FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Englert, B Senturker, S Dwyer, E Zhang, BL Shacter, E AF Englert, B Senturker, S Dwyer, E Zhang, BL Shacter, E TI Induction of different modes of cell death by different oxidants SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 US FDA, CBER, Immunol Lab, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 325 BP S106 EP S106 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200340 ER PT J AU Lawrence, SM Huddleston, KA Tomiya, N Nguyen, N Lee, YC Vann, WF Coleman, TA Betenbaugh, MJ AF Lawrence, SM Huddleston, KA Tomiya, N Nguyen, N Lee, YC Vann, WF Coleman, TA Betenbaugh, MJ TI Cloning and expression of human sialic acid pathway genes to generate CMP-sialic acids in insect cells SO GLYCOCONJUGATE JOURNAL LA English DT Article DE baculovirus; CMP-Neu5Ac; insect; KDN; sialic acid ID N-ACETYLNEURAMINIC ACID; CHINESE-HAMSTER OVARY; DEAMINATED NEURAMINIC ACID; 2-KETO-3-DEOXY-D-GLYCERO-D-GALACTO-NONONIC ACID; GLYCOSYLATION PATHWAY; GLYCAN PATTERNS; SYNTHETASE; KDN; IDENTIFICATION; GLYCOPROTEINS AB The addition of sialic acid residues to glycoproteins can affect important protein properties including biological activity and in vivo circulatory half-life. For sialylation to occur, the donor sugar nucleotide cytidine monophospho-sialic acid (CMP-SA) must be generated and enzymatically transferred to an acceptor oligosaccharide. However, examination of insect cells grown in serum-free medium revealed negligible native levels of the most common sialic acid nucleotide, CMP-N-acetylneuraminic acid (CMP-Neu5Ac). To increase substrate levels, the enzymes of the metabolic pathway for CMP-SA synthesis have been engineered into insect cells using the baculovirus expression system. In this study, a human CMP-sialic acid synthase cDNA was identified and found to encode a protein with 94% identity to the murine homologue. The human CMP-sialic acid synthase (Cmp-Sas) is ubiquitously expressed in human cells from multiple tissues. When expressed in insect cells using the baculovirus vector, the encoded protein is functional and localizes to the nucleus as in mammalian cells. In addition, co-expression of Cmp-Sas with the recently cloned sialic acid phosphate synthase with N-acetylmannosamine feeding yields intracellular CMP-Neu5Ac levels 30 times higher than those observed in unsupplemented CHO cells. The absence of any one of these three components abolishes CMP-Neu5Ac production in vivo. However, when N-acetylmannosamine feeding is omitted, the sugar nucleotide form of deaminated Neu5Ac, CMP-2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (CMP-KDN), is produced instead, indicating that alternative sialic acid glycoforms may eventually be possible in insect cells. The human CMP-SAS enzyme is also capable of CMP-N-glycolylneuraminic acid (CMP-Neu5Gc) synthesis when provided with the proper substrate. Engineering the CMP-SA metabolic pathway may be beneficial in various cell lines in which CMP-Neu5Ac production limits sialylation of glycoproteins or other glycans. C1 Johns Hopkins Univ, Dept Chem Engn, Baltimore, MD 21218 USA. Human Genome Sci, Prot Dev, Rockville, MD 20850 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. RP Betenbaugh, MJ (reprint author), Johns Hopkins Univ, Dept Chem Engn, 3400 N Charles St, Baltimore, MD 21218 USA. RI Betenbaugh, Michael J./A-3252-2010 OI Betenbaugh, Michael J./0000-0002-6336-4659 NR 38 TC 42 Z9 43 U1 2 U2 10 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0282-0080 J9 GLYCOCONJUGATE J JI Glycoconjugate J. PY 2001 VL 18 IS 3 BP 205 EP 213 DI 10.1023/A:1012452705349 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 482RX UT WOS:000171590000001 PM 11602804 ER PT J AU Meyer, JM Silliman, NP Dixon, CA Siepman, NY Sugg, JE Hopkins, RJ AF Meyer, JM Silliman, NP Dixon, CA Siepman, NY Sugg, JE Hopkins, RJ TI Helicobacter pylori and early duodenal ulcer status post-treatment: a review SO HELICOBACTER LA English DT Review DE ulcers; eradication; clinical trials; ranitidine-bismuth-citrate; lansoprazole; omeprazole ID RANITIDINE BISMUTH CITRATE; DOUBLE-BLIND; PEPTIC-ULCER; PLUS CLARITHROMYCIN; TRIPLE THERAPY; DUAL THERAPY; ERADICATION; AMOXICILLIN; RECURRENCE; METRONIDAZOLE AB Background. Data submit-red to the FDA were reviewed to analyze the relationship between Helicobacter pylori infection and the incidence of early duodenal ulcers, within 6 weeks, following treatment. Materials and Methods, Retrospective analyzes were performed on data from three H. pylori development programs submitted to the FDA: ranitidine-bismuth-citrate (RBC), lansoprazole (L) and omeprazole (O). Efficacy assessments for the RBC, L and O programs were made at end of a 4-week treatment period, 4-6 weeks following the end of a 14-day treatment period, and 4 weeks following the end of a 4-week treatment period, respectively. Results. Overall, there was a 15%, 21% and 23% decrease in the number of patients in the RBC, L and O programs, respectively, with ulcers among H. pylori cleared/eradicated patients post-treatment compared with patients with persistent infection. Among patients who did not have cleared/eradicated H. pylori in the RBC and O programs, where antisecretory agents were continued beyond the antimicrobial treatment period, the number of ulcers was lower in the antisecretory plus antimicrobial subgroups compared with the antimicrobial alone subgroups (37% vs. 46% for RBC and 33% vs. 42% for O). Among patients with cleared/eradicated H. pylori, the number of patients with ulcers in the antimicrobial alone subgroups and antisecretory plus antimicrobial subgroups were similar within each program. Antimicrobials alone had significantly lower rates of ulcers among patients with cleared/eradicated H. pylori as compared with patients without clearance/eradication. Conclusions. The early incidence of duodenal ulcers is significantly decreased in patients with H. pylori clearance/eradication. C1 US FDA, Ctr Drug Evaluat & Res, Div Special Pathogen & Immunol Drug Prod, Rockville, MD 20850 USA. TAP Pharmaceut Prod Inc, Lake Forest, IL USA. AstraZeneca LP, Wayne, PA USA. RP Meyer, JM (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Special Pathogen & Immunol Drug Prod, 9201 Corp Blvd,HFD-880, Rockville, MD 20850 USA. NR 27 TC 4 Z9 11 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1083-4389 J9 HELICOBACTER JI Helicobacter PY 2001 VL 6 IS 2 BP 84 EP 92 DI 10.1046/j.1523-5378.2001.00013.x PG 9 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 444YV UT WOS:000169428900002 PM 11422462 ER PT S AU Krause, PR AF Krause, PR BE Gershon, AA Calisher, CH Arvin, AM TI Evidence for frequent reactivation of the Oka varicella vaccine strain in healthy vaccinees SO IMMUNITY TO AND PREVENTION OF HERPES ZOSTER SE ARCHIVES OF VIROLOGY, SUPPLEMENTUM LA English DT Proceedings Paper CT International Conference on Immunity and Prevention of Herpes Zoster CY MAR 08-10, 1999 CL OSAKA, JAPAN ID ZOSTER VIRUS-INFECTIONS; FOLLOW-UP; HERPES-ZOSTER; CHILDREN; CHICKENPOX; EFFICACY; IMMUNIZATION; EPIDEMIOLOGY; IMMUNITY; LEUKEMIA AB Serum antibody levels and infection rates were followed for 4 years in 4,631 children immunized with the recently licensed Oka strain varicella vaccine. Anti-VZV titers declined over time in high-responder subjects, but rose in vaccinees with low titers. Among subjects with low anti-VZV titers, the frequency of clinical sequelae and immunological boosting significantly exceeded the 13%/yr rate of exposure to wild type varicella. These findings indicate that the Oka strain of VZV persisted in vivo, and reactivated as serum antibody titers declined after vaccination. This mechanism may improve vaccine-associated long-term immunity. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Krause, PR (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bldg 29A,Rm 1 C 16, Bethesda, MD 20892 USA. NR 29 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 0939-1983 BN 3-211-83555-5 J9 ARCH VIR S PY 2001 VL 17 BP 7 EP 15 PG 9 WC Public, Environmental & Occupational Health; Immunology; Virology SC Public, Environmental & Occupational Health; Immunology; Virology GA BS22Q UT WOS:000169113800002 ER PT J AU Bosio, CM Elkins, KL AF Bosio, CM Elkins, KL TI Susceptibility to secondary Francisella tularensis live vaccine strain infection in B-cell-deficient mice is associated with neutrophilia but not with defects in specific T-cell-mediated immunity SO INFECTION AND IMMUNITY LA English DT Article ID FACULTATIVE INTRACELLULAR BACTERIUM; PROTECTIVE IMMUNITY; GAMMA-INTERFERON; RESISTANCE; TULAREMIA; LVS; MACROPHAGES; GENERATION; PATHOGEN; REQUIREMENT AB Previous studies have demonstrated a role for B cells, not associated with antibody production, in protection against lethal secondary infection of mice with Francisella tularensis live vaccine strain (LVS). However, the mechanism by which B cells contribute to this protection is not known. To study the specific role of B cells during secondary LVS infection, we developed an in vitro culture system that mimics many of the same characteristics of in vivo infection. Using this culture system, we showed that B cells do not directly control LVS infection but that control of LVS growth is mediated primarily by LVS-primed T cells. Importantly, B cells were not required for the generation of effective memory T cells since LVS-primed, B-cell-deficient (BKO) mice generated CD4(+) and CD8(+) T cells that controlled LVS infection similarly to LVS-primed CD4(+) and CD8(+) T cells from wild-type mice. The control of LVS growth appeared to depend primarily on gamma interferon and nitric oxide and was similar in wild-type and BKO mice. Rather, the inability of BKO mice to survive secondary LVS infection was associated with marked neutrophil influx into the spleen very early after challenge. The neutrophilia was directly associated with B cells, since BKO mice reconstituted with naive B cells prior to a secondary challenge with LVS had decreased bacterial loads and neutrophils in the spleen and survived. C1 US FDA, CDER, Div Bacterial Parasit & Allergen Prod, Lab Mycobacteria, Rockville, MD 20852 USA. RP Elkins, KL (reprint author), US FDA, CDER, Div Bacterial Parasit & Allergen Prod, Lab Mycobacteria, 1401 Rockville Pike,HFM 431, Rockville, MD 20852 USA. NR 41 TC 77 Z9 79 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2001 VL 69 IS 1 BP 194 EP 203 DI 10.1128/IAI.69.1.194-203.2001 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 384LF UT WOS:000165943500025 PM 11119506 ER PT J AU Mitchell, GV Cook, KK Jenkins, MY Grundel, E AF Mitchell, GV Cook, KK Jenkins, MY Grundel, E TI Supplementation of rats with a lutein mixture preserved with vitamin E reduces tissue phylloquinone and menaquinone-4 SO INTERNATIONAL JOURNAL FOR VITAMIN AND NUTRITION RESEARCH LA English DT Article DE lutein; vitamin E; vitamin K; menaquinone; trans-phylloquinone; cis-phylloquinone; rats ID BETA-CAROTENE; ALPHA-TOCOPHEROL; HUMANS; PLASMA AB The modulation of tissue concentrations of vitamin K by a lutein supplement preserved with natural vitamin E was studied in Fischer 344 rats. Vitamin K is necessary for blood coagulation and may be essential for tissue and bone health. Weanling male rats were fed the AIN-93G diet (control) or modified AIN-93G diets containing 0.3, 0.6, 1.2, 2.4 and 4.8 g supplement/100 g diet for 8 weeks. The supplement contained 5% lutein, 0.22% zeaxanthin and 2.2% natural vitamin E as a preservative. Concentrations of trans-phylloquinone in the plasma (nmol/mmol triglycerides) and heart were significantly reduced (P less than or equal to 0.05) in rats fed the supplement. The reductions in trans-phylloquinone in the heart ranged from similar to 20 to 60% of the control. Concentrations of phylloquinone in the liver were significantly lower in the rats fed the supplement at levels greater than or equal to 1.2 g/100 g diet than in the control rats. Ratios Of cis/trans phylloquinone in liver and heart increased and concentrations of menaquinone-4 in heart decreased as the dietary level of the lutein supplement increased, The results suggest that the lutein supplement affected the absorption, tissue uptake and/or turnover rate of vitamin K, The presence Of-other components in the supplement confounded the interpretation of the biological effects of lutein alone on vitamin K metabolism. C1 US FDA, Off Nutr Prod Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Mitchell, GV (reprint author), US FDA, Off Nutr Prod Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 24 TC 5 Z9 5 U1 1 U2 3 PU VERLAG HANS HUBER PI BERN 9 PA LANGGASS-STRASSE 76, CH-3000 BERN 9, SWITZERLAND SN 0300-9831 J9 INT J VITAM NUTR RES JI Int. J. Vitam. Nutr. Res. PD JAN PY 2001 VL 71 IS 1 BP 30 EP 35 DI 10.1024/0300-9831.71.1.30 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 407HQ UT WOS:000167266500004 PM 11276919 ER PT J AU Schwetz, BA AF Schwetz, BA TI Toxicology at the food and drug administration: New century, new challenges SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, 5600 Fisher Lane,HF-2,Room 14-71, Rockville, MD 20857 USA. NR 0 TC 10 Z9 10 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. PY 2001 VL 20 IS 1 BP 3 EP 8 DI 10.1080/109158101750103297 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 406VB UT WOS:000167235800002 PM 11288931 ER PT J AU Duarte, CG Zhang, J Ellis, S AF Duarte, CG Zhang, J Ellis, S TI Review of studies establishing the aging male spontaneously hypertensive rat as a detector and quantifier of the kidney toxicity of radiocontrast media and other chemicals SO INVESTIGATIVE RADIOLOGY LA English DT Article DE spontaneously hypertensive rats; blood pressure; radiocontrast; mannitol; endothelin; renal damage ID ACUTE-RENAL-FAILURE; SYMPATHETIC-NERVE ACTIVITY; NITRIC-OXIDE SYNTHASE; BLOOD-PRESSURE; CONTRAST-MEDIA; NEPHROTOXICITY; ENDOTHELIN; MANNITOL; NEPHROPATHY; AGENTS AB RATIONALE AND OBJECTIVES. There is a need for practical and sensitive preclinical tests for detecting the kidney toxicity of chemicals. The spontaneously hypertensive rat (SHR), as it ages, develops renal and cardiovascular changes similar to those considered as human risk factors for radiocontrast-induced renal damage. Age, male gender, and uncontrolled hypertension make these animals susceptible to the volume and osmolality of the administered contrast agent and the effect of repeated contrast administration after a brief interval. This article reviews studies in which the role of these and other factors were evaluated to validate the male SHR as a small animal model for renal damage induced by contrast and other agents. METHODS. Systolic blood pressure was measured with a tail cuff before and after the administration of the experimental substances, and the left kidney and heart were studied histologically to determine the influence of age, dose of contrast repeated at a short interval, gender and strain, the role of the sympathetic adrenergic nervous system, osmolality, and apoptosis, RESULTS. AS the animals aged and the systolic blood pressure remained elevated, the animals developed progressive renal lesions that worsened after the administration of contrast. The most advanced renal lesions occurred in adult male SHRs that received two doses of contrast 6 hours apart. Female SHR rats and male Wistar Kyoto rats showed no effect or only minimal changes in heart and kidneys after the administration of contrast compared with age-matched male SHRs. Adrenergic blockade allowed only a small elevation in systolic blood pressure after contrast administration but did not protect the kidneys against renal damage by contrast. Hypaque, Omnipaque, and mannitol caused renal damage in proportion to their osmolality, Apoptosis with Hypaque, Omnipaque, and mannitol was observed in the kidney and heart. CONCLUSIONS. The results indicate that the aging male SHR develops spontaneous renal lesions that progress with age, increasing the susceptibility to the renal-damaging effects of contrast. Thus, the aging male SHR provides a laboratory tool for detecting the risk of renal damage of new contrast media as well as other pharmaceuticals and assessing methods to protect the kidneys and possible mechanisms of renal damage. C1 US FDA, Div Cardiorenal Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Duarte, CG (reprint author), US FDA, Div Cardiorenal Drug Prod, Ctr Drug Evaluat & Res, HFD-110,5600 Fishers Lane, Rockville, MD 20857 USA. NR 46 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JAN PY 2001 VL 36 IS 1 BP 56 EP 63 DI 10.1097/00004424-200101000-00008 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 389UW UT WOS:000166257900008 PM 11176262 ER PT J AU Heitkemper, DT Vela, NP Stewart, KR Westphal, CS AF Heitkemper, DT Vela, NP Stewart, KR Westphal, CS TI Determination of total and speciated arsenic in rice by ion chromatography and inductively coupled plasma mass spectrometry SO JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ATOMIC-ABSORPTION SPECTROMETRY; FDA TOTAL DIET; HPLC-ICP-MS; HYDRIDE GENERATION; BIOLOGICAL SAMPLES; SEAFOOD PRODUCTS; UNITED-STATES; WILD-RICE; FOOD AB A method is presented for arsenic speciation analysis in rice using ion chromatography coupled to inductively coupled plasma mass spectrometry. Several procedures for the extraction of arsenic species from rice were investigated and compared. Treatment of the samples with 2 M trifluoroacetic acid for 6 h at 100 degreesC provided good extraction efficiency. Fortification recoveries were 83, 88, 100, and 93% for arsenite (100 ng As g(-1)), arsenate (100 ng As g(-1)), methylarsonic acid (MMA, 50 ng As g(-1)), and dimethylarsinic acid (DMA, 200 ng As g(-1)), respectively. The arsenate fortification recovery was calculated using the sum of the increase in arsenate and arsenite concentrations because arsenate was partially reduced to arsenite during the extraction process. Thus the sum of their concentrations is reported in this method as total inorganic arsenic. The sum of the arsenic species determined in NIST SRM 1568a rice flour (0.27 mug g(-1)As), compared well with the certified total arsenic value (0.29 mug g(-1) As). The speciation results obtained for 5 samples of long grain rice and one sample of wild rice are compared with total arsenic concentrations as determined by ICP-MS. The total arsenic concentrations ranged from 0.11 to 0.34 mg kg(-1). The sum of the arsenic species extracted and determined by IC-ICP-MS ranged from 84 to 99% of the measured total arsenic concentrations. Inorganic arsenic accounted for 11-91% of the arsenic detected while DMA accounted for most of the remaining arsenic in the samples. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. Belcan Techserv, Cincinnati, OH 45249 USA. RP Heitkemper, DT (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. NR 39 TC 220 Z9 225 U1 8 U2 83 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD,, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0267-9477 J9 J ANAL ATOM SPECTROM JI J. Anal. At. Spectrom. PY 2001 VL 16 IS 4 BP 299 EP 306 DI 10.1039/b007241i PG 8 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 418CJ UT WOS:000167871900001 ER PT J AU Ciolino, LA McCauley, HA Fraser, DB Wolnik, KA AF Ciolino, LA McCauley, HA Fraser, DB Wolnik, KA TI The relative buffering capacities of saliva and moist snuff: Implications for nicotine absorption SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID LIQUID-CHROMATOGRAPHIC DETERMINATION; SMOKELESS TOBACCO; BUCCAL ABSORPTION; CHEWING TOBACCO; DRUG DELIVERY; PRODUCTS; MUCOSA; BICARBONATE; MEMBRANES; PLASMA C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Ciolino, LA (reprint author), US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. NR 42 TC 8 Z9 8 U1 0 U2 4 PU PRESTON PUBL INC PI NILES PA 6600 W TOUHY AVE, NILES, IL 60714-4588 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD JAN-FEB PY 2001 VL 25 IS 1 BP 15 EP 25 PG 11 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 396KM UT WOS:000166635600004 PM 11215994 ER PT J AU Hammack, TS Amaguana, RM Andrews, WH AF Hammack, TS Amaguana, RM Andrews, WH TI Rappaport-vassiliadis medium for recovery of Salmonella spp. from low microbial load foods: Collaborative study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID SELENITE CYSTINE BROTH; HIGHLY CONTAMINATED FOODS; RELATIVE EFFECTIVENESS; SELECTIVE ENRICHMENT; TETRATHIONATE BROTH; RAW FLESH AB Twenty-three laboratories participated in a collaborative study to compare the relative effectiveness of Rappaport-Vassiliadis (RV) medium incubated at 42 degreesC, selenite cystine (SC) broth (35 degreesC), and tetrathionate (TT) broth (35 and 43 degreesC) for recovery of Salmonella from the following foods with a low microbial load: dried egg yolk, dry active yeast, ground black pepper, guar gum, and instant nonfat dry milk. For dry active yeast, lauryl tryptose (LT) broth, incubated at 35 degreesC, was used instead of SC broth. All of the foods were artificially inoculated with single Salmonella serovars, that had been lyophilized before inoculation, at high and low target levels of 0.4 and 0.04 colony forming units/g food, respectively. For analysis of 870 test portions, representing all of the foods except yeast, 249 Salmonella-positive test portions were detected by RV medium, 265 by TT broth (43 degreesC), 268 by TT broth (35 degreesC), and 269 by SC broth (35 degreesC). For analysis of 225 test portions of yeast, 79 Salmonella-positive test portions were detected by RV medium, 79 by TT broth (43 degreesC), 84 by TT broth (35 degreesC), and 68 by LT broth (35 degreesC). RV medium was comparable to, or even more effective than, the other selective enrichments for recovery of Salmonella from all of the foods except guar gum. It is recommended that RV (42 degreesC) and TT (35 degreesC) be used with foods that have a low microbial load, except for guar gum for which SC (35 degreesC) and TT (35 degreesC) are recommended. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Hammack, TS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-516,200 C St SW, Washington, DC 20204 USA. NR 19 TC 9 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 JAN-FEB PY 2001 VL 84 IS 1 BP 65 EP 83 PG 19 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 402RK UT WOS:000167001800013 PM 11234854 ER PT J AU Ferreira, JL AF Ferreira, JL TI Comparison of amplified ELISA and mouse bioassay procedures for determination of botulinal toxins A, B, E, and F SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB The amplified enzyme-linked immunosorbent assay (amp-ELISA) was compared to the mouse bioassay for determination of botulinal neurotoxin types A, B, E, and F, Twelve different toxin-producing type A, 13 proteolytic type B, 9 nonproteolytic type B, 16 type E, 8 proteolytic type F, 5 nonproteolytic type F, and 6 nontoxigenic clostridial strains were tested, The cultures were inoculated into cooked meat medium (CMM) and tryptone-peptone-glucose-yeast extract (TPGY) medium, incubated for 5 days, and then examined for biological toxicity in mice and amp-ELISA endpoints, The amp-ELISA was less sensitive in detecting toxins produced by nonproteolytic than proteolytic strains of type B and F organisms. All of the toxin-producing strains tested were positive by the AOAC method and the amp-ELISA in either undiluted TPGY or CMM culture fluids regardless of mouse toxicity level, source, or strain. Cross-reactivity was observed between some but not all of the botulinal strains tested, None of the nontoxigenic strains were positive by the amp-ELISA, Purified botulinal toxins were also assayed using these 2 methods. The sensitivity of the amp-ELISA using purified neurotoxins was about 0.1 ng/mL for types A, B, and E and about 1.0 ng/mL for type F. C1 US FDA, SE Reg Lab, Atlanta, GA 30309 USA. RP Ferreira, JL (reprint author), US FDA, SE Reg Lab, 60 8th St, Atlanta, GA 30309 USA. NR 7 TC 24 Z9 25 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 2001 VL 84 IS 1 BP 85 EP 88 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 402RK UT WOS:000167001800014 PM 11234855 ER PT J AU Hepp, NM Cargill, AM Shields, WB AF Hepp, NM Cargill, AM Shields, WB TI Automated microwave digestion of certifiable color additives for determination of mercury by cold vapor atomic absorption spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID TOTAL HG; ONLINE; URINE AB A procedure using an automated microwave flow digestion technique was developed and validated for the digestion of samples of certifiable color additives before mercury determination by cold vapor atomic absorption spectrometry, Recovery studies were performed by spiking most of the color additives subject to batch certification by the U.S. Food and Drug Administration with inorganic mercury (HgNO3) and with organic mercury (CH3HgCl), Successful recoveries of 72-113% Hg added at the 1 mug/g level were obtained. A method detection limit of 0.2 mug Hg/g was estimated from a Hg-spiked FD&C Yellow No. 6 sample. At the specification level of 1 ppm Hg (1 mug Hg/g), the 95% confidence interval was +/- 0.2 ppm (0.2 mug Hg/g). C1 US FDA, Off Cosmet & Colors, Washington, DC 20204 USA. RP Hepp, NM (reprint author), US FDA, Off Cosmet & Colors, 200 C St SW, Washington, DC 20204 USA. NR 14 TC 6 Z9 6 U1 0 U2 1 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2001 VL 84 IS 1 BP 117 EP 122 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 402RK UT WOS:000167001800018 PM 11234797 ER PT J AU Schwetz, BA AF Schwetz, BA TI US Food and Drug Administration - A science-based regulatory agency SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US FDA, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, 5600 Fishers Ln, Rockville, MD 20857 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 JAN-FEB PY 2001 VL 84 IS 1 BP 171 EP 175 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 402RK UT WOS:000167001800026 PM 11234805 ER PT J AU Firestone, D AF Firestone, D TI Assuring the integrity of olive oil products SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LIQUID-CHROMATOGRAPHY; GAS-CHROMATOGRAPHY; VIRGIN; IDENTIFICATION; ADULTERATION; SPECTROSCOPY; TOCOPHEROLS; SQUALENE; STEROLS C1 US FDA, Washington, DC 20204 USA. RP Firestone, D (reprint author), 14801 Pennfield Circle 309, Silver Spring, MD 20906 USA. NR 39 TC 6 Z9 6 U1 0 U2 0 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2001 VL 84 IS 1 BP 176 EP 180 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 402RK UT WOS:000167001800027 PM 11234806 ER PT J AU Boone, G AF Boone, G TI A year of change and challenge for AOAC INTERNATIONAL SO JOURNAL OF AOAC INTERNATIONAL LA English DT Editorial Material C1 US FDA, Brooklyn, NY 11232 USA. RP Boone, G (reprint author), 2032 Haverford Dr, Crownsville, MD 21032 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 JAN-FEB PY 2001 VL 84 IS 1 BP 181 EP 182 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 402RK UT WOS:000167001800028 PM 11234807 ER PT J AU Trucksess, MW AF Trucksess, MW TI Mycotoxins SO JOURNAL OF AOAC INTERNATIONAL LA English DT Review ID SOLID-PHASE EXTRACTION; PERFORMANCE LIQUID-CHROMATOGRAPHY; OCHRATOXIN-A; FUSARIUM-GRAMINEARUM; CYCLOPIAZONIC ACID; MASS-SPECTROMETRY; FUMONISIN B-1; TRICHOTHECENE MYCOTOXINS; FLUOROMETRIC DETECTION; MEASURING AFLATOXIN C1 US FDA, Washington, DC 20204 USA. RP Trucksess, MW (reprint author), US FDA, 200 C St SW, Washington, DC 20204 USA. NR 117 TC 12 Z9 12 U1 0 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2001 VL 84 IS 1 BP 202 EP 211 PG 10 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 402RK UT WOS:000167001800033 PM 11234813 ER PT J AU Williams, KM AF Williams, KM TI Food allergens SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US FDA, Laurel, MD 20902 USA. RP Williams, KM (reprint author), US FDA, 8301 Muirkirk Rd, Laurel, MD 20902 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 JAN-FEB PY 2001 VL 84 IS 1 BP 211 EP 212 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 402RK UT WOS:000167001800034 PM 11234814 ER PT J AU Chase, GW AF Chase, GW TI Infant formula and medical diets SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID SOLID-PHASE DISPERSION C1 US FDA, Pacific Reg Lab NW, Bothell, WA 98021 USA. RP Chase, GW (reprint author), US FDA, Pacific Reg Lab NW, 22201 23rd Dr SE, Bothell, WA 98021 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2001 VL 84 IS 1 BP 218 EP 219 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 402RK UT WOS:000167001800037 PM 11234817 ER PT J AU Firestone, D Yurawecz, MP AF Firestone, D Yurawecz, MP TI Fats and oils SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; NUCLEAR-MAGNETIC-RESONANCE; GAS-LIQUID; OLIVE OIL; SPECTROSCOPY; CULTIVARS; MIXTURES; STEROLS C1 US FDA, Washington, DC 20204 USA. RP Firestone, D (reprint author), US FDA, HFS 175,200 C St SW, Washington, DC 20204 USA. NR 31 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 JAN-FEB PY 2001 VL 84 IS 1 BP 219 EP 222 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 402RK UT WOS:000167001800038 PM 11234818 ER PT J AU Baratta, E AF Baratta, E TI Radioactivity SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. RP Baratta, E (reprint author), US FDA, Winchester Engn & Analyt Ctr, 109 Holton St, Winchester, MA 01890 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 JAN-FEB PY 2001 VL 84 IS 1 BP 236 EP 237 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 402RK UT WOS:000167001800045 PM 11234825 ER PT J AU Parfitt, CH AF Parfitt, CH TI Multiclass multiresidue methods for organic compounds SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US FDA, Div Field Sci HFC141, Rockville, MD 20857 USA. RP Parfitt, CH (reprint author), US FDA, Div Field Sci HFC141, 5600 Fishers Ln, 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 JAN-FEB PY 2001 VL 84 IS 1 BP 239 EP 240 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 402RK UT WOS:000167001800047 PM 11234827 ER PT J AU Andrews, WH AF Andrews, WH TI Food microbiology - Non-dairy SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US FDA, 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 7 TC 0 Z9 0 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2001 VL 84 IS 1 BP 243 EP 250 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 402RK UT WOS:000167001800049 PM 11234830 ER PT J AU Boucher, PE Yang, MS Schmidt, DM Stibitz, S AF Boucher, PE Yang, MS Schmidt, DM Stibitz, S TI Genetic and biochemical analyses of BvgA interaction with the secondary binding region of the fha promoter of Bordetella pertussis SO JOURNAL OF BACTERIOLOGY LA English DT Article ID 2-COMPONENT SENSOR PROTEIN; ESCHERICHIA-COLI; RNA-POLYMERASE; VIRULENCE FACTORS; TOXIN PROMOTER; TRANSCRIPTIONAL ACTIVATION; UHPT PROMOTER; DNA-BINDING; LOCUS; SITES AB The BvgA-BvgS two-component signal transduction system regulates expression of virulence factors in Bordetella pertussis. The BvgA response regulator activates transcription by binding to target promoters, which include those for the genes encoding filamentous hemagglutinin (fha) and pertussis toxin (ptx). We have previously shown that at both promoters the phosphorylated form of BvgA binds multiple high- and low-affinity sites. Specifically, at the fha promoter, we proposed that there may be high- and a low-affinity binding sites for the BvgA dimer. In our present investigation, we used DNA binding analyses and in vitro and in vivo assays of promoters with substitutions and deletions to support and extend this hypothesis. Our observations indicate that (i) binding of BvgA similar toP to a primary (high-affinity) site and a secondary binding region (lo,ver affinity) is cooperative, (ii) although both the primary binding site and the secondary binding region are required for full activity of the wild-type (undeleted) promoter, deletion of two helical turns within the secondary binding region can produce a fully active or hyperactive promoter, and (iii) BvgA binding to the secondary binding region shows limited DNA sequence specificity. C1 US FDA, Ctr Biol Evaluat & Res, DBPAP, Bethesda, MD 20892 USA. RP Boucher, PE (reprint author), US FDA, Ctr Biol Evaluat & Res, DBPAP, Bldg 29,Room 526,HFM-440,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 46 TC 34 Z9 35 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JAN PY 2001 VL 183 IS 2 BP 536 EP 544 DI 10.1128/JB.183.2.536-544.2001 PG 9 WC Microbiology SC Microbiology GA 387KJ UT WOS:000166121500015 PM 11133947 ER PT J AU Turesin, F Gursel, I Hasirci, V AF Turesin, F Gursel, I Hasirci, V TI Biodegradable polyhydroxyalkanoate implants for osteomyelitis therapy: in vitro antibiotic release SO JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION LA English DT Article DE polyhydroxyalkanoates; biodegradable implants; osteomyelitis; controlled drug delivery; antibiotics ID BACTERIAL POLYHYDROXYALKANOATES; DELIVERY SYSTEM; INFECTIONS; BEADS; POLY(3-HYDROXYBUTYRATE); POLYHYDROXYBUTYRATE; DEGRADATION; INVITRO; INVIVO; ACID) AB Various random copolyesters of 3-hydroxybutyrate and 3-hydroxyvalerate (PHBV) and 3-hydroxybutyrate and l-hydroxybutyrate P(3HB-4HB) were used in the construction of biodegradable, implantable rods for the local delivery of antibiotics (Sulperazone(R) and Duocid(R)) in chronic osteomyelitis therapy. Drug loading, type of active agent, and additional coating of the implant surface all have significant contributions to the in vitro release profile. The rate and duration of Sulperaxone(R) release from P(3HB-4HB) rods were controlled by the polymer/drug ratio (drug loading). The rate of drug dissolution was substantially higher than that of polymer degradation. Therefore, the release phenomenon was more dependent on drug dissolution rather than on polymer degradation or diffusion. Coating rods with the same type of polymer substantially reduced the initial burst effect observed with the uncoated rods, and significantly decreased the release rate so that the release kinetics became almost zero order. Antibiotic release from coated rods was sustained for over a period of 2 weeks at a constant rate, whereas uncoated rods released their contents in less than a week. Impregnation of Duocid(R) into the hydrophobic polymer matrix yielded a rod with a smoother surface topography. The release from these rods was significantly higher than for rods loaded with Sulperazone(R) and a zero order release could not be obtained with these samples. C1 Middle E Tech Univ, Dept Biol Sci, Biotechnol Res Unit, TR-06531 Ankara, Turkey. US FDA, Biol Res Ctr, Lab Retroviral Immunol, Bethesda, MD 20892 USA. Univ Calgary, Hlth Sci Ctr, Calgary, AB T2N 4N1, Canada. RP Hasirci, V (reprint author), Middle E Tech Univ, Dept Biol Sci, Biotechnol Res Unit, TR-06531 Ankara, Turkey. OI Gursel, Ihsan/0000-0003-3761-1166 NR 39 TC 45 Z9 48 U1 3 U2 11 PU VSP BV PI ZEIST PA PO BOX 346, 3700 AH ZEIST, NETHERLANDS SN 0920-5063 J9 J BIOMAT SCI-POLYM E JI J. Biomater. Sci.-Polym. Ed. PY 2001 VL 12 IS 2 BP 195 EP 207 DI 10.1163/156856201750180924 PG 13 WC Engineering, Biomedical; Materials Science, Biomaterials; Polymer Science SC Engineering; Materials Science; Polymer Science GA 439DV UT WOS:000169096300006 PM 11403236 ER PT J AU Shi, LM Fang, H Tong, WD Wu, J Perkins, R Blair, RM Branham, WS Dial, SL Moland, CI Sheehan, DM AF Shi, LM Fang, H Tong, WD Wu, J Perkins, R Blair, RM Branham, WS Dial, SL Moland, CI Sheehan, DM TI QSAR models using a large diverse set of estrogens SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article ID MOLECULAR-FIELD ANALYSIS; R(2)-GUIDED REGION SELECTION; RECEPTOR-BINDING-AFFINITY; ANALYSIS COMFA; ENVIRONMENTAL ESTROGENS; ENDOCRINE DISRUPTORS; CHEMICALS; BETA; IDENTIFICATION; PHARMACOPHORE AB Endocrine disruptors (EDs) have a variety of adverse effects in humans and animals. About 58 000 chemicals, most having little safety data, must be tested in a group of tiered assays. As assays will take years, it is important to develop rapid methods to help in priority setting. For application to large data sets, we have developed an integrated system that contains sequential four phases to predict the ability of chemicals to bind to the estrogen receptor (ER), a prevalent mechanism for estrogenic EDs. Here we report the results of evaluating two types of QSAR models for inclusion in phase III to quantitatively predict chemical binding to the ER. Our data set for the relative binding affinities (RBAs) to the ER consists of 130 chemicals covering a wide range of structural diversity and a 6 orders of magnitude spread of RBAs. CoMFA and HQSAR models were constructed and compared for performance. The CoMFA model had a r(2) = 0.91 and a q(LOO)(2) = 0.66. HQSAR showed reduced performance compared to CoMFA with r(2) = 0.76 and q(LOO)(2) = 0.59. A number of parameters were examined to improve the CoMFA model. Of these, a phenol indicator increased the q(LOO)(2) to 0.71. When up to 50% of the chemicals were left out in the leave-N-out cross-validation, the q(2) remained significant. Finally, the models were tested by using two test sets; the q(pred)(2) for these were 0.71 and 0.62, a significant result which demonstrates the utility of the CoMFA model for predicting the RBAs of chemicals not included in the training set. If used in conjunction with phases I and II, which reduced the size of the data set dramatically by eliminating most inactive chemicals, the current CoMFA model (phase III) can be used to predict the RBA of chemicals with sufficient accuracy and to provide quantitative information for priority setting. C1 ROW Sci Inc, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Tong, WD (reprint author), ROW Sci Inc, Jefferson, AR 72079 USA. NR 37 TC 217 Z9 229 U1 2 U2 26 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD JAN-FEB PY 2001 VL 41 IS 1 BP 186 EP 195 DI 10.1021/ci000066d PG 10 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 395JY UT WOS:000166578300024 PM 11206373 ER PT J AU Beger, RD Freeman, JP Lay, JO Wilkes, JG Miller, DW AF Beger, RD Freeman, JP Lay, JO Wilkes, JG Miller, DW TI Use of C-13 NMR spectrometric data to produce a predictive model of estrogen receptor binding activity SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article ID PROPERTY RELATIONSHIP TREATMENT; AUTOMATED STRUCTURE EVALUATION; MOLECULAR-FIELD ANALYSIS; CHEMICAL-SHIFTS; CHROMATOGRAPHIC RETENTION; NEURAL-NETWORK; TOOL; SPECTRA; QSAR AB We have developed a spectroscopic data-activity relationship (SDAR) model based on C-13 NMR spectral data for 30 estrogenic chemicals whose relative binding affinities (RBA) are available for the alpha (ER alpha) and beta (ERP) estrogen receptors. The SDAR models segregated the 30 compounds into strong and medium binding affinities. The SDAR model gave a leave-one-out (LOO) cross-validation of 90%. Two compounds that were classified incorrectly in the SDAR model were in the transition zone between classifications. Real and predicted C-13 NMR chemical shifts were used with test compounds to evaluate the predictive behavior of the SDAR model. The C-13 NMR SDAR model using predicted C-13 NMR data for the test compounds provides a rapid, reliable, and simple way to screen whether a compound binds to the estrogen receptors. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Beger, RD (reprint author), 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 33 TC 26 Z9 33 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD JAN-FEB PY 2001 VL 41 IS 1 BP 219 EP 224 DI 10.1021/ci0000878 PG 6 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 395JY UT WOS:000166578300027 PM 11206376 ER PT J AU Reed, HL Reedy, KR Palinkas, LA Van Do, N Finney, NS Case, HS LeMar, HJ Wright, J Thomas, J AF Reed, HL Reedy, KR Palinkas, LA Van Do, N Finney, NS Case, HS LeMar, HJ Wright, J Thomas, J TI Impairment in cognitive and exercise performance during prolonged antarctic residence: Effect of thyroxine supplementation in the polar triiodothyronine syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 71st Annual Meeting of the American-Thyroid-Association CY SEP 16-20, 1998 CL PORTLAND, OR SP Amer Thyroid Assoc ID LOCAL COLD-ACCLIMATION; HYPERTHYROIDISM; HYPOTHYROIDISM; THYROTROPIN; EFFICIENCY; KINETICS; ILLNESS; TSH AB Humans who work in Antarctica display deficits in cognition, disturbances in mood, increased energy requirements, a decline of thyroid hormone products, and an increase of serum TSH. We compared measurements in 12 subjects, before deployment (baseline), with 11 monthly studies during Antarctic residence (AR). After 4 months of AR (period 1), half of the subjects (T(4) group) received L-thyroxine [64 nmol.day(-1) (0.05 mg.day(-1))]; and the other half, a placebo (placebo group) for the next 7 months of AR (period 2). During period 1, there was a 12.3 +/- 5.1% (P < 0.03) decline on the matching-to-sample (M-t-S) cognitive task and an increase in depressive symptoms, compared with baseline. During the intervention in period 2, M-t-S scores for the T(4)-treated group returned to baseline values; whereas the placebo group, in contrast, showed a reduced M-t-S score (11.2 +/- 1.3%; P < 0.0003) and serum free T(4) (5.9 +/- 2.4%; P < 0.02), compared with baseline. The change in M-t-S score was correlated with the change in free T(4) (P < 0.0003) during both periods, and increases in serum TSH preceded worsening scores in depression, tension, anger, lack of vigor, and total mood disturbance (P < 0.001) during period 2. Additionally, the submaximal work rate for a fixed O(2) use decreased 22.5 +/- 4.9% in period 1 and remained below baseline in period 2 (25.2 +/- 2.3%; P < 0.005) for both groups. After 4 months of AR, the L-thyroxine supplement was associated with improved cognition, which seems related to circulating T(4). Submaximal exercise performance decrements, observed during AR, were not changed with this L-thyroxine dose. C1 Madigan Army Med Ctr, Dept Med, Endocrine Serv, Tacoma, WA 98431 USA. Madigan Army Med Ctr, Dept Clin Invest, Tacoma, WA 98431 USA. US FDA, Rockville, MD 20857 USA. Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. Western Maryland Coll, Dept Exercise Sci & Phys Educ, Westminster, MD 21157 USA. Off Naval Res, Arlington, VA 22217 USA. RP Reed, HL (reprint author), Middlemore Hosp, Div Med, Private Bag 93311, Auckland 6, New Zealand. EM lreed@middlemore.co.nz NR 45 TC 39 Z9 45 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2001 VL 86 IS 1 BP 110 EP 116 DI 10.1210/jc.86.1.110 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 395KT UT WOS:000166580100019 PM 11231986 ER PT J AU Fleckenstein, JM Kopecko, DJ AF Fleckenstein, JM Kopecko, DJ TI Breaching the mucosal barrier by stealth: an emerging pathogenic mechanism for enteroadherent bacterial pathogens SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID INTESTINAL EPITHELIAL-CELLS; ENTEROAGGREGATIVE ESCHERICHIA-COLI; HELICOBACTER-PYLORI; VIRULENCE FACTORS; INTERLEUKIN-8; SECRETION; INVASION; EXPRESSION; ENTEROTOXIN; PATHWAYS C1 US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Tennessee, Dept Med, Memphis, TN 38104 USA. Vet Affairs Med Ctr, Memphis, TN 38104 USA. RP Kopecko, DJ (reprint author), US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. OI Fleckenstein, James/0000-0002-1148-697X NR 25 TC 29 Z9 30 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2001 VL 107 IS 1 BP 27 EP 30 DI 10.1172/JCI11792 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 389GY UT WOS:000166231300006 PM 11134175 ER PT J AU Feng, P Weagant, SD Monday, SR AF Feng, P Weagant, SD Monday, SR TI Genetic analysis for virulence factors in Escherichia coli O104 : H21 that was implicated in an outbreak of hemorrhagic colitis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; MULTIPLEX PCR; STRAINS; O157-H7; IDENTIFICATION; SEROTYPES; ENTEROHEMOLYSIN; O113-H21; GERMANY; DISEASE AB Isolates of enterohemorrhagic Escherichia coli (EHEC) of serotype O104:H21 implicated in a 1994 outbreak of hemorrhagic colitis in Montana were analyzed for the presence of trait EHEC virulence markers. By using a multiples PCR that specifically amplifies several genes, the O101:H21 strains were found to carry only the Shiga toxin 2 gene (stx2) and to express Stx2. They did not have the caeA gene for gamma -intimin, which is typically found in O157:H7, or the (alpha- or beta -intimin derivatives, which are common in other EHEC and enteropathogenic E. coli serotypes. Results of the multiplex PCR also indicated that the ehxA gene for enterohemolysin was absent from O104:H21. This, however, was not consistent with the results of a phenotypic assay that showed them to be hemolytic or a PCR analysis with another set of ehxA-specific primers, which indicated the presence of ehxA. To resolve this discrepancy, the ehxA region in O103:H21 and O157:H7 strains, to which the multiples PCR primers anneal, was cloned and sequenced. Comparison of the sequences showed that the upstream primer binding site in the ehxA gene of O104:H21 was not identical to that of O157:H7. Specifically, there were several base mutations, including an A-to-G substitution at the 3' end of the primer binding site. These base mutations are presumably not unique to O104:H21, since other enterohemolytic serotypes were also not detected with the ehxA primers used in the multiples PCR Comparison of the ehxA sequences of O104:H21 strains with those of other Stx-producing E. coli strains showed that they more closely resembled those of O8:H19 strains, which have cluster II ehxA genes, than those of O157:H7 strains, which have cluster I ehxA sequences. By modifying the upstream ehxA primer, the multiplex PCR was able to detect ehxA genes in both O157:H7 and O104:H21 strains. C1 US FDA, Div Microbiol Studies, Washington, DC 20204 USA. US FDA, Pacific Reg Lab, Bothell, WA 98041 USA. RP Feng, P (reprint author), US FDA, Div Microbiol Studies, HFS-516,200 C St SW, Washington, DC 20204 USA. NR 28 TC 33 Z9 36 U1 0 U2 5 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 JAN PY 2001 VL 39 IS 1 BP 24 EP 28 DI 10.1128/JCM.39.1.24-28.2001 PG 5 WC Microbiology SC Microbiology GA 393KZ UT WOS:000166468900004 PM 11136742 ER PT J AU Mahmood, I AF Mahmood, I TI Application of preclinical data to initiate the modified continual reassessment method for maximum tolerated dose-finding trials SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID PREDICTING CLEARANCE; HUMANS; DRUGS AB This study was conducted to evaluate whether the allometric approach can be used to predict maximum tolerated dose (MTD) in humans from animal data. Twenty-five anticancer drugs were taken from the literature and used in this analysis. The results of the study indicate that MTD can be predicted with reasonable accuracy using interspecies scaling. The predicted MTD can then be applied to the modified continual reassessment method retrospectively for the selection of initial and subsequent doses of anticancer drugs in the patient population. This approach can save time and avoid many unnecessary steps to attain MTD in humans if it could be applied prospectively. Journal of Clinical Pharmacology, 2001;41:19-24 (C) 2001 the American College of Clinical Pharmacology. C1 US FDA, Div Pharmaceut Evaluat 1, Off Clin Pharmacol & Biopharmaceut HFD860, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Div Pharmaceut Evaluat 1, Off Clin Pharmacol & Biopharmaceut HFD860, Room 4079,Woodmont Off Ctr 2,1451 Rockville Pike, Rockville, MD 20852 USA. NR 12 TC 7 Z9 8 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 2001 VL 41 IS 1 BP 19 EP 24 DI 10.1177/00912700122009791 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 384FP UT WOS:000165932400002 PM 11144990 ER PT J AU Effe, EI Williams, P Sun, H Fadiran, E Ajayi, FO Onyiah, LC AF Effe, EI Williams, P Sun, H Fadiran, E Ajayi, FO Onyiah, LC TI The process of knowledge discovery from large pharmacokinetic data sets SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID JACKKNIFE; GRAPHICS AB The advent of statistical software with powerful graphical and modeling capabilities has revolutionized the manner in which pharmacokinetic and pharmacodynamic analyses are performed. Knowledge discovery from a large (population) pharmacokinetic data set incorporates all steps taken from data assembly to the development of a population pharmacokinetic model and the communication of the results thereof. The process can be formalized into a number of steps: (1) creation of a data set for pharmacokinetic knowledge discovery, (2) data quality analysis, (3) data structure analysis (exploratory examination of raw data), (4) determination of the basic pharmacokinetic model that best describes the data and generating post hoc empiric individual Bayesian parameter estimates, (5) the search for patterns and relationships between parameters and parameters and covariates by visualization, (6) the use of modern statistical modeling techniques for data structure revelation and covariate selection, (7) consolidation of the discovered knowledge into irreducible form (i.e., developing a population pharmacokinetic model), (8) the determination of model robustness (determination of the reliability of model parameter estimates), and (9) the communication and integration of the discovered pharmacokinetic knowledge. This process is discussed, and a motivating example is presented. The use of modern graphical, modeling, and statistical techniques for knowledge discovery from large pharmacokinetic data sets has given the data analyst the freedom to choose statistical methodology appropriate to the problem at hand with the maximization of information extraction, rather than on the basis of mathematical/statistical tractability. Journal of Clinical Pharmacology, 2001;41:25-34 (C) 2001 the American College of Clinical Pharmacology. C1 Vertex Pharmaceut Inc, Cambridge, MA 02139 USA. Univ Pacific, Sch Pharm & Allied Hlth Profess, Stockton, CA 95211 USA. US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. St Cloud State Univ, Dept Stat, St Cloud, MN 56301 USA. RP Effe, EI (reprint author), Vertex Pharmaceut Inc, 130 Waverly St, Cambridge, MA 02139 USA. NR 21 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JAN PY 2001 VL 41 IS 1 BP 25 EP 34 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 384FP UT WOS:000165932400003 ER PT J AU Khan, AT Atkinson, A Graham, TC Shireen, KF AF Khan, AT Atkinson, A Graham, TC Shireen, KF TI Uptake and distribution of mercury in rats after repeated administration of mercuric chloride SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART A-TOXIC/HAZARDOUS SUBSTANCES & ENVIRONMENTAL ENGINEERING LA English DT Article DE mercury content; rats; kidney; liver; sex difference; food consumption; body weight AB This investigation was under taken to evaluate the effect of repeated exposure of mercuric chloride (MC) on food consumption, body weight gain and tissue distribution of mercury in rats. After two weeks of acclimation, male and female rats (45-50 days old) were orally gavaged with 0.00, 2.0, 4.0, 6.0, 8.0 or 10.0 mg/kg/day of MC for 14 consecutive days. The mortality and food consumption were recorded daily. The body weight gains were recorded on day 0, 4, 7, 10, and at day of termination. At the end of the experiment, all surviving rats were euthanized and tissue samples from their brains, gonads, hearts, kidneys, livers, lungs, pancreases and spleens were collected and analyzed for mercury content. Exposure of male and female rats to 4.0 mg/kg/day of MC showed a significant reduction in body weight gain and food consumption when compared to their controls. However, at 2.0 mg/kg/day dose group showed no change of body gain and food consumption. The mercury contents in brains, gonads, hearts, and spleens of male and female rats at 0.0 and 2.0 mg/kg/day were undetectable. Both male and female rats accumulated significantly more mercury in the kidneys than the other organs. Mercury content in the kidneys of females was 39.9 and 40.9 mug/g at 2.0 and 4.0 mg/kg/day, respectively and of males was 34.9 and 41.0 mug/g at 2.0 and 4.0 mg/kg/day, respectively. However, mercury content in the kidneys and livers of males and females did not show any significant difference. Mercury content in the kidneys of both of sexes was significantly higher than the other organs. C1 Tuskegee Univ, Coll Vet Med Nursing & Allied Hlth, Tuskegee, AL 36088 USA. Tuskegee Univ, Dept Food & Nutr Sci, Tuskegee, AL 36088 USA. RP Khan, AT (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St,SW,HFS-207, Washington, DC 20204 USA. NR 20 TC 7 Z9 7 U1 1 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1093-4529 J9 J ENVIRON SCI HEAL A JI J. Environ. Sci. Health Part A-Toxic/Hazard. Subst. Environ. Eng. PY 2001 VL 36 IS 10 BP 2039 EP 2045 DI 10.1081/ESE-100107446 PG 7 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA 493KV UT WOS:000172222500015 PM 11759913 ER PT J AU Fu, PP Chou, MW Xia, Q Yang, YC Yan, J Doerge, DR Chan, PC AF Fu, PP Chou, MW Xia, Q Yang, YC Yan, J Doerge, DR Chan, PC TI Genotoxic pyrrolizidine alkaloids and pyrrolizidine alkaloid N-oxides - Mechanisms leading to DNA adduct formation and tumorigenicity SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE pyrrolizidine alkaloids; mechanism; tumorigenicity; human exposure; DNA adducts ID VENO-OCCLUSIVE DISEASE; FLAVIN-CONTAINING MONOOXYGENASE; RAGWORT SENECIO-JACOBAEA; PROTEIN CROSS-LINKS; S-PHASE SYNTHESIS; RAT-LIVER; CARCINOGENIC ACTIVITY; GUINEA-PIG; MEDICINAL-PLANTS; IN-VITRO AB Plants that contain pyrrolizidine alkaloids and pyrrolizidine alkaloid N-oxides are widely distributed in the world. These plants are probably the most common poisonous plants affecting livestock, wildlife, and humans. Although pyrrolizidine alkaloids have been shown to be genotoxic, including tumorigenic in experimental animals, the mechanisms of tumor formation have not been fully understood. Our recent studies on riddelliine, riddelline N-oxide, and dehydroretronecine (DHR) provided evidence suggesting that pyrrolizidine alkaloids and pyrrolizidine alkaloid N-oxides induce tumors via a genotoxic mechanism, and that tumorigenicity is mediated by a set of eight DHR-derived DNA adducts. This mechanism may be general to other carcinogenic pyrrolizidine alkaloids and may also be responsible for the other genotoxicities of pyrrolizidine alkaloids, including mutagenicity and teratogenicity. It is hypothesized that these DHR-derived DNA adducts are potential biomarkers of pyrrolizidine alkaloid tumorigenicity. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 165 TC 38 Z9 40 U1 1 U2 17 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1059-0501 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PY 2001 VL 19 IS 2 BP 353 EP 385 DI 10.1081/GNC-100107580 PG 33 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 537VY UT WOS:000174781400002 ER PT J AU Rasooly, A AF Rasooly, A TI Surface plasmon resonance analysis of staphylococcal enterotoxin B in food SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ENZYME-IMMUNOASSAY; ARRAY IMMUNOSENSOR; BIOSENSOR; AFFINITY; AUREUS; SENSOR; ASSAY AB Surface plasmon resonance (SPR) biosensors are electro-optical instruments used for analyzing real-time protein-protein interactions. This work evaluates an SPR biosensor (Biacore 3000) in the detection of staphylococcal enterotoxin B (SEB) in foods. A sandwich SPR immunosensor involving two antibodies was used. The capturing antibody, bound covalently to the surface of the biosensor chip, performs the initial binding of the antigen and a second antibody binds to the captured antigen. The second antibody makes antigen verification possible and amplifies the signal. Pure SEE as well as SEE in spiked foods (milk and meat) were detected with Little interference from the food matrix. Ln the control experiments with uncontaminated food samples no significant signal was detected. The SPR biosensor assay detects SEE at similar to 10 ng/ml rapidly, with initial binding within 2 min. The entire measurement cycle (including washing and chip regeneration) may take 5 min using one antibody or 8 min using two antibodies. These results suggest that the SPR biosensor may be a useful tool for real-time analysis of toxin in foods. C1 US FDA, Div Microbiol Studies, Washington, DC 20204 USA. RP Rasooly, A (reprint author), US FDA, Div Microbiol Studies, Washington, DC 20204 USA. NR 34 TC 67 Z9 73 U1 0 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 JAN PY 2001 VL 64 IS 1 BP 37 EP 43 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 392LV UT WOS:000166413300007 PM 11198439 ER PT J AU Platek, SF Crowe, JB Ranieri, N Wolnik, KA AF Platek, SF Crowe, JB Ranieri, N Wolnik, KA TI Scanning electron microscopy determination of string mozzarella cheese in gastric contents SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; cheese; mozzarella cheese; stomach contents; gastric contents; stereoscopic light microscopy; scanning electron microscopy; glutaraldehyde AB As part of a suspected homicide investigation, a sampling of the gastric contents from the victim was forwarded to the U.S. Food and Drug Administration's Forensic Chemistry Center (FCC) for analysis of specific, selected components. The victim was known to have consumed string mozzarella cheese, as a snack, less than 24 h before his disappearance and the subsequent discovery of the body. The investigation sought to confirm or dismiss speculation the victim may have been fed a meal or eaten additional food prior to his death. Analysis of the stomach contents involved examination by stereoscopic light microscopy (SLM) and isolation, processing, and analysis of suspect materials by scanning electron microscopy (SEM). Several wax-like, off-white to cream-colored objects were noted by SLM examination and removed from the gastric contents. Through a series of fixation, sectioning, drying, and coating steps, these objects were prepared for analysis by SEM. Comparison of the suspect material with laboratory control string mozzarella cheese showed excellent correlation between the analyzed samples, confirming the suspect material from the stomach contents as string mozzarella cheese. C1 US FDA, Forens Chem Ctr, Inorgan Branch, Cincinnati, OH 45237 USA. US FDA, Forens Chem Ctr, Organ Branch, Cincinnati, OH 45237 USA. RP Platek, SF (reprint author), US FDA, Forens Chem Ctr, Inorgan Branch, 6751 Steger Dr, Cincinnati, OH 45237 USA. NR 8 TC 2 Z9 2 U1 0 U2 3 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD JAN PY 2001 VL 46 IS 1 BP 131 EP 134 PG 4 WC Medicine, Legal SC Legal Medicine GA 451JA UT WOS:000169797900021 PM 11210898 ER PT J AU Tomlinson, JA Crowe, JB Ranieri, N Kindig, JP Platek, SF AF Tomlinson, JA Crowe, JB Ranieri, N Kindig, JP Platek, SF TI Supermarket tampering: Cocaine detected in syringes and in fruit SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; tampering; cocaine; syringes; fruit; FTIR; GC/MS; polarized light microscopy AB Product tampering, as detailed by the Federal Anti-Tampering Act of 1983 (1), is a felony punishable by both fine and imprisonment. The rationale for product tampering ranges from pranks and attention seeking acts to extortion, terrorism, and homicide. One such case submitted for analysis involved four medical syringes found in a supermarket and suspected of being used to tamper with various products. One of the syringes was found piercing a pear while the other three syringes were found with needles exposed in other parts of the supermarket. Microscopic analysis was used to collect residue from the syringe barrels and the pear. A multidiscipline approach involving SLM, PLM, including microchemical analysis, FTIR, and GC/MS analyses, performed on the residual liquid found in the syringe barrels and in the suspect pear, confirmed the presence of cocaine. This multidisciplinary approach is often necessary when there is a possible health risk to the public and rapid response is important. With this approach, it was quickly determined which drugs or poisons were used in this tampering. C1 US FDA, Forens Chem Ctr, Cincinnati, OH USA. Magellan Labs Inc, Res Triangle Pk, NC USA. RP Crowe, JB (reprint author), 6751 Stege Dr, Cincinnati, OH 45237 USA. NR 3 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD JAN PY 2001 VL 46 IS 1 BP 144 EP 146 PG 3 WC Medicine, Legal SC Legal Medicine GA 451JA UT WOS:000169797900023 PM 11210900 ER PT J AU Chen, JJZ Yauk, CL Hebert, C Hebert, PDN AF Chen, JJZ Yauk, CL Hebert, C Hebert, PDN TI Genetic variation in mitochondrial DNA of North American herring gulls, Larus argentatus SO JOURNAL OF GREAT LAKES RESEARCH LA English DT Article DE genetic variation; DNA; cytochrome b gene; herring gulls; directed termination PCR; Great Lakes ID CONTROL-REGION SEQUENCES; COD GADUS-MORHUA; DIRECTED TERMINATION; POPULATION-STRUCTURE; MUTATION DETECTION; BRANTA-CANADENSIS; GREAT-LAKES; EVOLUTION; DIFFERENTIATION; CANADA AB The herring gull (Larus argentatus), which is one of the most abundant gulls in temperate North America, is used as an important bioindicator species, bur little is known about its patterns of genetic variation. This study examines DNA sequence diversity in the cytochrome b gene of mitochondrial DNA (mtDNA) from herring gull colonies in the Great Lakes basin and from a site in the Maritimes. A 307-bp fragment of the gene was analyzed using a rapid mutation screening procedure coupling directed termination PCR (DT-PCR) with single-stranded conformation polymorphism (SSCP). Seven mtDNA haplotypes were revealed in 224 specimens with a common haplotype dominating all populations. Direct sequencing of a 1063-bp fragment of the cytochrome b gene identified 8 additional haplotypes, but the sequence divergence among all 15 haplotypes was very low (average 0.24%). These data suggest that herring gulls experienced a bottleneck during the last glaciation that is now reflected in their low levels of genetic divergence. The geographic distribution of mtDNA haplotypes indicates that gene flow among herring gull populations is sufficient to ensure genetic homogeneity in the Great Lakes, but insufficient to homogenize generic variation between the Great Lakes and the Maritimes. Meanwhile, a comparison analysis of frozen egg specimens suggests a possible shift in the generic composition of the Great Lakes populations over the last 15 years. C1 Univ Guelph, Dept Zool, Guelph, ON N1G 2W1, Canada. McMaster Univ, Dept Biol, Hamilton, ON L8S 4L8, Canada. Canadian Wildlife Serv, Natl Wildlife Res Ctr, Ottawa, ON K1A 0H3, Canada. RP Chen, JJZ (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. RI Hebert, Paul/C-4161-2013; OI Hebert, Paul/0000-0002-3081-6700; Yauk, Carole/0000-0003-4919-876X NR 35 TC 13 Z9 13 U1 0 U2 4 PU INT ASSOC GREAT LAKES RES PI ANN ARBOR PA 2205 COMMONWEALTH BLVD, ANN ARBOR, MI 48105 USA SN 0380-1330 J9 J GREAT LAKES RES JI J. Gt. Lakes Res. PY 2001 VL 27 IS 2 BP 199 EP 209 PG 11 WC Environmental Sciences; Limnology; Marine & Freshwater Biology SC Environmental Sciences & Ecology; Marine & Freshwater Biology GA 446VY UT WOS:000169535900008 ER PT J AU Kotenko, SV Izotova, LS Mirochnitchenko, OV Dickensheets, H Donnelly, RP Pestka, S AF Kotenko, SV Izotova, LS Mirochnitchenko, OV Dickensheets, H Donnelly, RP Pestka, S TI Identification, cloning and characterization of a novel soluble receptor which binds IL-22 and neutralizes its activity SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet & Microbiol, Newark, NJ 07103 USA. US FDA, Div Therapeut