essential cellular proteins. The objective of this study was to evaluate the differential expression of four hsps in the renal cortex and medulla during experimental nephrotoxic injury using HgCl2. Male Sprague-Dawley rats received single injections of HgCl2 (0.25, 0.5, or 1 mg Hg/kg, iv). At 4, 8, 16, or 24 h after exposure, kidneys were removed and processed for histopathologic, immunoblot, and immunohistochemical analyses. Nephrosis was characterized as minimal or mild (cytoplasmic condensation, tubular epithelial degeneration, single cell necrosis) at the lower exposures, and progressed to moderate or severe (nuclear pyknosis, necrotic foci, sloughing of the epithelial casts into tubular lumens) at the highest exposures. Western blots of renal proteins were probed with monoclonal antibodies specific for 4 hsps. In whole kidney, Hg(II) induced a time- and dose-related accumulation of hsp72 and grp94. Accumulation of hsp72 was predominantly localized in the cortex and not medulla, while grp94 accumulated primarily in the medulla but not cortex. The high, constitutive expression of hsp73 did not change as a result of Hg(II) exposure, and it was equally localized in cortex and medulla. Hsp90 was not detected in kidneys of control or Hg-treated rats. Since hsp72 has been shown involved in cellular repair and recovery, and since Hg(II) damage occurs primarily in cortex, we investigated the cell-specific expression of this hsp. Hsp72 accumulated primarily in undamaged distal convoluted tubule epithelia, with less accumulation in undamaged proximal convoluted-tubule epithelia. These results demonstrate that expression of specific stress proteins in rat kidney exhibits regional heterogeneity in response to Hg(II) exposure, and a positive correlation exists between accumulation of some stress proteins and acute renal cell injury. While the role of accumulation of hsps and other stress proteins in vivo prior to or concurrent with nephrotoxicity remains to be completely understood, these stress proteins may be part of a cellular defense response to nephrotoxicants. Conversely, renal tubular epithelial cells that do not or are unable to express stress proteins, such as hsp72, may be more susceptible to nephrotoxicity. C1 US FDA, CDRH, Off Sci & Technol, Div Life Sci,Hlth Sci Branch, Rockville, MD 20857 USA. Pathol Associates Int, Frederick, MD 21701 USA. Covance Labs, Vienna, VA 22182 USA. RP Goering, PL (reprint author), US FDA, CDRH, Off Sci & Technol, Div Life Sci,Hlth Sci Branch, HFZ-112,12709 Twinbrook Pkwy, Rockville, MD 20857 USA. NR 62 TC 52 Z9 54 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD FEB PY 2000 VL 53 IS 2 BP 447 EP 457 DI 10.1093/toxsci/53.2.447 PG 11 WC Toxicology SC Toxicology GA 283ZP UT WOS:000085306200031 PM 10696793 ER PT J AU Schenck, FJ Lehotay, SJ AF Schenck, FJ Lehotay, SJ TI Does further clean-up reduce the matrix enhancement effect in gas chromatographic analysis of pesticide residues in food? SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE food analysis; matrix enhancement effect; clean-up methods; solid-phase extraction; pesticides ID MASS-SELECTIVE DETECTION; ORGANOPHOSPHORUS PESTICIDES; LIQUID-CHROMATOGRAPHY; RESPONSE ENHANCEMENT; EXTRACTION; VEGETABLES; FRUITS; SPLITLESS; INJECTION AB Sample extracts of apples, peas, green beans, oranges, raspberries, clementines, carrots, and wheat obtained using the Food and Drug Administration (acetone extraction) and Canadian Pest Management Regulatory Agency (acetonitrile extraction) multiresidue methods for pesticides were subjected to clean-up using different solid-phase extraction (SPE) cartridges in an attempt to reduce or eliminate the matrix enhancement effect. The matrix enhancement effect is related to the blocking of active sites on the injector liner by matrix components, thereby increasing signal in the presence of matrix versus standards in solvent in which the pesticides themselves interact with the active sites. Graphitized carbon black (GCB) was often used in combination with various anion-exchange SPE cartridges. The extracts were then spiked with organophosphorus insecticides. These process standards were then compared to standards in acetone of the same concentration using gas chromatography with flame photometric detection or ion trap mass spectrometric detection. Sample matrix enhancement varied from little to no effect for some pesticides (e.g. chlorpyrifos, malathion) to >200% in the case of certain susceptible pesticides. The GCB removed color components but showed little effect in reducing matrix enhancement by itself. The anion-exchange cartridges in combination with GCB or not, substantially reduced the matrix enhancement effect but did not eliminate it. Published by Elsevier Science B.V. C1 US FDA, Baltimore Dist Lab, Baltimore, MD 21201 USA. USDA ARS, Beltsville Agr Res Ctr, Beltsville, MD 20705 USA. RP Lehotay, SJ (reprint author), USDA ARS, ERRC, 600 E Mermaid Lane, Wyndmoor, PA 19038 USA. NR 21 TC 161 Z9 186 U1 2 U2 29 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JAN 28 PY 2000 VL 868 IS 1 BP 51 EP 61 DI 10.1016/S0021-9673(99)01137-1 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 277YJ UT WOS:000084960900005 PM 10677079 ER PT J AU Meng, QX Singh, N Heflich, RH Bauer, MJ Walker, VE AF Meng, QX Singh, N Heflich, RH Bauer, MJ Walker, VE TI Comparison of the mutations at Hprt exon 3 of T-lymphocytes from B6C3F1 mice and F344 rats exposed by inhalation to 1,3-butadiene or the racemic mixture of 1,2 : 3,4-diepoxybutane SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE butadiene; diepoxybutane; Hprt; lymphocytes; mutational spectra; mouse; rat ID LACI TRANSGENIC MICE; ETHYL-N-NITROSOUREA; BUTADIENE EPOXIDES; BONE-MARROW; MUTAGENICITY; LOCUS; CELLS; CARCINOGENICITY; FREQUENCY; SPECTRUM AB Experiments were conducted to define the spectra of mutations occurring in Hprt exon 3 of T-cells isolated from spleens of female B6C3F1 mice and F344 rats exposed by inhalation to 1,3-butadiene (BD) or its reactive metabolite, (+/-)-diepoxybutane (DEB). Hprt mutant frequencies (Mfs) in BD-exposed (1250 ppm for 2 weeks or 625 ppm for 4 weeks; 6 h/day, 5 days/week) and DEB-exposed (2 or 4 ppm for 4 weeks or 5 ppm for 6 weeks; 6 h/day, 5 days/week) mice and rats were significantly increased over concurrent control values. Mutant T-cell colonies from control and treated animals were screened for mutations in Hprt exon 3 using PCR amplification of genomic DNA and denaturing gradient gel electrophoresis, followed by sequence analysis. Exon 3 mutations were found at the following frequencies: 20/394 (5%) in control mice, 56/712 (8%) in BD-exposed mice, 59/1178 (5%) in BD-exposed rats, 66/642 (10%) in DEB-exposed mice, and 51/732 (7%) in DEB-exposed rats. Mutations in exposed animals included base substitutions, small deletions (1 to 74 bp), and small insertions (1 to 8 bp), with base substitutions predominating. Among the types of base substitutions observed in mice, the proportions of G . C --> A . T transitions (p = 0.035, Fisher's Exact Test) and G . C --> C . G transversions (p = 0.05) were significantly different in control vs. BD-exposed animals. Given the small number of exon 3 mutants analyzed, there was a high degree of overlap in the mutational spectra between BD-exposed mice and rats, between BD- and DEB-exposed mice, and between BD- and DEB-exposed rats in terms of the sites with base substitutions, the mutations found at those mutated sites, the relative occurrence of the most frequently observed base substitutions, and the occurrence of a consistent strand bias for the most frequently observed base substitutions. The spectra data suggest that adduction of both G . C and A . T bps is important in the induction of in vivo mutations by BD metabolites in exposed mice and rats. (C) 2000 Elsevier Science B.V. All rights reserved. C1 New York State Dept Hlth, Wadsworth Ctr Labs & Res, Albany, NY 12201 USA. SUNY Albany, Sch Publ Hlth, Albany, NY 12203 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Walker, VE (reprint author), New York State Dept Hlth, Wadsworth Ctr Labs & Res, POB 509, Albany, NY 12201 USA. NR 35 TC 26 Z9 27 U1 0 U2 2 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 24 PY 2000 VL 464 IS 2 BP 169 EP 184 DI 10.1016/S1383-5718(99)00157-6 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 278XP UT WOS:000085014500002 PM 10648904 ER PT J AU Epstein, JS AF Epstein, JS TI The US blood supply SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material C1 US FDA, Off Blood Res & Review, Rockville, MD 20857 USA. RP Epstein, JS (reprint author), US FDA, Off Blood Res & Review, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD JAN 15 PY 2000 VL 61 IS 2 BP 549 EP 550 PG 2 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 278KV UT WOS:000084989700018 PM 10670510 ER PT J AU Rieves, D Wright, G Gupta, G Shacter, E AF Rieves, D Wright, G Gupta, G Shacter, E TI Clinical trial (GUSTO-1 and INJECT) evidence of earlier death for men than women after acute myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY HEART-DISEASE; SEX-DIFFERENCES; CARDIAC-ARREST; CASE-FATALITY; MORTALITY; REPERFUSION; PREDICTORS; SURVIVORS; GENDER; TRENDS AB Epidemiologic studies of acute myocardial infarction (AMI) have described gender differences in the time of death after infarction, with greater numbers of men dying before hospitalization than women. However, in controlled, hospital-based clinical trials, women die at higher rates than men. We hypothesized that evidence of a gender difference in the time of death following AMI may be found in controlled studies of hospitalized AMI patients. We performed a retrospective analysis of the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) and International Joint Efficacy Comparison of Thrombolytics (INJECT) trial databases using logistic regression modeling and time-to-death analyses. The age-adjusted female-to-male odds ratio for mortality was 1.4 (95% confidence interval 1.3 to 1.5) in GUSTO-I and 1.5 (95% confidence interval 1.3 to 1.3) in INJECT. GUSTO-1 showed that among patients dying during the first 24 hours after symptom onset, men died an average of 1.7 hours earlier than women (p < 0.001). This difference was due to earlier deaths among men less than or equal to 65 years of age. Furthermore, in GUSTO-I, the analysis of time to death in hour increments demonstrated that greeter proportions of men died at earlier time points than women and a disproportionate number of early deaths occurred among younger men than among women of any age or older men. In INJECT, where time to death could only be analyzed in I-day increments, no gender differences were evident. These results raise the possibility that the pattern of earlier death for men in thrombolytic clinical trials represents the continuation of a gender-specific mortality pattern that began before hospitalization. The death of a disproportionate number of men before hospitalization may represent an inherent gender bias for clinical studies enrolling only hospitalized patients. More high-risk men would be excluded from these studies than women because of death before hospitalization, Hence, gender comparisons of in-hospital mortality rates may artificially inflate values for women. (C) 2000 by Excerpta Medica, Inc. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Shacter, E (reprint author), FBA, CBER, HFM-535,Bldg 29A,Room 2A-11,29 Lincoln Dr, Bethesda, MD 20892 USA. RI bashzar, salman/R-5748-2016 NR 28 TC 9 Z9 9 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 2000 VL 85 IS 2 BP 147 EP 153 DI 10.1016/S0002-9149(99)00652-9 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 275CG UT WOS:000084801400003 PM 10955368 ER PT J AU Khan, AA Nawaz, MS Khan, SA Cerniglia, CE AF Khan, AA Nawaz, MS Khan, SA Cerniglia, CE TI Detection of multidrug-resistant Salmonella typhimurium DT104 by multiplex polymerase chain reaction SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE multiplex PCR; Salmonella typhimurium DT104; multi-drug resistant; detection; ACSSuT-R type ID GENES; INTEGRONS; CHLORAMPHENICOL; IDENTIFICATION; PRODUCTS; EPIDEMIC; DT-104 AB Salmonella typhimurium definitive type 104 (DT104) is a virulent pathogen for humans and animals with many strains having multiple drug resistance characteristics. The organism typically carries resistance to ampicillin, chloramphenicol, florfenicol, streptomycin, sulfonamides, and tetracycline (ACSSuT-resistant). A multiplex PCR method was developed to simultaneously amplify four genes, florfenicol (flo(st)); virulence (spvC), invasion (invA), and integron (int) from S. typhimurium DT104 (ACSSuT-type). Twenty-two ACSSuT-resistant DT104 isolates in our collection gave 100% positive reactions to this PCR assay by amplifying 584-, 392-, 321- and 265-bp PCR products, using primers specific to the respective target genes. One Salmonella strain DT23, ACSSuT-resistant, phage type 711 failed to amplify the 584-bp fragment, indicating that this method is specific for DT104-type ACSSuT-resistant S. typhimurium strains. One clinical and one bovine ASSuT-resistant strains that were sensitive to chloramphenicol and florfenicol did not yield a 584-bp fragment, indicating the absence of the flo(st) gene. This method will be useful for rapid identification of ACSSuT-type DT104 strains from clinical, food and environmental samples. (C) 2000 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Khan, AA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 23 TC 72 Z9 76 U1 0 U2 2 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 JAN 15 PY 2000 VL 182 IS 2 BP 355 EP 360 DI 10.1111/j.1574-6968.2000.tb08921.x PG 6 WC Microbiology SC Microbiology GA 274LB UT WOS:000084766400027 PM 10620692 ER PT J AU Murphy, FJ Hayes, MP Burd, PR AF Murphy, FJ Hayes, MP Burd, PR TI Disparate intracellular processing of human IL-12 preprotein subunits: Atypical processing of the P35 signal peptide SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL STIMULATORY FACTOR; INTERFERON-GAMMA; HUMAN MONOCYTES; EXPRESSION; GENES; INTERLEUKIN-6; CLEAVAGE; RECEPTOR; DISTINCT; CYTOKINE AB IL-12 is a heterodimeric cytokine produced by APC that critically regulates cell-mediated immunity. Because of its crucial function during immune responses, IL-12 production is stringently regulated, in part through transcriptional control of its p35 subunit, which requires the differentiative effects of IFN-gamma for expression, To determine whether post-transcriptional aspects of IL-12 production might be regulated, we examined intracellular protein processing of each subunit, We report here that p40 and p35 subunits are processed by disparate pathways. Whereas processing of p40 conforms to the cotranslational model of signal peptide removal concomitant with translocation into the endoplasmic reticulum (ER), processing of p35 does not. Translocation of the p35 preprotein into the ER was not accompanied by cleavage of the signal peptide; rather, removal of the p35 signal peptide occurred via two sequential cleavages. The first cleavage took place within the ER, and the cleavage site localized to the middle of the hydrophobic region of the signal peptide, Although the preprotein was glycosylated upon entry into the ER, its glycosylation status did not affect primary cleavage. Subsequently, the remaining portion of the p35 signal peptide was removed by a second cleavage, possibly involving a metalloprotease, concomitant with additional glycosylation and secretion. Secretion could be inhibited by mutation of the second cleavage site or by inhibition of glycosylation,vith tunicamycin, In contrast, p40 secretion was not affected by inhibition of glycosylation. Our findings demonstrate that IL-12 subunits are processed by disparate pathways and suggest new modalities for regulation of IL-12 production. C1 US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Rockville, MD 20852 USA. RP Burd, PR (reprint author), Maxygen Inc, 515 Galveston Dr, Redwood City, CA 94063 USA. NR 30 TC 43 Z9 43 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2000 VL 164 IS 2 BP 839 EP 847 PG 9 WC Immunology SC Immunology GA 273LF UT WOS:000084708600039 PM 10623830 ER PT J AU Wu, KM DeGeorge, JG Atrakchi, A Barry, E Bigger, A Chen, C Du, T Freed, L Geyer, H Goheer, A Jacobs, A Jean, D Rhee, H Osterberg, R Schmidt, W Farrelly, JG AF Wu, KM DeGeorge, JG Atrakchi, A Barry, E Bigger, A Chen, C Du, T Freed, L Geyer, H Goheer, A Jacobs, A Jean, D Rhee, H Osterberg, R Schmidt, W Farrelly, JG TI Regulatory science: a special update from the United States Food and Drug Administration - Preclinical issues and status of investigation of botanical drug products in the United States SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT NIH Symposium on Complementary and Alternative Medicine in Chronic Liver Disease CY 1999 CL BETHESDA, MARYLAND SP NIH DE botanical products; dietary supplements; health care systems AB A recent survey was conducted across the therapeutic divisions within the CDER, U.S. FDA regarding the number of submissions related to botanical drug products over the past ten years. The overall number of botanical submissions as expressed in the parenthesis are as follows: 1990 (1), 1991 (4), 1992 (4), 1993 (5), 1994 (6), 1995 (5), 1996 (13), 1997 (16), 1998 (10). In the total of 64 counted, 50 of them are submitted in original IND and the rest (14) in pre-IND format. The therapeutic categories are focused on dermatological and topical (19), anti AIDS/antiviral (12), oncologic (13), neuropharmacologic (8), endocrine and metabolic (3), urologic (2), tobacco (2), and cardio-renal products (1). The regulatory actions taken on these submissions showed that 68% of them are evaluated as safe to proceed for the human trials, while the rest (32%) of submissions required agency's regulatory guidance. Among the submissions that required further guidance, 81% were deficient in preclinical pharmacology/toxicology information and the rest (19%) lacks information in other areas (chemistry, clinical protocols). Following agency's guidance, 93% of the submissions that were put on hold were allowed to proceed. In summary, a total of 94% of all the botanical INDs submitted to the agency were allowed to proceed without additional animal toxicity studies conducted. In conclusion, this survey indicates that the growing public interest in botanical supplements has prompted more formal evaluation of the efficacy/safety claims of these products. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Food & Drug Admin, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. RP Wu, KM (reprint author), Food & Drug Admin, Ctr Drug Evaluat & Res, 5600 Fishers Lane, Rockville, MD 20852 USA. NR 0 TC 11 Z9 11 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD JAN 5 PY 2000 VL 111 IS 3 BP 199 EP 202 DI 10.1016/S0378-4274(99)00152-6 PG 4 WC Toxicology SC Toxicology GA 274ZF UT WOS:000084794400002 PM 10643863 ER PT J AU Arichi, T Saito, T Major, ME Belyakov, IM Shirai, M Engelhard, VH Feinstone, SM Berzofsky, JA AF Arichi, T Saito, T Major, ME Belyakov, IM Shirai, M Engelhard, VH Feinstone, SM Berzofsky, JA TI Prophylactic DNA vaccine for hepatitis C virus (HCV) infection: HCV-specific cytotoxic T lymphocyte induction and protection from HCV-recombinant vaccinia infection in an HLA-A2.1 transgenic mouse model (Retracted Article. See vol 98, pg 5943, 2001) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Retracted Publication ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-RESPONSES; PLASMID DNA; CELL MEMORY; B-VIRUS; STRUCTURAL PROTEINS; CTL RESPONSES; CORE PROTEIN; IN-VIVO; MICE AB DNA vaccines express antigens intracellularly and effectively induce cellular immune responses. Because only chimpanzees can be used to model human hepatitis C virus (HCV) infections, we developed a small-animal model using HLA-A2.1-transgenic mice to test induction of HLA-A2.1-restricted cytotoxic T lymphocytes (CTLs) and protection against recombinant vaccinia expressing HCV-core, A plasmid encoding the HCV-core antigen induced CD8(+) CTLs specific for three conserved endogenously expressed core peptides presented by human HLA-A2.1, When challenged, DNA-immunized mice showed a substantial (5-12 log(10)) reduction in vaccinia virus titer compared with mock-immunized controls. This protection, lasting at least 14 mo, was shown to be mediated by CD8+ cells. Thus, a DNA vaccine expressing HCV-core is a potential candidate for a prophylactic vaccine for HLA-A2.1(+) humans. C1 NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis Viruses, Div Viral Prod, Bethesda, MD 20892 USA. Yamaguchi Univ, Sch Med, Dept Microbiol, Ube, Yamaguchi 755, Japan. Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA. RP Berzofsky, JA (reprint author), NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bldg 10,Room 6B-12,MSC 1578, Bethesda, MD 20892 USA. EM berzofsk@helix.nih.gov NR 58 TC 25 Z9 26 U1 3 U2 7 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 JAN 4 PY 2000 VL 97 IS 1 BP 297 EP 302 DI 10.1073/pnas.97.1.297 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 271ZA UT WOS:000084624500055 PM 10618412 ER PT B AU McDermott, PF AF McDermott, PF GP CORNELL UNIVERSITY CORNELL UNIVERSITY TI Microbial resistance and antibiotics SO 2000 CORNELL NUTRITION CONFERENCE FOR FEED MANUFACTURERS, PROCEEDINGS LA English DT Proceedings Paper CT 62nd Cornell Nutrition Conference for Feed Manufacturers CY OCT 24-26, 2000 CL Rochester, NY SP New York State Coll Agr & Life Sci, Dept Anim Sci, New York State Coll Agr & Life Sci, Div Nutr Sci ID ESCHERICHIA-COLI; ANTIMICROBIAL RESISTANCE; SALMONELLA-TYPHIMURIUM; ENTEROCOCCUS-FAECIUM; VETERINARY-MEDICINE; CAMPYLOBACTER; DETERMINANTS; AVOPARCIN; BACTERIA; ANIMALS C1 US FDA, Ctr Vet Med, Rockville, MD 20857 USA. RP McDermott, PF (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20857 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU CORNELL UNIV DEPT ANIMAL SCIENCE PI ITHACA PA 272 MORRISON HALL, ITHACA, NY 14853-4801 USA PY 2000 BP 81 EP 88 PG 8 WC Agriculture, Dairy & Animal Science SC Agriculture GA BR22U UT WOS:000165905200010 ER PT S AU Wear, KA AF Wear, KA BE Schneider, SC Levy, M McAvoy, BR TI Anisotropy of attenuation and backscatter in cancellous bone SO 2000 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2 SE ULTRASONICS SYMPOSIUM LA English DT Proceedings Paper CT IEEE Ultrasonics Symposium CY OCT 22-25, 2000 CL SAN JUAN, PR SP IEEE Ultrason, Ferroelect, & Frequency Control Soc ID ULTRASOUND; INVITRO AB Although bone sonometry is useful in the diagnosis of osteoporosis, the interactions between ultrasound and bone are not well understood yet. In order to investigate these processes, ultrasonic attenuation and backscatter in two orientations were measured in 43 human calcaneal specimens in vitro. In the mediolateral (ML) orientation, the ultrasound propagation direction is approximately perpendicular to the trabecular axes. In the anteroposterior (AP) orientation, a wide range of angles between the ultrasound propagation direction and trabecular axes is encountered. Average attenuation slope was 18% greater while average backscatter coefficient was 50% lower in the AP orientation compared with the ML orientation. These results support the idea that absorption is a greater component of attenuation than scattering in human calcaneal trabecular bone. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-142, Rockville, MD 20852 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-0117 BN 0-7803-6365-5 J9 ULTRASON PY 2000 BP 1325 EP 1328 PG 4 WC Acoustics; Engineering, Industrial; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BT07X UT WOS:000171881300289 ER PT J AU Murray, JS AF Murray, JS TI Regulatory issues in the era of highly active antiretroviral therapy SO AIDS LA English DT Article DE quadruple regimens; equivalence; superiority; margin of inferiority ID IMMUNODEFICIENCY-VIRUS-INFECTION; PLACEBO-CONTROLLED TRIAL; ZIDOVUDINE COMBINATION THERAPY; SAQUINAVIR-CONTAINING REGIMEN; RITONAVIR PLUS SAQUINAVIR; CD4 CELL COUNTS; CUBIC MILLIMETER; DOUBLE-BLIND; HIV-INFECTION; EFFICACY C1 US FDA, Ctr Drug Evaluat & Res, Div Antivrial Drug Prod, Rockville, MD 20857 USA. RP Murray, JS (reprint author), 1429 Swann St NW, Washington, DC 20009 USA. NR 48 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PY 2000 VL 14 SU 3 BP S219 EP S225 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 371RN UT WOS:000165192100023 PM 11086865 ER PT S AU McNeal, TP Biles, JE Begley, TH Craun, JC Hopper, ML Sack, CA AF McNeal, TP Biles, JE Begley, TH Craun, JC Hopper, ML Sack, CA BE Keith, LH JonesLepp, TL Needham, LL TI Determination of suspected endocrine disruptors in foods and food packaging SO ANALYSIS OF ENVIRONMENTAL ENDOCRINE DISRUPTORS SE ACS SYMPOSIUM SERIES LA English DT Article; Proceedings Paper CT 216th National Meeting of the American-Chemical-Society CY AUG 21-27, 1998 CL BOSTON, MASSACHUSETTS SP Amer Chem Soc, Div Polymer Mat, Sci & Engn Inc, Div Polymer Mat, Exxon Res & Engn Co, Amer Chem Soc, Petr Res Fund, Amer Chem Soc, Div Fluorine Chem, Amer Chem Soc, Div Organ Chem, Amer Chem Soc, Corp Associates, Dow Agrosci, Monsanto Co, Eastman Kodak Co, Schering Plough, Merck Res Labs, Cent Glass Int Inc, Daikin Ind, Kanto Denka Kogyo Co, Asahi Glass Co, Div Agr & Food Chem ID BISPHENOL-A; CHEMICALS; COATINGS AB Bisphenol-A (BPA), nonyl phenol (NP), and certain phthalate esters are common industrial chemicals employed in a variety of ways to manufacture, stabilize or modify the characteristics and performance of polymers, including those that are approved for use in food packaging. BPA is used as the starting material for the synthesis of polycarbonate (PC) plastics used to make baby bottles and reusable water carboys. BPA is also used to make epoxy adhesives and can coatings. The major source of NP residues in food packaging is the oxidation of tris-nonylphenyl phosphite (TNPP), an antioxidant/antiozonant, added to polymeric materials such as polyvinylchloride (PVC), polyolefins and acrylics. Ortho- phthalate esters such as dibutyl, butylbenzyl, and di-2-ethylhexyl phthalate have been widely used as plasticizers in PVC and are also used in adhesives and printing inks. Phthalate esters are commonly found in the environment and are generally considered ubiquitous. Recently, preliminary data reported in the literature, primarily from in vitro studies, suggest that some of these chemicals may have weak estrogenic activity, although their effects in animals and humans are far from clear. We will refer to BPA, NP and phthalates as suspected endocrine disruptors (EDs). Because these suspected ED's are present as additives or residues in food-contact materials, they can be expected to migrate to some foods in very low amounts. Larger amounts of migration can be expected from polymers exposed to food at elevated temperatures, i.e., heat-processed foods. The levels of these chemicals that migrate into foods are of interest to the Food and Drug Administration (FDA) because estimates of dietary exposure are FDA's indirect additives laboratory conducted a limited survey of food packaging for suspected EDs. A portion of each package was extracted with hexane or methanol, and suspected EDs determined by HPLC with fluorescence detection or gas chromatography with mass selective detection. The methodology was straightforward and yielded many sources of suspected EDs. BPA residues were detected in all PC items tested, and trace amounts in many epoxy-based enamels, including infant formula cans. NP residues were found in many food contact plastics from rigid polystyrene cold drink cups to laminated films. Traces of the phthalate esters were predominantly found in colored laminated films and are thought to be associated with color or ink formulations. Analytical techniques for the determination of suspected ED residues in foods are matrix- and analyte- dependant. BPA residues migrating from PC food contact plastics to food simulating solvents and infant formulas were determined after dilution with mobile phase and HPLC analysis with fluorescence detection. NP and BPA residues from can enamels and jar lid gaskets were determined in many aqueous foods by using solid phase extraction with a porous polymer and then analysis with either capillary GC with mass selective detection, or HPLC with fluorescence detection. Another study, an FDA field assignment on phthalates in infant formulas, was conducted by FDA's Total Diet Laboratory in Lenexa, KS. Composites representing 81 different powdered and liquid infant formula samples were analyzed for dibutyl, butylbenzyl, and di-2-ethylhexyl phthalates. The samples were subjected to multi-residue FDA Pesticide Analytical Manual extraction protocols and the phthalates determined by capillary GC-MS. In general, either non-detectable or low mug/kg amounts of the suspected EDs were found in the foods analyzed. C1 US FDA, Washington, DC 20204 USA. US FDA, Lenexa, KS 66214 USA. RP McNeal, TP (reprint author), US FDA, 200 C St SW, Washington, DC 20204 USA. NR 17 TC 21 Z9 23 U1 8 U2 31 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 0-8412-3650-X J9 ACS SYM SER PY 2000 VL 747 BP 33 EP 52 PG 20 WC Chemistry, Multidisciplinary SC Chemistry GA BT14D UT WOS:000172068100004 ER PT J AU Best, CJM Gillespie, JW Englert, CR Swalwell, JI Pfeifer, J Krizman, DB Petricoin, EF Liotta, LA Emmert-Buck, MR AF Best, CJM Gillespie, JW Englert, CR Swalwell, JI Pfeifer, J Krizman, DB Petricoin, EF Liotta, LA Emmert-Buck, MR TI New approaches to molecular profiling of tissue samples SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Review ID LASER CAPTURE MICRODISSECTION; PROSTATIC INTRAEPITHELIAL NEOPLASIA; POLYMERASE CHAIN-REACTION; GENE-EXPRESSION; DNA CHIPS; CANCER; CELLS; POPULATIONS; PROTEOMICS; GENOMICS C1 NCI, NIH, Pathol Lab, Pathogenet Unit, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD USA. NCI, Ctr Adv Technol, Canc Genome Anat Project, Gaithersburg, MD USA. US FDA, Ctr Biol & Res, Div Cytokine Biol, Bethesda, MD USA. RP Emmert-Buck, MR (reprint author), NCI, NIH, Pathol Lab, Pathogenet Unit, Bldg 10,Room 2A33,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 38 TC 13 Z9 13 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0921-8912 J9 ANAL CELL PATHOL JI Anal. Cell. Pathol. PY 2000 VL 20 IS 1 BP 1 EP 6 PG 6 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 338GB UT WOS:000088409200001 PM 11007432 ER PT J AU Gurunathan, S Klinman, DM Seder, RA AF Gurunathan, S Klinman, DM Seder, RA TI DNA vaccines: Immunology, application, and optimization SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE CpG sequences; plasmid DNA ID CYTOTOXIC T-LYMPHOCYTES; IMMUNODEFICIENCY-VIRUS TYPE-1; HEPATITIS-B VIRUS; HUMORAL IMMUNE-RESPONSES; ANTIGEN-PRESENTING CELLS; DIRECT GENE-TRANSFER; CPG-CONTAINING OLIGODEOXYNUCLEOTIDES; DEOXYRIBONUCLEIC-ACID VACCINES; SYSTEMIC LUPUS-ERYTHEMATOSUS; INDUCE AUTOIMMUNE-DISEASE AB The development and widespread use of vaccines against infectious agents have been a great triumph of medical science. One reason for the success of currently available vaccines is that they are capable of inducing long-lived antibody responses, which are the principal agents of immune protection against most viruses and bacteria. Despite these successes, vaccination against intracellular organisms that require cell-mediated immunity, such as the agents of tuberculosis, malaria, leishmaniasis, and human immunodeficiency virus infection, are either not available or not uniformly effective. Owing to the substantial morbidity and mortality associated with these diseases worldwide, an understanding of the mechanisms involved in generating long-lived cellular immune responses has tremendous practical importance. For these reasons, a new form of vaccination, using DNA that contains the gene for the antigen of interest, is under intensive investigation, because it can engender both humoral and cellular immune responses. This review focuses on the mechanisms by which DNA vaccines elicit immune responses. In addition, a list of potential applications in a variety of preclinical models is provided. C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. RP Gurunathan, S (reprint author), NIAID, Clin Invest Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Liu, Xia/L-9425-2013 NR 245 TC 871 Z9 954 U1 9 U2 153 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2000 VL 18 BP 927 EP 974 DI 10.1146/annurev.immunol.18.1.927 PG 48 WC Immunology SC Immunology GA 317PX UT WOS:000087236500030 PM 10837079 ER PT J AU Mohan, KVK Atreya, CD AF Mohan, KVK Atreya, CD TI Comparative sequence analysis identified mutations outside the NSP4 cytotoxic domain of tissue culture-adapted ATCC-Wa strain of human rotavirus and a novel inter-species variable domain in its C-terminus SO ARCHIVES OF VIROLOGY LA English DT Article ID NONSTRUCTURAL GLYCOPROTEIN NSP4; GROUP-A; INFECTION; DIARRHEA; CELLS; CA2+; AGE AB Complete nucleotide sequence of the tissue culture-adapted ATCC*-Wa strain of human rotavirus NSP4 was determined. Sequence analysis detected two alternate forms of the gene with a nucleotide difference at position 331 (A or G) in the coding sequence (NSP4-A or NSP4-G) leading to a change from neutral glutamine(97) in NSP4-A to a positively charged arginine(97) in NSP4-G originating from the same ATCC-Wa preparation. In addition to this, both forms of ATCC-Wa NSP4 revealed three mutations at nucleotide positions 88 (T to C), 142 (C to T) and 572 (G to A), when compared to the previously reported NSP4 sequence from virulent Wa strain. The former two mutations were in the coding sequence and resulted in a leucine(16) to serine(16) and a proline(34) to leucine(34) change, while the third mutation was in the 3' non-coding region of the gene. The two amino acid changes may contribute to the 'tissue culture-adaptation' of ATCC-Wa strain. The ATCC-Wa NSP4 sequence was found to differ from the previously reported NSP4 sequence of attenuated Wa strain by lacking a mutation at 133 (T to C), though the mutations at 88 and 142 were present in both strains. Furthermore, comparison of deduced amino acid sequence of NSP4 from human, bovine, porcine and simian rotavirus strains identified a seven-residue (positions 135-141) inter-species variable domain in its C-terminal region. C1 US FDA, Ctr Biol Evaluat & Res, Sect Viral Pathogenesis & Adverse React, Lab Pediat & Resp Viral Dis,Div Viral Prod, 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,Div Viral Prod, Bldg 29A,Room 2C-11,HFM-460,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 17 TC 22 Z9 24 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. PY 2000 VL 145 IS 9 BP 1789 EP 1799 PG 11 WC Virology SC Virology GA 358XL UT WOS:000089582400003 PM 11043941 ER PT J AU Sapirstein, W AF Sapirstein, W TI The conduct of clinical trials: A food and drug agency perspective SO ASAIO JOURNAL LA English DT Editorial Material C1 US FDA, Ctr Devices & Radiol Hlth, Div Cardiovasc & Resp Devices, Rockville, MD USA. RP Sapirstein, W (reprint author), US FDA, Off Divice Evaluat, Div Cardiovasc Resp & Neurol Devices, 9200 Corp Blvd, Rockville, MD 20878 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD JAN-FEB PY 2000 VL 46 IS 1 BP 29 EP 30 DI 10.1097/00002480-200001000-00009 PG 2 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 392UK UT WOS:000166430800009 PM 10667711 ER PT B AU Layloff, GA AF Layloff, GA GP ASQ ASQ TI The quality system inspection technique (QSIT) SO ASQ'S 54TH ANNUAL QUALITY CONGRESS PROCEEDINGS LA English DT Proceedings Paper CT 54th Annual Quality Congress CY MAY 08-10, 2000 CL INDIANAPOLIS, IN SP Amer Soc Qual DE compliance; investigator; regulation AB This presentation will provide an overview of the new inspection technique currently being utilized by the U.S. Food and Drug Administration (FDA) investigators to assess compliance of medical device manufacturers with the quality system regulation. The development and implementation of the quality system inspection technique (QSIT) as well as the regulatory impact of inspectional findings will be addressed. C1 US FDA, St Louis, MO 63143 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC QUALITY CONTROL PI MILWAUKEE PA 611 E WISCONSIN AVENUE, MILWAUKEE, WI 53202 USA PY 2000 BP 266 EP 267 PG 2 WC Engineering, Manufacturing; Management SC Engineering; Business & Economics GA BX89F UT WOS:000186757800052 ER PT J AU Dykewicz, CA Jaffe, HW Kaplan, JE AF Dykewicz, CA Jaffe, HW Kaplan, JE CA CDC Infect Dis Soc Amer Amer Soc Blood Marrow Transplation TI Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients - Recommendations of CDC, the Infectious Diseases Society of America, and the American Society of Blood and Marrow Transplation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review ID VERSUS-HOST DISEASE; PNEUMOCYSTIS-CARINII PNEUMONIA; RESPIRATORY SYNCYTIAL VIRUS; HERPES-SIMPLEX-VIRUS; CYTOMEGALOVIRUS PP65 ANTIGENEMIA; HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; LIPOSOMAL AMPHOTERICIN-B; HLA-IDENTICAL SIBLINGS; VARICELLA-ZOSTER VIRUS AB CDC, the Infectious Diseases Society of America, and the American Society of Blood and Marrow Transplantation have cosponsored these guidelines for preventing opportunistic infections (OIs) among hematopoietic stem cell transplant (HSCT) recipients. The guidelines were drafted with the assistance of a working group of experts in infectious diseases, transplantation, and public health. For the purposes of this report, HSCT is defined as any transplantation of blood- or marrow-derived hematopoietic stem cells, regardless of transplant type (i.e., allogeneic or autologous) or cell source (i.e., bone marrow, peripheral blood, or placental or umbilical cord blood). Such OIs as bacterial, viral, fungal, protozoal, and helminth infections occur with increased frequency or severity among HSCT recipients. These evidence-based guidelines contain information regarding preventing OIs, hospital infection control, strategies for safe living after transplantation, vaccinations, and hematopoietic stem cell safety. The disease-specific sections address preventing exposure and disease for pediatric and adult and autologous and allogeneic HSCT recipients. The goal of these guidelines is twofold: to summarize current data and provide evidence-based recommendations regarding preventing OIs among HSCT patients. The guidelines were developed for use by HSCT recipients, their household and close contacts, transplant and infectious diseases physicians, HSCT center personnel, and public health professionals. For all recommendations, prevention strategies are rated by the strength of the recommendation and the quality of the evidence supporting the recommendation. Adhering to these guidelines should reduce the number and severity of OIs among HSCT recipients. C1 CDC, Div AIDS STD & TB Lab Res, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. CDC, Div HIV AIDS Prevent Surveillance & Epidemiol, Natl Ctr HIV STD & TB Prevent, Atlanta, GA 30333 USA. CDC, Hosp Infect Program, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. CDC, Epidemiol & Surveillance Div, Natl Immunizat Program, Atlanta, GA 30333 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Duke Univ, Durham, NC USA. Indiana Univ, Indianapolis, IN 46204 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Med Coll Wisconsin, Int Bone Marrow Transplant Registry, Autologous Blood & Marrow Transplant Registry, Milwaukee, WI 53226 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Florida, Gainesville, FL USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. US FDA, Rockville, MD 20857 USA. Univ Pittsburgh, Pittsburgh, PA USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Univ Colorado, Denver, CO 80202 USA. Johns Hopkins Univ, Baltimore, MD USA. Kaiser Permanente Med Ctr, Santa Rosa, CA USA. RP Dykewicz, CA (reprint author), CDC, Div AIDS STD & TB Lab Res, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. NR 401 TC 86 Z9 86 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PY 2000 VL 6 IS 6A BP 659 EP + PG 67 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 378DR UT WOS:000165570200001 ER PT S AU Henney, J AF Henney, J BE Downing, GJ TI A regulatory agency's perspective on the application of biomarkers and surrogate end points in clinical trials SO BIOMARKERS AND SURROGATE ENDPOINTS: CLINICAL RESEARCH AND APPLICATIONS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT Conference on Biomarkers and Surrogate Endpoints: Clinical Research and Applications CY APR 15-16, 1999 CL BETHESDA, MD SP NIH, US FDA C1 US FDA, Rockville, MD 20852 USA. RP Henney, J (reprint author), US FDA, 5600 Fishers Lane,Room 1471, Rockville, MD 20852 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50316-1 J9 INT CONGR SER PY 2000 VL 1205 BP XIV EP XVIII PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA BR67J UT WOS:000167122700002 ER PT S AU Sistare, FD Morrow, JD Olden, K AF Sistare, FD Morrow, JD Olden, K BE Downing, GJ TI Biomarkers of toxicity and surrogate endpoints for safety SO BIOMARKERS AND SURROGATE ENDPOINTS: CLINICAL RESEARCH AND APPLICATIONS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT Conference on Biomarkers and Surrogate Endpoints: Clinical Research and Applications CY APR 15-16, 1999 CL BETHESDA, MD SP NIH, US FDA ID CARDIAC TROPONIN-T; TANDEM MASS-SPECTROMETRY; DNA-ADDUCTS; DOXORUBICIN; MICE C1 US FDA, Rockville, MD 20857 USA. RP Sistare, FD (reprint author), US FDA, Rockville, MD 20857 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50316-1 J9 INT CONGR SER PY 2000 VL 1205 BP 165 EP 175 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA BR67J UT WOS:000167122700034 ER PT J AU Layloff, T Nasr, M Baldwin, R Caphart, M Drew, H Hanig, J Hoiberg, C Koepke, S Lunn, G MacGregor, JT Mille, Y Murphy, E Ng, L Rajagopalan, R Sheinin, E Smela, M Welschenbach, M Winkle, H Williams, R AF Layloff, T Nasr, M Baldwin, R Caphart, M Drew, H Hanig, J Hoiberg, C Koepke, S Lunn, G MacGregor, JT Mille, Y Murphy, E Ng, L Rajagopalan, R Sheinin, E Smela, M Welschenbach, M Winkle, H Williams, R TI The FDA regulatory methods validation program for new and abbreviated new drug applications SO BIOPHARM-THE APPLIED TECHNOLOGIES OF BIOPHARMACEUTICAL DEVELOPMENT LA English DT Article AB The FDA methods validation program for proposed regulatory methods submitted through the new and abbreviated new drug application processes is conducted by the Center for Drug Evaluation and Research (CDER) and the Office of Regulatory Affairs to ensure that scientifically well-founded regulatory methods are available to assess the quality of the CDER-approved products (1). The industry, FDA, and United States Pharmacopeia (2) and National Formulary have the common objective of ensuring that drugs in the U.S. marketplace have consistent standards for drug substances and drug product regardless of the synthesis and manufacturing process. This may be accomplished by ensuring that the analytical methods for new drug products are submitted for adoption ns public standards soon after approval for marketing. The public standard provides a yardstick for the named product that allows conscientious practitioners and consumers to determine if a product is as purported and thereby be able to detect spurious and substandard products in the marketplace. C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Layloff, T (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, HFD 003,5600 Fishers Lane, Rockville, MD 20857 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 1040-8304 J9 BIOPHARM-APPL T BIO JI Biopharm-Appl Technol. Biopharm. Dev. PD JAN PY 2000 VL 13 IS 1 BP 30 EP + PG 7 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 279TZ UT WOS:000085062400005 ER PT J AU Mantile, G Fuchs, C Cordella-Miele, E Peri, A Mukherjee, AB Miele, L AF Mantile, G Fuchs, C Cordella-Miele, E Peri, A Mukherjee, AB Miele, L TI Stable, long-term bacterial production of soluble, dimeric, disulfide-bonded protein pharmaceuticals without antibiotic selection SO BIOTECHNOLOGY PROGRESS LA English DT Article ID RANGE PLASMID RK2; RECOMBINANT HUMAN UTEROGLOBIN; SITE-SPECIFIC RECOMBINATION; CELL 10-KDA PROTEIN; ESCHERICHIA-COLI; PAR LOCUS; NUCLEOTIDE-SEQUENCE; PARTITION-FUNCTIONS; BACILLUS-SUBTILIS; VIRULENCE PLASMID AB Numerous biopharmaceuticals and other recombinant biotechnology products are made in prokaryotic hosts. However, bacterial production of native, biologically active eukaryotic proteins is rarely possible for disulfide-bonded and/or multisubunit proteins. We previously described the production of soluble, native disulfide-bonded dimeric proteins in the Escherichia coli cytoplasm (Miele et al., 1990; Mantile et al., 1993). Native, biologically active proteins with up to six disulfide bonds have been produced with our expression system (Garces et al., 1997). However, plasmid instability during induction limited its usefulness. We now report the stable, high-level expression of soluble, disulfide-bonded human uteroglobin without antibiotic selection. We designed a new vector containing a multifunctional stabilization region that confers complete plasmid stability and increased protein yields without copy number increases. Recombinant expression remains fully inducible after long-term continuous culture in nonselective liquid medium (at least 260 generations). This system may significantly expand the applications of bacterial expression to recombinant production of soluble, bioactive proteins for biochemical studies and biopharmaceutical/industrial purposes. As a result of the very broad activity spectrum of the stabilization region we selected, its use could be extended to bacterial hosts other than enterobacteria. C1 Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Canc Immunol Program, Maywood, IL 60153 USA. NICHD, Sect Dev Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. US FDA, Cell Biol Lab, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Miele, L (reprint author), Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Canc Immunol Program, 2160 S 1st Ave,Room 204, Maywood, IL 60153 USA. NR 54 TC 6 Z9 6 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD JAN-FEB PY 2000 VL 16 IS 1 BP 17 EP 25 DI 10.1021/bp990129g PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 282HT UT WOS:000085212900003 PM 10662484 ER PT J AU Liotta, LA Petricoin, EF AF Liotta, LA Petricoin, EF TI Beyond the genome to tissue proteomics SO BREAST CANCER RESEARCH LA English DT Review ID LASER CAPTURE MICRODISSECTION; CELLS C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Div Therapeut Prot, CBER, Food & Drug Adm,NIH, Bethesda, MD 20892 USA. RP Liotta, LA (reprint author), NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 9 Z9 11 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2000 VL 2 IS 1 BP 13 EP 14 PG 2 WC Oncology SC Oncology GA 408PQ UT WOS:000167334900004 PM 11250687 ER PT J AU Wang, SA Tokars, JI Bianchine, PJ Carson, LA Arduino, MJ Smith, AL Hansen, NC Fitzgerald, EA Epstein, JS Jarvis, WR AF Wang, SA Tokars, JI Bianchine, PJ Carson, LA Arduino, MJ Smith, AL Hansen, NC Fitzgerald, EA Epstein, JS Jarvis, WR TI Enterobacter cloacae bloodstream infections traced to contaminated human albumin SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INTENSIVE-CARE-UNIT; NATIONWIDE EPIDEMIC; OUTBREAK; PRODUCTS; FLUIDS AB In August 1996, a patient in Kansas developed an Enterobacter cloacae bloodstream infection (BSI) shortly after receiving Albuminar, a brand of human albumin. Albuminar contamination was suspected, A case-control study of patients with primary gram-negative bacterial BSIs showed that patients with E. cloacae BSIs were significantly more likely than patients with non-E, cloacae gram-negative BSIs to have received Albuminar within 3 days of developing their BSIs (3 of 5 vs. 0 of 9; OR, undefined; P = .03), The E, cloacae isolate from the Kansas patient was found by pulsed-held gel electrophoresis to be identical to the isolate from the patient's Albuminar vial, to isolates from 2 previously unopened Albuminar vials, and to an isolate from a Wisconsin patient who had received Albuminar, A worldwide recall of similar to 116,000 Albuminar vials took place. This multistate outbreak was detected because of clinical astuteness and prompt reporting. Combined epidemiological and laboratory approaches are valuable when investigating potentially contaminated blood components and plasma derivatives. C1 Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Hosp Infect Program, Atlanta, GA 30333 USA. Ctr Biol Evaluat & Res, Off Blood Res & Review, Rockville, MD USA. US FDA, Ctr Biol Evaluat & Res, Div Prod Qual Control, Rockville, MD 20857 USA. Via Christi Reg Med Ctr, Wichita, KS USA. Bellin Mem Hosp, Green Bay, WI USA. RP Tokars, JI (reprint author), Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Hosp Infect Program, Mailstop E-69,1600 Clifton Rd, Atlanta, GA 30333 USA. RI Arduino, Matthew/C-1461-2012 OI Arduino, Matthew/0000-0001-7072-538X NR 20 TC 15 Z9 17 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN PY 2000 VL 30 IS 1 BP 35 EP 40 DI 10.1086/313585 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 278TJ UT WOS:000085004800009 PM 10619730 ER PT J AU Viraraghavan, R Jantausch, B AF Viraraghavan, R Jantausch, B TI Congenital malaria: Diagnosis and therapy SO CLINICAL PEDIATRICS LA English DT Letter C1 US FDA, Div Antiinfect Drug Prod, Rockville, MD 20857 USA. George Washington Univ, Childrens Natl Med Ctr, Dept Infect Dis, Washington, DC USA. RP Viraraghavan, R (reprint author), US FDA, Div Antiinfect Drug Prod, 9201 Corp Blvd,Room S316,HFD-520, Rockville, MD 20857 USA. RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 NR 5 TC 3 Z9 5 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD JAN PY 2000 VL 39 IS 1 BP 66 EP 67 DI 10.1177/000992280003900117 PG 2 WC Pediatrics SC Pediatrics GA 274QN UT WOS:000084776700012 PM 10660824 ER PT J AU McMahon, FG Vargas, R Hochstein, HD AF McMahon, FG Vargas, R Hochstein, HD TI Antipyretic efficacy of aspirin or acetaminophen SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Letter C1 Clin Res Ctr, New Orleans, LA USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP McMahon, FG (reprint author), Clin Res Ctr, New Orleans, LA USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 2000 VL 67 IS 1 BP 70 EP 70 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 280DP UT WOS:000085087200009 PM 10668855 ER PT J AU Taylor, JM Stein, GC AF Taylor, JM Stein, GC TI Historical perspective (Reprinted from Good Laboratory Practice Regulations, vol 69, pg 1-22, 1995) SO CLINICAL RESEARCH AND REGULATORY AFFAIRS LA English DT Reprint C1 US FDA, Washington, DC 20204 USA. Weinberg Spelton & Sax Inc, Boothwyn, PA USA. RP Taylor, JM (reprint author), US FDA, Washington, DC 20204 USA. NR 20 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 1060-1333 J9 CLIN RES REGUL AFF JI Clin. Res. Regul. Affairs PY 2000 VL 17 IS 3 BP 151 EP 172 DI 10.3109/10601330009005320 PG 22 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 365UK UT WOS:000089968700001 ER PT J AU Blodgett, RJ AF Blodgett, RJ TI Finding bounds applied to serial dilution experiments SO COMMUNICATIONS IN STATISTICS-SIMULATION AND COMPUTATION LA English DT Article DE summation; iteration; maximum likelihood; microbial concentration AB A method of finding bounds for a parameter in a sum of similar functions is introduced. Such bounds can help an iteration procedure to estimate the parameter. This method applies to the equations for finding maximum likelihood estimates of concentration for a serial dilution experiment. For serial dilution experiments these bounds are calculated as an example of the method. C1 US FDA, Washington, DC 20204 USA. NR 3 TC 1 Z9 1 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0361-0918 J9 COMMUN STAT-SIMUL C JI Commun. Stat.