Proteins, Rockville, MD 20857 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 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 32 BP 26 EP 26 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200033 ER PT J AU Bacot, SM Jessen, M Feldman, GM AF Bacot, SM Jessen, M Feldman, GM TI Prion protein activation of the NFkB signalling pathway in human monocyte derived dendritic cells SO JOURNAL OF LEUKOCYTE BIOLOGY 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 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 63 BP 33 EP 33 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200064 ER PT J AU Bertholet, S Dickensheets, HL Donnelly, RP Sacks, D Kenney, RT AF Bertholet, S Dickensheets, HL Donnelly, RP Sacks, D Kenney, RT TI An impaired interferon gamma signaling pathway in Leishmania-infected human macrophages is associated with the induction of Suppressor Of Cytokine Signaling-3 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 US FDA, CBER, OVRR, Rockville, MD 20857 USA. US FDA, CBER, OTRR, Rockville, MD 20857 USA. NIH, NIAID, LPD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 214 BP 67 EP 67 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200214 ER PT J AU Reepmeyer, JC AF Reepmeyer, JC TI Screening for corticosteroids in topical pharmaceuticals by HPLC with a scanning ultraviolet detector SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID LIQUID-CHROMATOGRAPHIC SEPARATION; FORMULATIONS; EXTRACTION; URINE AB A screening procedure was developed for the detection of 49 corticosteroids in topical pharmaceutical products. These products were analyzed by reversed-phase HPLC using two gradient systems: a linear gradient of 18-82% acetonitrile over 12 min and a linear gradient of 38-88% methanol over 12 min. Although all corticosteroids were not resolved during a single 12-min gradient analysis, a peak retention time from a sample analysis was usually sufficient to limit an unknown to 1-3 probable corticosteroids. Steroids unresolved with the first gradient system were resolved with the second one, with the exception of three steroid pairs. Assignments based on retention times were supported by spectra provided by a rapid scanning ultraviolet detector. Two extraction procedures were developed to isolate corticosteroids from both water-soluble and lipid-soluble sample components. When applied to a variety of topical formulations, the two extraction methods eliminated most of the sample excipients, recovered corticosteroids in high yield, and allowed for detection to a level of 0.001% of the sample. C1 US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Reepmeyer, JC (reprint author), US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. NR 12 TC 8 Z9 8 U1 0 U2 0 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 2001 VL 24 IS 5 BP 693 EP 709 DI 10.1081/JLC-100103404 PG 17 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 439JL UT WOS:000169113300007 ER PT J AU Kenyon, AS Layloff, T Sherma, J AF Kenyon, AS Layloff, T Sherma, J TI Rapid screening of tuberculosis pharmaceuticals by thin layer chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article AB A quick, economical, and reliable thin layer chromatography (TLC) method for rapid screening of tuberculosis pharmaceuticals is described, The methods are based on the use of a portable kit involving grinding of samples, development with mobile phase, and application of detection reagents in polyethylene bags, or detection under ultraviolet light. Sample zones are compared to high and low reference standards developed on the same layer to determine if the drug content is within the specification range. Detailed instructions are given for specific drugs for which the TLC analysis has been successfully applied. C1 Lafayette Coll, Dept Chem, Easton, PA 18042 USA. US FDA, Div Testing & Appl Analyt Dev, St Louis, MO 63101 USA. US Pharmacopeia, Div Pharmaceut, Rockville, MD 20852 USA. RP Sherma, J (reprint author), Lafayette Coll, Dept Chem, Easton, PA 18042 USA. NR 5 TC 11 Z9 11 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2001 VL 24 IS 10 BP 1479 EP 1490 DI 10.1081/JLC-100103924 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 455BV UT WOS:000170008400009 ER PT J AU Henney, JE AF Henney, Jane E. TI Cyberpharmacies and the role of the US Food And Drug Administration SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Editorial Material DE Internet; Drug and Narcotic Control; Prescriptions, Drug; Commerce; Physician's Practice Patterns; Impotence; United States Food and Drug Administration; Phosphodiesterase Inhibitors; Piperazines; Quality of Health Care AB The sale of consumer products over the Internet has grown rapidly, including the sale of drugs. While the growth in online drug sales by reputable pharmacies is a trend that may provide benefits to consumers, online drug sales also present risks to purchasers and some unique challenges to regulators, law enforcement officials and policy makers. The Food and Drug Administration (FDA or the Agency) is concerned about the public health implications of Internet drug sales, and we are responding to these concerns as part of our overall goal of developing and implementing risk-based strategies to protect public health and safety. Although other products regulated by the Agency, such as medical devices, medical test products, foods, dietary supplements and animal drugs also are sold online, this paper focuses on online drug sales. We discuss the advantages and risks of online drug sales, outline FDA's authority and enforcement activities in this area, and describe new initiatives we are taking to better respond to the regulatory challenges we face. C1 US FDA, Rockville, MD 20857 USA. RP Henney, JE (reprint author), US FDA, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 0 TC 18 Z9 18 U1 0 U2 2 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PY 2001 VL 3 IS 1 AR e3 DI 10.2196/jmir.3.1.e3 PG 6 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA V12UO UT WOS:000207624300010 PM 11720945 ER PT J AU Fritsche, J Yurawecz, MP Pawlosky, R Flanagan, VP Steinhart, H Ku, Y AF Fritsche, J Yurawecz, MP Pawlosky, R Flanagan, VP Steinhart, H Ku, Y TI Spectroscopic characterization of unusual conjugated linoleic acid (CLA) isomers SO JOURNAL OF SEPARATION SCIENCE LA English DT Article DE CLA; GC-MS; Ag-HPLC; fatty acids ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SEPARATION C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. USDA ARS, Beltsville, MD 20705 USA. RP Fritsche, J (reprint author), Unilever Res Labs Vlaardingen, NL-3130 AC Vlaardingen, Netherlands. NR 4 TC 8 Z9 9 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 1615-9314 J9 J SEP SCI JI J. Sep. Sci. PD JAN PY 2001 VL 24 IS 1 BP 59 EP 61 DI 10.1002/1615-9314(20010101)24:1<59::AID-JSSC59>3.0.CO;2-Z PG 3 WC Chemistry, Analytical SC Chemistry GA 410TC UT WOS:000167454400010 ER PT J AU Lee, SJ AF Lee, SJ TI On the assessment of tolerance limits under inverse Gaussian distribution SO JOURNAL OF STATISTICAL COMPUTATION AND SIMULATION LA English DT Article DE tolerance limit; confidence interval; Bonferroni inequality; Monte Carlo simulation ID FAILURE; MODELS AB Inverse Gaussian distribution has been used in a wide range of applications in modeling duration and failure phenomena. In these applications, one-sided lower tolerance limits are employed, for instance, for designing safety limits of medical devices, Tang and Chang (1994) proposed lowersided tolerance limits via Bonferroni inequality when parameters in the inverse Gaussian distribution are unknown. However, their simulation results showed conservative coverage probabilities, and consequently larger interval width. In their paper, they also proposed an alternative to construct lesser conservative limits. But simulation results yielded unsatisfactory coverage probabilities in many cases. In this article, the exact lower-sided tolerance limit is proposed. The proposed limit has a similar form to that of the confidence interval for mean under inverse Gaussian. The comparison between the proposed limit and Tang and Chang's method is compared via extensive Monte Carlo simulations. Simulation results suggest that the proposed limit is superior to Tang and Chang's method in terms of narrower interval width and approximate to nominal level of coverage probability Similar argument can be applied to the formulation of two-sided tolerance limits, A summary and conclusion of the proposed limits is included. C1 US FDA, CDER, Div BIometr 3, Rockville, MD 20857 USA. RP Lee, SJ (reprint author), US FDA, CDER, Div BIometr 3, Rockville, MD 20857 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK,, ABINGDON OX14 4RN, OXON, ENGLAND SN 0094-9655 J9 J STAT COMPUT SIM JI J. Stat. Comput. Simul. PY 2001 VL 71 IS 3 BP 245 EP 265 DI 10.1080/00949650108812146 PG 21 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 521QC UT WOS:000173851400005 ER PT J AU Al-Osh, MA Lee, SJ AF Al-Osh, MA Lee, SJ TI A simple approach for generating correlated binary variates SO JOURNAL OF STATISTICAL COMPUTATION AND SIMULATION LA English DT Article DE correlated binary variates; correlated poisson variates; simulation AB Correlated binary data arise frequently in medical as well as other scientific disciplines; and statistical methods, such as generalized estimating equation (GEE), have been widely used for their analysis. The need for simulating correlated binary variates arises for evaluating small sample properties of the GEE estimators when modeling such data. Also, one might generate such data to simulate and study biological phenomena such as tooth decay or periodontal disease. This article introduces a simple method for generating pairs of correlated binary data. A simple algorithm is also provided for generating an arbitrary dimensional random vector of non-negatively correlated binary variates. The method relies on the idea that correlations among the random variables arise as a result of their sharing some common components that induce such correlations. It then uses some properties of the binary variates to represent each variate in terms of these common components in addition to its own elements. Unlike most previous approaches that require solving nonlinear equations or use some distributional properties of other random variables, this method uses only some properties of the binary variate. As no intermediate random variables are required for generating the binary variates, the proposed method is shown to be faster than the other methods. To verify this claim, we compare the computational efficiency of the proposed method with those of other procedures. C1 US FDA, Div Biometr 3, OB, CDER, Rockville, MD 20850 USA. RP Al-Osh, MA (reprint author), US FDA, Div Biometr 3, OB, CDER, 9201 Corp Blvd ,HFD-725, Rockville, MD 20850 USA. NR 11 TC 1 Z9 1 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK,, ABINGDON OX14 4RN, OXON, ENGLAND SN 0094-9655 J9 J STAT COMPUT SIM JI J. Stat. Comput. Simul. PY 2001 VL 70 IS 3 BP 231 EP 255 PG 25 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 507DG UT WOS:000173011300003 ER PT J AU Modlin, JF Snider, DE Brooks, DA Clover, RD Guerra, FA Helms, CM Johnson, DR Le, CT Offit, PA Rennels, MB Tompkins, LS Word, BM Bradshaw, D Cheek, JE Evans, GS Graydon, TR Myers, MG Heilman, C Midthun, K Myers, MG Nichol, KL Mahoney, M Pickering, L Abramson, J France, EK Gall, SA Gardner, P Schaffner, W Wilson, HD McKinney, WP Marchessault, V Siegel, JD Katz, SL Santos, JI Jackson, RE Peter, G Howe, BJ Ashford, DA Perkins, B Rotz, LD AF Modlin, JF Snider, DE Brooks, DA Clover, RD Guerra, FA Helms, CM Johnson, DR Le, CT Offit, PA Rennels, MB Tompkins, LS Word, BM Bradshaw, D Cheek, JE Evans, GS Graydon, TR Myers, MG Heilman, C Midthun, K Myers, MG Nichol, KL Mahoney, M Pickering, L Abramson, J France, EK Gall, SA Gardner, P Schaffner, W Wilson, HD McKinney, WP Marchessault, V Siegel, JD Katz, SL Santos, JI Jackson, RE Peter, G Howe, BJ Ashford, DA Perkins, B Rotz, LD CA Advisory Comm Immunization Practic TI Use of anthrax vaccine in the United States: Recommendations of the advisory committee on immunization practices (Reprinted from Morbidity and Mortality Weekly Report, vol 49, pg 1-20, 2000) SO JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY LA English DT Article ID BACILLUS-ANTHRACIS; INHALATION ANTHRAX; BIOLOGICAL WARFARE; COMPARATIVE EFFICACY; PROTECTIVE ANTIGEN; LETHAL FACTOR; GUINEA-PIGS; ANTIBODIES; MANAGEMENT; OUTBREAK C1 Dartmouth Med Sch, Lebanon, NH 03756 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Johnson Med Ctr, Baltimore, MD USA. Univ Louisville, Sch Med, Louisville, KY 40292 USA. San Antonio Metropolitan Hlth Dist, San Antonio, TX USA. Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. Michigan Dept Community Hlth, Lansing, MI USA. Kaiser Permanente Med Ctr, Santa Rosa, CA USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. USAF, Med Operat Agcy, Washington, DC 20330 USA. Indian Hlth Serv, Albuquerque, NM USA. US Hlth Resources & Serv Adm, Rockville, MD 20857 USA. US Hlth Care Financing Adm, Baltimore, MD 21207 USA. NIH, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20014 USA. VA Med Ctr, Minneapolis, MN USA. Amer Acad Family Physicians, Clarence, NY USA. Amer Acad Pediat, Norfolk, VA USA. Amer Assoc Hlth Plans, Denver, CO USA. Amer Coll Obstetricians & Gynecologists, Louisville, KY USA. Amer Coll Phys, Stony Brook, NY USA. Amer Hosp Assoc, Nashville, TN USA. Amer Med Assoc, Grand Forks, ND USA. Assoc Teachers Prevent Med, Louisville, KY USA. Canadian Natl Advisory Comm Immunizat, Cumberland, ON, Canada. Healthcare Infect Control Practices Advisory Comm, Dallas, TX USA. Infect Dis Soc Amer, Durham, NC USA. Natl Immunizat Council & Child Hlth Program, Mexico City, DF, Mexico. Natl Med Assoc, Atlanta, GA USA. Natl Vaccine Advisory Comm, Providence, RI USA. Pharmaceut Res & Manufacturers Amer, Collegeville, PA USA. RP Modlin, JF (reprint author), Dartmouth Med Sch, Lebanon, NH 03756 USA. NR 85 TC 3 Z9 3 U1 1 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0731-3810 J9 J TOXICOL-CLIN TOXIC JI J. Toxicol.-Clin. Toxicol. PY 2001 VL 39 IS 1 BP 85 EP 100 PG 16 WC Toxicology SC Toxicology GA 456DF UT WOS:000170067300014 ER PT J AU Herman, EH Vick, JA Strong, JM Parker, RJ Geyer, HM Kramer, ED Higgins, KM Sistare, FC AF Herman, EH Vick, JA Strong, JM Parker, RJ Geyer, HM Kramer, ED Higgins, KM Sistare, FC TI Cardiovascular effects of buccal exposure to dermal nicotine patches in the dog: A comparative evaluation SO JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY LA English DT Article ID TRANSDERMAL NICOTINE; SMOKING CESSATION; THERAPY; METAANALYSIS; COTININE; FLUIDS AB Objective: Safety concerns have been raised over the possible effects of inappropriate exposure to transdermal nicotine patches. This study was initiated to determine whether placement of these products into the mouth could affect cardiovascular function. Methods: In a series of 10 anesthetized beagle clogs. Nicoderm(R), Habitrol(R), ProStep(R) I (Intact), ProStep(R) D (Damaged) transdermal nicotine products or the Skoal Bandit(R) smokeless tobacco plug were placed in the buccal cavity for 5 minutes. Systemic arterial blood pressure and the electrocardiogram were monitored for LIP to 90 minutes after exposure,vith blood samples at intervals during the first 10 minutes for plasma nicotine concentration. Results: The systolic and diastolic arterial blood pressures and heart rate increased within 2 minutes of buccal exposure to either the intact or the damaged ProStep nicotine product. Ventricular arrhythmias were observed in 6 of 10 dogs exposed to the intact patch and 7 of 10 dogs exposed to the damaged patch during the period of maximal cardiovascular response. Modest increases in systemic blood pressure and heart rate were seen with the Nicoderm and Habitrol products but not with the Skoal Bandit. The increases in systemic arterial pressure and heart rare occurring after exposure to ProStep were significantly more severe than those observed after Nicoderm and Habitrol. Mean peak nicotine levels of 9.8 mug/mL (ProStep 1), 5.4 mug/mL (ProStep D), 3.4 mug/mL (Habitrol), 2.5 mug/mL (Nicoderm), and 0.12 mug/mL (Skoal Bandit) were detected within 2 to 10 minutes after buccal placement of the product. Conclusions: Certain transdermal nicotine patches, when applied to a nondermal site such as the buccal cavity for a short period (5 minutes) can rapidly provoke significant cardiovascular alterations (hypertension, tachycardia, and ventricular arrhythmias). The magnitude of the cardiovascular responses occurring after buccal exposure to a product of the cardiovascular responses occurring after buccal exposure to a product such as ProStep could pose a risk to susceptible individuals. C1 US FDA, Div Appl Pharmacol Res, Off Testing & Res, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. RP Herman, EH (reprint author), US FDA, Div Appl Pharmacol Res, Off Testing & Res, Ctr Drug Evaluat & Res, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 16 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 0731-3810 J9 J TOXICOL-CLIN TOXIC JI J. Toxicol.-Clin. Toxicol. PY 2001 VL 39 IS 2 BP 135 EP 142 PG 8 WC Toxicology SC Toxicology GA 456DG UT WOS:000170067400004 PM 11407499 ER PT J AU Bronaugh, RL Kraeling, MEK Yourick, JJ Hood, HL AF Bronaugh, RL Kraeling, MEK Yourick, JJ Hood, HL TI Cutaneous metabolism during in vitro percutaneous absorption (Reprinted from Percutaneous Adsorption, pg 57-64, 1999) SO JOURNAL OF TOXICOLOGY-CUTANEOUS AND OCULAR TOXICOLOGY LA English DT Reprint ID HAIRLESS GUINEA-PIG; SKIN PENETRATION; INVITRO; VIABILITY C1 US FDA, Laurel, MD USA. RP Bronaugh, RL (reprint author), US FDA, Laurel, MD USA. NR 16 TC 0 Z9 0 U1 1 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0731-3829 J9 J TOXICOL-CUTAN OCUL JI J. Toxicol.-Cutan. Ocul. Toxicol. PY 2001 VL 20 IS 2-3 BP 271 EP 277 PG 7 WC Ophthalmology; Toxicology SC Ophthalmology; Toxicology GA 505NE UT WOS:000172918200008 ER PT J AU Bronaugh, RL Hood, HL Kraeling, MEK Yourick, JJ AF Bronaugh, RL Hood, HL Kraeling, MEK Yourick, JJ TI Determination of percutaneous absorption by in vitro techniques (Reprinted from Percutaneous Adsorption, pg 229-234, 1999) SO JOURNAL OF TOXICOLOGY-CUTANEOUS AND OCULAR TOXICOLOGY LA English DT Reprint ID HAIRLESS GUINEA-PIG; HUMAN-SKIN; METABOLISM; BENZOCAINE C1 US FDA, Laurel, MD USA. RP Bronaugh, RL (reprint author), US FDA, Laurel, MD USA. NR 12 TC 2 Z9 2 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0731-3829 J9 J TOXICOL-CUTAN OCUL JI J. Toxicol.-Cutan. Ocul. Toxicol. PY 2001 VL 20 IS 4 BP 423 EP 427 PG 5 WC Ophthalmology; Toxicology SC Ophthalmology; Toxicology GA 505NF UT WOS:000172918300003 ER PT J AU Silberstein, E Dveksler, G Kaplan, GG AF Silberstein, E Dveksler, G Kaplan, GG TI Neutralization of hepatitis A virus (HAV) by an immunoadhesin containing the cysteine-rich region of HAV cellular receptor-1 SO JOURNAL OF VIROLOGY LA English DT Article ID MONKEY KIDNEY-CELLS; A VIRUS; MONOCLONAL-ANTIBODIES; PROTECTIVE MONOCLONAL-ANTIBODY-190/4; POLIOVIRUS RECEPTOR; CULTURE; ADAPTATION; IDENTIFICATION; DETERMINANTS; PROPAGATION AB Hepatitis A virus (HAV) infects African green monkey kidney (AGR IK) cells via the HAV cellular receptor-1 (havcr-1), a mucin-like type 1 integral-membrane glycoprotein of unknown natural function. The ectodomain of havcr-1 contains an N-terminal immunoglobulin-like cysteine-rich region (D1), which binds protective monoclonal antibody (MAb) 190/4, followed by an O-glycosylated mucin-like threonine-serine-proline-rich region that extends D1 well above the cell surface. To study the interaction of HAV with havcr-1, we constructed immunoadhesins fusing the hinge and Fc portion of human IgG1 to D1 (D1-Fc) or the ectodomain of the poliovirus receptor (PVR-Fc) and expressed them in CHO cells. These immunoadhesins,were secreted to the cell culture medium and purified through protein A-agarose columns. In a solid-phase assay, HAV bound to D1-Fc in a concentration-dependent manner whereas background levels of HAV bound to PVR-Fc. Binding of HAV to D1-Fc was blocked by treatment with MAb 190/4 but not with control MAb, M2, which binds to a tag epitope introduced between the D1 and Fe portions of the immunoadhesin. D1-Fc neutralized approximately 1 log unit of the HAV infectivity in AGMK cells, whereas PVR-Fc had no effect in the HAV titers. A similarly poor reduction in HAV titers was observed after treating the same stock of HAV with murine neutralizing MAbs K2-4F2, K3-4C8, and VHA 813. Neutralization of poliovirus by PVR-Fc but not by D1-Fc indicated that the virus-receptor interactions were specific. These results show that D1 is sufficient for binding and neutralization of HAV and provide further evidence that havcr-1 is a functional cellular receptor for HAV. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Hepatatis Viruses, Bethesda, MD 20014 USA. Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. RP Kaplan, GG (reprint author), NIH, 8800 Rockville Pike,Bldg 29A,Rm 1D10,HFM-448, Bethesda, MD 20892 USA. NR 40 TC 25 Z9 30 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 JAN PY 2001 VL 75 IS 2 BP 717 EP 725 DI 10.1128/JVI.75.2.717-725.2001 PG 9 WC Virology SC Virology GA 385QK UT WOS:000166015000018 PM 11134285 ER PT S AU Waynant, RW Ilev, IK Mitra, K AF Waynant, RW Ilev, IK Mitra, K BE Anderson, RR Bartels, KE Bass, LS Garrett, CG Gregory, KW Katzir, A Kollias, N Lucroy, MD Malek, RS Nelson, JS Peavy, GM Reidenbach, HD Reinisch, L Robinson, DS Tate, LP Trowers, EA Woodward, TA TI Waveguide delivery of x-rays for minimally invasive tumor therapy SO LASERS IN SURGERY: ADVANCED CHARACTERIZATION THERAPEUTICS, AND SYSTEMS XI SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Lasers in Surgery - Advanced Characterization, Therapeutics, and Systems XI CY JAN 20-23, 2001 CL SAN JOSE, CA SP SPIE DE x-rays; hollow waveguides; tumor irradiation; dosimetry; minimally invasive therapy ID HOLLOW TAPER; RADIATION; OPTICS; LIGHT AB We are studying the potential use of x-rays, which are collected by non-imaging optics and delivered through stereotactically guided needles by hollow waveguides, for irradiation of tumors. X-rays have greater transparency in tissue than most longer optical wavelengths and may provide a more uniform dose to a tumor without harming normal tissue. Dosimetry is the key to minimal damage. We are investigating the use of fiber optics, tipped with calibrated scintillators and strategically located near the tumor, to measure the delivered dose. We are testing this procedure by using a 3 ns, variable accelerator voltage Fexitron 706 to produce approximately 50 mrads of x-ray energy. We concentrate, homogenize and inject this radiation into meter length, submillimeter hollow waveguides. We place the waveguides in a simulated tumor (a phantom breast). Streak and thermal cameras monitor the energy distribution during the irradiation by observing the distribution of energy as evidenced by fluorescence and heat. Once optimum exposure conditions of placement and dose are determined, tissue studies will begin. C1 US FDA, Rockville, MD 20857 USA. RP US FDA, Rockville, MD 20857 USA. OI Mitra, Kunal/0000-0002-7277-4908 NR 12 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3922-3 J9 PROC SPIE PY 2001 VL 4244 BP 492 EP 499 DI 10.1117/12.427840 PG 8 WC Engineering, Biomedical; Optics; Physics, Applied; Surgery SC Engineering; Optics; Physics; Surgery GA BS36N UT WOS:000169641700067 ER PT J AU Brown, R Caphart, M Faustino, P Frankewich, R Gibbs, J Leutzinger, E Lunn, G Ng, L Rajagopalan, R Chiu, Y Sheinin, E AF Brown, R Caphart, M Faustino, P Frankewich, R Gibbs, J Leutzinger, E Lunn, G Ng, L Rajagopalan, R Chiu, Y Sheinin, E TI Analytical procedures and method validation: Highlights of the FDA's draft guidance SO LC GC NORTH AMERICA LA English DT Article C1 US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Rajagopalan, R (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 9 TC 13 Z9 13 U1 0 U2 1 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 1527-5949 J9 LC GC N AM JI LC GC N. AM. PD JAN PY 2001 VL 19 IS 1 BP 74 EP + PG 5 WC Chemistry, Analytical SC Chemistry GA 394JE UT WOS:000166519600006 ER PT S AU Ilev, IK Waynant, RW Ediger, MN AF Ilev, IK Waynant, RW Ediger, MN GP IEEE IEEE TI Ultraviolet broadband (190-450 nm) nonlinear frequency conversion in optical fibers for biomedical use SO LEOS 2001: 14TH ANNUAL MEETING OF THE IEEE LASERS & ELECTRO-OPTICS SOCIETY, VOLS 1 AND 2, PROCEEDINGS SE IEEE Lasers and Electro-Optics Society (LEOS) Annual Meeting LA English DT Proceedings Paper CT 14th Annual Meeting of the IEEE Lasers-and-Electro-Optics-Society CY NOV 11-15, 2001 CL SAN DIEGO, CA SP IEEE, IEE Lasers and Electro Opt Soc ID RAMAN LASER C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-134, Rockville, MD 20857 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1092-8081 BN 0-7803-7105-4 J9 IEEE LEOS ANN MTG PY 2001 BP 750 EP 751 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Condensed Matter SC Engineering; Optics; Physics GA BU32T UT WOS:000175700800374 ER PT J AU Verthelyi, D Petri, M Ylamus, M Klinman, DM AF Verthelyi, D Petri, M Ylamus, M Klinman, DM TI Disassociation of sex hormone levels and cytokine production in SLE patients SO LUPUS LA English DT Article DE estrogen; dehydroepiandrosterone-sulphate; cytokines; systemic lupus erythematosus ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; MRL LPR/LPR MICE; PERIPHERAL-BLOOD; T-CELLS; INTERLEUKIN-2 ACTIVITY; ANDROGEN RECEPTORS; ESTROGEN-RECEPTORS; AUTOIMMUNE-DISEASE; IMMUNE-SYSTEM; DEHYDROEPIANDROSTERONE AB This study examines whether changes in the cytokine milieu of patients with systemic lupus erythematosus (SLE) are associated with abnormal levels of sex hormone levels in serum. The concentration of 17 beta -estradiol (E2), progesterone (Pg) and dehydroepiandrosterone-sulphate (DHEAS) was monitored in sera from 128 lupus patients and 96 controls, and correlated with the activity of their cytokine secreting cells. Results indicate that SLE patients have (i) significantly fewer cells secreting IFN gamma, (ii) increased serum E2 and Pg levels, and (iii) reduced serum DHEAS levels compared to normal controls. However, the observed abnormalities in the cytokine milieu of SLE patients did not correlate with abnormalities in serum sex hormone levels. Instead, the association between IFN gamma production and DHEAS levels evident in healthy controls is absent in SLE patients, suggesting that cells from lupus patients are defective in their ability to produce IFN gamma in response to physiologic stimuli. Similarly, the normal correlation between IL-4 production and E2 levels was Lost in patients with severe disease. Thus, while it remains possible that increased E2 and reduced DHEAS levels in lupus patients may help induce cytokine abnormalities early in disease, the subsequent cytokine imbalance does not correlate with sex hormone levels. C1 US FDA, Ctr Biol Evaluat & Res, Retroviral Immunol Sect, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Div Rheumatol, Baltimore, MD USA. RP Verthelyi, D (reprint author), US FDA, Ctr Biol Evaluat & Res, Retroviral Immunol Sect, Bldg 29A Rm 3 D2, Bethesda, MD 20892 USA. FU NCRR NIH HHS [RR00722]; NIAMS NIH HHS [R01 AR43727] NR 49 TC 28 Z9 29 U1 0 U2 2 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 2001 VL 10 IS 5 BP 352 EP 358 DI 10.1191/096120301674365881 PG 7 WC Rheumatology SC Rheumatology GA 437XQ UT WOS:000169025000007 PM 11403266 ER PT S AU Badano, A Kanicki, J AF Badano, A Kanicki, J BE Krupinski, EA Chakraborty, DP TI Color and contrast perception in monochrome medical imaging flat-panel displays SO MEDICAL IMAGING 2001: IMAGE PERCEPTION AND PERFORMANCE SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2001 Conference CY FEB 18-22, 2001 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE contrast perception; achromatic contrast; flat-panel display; medical display AB The interpretation of diagnostic grayscale images by human beings relies on luminance discrimination at photopic levels. The observer in his search for abnormality relies on luminance modulation. If this hypothesis is valid, then the color of a monochrome presentation should not affect diagnostic performance when the image luminance is equivalent to grayscale levels. Does observer preference for a particular tint influence his performance defining an ideally colored grayscale? In this paper, we studied the variations in supra-threshold contrast perception when using different colored scales to display psychophysics targets on uniform background. We used targets with six different colored scales based upon the hue and saturation levels, while maintaining a constant luminosity. The six colored scales and the "white" grayscale constituted our set of seven colored scales used in a two-alternative forced choice scheme with random presentation and eighteen observers. All image targets contained the same degree of physical contrast and the same luminance values. We computed the degree of preference for all possible combinations of two colored scales. In spite of large inter-observer variability, we found that green and blue scales result in higher perceived contrast. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP US FDA, Ctr Devices & Radiol Hlth, 12720 Twinbrook Pkwy,HFZ-142, Rockville, MD 20857 USA. EM agb@cdrh.fda.gov OI badano, aldo/0000-0003-3712-6670 NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4010-8 J9 PROC SPIE PY 2001 VL 4324 BP 1 EP 7 DI 10.1117/12.431170 PG 7 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BS89P UT WOS:000171334600001 ER PT S AU Beiden, SV Wagner, RF Campbell, G Metz, CE Chan, HP Nishikawa, RM Schnall, MD Jiang, YL AF Beiden, SV Wagner, RF Campbell, G Metz, CE Chan, HP Nishikawa, RM Schnall, MD Jiang, YL BE Krupinski, EA Chakraborty, DP TI Analysis of components of variance in multiple-reader studies of computer-aided diagnosis with different tasks SO MEDICAL IMAGING 2001: IMAGE PERCEPTION AND PERFORMANCE SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2001 Conference CY FEB 18-22, 2001 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol AB In recent years, the multiple-reader, multiple-case (MRMC) study paradigm has become widespread for receiver operating characteristic (ROC) assessment of systems for diagnostic imaging and computer-aided diagnosis. We review how MRMC data can be analyzed in terms of the multiple components of the variance (case, reader, interactions) observed in those studies. Such information is useful for the design of pivotal studies from results of a pilot study and also for studying the effects of reader training. Recently, several of the present authors have demonstrated methods to generalize the analysis of multiple variance components to the case where unaided readers of diagnostic images are compared with readers who receive the benefit of a computer assist (CAD). For this case it is necessary to model the possibility that several of the components of variance might be reduced when readers incorporate the computer assist-compared to the unaided reading condition. We review results of this kind of analysis on three previously published MRMC studies, two of which were applications of CAD to diagnostic mammography and one was an application of CAD to screening mammography. The results for the three cases are seen to differ, depending on the reader population sampled and the task of interest. Thus, it is not possible to generalize a particular analysis of variance components beyond the tasks and populations actually investigated. C1 US FDA, Ctr Devices & radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. RP US FDA, Ctr Devices & radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. OI Nishikawa, Robert/0000-0001-7720-9951 NR 15 TC 2 Z9 2 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4010-8 J9 PROC SPIE PY 2001 VL 4324 BP 167 EP 176 DI 10.1117/12.431185 PG 10 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BS89P UT WOS:000171334600021 ER PT S AU Gagne, RM Quinn, PW Chen, LY Myers, KJ Doyle, R AF Gagne, RM Quinn, PW Chen, LY Myers, KJ Doyle, R BE Antonuk, LE Yaffe, MJ TI Optically coupled digital radiography: sources of inefficiency SO MEDICAL IMAGING 2001: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2001 Conference CY FEB 18-22, 2001 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE lens coupling; detective quantum efficiency; secondary quantum sink ID RAY-IMAGING SYSTEMS; EFFICIENCY; SIGNAL AB Imaging systems comprised of a small detector which "looks" at a large area of a light emitting phosphor with a lens coupling system are commercially available. These imaging systems can be quite inefficient depending on the characteristics of the optical coupling. We have implemented an optically coupled imaging system in our laboratory for use as a test bed. The system includes a Kodak MR-2190 screen and a digital detector, i.e., a CCD camera. The laboratory system has provided the ability to investigate when a system of this configuration starts to develop a "secondary quantum sink" as a result of poor optical coupling. Experimental measurements have been made of the large area gray-scale transfer, resolution and noise properties of the imaging system at two different values of optical demagnification factor and three levels of x-ray exposure. The values of the detective quantum efficiency calculated from these measurements demonstrate a significant increase in absolute value and bandwidth when the demagnification decreases by a factor of approximately two. C1 FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. EM rmg@cdrh.fda.gov NR 11 TC 3 Z9 3 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4006-X J9 PROC SPIE PY 2001 VL 4320 BP 156 EP 162 DI 10.1117/12.430937 PG 7 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BS75D UT WOS:000171047400018 ER PT S AU Gagne, RM Boswell, JS Myers, KJ Peter, G AF Gagne, RM Boswell, JS Myers, KJ Peter, G BE Antonuk, LE Yaffe, MJ TI Lesion detectability in digital radiography SO MEDICAL IMAGING 2001: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2001 Conference CY FEB 18-22, 2001 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE detectability; Hotelling; nonprewhitening matched filter; SNR; digital radiography; model observer ID OBSERVER DETECTION PERFORMANCE; AMORPHOUS SELENIUM; IMAGING-SYSTEMS; NOISE; MODEL; OPTIMIZATION; REDUCTION; DETECTORS; RADIOLOGY; IMAGES AB The usefulness of Fourier-based measures of imaging performance has come into question for the evaluation of digital imaging systems. Figures of merit such as detective quantum efficiency (DQE) are relevant for linear, shift-invariant systems with stationary noise. However, no digital imaging system is shift invariant, and realistic images do not satisfy the stationarity condition. Our methods for task-based evaluation of imaging systems, based on lesion delectability, do not require such assumptions. We have computed the performance of Hotelling and nonprewhitening matched-filter observers for the task of lesion detection in digital radiography. Theoretical signal-to-noise-ratios (SNRs) have been compared to results obtained from a Monte Carlo simulation of the digital image-acquisition process that incorporates the effects of random amplification and secondary quantum blur, integration over pixel area, and electronic noise. Lesion delectability has been determined for a variety of imaging conditions, including ones where the assumptions of shift-invariance and stationarity are far from valid, in order to assess the effects of lesion size, background correlation length, optical blur in the phosphor, pixel size, and electronic noise. These observer figures of merit directly specify the usefulness of the images for the stated diagnostic task. More importantly, these model observers have been previously shown to bracket human performance. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP US FDA, Ctr Devices & Radiol Hlth, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. EM rmg@chrd.fda.gov NR 39 TC 3 Z9 3 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4006-X J9 PROC SPIE PY 2001 VL 4320 BP 316 EP 325 DI 10.1117/12.430902 PG 10 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BS75D UT WOS:000171047400035 ER PT S AU Gagne, RM Myers, KJ Quinn, PW AF Gagne, RM Myers, KJ Quinn, PW BE Antonuk, LE Yaffe, MJ TI Effect of shift invariance and stationarity assumptions on simple detection tasks: spatial and spatial frequency domains SO MEDICAL IMAGING 2001: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2001 Conference CY FEB 18-22, 2001 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE shift invariance; stationarity; pre-whitening matched filter; DC suppressed matched filter; SNR ID IMAGING-SYSTEMS; DIGITAL RADIOGRAPHY; NOISE MEASUREMENTS; EFFICIENCY; SIGNAL; SNR AB A tens-coupled digital radiography system was used to investigate the impact of shift invariance and stationarity assumptions on task-based measures of performance. Experimental data are available on the imaging system's large area gray-scale transfer (sensitivity), resolution (modulation transfer function) and noise (variance map, autocovariance function, and noise power spectrum) properties in different regions of the field of view. These data were obtained for two different values of optical demagnification factor and three levels of x-ray exposure. Evidence of shift variant and non-stationary behavior is seen in the position dependence of the sensitivity, resolution and noise properties of the imaging system. Estimates of observer performance in terms of signal-to-noise-ratio were obtained from one algorithmic observer (DC-suppressed matched filter) and from one analytic observer (pre-whitening matched filter) for the task of detecting a known object (CDMAM phantom) on a flat background. For the special case of a large object at the center of the field-of-view, estimates of observer performance were essentially the same whether based on spatial or spatial frequency domain measures. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. EM rmg@cdrh.fda.gov NR 16 TC 2 Z9 2 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4006-X J9 PROC SPIE PY 2001 VL 4320 BP 373 EP 380 DI 10.1117/12.430938 PG 8 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BS75D UT WOS:000171047400041 ER PT S AU Wagner, RF Beiden, SV Campbell, G AF Wagner, RF Beiden, SV Campbell, G BE Antonuk, LE Yaffe, MJ TI Multiple-reader studies, digital mammography, computer-aided diagnosis - and the Holy Grail of imaging physics (I) SO MEDICAL IMAGING 2001: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2001 Conference CY FEB 18-22, 2001 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol ID ROC ANALYSIS; RADIOLOGISTS; VARIABILITY; DESIGN AB There are multiple sources of variability in clinical studies of imaging systems. The variation of the reader "mindset" establishes the need for ROC analysis to control for that fundamental variable. The demonstration of the range of reader skills in mammography shows the need for a multivariate approach to ROC analysis. The multiple-reader, multiple-case (MRMC) ROC experimental paradigm addresses this need and several practical solutions to the problem of analysis of MRMC data have been developed. We review the application of these methods to an important clinical comparison of digital and conventional mammography. In a companion paper we review a more general problem-in which unaided readers of mammographic images are compared with readers aided by a computer processing and data fusion algorithm. The analysis there will suggest that the computer assist may allow incremental improvements in imaging physics and technology to make a clinically observable difference-by reducing the masking effect of reader variability. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. RP US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. NR 26 TC 7 Z9 7 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4006-X J9 PROC SPIE PY 2001 VL 4320 BP 611 EP 618 DI 10.1117/12.430881 PG 8 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BS75D UT WOS:000171047400066 ER PT S AU Beiden, SV Wagner, RF Campbell, G Metz, CE Jiang, YL Chan, HP AF Beiden, SV Wagner, RF Campbell, G Metz, CE Jiang, YL Chan, HP BE Antonuk, LE Yaffe, MJ TI Multiple-reader studies, digital mammography, computer-aided diagnosis - and the Holy Grail of imaging physics (II) SO MEDICAL IMAGING 2001: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2001 Conference CY FEB 18-22, 2001 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol AB The metaphor of the Holy Grail is used here to refer to the classic and elusive problem in medical imaging of predicting the ranking of the clinical performance of competing imaging modalities from the ranking obtained from physical laboratory measurements and signal-detection analysis, or from simple phantom studies. In recent years a number of investigators have demonstrated the ability to predict the ranking of systems in simple phantom studies from the physical laboratory measurements and signal-detection theory. The ability to extrapolate from this point to clinical performance has been complicated by both the complexity of clinical images and the masking effect of reader variability. We show how the use of the multiple-reader, multiple-case (MRMC) ROC paradigm and new analytical techniques allows this masking effect to be quantified in terms of components-of-variance models. Moreover, we demonstrate how the components of variance associated with reader variability may be reduced when readers have the benefit of computer-assist reading aids. The remaining variability will be due to the case components, and these reflect the contribution of the technology without the masking effect of the reader. This suggests that prediction of clinical ranking of imaging systems in terms of physical measurements may become a much more tractable task in a world that includes MRMC ROC analysis of performance of radiologists with the advantage of computer-assisted reading. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. RP US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. NR 16 TC 2 Z9 2 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4006-X J9 PROC SPIE PY 2001 VL 4320 BP 619 EP 626 DI 10.1117/12.430882 PG 8 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BS75D UT WOS:000171047400067 ER PT S AU Wear, KA AF Wear, KA BE Insana, MF Shung, KK TI Computer simulation and experiments to investigate the effects of frequency-dependent attenuation and dispersion on speed of sound estimates in cancellous bone SO MEDICAL IMAGING 2001: ULTRASONIC IMAGING AND SIGNAL PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2001 Conference CY FEB 18-22, 2001 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE ultrasound; speed; velocity; dispersion; cancellous bone; frequency dependent attenuation ID ULTRASOUND ATTENUATION; TRABECULAR BONE; HIP FRACTURE; QUANTITATIVE ULTRASOUND; MECHANICAL-PROPERTIES; HUMAN CALCANEUS; GROUP-VELOCITY; OS CALCIS; IN-VITRO; DENSITY AB Many studies have demonstrated that time-domain speed-of-sound (SOS) measurements in calcaneus are predictive of osteoporotic fracture risk. However there is a lack of standardization for this measurement. Consequently, different investigators using different measurement systems and analysis algorithms obtain disparate quantitative values for calcaneal SOS, impairing and often precluding meaningful comparison and/or pooling of measurements. A numerical method has been developed to model the effects of frequency-dependent attenuation and dispersion on transit-time-based SOS estimates. The numerical technique is based on a previously developed linear system analytic model for Gaussian pulses propagating through linearly attenuating, weakly dispersive media. The numerical approach is somewhat more general in that it can be used to predict the effects of arbitrary pulse shapes and dispersion relationships. The numerical technique however utilizes several additional assumptions (compared with the analytic model) which would be required for the practical task of correcting existing clinical databases. These include a single dispersion relationship for all calcaneus samples, a simple linear model relating phase velocity to broadband ultrasonic attenuation, and a constant calcaneal thickness. Measurements on a polycarbonate plate and thirty human calcaneus samples were in good quantitative agreement with numerical predictions. In addition, the numerical approach predicts that in cancellous bone, frequency-dependent attenuation tends to be a greater contributor to variations in transit-time-based SOS estimates than dispersion. This approach may be used to adjust previously acquired individual measurements so that SOS data recorded with different devices using different algorithms may be compared in a meaningful fashion. 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. NR 29 TC 0 Z9 0 U1 1 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4011-6 J9 PROC SPIE PY 2001 VL 4325 BP 356 EP 364 DI 10.1117/12.428211 PG 9 WC Engineering, Electrical & Electronic; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BS89Q UT WOS:000171334900035 ER PT S AU Wear, KA AF Wear, KA BE Insana, MF Shung, KK TI Fundamental mechanisms underlying broadband ultrasonic attenuation in calcaneus SO MEDICAL IMAGING 2001: ULTRASONIC IMAGING AND SIGNAL PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2001 Conference CY FEB 18-22, 2001 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol ID SOUND 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. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4011-6 J9 PROC SPIE PY 2001 VL 4325 BP 427 EP 429 DI 10.1117/12.428220 PG 3 WC Engineering, Electrical & Electronic; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BS89Q UT WOS:000171334900043 ER PT J AU Golding, B Scott, DE Scharf, O Huang, LY Zaitseva, M Lapham, C Eller, N Golding, H AF Golding, B Scott, DE Scharf, O Huang, LY Zaitseva, M Lapham, C Eller, N Golding, H TI Immunity and protection against Brucella abortus SO MICROBES AND INFECTION LA English DT Review DE Brucella abortus; T helper type 1; dendritic cells; interferon-gamma; IL-12 ID T-CELLS; IFN-GAMMA; B-ABORTUS; VIRAL-INFECTIONS; DENDRITIC CELLS; V3 LOOP; RESPONSES; MICE; ANTIBODIES; CYTOKINES AB Brucella abortus is an intracellular pathogen that causes disease in cattle and in humans. The response against B, abortus involves the whole gamut of the immune system, from innate to adaptive immunity resulting from stimulation of antigen-presenting cells, NK cells, CD4(+) and CD8(+) T cells, and B cells. (C) 2001 Editions scientifiques et medicales Elsevier SAS. C1 US FDA, Div Hematol, Off Blood & Blood Res, Ctr Biol Res & Review, Rockville, MD 20852 USA. US FDA, Div Viral Prod, Off Vaccines & Vaccine Res, Ctr Biol Res & Review, Rockville, MD 20852 USA. RP Golding, B (reprint author), US FDA, Div Hematol, Off Blood & Blood Res, Ctr Biol Res & Review, 1401 Woodmont,Rockville Pike, Rockville, MD 20852 USA. NR 41 TC 121 Z9 130 U1 1 U2 13 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JAN PY 2001 VL 3 IS 1 BP 43 EP 48 DI 10.1016/S1286-4579(00)01350-2 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 399WM UT WOS:000166837300005 PM 11226853 ER PT S AU Lee, CJ Lee, LH Lu, CS Wu, A AF Lee, CJ Lee, LH Lu, CS Wu, A BE Wu, AM TI Bacterial polysaccharides as vaccines - Immunity and chemical characterization SO MOLECULAR IMMUNOLOGY OF COMPLEX CARBOHYDRATES-2 SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT International Symposium on the Molecular Immunology of Complex Carbohydrates-2 CY AUG 28-SEP 02, 1999 CL TAIPEI, TAIWAN ID VI-CAPSULAR POLYSACCHARIDE; ESCHERICHIA-COLI O157-H7; B NEISSERIA-MENINGITIDIS; PNEUMOCOCCAL CONJUGATE VACCINE; SIALIC-ACID POLYSACCHARIDE; HEMOLYTIC UREMIC SYNDROME; TETANUS TOXOID CONJUGATE; STREPTOCOCCUS-PNEUMONIAE; UNITED-STATES; SALMONELLA-TYPHI C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Ctr Dis Control, Taipei, Taiwan. Chang Gung Med Coll, Inst Mol & Cellular Biol, Tao Yuan 333, Taiwan. RP Lee, CJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 118 TC 18 Z9 21 U1 0 U2 2 PU KLUWER ACADEMIC / PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46532-9 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2001 VL 491 BP 453 EP 471 PG 19 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BS37N UT WOS:000169678200030 PM 14533815 ER PT S AU Lee, CJ Li, ZM AF Lee, CJ Li, ZM BE Wu, AM TI Protective immunity and gene expression related to pneumococcal glycoconjugate SO MOLECULAR IMMUNOLOGY OF COMPLEX CARBOHYDRATES-2 SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT International Symposium on the Molecular Immunology of Complex Carbohydrates-2 CY AUG 28-SEP 02, 1999 CL TAIPEI, TAIWAN ID STREPTOCOCCUS-PNEUMONIAE; IMMUNIZATION; PNEUMOLYSIN; MICE; POLYSACCHARIDE; CHALLENGE; VIRULENCE C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Lee, CJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 22 TC 1 Z9 2 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46532-9 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2001 VL 491 BP 505 EP 514 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BS37N UT WOS:000169678200033 PM 14533818 ER PT S AU Tsai, CM AF Tsai, CM BE Wu, AM TI Molecular mimicry of host structures by lipooligosaccharides of Neisseria meningitidis: Characterization of sialylated and nonsialylated lacto-N-neotetraose (Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc) structures in lipooligosaccharides using monoclonal antibodies and specific lectins SO MOLECULAR IMMUNOLOGY OF COMPLEX CARBOHYDRATES-2 SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT International Symposium on the Molecular Immunology of Complex Carbohydrates-2 CY AUG 28-SEP 02, 1999 CL TAIPEI, TAIWAN ID LIPOPOLYSACCHARIDE CORE OLIGOSACCHARIDES; OUTER-MEMBRANE PROTEINS; MENINGOCOCCAL LIPOPOLYSACCHARIDES; SERUM RESISTANCE; GONORRHOEAE LIPOOLIGOSACCHARIDES; ANTIGENIC SIMILARITIES; HUMAN-ERYTHROCYTES; POTENTIAL VACCINE; MAACKIA-AMURENSIS; HUMAN-NEUTROPHILS C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, Bethesda, MD 20892 USA. RP Tsai, CM (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, Bethesda, MD 20892 USA. NR 79 TC 20 Z9 20 U1 0 U2 2 PU KLUWER ACADEMIC / PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46532-9 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2001 VL 491 BP 525 EP 542 PG 18 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BS37N UT WOS:000169678200035 PM 14533820 ER PT S AU Paule, MG Popke, EJ Allen, RR Pearson, E Hammond, T AF Paule, MG Popke, EJ Allen, RR Pearson, E Hammond, T BE Slikker, W Trembly, B TI Effects of chronic NMDA receptor and fast sodium channel blockade during development on the acquisition of visual discriminations and learning abilities in rhesus monkeys SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 5th International Conference on Neuroprotective Agents CY SEP 17-21, 2000 CL LAKE TAHOE, NEVADA SP Natl Ctr Toxicol Res /FDA, Cent Arkansas Chapter Sigma Xi DE dizocilpine; chronic toxicity; behavioral toxicity; operant behavior C1 Natl Ctr Toxicol Res, Behav Toxicol Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. Peak Stat Serv, Evergreen, CO USA. AstraZeneca Charnwood, Safety Assessment, Loughborough, Leics, England. RP Paule, MG (reprint author), Natl Ctr Toxicol Res, Behav Toxicol Lab, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-352-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 939 BP 237 EP 237 PG 1 WC Multidisciplinary Sciences; Clinical Neurology SC Science & Technology - Other Topics; Neurosciences & Neurology GA BT12V UT WOS:000172028600026 ER PT S AU Pletnikov, MV Jones, ML Rubin, SA Moran, TH Carbone, KM AF Pletnikov, MV Jones, ML Rubin, SA Moran, TH Carbone, KM BE Slikker, W Trembly, B TI Rat model of Autism Spectrum Disorders - Genetic background effects on Borna disease virus-induced developmental brain damage SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 5th International Conference on Neuroprotective Agents CY SEP 17-21, 2000 CL LAKE TAHOE, NEVADA SP Natl Ctr Toxicol Res /FDA, Cent Arkansas Chapter Sigma Xi DE rat model; Autism Spectrum Disorder; genetic background; Borna disease; brain damage ID BDV INFECTION C1 Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. US FDA, CBER, OVRR, DVP,LPRVD, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. RP Pletnikov, MV (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. NR 12 TC 7 Z9 7 U1 0 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-352-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 939 BP 318 EP 319 PG 2 WC Multidisciplinary Sciences; Clinical Neurology SC Science & Technology - Other Topics; Neurosciences & Neurology GA BT12V UT WOS:000172028600036 PM 11462786 ER PT S AU Binienda, ZK Sadovova, NV Rountree, RL Scallet, AC Ali, SF AF Binienda, ZK Sadovova, NV Rountree, RL Scallet, AC Ali, SF BE Slikker, W Trembly, B TI Effect of L-carnitine pretreatment on 3-nitropropionic acid-induced inhibition of rat brain succinate dehydrogenase activity SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 5th International Conference on Neuroprotective Agents CY SEP 17-21, 2000 CL LAKE TAHOE, NEVADA SP Natl Ctr Toxicol Res /FDA, Cent Arkansas Chapter Sigma Xi DE L-carnitine; neuroprotection; rat brain; succinate dehydrogenase activity ID ACETYL-L-CARNITINE; DEGENERATION; CELLS AB L-Carnitine (LC) plays an important regulatory role in the mitochondrial transport of long chain free fatty acids (FFA). 3-Nitropropionic acid (3-NPA) is known to induce cellular energy deficit and oxidative stress-related neurotoxicity via an irreversible inhibition of mitochondrial succinate dehydrogenase (SDH). In the present study, activity of SDH was measured in order to evaluate neuroprotective effects of LC against the 3-NPA-induced neurotoxicity. Male, CD Sprague-Dawley rats, three months old, were injected with either 50 or 100 mg/kg of LC, i.p., 30 min prior to 3-NPA (30 mg/kg, s.c.) or with 3-NPA alone. The activity of brain SDH was quantified spectrophotometrically in caudate nucleus (CN), frontal cortex (F), and hippocampus (HIP) 60 min after the 3-NPA injection. The SDH activity in the animals treated with 3-NPA alone was 38% (CN), 50% (FC), and 36% (HIP) that of saline controls. Pretreatment with LC prior to 3-NPA injection attenuated decreases of SDH activity by approximately 15 and 29% (LC low and high dose, respectively). Despite the attenuation of SDH inhibitions the activity of SDH in these regions remained significantly lower in treated than in control rats (P < 0.05). It appears that the protective effect of LC against 3-NPA-induced oxidative stress cannot be explained by the direct action of LC to interfere with the SDH inhibition but are rather achieved by LC actions downstream of the SDH inhibition. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Binienda, ZK (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132, Jefferson, AR 72079 USA. NR 23 TC 5 Z9 5 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 1-57331-352-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 939 BP 359 EP 365 PG 7 WC Multidisciplinary Sciences; Clinical Neurology SC Science & Technology - Other Topics; Neurosciences & Neurology GA BT12V UT WOS:000172028600041 PM 11462791 ER PT S AU Imam, SZ El-Yazal, J Newport, GD Itzhak, Y Cadet, JL Slikker, W Ali, SF AF Imam, SZ El-Yazal, J Newport, GD Itzhak, Y Cadet, JL Slikker, W Ali, SF BE Slikker, W Trembly, B TI Methamphetamine-induced dopaminergic neurotoxicity: Role of peroxynitrite and neuroprotective role of antioxidants and peroxynitrite decomposition catalysts SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 5th International Conference on Neuroprotective Agents CY SEP 17-21, 2000 CL LAKE TAHOE, NEVADA SP Natl Ctr Toxicol Res /FDA, Cent Arkansas Chapter Sigma Xi DE methamphetamine; dopaminergic neurotoxicity; peroxynitrite; antioxidant; decomposition catalysts ID NITRIC-OXIDE SYNTHASE; GLUTATHIONE-PEROXIDASE; TYROSINE-HYDROXYLASE; BEHAVIORAL SENSITIZATION; SUPEROXIDE-DISMUTASE; CRYSTAL-STRUCTURE; NADPH-DIAPHORASE; FREE-RADICALS; MICE; BRAIN AB Oxidative stress, reactive oxygen (ROS), and nitrogen (RNS) species have been known to be involved in a multitude of neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). Both ROS and RNS have very short half-lives, thereby making their identification very difficult as a specific cause of neurodegeneration. Recently, we have developed a high performance liquid chromatography/electrochemical detection (HPLC/EC) method to identify 3-nitrotyrosine (3-NT), an in vitro and in vivo biomarker of peroxynitrite production, in cell cultures and brain to evaluate if an agent-driven neurotoxicity is produced by the generation of peroxynitrite. We show that a single or multiple injections of methamphetamine (METH) produced a significant increase in the formation of 3-NT in the striatum. This formation of 3-NT correlated with the striatal dopamine depletion caused by METH administration. We also show that PC12 cells treated with METH has significantly increased formation of 3-NT and dopamine depletion. Furthermore, we report that pretreatment with antioxidants such as selenium and melatonin can completely protect against the formation of 3-NT and depletion of striatal dopamine. We also report that pretreatment with peroxynitrite decomposition catalysts such as 5,10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato iron III (FeTMPyP) and 5, 10, 15, 20-tetrakis (2,4,6-trimethyl-3,5-suffonatophenyl) porphinato iron III (FETPPS) significantly protect against METH-induced 3-NT formation and striatal dopamine depletion. We used two different approaches, pharmacological manipulation and transgenic animal models, in order to further investigate the role of peroxynitrite. We show that a selective neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7-NI), significantly protect against the formation of 3-NT as well as striatal dopamine depletion. Similar results were observed with nNOS knockout and copper zinc superoxide dismutase (CuZnSOD)-overexpressed transgenic mice models. Finally, using the protein data bank crystal structure of tyrosine hydroxylase, we postulate the possible nitration of specific tyrosine moiety in the enzyme that can be responsible for dopaminergic neurotoxicity. Together, these data clearly support the hypothesis that the reactive nitrogen species, peroxynitrite, plays a major role in METH-induced dopaminergic neurotoxicity and that selective antioxidants and peroxynitrite decomposition catalysts can protect against METH-induced neurotoxicity. These antioxidants and decomposition catalysts may have therapeutic potential in the treatment of psychostimulant addictions. C1 US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL USA. Natl Inst Drug Abuse, Mol Neuropsychiat Sect, Intramural Res Program, Baltimore, MD USA. 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 59 TC 121 Z9 125 U1 2 U2 9 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-352-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 939 BP 366 EP 380 PG 15 WC Multidisciplinary Sciences; Clinical Neurology SC Science & Technology - Other Topics; Neurosciences & Neurology GA BT12V UT WOS:000172028600042 PM 11462792 ER PT S AU Scallet, AC Nony, PL Rountree, RL Binienda, ZK AF Scallet, AC Nony, PL Rountree, RL Binienda, ZK BE Slikker, W Trembly, B TI Biomarkers of 3-nitropropionic acid (3-NPA)-induced mitochondrial dysfunction as indicators of neuroprotection SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 5th International Conference on Neuroprotective Agents CY SEP 17-21, 2000 CL LAKE TAHOE, NEVADA SP Natl Ctr Toxicol Res /FDA, Cent Arkansas Chapter Sigma Xi DE biomarker; 3-nitropropionic acid; mitochondrial dysfunction; neuroprotection; succinate dehydrogenase ID SUCCINATE-DEHYDROGENASE; RAT-BRAIN; STRIATUM; INHIBITION; DISORDERS; LESIONS; DAMAGE AB In humans or animals, symptoms of mitochondrial energy dysfunction may be produced by mutations or inborn errors of the necessary enzymes, as well as by enzyme inhibitors or uncouplers of the oxidative phosphorylation process. 3-Nitropropionic acid (3-NPA) is a toxin that is sometimes produced on moldy crops (sugarcane, peanuts, etc.) in amounts sufficient to cause severe neuromuscular disorders when consumed by humans. In vitro 3-NPA irreversibly inactivates SDH, a Complex II respiratory enzyme important for mitochondrial energy production. We have been studying biomarkers of 3-NPA exposure in the expectation that such markers may be useful in the screening process to identify neuroprotective agents against neurotoxicity produced by mitochondrial energy dysfunction. Animals were sacrificed at various times after 3-NPA exposure for histochemical visualization of SDH activity and measurement of immediate postmortem rectal temperature. 3-NPA-treated rats experienced progressive hypothermia that reached a loss of 3 degreesC or more in core body temperature by three hours after dosing. The optical density of the SDH stain in brain was: reduced, following a similar time course, most prominently in the cerebellum and least sharply in the thalamus. Some rats were given injections of L-carnitine (an enhancer of fatty acid transport) either alone, or as a pretreatment prior to a dose of 3-NPA. Although L-carnitine deficiency by itself can produce mitochondrial dysfunction:, pretreatment with L-carnitine was of limited efficacy at overcoming the effects of 3-NPA on either body temperature or quantitative SDH histochemistry. Body temperature and SDH histochemistry may be useful biomarkers for evaluating the efficacy of neuroprotective agents against lower doses of 3-NPA, against other pharmacological models of mitochondrial dysfunction, or even against genetic mitochondrial diseases. C1 US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR USA. RP Scallet, AC (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, 3900 NCTR Dr, Jefferson, AR 72079 USA. NR 20 TC 11 Z9 11 U1 1 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-352-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 939 BP 381 EP 392 PG 12 WC Multidisciplinary Sciences; Clinical Neurology SC Science & Technology - Other Topics; Neurosciences & Neurology GA BT12V UT WOS:000172028600043 PM 11462793 ER PT S AU Ali, SF Imam, SZ Newport, GD Itzhak, Y Slikker, W AF Ali, SF Imam, SZ Newport, GD Itzhak, Y Slikker, W BE Slikker, W Trembly, B TI Role of peroxynitrite in neurodegeneration and neuroprotective role of antioxidants and peroxynitrite decomposition catalysts SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 5th International Conference on Neuroprotective Agents CY SEP 17-21, 2000 CL LAKE TAHOE, NEVADA SP Natl Ctr Toxicol Res /FDA, Cent Arkansas Chapter Sigma Xi DE peroxynitrite; neurodegeneration; antioxidant; decomposition catalyst C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL USA. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-352-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 939 BP 393 EP 394 PG 2 WC Multidisciplinary Sciences; Clinical Neurology SC Science & Technology - Other Topics; Neurosciences & Neurology GA BT12V UT WOS:000172028600044 ER PT J AU Ferguson, SA Paule, MG Holson, RR AF Ferguson, SA Paule, MG Holson, RR TI Neonatal dexamethasone on Day 7 in rats causes behavioral alterations reflective of hippocampal, but not cerebellar, deficits SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE glucocorticoid; dexamethasone; activity; water maze ID TEMPORAL RESPONSE DIFFERENTIATION; ACOUSTIC STARTLE; CORTICOSTERONE; GLUCOCORTICOIDS; STRESS; BRAIN; PERFORMANCE; LACTATION; CORTISOL; PLAY AB Developmental glucocorticoid treatment in rats has been shown to cause body and brain weight decrements concurrent with behavioral alterations. Here, Sprague-Dawley rats were treated with the synthetic glucocorticoid, dexamethasone (DEX), on postnatal day (PND) 7 (1.5 mg/kg, sc, injected in the morning and afternoon). Behavioral assessments of negative geotaxis, locomotor activity (open field, maze exploration, residential running wheel, residential figure 8 maze), open-field activity response to amphetamine, acoustic startle, prepulse inhibition (PPT) of acoustic startle, juvenile play behavior, anxiety (emergence tests), motor coordination (rotarod performance), spatial learning (Morris water maze and food-reinforced complex maze), and operant performance (time estimation and response inhibition) were assessed in male rats. Body weight was decreased beginning at PND 43 until sacrifice on PND 127. Whole and regional brain weights were less, especially hippocampus, cerebellum, brainstem, and cortical remnant. Indications of delayed development were apparent; specifically, DEX-treated rats took significantly longer to turn on PND 8, but not PND 9, in the negative geotaxis test. DEX treatment induced deficits in the Morris water maze that were similar to hippocampal deficits. Open-field activity changes were inconsistent; however, DEX-treated rats were hyperactive during the dark period in running wheel tests. There were no indications of changes in reactivity or emotionality. (C) 2001 Elsevier Science Inc. All rights reserved. C1 US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 45 TC 38 Z9 38 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JAN-FEB PY 2001 VL 23 IS 1 BP 57 EP 69 DI 10.1016/S0892-0362(00)00115-X PG 13 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 416ZY UT WOS:000167811700006 PM 11274876 ER PT J AU Djuric, Z Lewis, SM Lu, MH Mayhugh, M Tang, N Hart, RW AF Djuric, Z Lewis, SM Lu, MH Mayhugh, M Tang, N Hart, RW TI Effect of varying dietary fat levels on rat growth and oxidative DNA damage SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID MAMMARY-TUMORS; BREAST-CANCER; GAS-CHROMATOGRAPHY; ANTIOXIDANT STATUS; MASS-SPECTROMETRY; TUMORIGENESIS; BLOOD; CELLS; 5-(HYDROXYMETHYL)URACIL; MECHANISMS AB Dietary fat has previously been shown to have somewhat complicated relationships to levels of oxidative stress in rats. In this study, we examined the effects of five different dietary fat intakes on levels of oxidative DNA damage in rats. Animals fed diets containing 3%, 5%, 10%, or 15% corn oil had body weights that were similar after 20 weeks. Animals fed a 20% fat diet, however, had significantly higher mean body weight than any other group. Levels of 5-hydroxymethyl-2'-deoxyuridine, one marker of oxidative DNA damage, had different relationships to dietary fat in blood and mammary gland. In blood, levels increased with dietary fat levels, and the highest levels were observed with the 20% fat diet (65% higher levels than with the 3% fat diet). In mammary gland, a plateau-type effect was observed, with maximal levels of oxidative DNA damage being obtained using 10% fat (representing a 68% increase relative to the 3% fat diet). This could be a result of induction of compensatory mechanisms in response to a high fat diet in mammary gland but not in the short-lived nucleated blood cells. Oxidative DNA damage levels in blood thus appear to be a marker of dietary fat intake. In mammary gland, however, levels of DNA damage are consistent with previously observed promotional effects of dietary fat on mammary gland tumorigenesis at lower levels of fat intake with little or no incremental promoting effects at higher levels of fat intake. C1 Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Djuric, Z (reprint author), Wayne State Univ, Karmanos Canc Inst, 100 E Warren, Detroit, MI USA. RI Djuric, Zora/H-5147-2013 OI Djuric, Zora/0000-0002-8886-8853 FU PHS HHS [NC93B61] NR 35 TC 24 Z9 25 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2001 VL 39 IS 2 BP 214 EP 219 DI 10.1207/S15327914nc392_9 PG 6 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 492AG UT WOS:000172142800009 PM 11759283 ER PT J AU Yetley, EA AF Yetley, EA TI Energy for a new millennium - Regulatory perspectives SO NUTRITION REVIEWS LA English DT Article; Proceedings Paper CT Conference on Defining Energy for a New Millennium CY APR 04-05, 2000 CL WASHINGTON, D.C. SP ILSI N Amer Project Comm Energy C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Yetley, EA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT LIFE SCIENCES INST PI LAWRENCE PA 810 EAST 10TH ST SUBSCRIPTION OFFICE, LAWRENCE, KS 66044 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD JAN PY 2001 VL 59 IS 1 BP S33 EP S34 PN 2 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 409ZT UT WOS:000167416100011 PM 11255803 ER PT J AU Cada, AM Hansen, DK LaBorde, JB Ferguson, SA AF Cada, AM Hansen, DK LaBorde, JB Ferguson, SA TI Minimal effects from developmental exposure to St. John's Wort (Hypericum perforatum) in Sprague-Dawley rats SO NUTRITIONAL NEUROSCIENCE LA English DT Article DE St. John's Wort; development; behavior ID PROTEIN-KINASE-C; DEPRESSION; EXTRACT; FLUOXETINE; INHIBITION; APOPTOSIS; GROWTH AB Increasing widespread use of St. John's Wort (SJW, Hypericum perforatum) has led to concerns about its use in pregnant women. Behavioral and physiological alterations resulting from developmental treatment were investigated in Sprague-Dawley rats exposed to diets containing 0, 180, 900, 1800 or 4500 ppm SJW beginning on gestational day 3 and ending at offspring weaning on postnatal day (PND) 21. These dietary doses span 1-25 times the recommended human dose. Post-weaning behavioral assessments of male and female offspring included: open field activity, acoustic startle, performance of complex and Morris water mazes, and activity in an elevated plus-maze. There were no SJW effects on maternal weight gain or duration of gestation; offspring body weights were similar to controls from PND 2 through PND 56 after which, some treated groups weighed significantly less than the controls. There were no SJW-related behavioral alterations on any measure. Whole and regional brain weights of offspring at adulthood indicated no significant effects of SJW. These results indicate that there are few neurobehavioral alterations resulting from developmental SJW treatment in rats. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 16 TC 9 Z9 10 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1028-415X J9 NUTR NEUROSCI JI Nutr. Neurosci. PY 2001 VL 4 IS 2 BP 135 EP 141 PG 7 WC Neurosciences; Nutrition & Dietetics SC Neurosciences & Neurology; Nutrition & Dietetics GA 457LG UT WOS:000170138100005 PM 11842881 ER PT J AU Garthoff, LH Sobotka, TJ AF Garthoff, LH Sobotka, TJ TI From farm to table to brain: Foodborne pathogen infection and the potential role of the neuro-immune-endocrine system in neurotoxic sequelae SO NUTRITIONAL NEUROSCIENCE LA English DT Review DE foodborne pathogen; hazard identification; neuro-immune-endocrine system; neurotoxic sequelae ID TUMOR-NECROSIS-FACTOR; CENTRAL-NERVOUS-SYSTEM; HEMOLYTIC-UREMIC SYNDROME; ESCHERICHIA-COLI O157-H7; PITUITARY-ADRENAL AXIS; LISTERIA-MONOCYTOGENES INFECTION; NITRIC-OXIDE PRODUCTION; GUILLAIN-BARRE-SYNDROME; EXPERIMENTAL BACTERIAL-MENINGITIS; INTERLEUKIN-1 RECEPTOR ANTAGONIST AB The American diet is among the safest in the world; however, diseases transmitted by foodborne pathogens (FBPs) still pose a public health hazard. FBPs are the second most frequent cause of all infectious illnesses in the United States. Numerous anecdotal and clinical reports have demonstrated that central nervous system inflammation, infection, and adverse neurological effects occur as complications of foodborne gastroenteritis. Only a few well-controlled clinical or experimental studies, however, have investigated the neuropathogenesis. The full nature and extent of neurological involvement in foodborne illness is therefore unclear. To our knowledge, this review and commentary is the first effort to comprehensively discuss the issue of FBP induced neurotoxicity. We suggest that much of this information supports the role of a theoretical model, the neuro-immune-endocrine system, in organizing and helping to explain the complex pathogenesis of FBP neurotoxicity. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Toxicol & Nutr Prod Studies,Neurotoxicol Bran, Laurel, MD 20708 USA. RP Garthoff, LH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Toxicol & Nutr Prod Studies,Neurotoxicol Bran, 8301 Muirkirk Rd,MOD-1 Res Facil, Laurel, MD 20708 USA. EM lgarthof@cfsan.fda.gov NR 526 TC 3 Z9 3 U1 3 U2 3 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1028-415X J9 NUTR NEUROSCI JI Nutr. Neurosci. PY 2001 VL 4 IS 5 BP 333 EP 374 PG 42 WC Neurosciences; Nutrition & Dietetics SC Neurosciences & Neurology; Nutrition & Dietetics GA 499UN UT WOS:000172588900001 PM 11845817 ER PT J AU Cohen, MH Hirschfeld, S Honig, SF Ibrahim, A Johnson, JR O'Leary, JJ White, RM Williams, GA Pazdur, R AF Cohen, MH Hirschfeld, S Honig, SF Ibrahim, A Johnson, JR O'Leary, JJ White, RM Williams, GA Pazdur, R TI Drug approval summaries: Arsenic trioxide, tamoxifen citrate, anastrazole, paclitaxel, bexarotene SO ONCOLOGIST LA English DT Article DE arsenic trioxide; tamoxifen citrate; anastrazole; paclitaxel; bexarotene ID ACUTE PROMYELOCYTIC LEUKEMIA; SURGICAL-ADJUVANT-BREAST; T-CELL LYMPHOMA; CARCINOMA IN-SITU; AROMATASE INHIBITORS; MYCOSIS-FUNGOIDES; OVARIAN-CANCER; CISPLATIN; NEUROTOXICITY; THERAPIES AB This report summarizes information on drugs recently approved by the Food and Drug Administration, Office or Drug Evaluation 1, Division or Oncology Drug Products. Five applications supporting new claims will be discussed: Trisenox(TM) (arsenic trioxide) for induction of remission and consolidation in patients with acute promyelocytic leukemia who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose disease is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression; Nolvadex(R) (tamoxifen citrate) in women with ductal carcinoma in situ, following breast surgery and radiation, to reduce the risk of invasive breast cancer; Arimidex(R) (anastrazole) for first-line treatment of postmenopausal women with hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer; Taxol(R) (pachtaxel), 175 mg/m(2) by 3 h infusion in combination with cisplatin for first-line treatment of advanced ovarian cancer; and Targretin(R) gel (bexarotene) for the topical treatment of cutaneous lesions in patients with stage IA and IB cutaneous T-cell lymphoma who have not tolerated other therapies or who have refractory or persistent disease. Information provided includes rationale for drug development, study design, efficacy and safety results, and pertinent literature references. C1 US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20852 USA. RP Cohen, MH (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, WOC-1,1451 Rockville Pike, Rockville, MD 20852 USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 26 TC 61 Z9 63 U1 2 U2 4 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2001 VL 6 IS 1 BP 4 EP 11 DI 10.1634/theoncologist.6-1-4 PG 8 WC Oncology SC Oncology GA 528MN UT WOS:000174247700003 PM 11161223 ER PT J AU Kawakami, M Leland, P Kawakami, K Puri, RK AF Kawakami, M Leland, P Kawakami, K Puri, RK TI Mutation and functional analysis of IL-13 receptors in human malignant glioma cells SO ONCOLOGY RESEARCH LA English DT Article DE glioblastoma multiforme; interleukin-13; interleukin-13 receptors; PCR-SSCP; adhesion molecules ID ADHESION MOLECULE-1 EXPRESSION; INTERLEUKIN-13 RECEPTOR; PSEUDOMONAS EXOTOXIN; GROWTH-FACTOR; ENDOTHELIAL-CELLS; ALPHA CHAIN; SIGNAL-TRANSDUCTION; CARCINOMA-CELLS; BRAIN-TUMORS; E-SELECTIN AB We have previously demonstrated that human brain tumor cells, in particular glioblastoma multiforme (GBM), express abundant receptors for interleukin-13 on the cell surface. These receptors are composed of IL-13 receptor (IL-13R)alpha1, IL-13Ralpha2, and IL-4Ralpha chains. The significance of overexpression of H-13R on tumor cells is not known. Because expression of IL-13R on glioma cells is an unexpected phenomenon, we examined whether these receptors are polymorphic. Therefore, we analyzed cDNA for IL-13Ralpha1 and IL-13Ralpha2 chain genes by PCR-based single-strand conformation polymorphism and direct sequencing techniques for a possible polymorphism in 19 GBM, one normal human astrocyte, and two fibroblast cell lines. All analyzed samples except normal astrocytes overexpressed IL-13Ralpha2; however, none of these cell lines showed a mutation in cDNA for IL-13Ra2 chain. In contrast, all GBM samples, normal astrocytes, and fibroblasts expressed mRNA for IL-13Ralpha1 with apparent single nucleotide polymorphism in the transmembrane domain. To study the function of IL-13R on brain tumor cells, we investigated the regulation of adhesion molecules by IL-13 as assessed by flow cytometric analysis. A172 cell line expressed a low level of vascular cell adhesion molecule-1 (VCAM-1), while U251 and LA(1)-5g cell lines expressed intercellular adhesion molecule-1 (ICAM-1). On the other hand E-selectin was not expressed in any cell lines. Interestingly, IL-13 increased the expression level of VCAM-l in A172 cell line in a dose- and time-dependent manner. However, IL-13 did not modulate any other adhesion molecules. These results suggest that IL-13R on GBM cells are not rearranged but appear to be functional. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr MSC4555, Bethesda, MD 20892 USA. NR 40 TC 41 Z9 42 U1 1 U2 2 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0965-0407 J9 ONCOL RES JI Oncol. Res. PY 2001 VL 12 IS 11-12 BP 459 EP 467 PG 9 WC Oncology SC Oncology GA 533MH UT WOS:000174533800003 PM 11939409 ER PT S AU Ilev, IK Waynant, RW Bonaguidi, MA AF Ilev, IK Waynant, RW Bonaguidi, MA BE Gannot, I TI Evanescent wave delivery into a precise tissue area using fiber-optic probes SO OPTICAL FIBERS AND SENSORS FOR MEDICAL APPLICATIONS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optical Fibers and Sensors for Medical Applications CY JAN 20-21, 2001 CL SAN JOSE, CA SP SPIE DE evanescent wave delivery; hollow taper; optical fiber; grazing incidence ID UNCOATED HOLLOW TAPER; LASER DELIVERY AB We demonstrate a novel all-optical-fiber system for infrared (IR) laser radiation delivery into a precise tissue area. The operating principal of the laser delivery system is based on the use of a direct laser-to-taper coupling and an IR delivery fiber with angle-shaped tip. In our experiment, instead of a conventional lens-based laser-to-fiber coupling we use an uncoated glass hollow taper for a laser-to-fiber coupling. It is a funnel-shaped grazing-incidence-based hollow taper. The laser emission is launched directly, without any focusing elements, into the taper and next into the delivery fiber by a direct taper-to-fiber coupling. The IR fiber delivers the forward emission from a Er:YAG laser (lambda =2.94 mum) to the tissue to be treated. Moreover, in order to realize a regime of evanescent wave delivery, we use a specially shaped fiber tip with an angled (porro-prism) profile. When the fiber tip is out of the tissue area, the laser emission is backreflected at the angled tip due to total-internal-reflection. However, when the fiber tip is placed on absorbing tissue, it becomes "transparent" for laser emission because of the frustrated-total-internal-reflectance and the energy then is coupled into the absorber. When sufficient energy is transferred, dermatology or other precise surgical processes can be controlled or stopped. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP US FDA, Ctr Devices & Radiol Hlth, HFZ-134, Rockville, MD 20857 USA. NR 15 TC 2 Z9 2 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3931-2 J9 PROC SPIE PY 2001 VL 4253 BP 161 EP 167 DI 10.1117/12.427918 PG 7 WC Engineering, Biomedical; Optics; Physics, Applied SC Engineering; Optics; Physics GA BS73G UT WOS:000171028200019 ER PT S AU Benton, KA Misplon, JA Lo, CY Epstein, SL AF Benton, KA Misplon, JA Lo, CY Epstein, SL BE Osterhaus, ADM Cox, N Hampson, AW TI Susceptibility and immunity to influenza A strains in Ig-/-mice SO OPTIONS FOR THE CONTROL OF INFLUENZA IV SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 4th World Congress on Options for the Control of Influenza CY SEP 23-28, 2000 CL HERSONISSOS, GREECE DE viral immunity; in vivo animal models; T lymphocytes ID CELL-DEFICIENT MICE; VIRUS-INFECTION; A VIRUS; B-CELLS; T-CELLS; ABSENCE; PROTECTION; CLEARANCE; RECOVERY; MEMORY AB Background: Broad cross-protection to influenza strains of different subtypes, termed heterosubtypic immunity, can be observed in animal models and is the goal of new approaches to human vaccines. Knockout mouse models, such as doubly inactivated (DI) mice lacking B cells and Ig, can be used to focus on the role of T cells in heterosubtypic immunity. We previously demonstrated that DI mice immunized with influenza B/Ann Arbor were protected from homologous challenge. We wished to identify influenza A strains that could be used in DI mice to examine the contributions of T-cell subsets to heterosubtypic immunity. Methods: DI mice were infected intranasally (i.n.) under anesthesia with influenza strains at varying doses. Mice were monitored for mortality, and lung titers were assessed for non-lethal strains. Results Commonly used mouse-tropic influenza A strains were lethal to DI mice, even at low doses. Several other isolates were found to replicate to high titers in the lungs for several days until being cleared to undetectable levels. Conclusion: Non-lethal strains that replicate in the lungs can be used to study heterosubtypic protection in DI mice measured as reduction in lung virus titers. Published by Elsevier Science B.V. C1 US FDA, Ctr Biol Evaluat & Res, Lab Immunol & Dev Biol, Div Cellular & Gene Therapies, Bethesda, MD USA. RP Benton, KA (reprint author), US FDA, CBER, 1401 Rockville Pike,HFM 521, Rockville, MD 20852 USA. NR 14 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 0-444-50575-X J9 INT CONGR SER PY 2001 VL 1219 BP 327 EP 332 DI 10.1016/S0531-5131(01)00343-0 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases; Virology SC Public, Environmental & Occupational Health; Infectious Diseases; Virology GA BT73L UT WOS:000173897700045 ER PT S AU Ye, ZP Liu, T Huang, XY Offringa, DP McInnis, J Levandowski, RA AF Ye, ZP Liu, T Huang, XY Offringa, DP McInnis, J Levandowski, RA BE Osterhaus, ADM Cox, N Hampson, AW TI Identification of the functional domains of the matrix protein of influenza A/WSN/33 virus SO OPTIONS FOR THE CONTROL OF INFLUENZA IV SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 4th World Congress on Options for the Control of Influenza CY SEP 23-28, 2000 CL HERSONISSOS, GREECE DE Ml protein; RNP binding; RNA binding ID M1 PROTEIN; A VIRUS; RNA; PEPTIDES; ZINC AB Background: The matrix protein (M1) of influenza virus plays a central role in viral replication and has been ascribed a variety of functions including association with viral RNA and ribonucleoprotein (RNP). It is essential to understand the binding mechanism by identification of the functional domains of M1. Methods: The RNA and RNP-binding domains of M1 protein were identified by introducing amino-acid substitutions and deletions. The RNA-protein interaction was investigated by measuring the binding of radiolabeled RNA to immobilized M1 protein. Reconstitution of M1 with RNP was studied by incubation of radiolabeled M1 with purified RNP. Results: We characterized RNA-binding domains of M1 protein by mutating M1, and show that M1 binds to RNA through two independent domains, a zinc-finger motif and a series of basic amino acids (RKLKR). One of the RNA-binding domains consisting of a series of basic amino acids is also involved in RNP binding. An independent domain located in the N-terminal 76 amino acids of M1 also participates in RNP-binding activity. Conclusions: The data suggest that M1 interacts with both the RNA and protein components of RNP in assembly/disassembly of influenza A viruses. (C) 2001 Elsevier Science B.V. All rights reserved. C1 US FDA, Lab Pediat & Resp Viral Dis, Div Viral Prod, Off Vaccines Res & Review,Ctr Biol & Evaluat & Re, Bethesda, MD 20014 USA. RP Ye, ZP (reprint author), Room 2B17,Bldg 29A,8800 Rockville Pike, Bethesda, MD 20982 USA. NR 13 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 0-444-50575-X J9 INT CONGR SER PY 2001 VL 1219 BP 421 EP 426 DI 