-Simul. Comput. PY 2000 VL 29 IS 3 BP 793 EP 799 DI 10.1080/03610910008813640 PG 7 WC Statistics & Probability SC Mathematics GA 348NY UT WOS:000088992400006 ER PT J AU Chang, JY Ahn, HS AF Chang, JY Ahn, HS TI On sequential closed testing procedures for a comparison of dose groups with a control SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE dose-response; familywise error rate; Cochran-Armitage test; peto cause-of-death test; poly-3 test; trend ID CARCINOGENICITY; MORTALITY; ANIMALS AB Methods for a sequential test of a dose-response effect in pre-clinical studies are investigated. The objective of the test procedure is to compare several dose groups with a zero-dose control. The sequential testing is conducted within a closed family of one-sided tests. The procedures investigated are based on a monotonicity assumption. These closed procedures strongly control the familywise error rate while providing information about the shape of the dose-response relationship. Performances of sequential testing procedures are compared via a Monte Carlo simulation study. We illustrate the procedures by application to a real data set. C1 SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. NR 14 TC 3 Z9 3 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0361-0926 J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PY 2000 VL 29 IS 5-6 BP 941 EP 956 DI 10.1080/03610920008832525 PG 16 WC Statistics & Probability SC Mathematics GA 308RV UT WOS:000086727400004 ER PT J AU Wang, CY Chen, TT Tyan, I AF Wang, CY Chen, TT Tyan, I TI Designs for phase I cancer clinical trials with differentiation of graded toxicity SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE dose-ranging study; maximum tolerated dose; continual reassessment method AB For phase I cancer clinical trials, toxicity is a major concern. Commonly, toxicity is categorized to five levels of severity. In addition to the traditional standard dose-escalation design, the Continual Reassessment Method (CRM) provides a promising alternative to estimate the maximum tolerated dose of a drug. However, in both standard design (STD) and CRM, the severity level of toxicity on grade 3/4 of a previous patient's response would not be a differentiated factor for the next dose level assignment. In this study, we extend the procedure incorporating the idea of unequal weights on the assessments of grade 3 and grade 4 toxicity in the dose escalation. The simulation results show that the proposed extended procedures by taking the impact of grade 4 toxicity into account, both for STD and CRM, reduce the chance of recommendation to the higher dose levels. Similar trends are observed for patient allocation to the higher levels. Additionally, for CRM which performs more accurately on the estimation of maximum tolerated dose (MTD), the proposed extended CRM maintains the same characteristic. C1 US FDA, CBER, Div Biostat & Epidemiol, Rockville, MD 20852 USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Stanford Univ, Stanford, CA 94305 USA. NR 8 TC 12 Z9 12 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0361-0926 J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PY 2000 VL 29 IS 5-6 BP 975 EP 987 DI 10.1080/03610920008832527 PG 13 WC Statistics & Probability SC Mathematics GA 308RV UT WOS:000086727400006 ER PT J AU Permutt, T Berger, VW AF Permutt, T Berger, VW TI New look at rank tests in ordered 2xk contingency tables SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE van der Waerden test; maximum chi-square; operating characteristic; P-P plot; stochastic order ID CHI-SQUARE STATISTICS; SAMPLES AB We consider testing for association in contingency tables with 2 rows and k columns, where the columns represent ordered categories. If the rows are treatments and the columns are outcomes, this may be treated as a two-sample problem with all, the outcomes tied at one of only k values. Then rank tests may be applied even without knowing the values. Some special considerations apply, however, and the most usual rank tests may not be the best ones. We use a graphical technique to compare the properties of various rank tests. C1 US FDA, Rockville, MD 20857 USA. NR 15 TC 8 Z9 8 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0361-0926 J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PY 2000 VL 29 IS 5-6 BP 989 EP 1003 DI 10.1080/03610920008832528 PG 15 WC Statistics & Probability SC Mathematics GA 308RV UT WOS:000086727400007 ER PT J AU Miller, JB Suits, BH Garroway, AN Hepp, MA AF Miller, JB Suits, BH Garroway, AN Hepp, MA TI Interplay among recovery time, signal, and noise: Series- and parallel-tuned circuits are not always the same SO CONCEPTS IN MAGNETIC RESONANCE LA English DT Article DE signal; noise; recovery time; preamplifier; tuned circuit; overcoupling ID NMR PROBE; DESIGN; NQR AB The quality factor, Q, of the magnetic resonance probe and the manner in which the probe is coupled to the spectrometer play important roles in the quality of the obtained experimental data, affecting the signal-to-noise ratio (SNR), the probe recovery time, radiation-damping, and the coupling between multiple coils. For example, high SNR often requires a high-Q probe, while a short recovery time to observe of broad signals generally requires low Q. Here, we discuss effecting a compromise between SNR and recovery time by adjusting the coupling of the probe and preamplifier by mismatching their impedances. Unlike the more common impedance-matched case, the conditions for optimum performance for parallel- and series-tuned probes are found to differ significantly. (C) 2000 John Wiley & Sons, Inc. Concepts Magn Reson 12: 125-136, 2000. C1 USN, Res Lab, Div Chem, Washington, DC 20375 USA. Michigan Technol Univ, Dept Phys, Houghton, MI 49931 USA. US FDA, Off Premarket Approval, Washington, DC 20204 USA. RP Miller, JB (reprint author), USN, Res Lab, Div Chem, Code 6120, Washington, DC 20375 USA. NR 28 TC 8 Z9 10 U1 2 U2 10 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1043-7347 J9 CONCEPT MAGNETIC RES JI Concepts Magn. Resonance PY 2000 VL 12 IS 3 BP 125 EP 136 DI 10.1002/(SICI)1099-0534(2000)12:3<125::AID-CMR2>3.0.CO;2-P PG 12 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Chemistry; Physics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 305XV UT WOS:000086567800002 ER PT J AU Bianchine, PJ AF Bianchine, PJ TI Use of immune globulin intravenous (human) to prevent infection in the multiple trauma patient SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE intravenous human immunoglobulin; trauma patients; prophylaxis of infection ID IMMUNOGLOBULINS; PROPHYLAXIS; TRIAL; SEPSIS; CARE C1 Quintiles Consulting, Rockville, MD USA. RP Bianchine, PJ (reprint author), US FDA, Ctr Biol Evaluat & Res, 5820 Phoenix Dr, Bethesda, MD 20817 USA. NR 12 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2000 VL 28 IS 1 BP 254 EP 255 DI 10.1097/00003246-200001000-00045 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 279QV UT WOS:000085057400045 PM 10667535 ER PT J AU Shi, XR Fung, DYC AF Shi, XR Fung, DYC TI Control of foodborne pathogens during sufu fermentation and aging SO CRITICAL REVIEWS IN BIOTECHNOLOGY LA English DT Review ID MICROBIOLOGICAL QUALITY; TOFU; FOODS AB Control of the foodborne pathogens Escherichia coli O157:H7, Salmonella typhimurium, Staphylococcus aureus, and Listeria monocytogenes during sufu fermentation was evaluated. Before fermentation, pathogens were inoculated onto tofu (substrate for sufu) at 5 log cfu/g or 3 log cfu/g, and starter culture (Actinomucor elegans) was inoculated at 3 log cfu/g. After 2 days of fermentation at 30 degreesC, the four pathogens reached 7 to 9 log cfu/g, and the mold count reached 6 to 7 log cfu/g. After fermentation, sufu samples were aged in a solution of 10% alcohol + 12% NaCl. After 1 month of aging, the total bacterial count was 6 to 7 log cfu/g, but all foodborne pathogens and mold were reduced to nondetectable levels. The total bacterial count decreased after aging for 2 months and 3 months, but the differences were not significant (P > 0.05) compared with the count after 1 month. Microorganism in experimental sufu from different aging periods and in commercial sufu were compared. A total of 270 isolates were purified and identified by the BBL Crystal identification System. From the experimental sufu samples, 49 Bacillus spp. (20.4%), 167 Enterococcus spp. (69.6%), 6 Shewanella putrefaciens (2.4%), and 18 miscellaneous Gram-negative bacilli (7.5%) were identified. From commercial sufu samples, 17 Bacillus spp. (56.7%), 2 Enterococcus durans (6.7%), 5 miscellaneous Gramnegative bacilli (16.7%), 5 Corynbacterium aquaticum (16.7%), and 1 Shewanella putrefaciens (3.3%) were obtained. Although the longer aging period did not significantly decrease the total bacterial count, it may help in the development of sufu flavor. This study showed that sufu fermentation and aging can control common foodborne pathogens, so sufu is a safe product even though its preparation does not include pasteurization. C1 Kansas State Univ, Dept Anim Sci & Ind, Manhattan, KS 66506 USA. RP Shi, XR (reprint author), US FDA, Natl Ctr Toxicol Res, HFT-230,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 52 TC 2 Z9 4 U1 2 U2 8 PU CRC PRESS LLC PI BOCA RATON PA 2000 CORPORATE BLVD NW, JOURNALS CUSTOMER SERVICE, BOCA RATON, FL 33431 USA SN 0738-8551 J9 CRIT REV BIOTECHNOL JI Crit. Rev. Biotechnol. PY 2000 VL 20 IS 4 BP 265 EP 291 PG 27 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 390KE UT WOS:000166293600002 PM 11192025 ER PT J AU Gubina, E Ruiz-Hidaigo, MJ Baladron, V Laborda, J AF Gubina, E Ruiz-Hidaigo, MJ Baladron, V Laborda, J TI Assignment of dlk (Dlk1) to mouse chromosome band 12E-F1 by in situ hybridization SO CYTOGENETICS AND CELL GENETICS LA English DT Article; Proceedings Paper CT 4th International Chromosome 6 Workshop CY JUN 10-12, 1999 CL CAMBRIDGE, ENGLAND ID ADIPOCYTE DIFFERENTIATION; REPEAT MOTIFS; PROTEIN; IDENTIFICATION; EXPRESSION; VARIANTS; PREF-1 C1 US FDA, Immunobiol Lab, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Laborda, J (reprint author), Univ Castilla La Mancha, Dept Biochem, Sch Med, Benjamin Palencia Bldg,Avda Espana S-N,Campus Alb, Albacete 02071, Spain. RI Laborda, Jorge/L-5726-2014; Ruiz-Hidalgo, Maria/L-1956-2014; Baladron, Victoriano/L-1758-2014 OI Laborda, Jorge/0000-0002-9210-838X; Baladron, Victoriano/0000-0003-4574-8760 NR 9 TC 8 Z9 8 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2000 VL 88 IS 3-4 BP 322 EP 323 DI 10.1159/000015519 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 319PV UT WOS:000087351100040 PM 10828620 ER PT J AU Paweletz, CP Gillespie, JW Ornstein, DK Simone, NL Brown, MR Cole, KA Wang, QH Huang, J Hu, N Yip, TT Rich, WE Kohn, EC Linehan, WM Weber, T Taylor, P Emmert-Buck, MR Liotta, LA Petricoin, EF AF Paweletz, CP Gillespie, JW Ornstein, DK Simone, NL Brown, MR Cole, KA Wang, QH Huang, J Hu, N Yip, TT Rich, WE Kohn, EC Linehan, WM Weber, T Taylor, P Emmert-Buck, MR Liotta, LA Petricoin, EF TI Rapid protein display profiling of cancer progression directly from human tissue using a protein biochip SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE SELDI; proteomics; biomarker; microdissection; laser; pharmacoproteomics; pharmacogenomics; mass spectrometry ID LASER-CAPTURE MICRODISSECTION; 2-DIMENSIONAL ELECTROPHORESIS; MOLECULAR ANALYSIS; SAMPLE PREPARATION AB The complicated, changing pattern of protein expression should contain important information about the pathologic process taking place in the cells of actual tissue. Utilization of this information for the selection of druggable targets could be possible if a means existed to rapidly analyze and display changes in protein expression in defined microscopic cellular subpopulations. As a demonstration of feasibility, we show the generation of sensitive, rapid, and reproducible molecular weight protein profiles of patient-matched normal, premalignant, malignant, and metastatic microdissected cell populations from stained human esophageal, prostate, breast, ovary, colon, and hepatic tissue sections through the application of an affinity-based biochip. Reproducible, discriminatory protein biomarker profiles can be obtained from as few as 25 cells in less than 5 min from dissection to the generation of the protein fingerprint. Furthermore, these protein pattern profiles reveal reproducible changes in expression as cells undergo malignant transformation, and are discriminatory for different tumor types. Consistent protein changes were identified in the microdissected cells from patient-matched tumor and normal epithelium from eight out of eight different malignant esophageal tissue sets and three out of three malignant prostate tissue sets. A means to rapidly generate a display of expressed proteins from microscopic cellular populations sampled from tissue could be an important enabling technology for pharmacoproteomics, molecular pathology, drug intervention strategies, therapeutic assessment of drug entities, disease diagnosis, toxicity, and gene therapy monitoring. Published 2000 Wiley-Liss, Inc.(+) C1 US FDA, Ctr Biol Evaluat & Res, Tissue Prote Unit, Div Cytokine Biol, Bethesda, MD 20892 USA. NCI, Canc Genome Anant Project, Off Director, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NCI, Mol Signalling Unit, Bethesda, MD 20892 USA. NCI, Pathogenet Unit, Bethesda, MD 20892 USA. NCI, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. Shanxi Canc Hosp, Pathol Lab, Taiyuan, Peoples R China. Ciphergen Biosyst Inc, Palo Alto, CA USA. Georgetown Univ, Dept Chem, Washington, DC 20057 USA. Roswell Pk Med Ctr, Buffalo, NY USA. RP Petricoin, EF (reprint author), US FDA, Ctr Biol Evaluat & Res, Tissue Prote Unit, Div Cytokine Biol, 8800 Rockville Pike,Bldg 29A, Bethesda, MD 20892 USA. RI Cole, Kristina/M-3922-2015 NR 15 TC 119 Z9 126 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD JAN PY 2000 VL 49 IS 1 BP 34 EP 42 DI 10.1002/(SICI)1098-2299(200001)49:1<34::AID-DDR6>3.0.CO;2-W PG 9 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 296JD UT WOS:000086020500006 ER PT J AU Beernaert, H Caroli, S Clausing, P Doherty, B Edelmann, A Hede, R Helder, T Lange, J Lehn, H McCormack, J Seiler, JP Turnheim, D AF Beernaert, H Caroli, S Clausing, P Doherty, B Edelmann, A Hede, R Helder, T Lange, J Lehn, H McCormack, J Seiler, JP Turnheim, D TI The Revised Principles of Good Laboratory Practice of the Organisation for Economic Cooperation and Development - Changes, chances, and controversies SO DRUG INFORMATION JOURNAL LA English DT Article DE study; definitions; responsibilities; short-term studies; sponsor; principal investigator; information technology; validation AB This paper is the condensed result of the presentations and discussions held at the DIA Workshop "The Revised OECD Principles of Good Laboratory Practice," held September 3 and 4, 1998, in Brussels. The workshop brought together inspectors from compliance monitoring authorities and quality assurance units in industry, as well as study directors working according to the rules of Good Laboratory Practice (GLP). They discussed a number of issues important to the successful implementation of the revised Principles of Good Laboratory Practice of the Organisation for Economic Cooperation and Development (OECD), Here informed about the changes which had taken place in this set of rules, debated areas of controversy and looked at opportunities in the revised principles to improve the quality of safety studies. Specific areas covered included the nov definitions given in the revised principles and their pragmatic application, the question of whether the new position of the principal investigator, would offer any benefits to the procedures in the pharmaceutical industry the issue of what constitutes a short-term rest and how a test facility and its quality assurance unit could sensibly deal with it, and the impact of information technology, including the possibility of electronic signatures on Good Laboratory Practice and its implementation in the future. There are no easy solutions or handy recipies for any of the issues tackled in these discussions, nor Ir ere they expected. The result of the workshop rr as a better understanding of the various viewpoints that could be taken when it comes to interpreting and implementing the Principles of Good Laboratory Practice. The rules governing this quality system are general terms, which must be adapted in a pragmatical manner to widely differing situations, and a workshop such as this can help to bridge the gaps bet een this wide array of disciplines working under GLP. In this, the DIA workshop on the "The Revised OECD Principles of Good Laboratory Practice" succeeded in full measure. C1 Intercantonal Off Control Med, GLP Compliance Monitoring Unit, CH-3000 Bern, Switzerland. Org Econ Cooperat & Dev, Environm Hlth & Safety Div, Paris, France. Sci Inst Publ Hlth Louis Pasteur, Brussels, Belgium. Inst Super Sanita, Tossicol Applicata Lab, Rome, Italy. Scantox AS, Lille Skensved, Denmark. F Hoffmann La Roche & Co Ltd, Pharma Res Nonclin Dev, GLP QAU, Basel, Switzerland. Med Prod Agcy, Uppsala, Sweden. Minist Hlth Welf & Sport, GLP Monitoring Unit, Rijswijk, Netherlands. Schering AG, D-1000 Berlin, Germany. Bayer AG, Pharma QA Compliance GLP, Wuppertal, Germany. US FDA, Div Compliance Policy, Rockville, MD 20857 USA. RP Seiler, JP (reprint author), Intercantonal Off Control Med, GLP Compliance Monitoring Unit, Erlachstr 8, CH-3000 Bern, Switzerland. NR 4 TC 0 Z9 0 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. PD JAN-MAR PY 2000 VL 34 IS 1 BP 33 EP 45 PG 13 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 286GV UT WOS:000085436000004 ER PT J AU Chasin, SH AF Chasin, SH TI Project management performance measures in a regulatory environment: An initial examination SO DRUG INFORMATION JOURNAL LA English DT Article DE Government Performance and Results Act; GPRA; Results Act; performance measurement; Food and Drug Administration AB This paper's first section provides background on basic measurement concepts under the Government Performance and Results Act (GPRA, Results Act). GPRA revolutionized government officials' thinking about effectiveness and efficiency with its emphasis on measurable goals. Here a broad background for the law and the implications of its enactment are provided. Next, the paper presents several types of measures for government work and their relationships to each other: The second half of the paper touches on some of the unique reasons that measuring project management by the Food and Drug Administration (FDA) is particularly difficult. With this in mind, the paper concludes with possible measures for FDA project managers and suggests possible areas for research and thought. C1 US FDA, Off Planning, Rockville, MD 20857 USA. RP Chasin, SH (reprint author), 5600 Fishers Lane,Room 11B04, Rockville, MD 20857 USA. NR 2 TC 0 Z9 0 U1 1 U2 2 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. PD JAN-MAR PY 2000 VL 34 IS 1 BP 87 EP 90 PG 4 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 286GV UT WOS:000085436000011 ER PT J AU Yager, JA Kallgren, DL AF Yager, JA Kallgren, DL TI Roles of regulatory project managers in the US Food and Drug Administration's Center for Drug Evaluation and Research SO DRUG INFORMATION JOURNAL LA English DT Article DE project management; regulatory; review team; matrix AB The 1992 Prescription Drug User Fee Act (PDUFA) mandate to implement project management within the Center for Drug Evaluation and Research's new drug review process was clearly the springboard for the evolution of the regulatory project manager position. This role represents a challenging melding of two traditionally separate and fundamentally different functions: regulatory affairs and project management. The creation of this "hybrid" position was initially accomplished within the center by expanding the former consumer safety officer role within the Office of Review Management, an historically coordinator-type position with strong regulatory focus, to include that of project management principles. Regulatory project managers play key roles as coleaders of the review team, managers of the review process, regulatory managers, central communication points, and effectors of the center's matrix functionality. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Yager, JA (reprint author), US FDA, Ctr Drug Evaluat & Res, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 3 TC 0 Z9 0 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. PD JAN-MAR PY 2000 VL 34 IS 1 BP 289 EP 293 PG 5 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 286GV UT WOS:000085436000036 ER PT J AU Schilsky, RL AF Schilsky, RL TI Preparing for FDA advisory committee presentations: Perspective of an advisory committee member SO DRUG INFORMATION JOURNAL LA English DT Article DE Food and Drug Administration; advisory committees; sponsor AB Advisory committees play an important role in the interactions that occur between the pharmaceutical industry and the Food and Drug Administration (FDA). This article highlights the time points at which advisory committee meetings are typically held-end of Phase I and end of Phase II; prior to New Drug Application (NDA) submission; and following FDA review of an NDA-and the type of discussions held at each meeting. The role of advisory committees, and the presentations made by the sponsor and the FDA at advisory committee meetings, are explained. Each advisory committee member must satisfy him/herself that the proposed new drug is safe and effective before recommending that it be approved by FDA. C1 Univ Chicago, Div Biol Sci, Chicago, IL 60637 USA. US FDA, Oncol Drugs Advisory Comm, Rockville, MD 20857 USA. RP Schilsky, RL (reprint author), Univ Chicago, Div Biol Sci, 5841 S Maryland Ave,MC 1000, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 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. PD JAN-MAR PY 2000 VL 34 IS 1 BP 301 EP 304 PG 4 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 286GV UT WOS:000085436000038 ER PT J AU Bowen, D AF Bowen, D TI Nonprescription drug regulation in the United States SO DRUG INFORMATION JOURNAL LA English DT Article DE nonprescription drug; over-the-counter drug; regulation; monograph AB In the United States, nonprescription drug products are regulated through implementation of laws enacted by Congress. The Food and Drug Administration (FDA) follows specific procedures that allow for public notice and comment when promulgating implementing regulations. Drug products may be marketed directly to consumers, unless they are limited to prescription use only because they meet certain criteria. Nonprescription drug products are marketed over the counter (OTC) pursuant to drug ingredient-use monographs or as approved new drugs for an OTC use. These United States regulatory pathways require evidence of safety, efficacy, and labeling that consumers cart understand that renders the product not adulterated or misbranded All new drugs are required to comply with specific postmarketing surveillance practices. C1 US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 5, Rockville, MD 20857 USA. RP Bowen, D (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 5, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 3 TC 1 Z9 1 U1 2 U2 2 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. PD JAN-MAR PY 2000 VL 34 IS 1 BP 323 EP 327 PG 5 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 286GV UT WOS:000085436000041 ER PT J AU Casciano, DA AF Casciano, DA TI Development and utilization of primary hepatocyte culture systems to evaluate metabolism, dna binding, and dna repair of xenobiotics SO DRUG METABOLISM REVIEWS LA English DT Review ID PRIMARY RAT HEPATOCYTES; CALORIC RESTRICTION; CHEMICAL CARCINOGENS; FISCHER-344 RATS; CELL-CULTURES; ASSAY; ADDUCTS; 6-NITROCHRYSENE; IDENTIFICATION; METHAPYRILENE AB The use of isolated hepatocytes as an approach to evaluate hepatotoxic and hepatocarcinogenic compounds and investigate mechanisms by which chemicals induce liver lesions is well established. This review discusses techniques developed in the author's laboratory describing (1) isolation and primary culture of rodent hepatocytes detailing methods which are optimal for obtaining large numbers of viable cells, (2) DNA damage induced by physical and chemical agents in rodent hepatocytes measured as unscheduled DNA synthesis, and (3) metabolic activation of model hepatocarcinogens, their binding to DNA, and identification of individual adducts thought to be responsible for induction of DNA repair. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. RP Casciano, DA (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. NR 36 TC 19 Z9 21 U1 0 U2 0 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 2000 VL 32 IS 1 BP 1 EP 13 DI 10.1081/DMR-100100561 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 284LV UT WOS:000085334600001 PM 10711405 ER PT J AU Gaylor, DW AF Gaylor, DW TI New issues in cancer risk assessment SO DRUG METABOLISM REVIEWS LA English DT Article; Proceedings Paper CT 1998 Arkansas Toxicology Symposium: Can Rodent Cancer Tests Predict for Human Cancers - Honoring Dr David P Rall CY NOV 12-13, 1998 CL LITTLE ROCK, ARKANSAS SP Dorothy Snider Fdn ID LINEARIZED MULTISTAGE MODEL; POTENCY AB When a nonlinear dose-response at low doses can be justified, an acceptable daily intake for a carcinogen can be obtained by dividing a benchmark dose, associated with a low incidence of tumors in animals, by uncertainty factors to account for animal-to-human extrapolation, human variability, and risk reduction from a low observed adverse-effect level. This approach can utilize mechanistic information to justify smaller uncertainty factors than typical default values of 10. If a nonlinear dose-response cannot be justified, traditional linear extrapolation from the benchmark dose to zero sometimes gives similar results. This suggests a unified risk-assessment procedure based on uncertainty factors. The issue of cross-species extrapolation based on the risk relative to background risks, rather than excess risk, is examined. The relative risk approach reduces the estimates of cancer risk in humans based on common rodent tumors, such as the liver in some strains of mice. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Gaylor, DW (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd,HFT-1, Jefferson, AR 72079 USA. NR 16 TC 3 Z9 3 U1 0 U2 0 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 2000 VL 32 IS 2 BP 187 EP 192 DI 10.1081/DMR-100100571 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 307QV UT WOS:000086665200008 PM 10774774 ER PT J AU Schwetz, BA AF Schwetz, BA TI Thoughts on carcinogenesis testing: The FDA today SO DRUG METABOLISM REVIEWS LA English DT Article; Proceedings Paper CT 1998 Arkansas Toxicology Symposium: Can Rodent Cancer Tests Predict for Human Cancers - Honoring Dr David P Rall CY NOV 12-13, 1998 CL LITTLE ROCK, ARKANSAS SP Dorothy Snider Fdn AB Prevention of human cancer in the future will depend on using the results of epidemiologic and animal studies and strategies to minimize exposure. Changes are occurring in the area of animal testing and research that potentially represent significant steps toward reducing our dependence on the traditional 2-year bioassay as our primary tool for identification of chemical carcinogens and management of risk. Efforts to prevent cancer would be enhanced by more attention to describing modes of action so that the development of tumors would not be the only basis for predicting carcinogenic potential. These markers might also serve for early detection of cancer at a stage more amenable to treatment. What carcinogens do we want to detect through animal tests in the future? Whether the goal is to identify weak or potent carcinogens, or both, there will still be a need for 2-year bioassays, but hopefully for confirmatory rather than screening purposes. C1 US FDA, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, 5600 Fishers Lane,Room 17-35,HF-33, Rockville, MD 20857 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 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 2000 VL 32 IS 2 BP 211 EP 214 DI 10.1081/DMR-100100573 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 307QV UT WOS:000086665200010 PM 10774776 ER PT J AU Fu, PP Von Tungelin, LS Hammons, GJ McMahon, G Wogan, G Flammang, TJ Kadlubar, FF AF Fu, PP Von Tungelin, LS Hammons, GJ McMahon, G Wogan, G Flammang, TJ Kadlubar, FF TI Metabolic activation capacity of neonatal mice in relation to the neonatal mouse tumorigenicity bioassay SO DRUG METABOLISM REVIEWS LA English DT Article; Proceedings Paper CT 1998 Arkansas Toxicology Symposium: Can Rodent Cancer Tests Predict for Human Cancers - Honoring Dr David P Rall CY NOV 12-13, 1998 CL LITTLE ROCK, ARKANSAS SP Dorothy Snider Fdn ID DNA ADDUCT FORMATION; X C3H-HEJ F1-MICE; MALE B6C3F1 MOUSE; H-RAS ONCOGENE; NEWBORN MICE; LIVER-TUMORS; CARCINOGENIC METABOLITE; CHEMICAL CARCINOGENESIS; CALORIC RESTRICTION; 61ST CODON AB The neonatal mouse tumorigenicity bioassay is a well-developed animal model that has recently been recommended as an alternative tumorigenicity bioassay by the International Conference on Harmonization (ICH) for Technical Requirements for the Registration of Pharmaceuticals for Human Use. There are sufficient data to conclude that this animal model is highly sensitive to genotoxic chemical carcinogens that exert their tumorigenicity through mechanisms involving the formation of covalently bound exogenous DNA adducts that lead to mutation. On the other hand, it is not sensitive to chemical carcinogens that exert tumorigenicity through a secondary mechanism. The metabolizing enzymes present in the neonatal mouse, particularly the cytochromes P450, are critical factors in determining the tumorigenic potency of a chemical tested in this bioassay. However, compared to the metabolizing enzymes of the adult mouse and rat, the study of the metabolizing enzymes in neonatal mouse tissues has been relatively limited. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. MIT, Div Toxicol, Cambridge, MA 02139 USA. RP Fu, PP (reprint author), 3900 NCTR Rd,HFT-110, Jefferson, AR 72079 USA. NR 94 TC 13 Z9 14 U1 0 U2 0 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 2000 VL 32 IS 2 BP 241 EP 266 DI 10.1081/DMR-100100575 PG 26 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 307QV UT WOS:000086665200012 PM 10774778 ER PT J AU Shacter, E AF Shacter, E TI Quantification and significance of protein oxidation in biological samples SO DRUG METABOLISM REVIEWS LA English DT Review DE protein oxidation; disease; oxidative stress; markers; methods; therapeutic proteins ID LOW-DENSITY-LIPOPROTEIN; METAL-CATALYZED OXIDATION; MIXED-FUNCTION OXIDATION; CARBONIC-ANHYDRASE-III; AMINO-ACID-RESIDUES; PERFORMANCE LIQUID-CHROMATOGRAPHY; INITIATED LIPID-PEROXIDATION; TRITIATED SODIUM-BOROHYDRIDE; HYDROXYL-RADICAL DAMAGE; BOVINE SERUM-ALBUMIN AB Protein oxidation is defined here as the covalent modification of a protein induced either directly by reactive oxygen species or indirectly by reaction with secondary by-products of oxidative stress. Oxidative modification of proteins can be induced experimentally by a wide array of prooxidant agents and occurs in vivo during aging and in certain disease conditions. Oxidative changes to proteins can lead to diverse functional consequences, such as inhibition of enzymatic and binding activities, increased susceptibility to aggregation and proteolysis, increased or decreased uptake by cells, and altered immunogenicity. There are numerous types of protein oxidative modification and these can be measured with a variety of methods. Protein oxidation serves as a useful marker for assessing oxidative stress in vivo. There are both advantages and disadvantages to using proteins for this purpose compared to lipids and DNA. Finally, it is important to monitor the degree of oxidative modification of therapeutic proteins manufactured for commercial use. This review will examine various aspects of protein oxidation, with emphasis on using proteins as markers of oxidative stress in biological samples. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Shacter, E (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29A,Room 2A-11,HFM 535,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 130 TC 397 Z9 424 U1 7 U2 78 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 2000 VL 32 IS 3-4 BP 307 EP 326 DI 10.1081/DMR-100102336 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 388LA UT WOS:000166181000003 PM 11139131 ER PT J AU Hanna, GM AF Hanna, GM TI H-1-NMR studies of drugs with chiral solvating agent: The direct enantiomeric purity determination of the chiral anesthetic, prilocaine SO ENANTIOMER LA English DT Article; Proceedings Paper CT 11th International Symposium on Chiral Discrimination CY JUL 25-28, 1999 CL CHICAGO, ILLINOIS DE chiral solvating agent; diastereomeric solvates; enantiomeric purity determination; H-1-NMR spectroscopy; local anesthetics; prilocaine enantiomers ID MAGNETIC-RESONANCE SPECTROSCOPY; MEDICINAL CHEMISTRY; PHARMACOKINETICS; STEREOCHEMISTRY; METABOLISM AB Chiral recognition of prilocaine was obtained on a 400 MHz H-1-NMR spectrometer by fast diastereomeric interactions with the chiral solvating agent (S)-(+)-2,2,2-trifluoro-1-(9-anthryl) ethanol (TFAE). Assignment of absolute configuration was based on relative field position of the resolved enantiomeric signals. influence of temperature, substrate concentration and solvating agent to substrate molar ratio on enantiomeric resolution were studied and evaluated. Optimization of experimental conditions provided two significant resolved signals for quantitative use. Utilizing the relative intensities of the resolved enantiomeric signals of the methine proton attached to the stereogenic center assigned to (S)-(+)- and (R)-(-)-prilocaine, the analysis of synthetic mixtures of the enantiomers by the proposed NMR method resulted in assay values which agreed closely with the known quantities of each enantiomer in the tested mixtures. The mean + SD recovery values for the (S)-(+)-enantiomer was 99.9 +/- 0.2% of added antipode (n = 7). The optically pure enantiomers were used to establish the minimum amount detected by the proposed NMR spectroscopic method. C1 US FDA, NE Reg Lab, Jamaica, NY 11433 USA. RP Hanna, GM (reprint author), US FDA, NE Reg Lab, 158-15 Liberty Ave, Jamaica, NY 11433 USA. NR 23 TC 8 Z9 8 U1 0 U2 1 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1024-2430 J9 ENANTIOMER JI Enantiomer PY 2000 VL 5 IS 3-4 BP 303 EP 312 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 377NV UT WOS:000165520400012 PM 11126871 ER PT J AU Witt, KL Knapton, A Wehr, CM Hook, GJ Mirsalis, J Shelby, MD MacGregor, JT AF Witt, KL Knapton, A Wehr, CM Hook, GJ Mirsalis, J Shelby, MD MacGregor, JT TI Micronucleated erythrocyte frequency in peripheral blood of B6C3F(1) mice from short-term, prechronic, and chronic studies of the NTP carcinogenesis bioassay program SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE micronucleus assay; normochromatic erythrocytes; polychromatic erythrocytes; genetic damage; B6C3F(1) mice; chemical exposures ID FISCHER 344 RATS; INDUCTION; TOXICITY; 1,3-BUTADIENE; PERSISTENCE; INHALATION; EXPOSURES; PROTOCOL; BENZENE; DAMAGE AB The mouse peripheral blood micronucleus (MN) test was performed on samples collected from 20 short-term, 67 subchronic, and 5 chronic toxicity and carcinogenicity studies conducted by the National Toxicology Program (NTP). Data are presented for studies not previously published. Aspects of protocol that distinguish this test from conventional short-term bone marrow MN tests are duration of exposure, and absence of repeat tests and concurrent positive controls. Furthermore, in contrast to short-term bone marrow MN tests where scoring is limited to polychromatic erythrocytes (PCE), longer term studies using peripheral blood may evaluate MN in both, or either, the normochromatic (NCE) or PCE populations. The incidence of MN-PCE provides on index of damage induced within 72 hr of sampling, whereas the incidence of MN in the NCE population at steady state provides an index of average damage during the 30-day period preceding sampling. The mouse peripheral blood MN test has been proposed as a useful adjunct to rodent toxicity tests and has been effectively incorporated as a routine part of overall toxicity testing by the NTP. Data derived From peripheral blood MN analyses of dosed animals provide a useful indication of the in vivo potential for induced genetic damage and supply an important piece of evidence to be considered in the overall assessment of toxicity and health risk of a particular chemical. Although results indicate that the test has low sensitivity for prediction of carcinogenicity, a convincingly positive result in this assay appears to be highly predictive of rodent carcinogenicity. (C) 2000 Wiley-Liss, Inc. C1 ILS Inc, Res Triangle Pk, NC 27709 USA. US FDA, Laurel, MD USA. USDA, Western Reg Res Ctr, Albany, CA 94710 USA. NIEHS, Res Triangle Pk, NC 27709 USA. SRI Int, Menlo Park, CA 94025 USA. RP Witt, KL (reprint author), ILS Inc, POB 13501, Res Triangle Pk, NC 27709 USA. NR 45 TC 54 Z9 56 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2000 VL 36 IS 3 BP 163 EP 194 DI 10.1002/1098-2280(2000)36:3<163::AID-EM1>3.0.CO;2-P PG 32 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 369HJ UT WOS:000165059600001 PM 11044899 ER PT J AU Shelton, SD Cherry, V Manjanatha, MG AF Shelton, SD Cherry, V Manjanatha, MG TI Mutant frequency and molecular analysis of in vivo lacI mutations in the bone marrow of Big Blue (R) rats treated with 7,12-dimethylbenz[a]anthracene SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE mutant frequency; DBMA; transgenic model; genotoxicity; carcinogenesis; mutagenesis ID TRANSGENIC MICE; IN-VIVO; MAMMARY CARCINOGENESIS; DNA; CELLS; GENE; MUTAGENICITY; SEQUENCE; SPECTRA; TISSUES AB Recently, we evaluated lacl mutations in lymphocytes and mammary tissue of Big Blue (BB) rats exposed to 7,12-dimethylbenz[a]anthracene (DMBA). The results on the time course of mutant induction suggested that the lacl gene may manifest a tissuespecific increase in mutant frequency (MF). To test whether a tissue-specific increase in lacl MF is dependent on the cell proliferation rate of a tissue, we examined rapidly proliferating bone marrow cells for DMBA-induced loci mutations. Seven-week-old female BE rats were given single doses of 0, 20, and 130 mg/kg DMBA by gavage and the lad MFs in the bone marrow were measured over a period of 14 weeks following treatment. Bone marrow cells had a remarkably low average background MF (3.1 +/- 1.6 x 10(-6) plaque-forming units) and the DMBA-induced loci MFs were significantly higher than control MFs for both doses and at all time points (P < 0.01). The lacl MF in the bone marrow increased for 2 weeks and then remained relatively constant; 20 and 130 mg/kg DMBA produced 34- and 106-fold increases in MF over control MF. DNA sequencing revealed that the majority of DMBA-induced lacl mutations were bose-pair substitutions and that A:T -> T:A (48%) and G:C -> T:A (24%) transversions were the predominant types. Thus, the different loci mutation fixation times observed for bone marrow (2 weeks), mammary(10 weeks), and lymphocytes (6 weeks) suggest that the loci gene manifests a tissuespecific mutation fixation time, which may depend on the cell proliferation rate of a tissue. In addition, the relatively low spontaneous MF in bone marrow compared with that in other tissues may be useful for increasing the sensitivity of the assay for detecting induced MFs in BE rats. Published 2000 Wiley-Liss, Inc.(dagger) C1 US FDA, Natl Ctr Toxicol Res, Div Genet Toxicol, Jefferson, AR 72079 USA. Louisiana Tech Univ, Ruston, LA 71270 USA. RP Manjanatha, MG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet Toxicol, HFT-120, Jefferson, AR 72079 USA. NR 31 TC 10 Z9 10 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2000 VL 36 IS 3 BP 235 EP 242 DI 10.1002/1098-2280(2000)36:3<235::AID-EM7>3.0.CO;2-D PG 8 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 369HJ UT WOS:000165059600007 PM 11044905 ER PT J AU Sotomayor, RE Sega, GA AF Sotomayor, RE Sega, GA TI Unscheduled DNA synthesis assay in mammalian spermatogenic cells: An update SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE UDS assay; specific-locus mutation assay; germ cells; review ID DOMINANT-LETHAL MUTATIONS; MOUSE GERM-CELLS; INDUCED SPECIFIC-LOCUS; MALE-MICE; METHYL METHANESULFONATE; ETHYL METHANESULFONATE; X-RAYS; ISOPROPYL METHANESULFONATE; TEMPORAL PATTERNS; ADDUCT FORMATION AB The unscheduled DNA synthesis (UDS) assay measures DNA repair in response to DNA damage. To date, 59 chemicals plus UV and X rays have been tested for UDS in spermatogenic cells of humans, rabbits, rats, and mice. In vivo, in vitro, and combined in vivo/in vitro procedures have been used. UDS has been shown to occur in spermatogonia, meiotic spermatocytes, and early spermatid stages. Fifty-nine percent of the agents tested gave a positive UDS response in one or more germ-cell stages. Results show 95% concordance (positive or negative) between different mammalian species. Some well-known genotoxic chemicals, for example, aflatoxin B-1 (AFB(1)), benzo[a] pyrene (B[a]P), and N-methyl-N'-nitro-Nnitrosoguanidine (MNNG), did not induce significant levels of UDS. Possible explanations are discussed. Results From the UDS assay were compared with those from the mouse specific-locus mutation (SLM) test to determine correlations between the two assays. Only two chemicals, ethyl- and methyl-nitrosourea (ENU and MNU), have been tested for UDS and SLM induction in spermatogonial stages. Results show full concordance between the two assays. In postspermatogonial stages, 25 chemicals and X rays have been tested for UDS and SLM induction. Seventy-seven percent of these agents showed similar results (positive or negative) in these germ-cell stages. Although the UDS assay cannot replace the SLM test, the strong correlations between the two assays suggest the usefulness of the UDS assay as a predictor of germ-cell mutations in mammalian systems. Environ. Mol. Mutagen. 36.255-265, 2000. Published 2000 Wiley-Liss, Inc.dagger C1 US FDA, Div Toxicol Res, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. Oak Ridge Natl Lab, Div Chem & Analyt Sci, Oak Ridge, TN 37831 USA. RP Sotomayor, RE (reprint author), US FDA, Div Toxicol Res, Ctr Food Safety & Appl Nutr, HFS-509,MOD-1,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 95 TC 26 Z9 27 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2000 VL 36 IS 4 BP 255 EP 265 DI 10.1002/1098-2280(2000)36:4<255::AID-EM1>3.0.CO;2-O PG 11 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 383ZD UT WOS:000165913800001 PM 11152558 ER PT J AU Dobrovolsky, VN Shaddock, JG Heflich, RH AF Dobrovolsky, VN Shaddock, JG Heflich, RH TI 7,12-Dimethylbenz[a]anthracene-induced mutation in the Tk gene of Tk(+/-) mice: Automated scoring of lymphocyte clones using a fluorescent viability indicator SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE loss of heterozygosity; 5-bromodeoxyuridine; spleen lymphocytes; alamarBlue ID ETHYL-N-NITROSOUREA; IN-VIVO MUTATION; TRANSGENIC MICE; THYMIDINE KINASE; MOLECULAR ANALYSIS; MOUSE LYMPHOCYTES; SHUTTLE VECTORS; MAMMALIAN-CELLS; HIGH-FREQUENCY; DNA-SEQUENCE AB 7,12-Dimethylbenz[a]anrhracene (DMBA) is a rodent carcinogen and a potent in vivo mutagen for the X-linked hypoxanthine guanine phosphoribosyl transferase (hprt) gene of rats and for the loci transgene of Big Blue mice and rats. Although DMBA is also a powerful clastogen, molecular analysis of these DMBA-induced hprt and loci mutations indicates that most are single base-pair (bp) substitutions and 1- to 3-bp frameshifts. In the present study, we evaluated the types of mutations induced by DMBA in the autosomal thymidine kinase (Tk) gene of Tk(+/-) mice. Male and female 5- to 6-week-old animals were injected i.p. with DMBA at a dose of 30 mg/kg. Five weeks after the treatment, hprt and Tk mutant frequencies were determined using a limiting dilution clonal assay in 96-well plates. We established conditions For the automated identification of wells containing expanded lymphocyte clones using the fluorescent indicator alamarBlue. This procedure allowed the unbiased identification of viable clones and calculation of mutant frequencies. In male mice, DMBA treatment increased the frequency of hprt mutants from 1.8 +/- 1.1 to 34 +/- 9 x 10(-6), and Tk mutants from 33 +/- 12 to 78 +/- 26 x 10(-6); treated female mice had a significant but lower increase in hprt mutant frequency than did males. Molecular analysis of DMBA-induced Tk mutants revealed that at least 75% had the entire wild-type Tk allele missing. The results indicate that the predominant types of DMBA-induced mutation detected by the autosomal Tk gene are different From those detected by the X-linked hprt gene. The Tk gene mainly detects loss of heterozygosity mutation, whereas the majority of mutations previ ovsly found in the hprt gene were point mutations. Environ. Mel. Mutagen. 36.283-291, 2000. Published 2000 Wiley-Liss, Inc.dagger C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Dobrovolsky, VN (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 43 TC 23 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2000 VL 36 IS 4 BP 283 EP 291 DI 10.1002/1098-2280(2000)36:4<283::AID-EM4>3.0.CO;2-8 PG 9 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 383ZD UT WOS:000165913800004 PM 11152561 ER PT J AU Kirkland, DJ Hayashi, M MacGregor, JT Muller, L Schechtman, L Sofuni, T AF Kirkland, DJ Hayashi, M MacGregor, JT Muller, L Schechtman, L Sofuni, T TI Summary of major conclusions from the International Workshop on Genotoxicity Test Procedures SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Editorial Material DE genotoxicity; guidelines; recommendations; methods C1 Covance Labs Ltd, Harrogate HG3 1PY, England. Natl Inst Hlth Sci, Tokyo 158, Japan. US FDA, CDER, Off Testing & Res, Rockville, MD 20857 USA. BfArM, Berlin, Germany. RP Kirkland, DJ (reprint author), Covance Labs Ltd, Otley Rd, Harrogate HG3 1PY, England. NR 4 TC 13 Z9 13 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2000 VL 35 IS 3 BP 162 EP 166 DI 10.1002/(SICI)1098-2280(2000)35:3<162::AID-EM2>3.0.CO;2-O PG 5 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 300ZF UT WOS:000086283100002 PM 10737950 ER PT J AU Gocke, E Muller, L Guzzie, PJ Brendler-Schwaab, S Bulera, S Chignell, CF Henderson, LM Jacobs, A Murli, H Snyder, RD Tanaka, N AF Gocke, E Muller, L Guzzie, PJ Brendler-Schwaab, S Bulera, S Chignell, CF Henderson, LM Jacobs, A Murli, H Snyder, RD Tanaka, N TI Considerations on photochemical genotoxicity: Report of the International Workshop on Genotoxicity Test Procedures Working Group SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Editorial Material DE photochemical genotoxicity; UV radiation; V79 cells; dose-response curve ID PHOTOMUTAGENESIS TEST DEVELOPMENT; DNA-DAMAGE; CHROMOSOMAL ABERRATION; SUNSCREEN COMPOUNDS; GENE CONVERSION; VISIBLE-LIGHT; CHO CELLS; ASSAY; 8-METHOXYPSORALEN; CHLORPROMAZINE AB Recent toxicological observations have caused concern regarding the need to test, For example, pharmaceuticals and cosmetic products For photochemical genotoxicity. The objective of this report is to give assistance on how to adapt existing test methods to investigate the potential of light-absorbing compounds to induce genotoxic effects on photoactivation. In general, the Organization For Economic Co-Operation & Economic Development (OECD) draft guideline on in vitro phototoxicity testing served as a basis for consideration. Concomitant exposure of the cells to the test compound and solar simulated light was considered appropriate as the initial, basic test condition. Optimization of the exposure scheme, e.g., a change of the irradiation spectrum, might be indicated depending on the initial test results. Selection of test compound concentrations should be based on results obtained with the dark version of the respective test system but might have to be modified if phototoxic effects are observed. Selection of the irradiation dose has to be performed individually For each test system based on dose-effect studies. The irradiation should induce per se a small, reproducible toxic or genotoxic effect. The report includes a specification of necessary controls, discusses Factors that might have an impact on the irradiation characteristics, and gives a rationale for the omission of an external metabolic activation system. It also addresses the question that physicochemical and pharmacokinetic properties might trigger the need to test cc chemical For photochemical genotoxicity. Relevant experimental observations are presented to back up the recommendations. The working group did not reach a consensus as to whether a single, adequately perfomed in vitro test for clastogenicity would be sufficient to exclude a photogenotoxic liability or whether a test battery including a gene mutation assay would be needed for product safety testing regarding photochemical genotoxicity. (C) 2000 Wiley-Liss, Inc. C1 F Hoffmann La Roche & Co Ltd, PRNS, CH-4070 Basel, Switzerland. BfaRM, Berlin, Germany. Pfizer Inc, Groton, CT 06340 USA. Bayer AG, D-5600 Wuppertal, Germany. Parke Davis Pharmaceut Res, Ann Arbor, MI USA. NIEHS, LPC, Res Triangle Pk, NC 27709 USA. US FDA, Rockville, MD 20857 USA. Covance Labs Inc, Vienna, Austria. Dupont Merck Pharmaceut Co, Newark, DE USA. Hatano Res Inst, Kanagawa, Japan. RP Gocke, E (reprint author), F Hoffmann La Roche & Co Ltd, PRNS, Bldg 73-215, CH-4070 Basel, Switzerland. NR 27 TC 44 Z9 45 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2000 VL 35 IS 3 BP 173 EP 184 DI 10.1002/(SICI)1098-2280(2000)35:3<173::AID-EM4>3.0.CO;2-E PG 12 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 300ZF UT WOS:000086283100004 PM 10737952 ER PT J AU Phillips, DH Farmer, PB Beland, FA Nath, RG Poirier, MC Reddy, MV Turteltaub, KW AF Phillips, DH Farmer, PB Beland, FA Nath, RG Poirier, MC Reddy, MV Turteltaub, KW TI Methods of DNA adduct determination and their application to testing compounds for genotoxicity SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article; Proceedings Paper CT International Workshop on Genotoxicity Test Procedures CY MAR 25-26, 1999 CL WASHINGTON, D.C. DE DNA adducts; genotoxicity; radioactivity; (32)P-postlabeling; immunoassay; mass spectrometry; endogenous DNA damage ID CHROMATOGRAPHY MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; RISK ASSESSMENT; IN-VITRO; 1,N-2-PROPANODEOXYGUANOSINE ADDUCTS; P-32-POSTLABELING ASSAY; QUANTITATIVE-ANALYSIS; ALKALINE-HYDROLYSIS; CARCINOGEN EXPOSURE; LIPID-PEROXIDATION AB At the International Workshop on Genotoxicity Test Procedures (IWGTP) held in Washington, DC (March 25-26, 1999), a working group considered the uses of DNA adduct determination methods For testing compounds for genotoxicity. When a drug or chemical displays an unusual or inconsistent combination of positive and negative results in in vitro and in vivo genotoxicity assays and/or in carcinogenicity experiments, investigations into whether or not DNA adducts are formed may be helpful in assessing whether or not the test compound is a genotoxin. DNA adduct determinations can be carried out using radiolabeled compounds and measuring radioactive decay (scintillation counting) or isotope ratios (accelerator mass spectrometry) in the isolated DNA. With unlabeled compounds adducts may be measured by (32)p-post-labeling analysis of the DNA, or by physicochemical methods including moss spectrometry, fluorescence spectroscopy, or electrochemical detection, or by immunochemical methods. Each of these approaches has different strengths and limitations, influenced by sensitivity, cost, time, and interpretation of results. The design of DNA binding studies needs to be on a case-by-case basis, depending on the compound's profile of activity. DNA purity becomes increasingly important the more sensitive, and less chemically specific, the assay. While there may be adduct levels at which there is no observable biological effect, there are at present insufficient data on which to set a threshold level For biological significance. (C) 2000 Wiley-Liss, Inc. C1 Inst Canc Res, Haddow Labs, Sutton SM2 5NG, Surrey, England. Univ Leicester, MRC, Toxicol Unit, Leicester, Leics, England. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NCI, Bethesda, MD 20892 USA. Covance Labs Inc, Genet & Cellular Toxicol, Vienna, VA USA. Merck Res Labs, West Point, PA USA. Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Livermore, CA USA. RP Phillips, DH (reprint author), Inst Canc Res, Haddow Labs, Cotswold Rd, Sutton SM2 5NG, Surrey, England. EM davidp@icr.ac.uk NR 98 TC 91 Z9 98 U1 0 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2000 VL 35 IS 3 BP 222 EP 233 DI 10.1002/(SICI)1098-2280(2000)35:3<222::AID-EM9>3.0.CO;2-E PG 12 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 300ZF UT WOS:000086283100009 PM 10737957 ER PT J AU Hayashi, M MacGregor, JT Gatehouse, DG Adler, ID Blakey, DH Dertinger, SD Krishna, G Morita, T Russo, A Sutou, S AF Hayashi, M MacGregor, JT Gatehouse, DG Adler, ID Blakey, DH Dertinger, SD Krishna, G Morita, T Russo, A Sutou, S TI In vivo rodent erythrocyte micronucleus assay. II. Some aspects of protocol design including repeated treatments, integration with toxicity testing, and automated scoring SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article; Proceedings Paper CT International Workshop on Genotoxicity Test Procedures CY MAR 25-26, 1999 CL WASHINGTON, D.C. DE micronucleus assay; chronic treatment; automation; aneugen; germ cell; transplacental; somatic cell ID MOUSE BONE-MARROW; GERM-CELL MUTAGENICITY; IN-SITU HYBRIDIZATION; TRANSPLACENTALLY ACTIVE CARCINOGENS; PERIPHERAL-BLOOD RETICULOCYTES; SISTER CHROMATID EXCHANGES; COVALENT DNA MODIFICATIONS; FLOW-CYTOMETRIC ANALYSIS; SHORT-TERM TESTS; EARLY SPERMATIDS AB An expert working group on the in vivo micronucleus assay, formed as part of the International Workshop on Genotoxicity Test Procedures (IWGTP), discussed protocols for the conduct of established and proposed micronucleus assays at a meeting held March 25-26, 1999 in Washington, DC, in conjunction with the annual meeting of the Environmental Mutagen Society. The working group reached consensus on a number issues, including: (1) protocols using repeated dosing in mice and mts; (2) integration of the (rodent erythrocyte) micronucleus assay into general toxicology studies; (3) the possible omission of concurrently-treated positive control animals from the assay; (4) automation of micronucleus scoring by flow cytometry or image analysis; (5) criteria for regulatory acceptance; (6) detection of aneuploidy induction in the micronucleus assay; and (7) micronucleus assays in tissues (germ cells, other organs, neonatal tissue) of her than bone marrow. This report summarizes the discussions and recommendations of this working group. In the classic rodent erythrocyte assay, treatment schedules using repeated dosing of mice or rats, and integration of assays using such schedules into short-term toxicology studies, were considered acceptable as long as certain study criteria were met. When the micronucleus assay is integrated into ongoing toxicology studies, relatively short-ierm repeated-dose studies should be used preferentially because there is not yet sufficient data to demonstrate that conservative dose selection in longer term studies (longer than 1 month) does nor reduce the sensitivity of the essay. Additional validation data are needed to resolve this point. In studies with mice, either bone marrow or blood was considered acceptable as the tissue For assessing micronucleus induction, provided that the absence of spleen Function has been verified in the animal strains used. In studies with rats, the principal endpoint should be the frequency of micronucleated immature erythrocytes in bone marrow, although scoring of peripheral blood samples gives important supplementary data about the time course of micronucleus induction. When dose con centration and stability are verified appropriately, concurrent treatment with ct positive control agent is not necessary. Control of staining and scoring procedures can be obtained by including appropriate reference samples that have been obtained from a separate experiment. For studies in mts or mice, treatment/sampling regimens should include treatment at intervals of no more than 24 hr (unless the test article has a half-life of more than 24 hr) with sampling of bone marrow or blood, respectively, within 24 or 40 hr after the last treatment. The use of a DNA specific stain is recommended For the identification of micronuclei, especially for studies in the rat. In the case of a negative assay result with a non-toxic test article, it is desirable that systemic exposure to the test article is demonstrated. The group concluded that successful application of automated scoring by both flow cytometry and image analysis had been achieved, and defined criteria that should be met if automated scoring is employed. It Nas not felt appropriate to attempt to define specific recommended protocols for automated scoring at the present time. Other issues re viewed and discussed by the working group included micronucleus assays that have been developed in a number of tissues other than bone marrow. The group felt that these assays were useful research tools that could also be used to elucidate mechanisms in certain regulatory situations, but that these assays had not yet been standardized and validated for routine regulatory application. (C) 2000 Wiley-Liss, Inc. C1 Natl Inst Hlth Sci, Div Genet & Mutagenesis, Setagaya Ku, Tokyo 1588501, Japan. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Glaxo Wellcome Res & Dev Ltd, Med Safety Evaluat Div, Genet Toxicol, Ware, Herts, England. GSF, Inst Saugetiergenet, Neuherberg, Germany. Hlth Canada, Ctr Environm Hlth, Ottawa, ON K1A 0L2, Canada. Litron Labs, Rochester, NY USA. Parke Davis Pharmaceut Res, Dept Pathol & Expt Toxicol, Ann Arbor, MI USA. Glaxo Wellcome KK, Tsukuba Res Labs, Ibaraki, Osaka, Japan. Univ Insubria, DBSF, Dept Struct & Funct Biol, Varese, Italy. Natl Inst Biosci & Human Technol, Cent Res Inst, Tsukuba, Ibaraki, Japan. RP Hayashi, M (reprint author), Natl Inst Hlth Sci, Div Genet & Mutagenesis, Setagaya Ku, 1-18-1 Kamiyoga, Tokyo 1588501, Japan. EM hayashi@nihs.go.jb RI Russo, Antonella/K-8970-2016 OI Russo, Antonella/0000-0001-6691-257X NR 162 TC 155 Z9 167 U1 1 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2000 VL 35 IS 3 BP 234 EP 252 DI 10.1002/(SICI)1098-2280(2000)35:3<234::AID-EM10>3.0.CO;2-L PG 19 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 300ZF UT WOS:000086283100010 PM 10737958 ER PT J AU Heddle, JA Dean, S Nohmi, T Boerrigter, M Casciano, D Douglas, GR Glickman, BW Gorelick, NJ Mirsalis, JC Martus, HJ Skopek, TR Thybaud, V Tindall, KR Yajima, N AF Heddle, JA Dean, S Nohmi, T Boerrigter, M Casciano, D Douglas, GR Glickman, BW Gorelick, NJ Mirsalis, JC Martus, HJ Skopek, TR Thybaud, V Tindall, KR Yajima, N TI In vivo transgenic mutation assays SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article; Proceedings Paper CT International Workshop on Genotoxicity Test Procedures CY MAR 25-26, 1999 CL WASHINGTON, D.C. DE transgenic mutation assays; Muta (TM) Mouse; BigBlue (R) mouse/rat; lacl; lacZ ID ENDOGENOUS HPRT GENE; BLUE(TM) B6C3F1 MICE; IN-VIVO; MOUSE MODEL; STATISTICAL-ANALYSIS; SOMATIC MUTATIONS; LACI TRANSGENE; MUTAGENICITY; LYMPHOCYTES; ACCUMULATION AB Transgenic rodent gene mutation models provide quick and statistically reliable assays for mutations in the DNA From any tissue. For regulatory applications, assays should be based on neutral genes, be generally available in several laboratories, and be readily transferable. Five or Fewer repeated treatments are inadequate to conclude that a compound is negative but more than 90 daily treatments may risk complications. A sampling time of 35 days is suitable for most tissues and chemicals, while shorter sampling times might be appropriate for highly proliferative tissues. For phage-based assays, 5 to 10 animals per group should be analyzed, assuming a spontaneous mutant frequency (MF) of similar to 3 x 10(-5) mutants/locus and 125,000-300,000 plaque or colony forming units (PFU or CFU) per tissue. Data should be generated For two dose groups but three should be treated, at the maximum tolerated dose (MTD), two-thirds the MTD, and one-third the MTD. Concurrent positive control animals are only necessary during validation, but positive control DNA must be included in each plating. Tissues should be processed and analyzed in a block design and the total number of PFUs or CFUs and the MF for each tissue and animal reported. Sequencing data would not normally be required but might provide useful additional information in specific circumstances. Statistical tests used should consider the animal as the experimental unit. Nonparametric statistical tests are recommended. A positive result is a statistically significant dose-response and/or statistically significant increase in any dose group compared to concurrent negative controls using an appropriate statistical model. A negative result is statistically nonsignificant with all mean MF within two standard deviations of the control. (C) 2000 Wiley-Liss, Inc. C1 York Univ, Dept Biol, Toronto, ON M3J 1P3, Canada. Res Toxicol Ctr, Rome, Italy. Natl Inst Hlth Sci, Div Genet & Mutagenesis, Tokyo 158, Japan. Leven Inc, Bogart, GA 30622 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Hlth Canada, Ctr Environm Hlth, Mutagenesis Sect, Ottawa, ON K1A 0L2, Canada. Univ Victoria, Ctr Environm Hlth, Victoria, BC, Canada. Procter & Gamble Co, Ivorydale Tech Ctr, Cincinnati, OH 45217 USA. SRI Int, Toxicol Lab, Menlo Park, CA 94025 USA. Novartis Pharma AG, PCS Tox Path, Genet & Expt Toxicol, Basel, Switzerland. Merck Res Labs, W Point, PA USA. Rhone Poulenc Rorer, Nonclin Safety Assessment, Vitry Sur Seine, France. NIEHS, Mol Mutagenesis Grp, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. Snow Brand Milk Prod Co Ltd, Res Inst Life Sci, Ishibashi, Tochigi, Japan. RP Heddle, JA (reprint author), York Univ, Dept Biol, Room 247,Farquaharson Life Sci Bldg,4700 Keele St, Toronto, ON M3J 1P3, Canada. NR 48 TC 72 Z9 73 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2000 VL 35 IS 3 BP 253 EP 259 DI 10.1002/(SICI)1098-2280(2000)35:3<253::AID-EM11>3.0.CO;2-J PG 7 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 300ZF UT WOS:000086283100011 PM 10737959 ER PT J AU Sams, R Blaydes, B Warbritton, A Lomax, LG Bucci, T Delclos, KB AF Sams, R Blaydes, B Warbritton, A Lomax, LG Bucci, T Delclos, KB TI Differences in the response to oxidative stress and mutant frequency in CD (Sprague-Dawley) and Fisher 344 rats due to an induced inflammatory response SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE rodent air pouch; hprt mutation; apoptosis; 8-hydroxy-2 '-deoxyguanosine; strain differences ID REACTIVE OXYGEN; DNA DAMAGE; HPRT GENE; INHALATION; INVIVO; CARCINOGENESIS; SYSTEM; CANCER; SILICA; URINE AB In this study. the rodent air pouch model was used to examine the production and processing of oxidative DNA damage in two strains of rats commonly used in toxicity testing. An inflammatory response was induced by injecting zymosan A (50 mg) into an air pouch on mole CD (Sprague-Dawley [S-D]) and Fisher 344 F-344 rats, and the animals were then sacrificed at 1, 3, 7, 14, and 28 days (n = 6 per time point per strain). Tissues From the lining of the air pouch were collected for 8-hydroxy-2'-deoxyguonosine (8-OH-dG) analysis and for paraffin embedding. Significant (P < 0.01) increases in 8-OH-dG were observed after day in the DNA from cells lining the air pouch of zymosan A-treated versus control S-D (101.5 +/- 27.1 vs. 23.1 +/- 2.7 8-OH-dG/dG x 10(5)) and F-344 (51.4 +/- 5.3 vs. 14.4 +/- 0.6 8-OH-dG/dG x 10(5)) rats. By 28 days. 8-OH-dG levels had returned to F-344 rats. The frequency of apoptosis was evaluated using the in situ end-labeling (TUNEL) assay, which revealed that zymosan A-treated S-D rats had a significantly (P < 0.05) higher Frequency of apoptosis compared to zymosan A-treated F-344 rats. To examine the potential consequences of these differences in endogenously produced DNA damage and apoptosis, we measured mutations at the hprt locus in fibroblasts of the pouch lining and observed a significant (P < 0.05) increase in the mutant frequency at day 28 in F-344 rats (54.2 +/- 13.6 mutants per 10(6) cells) compared to controls (4.5 +/- 2.0 mutants per 10(6) cells). The mutant frequency was not increased in SD rob. These data demonstrate that strain differences in the production and processing of oxidative DNA damage due to an inflammatory response may impact the long-term pathologic consequences of chronic inflammation. Published 2000 Wiley-Liss, Inc.dagger C1 Natl Ctr Toxicol Res, DBT, Jefferson, AR 72079 USA. Pathol Associates Int, Jefferson, AR USA. RP Sams, R (reprint author), Natl Ctr Toxicol Res, DBT, HFT-110,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 31 TC 3 Z9 3 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2000 VL 35 IS 4 BP 336 EP 342 DI 10.1002/1098-2280(2000)35:4<336::AID-EM8>3.0.CO;2-8 PG 7 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 326PH UT WOS:000087743600008 PM 10861952 ER PT J AU Williams, RL Adams, W Chen, ML Hare, D Hussain, A Lesko, L Patnaik, R Shah, V AF Williams, RL Adams, W Chen, ML Hare, D Hussain, A Lesko, L Patnaik, R Shah, V CA FDA Biopharmaceutics Coordinating TI Where are we now and where do we go next in terms of the scientific basis for regulation on bioavailability and bioequivalence? SO EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS LA English DT Article; Proceedings Paper CT FIP Bio-International 99 Conference CY SEP 29-OCT 01, 1999 CL LONDON, ENGLAND SP Int Pharmacetu Federat, Acad Pharmaceut Sci & Technol, Agcy Evaluat Med Prod, Human Med Evaluat Unit, Bundesinstitut Arzneimmittel & Med Prod, European Federat Pharmaceut Sci, Japan Pharmaceut Assoc, Japan Pharmacuet MFG Assoc, Royal Pharmaceut Soc Great Britain, US Pharmacopoe Convent Inc, Therapeutic Prod Programme, Hlth Canada, US FAO DE bioavailability; bioequivalence; pharmaceutical equivalence; clinical pharmacology; BioInternational ID ABSORPTION C1 US FDA, CDER, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Williams, RL (reprint author), US Pharmacopeia, 12601 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 24 TC 8 Z9 8 U1 1 U2 1 PU MEDECINE ET HYGIENE PI GENEVA 4 PA 78 AVE ROSERALE, 1211 GENEVA 4, SWITZERLAND SN 0378-7966 J9 EUR J DRUG METAB PH JI Eur. J. Drug Metabol. Pharmacokinet. PD JAN-MAR PY 2000 VL 25 IS 1 BP 7 EP 12 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 358PN UT WOS:000089566600003 PM 11032082 ER PT J AU Williams, RL Patnaik, RN Chen, ML AF Williams, RL Patnaik, RN Chen, ML CA FDA Population Individual Bioequiv TI The basis for individual bioequivalence SO EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS LA English DT Article; Proceedings Paper CT FIP Bio-International 99 Conference CY SEP 29-OCT 01, 1999 CL LONDON, ENGLAND SP Int Pharmacetu Federat, Acad Pharmaceut Sci & Technol, Agcy Evaluat Med Prod, Human Med Evaluat Unit, Bundesinstitut Arzneimmittel & Med Prod, European Federat Pharmaceut Sci, Japan Pharmaceut Assoc, Japan Pharmacuet MFG Assoc, Royal Pharmaceut Soc Great Britain, US Pharmacopoe Convent Inc, Therapeutic Prod Programme, Hlth Canada, US FAO DE individual bioequivalence; replicate; non-replicate; bioequivalence criterion; average bioequivalence; subject-by-formulation interaction C1 US FDA, CDER, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Williams, RL (reprint author), US Pharmacopeia, 12601 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 10 TC 6 Z9 6 U1 0 U2 0 PU MEDECINE ET HYGIENE PI GENEVA 4 PA 78 AVE ROSERALE, 1211 GENEVA 4, SWITZERLAND SN 0378-7966 J9 EUR J DRUG METAB PH JI Eur. J. Drug Metabol. Pharmacokinet. PD JAN-MAR PY 2000 VL 25 IS 1 BP 13 EP 17 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 358PN UT WOS:000089566600004 PM 11032083 ER PT J AU Lesko, LJ Bashaw, D Conner, DP Honig, PK AF Lesko, LJ Bashaw, D Conner, DP Honig, PK TI Clinical consequences of 'failed' bioequivalence studies SO EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS LA English DT Article; Proceedings Paper CT FIP Bio-International 99 Conference CY SEP 29-OCT 01, 1999 CL LONDON, ENGLAND SP Int Pharmacetu Federat, Acad Pharmaceut Sci & Technol, Agcy Evaluat Med Prod, Human Med Evaluat Unit, Bundesinstitut Arzneimmittel & Med Prod, European Federat Pharmaceut Sci, Japan Pharmaceut Assoc, Japan Pharmacuet MFG Assoc, Royal Pharmaceut Soc Great Britain, US Pharmacopoe Convent Inc, Therapeutic Prod Programme, Hlth Canada, US FAO C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Lesko, LJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MEDECINE ET HYGIENE PI GENEVA 4 PA 78 AVE ROSERALE, 1211 GENEVA 4, SWITZERLAND SN 0378-7966 J9 EUR J DRUG METAB PH JI Eur. J. Drug Metabol. Pharmacokinet. PD JAN-MAR PY 2000 VL 25 IS 1 BP 69 EP 69 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 358PN UT WOS:000089566600019 ER PT J AU Takeshita, F Ishii, J Ueda, A Ishigatsubo, Y Klinman, DN AF Takeshita, F Ishii, J Ueda, A Ishigatsubo, Y Klinman, DN TI Positive and negative regulatory elements contribute to CpG oligonucleotide-mediated regulation of human IL-6 gene expression SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE IL-6; regulation; CpG oligodeoxynucleotide ID NF-KAPPA-B; HUMAN INTERLEUKIN-6 GENE; NECROSIS-FACTOR-ALPHA; BACTERIAL-DNA; TRANSCRIPTIONAL REGULATION; INTERFERON-GAMMA; PROMOTER; MOTIFS; ACTIVATION; INDUCTION AB Oligonucleotides (ODN) expressing immunostimulatory "CpG motifs" activate human RPMI 8226 myeloma cells to secrete IL-6. Using deletion and site-directed mutagenesis of the human (h)IL-6 promoter region, two positive regulatory elements (the binding sites for the 5'-CCAAT/enhancer binding protein-beta and NF-kappa B) were identified. Two negative regulatory elements, the 3'-retinoblastoma control element (RCE) and the binding site for Epstein-Barr virus C-promoter binding factor 1 (CBF1), also contributed to CpG ODN induction of hIL-6 gene expression. Of interest, CpG ODN treatment induced the dissociation of a repressor protein from its 3'-RCE binding site. Thus, CpG ODN regulation of hIL-6 gene expression involves both enhancer and derepression mechanisms. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. Yokohama City Univ, Sch Med, Dept Internal Med 1, Yokohama, Kanagawa 232, Japan. RP Klinman, DN (reprint author), US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bldg 29A Rm 3 D 10, Bethesda, MD 20892 USA. OI Ishii, Ken/0000-0002-6728-3872 NR 22 TC 28 Z9 28 U1 3 U2 3 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 2000 VL 30 IS 1 BP 108 EP 116 DI 10.1002/1521-4141(200001)30:1<108::AID-IMMU108>3.0.CO;2-4 PG 9 WC Immunology SC Immunology GA 271KM UT WOS:000084592800012 PM 10602032 ER PT S AU Chen, J Dagher, SM Fisher, CE Grunow, W Hattan, DG Kawamura, Y Knaap, AGAC Kuznesof, PM Larsen, JC Meyland, I Pascal, G Riordan, M Walker, R Wilson, JD Akkelidou, D Bellinger, DC Bolger, M Carrington, C Dewailly, E DiNovi, M Eriksen, GS Greig, J Hecker, EFF Herrman, JL Hotchkiss, JH Madsen, C Magos, LPA Mattia, A Moy, G Munro, IC Nishikawa, A Pennington, JA Petersen, B Renwick, AG Resnik, S Schlatter, J Sipes, GI Speijers, GJA Vavasour, E Verger, JP Vilu, R Wallin, H Weatherwax, J Whitehouse, DB AF Chen, J Dagher, SM Fisher, CE Grunow, W Hattan, DG Kawamura, Y Knaap, AGAC Kuznesof, PM Larsen, JC Meyland, I Pascal, G Riordan, M Walker, R Wilson, JD Akkelidou, D Bellinger, DC Bolger, M Carrington, C Dewailly, E DiNovi, M Eriksen, GS Greig, J Hecker, EFF Herrman, JL Hotchkiss, JH Madsen, C Magos, LPA Mattia, A Moy, G Munro, IC Nishikawa, A Pennington, JA Petersen, B Renwick, AG Resnik, S Schlatter, J Sipes, GI Speijers, GJA Vavasour, E Verger, JP Vilu, R Wallin, H Weatherwax, J Whitehouse, DB CA Joint FAO WHO Expert Committee Foo GP WHO WHO TI Evaluation of certain food additives and contaminants SO EVALUATION OF CERTAIN FOOD ADDITIVES AND CONTAMINANTS, 53RD REPORT SE WHO Technical Report Series LA English DT Article; Proceedings Paper CT 53rd Joint Meeting of the FAO/WHO on Food Additives CY JUN 01-10, 1999 CL ROME, ITALY SP FAO, WHO C1 Chinese Acad Prevent Med, Inst Nutr & Food Hyg, Beijing, Peoples R China. Food Regulatory Affairs, Bowden, Cheshire, England. FAO, Food & Nutr Div, Food Qual & Stand Serv, I-00100 Rome, Italy. Natl Food Adm Toxicol Lab, Helsinki, Finland. Tallinn Univ Technol, Dept Biochem, EE-200108 Tallinn, Estonia. Natl Ctr Study & Res Nutr & Food, Observ Food Consumpt, Paris, France. Hlth Canada, Chem Hlth Hazard Assessment Div, Bur Chem Safety, Food Directorate,Hlth Protect Branch, Ottawa, ON K1A 0L2, Canada. Natl Inst Publ Hlth & Environm Protect, Ctr Subst & Risk Assessment, NL-3720 BA Bilthoven, Netherlands. Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA. Univ Zurich, Inst Vet Pharmacol & Toxicol, Fed Off Publ Hlth, Zurich, Switzerland. Fac Exact & Nat Sci, Dept Ind, Buenos Aires, DF, Argentina. Univ Southampton, Clin Pharmacol Grp, Southampton, Hants, England. Novigen Sci Inc, Washington, DC USA. NIH, Div Nutr Res Coordinat, Bethesda, MD 20892 USA. Natl Inst Hlth Sci, Div Pathol, Biol Safety Res Ctr, Tokyo 158, Japan. CanTox Hlth Sci Int, Mississauga, ON, Canada. WHO, Programme Food Safety, CH-1211 Geneva, Switzerland. US FDA, Div Prod Policy, Off Premarket Approval, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. TNO BIBRA Int Ltd, Carshalton, Surrey, England. Minist Food Agr & Fisheries, Inst Food Safety & Toxicol, Danish Vet & Food Adm, Dept Biochem & Mol Toxicol, Soborg, Denmark. Cornell Univ, Dept Food Sci, Ithaca, NY 14853 USA. WHO, Int Programme Chem Safety, CH-1211 Geneva, Switzerland. Minist Agr Nat Management & Fisheries, Codex Comm Food Addit & Contaminants, Risk Subst & Nut Div, Dept Environm Qual & Hlth, The Hague, Netherlands. Dept Hlth, Joint Food Safety & Stand Grp, London SE1 6TE, England. Swedish Univ Agr Sci, Dept Anim Nutr & Management, S-75007 Uppsala, Sweden. US FDA, Div Prod Manufacture & Use, Off Premarket Approval, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Publ Hlth Ctr Quebec, Environm Hlth Serv, Beauport, PQ, Canada. US FDA, Contaminants Branch, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Harvard Univ, Sch Med, Childrens Hosp, Neuroepidemiol Unit, Boston, MA USA. Minist Hlth, State Gen Lab, Nicosia, Cyprus. Australia New Zealand Food Author, Canberra, ACT, Australia. Univ Surrey, Sch Biol Sci, Guildford GU2 5XH, Surrey, England. Minist Hlth, Food & Nutr Sect, Wellington, New Zealand. Natl Inst Agr Res, Sci Steering Comm European Union, Paris, France. Minist Food Agr & Fisheries, Inst Food Res & Nutr, Danish Vet & Food Adm, Soborg, Denmark. Natl Inst Hlth Sci, Div Food Addit, Tokyo 158, Japan. US FDA, Div Hlth Effects Evaluat, Off Premarket Approval, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Fed Int Hlth Protect Consumers & Vet Med, Food Toxicol Div, Berlin, Germany. Minsist Agr Fisheries & Food, Risk Anal & Int Coordinat Branch, London, England. Amer Univ Beirut, Dept Biol, Beirut, Lebanon. RP Chen, J (reprint author), Chinese Acad Prevent Med, Inst Nutr & Food Hyg, Beijing, Peoples R China. NR 191 TC 6 Z9 6 U1 1 U2 5 PU WORLD HEALTH ORGANIZATION PI GENEVA PA DISTRIBUTION & SALES SERVICE, 1211 27 GENEVA, SWITZERLAND SN 0512-3054 BN 92-4-120896-1 J9 WHO TECH REP SER JI WHO Tech. Rep. Ser. PY 2000 VL 896 BP 1 EP 128 PG 128 WC Chemistry, Applied; Food Science & Technology; Public, Environmental & Occupational Health; Toxicology SC Chemistry; Food Science & Technology; Public, Environmental & Occupational Health; Toxicology GA BS11W UT WOS:000168725000001 ER PT S CA Joint FAO WHO Expert Comm Food GP WHO TI Evaluation of certain veterinary drug residues in food - Introduction SO EVALUATION OF CERTAIN VETERINARY DRUG RESIDUES IN FOOD, 52ND REPORT SE WHO TECHNICAL REPORT SERIES LA English DT Article; Proceedings Paper CT 52nd Joint Meeting of the FAO/WHO Expert Committe on Food Additives CY FEB 02-11, 1999 CL FAO HEADQUARTERS, ROME, ITALY SP WHO HO FAO HEADQUARTERS ID INTESTINAL MICROFLORA; FLORA C1 Swedish Univ Agr Sci, Fac Vet Med, Dept Pharmacol & Toxicol, Uppsala, Sweden. Fed Inst Hlth Protect Consumers & Vet Med, Berlin, Germany. Univ Zimbabwe, Fac Vet Sci, Dept Preclin Vet Studies, Harare, Zimbabwe. Natl Ctr Vet & Food Studies, Natl Agcy Vet Med, Fougeres, France. Imperial Coll Sch Med, Div Med, Clin Pharmacol Sect, London, England. NIEHS, Res Triangle Pk, NC 27709 USA. USDA, Off Publ Hlth & Sci, Food Safety & Inspect Serv, Washington, DC 20250 USA. Sokoine Univ Agr, Dept Vet Physiol Biochem Pharmacol & Toxicol, Morogoro, Tanzania. Canadian Food Inspect Agcy, Hlth Anim Lab, Ctr Vet Drug Residues, Saskatoon, SK, Canada. US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, Rockville, MD 20857 USA. Univ Nairobi, Coll Agr & Vet Sci, Fac Vet Med, Dept Publ Hlth Pharmacol & Toxicol, Kabete, Kenya. Univ Sao Paulo, Sch Vet Med, Dept Pathol, Appl Pharmacol & Toxicol Lab, Sao Paulo, Brazil. Vet Org Iran, Vet Diagnost Ctr, Pharmacokinet Unit, Tehran, Iran. Natl Inst Publ Hlth & Environm, Lab Residue Anal, NL-3720 BA Bilthoven, Netherlands. US FDA, Natl Ctr Toxicol Res, Div Microbiol & Chem, Jefferson, AR 72079 USA. Aviano Canc Ctr, Epidemiol Unit, I-33081 Aviano, Italy. WHO, Int Programme Chem Safety, CH-1211 Geneva, Switzerland. US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20857 USA. US FDA, Ctr Vet Med, Rockville, MD 20857 USA. Int Agcy Res Canc, Unit Carcinogen Identificat & Evaluat, F-69372 Lyon, France. Natl Inst Hlth Sci, Biol Safety Res Ctr, Div Pathol, Sect 3, Tokyo 158, Japan. Inst Food Res, Dept Biochem, Norwich NR4 7UA, Norfolk, England. Danish Vet & Food Adm, Inst Food Safety & Toxicol, Soborg, Denmark. Natl Inst Publ Hlth & Environm, Ctr Subst & Risk Assessment, NL-3720 BA Bilthoven, Netherlands. Univ Guelph, Canadian Network Toxicol Ctr, Guelph, ON N1G 2W1, Canada. Minist Agr, Kimron Vet Inst, Natl Residue Lab, Bet Dagan, Israel. US FDA, Ctr Vet Med, Rockville, MD 20857 USA. Univ Leipzig, Fac Vet Med, Inst Pharmacol Pharm & Toxicol, D-7010 Leipzig, Germany. FAO, Food & Nutr Div, Food Qual & Stand Serv, Food Qual Liaison Grp, I-00100 Rome, Italy. US FDA, Ctr Vet Med, Residue Chem Team, Off New Anim Drug Evaluat, Rockville, MD 20857 USA. Natl Inst Vet Res, Dept Pharmacol & Toxicol, Pulawy, Poland. RP Swedish Univ Agr Sci, Fac Vet Med, Dept Pharmacol & Toxicol, Uppsala, Sweden. NR 24 TC 0 Z9 0 U1 1 U2 2 PU WORLD HEALTH ORGANIZATION PI GENEVA PA 1211 27 GENEVA, SWITZERLAND SN 0512-3054 BN 92-4-120893-7 J9 WHO TECH REP SER PY 2000 VL 893 BP 1 EP 89 PG 89 WC Chemistry, Applied; Food Science & Technology; Public, Environmental & Occupational Health; Toxicology SC Chemistry; Food Science & Technology; Public, Environmental & Occupational Health; Toxicology GA BS11V UT WOS:000168724800001 ER PT J AU Flurer, CL Crowe, JB Wolnik, KA AF Flurer, CL Crowe, JB Wolnik, KA TI Detection of adulteration of locust bean gum with guar gum by capillary electrophoresis and polarized light microscopy SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE capillary electrophoresis; polarized light microscopy; locust bean gum; guar gum; protein profiles; product adulteration ID CHROMATOGRAPHY AB Capillary electrophoresis (CE) and polarized light microscopy (PLM) were utilized in the detection of the adulteration of locust bean gum with guar gum. For CE analyses, standards of locust bean and guar gums were extracted with 30% CH3CN, removing the residual proteins from the gum matrix. a 8.75 mM NaH2PO4-20.6 mM Na2B4O7 buffer, pH 9, was used to separate these proteins and to identify marker proteins that were present in the guar gum. These markers did not co-migrate with components in the extracts of mechanically processed locust bean gum, and are used as indicators of adulteration. Using PLM with toluidine blue and iodine staining techniques, unadulterated locust bean gum samples were distinguished from mixed samples through the differential staining of components in locust bean versus guar and tara gums. These experiments in the use of CE and PLM provide orthogonal and complementary methods for the verification of 'true' positives and the elimination of 'false' positives. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Flurer, CL (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. NR 23 TC 12 Z9 13 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD JAN PY 2000 VL 17 IS 1 BP 3 EP 15 DI 10.1080/026520300283540 PG 13 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 298WQ UT WOS:000086162900001 PM 10793850 ER PT J AU Henney, JE AF Henney, JE TI Remarks of the commissioner of food and drugs SO FOOD AND DRUG LAW JOURNAL LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Henney, JE (reprint author), US FDA, Rockville, MD 20857 USA. NR 2 TC 6 Z9 6 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 2000 VL 55 IS 1 BP 1 EP 4 PG 4 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 306RY UT WOS:000086611100001 PM 12269355 ER PT B AU Kaferstein, FK Jonas, DA AF Kaferstein, FK Jonas, DA BE Grimme, LH Dumontet, S TI Genetic modification and food safety: Views of the world health organization SO FOOD QUALITY, NUTRITION AND HEALTH LA English DT Proceedings Paper CT 5th Heidelberg Nutrition Forum/ECBA Symposium and Workshop CY FEB 27-MAR 01, 1998 CL HEIDELBERG, GERMANY SP European Countries Biologists Assoc C1 Joint Inst Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Kaferstein, FK (reprint author), Joint Inst Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 7 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 3-540-65997-8 PY 2000 BP 93 EP 99 PG 7 WC Food Science & Technology SC Food Science & Technology GA BQ01J UT WOS:000086854300008 ER PT J AU Alayash, AI AF Alayash, AI TI Hemoglobin-based blood substitutes and the hazards of blood radicals SO FREE RADICAL RESEARCH LA English DT Review DE hemoglobin; blood substitutes; free radicals ID CROSS-LINKED HEMOGLOBIN; CELL-FREE HEMOGLOBIN; NITRIC-OXIDE; OXYGEN CARRIERS; FERRYL INTERMEDIATE; HYDROGEN-PEROXIDE; MYOGLOBIN; PHARMACOLOGY; OXIDATION; EFFICACY AB Cell-free hemoglobins, chemically altered or genetically expressed in microbial host systems, have been developed as oxygen-carrying therapeutics. Site-directed modifications are introduced and serve to stabilize the protein molecules in a tetrameric and/or a polymeric functional form. Animal studies, as well as recent clinical studies, have suggested these proteins probably deliver oxygen to tissues. However, concerns still persist regarding the interference of hemoglobin and its oxidation products with the vascular redox balance, potentially impeding its clinical usefulness. This article reviews our current understanding of heme-mediated toxicities and some of the emerging protective strategies used to overcome hemoglobin side reactions. C1 US FDA, Ctr Biol Evaluat & Res, Lab Plasma Derivat, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Plasma Derivat, Natl Inst Hlth Campus,Bldg 29,Rm 112,8800 Rockvil, Bethesda, MD 20892 USA. NR 42 TC 28 Z9 29 U1 0 U2 4 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 2000 VL 33 IS 4 BP 341 EP 348 DI 10.1080/10715760000300881 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 358PX UT WOS:000089567400001 PM 11022843 ER PT J AU Harris, C Boivin, W Boyd, S Coletta, J Kerr, L Kempa, K Aronow, S AF Harris, C Boivin, W Boyd, S Coletta, J Kerr, L Kempa, K Aronow, S TI Electromagnetic field strength levels surrounding electronic article surveillance (EAS) systems SO HEALTH PHYSICS LA English DT Article DE electromagnetic fields; instruments; magnetic fields; medical radiation ID PACEMAKER; DEVICES AB Electronic article surveillance (EAS) is used in many applications throughout the world to prevent theft. EAS systems produce electromagnetic (EM) energy around exits to create an FM interrogation zone through which protected items must pass before leaving the establishment. Specially designed EAS tags are attached to these items and must either be deactivated or removed prior to passing through the EAS EM interrogation zone to prevent the alarm from sounding. Recent reports in the scientific literature have noted the possibility that EM energy transmitted by EAS systems may interfere with the proper operation of sensitive electronic medical devices. The Food and Drug Administration has the regulatory responsibility to ensure the safety and effectiveness of medical devices. Because of the possibility of electromagnetic interference (EMI) between EAS systems and electronic medical devices, irt situ measurements of the electric and magnetic fields were made around various types of EAS systems. Field strength levels were measured around four types of EAS systems: audio frequency magnetic, pulsed magnetic resonant, radio frequency, and microwave. Field strengths from these EAS systems varied with magnetic fields as high as 1073.6 Am-1 (in close proximity to the audio frequency magnetic FAS system towers), and electric fields up to 23.8 Vm(-1) (in close proximity to the microwave EAS system towers). Medical devices are only required to withstand 3 Vm(-1) by the International Electrotechnical Commission's current medical device standards. The modulation scheme of the signal transmitted by some types of EAS systems (especially the pulsed magnetic resonant) has been shown to be more likely to cause EMI with electronic medical devices. This study complements other work in the field by attaching specific characteristics to EAS transmitted EM energy. The quantitative data could be used to relate medical device EMI with specific field strength levels and signal waveforms. This is one of several efforts being made by the FDA, the electronic medical device industry and the FAS industry to mitigate the potential for EMI between EAS and medical devices. C1 US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. NR 13 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD JAN PY 2000 VL 78 IS 1 BP 21 EP 27 DI 10.1097/00004032-200001000-00005 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 266RL UT WOS:000084313700005 PM 10608306 ER PT J AU Major, ME Feinstone, SM AF Major, ME Feinstone, SM TI Characterization of hepatitis C virus infectious clones in chimpanzees: Long-term studies SO HEPATITIS C VIRUSES SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID CYTOTOXIC T-LYMPHOCYTES; HUMORAL IMMUNE-RESPONSE; NON-B HEPATITIS; HYPERVARIABLE REGION-1; ANTIBODY-RESPONSE; CDNA CLONE; NONSTRUCTURAL PROTEIN-3; ENVELOPE PROTEINS; VIRAL-HEPATITIS; GENETIC DRIFT C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Hepatitis Viruses, Bethesda, MD 20892 USA. RP Major, ME (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Hepatitis Viruses, Bldg 29A,Rm 1D14,HFM448,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 54 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2000 VL 242 BP 279 EP 298 PG 20 WC Immunology; Microbiology SC Immunology; Microbiology GA BP10M UT WOS:000084132500013 PM 10592665 ER PT J AU Laborda, J AF Laborda, J TI The role of the epidermal growth factor-like protein dlk in cell differentiation SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Review DE EGF-like; homeotic genes; adipogenesis; neuroendocrine; differentiation ID FETAL ANTIGEN-1 FA1; ADIPOCYTE DIFFERENTIATION; BONE-MARROW; TRANSCRIPTIONAL CONTROL; STROMAL CELLS; REPEAT MOTIFS; PREF-1; GENE; PG2; ADIPOGENESIS AB This review focuses on the current knowledge about the function of the EGF-like homeotic protein dlk. dlk is a transmembrane protein that possesses six Epidermal Growth Factor-like sequences at the extracellular domain, a single transmembrane domain and a short intracellular tail. Because of its overall structure and amino acid homology, dlk belongs to the EGF-like homeotic protein family. This family includes proteins such as the Notch receptor and its homologues, as well as Notch ligands, such as Delta, Serrate, and their mammalian homologues D111, D112 and D113 and Jagged 1 and Jagged 2. (For a recent review see Fleming, 1998). dlk is highly expressed by preadipose cell lines, and neuroendocrine tumors, such as pheochromocytomas and neuroblastomas. dlk has been involved in several differentiation processes, such as adipogenesis, hematopoiesis and B cell lymphopoiesis, and neuroendocrine differentiation, including the differentiation of pancreas and the adrenal gland. The extracellular region of dlk can be released by action of an unknown protease and this soluble dlk variant accumulates in the amniotic fluid and is able to inhibit adipocyte differentiation in vitro. Recent evidence indicates, however, that membrane-associated dlk variants play a positive role in the differentiation process. These findings suggest that dlk plays an important role in differentiation and tumorigenesis of several cellular types. C1 Ctr Biol Evaluat & Res, Immunobiol Lab, Div Monoclonal Antibodies, Rockville, MD USA. RP Laborda, J (reprint author), Univ Castilla La Mancha, Fac Med, Edificio Benjamin Palencia S-N,Campus Albacete, Albacete 02071, Spain. RI Laborda, Jorge/L-5726-2014 OI Laborda, Jorge/0000-0002-9210-838X NR 40 TC 121 Z9 127 U1 0 U2 5 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD JAN PY 2000 VL 15 IS 1 BP 119 EP 129 PG 11 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 277VU UT WOS:000084954900015 PM 10668203 ER PT J AU Curry, J Khaidakov, M Glickman, BW AF Curry, J Khaidakov, M Glickman, BW TI Russian mutational spectrum differs from that of their western counterparts SO HUMAN MUTATION LA English DT Article DE monozygotic twins; Russian; T-cell clonal assay; HPRT; mutational spectra ID T-LYMPHOCYTES; MUTANT FREQUENCIES; HPRT MUTANT; MUTAGENESIS; GENE; CELLS; CDNA; AGE AB It has been previously noted that the hypoxanthine-guanine phosphoribosyltransferase (HPRT) mutant frequency of Russian subjects is significantly higher than age-matched Western counterparts. To further explore this difference, approximately 100 mutants collected from Russian twins reported in a previous study have been sequenced and compared to an aged matched Western mutant dataset, The mutational spectrum of the Russian subjects was significantly different (Adams and Skopek Monte Carlo rest, P = 0.004). Curiously, this younger Russian spectrum resembles that recovered from older individuals in the West. Specifically, A:T-->C:G transversions are significantly over-represented (Fisher's Exact test, P = 0.003) in the twin spectrum as compared to the young (age less than or equal to 35) Western spectrum. Even more noteworthy is the observation that 42% (23/55) of the base substitutions, almost double the expected value, have not been previously reported. These observations lead to the conclusion that this group of young Russian subjects has a mutational pattern which is distinct from the pattern of mutation observed in Western counterparts. The origin of this difference, whether related to genotoxic challenge, repair, or avoidance, cannot be distinguished, but diet and other lifestyle factors clearly may be responsible. Hum Mutat 15:439-446, 2000. (C) 2000 Wiley-Liss, Inc. C1 Univ Victoria, Ctr Environm Hlth, Victoria, BC, Canada. US FDA, Natl Ctr Toxicol Res, Dept Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Univ Victoria, Dept Biol, Victoria, BC V8W 2Y2, Canada. RP Curry, J (reprint author), Univ Calif Berkeley, Sch Publ Hlth, 140 Warren Hall, Berkeley, CA 94720 USA. NR 19 TC 2 Z9 2 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 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2000 VL 15 IS 5 BP 439 EP 446 DI 10.1002/(SICI)1098-1004(200005)15:5<439::AID-HUMU5>3.0.CO;2-Q PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 310NR UT WOS:000086834700005 PM 10790205 ER PT J AU Wear, KA AF Wear, KA TI The effects of frequency-dependent attenuation and dispersion on sound speed measurements: Applications in human trabecular bone SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID ULTRASONIC-ATTENUATION; ACOUSTIC PROPERTIES; CANCELLOUS BONE; HIP FRACTURE; IN-VITRO; WAVE-PROPAGATION; OS CALCIS; 100 MHZ; VELOCITY; DENSITY AB Sound speed may be measured by comparing the transit time of a broadband ultrasonic pulse transmitted through an object with that transmitted through a reference water path. If the speed of sound in water and the thickness of the sample are known, the speed of sound in the object may be computed. To measure the transit time differential, a marker such as a zero-crossing, may be used. A sound speed difference between the object and water shifts all markers backward or forward. Frequency-dependent attenuation and dispersion may alter the spectral characteristics of the waveform, thereby distorting the locations of markers and introducing variations in sound-speed estimates. Theory is derived to correct for this distortion for Gaussian pulses propagating through linearly attenuating, weakly dispersive media. The theory is validated using numerical analysis, measurements on a tissue mimicking phantom, and on 24 human calcaneus samples in vitro. Variations in soft tissue-like media are generally not exceptionally large for most applications but can be substantial, particularly for high bandwidth pulses propagating through media with high attenuation coefficients. At 500 kHz, variations in velocity estimates in bone can be very substantial, on the order of 40 to 50 m/s because of the high attenuation coefficient of bone. In trabecular bone, the effects of frequency-dependent attenuation are considerable, and the effects of dispersion are negligible. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-142, Rockville, MD 20852 USA. NR 49 TC 79 Z9 80 U1 2 U2 8 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0885-3010 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD JAN PY 2000 VL 47 IS 1 BP 265 EP 273 DI 10.1109/58.818770 PG 9 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 280KN UT WOS:000085102100028 PM 18238539 ER PT J AU Klinman, DM Ishii, KJ Verthelyi, D AF Klinman, DM Ishii, KJ Verthelyi, D TI CpG DNA augments the immunogenicity of plasmid DNA vaccines SO IMMUNOBIOLOGY OF BACTERIAL CPG-DNA SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID BACTERIAL-DNA; IMMUNOSTIMULATORY DNA; IMMUNE-RESPONSES; INTERFERON-GAMMA; B-CELL; CIRCUMSPOROZOITE PROTEIN; DENDRITIC CELLS; MICE; IMMUNIZATION; ACTIVATION C1 US FDA, Sect Retroviral Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Sect Retroviral Immunol, Ctr Biol Evaluat & Res, Bldg 29A,Room 3D10, Bethesda, MD 20892 USA. RI Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 35 TC 25 Z9 27 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2000 VL 247 BP 131 EP 142 PG 12 WC Immunology; Microbiology SC Immunology; Microbiology GA BQ27J UT WOS:000087771800009 PM 10689784 ER PT J AU Garcia-Ojeda, PA Monser, ME Rubinstein, LJ Jennings, HJ Stein, KE AF Garcia-Ojeda, PA Monser, ME Rubinstein, LJ Jennings, HJ Stein, KE TI Murine immune response to Neisseria meningitidis group C capsular polysaccharide: Analysis of monoclonal antibodies generated in response to a thymus-independent antigen and a thymus-dependent toxoid conjugate vaccine SO INFECTION AND IMMUNITY LA English DT Article ID INFLUENZAE TYPE-B; RANDOMIZED CONTROLLED TRIAL; MEMBRANE PROTEIN COMPLEX; VH GENE SEGMENTS; GROUP-A; MOLECULAR CHARACTERIZATION; CRYPTOCOCCUS-NEOFORMANS; IMMUNOLOGICAL MEMORY; REPERTOIRE SHIFT; VARIABLE REGIONS AB Antibody (Ab) responses to polysaccharides (PSs) such as Neisseria meningitidis group C PS (MCPS) are characterized as being thymus independent (TI) and are restricted with regard to clonotype and isotype expression. PS conjugated to proteins, e.g., MCPS coupled to tetanus toroid (MCPS-TT), elicits a thymus-dependent (TD) response. In order to understand the influence of the form of a vaccine (TI versus TD) on the Ab repertoire, we generated monoclonal antibody (MAb) panels from mice immunized and boosted with MCPS or MCPS-TT in different ways. The panels of MAbs were examined for isotype, fine specificity, affinity, and V-H gene family usage. The use of MCPS-TT resulted in a shift in the isotype from immunoglobulin M (IgM) and IgG3 elicited in response to the MCPS to primarily IgG1. This isotype shift was accompanied by a change in the fine specificity of the response to the conjugate compared to that of PS. New fine specificities and increased affinity were observed in response to the TD antigen (Ag). Dot blot and Northern analyses of MCPS MAbs revealed that V-H gene family usage is dominated by V(H)J558, used by 23 of 39 MAbs. V(H)3609 was seen in three MAbs of restricted fine specificity. V(H)Q52, V(H)7183, and V(H)VGAM3-8 were seen in more than one MAb across these panels, while V(H)10 and V(H)X24 were detected only once in response to the TI-2 Ag. All MAbs in the panels utilized kappa light chains, and all functional J(kappa) genes were expressed. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. Natl Res Council Canada, Div Biol Sci, Ottawa, ON K1A 0R6, Canada. RP Stein, KE (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, 29 Lincoln Dr, Bethesda, MD 20892 USA. NR 69 TC 24 Z9 25 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2000 VL 68 IS 1 BP 239 EP 246 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 266LQ UT WOS:000084301800035 PM 10603394 ER PT J AU Epstein, SL Stack, A Misplon, JA Lo, CY Mostowski, H Bennink, J Subbarao, K AF Epstein, SL Stack, A Misplon, JA Lo, CY Mostowski, H Bennink, J Subbarao, K TI Vaccination with DNA encoding internal proteins of influenza virus does not require CD8(+) cytotoxic T lymphocytes: either CD4(+) or CD8(+) T cells can promote survival and recovery after challenge SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE infectious immunity-virus; influenza; T lymphocytes; lung; transgenic/knockout ID I-DEFICIENT MICE; A VIRUS; BETA(2)-MICROGLOBULIN-DEFICIENT MICE; VACCINIA VIRUS; BETA-2-MICROGLOBULIN-DEFICIENT MICE; RESPIRATORY-INFECTION; MONOCLONAL-ANTIBODIES; HETEROTYPIC IMMUNITY; PROTECTIVE IMMUNITY; EFFECTOR FUNCTION AB DNA vaccination offers the advantages of viral gene expression within host cells without the risks of infectious virus. Like viral vaccines, DNA vaccines encoding internal influenza virus proteins can induce immunity to conserved epitopes and so may defend the host against a broad range of viral variants, CD8(+) cytotoxic T lymphocytes (CTL) have been described as essential effecters in protection by influenza nucleoprotein (NP), although a lesser role of CD4(+) cells has been reported. We immunized mice with plasmids encoding influenza virus NP and matrix (M). NP + M DNA allowed B6 mice to survive otherwise lethal challenge infection, but did not protect BG-beta(2)m(-/-) mice defective in CD8(+) CTL. However, this does not prove CTL are required, because beta(2)m(-/-) mice have multiple immune abnormalities. We used acute T cell depletion in vivo to identify effecters critical for defense against challenge infection. Since lung lymphocytes are relevant to virus clearance, surface phenotypes and cytolytic activity of lung lymphocytes were analyzed in depleted animals, along with lethal challenge studies. Depletion of either CD4(+) or CD8(+) T cells in NP + M DNA-immunized BALB/c mice during the challenge period did not significantly decrease survival, while simultaneous depletion of CD4+ and CD8(+) cells or depletion of all CD90(+) cells completely abrogated survival. We conclude that T cell immunity induced by NP + M DNA vaccination is responsible for immune defense, but CD8(+) T cells are not essential in the active response to this vaccination. Either CD4(+) or CD8(+) T cells can promote survival and recovery in the absence of the other subset. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Mol Immunol Lab, Bethesda, MD 20892 USA. NIAID, Viral Dis Lab, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Influenza Branch, Atlanta, GA 30333 USA. RP Epstein, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Mol Immunol Lab, HFM-521,Bldg 29B,Room 2G15,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 75 TC 54 Z9 56 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JAN PY 2000 VL 12 IS 1 BP 91 EP 101 DI 10.1093/intimm/12.1.91 PG 11 WC Immunology SC Immunology GA 277HD UT WOS:000084925900011 PM 10607754 ER PT J AU Jacobs, A Brown, P Wilkin, J AF Jacobs, A Brown, P Wilkin, J TI Letter to the Editor SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Letter ID TITANIUM-DIOXIDE; SKIN C1 US FDA, CDER, Div Dermatol & Dent Drug Prod, Rockville, MD 20857 USA. RP Jacobs, A (reprint author), US FDA, CDER, Div Dermatol & Dent Drug Prod, Rockville, MD 20857 USA. OI Bescos, Monica/0000-0002-6203-4690 NR 13 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD JAN-FEB PY 2000 VL 19 IS 1 BP 67 EP 68 PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 295JX UT WOS:000085963900010 ER PT J AU Laughren, T AF Laughren, T TI Regulatory issues on behavioral and psychological symptoms of dementia in the United States SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Article; Proceedings Paper CT Meeting of the International-Psychogeriatric-Association on Behavioral and Psychological Symptoms of Dementia CY 1999 CL LANSDOWNE, VIRGINIA SP Int Psychogeriatr Assoc C1 US FDA, Psychiat Drug Prod Grp, Div Neuropharmacol Drug Prod, Rockville, MD 20857 USA. RP Laughren, T (reprint author), US FDA, Psychiat Drug Prod Grp, Div Neuropharmacol Drug Prod, HFD-120,5600 Fishers Lane, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PY 2000 VL 12 SU 1 BP 331 EP 336 DI 10.1017/S1041610200007237 PG 6 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 410HL UT WOS:000167434500055 ER PT J AU Colman, E AF Colman, E TI Robert Graves and the origins of Irish medical journalism SO IRISH JOURNAL OF MEDICAL SCIENCE LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Colman, E (reprint author), US FDA, Rockville, MD 20857 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU ROYAL ACADEMY MEDICINE PI DUBLIN PA 6 KILDARE ST, DUBLIN 2, IRELAND SN 0021-1265 J9 IRISH J MED SCI JI Irish J. Med. Sci. PD JAN-MAR PY 2000 VL 169 IS 1 BP 10 EP 11 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 316KN UT WOS:000087166300002 PM 10846848 ER PT J AU Baier, R Axelson, E Meyer, A Carter, L Kaplan, D Picciolo, G Jahan, S AF Baier, R Axelson, E Meyer, A Carter, L Kaplan, D Picciolo, G Jahan, S TI The body's response to deliberate implants: Phagocytic cell responses to large substrata vs. small particles SO JOURNAL OF ADHESION LA English DT Article DE particles; phagocytosis; monocyte-derived macrophages; reactive oxygen intermediates; implants; spreading; chemiluminescence ID RESPIRATORY BURST; HYDROGEN-PEROXIDE; MACROPHAGES; SUPEROXIDE AB It is important to characterize possible inflammatory responses to small particles, and to separate clearly these effects from responses to larger objects nearby. This research used a chemiluminescent assay. scanning electron micrographs, and energy dispersive X-ray spectra to monitor inflammation-related reactive oxygen intermediate (ROI) production and morphological alterations of human monocyte-derived macrophages interacting with the walls of apolar and polar polystyrene cuvettes, in the absence and presence of small particles of surface-characterized Teflon(TM) polyethylene, Co-Cr-Mo alloy. titanium and alumina. The two types of polystyrene substrata represent the "bacterial" las produced) and "tissue culture" (gas-plasma-treated [GPT]) materials widely used in biological testing and tissue culture. Monocyle-derived macrophage spreading during contact with the higher-surface-energy, more polar substratum suppressed "oxidative bursts'' to lower levels than expressed from rounded cells in contact with the lower-energy, apolar substratum, Particulate matter engulfed by both rounded and spread cells did not significantly enhance ROI production beyond levels observed for no-particle controls during the one-hour exposure time. Biocompatibility of some implants might be related to cell-spreading-induced suppression of ROI production, improving the tissue integration of GPT implants. C1 SUNY Buffalo, Ind Univ Ctr Biosurfaces, Buffalo, NY 14214 USA. SUNY Buffalo, Dept Oral Diagnost Sci, Buffalo, NY 14214 USA. US FDA, Rockville, MD 20857 USA. Univ Memphis, Memphis, TN 38152 USA. RP Baier, R (reprint author), SUNY Buffalo, Ind Univ Ctr Biosurfaces, 110 Parker Hall, Buffalo, NY 14214 USA. NR 34 TC 3 Z9 3 U1 1 U2 4 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 0021-8464 J9 J ADHESION JI J. Adhes. PY 2000 VL 74 IS 1-4 BP 79 EP + DI 10.1080/00218460008034525 PG 25 WC Engineering, Chemical; Materials Science, Multidisciplinary; Mechanics SC Engineering; Materials Science; Mechanics GA 408UF UT WOS:000167345500005 ER PT J AU Chen, Z Rihs, HP Slater, JE Paupore, EJ Schneider, EM Baur, X AF Chen, Z Rihs, HP Slater, JE Paupore, EJ Schneider, EM Baur, X TI The absence of Hev b 5 in capture antigen may cause false-negative results in serologic assays for latex-specific IgE antibodies SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 BGFA, Bochum, Germany. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 249 BP S83 EP S83 DI 10.1016/S0091-6749(00)90679-1 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100247 ER PT J AU Choudhury, BK Wild, JS Mileski, WJ Klinman, DM Alam, R Sur, S AF Choudhury, BK Wild, JS Mileski, WJ Klinman, DM Alam, R Sur, S TI Internalization of CpG DNA by alveolar macrophages rapidly phosphorylates p38 MAP kinase and induces IFN-g, IL-12 mRNA expression, and IL-18 production SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Univ Texas, Med Branch, NIH Asthma Ctr, Galveston, TX 77550 USA. Univ Texas, Med Branch, Dept Surg, Galveston, TX 77550 USA. US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 489 BP S160 EP S160 DI 10.1016/S0091-6749(00)90918-7 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100486 ER PT J AU de Silva, H Sutherland, M Suphioglu, C McLellan, S Slater, J Rolland, J O'Hehir, R AF de Silva, H Sutherland, M Suphioglu, C McLellan, S Slater, J Rolland, J O'Hehir, R TI Human T cell epitopes of the latex allergen hev b 5 in health care SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Monash Univ, Sch Med, Dept Allergy Asthma & Clin Immunol, Alfred Hosp, Prahran, Vic, Australia. US FDA, Ctr Biol Evaluat & Res, Lab Immunobiochem, Rockville, MD 20857 USA. RI O'Hehir, Robyn/H-3627-2011 OI O'Hehir, Robyn/0000-0002-3489-7595 NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 713 BP S241 EP S241 DI 10.1016/S0091-6749(00)91141-2 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100709 ER PT J AU Paupore, EJ Slater, JE AF Paupore, EJ Slater, JE TI Site-directed mutagenesis of the latex allergen Hev b 5 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 712 BP S241 EP S241 DI 10.1016/S0091-6749(00)91140-0 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100708 ER PT J AU Poley, GE Slater, JE AF Poley, GE Slater, JE TI Mice immunized with avocado have high titer specific IgG antibody to natural rubber latex proteins SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Childrens Natl Med Ctr, Childrens Res Inst, Washington, DC 20010 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 708 BP S239 EP S239 DI 10.1016/S0091-6749(00)91136-9 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100704 ER PT J AU Slater, JE Pastor, RW AF Slater, JE Pastor, RW TI The determination of equivalent doses of standardized allergen vaccines SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 212 BP S69 EP S69 DI 10.1016/S0091-6749(00)90642-0 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100210 ER PT J AU Solanki, MD Slater, JE AF Solanki, MD Slater, JE TI The effects of lipopolysaccharide (LPS) on lower airway and immune responses in mice SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 354 BP S118 EP S118 DI 10.1016/S0091-6749(00)90783-8 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100351 ER PT J AU Soldatova, LN Bakst, JB Hoffman, DR Slater, JE AF Soldatova, LN Bakst, JB Hoffman, DR Slater, JE TI Molecular cloning of a new honeybee venom allergen, acid phosphatase SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 E Carolina Univ, Sch Med, Greenville, NC USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 12 Z9 12 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 1105 BP S378 EP S378 DI 10.1016/S0091-6749(00)91531-8 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530101099 ER PT J AU Tomazic-Jezic, VJ Beezhold, DH AF Tomazic-Jezic, VJ Beezhold, DH TI Evaluation of the ELISA inhibition assay for natural rubber latex (NRL) proteins: Comparison with other methods for protein and allergen measurements SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA, CDRH, Rockville, MD 20857 USA. GRI, Syare, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 169 BP S56 EP S56 DI 10.1016/S0091-6749(00)90600-6 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100168 ER PT J AU Luo, WH Ang, CYW AF Luo, WH Ang, CYW TI Determination of amoxicillin residues in animal tissues by solid-phase extraction and liquid chromatography with fluorescence detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MUSCLE; CATFISH AB Trace levels of amoxicillin residues were determined in animal tissues by liquid chromatography (LC) with fluorescence detection. An improved solid-phase extraction (SPE) procedure requiring less flammable solvent (diethyl ether) was developed for sample preparation. Muscle samples of beef, pork, chicken, and tilapia were extracted with a phosphate buffer followed by the modified SPE procedure for cleanup and concentration prior to the LC-fluorescence analysis. Average recoveries of fortified amoxicillin at 5, 10, and 20 mu g/kg ranged from 83.9 to 85.8% in beef, 86.1 to 88.1% in pork, 81.7 to 82.9% in chicken, and 92.5 to 95.4% in tilapia, Relative standard deviations were <4%. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Ang, CYW (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 5 TC 17 Z9 17 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 2000 VL 83 IS 1 BP 20 EP 25 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 280MG UT WOS:000085106100004 PM 10693000 ER PT J AU Pfenning, AP Roybal, JE Rupp, HS Turnipseed, SB Gonzales, SA Hurlbut, JA AF Pfenning, AP Roybal, JE Rupp, HS Turnipseed, SB Gonzales, SA Hurlbut, JA TI Simultaneous determination of residues of chloramphenicol, florfenicol, florfenicol amine, and thiamphenicol in shrimp tissue by gas chromatography with electron capture detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MASS-SPECTROMETRY; MILK; ANIMALS; MUSCLES; FISH AB A gas chromatographic (GC) method is presented for determining residues of chloramphenicol (CAP), florfenicol (FF), florfenicol amine (FFa), and thiamphenicol (TAP) in shrimp tissues, with meta-nitrochloramphenicol (mCAP) as the internal standard. The composited shrimp is extracted with basic ethyl acetate, followed by an acetonitrile-basic ethyl acetate mixture. This extract is centrifuged, filtered, evaporated, and reconstituted in water; the reconstituted extract is acidified, defatted with hexane, and passed through a propylsulfonic acid (PRS) and C-18 solid-phase extraction (SPE) system. The C-18 SPE column is eluted with methanol, and the PRS SPE column is eluted with basic MeOH plus counter ion. The combined eluates are evaporated, reconstituted in acetonitrile, and derivatized with Sylon BFT. After derivatization, the addition of toluene directly to the sample, followed by the addition of basic water, quenches the derivatization process. After centrifugation, the organic layer is carefully removed, and the analytes are determined by GC with electron capture detection. Shrimp tissues were fortified with fenicols (i.e., CAP, FF, FFa, and TAP) at 5, 10, 20, 40, and 80 ng/mL. Overall recoveries were 88, 101,91, and 84% with overall interassay (between-day) variabilities (i.e., relative standard deviations) of 5.3, 9.4, 12.8, and 7.4% for CAP, FF, FFa, and TAP, respectively. The method detection limits were calculated as 0.7, 1.4, 2.4, and 1.3 ng/g (ppb) for CAP, FF, FFa, and TAP, respectively, based on a 10 g sample. The quantitation limit as determined empirically by this method is the lower limit of the standard curve, which is about 5 ng/g (ppb) for each analyte. C1 US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Lakewood, CO 80225 USA. RP Pfenning, AP (reprint author), US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Lakewood, CO 80225 USA. NR 10 TC 105 Z9 126 U1 3 U2 15 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 2000 VL 83 IS 1 BP 26 EP 30 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 280MG UT WOS:000085106100005 PM 10693001 ER PT J AU Kerdahi, KF Istafanos, PF AF Kerdahi, KF Istafanos, PF TI Rapid determination of Listeria monocytogenes by automated enzyme-linked immunoassay and nonradioactive DNA probe SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A rapid and reliable analytical method was developed to detect and confirm the presence of Listeria monocytogenes in raw and partially processed foods. Forty-nine food samples (25 mixed cut vegetable salad, 12 smoked salmon, and 12 sterile smoked salmon) were individually inoculated with high levels [10-100 colony forming units (cfu)/25 g sample] and low levels (1-10 cfu/25 g sample) of L. monocytogenes, and were screened using the Vitek Immune Diagnostic Assay (VIDAS) Listeria monocytogenes (VIDAS LMO)], Positive test results were confirmed as L. monocytogenes by nonradioactive DNA probe. All samples inoculated with high levels of L. monocytogenes were detected by VIDAS and 96% were confirmed as L. monocytogenes by DNA probe, VIDAS LMO detected 89% of samples inoculated with low levels of L, monocytogenes, and 87% of these were confirmed as positive by DNA probe, In addition, 12 other samples (4 from each of mixed cut vegetable salad, smoked salmon, and sterile smoked salmon) were inoculated with high levels of L, ivanovii, L. seeligeri, L. welshimeri, L, innocua, L, grayi, and L. murrayi, Samples were assayed by the same protocol and all gave negative results. Compared with the cultural method, the VIDAS LMO nonradioactive DNA probe combination is highly specific, discriminates between L, monocytogenes and all other Listeria species, and reduces analytical time. C1 US FDA, NE Reg Lab, Brooklyn, NY 11232 USA. RP Istafanos, PF (reprint author), US FDA, NE Reg Lab, 850 3rd Ave, Brooklyn, NY 11232 USA. NR 14 TC 8 Z9 9 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 2000 VL 83 IS 1 BP 86 EP 88 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 280MG UT WOS:000085106100011 PM 10693007 ER PT J AU Roach, JAG White, KD Trucksess, MW Thomas, FS AF Roach, JAG White, KD Trucksess, MW Thomas, FS TI Capillary gas chromatography/mass spectrometry with chemical ionization and negative ion detection for confirmation of identity of patulin in apple juice SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Gas chromatography/mass spectrometry (GC/MS) with negative ion chemical ionization permits detection of underivatized patulin in apple juice extracts while minimizing co-extractive responses. The technique has been used with a variety of capillary columns in quadrupole, ion trap, and magnetic sector GC/MS instruments to confirm presumptive findings of patulin in apple juice at concentrations ranging from 68 to 3700 mu g/L. The demonstrated ability to use any of these 3 mass spectrometers and several capillary columns to confirm the identity of patulin are significant strengths of the technique. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Roach, JAG (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 15 TC 24 Z9 24 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 2000 VL 83 IS 1 BP 104 EP 112 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 280MG UT WOS:000085106100015 PM 10693011 ER PT J AU Danielson, JW Zuroski, KE Twohy, C Thompson, RD Bell, E McClure, F AF Danielson, JW Zuroski, KE Twohy, C Thompson, RD Bell, E McClure, F TI Recovery and sporicidal resistance of various B-subtilis spore preparations on porcelain penicylinders compared with results from AOAC test methods SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MINERALIZATION; HEAT AB Sporicidal test results obtained from carriers inoculated with 4 types of defined Bacillus subtilis spore preparations were compared with the standard AOAC sporicidal test using soil extract nutrient broth (SENB) B. subtilis 19659 spores. Recoveries of spores inoculated on penicylinders from B, subtilis clean spores (washed and suspended in water) and B, subtilis 19659 spores inoculated from culture filtrates according to the AOAC method were compared, Spores were exposed to 6 concentrations (0.5-3.0% w/v) of glutaraldehyde in phosphate buffer (pH 7.5) for 10 h, Concentrations were established by titrimetry and liquid chromatography, Recoveries of surviving spores were determined for 3 types of clean S, subtilis var, niger preparations, one clean S, subtilis 19659 preparation, and the SENB S, subtilis 19659 filtrates, Spore carriers, inoculated by the standard AOAC protocol, resulted in as much as a 2-log number difference in runs 1-12, but not more than 0.5 log number for each clean spore preparation, The SENB spores varied most in resistance to glutaraldehyde, with no growth in recovery media from 3 different batches of 1, 1.5, and 2% glutaraldehyde, Separate batches of SENB preparations of B, subtilis 19659 were resistant and destroyed by 1.0% glutaraldehyde, with 3.98 and 6.0 log numbers of spores on penicylinders, respectively, Clean spore preparations of B, subtilis 19659 on porcelain penicylinders were more resistant to glutaraldehyde than were SENB spores. Nutrient agar/Mg/Ca and nutrient agar/Mg spore preparations of S. subtilis var, niger showed the most uniform resistance to glutaraldehyde, Spores with calcium added showed increased resistance to glutaraldehyde, S, subtilis 19659 spores from the Columbia broth spore preparation were the most resistant and were recovered after exposure to 3.0% glutaraldehyde. C1 Gustavus Adolphus Coll, Biochem Program, St Peter, MN 56082 USA. US FDA, Minneapolis, MN 55401 USA. US FDA, Washington, DC 20204 USA. US FDA, Cent Lab Microbiol Invest, Minneapolis, MN 55401 USA. RP Bell, E (reprint author), Gustavus Adolphus Coll, Biochem Program, St Peter, MN 56082 USA. NR 18 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 2000 VL 83 IS 1 BP 145 EP 155 PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 280MG UT WOS:000085106100020 PM 10693016 ER PT J AU Capar, SG Cunningham, WC AF Capar, SG Cunningham, WC TI Element and radionuclide concentrations in food: FDA total diet study 1991-1996 SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID UNITED-STATES; COMPOSITES; HISTORY; NICKEL; COBALT AB Foods purchased throughout the United States during 1991-1997 under the U.S. Food and Drug Administration's Total Diet Study (TDS) program were analyzed for elements and radionuclides, The program is described with emphasis on food analysis and quality control, including independent interlaboratory exercises, Analytical results are summarized for Cd, Pb, Ni, As, Hg, Se, Cu, Zn, Mn, Fe, Mg, Ca, P, K, and Na and for Cs-137, I-131, Ru-106, and Sr-90. Concentration data are provided to expand the information base used to support assessments of the safety and nutritive value of the U.S. food supply and for their potential use in food composition databases, For selected foods, comparisons were made with past TDS results and with those reported in the literature, An extensive listing of the analytical data is available on the FDA CFSAN Website. C1 US FDA, Ctr Food Safety & Appl Nutr, Elemental Res Branch HFS338, Washington, DC 20204 USA. RP Capar, SG (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Elemental Res Branch HFS338, Washington, DC 20204 USA. NR 34 TC 29 Z9 35 U1 0 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2000 VL 83 IS 1 BP 157 EP 177 PG 21 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 280MG UT WOS:000085106100021 PM 10693017 ER PT J AU Jenkins, GR Tolleson, WH Newkirk, DK Roberts, DW Rowland, KL Saheki, T Kobayashi, K Howard, PC Melchior, WB AF Jenkins, GR Tolleson, WH Newkirk, DK Roberts, DW Rowland, KL Saheki, T Kobayashi, K Howard, PC Melchior, WB TI Identification of fumonisin B-1 as an inhibitor of argininosuccinate synthetase using fumonisin affinity chromatography and in vitro kinetic studies SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Article DE fumonisin B-1; argininosuccinate synthetase; urea cycle; mycotoxin; enzyme inhibitor; kinetics; affinity chromatography ID COA-SPHINGOSINE ACYLTRANSFERASE; NOVO SPHINGOLIPID BIOSYNTHESIS; RAT-LIVER; FUSARIUM-MONILIFORME; IN-SITU; BRAIN; CELLS; APOPTOSIS; TOXICITY; SOLUBILIZATION AB Fumonisin B-1, a fungal mycotoxin that grows on corn and other agricultural products, alters sphingolipid metabolism by inhibiting ceramide synthase; The precise mechanism of fumonisin B-1 toxicity has not been completely elucidated; however, a central feature in the cytotoxicity is alteration of sphingolipid metabolism through interruption of de novo ceramide synthesis. An affinity column consisting of fumonisin B-1 covalently bound to an HPLC column matrix was used to isolate a rat liver protein that consistently bound to the column. The protein was identified as argininosuccinate synthetase by protein sequencing. The enzyme-catalyzed formation of argininosuccinic acid from citrulline and aspartate by recombinant human and rat liver argininosuccinate synthetase was inhibited by fumonisin B-1. Fumonisin B-1 showed mixed inhibition against citrulline, aspartate, and Am to the enzyme. Fumonisin B-1 had a K-i' of approximately 6 mM with the recombinant human argininosuccinate synthase and a K-i' of 35 mM with a crude preparation of enzyme prepared from rat liver. Neither tricarballylic acid nor hydrolyzed fumonisin B-1 inhibited recombinant human argininosuccinate synthetase. This is the first demonstration of fumonisin B-1 inhibition of argininosuccinate synthethase, a urea cycle enzyme, which adds to the list of enzymes that are inhibited in vitro by fumonisin B-1 (ceramide synthase, protein serine/threonine phosphatase). The extent of the inhibition of argininosuccinate synthetase in cells, and the possible role of this enzyme inhibition in the cellular toxicity of FB1, remains to be established. (C) 2000 John Wiley & Sons, Inc. C1 US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Kagoshima Univ, Fac Med, Dept Biochem, Kagoshima 8908520, Japan. RP Melchior, WB (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. FU NIA NIH HHS [IAG 224-93-0001] NR 35 TC 7 Z9 7 U1 1 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PY 2000 VL 14 IS 6 BP 320 EP 328 DI 10.1002/1099-0461(2000)14:6<320::AID-JBT4>3.0.CO;2-9 PG 9 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 363JY UT WOS:000089833600004 PM 11083085 ER PT J AU Hornberger, C Knoop, P Nahm, W Matz, H Konecny, E Gehring, H Bonk, R Frankenberger, H Meyfroidt, G Wouters, P Gil-Rodriguez, J Ponz, L Benekos, K Valais, J Avgerinos, J Karoutis, A Ikiades, A Weininger, S AF Hornberger, C Knoop, P Nahm, W Matz, H Konecny, E Gehring, H Bonk, R Frankenberger, H Meyfroidt, G Wouters, P Gil-Rodriguez, J Ponz, L Benekos, K Valais, J Avgerinos, J Karoutis, A Ikiades, A Weininger, S TI A prototype device for standardized calibration of pulse oximeters SO JOURNAL OF CLINICAL MONITORING AND COMPUTING LA English DT Article DE pulse oximetry; calibration ID TEST SYSTEM; ACCURACY AB Objective. To develop and test a method for standardized calibration of pulse oximeters. Methods. A novel pulse oximeter calibration technique capable of simulating the behavior of real patients is discussed. It is based on an artificial finger with a variable spectral-resolved light attenuator in conjunction with an extensive clinical database of time-resolved optical transmission spectra of patients fingers in the wavelength range 600-1000 nm. The arterial oxygen saturation of the patients at the time of recording was derived by analyzing a corresponding blood sample with a CO-oximeter. These spectra are used to compute the modulation of the light attenuator which is attached to the artificial finger. This calibration method was tested by arbitrarily playing back recorded spectra to pulse oximeters and comparing their display to the value they displayed when the spectra were recorded. Results. We were able to demonstrate that the calibrator could generate physiological signals which are accepted by a pulse oximeter. We also present some experience of playing back recorded patient spectra. The mean difference between the original reading of the pulse oximeters and the display when attached to the calibrator is 1.2 saturation points (displayed oxygen saturation SpO(2)) with a standard deviation of 1.9 saturation points. Conclusions. The tests have shown the capabilities of a spectral light modulator for use as a possible calibration standard for pulse oximeters. If some improvements of the current prototype can be achieved we conclude from the experience with the device that this novel concept for the calibration of pulse oximeters is feasible and that it could become an important tool for assessing the performance of pulse oximeters. C1 Med Univ Lubeck, Inst Med Tech, D-23538 Lubeck, Germany. Med Univ Lubeck, Anasthesiol Klin, D-23538 Lubeck, Germany. FH Lubeck, Lab Biomed Tech, Lubeck, Germany. Katholieke Univ Leuven, Louvain, Belgium. St Marys Hosp, London, England. Inst Oncol, San Sebastian, Spain. TEI Athens, Athens, Greece. ERGO SA, Athens, Greece. FORTH, Crete, Greece. US FDA, Rockville, MD 20857 USA. RP Hornberger, C (reprint author), Med Univ Lubeck, Inst Med Tech, Ratzeburger Allee 160, D-23538 Lubeck, Germany. RI Wouters, Patrick/E-1988-2011; Nahm, Werner/I-6365-2012 NR 18 TC 4 Z9 5 U1 0 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1387-1307 J9 J CLIN MONITOR COMP JI J. Clin. Monitor. Comp. PY 2000 VL 16 IS 3 BP 161 EP 169 DI 10.1023/A:1009931527538 PG 9 WC Anesthesiology SC Anesthesiology GA 375BK UT WOS:000165379500001 PM 12578099 ER PT J AU Ibrahim, S Honig, P Huang, SM Gillespie, W Lesko, LJ Williams, RL AF Ibrahim, S Honig, P Huang, SM Gillespie, W Lesko, LJ Williams, RL TI Clinical pharmacology studies in patients with renal impairment: Past experience and regulatory perspectives SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID DISEASE-INDUCED VARIATIONS; PLASMA-PROTEIN LEVELS; DRUG-DOSAGE REGIMENS; FAILURE; PHARMACOKINETICS; METABOLISM; BINDING AB The objective of this report is to provide a regulatory perspective on the quality of pharmacokinetic studies in renal impairment (RI) studies submitted in support of new drug applications (NDAs) or supplements to NDAs (sNDAs) submitted to the Food and Drug Administration (FDA). Fifty-one NDA and 20 sNDA submissions reviewed between 1996 and 1997 by the Office of Clinical Pharmacology and Biopharmaceutics were evaluated for the following: (1) whether an RI study was conducted; (2) contribution of the renal clearance to the overall clearance in subjects without renal impairment; (3) degree of plasma protein binding (%PB) in subjects without renal impairment; (4) dose proportionality of single and multiple doses; (5) study design, including dosing regimen; (6) definition of renal impairment; (7) stratification of renal functions; (8) number of subjects/group; (9) data analysis and interpretation; and (10) impact on labeling. Results of the analysis indicated that 67% of the NDAs and 30% of supplemental NDAs contained RI studies (34/51 for NDAs and 6/20 for sNDAs). No obvious differences in the pharmacokinetic characteristics (e.g., percentage excreted unchanged in urine and %PB) were observed between drugs for which RI studies were conducted versus those not conducted. Most studies conducted were designed as single dose (70%). Seventy-five percent of the studies used doses within the therapeutic dosage range of the drug. The measured 24-hour creatinine clearance was most often used to assess the renal function. Stratification of renal function ranged from one to five groups, with 6 to 8 subjects enrolled per group. In most studies conducted (38/40), data were analyzed by point estimate using ANOVA. Results of RI studies were adequately reflected in the labeling. The survey reveals that RI study design can be improved for regulatory review purposes. In part based on this analysis, the FDA has prepared a guidance that provides recommendations on the design, analysis, and impact on dosing and labeling for RI studies to include recommendations on when RI studies do not need to be performed. The guidance proposes an equivalence approach with confidence intervals, as opposed to a point estimate approach, to assess the impact of RI on systemic exposure measures. (C) 2000 the American College of Clinical Pharmacology. C1 US FDA, CDER, OCPB, DPE1, Rockville, MD 20857 USA. US FDA, CDER, Off Pharmaceut Sci, Rockville, MD 20857 USA. US FDA, CDER, Off Review Management, Rockville, MD 20857 USA. GloboMax LLC, Hanover, MD USA. RP Ibrahim, S (reprint author), US FDA, CDER, OCPB, DPE1, HFD-860,WOC-2,Room 2083,5600 Fishers Lane, Rockville, MD 20857 USA. NR 24 TC 12 Z9 12 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JAN PY 2000 VL 40 IS 1 BP 31 EP 38 DI 10.1177/00912700022008658 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 269FH UT WOS:000084465700003 PM 10631619 ER PT J AU Cisar, JO Xu, DQ Thompson, J Swaim, W Hu, L Kopecko, D AF Cisar, JO Xu, DQ Thompson, J Swaim, W Hu, L Kopecko, D TI Absence of nanobacteria in human saliva and dental plaque. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDCR, NIH, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2231 BP 422 EP 422 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002222 ER PT J AU Schenck, FJ Howard-King, V AF Schenck, FJ Howard-King, V TI Determination of organochlorine and organophosphorus pesticide residues in low moisture, nonfatty products using a solid phase extraction cleanup and gas chromatography SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART B-PESTICIDES FOOD CONTAMINANTS AND AGRICULTURAL WASTES LA English DT Article DE pesticides; feeds; grains; low moisture products AB A multiresidue solid-phase extraction (SPE) method for the isolation and subsequent gas chromatographic determination of organochlorine and organophosphorus pesticide residues in low-moisture, nonfatty products is described. Residues are extracted from samples with an acetonitrile/water mixture. Cleanup of the extract is performed using graphitized carbon black and anion exchange SPE columns, and analysis is performed by gas chromatography with Hall electrolytic conductivity and flame photometric detection. Recovery data was obtained by fortifying corn, oats and wheat with pesticides. The average recoveries were 79-123% for eight organochlorine and 51-122% for 28 organophosphorus pesticide residues. The limit of quantitation for chlorpyriphos was 0.05 ppm using the Hall electrolytic conductivity detector and <0.005 ppm using the flame photometric detector. C1 US FDA, Baltimore Dist Lab, Baltimore, MD 21201 USA. RP Schenck, FJ (reprint author), US FDA, SE Reg Lab, 60 8th St NE, Atlanta, GA 30309 USA. NR 7 TC 7 Z9 9 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-1234 J9 J ENVIRON SCI HEAL B JI J. Environ. Sci. Health Part B-Pestic. Contam. Agric. Wastes PY 2000 VL 35 IS 1 BP 1 EP 12 DI 10.1080/03601230009373250 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 284WE UT WOS:000085355200001 PM 10693051 ER PT J AU Chase, GW Eitenmiller, RR Long, AR AF Chase, GW Eitenmiller, RR Long, AR TI The liquid chromatographic analysis of vitamin K-1 in soy based infant formula using matrix solid phase dispersion SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID PHYLLOQUINONE CONTENT; AMERICAN DIET; FOOD SOURCES; DIHYDRO-VITAMIN-K-1; PLASMA; OILS AB A liquid chromatographic method is described for vitamin K-1 in soy based infant formula. The vitamins are extracted from infant formula by matrix solid phase dispersion (MSPD) and quantitated by reversed phase chromatography with fluorescence detection. Vitamin K-1 is converted to the fluorescent hydroquinone with a post column zinc reductive reactor. The limit of detection is 12 pg and the limit of quantitation is 38 pg on- column. Linear response ranged from 0.70 - 11.0 ng/mL (r(2) = 0.998). Recoveries were determined on an analyte-fortified blank material for soy based infant formula and averaged 92.5% (n = 25) for vitamin K-1. The method provides a rapid, specific, and easily controlled assay for the analysis of vitamin K-1 in fortified soy based infant formula. C1 US FDA, SE Reg Lab, Atlanta, GA 30309 USA. Univ Georgia, Dept Food Sci & Technol, Athens, GA 30602 USA. US FDA, NW Reg lab, Bothell, WA 98021 USA. RP Chase, GW (reprint author), US FDA, SE Reg Lab, 60 8th St, Atlanta, GA 30309 USA. NR 17 TC 6 Z9 6 U1 0 U2 3 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 2000 VL 23 IS 3 BP 423 EP 432 DI 10.1081/JLC-100101461 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 274MQ UT WOS:000084770000007 ER PT J AU Heller, DN Clark, SB Righter, HF AF Heller, DN Clark, SB Righter, HF TI Confirmation of gentamicin and neomycin in milk by weak cation-exchange extraction and electrospray ionization/ion trap tandem mass spectrometry SO JOURNAL OF MASS SPECTROMETRY LA English DT Article DE ion trap mass spectrometry; aminoglycoside antibiotics; confirmation; bovine milk; electrospray ionization ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ION-TRAP; AMINOGLYCOSIDE ANTIBIOTICS; SEPARATION; SULFATE; TISSUE AB A new procedure for the confirmation of two aminoglycoside antibiotics in milk was developed and validated. This work is among the early applications of ion trap mass spectrometry for regulatory methodology, and it incorporates a novel weak cation-exchange extraction. The procedure was validated for the confirmation of both gentamicin and neomycin at 30 ng ml(-1) and above. Milk is first treated with acid and centrifuged. The supernate, excluding the fat layer, is buffered with sodium citrate to neutral pH, The extract is applied to a weak cation-exchange solid-phase extraction column. Aminoglycosides are eluted with acidified methanol, Following separation by ion-pair liquid chromatography, analytes are ionized with an electrospray interface, Protonated molecular ions are selectively stored in an ion trap mass spectrometer, then collisionally dissociated to yield unique product ion spectra, Confirmation is based on matching spectral responses between samples and comparison standards consisting of a bona fide standard spiked into control extracts. Method performance was demonstrated with replicate samples of control milk, fortified milk, and milk containing incurred residues of each compound, Copyright (C) 2000 John Wiley & Sons, Ltd. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. US FDA, Denver Dist Lab, Denver Fed Ctr, Denver, CO 80225 USA. RP Heller, DN (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 28 TC 74 Z9 81 U1 1 U2 11 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1076-5174 J9 J MASS SPECTROM JI J. Mass Spectrom. PD JAN PY 2000 VL 35 IS 1 BP 39 EP 49 DI 10.1002/(SICI)1096-9888(200001)35:1<39::AID-JMS911>3.3.CO;2-P PG 11 WC Biophysics; Chemistry, Organic; Spectroscopy SC Biophysics; Chemistry; Spectroscopy GA 277ZV UT WOS:000084964200005 PM 10633233 ER PT J AU Bichsel, VE Petricoin, EF Liotta, LA AF Bichsel, VE Petricoin, EF Liotta, LA TI The state of the art microdissection and its downstream applications SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article; Proceedings Paper CT EuroConference on Microdissection and its Downstream Tools CY SEP 15-17, 2000 CL BONN, GERMANY SP European Commiss ID LASER CAPTURE MICRODISSECTION C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Liotta, LA (reprint author), NCI, Pathol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 6 TC 6 Z9 7 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PY 2000 VL 78 IS 7 BP B20 EP B20 PG 1 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 357CY UT WOS:000089482000006 PM 11043383 ER PT J AU Rashid, MM Chen, MH Ganter, SL AF Rashid, MM Chen, MH Ganter, SL TI Nonparametric analysis of a multi-group incompletely ranked item response data SO JOURNAL OF NONPARAMETRIC STATISTICS LA English DT Article DE f test; interactions; multiple comparisons; simulation; simultaneous confidence intervals ID TESTS AB Nonparametric procedures to analyze multi-group ranked item response data where each subject ranks only the top p items out of t items are considered. A Durbin-type statistic with small sample adjustment for testing interactions between the groups and the items is developed. For post-hoc analysis, various multiple comparison procedures to detect which interaction contrast is responsible for rejection are proposed. Another Durbin-type statistic is also discussed in establishing no overall preference for the items, assuming there is no group and item interaction. Several multiple comparison procedures for detecting the items that are responsible for rejection are employed. A small scale simulation study is conducted for investigating small sample properties of the proposed methods. A real data example is used to illustrate the methodology. C1 US FDA, Ctr Drug Evaluat & Res, Div Biometr 2, Rockville, MD 20857 USA. Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA. Amer Assoc Higher Educ, Washington, DC 20036 USA. RP Rashid, MM (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Biometr 2, HFD 715,Room 9B07,5600 Fishers Lane, Rockville, MD 20857 USA. NR 19 TC 0 Z9 0 U1 0 U2 1 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1048-5252 J9 J NONPARAMETR STAT JI J. Nonparametr. Stat. PY 2000 VL 12 IS 2 BP 245 EP 264 DI 10.1080/10485250008832807 PG 20 WC Statistics & Probability SC Mathematics GA 300JH UT WOS:000086249500005 ER PT J AU D'Cruz, D Keser, G Khamashta, MA Direskeneli, H Targoff, IN Miller, F Hughes, GRV AF D'Cruz, D Keser, G Khamashta, MA Direskeneli, H Targoff, IN Miller, F Hughes, GRV TI Antiendothelial cell antibodies in inflammatory myopathies: Distribution among clinical and serologic groups and association with interstitial lung disease SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE antiendothelial cell antibodies; antisynthetase antibodies; interstitial lung disease; idiopathic inflammatory myopathies ID SYSTEMIC LUPUS-ERYTHEMATOSUS; MYOSITIS-SPECIFIC AUTOANTIBODIES; ENDOTHELIAL-CELLS; MONONUCLEAR-CELLS; DERMATOMYOSITIS; POLYMYOSITIS; RECOGNITION AB Objective. To determine the prevalence and associations of antiendothelial cell antibodies (AECA) in a well characterized cohort of patients with idiopathic inflammatory myopathies (IIM), Methods. Clinical characteristics, AECA, and myositis-specific autoantibodies were assessed by standard methods in 56 subjects with IIM. Results. AECA were found in 20/56 patients with IIM, were seen in all the major clinical and serologic IIM groups, and were found in 10/15 patients with interstitial lung disease (ILD) (chi squared 6.5, p < 0.01 with Yates' correction, relative risk 2.7, specificity 86% and sensitivity 50%). Antisynthetase antibodies, also associated with ILD as described (chi squared = 26.5, p < 0.001 with Yates' correction, relative risk 8.7, specificity 95%, sensitivity 77%), did not correlate with the presence of AECA, Conclusion. AECA appear to be present in all forms of IIM and are markers for no that are independent of anti-synthetase autoantibodies. AECA may be a useful serologic marker for ILD in IIM. C1 St Thomas Hosp, Rayne Inst, Lupus Arthrit Res Unit, London SE1 7EH, England. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. US FDA, Mol Immunol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP D'Cruz, D (reprint author), St Bartholomews & Royal London Sch Med & Dent, Bone & Joint Res Unit, 25-29 Ashfield St, London E1 2AD, England. OI Miller, Frederick/0000-0003-2831-9593 NR 16 TC 15 Z9 15 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 JAN PY 2000 VL 27 IS 1 BP 161 EP 164 PG 4 WC Rheumatology SC Rheumatology GA 274RC UT WOS:000084778000027 PM 10648033 ER PT J AU Guthrie, JF Morton, JF AF Guthrie, JF Morton, JF TI Food sources of added sweeteners in the diets of Americans SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article AB Objective To identify food sources of added sweeteners in the US diet. Design A descriptive study using data from the US Department of Agriculture (USDA) 1994-1996 Continuing Survey of Food Intakes by Individuals. Each subject provided one 24-hour dietary recall. Intake of added sweeteners was calculated using the USDA Food Guide Pyramid servings database. Subjects/setting A national sample of noninstitutionalized persons aged 2 years and older (N=15,010). Statistical analyses Mean intakes of added sweeteners from all food sources and from specific food categories; percentage contribution of added sweeteners to total energy intake; and percentage contribution of each food category to total intake of added sweeteners. All analyses were conducted for the total sample and for 12 age-gender groups. Results During 1994 to 1996, Americans aged 2 years and older consumed the equivalent of 82 g carbohydrate per day from added sweeteners, which accounted for 16% of total energy intake. In absolute terms, adolescent males consumed the most; as a percentage of energy, male and female adolescents had the highest intakes (averaging 20% of total energy from added sweeteners). The largest source of added sweeteners was regular soft drinks, which accounted for one third of intake. Other sources were table sugars, syrups, and sweets; sweetened grains; regular fruitades/drinks; and milk products. Applications/conclusions Intakes of added sweeteners exceed levels compatible with meeting current dietary recommendations. Knowing food sources of added sweeteners for the overall population and for specific age-gender groups can help dietitians provide appropriate nutrition education. C1 US FDA, Ctr Food Safety & Appl Nutr, OSAS Mkt Studies, Washington, DC 20204 USA. USDA, Ctr Nutr Policy & Promot, Washington, DC USA. RP Guthrie, JF (reprint author), US FDA, Ctr Food Safety & Appl Nutr, OSAS Mkt Studies, 200 C St,SW HFS-727, Washington, DC 20204 USA. NR 25 TC 241 Z9 249 U1 3 U2 26 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 JAN PY 2000 VL 100 IS 1 BP 43 EP 51 DI 10.1016/S0002-8223(00)00018-3 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 460MB UT WOS:000170310400014 PM 10646004 ER PT J AU Ahn, H Moon, H AF Ahn, H Moon, H TI Attribution of tumour lethality and estimation of the time to onset of occult tumours in the absence of cause-of-death information SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE bioassay; competing risk; incidental tumour; interval sacrifice; likelihood ID RODENT TUMORIGENICITY EXPERIMENTS; ANIMAL CARCINOGENESIS; ASSIGNMENT; SURVIVAL; RATES; MODEL AB A new statistical approach is developed for estimating the carcinogenic potential of drugs and other chemical substances used by humans. Improved statistical methods are developed for rodent tumorigenicity assays that have interval sacrifices but not cause-of-death data. For such experiments, this paper proposes a nonparametric maximum likelihood estimation method for estimating the distributions of the time to onset of and the time to death from the tumour. The log-likelihood function is optimized by using a constrained direct search procedure. Using the maximum likelihood estimators, the number of fatal tumours in an experiment can be imputed. By applying the procedure proposed to a real data set, the effect of calorie restriction is investigated. In this study, we found that calorie restriction delays the tumour onset time significantly for pituitary tumours. The present method can result in substantial economic savings by relieving the need for a case-by-case assignment of the cause of death or context of observation by pathologists. The ultimate goal of the method proposed is to use the imputed number of fatal tumours to modify Peto's International Agency for Research on Cancer test for application to tumorigenicity assays that lack cause-of-death data. C1 SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. US FDA, Jefferson, AR USA. RP Ahn, H (reprint author), SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. NR 21 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0035-9254 J9 J ROY STAT SOC C-APP JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 2000 VL 49 BP 157 EP 169 DI 10.1111/1467-9876.00185 PN 2 PG 13 WC Statistics & Probability SC Mathematics GA 314CY UT WOS:000087038300001 ER PT J AU Wilson, CA Wong, S VanBrocklin, M Federspiel, MJ AF Wilson, CA Wong, S VanBrocklin, M Federspiel, MJ TI Extended analysis of the in vitro tropism of porcine endogenous retrovirus SO JOURNAL OF VIROLOGY LA English DT Article ID LEUKEMIA-VIRUS; HUMAN-CELLS; RECEPTOR; INFECTION; MURINE AB We previously reported that mitogenic activation of porcine peripheral blood mononuclear cells resulted in production of porcine endogenous retrovirus(es) (PERV[s]) capable of productively infecting human cells (C. Wilson et al., J. Virol. 72:3082-3087, 1998). We now extend that analysis to show that additional passage of isolated virus, named here PERV-NIH, through a human cell line yielded a viral population with a higher titer of infectious virus on human cells than the initial isolate. We show that in a single additional passage on a human cell line, the increase in infectivity for human cells is accounted for by selection against variants carrying pig-tropic envelope sequences (PERV-C) as well as by enrichment for replication-competent genomes, Sequence analysis of the envelope cDNA present in virions demonstrated that the envelope sequence of PERV-NIH is related to but distinct from previously reported PERV envelopes. The in vitro host range of PERV was studied in human primary cells and cell lines, as well as in cell lines from nonhuman primate and other species. This analysis reveals three patterns of susceptibility to infection among these host cells: (i) cells are resistant to infection in our assay; (ii) cells are infected by virus, as viral RNA is detected in the supernatant by reverse transcription-PCR, but the cells are not permissive to productive replication and spread; and (iii) cells are permissive to low-level productive replication. Certain cell lines were permissive for efficient productive infection and spread. These results may prove useful in designing appropriate animal models to assess the in vivo infectivity properties of PERV. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Program Mol Med, Rochester, MN 55905 USA. RP Wilson, CA (reprint author), Bldg 29B,Room 2NN11,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 20 TC 163 Z9 169 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2000 VL 74 IS 1 BP 49 EP 56 PG 8 WC Virology SC Virology GA 263QQ UT WOS:000084137100007 PM 10590090 ER PT S AU Beiden, SV Campbell, G Meier, KL Wagner, RF AF Beiden, SV Campbell, G Meier, KL Wagner, RF BE Krupinski, EA TI On the problem of ROC analysis without truth: The EM algorithm and the information matrix. SO MEDICAL IMAGING 2000: IMAGE PERCEPTION AND PERFORMANCE SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2000 Conference CY FEB 13-17, 2000 CL SAN DIEGO, CA SP SPIE, Merge Technologies Inc, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, IEEE, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol ID MAXIMUM LIKELIHOOD AB Henkelman, Kay, and Bronskill (HKB) showed that although the problem of ROC analysis without truth is underconstrained and thus not uniquely solvable in one dimension (one diagnostic test), it is in principle solvable in two or more dimensions. However, they gave no analysis of the resulting uncertainties. The present work provides a maximum-likelihood solution using the EM (expectation-maximization) algorithm for the two-dimensional case. We also provide an analysis of uncertainties in terms of Monte Carlo simulations as well as estimates based on Fisher Information Matrices for the complete- and the missing-data problem. We find that the number of patients required for a given precision of estimate for the truth-unknown problem is a very large multiple of that required for the corresponding truth-known case. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. RP Beiden, SV (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. NR 12 TC 21 Z9 21 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3598-8 J9 PROC SPIE PY 2000 VL 3981 BP 126 EP 134 DI 10.1117/12.383099 PG 9 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BQ28P UT WOS:000087811800015 ER PT S AU Wear, KA AF Wear, KA BE Shung, KK Insana, MF TI Variations in transit-time-based ultrasonic velocity estimates in human calcaneus due to frequency-dependent attenuation and dispersion SO MEDICAL IMAGING 2000: ULTRASONIC IMAGING AND SIGNAL PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2000 Conference CY FEB 13-17, 2000 CL SAN DIEGO, CA SP SPIE, Merge Technologies Inc, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, IEEE, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE ultrasound; bone; osteoporosis; velocity; frequency-dependent attenuation; dispersion ID CANCELLOUS BONE; ACOUSTIC PROPERTIES; HIP FRACTURE; IN-VITRO; WAVE-PROPAGATION; OS CALCIS; 100 MHZ; DENSITY; WOMEN; SOUND AB Transit-time-based methods for ultrasonic velocity estimation generally involve measurement of arrival times of broadband pulses. A marker on the pulse waveform, such as a zero crossing, is often used. Variations in sound-speed estimates may arise from frequency-dependent attenuation and dispersion which alter spectral characteristics of waveform and shift locations of markers. Theory is presented to correct for this distortion for Gaussian pulses propagating through linearly-attenuating, weakly-dispersive media. The theory is validated on 21 human calcaneus samples in vitro using diagnostic frequencies for bone sonometry. While the effects of dispersion can be shown to be small, variations in velocity estimates due to frequency-dependent attenuation have substantial magnitude relative to the difference in average sound speeds between normal and osteoporotic bone. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. NR 48 TC 0 Z9 0 U1 1 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3599-6 J9 PROC SPIE PY 2000 VL 3982 BP 187 EP 195 DI 10.1117/12.382224 PG 9 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BQ28Q UT WOS:000087812200021 ER PT J AU Yuspa, SH Hansen, L Li, LW Joseloff, E Weinberg, W Fernandez-Salas, E AF Yuspa, SH Hansen, L Li, LW Joseloff, E Weinberg, W Fernandez-Salas, E TI Interacting signaling pathways in the pathogenesis of squamous cell carcinoma SO MEDICINA-BUENOS AIRES LA English DT Article; Proceedings Paper CT XLV Scientific Meeting of the Argentine-Society-of-Clinical-Investigation/XLVIII Scientific Meeting of the Argentine-Society-of-Immunology CY NOV 22-25, 2000 CL MAR DEL PLATA, ARGENTINA SP Argentine Soc Clin Investigat, Argentine Soc Immunol ID GROWTH-FACTOR RECEPTOR; KINASE-C-DELTA; FACTOR-ALPHA; TYROSINE PHOSPHORYLATION; EPIDERMAL-KERATINOCYTES; MALIGNANT CONVERSION; TARGETED DISRUPTION; SKIN CARCINOGENESIS; V-RAS(HA) ONCOGENE; P53 LOSS C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Immunobiol Lab, Bethesda, MD 20892 USA. RP Yuspa, SH (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. NR 26 TC 1 Z9 2 U1 0 U2 0 PU MEDICINA (BUENOS AIRES) PI BUENOS AIRES PA DONATO ALVAREZ 3150, 1427 BUENOS AIRES, ARGENTINA SN 0025-7680 J9 MEDICINA-BUENOS AIRE JI Med.-Buenos Aires PY 2000 VL 60 IS 5 BP 689 EP 692 PN 2 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 382DM UT WOS:000165804000007 PM 11188883 ER PT J AU Moysich, KB Freudenheim, JL Baker, JA Ambrosone, CB Bowman, ED Schisterman, EF Vena, JE Shields, PG AF Moysich, KB Freudenheim, JL Baker, JA Ambrosone, CB Bowman, ED Schisterman, EF Vena, JE Shields, PG TI Apolipoprotein E genetic polymorphism, serum lipoproteins, and breast cancer risk SO MOLECULAR CARCINOGENESIS LA English DT Article; Proceedings Paper CT 12th International Conference on Carcinogenesis and Risk Assessment CY DEC 02-05, 1998 CL AUSTIN, TEXAS DE breast neoplasms; molecular epidemiology; apolipoprotein E allelic frequency; dietary fat; serum lipoproteins ID PLASMA-LIPIDS; DIETARY-FAT; NUTRITIONAL EPIDEMIOLOGY; INSULIN-RESISTANCE; CIGARETTE-SMOKING; E PHENOTYPE; FOLLOW-UP; CHOLESTEROL; WOMEN; TRIGLYCERIDE AB Apolipoprotein E (apoE) is a polymorphic gene involved in lipid metabolism with three common variant alleles (epsilon 2, epsilon 3 and epsilon 4). The epsilon 4 allele has been associated with elevated levels of cholesterol as well as greater risk of coronary heart disease and Alzheimer's disease. In this case-control study we examined whether apoE genotype affected the association between serum lipids and breast cancer risk. In a subset of a study in western New York, 260 women with incident, primary breast cancer and 332 community controls were interviewed and provided blood samples. Polymerase chain reaction-restriction fragment length polymorphism analyses of the apoE polymorphism were performed. Participants were classified as apoE2 (epsilon 2, epsilon 2 or epsilon 2, epsilon 3), apoE2 (epsilon 3, epsilon 3), or apoE4 (epsilon 4, epsilon 4 or epsilon 4, epsilon 3). no unconditional logistic regression was used to compute adjusted odds ratios (ORs) and 95% confidence intervals (CI). Compared with women with the apoE3 genotype, there were no association with the risk for women with the apoE2 (OR = 1.0; 95% CI = 0.91 - 1.64) or apoE4 genotype (OR = 0.97; 95% CI = 0.63 - 1.54). higher serum levels of total cholesterol, HDL cholesterol, and LDL cholesterol were not associated with risk, either in the total sample or among subgroups of women defined by the apoE genotype. Women with the highest serum triglyceride levels had an increase in risk (OR = 1.63; 95% CI = 1.03 - 2.59) compared to women with the lowest levels. This effect was not apparent among women with the apoE2 or apoE3 genotype, but much stronger among women with the apoE4 genotype (OR = 4.69; 95% CI = 1.49 - 14.7). These data suggest that the apoE4 genotype may modify the association between serum triglycerides and brest cancer risk. (C) 2000 Wiley-Liss, Inc. C1 Roswell Pk Canc Inst, Dept Canc Prevent Epidemiol & Biostat, Buffalo, NY 14263 USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NCI, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Moysich, KB (reprint author), Roswell Pk Canc Inst, Dept Canc Prevent Epidemiol & Biostat, Elm & Carlton St, Buffalo, NY 14263 USA. RI Shields, Peter/I-1644-2012; OI Schisterman, Enrique/0000-0003-3757-641X NR 56 TC 37 Z9 40 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JAN PY 2000 VL 27 IS 1 BP 2 EP 9 DI 10.1002/(SICI)1098-2744(200001)27:1<2::AID-MC2>3.0.CO;2-W PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 280LA UT WOS:000085103200002 PM 10642431 ER PT S AU Itzhak, Y Martin, JL Ali, SF AF Itzhak, Y Martin, JL Ali, SF BE Ali, SF TI Comparison between the role of the neuronal and inducible nitric oxide synthase in methamphetamine-induced neurotoxicity and sensitization SO NEUROBIOLOGICAL MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Neurobiological Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY AUG 04-06, 1999 CL COPENHAGEN, DENMARK SP Int Soc Neurochem, Neuroresearch, Sevier Amer, Bie & Berntsen AS, Parke Davis, Neurosci Res Div, USDA, Natl Ctr Toxicol Res ID TYROSINE-HYDROXYLASE ACTIVITY; STRIATAL DOPAMINE; BEHAVIORAL SENSITIZATION; NERVOUS-SYSTEM; DEFICIENT MICE; FREE-RADICALS; RAT-BRAIN; IN-VIVO; 7-NITROINDAZOLE; AMPHETAMINE AB The involvement of the neuronal and inducible nitric oxide synthase (nNOS and iNOS, respectively) in methamphetamine (METH)-induced dopaminergic neurotoxicity and behavioral sensitization was investigated. To determine METH-induced neurotoxicity, mice deficient in the nNOS and iNOS genes, nNOS(-/-) and iNOS(-/-) mice, and wild-type controls received either saline or METH (5 mg/kg x 3). After 72 h the level of striatal dopaminergic markers were measured. Administration of METH to nNOS(-/-) mice had no significant effect on the level of striatal dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), or dopamine transporter (DAT) binding sites. However, METH caused 25-40% depletion of dopaminergic markers in iNOS(-/-) mice and 63-69% depletion in the wild-type mice. METH-induced locomotor activity was measured following the administration of a low dose (1 mg/kg) on day 1. Subsequently animals received the high dose of METH (5 mg/kg x 3). On day 4, after a 68-72 h drug free period, animals were challenged with 1 mg/kg METH, and locomotor activity was recorded. The intensity of METH-induced locomotion in nNOS(-/-) mice on day I and 4 was similar, suggesting that locomotor sensitization did not develop. However, the intensity of METH-induced locomotion in the iNOS(-/-,) and wild-type mice on day 4 was doubled compared to day 1, suggesting the development of sensitization. The present findings indicate that nNOS(-/-) mice are more resistant to METH-induced neurotoxicity and behavioral sensitization than iNOS(-/-) mice. These results suggest a major role for nNOS rather than iNOS in the effects of METH. C1 Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33101 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, R-629,Gautier Bldg,1011 NE 15th St, Miami, FL 33101 USA. FU NIDA NIH HHS [R01DA08584] NR 30 TC 15 Z9 16 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 1-57331-279-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 914 BP 104 EP 111 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BT09R UT WOS:000171939100011 PM 11085313 ER PT S AU Imam, SZ Islam, F Itzhak, Y Slikker, W Ali, SF AF Imam, SZ Islam, F Itzhak, Y Slikker, W Ali, SF BE Ali, SF TI Prevention of dopaminergic neurotoxicity by targeting nitric oxide and peroxynitrite: Implications for the prevention of methamphetamine-induced neurotoxic damage SO NEUROBIOLOGICAL MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Neurobiological Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY AUG 04-06, 1999 CL COPENHAGEN, DENMARK SP Int Soc Neurochem, Neuroresearch, Sevier Amer, Bie & Berntsen AS, Parke Davis, Neurosci Res Div, USDA, Natl Ctr Toxicol Res ID DISMUTASE TRANSGENIC MICE; EXCITATORY AMINO-ACIDS; BEHAVIORAL SENSITIZATION; DECOMPOSITION CATALYSTS; TYROSINE-HYDROXYLASE; SUPEROXIDE; SYNTHASE; 7-NITROINDAZOLE; INHIBITION; PROTECTS AB Methamphetamine (METH) is a neurotoxic psychostimulant that produces catecholaminergic brain damage by producing oxidative stress and free radical generation. The role of oxygen and nitrogen radicals is well documented as a cause of METH-induced neurotoxic damage. In this study, we have obtained evidence that METH-induced neurotoxicity is the resultant of interaction between oxygen and nitrogen radicals, and it is mediated by the production of peroxynitrite. we have also assessed the effects of inhibitors of neuronal nitric oxide synthase (nNOS) as well as scavenger of nitric oxide and a peroxynitrite decomposition catalyst. Significant protective effects were observed with the inhibitor of nNOS, 7-nitroindazole (7-NI), as well as by the selective peroxynitrite scavenger or decomposition catalyst, 5,10,15,20-tetrakis(2,4,6-trimethyl-3,5-sulfonatophenyl)porphyrinato iron III (FeTPPS). However, the use of a nitric oxide scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), did not provide any significant protection against METH-induced hyperthermia or peroxynitrite generation and the resulting dopaminergic neurotoxicity. In particular, treatment with FeTPPS completely prevented METH-induced hyperthermia, peroxynitrite production, and METH-induced dopaminergic depletion. Together, these data demonstrate that METH-induced dopaminergic neurotoxicity is mediated by the generation of peroxynitrite, which can be selectively protected by nNOS inhibitors or peroxynitrite scavenger or decomposition catalysts. C1 US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. Hamdard Univ, Dept Med Elementary & Toxicol, Neurotoxicol Lab, New Delhi, India. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 45 TC 35 Z9 36 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 1-57331-279-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 914 BP 157 EP 171 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BT09R UT WOS:000171939100016 PM 11085318 ER PT S AU Miller, DB O'Callaghan, JP Ali, SF AF Miller, DB O'Callaghan, JP Ali, SF BE Ali, SF TI Age as a susceptibility factor in the striatal dopaminergic neurotoxicity observed in the mouse following substituted amphetamine exposure SO NEUROBIOLOGICAL MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Neurobiological Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY AUG 04-06, 1999 CL COPENHAGEN, DENMARK SP Int Soc Neurochem, Neuroresearch, Sevier Amer, Bie & Berntsen AS, Parke Davis, Neurosci Res Div, USDA, Natl Ctr Toxicol Res ID FIBRILLARY ACIDIC PROTEIN; METHAMPHETAMINE NEUROTOXICITY; C57BL/6J MOUSE; NEONATAL RAT; MICE; BRAIN; HYPERTHERMIA; ONTOGENY; ASSAYS; RNA AB A number of substituted amphetamines, including methamphetamine (METH) are considered dopaminergic neurotoxicants. METH causes long-term depletions of striatal dopamine (DA) and its metabolites (DOPAC and HVA) that are accompanied by other changes indicative of nerve terminal degeneration. These include argyrophilia as detected by silver degeneration stains and an elevation in glial fibrillary acidic protein (GFAP), a marker of reactive gliosis in response to injury, as well as a long-term decrease in tyrosine hydroxylase (TH) protein levels. The susceptibility to the dopaminergic neurotoxicity of METH and the other amphetamines can be affected by a number of factors including age, gender, stress, and environment. Many of these susceptibility factors have been extensively investigated in the rat but less so in the mouse. As the availability of genetically altered mice continues to expand, this species is increasingly selected for study. Thus, in previous work we determined that stress, gender, and the environment can significantly impact the neurotoxicity of the amphetamines. Here we determined how age affects the striatal DA depletion and GFAP elevation induced by d-METH in C57BL/6 mice. Age was a significant determinant of the ability of a known neurotoxic regimen of d-METH (10 mg/kg x 4) to produce striatal DA depletion with one-month-old C57BL/6 mice displaying minimal and nonpersistent depletion of DA or its metabolites while mice 12 months of age displayed large and persistent depletions of DA (87%), DOPAC (71%), and HVA (94%). Large elevations in striatal GFAP were induced in mice 2-23 months of age by d-METH, with lower dosages of d-METH being effective in the older mice. In contrast, the usual neurotoxic regimen of d-METH was minimally effective in inducing GFAP elevations (49% over control) in one-month-old mice, despite elevations in body temperature equivalent to those observed in older mice. Although increasing the dosage of d-METH (20 to 80 mg/kg) did increase the GFAP response (100% over control), it was still well below that usually exhibited at the usual neurotoxic dosage (300-400% over control) in fully mature mice. These data suggest maturity of striatal dopamine systems may be an essential element in the striatal damage induced by the neurotoxic amphetamines. C1 NIOSH, CDC, Toxicol & Mol Biol Branch, Hlth Effects Lab Div, Morgantown, WV 26505 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Miller, DB (reprint author), NIOSH, CDC, Toxicol & Mol Biol Branch, Hlth Effects Lab Div, 1095 Willowdale Rd, Morgantown, WV 26505 USA. RI Miller, Diane/O-2927-2013; O'Callaghan, James/O-2958-2013 NR 30 TC 23 Z9 23 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-279-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 914 BP 194 EP 207 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BT09R UT WOS:000171939100019 PM 11085321 ER PT S AU Ray, SK Wilford, GG Ali, SF Banik, NL AF Ray, SK Wilford, GG Ali, SF Banik, NL BE Ali, SF TI Calpain upregulation in spinal cords of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease SO NEUROBIOLOGICAL MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Neurobiological Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY AUG 04-06, 1999 CL COPENHAGEN, DENMARK SP Int Soc Neurochem, Neuroresearch, Sevier Amer, Bie & Berntsen AS, Parke Davis, Neurosci Res Div, USDA, Natl Ctr Toxicol Res ID ACTIVATED NEUTRAL PROTEASE; DOPAMINERGIC NEUROTOXICITY; SUBSTANTIA-NIGRA; MPTP; APOPTOSIS; 1-METHYL-4-PHENYL-1,2,5,6-TETRAHYDROPYRIDINE; DESTRUCTION; PROTECTION; INHIBITORS; COERULEUS AB 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a heroin analogue, is a neurotoxin that undergoes in vivo oxidation by monoamine oxidase-B (MAO-B) to 1-methyl-4-phenylpyridinium ion (MPP+) which preferentially exerts its toxic effects on the dopaminergic neurons of the substantia nigra in brain. Spinal interneuronal pathways are also likely to be affected in the course of MPP+ neurotoxicity. The primary effect of MPP+ is mediated by irreversible inhibition of mitochondrial complex I, releasing free radicals. MPP+ may also activate N-methyl-D-aspartate (NMDA) receptors, increasing the cytosolic concentration of free Ca2+. Intracellular free radicals indirectly and free Ca2+ directly can activate Ca2+-dependent proteases such as calpain. We investigated involvement of calpain in spinal cord degeneration due to neurotoxin by subjecting male C57BL/6N mice (17 months old) to MPTP administration (12.5 mg/kg for 0.5 h; 25 mg/kg for 0.25 h; and 50 mg/kg for 0.25, 0.5, 1, 2, and 24 h). RT-PCR and Western. blot analysis were performed using the thoracic segment of spinal cords from control and MPTP-administered mice. The administration of MPTP caused calpain upregulation at the mRNA and protein levels to various extents, compared to control mice. Calpain activity was measured by 68 kDa neurofilament protein (NFP) degradation, which was increased in MPTP-induced PD mice. These results suggest that calpain may play a role in spinal cord degeneration in mice with MPTP-induced PD. C1 Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Banik, NL (reprint author), Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. FU NINDS NIH HHS [NS-31622, NS-38146] NR 42 TC 21 Z9 21 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-279-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 914 BP 275 EP 283 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BT09R UT WOS:000171939100025 PM 11085327 ER EF