10.1016/S0531-5131(01)00350-8 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases; Virology SC Public, Environmental & Occupational Health; Infectious Diseases; Virology GA BT73L UT WOS:000173897700058 ER PT S AU Epstein, SL Stack, A Misplon, JA Lo, CY Mostowski, H Bennink, J Benton, KA Cooper, L Hodges, A Subbarao, K AF Epstein, SL Stack, A Misplon, JA Lo, CY Mostowski, H Bennink, J Benton, KA Cooper, L Hodges, A Subbarao, K BE Osterhaus, ADM Cox, N Hampson, AW TI Vaccination with DNA encoding conserved influenza viral proteins SO OPTIONS FOR THE CONTROL OF INFLUENZA IV SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 4th World Congress on Options for the Control of Influenza CY SEP 23-28, 2000 CL HERSONISSOS, GREECE DE DNA vaccines; viral immunity; T lymphocytes; mice; protective immunity ID CYTOTOXIC T-LYMPHOCYTES; VIRUS; MICE; PROTECTION; CHALLENGE AB Background: DNA vaccines encoding conserved antigens of influenza A virus can induce broad cross-protection against multiple influenza A subtypes. Better understanding of the mechanisms of this protection can help guide vaccine development. Methods: Mice were vaccinated with plasmids expressing nucleoprotein (NP) and matrix (M) given i.m., followed by lethal i.n. challenge with influenza virus. CTL were analyzed by Cr-51-release using fresh lung lymphocytes. Results: A/NP + A/ M vaccination promoted viral clearance and led to recovery, at challenge virus doses that were lethal to controls. CD8+ CTL were induced and were highly specific for influenza A antigens, but were not required for protection. Depletion of both CD4+ and CD8+ T cells during the challenge period abrogated protection. A plasmid expressing influenza B/NP was used to demonstrate specificity of antibodies produced and of protection against influenza B vs. A challenge. Discussion: DNA vaccination gave protection corresponding to the influenza A vs. B inserted genes, confirming immunological specificity. For A/NP + A/M DNA, T cells are required, but either CD4+ or CD8+ T cells protected in the absence of the other subset. These findings about DNA vaccines encoding antigens conserved among viral subtypes can be applied to human vaccine development for protection against new pandemic viruses. (C) 2001 Elsevier Science B.V. All rights reserved. C1 DCGT, OTRR, CBER, FDA, Rockville, MD 20852 USA. RP Epstein, SL (reprint author), DCGT, OTRR, CBER, FDA, 1401 Rockville Pike HFM-521, Rockville, MD 20852 USA. NR 11 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 0-444-50575-X J9 INT CONGR SER PY 2001 VL 1219 BP 905 EP 910 DI 10.1016/S0531-5131(01)00403-4 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases; Virology SC Public, Environmental & Occupational Health; Infectious Diseases; Virology GA BT73L UT WOS:000173897700122 ER PT J AU Pillai, R Shah, V Abriola, L Caetano, P Flynn, GL AF Pillai, R Shah, V Abriola, L Caetano, P Flynn, GL TI Release of hydrocortisone from a cream matrix: Dependency of release on suspension concentration and measurement of solubility and diffusivity SO PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY LA English DT Article DE concentration dependency; creams; diffusion coefficients; matrix release; release testing; reproducibility; solubility measurement; suspensions; root t-kinetics; root t-release theory ID DRUG AB The principal object of the present research was to investigate the sensitivity of drug release from a semisolid system to the manner of its preparation and to the concentration of drug placed within it. Established theory indicated that release should be concentration dependent, with the specific dependency determined by whether the drug in the system is filly in solution or is present substantially as suspended matter. To purposefully explore these relatively, untested performance expectations, the total amount of drug in the formula was varied from a low concentration of 0.25% to a high concentration of 3%. Conditions were established such that drug release conformed to release from a semi-infinite medium into a receptor sink. At every concentration, release profiles were well reproduced in replicate samples and, where multiple lots of a kind were employed, from lot to identical lot. In all cases square root of time release kinetics were observed. Moreover and without exception, the square root of time release rate from run to run was directly proportional to the square root of the total concentration of hydrocortisone placed in the formulations. The amount released per square root of time per square root of total concentration was nearly identical from run to run irrespective of total concentration. The overall behavior fit theoretical expectations for suspensions having only a small fraction of the drug they contain in solution. That this condition prevailed even at the lowest 0.25% hydrocortisone strength was proven by independently measuring hydrocortisone's solubility (0.02%). Measurement of solubility permitted estimation of the effective diffusivity of the drug through the cream (2 x 10(-7) cm(2)/s). C1 Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. CDER OPS, Off Pharmaceut Sci, Rockville, MD 20857 USA. Univ Michigan, Coll Engn, Ann Arbor, MI 48109 USA. Procter & Gamble Pharmaceut, Mason, OH 45040 USA. DPT Labs, San Antonio, TX 78215 USA. RP Flynn, GL (reprint author), Univ Michigan, Coll Pharm, 428 Church St, Ann Arbor, MI 48109 USA. NR 9 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 1083-7450 J9 PHARM DEV TECHNOL JI Pharm. Dev. Technol. PY 2001 VL 6 IS 3 BP 373 EP 384 DI 10.1081/PDT-100002619 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 456VL UT WOS:000170102900009 PM 11485179 ER PT J AU Lee, PID AF Lee, PID TI Design and power of a population pharmacokinetic study SO PHARMACEUTICAL RESEARCH LA English DT Article DE population pharmacokinetics; study power; study simulation ID PARAMETER-ESTIMATION AB Purpose. This paper investigated the influence of critical design factors on the power of a population pharmacokinetic (PK) study for identifying subpopulations that have different drug clearance than the typical population. Methods. A study simulation approach was used for the power estimation. The design factors included the number of subjects, sampling scheme, and compliance. Results. The false positive rates of incorrectly identifying a subpopulation were estimated for several scenarios. The false positive rates of the population PK study was relatively low, except when the numbers of subjects with full profiles and the subjects with troughs were distributed between populations in an unbalanced manner. The total number of subjects did not seem to have as much influence on study power as the number of subjects in the subpopulation, as long as the total number of subjects was significantly larger than the subpopulation. The variability of sampling time played an important role in both the statistical power and the accuracy of the estimated difference in clearance. Taking three samples provided greater power and better accuracy than taking two samples per subject. Taking only trough samples provided little power and poor estimation of clearance difference. Adding subjects with full profiles to a study with only trough samples taken in other subjects did not satisfactorily improve the clearance estimation. It was critical to account for dosing record in the population PK analysis to achieve appropriate power and accuracy. If the variability in dosing time was accounted for in the analysis, it improved the accuracy of the estimated difference in clearance. Missing dose administrations reduced the study power and resulted in deviation of estimated clearance difference. Conclusions. The power of a study should be determined prospectively to ensure appropriate study design for specific study objectives. C1 US FDA, CDER, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. RP Lee, PID (reprint author), US FDA, CDER, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. NR 6 TC 27 Z9 27 U1 0 U2 2 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 JAN PY 2001 VL 18 IS 1 BP 75 EP 82 DI 10.1023/A:1011030827847 PG 8 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 424EH UT WOS:000168218800011 PM 11336356 ER PT J AU Gagne, RM Shope, TB AF Gagne, RM Shope, TB TI Regulatory initiatives and framework in the USA: Interventional radiology SO RADIATION PROTECTION DOSIMETRY LA English DT Article; Proceedings Paper CT Workshop on Dosr and Image Quality in Digital Imaging and Interventional Radiology CY JUN, 1999 CL DUBLIN, IRELAND ID CARDIAC-CATHETERIZATION; SKIN INJURIES; RADIODERMATITIS; FLUOROSCOPY; EXPOSURE; ABLATION AB Therapeutic procedures using interventional radiology equipment as the imaging tool are often the only available treatment for serious, life-threatening conditions. Many of these procedures require extended periods of radiation exposure often at one location on the patient. As a result, the US Food and Drug Administration (FDA) continues to receive reports of radiation-induced injuries to the skin in patients undergoing some of these therapeutic procedures. The regulatory scheme applicable to interventional radiology equipment in the US is described including federal, state and local aspects, and the impact of professional and non-governmental organisations. Current activities within the FDA and other organisations which have or will affect the use, maintenance and manufacture of interventional radiology equipment are also described. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Gagne, RM (reprint author), US FDA, Ctr Devices & Radiol Hlth, 9200 Corp Blvd HFZ-142, Rockville, MD 20850 USA. NR 29 TC 1 Z9 1 U1 0 U2 0 PU NUCLEAR TECHNOLOGY PUBL PI ASHFORD PA PO BOX 7, ASHFORD TN23 1YW, KENT, ENGLAND SN 0144-8420 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PY 2001 VL 94 IS 1-2 BP 13 EP 18 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 424JE UT WOS:000168228500002 PM 11487821 ER PT J AU Hansen, DK Barbee, SA Grafton, TF Gu, Y Streck, RD AF Hansen, DK Barbee, SA Grafton, TF Gu, Y Streck, RD TI Antisense modulation of 5,10-methylenetetrahydrofolate reductase expression produces neural tube defects in mouse embryos SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE folic acid; neural tube defects; 5,10-methylenetetrahdyrofolate; MTHFR; gene expression; antisense; whole embryo culture; mouse animal model ID CYSTATHIONINE-BETA-SYNTHASE; METHYLENETETRAHYDROFOLATE REDUCTASE; SPINA-BIFIDA; RAT EMBRYOS; RISK FACTOR; HOMOCYSTEINE METABOLISM; GENETIC-POLYMORPHISM; THERMOLABILE VARIANT; 677C->T MUTATION; FOLATE STATUS AB The role of folate metabolism in producing neural tube defects (NTDs) in humans is unknown. In the current study, antisense oligodeoxyribonucleotide technology was utilized to disrupt normal expression of the gene for 5,10-methylenetrtrahydrofolate reductase (MTHFR) in organogenesis-stage mouse embryos. Two different antisense probes were microinjected into the amniotic sac of gestation day (CD) 8 mouse embryos with PBS or scrambled sense oligodeoxyribonucleotides injected into control embryos. Concentration-dependent increases in the frequencies of embryos with NTDs were observed for both antisense sequences. The level of mRNA for MTHFR was decreased in embryos treated with the higher concentration of one antisense sequence, indicating that the sequence is able to decrease gene expression. 5-methyltetrahydrofolate, the product of the MTHFR reaction, was able to decrease the incidence of antisrnse-induced NTDs, but co-injection with L-methionine did not. These results suggest that reduced expression of MTHFR may play a role in producing NTDs:. (C) 2001 Elsevier Science Inc. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Hansen, DK (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 58 TC 7 Z9 9 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD JAN-FEB PY 2001 VL 15 IS 1 BP 21 EP 29 PG 9 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 391TW UT WOS:000166372500004 PM 11137375 ER PT J AU Hansen, DK LaBorde, JB Wall, KS Hinson, WG Pipkin, JL Shaddock, J Lyn-Cook, L Young, JF AF Hansen, DK LaBorde, JB Wall, KS Hinson, WG Pipkin, JL Shaddock, J Lyn-Cook, L Young, JF TI Dose-response of retinoic acid induced stress protein synthesis and teratogenesis in mice SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE stress proteins; heat shock proteins; retinoic acid; teratogenesis; malformations; pregnancy; mice ID POSTIMPLANTATION RAT EMBRYOS; HEAT-SHOCK RESPONSE; DEVELOPMENT IN-VITRO; CELL-DEATH; SODIUM ARSENITE; MOUSE DEVELOPMENT; BIRTH-DEFECTS; HL-60 CELLS; INDUCTION; HYPERTHERMIA AB Stress proteins are synthesized in response to a variety of stressors, including several teratogenic agents. However, their role, if any, in the teratogenic process is unknown. We have previously demonstrated that all-trans-retinoic acid administered to pregnant CD-1 mice on gestational day 11 or 13 produced limb defects and cleft palate near term in a dose-responsive manner. This chemical also induced the synthesis of several nuclear stress proteins in embryonic tissues within several hours of dosing. The stress proteins were only observed in tissues that eventually became malformed and not in tissues that appeared normal at term. In the current work, we examined the stress response in embryonic target tissues after several different doses of retinoic acid. The nuclear stress proteins were synthesized in a dose-related manner and at a lower retinoic acid dose than doses producing malformations in the corresponding tissue at birth. Each individual stress protein and the total stress protein response were highly correlated, across dose, with the respective malformations observed at term. (C) 2001 Elsevier Science inc. All rights reserved. C1 Natl Ctr Toxicol Res, Div Genet & Reprod toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Pathol Associates Int, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Facil Engn & Maintenance, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Hansen, DK (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 56 TC 5 Z9 5 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD JAN-FEB PY 2001 VL 15 IS 1 BP 31 EP 41 PG 11 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 391TW UT WOS:000166372500005 PM 11137376 ER PT J AU Park, DL Price, WD AF Park, DL Price, WD TI Reduction of aflatoxin hazards using ammoniation SO REVIEWS OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY, VOL 171 SE REVIEWS OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY LA English DT Review ID NATURALLY CONTAMINATED CORN; REACTION-PRODUCTS; AMBIENT-TEMPERATURE; COTTONSEED MEALS; MILK; PEANUT; COWS; FEED; DECONTAMINATION; IDENTIFICATION C1 US FDA, Ctr Food Safety & Appl Nutr, Off Plant & Dairy Foods & Beverages, Div Nat Prod, Washington, DC 20204 USA. US FDA, Ctr Vet Med, Off Surveillance & Compliance, Rockville, MD 20855 USA. RP Park, DL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Plant & Dairy Foods & Beverages, Div Nat Prod, Washington, DC 20204 USA. NR 109 TC 9 Z9 9 U1 1 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0179-5953 J9 REV ENVIRON CONTAM T PY 2001 VL 171 BP 139 EP 175 PG 37 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA BT01K UT WOS:000171629700004 ER PT S AU Kobayashi, K DeLap, RJ AF Kobayashi, K DeLap, RJ BE Anthony, M Dunn, BK Sherman, S TI FDA review practices and priorities for drugs used in cancer treatment SO SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT NIH Workshop on Selective Estrogen Receptor Modulators (SERMs) CY APR 26-28, 2000 CL BETHESDA, MARYLAND SP NIA, NCI, Div Canc Prevent, NHLBI, NIDDKD, NIAMSK, NIDCR, NIEHS, NICHHD, NIH Off Res Womens Hlth, Dept Hlth & Human Serv, Amer Federat Aging Res DE FDA review; investigational new drug (IND) application; cancer treatment AB The Federal Food, Drug, and Cosmetic Act and related regulations (21 U.S.C. 301 et seq.) give FDA staff the legal authority and responsibility to review the safety and effectiveness of drugs and biological products (including products used in cancer treatment), from preclinical testing through all phases of clinical research and marketing. FDA review activities in the oncology arena can be divided into five major categories: (1) initial review of investigational new drug (IND) applications; (2) ongoing review of premarketing research (including new research protocols submitted to existing INDs and IND safety reports describing adverse events with the new drug); (3) discussions with commercial sponsors regarding their clinical development plans, including the design and conduct of key studies that are intended to support initial marketing approval for a new product or to support the addition of new indications to the prescribing information for currently marketed products; (4) review of submitted new drug applications (NDAs) or biological licensing applications (BLAs); and (5) continuing review of the safety and effectiveness of marketed products. Through these review activities, FDA staff work to ensure that products approved for marketing for cancer treatment are effective and adequately safe for their intended uses and to ensure that the quality, effectiveness, and safety of products on the market are preserved or enhanced, so patients and physicians may use these products with confidence and with adequate safety. Because these review activities generally fall into a chronologic sequence, the following discussion parallels the development course of a typical new drug. C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Off Drug Evaluat 5, Rockville, MD 20857 USA. RP Kobayashi, K (reprint author), US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Off Drug Evaluat 5, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 U1 0 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-358-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 949 BP 341 EP 344 PG 4 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Reproductive Biology SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Reproductive Biology GA BT69G UT WOS:000173775800047 PM 11795373 ER PT S AU Honig, SF AF Honig, SF BE Anthony, M Dunn, BK Sherman, S TI Tamoxifen for the reduction in the incidence of breast cancer in women at high risk for breast cancer SO SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT NIH Workshop on Selective Estrogen Receptor Modulators (SERMs) CY APR 26-28, 2000 CL BETHESDA, MARYLAND SP NIA, NCI, Div Canc Prevent, NHLBI, NIDDKD, NIAMSK, NIDCR, NIEHS, NICHHD, NIH Off Res Womens Hlth, Dept Hlth & Human Serv, Amer Federat Aging Res DE tamoxifen; breast cancer; high risk; prevention AB Recent legislation, including the Prescription Drug User Fee Act (1992) and the FDA Modernization Act (FDAMA) (1997), has provided an environment in which new drug applications (NDA) can be efficiently reviewed, resulting in rapid access to new drugs or to new uses for approved drugs by the public. The recent submission of a supplemental NDA for tamoxifen for the reduction in the incidence of breast cancer in women at high risk for breast cancer is an excellent example of the application of this legislation. First, the application received expedited but thorough multidisciplinary and interdivisional review by the FDA. Second, it required collaboration between the manufacturer (AstraZeneca Pharmaceuticals), the National Surgical Adjuvant Breast and Bowel Project (NSABP), the National Cancer Institute (NCI), and the FDA. This process worked well and demonstrated that cooperative group data can be used effectively to support an application. Third, a single large adequate and well-controlled trial was sufficient to support the effectiveness of tamoxifen for this indication. The quantity of evidence required to support approval has been discussed in FDA guidances ("Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products") and is part of FDAMA. C1 US FDA, Div Oncol Drug Prod, Rockville, MD 20852 USA. RP Honig, SF (reprint author), US FDA, Div Oncol Drug Prod, HFD-150,5600 Fishers Lane, Rockville, MD 20852 USA. NR 0 TC 9 Z9 10 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 1-57331-358-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 949 BP 345 EP 348 PG 4 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Reproductive Biology SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Reproductive Biology GA BT69G UT WOS:000173775800048 PM 11795374 ER PT J AU Weigmann, HJ Lademann, J Schanzer, S Lindemann, U von Pelchrzim, R Schaefer, H Sterry, W Shah, V AF Weigmann, HJ Lademann, J Schanzer, S Lindemann, U von Pelchrzim, R Schaefer, H Sterry, W Shah, V TI Correlation of the local distribution of topically applied substances inside the stratum corneum determined by tape-stripping to differences in bioavailability SO SKIN PHARMACOLOGY AND APPLIED SKIN PHYSIOLOGY LA English DT Article; Proceedings Paper CT Workshop on Structure and Function of the Stratum Corneum as a Border Organ CY NOV, 2000 CL BERLIN, GERMANY SP Ctr Exptl & Appl Cutaneous Physiol, L Oreal DE bioavailability; tape-stripping; optical spectroscopy; horny layer profile; clobetasol propionate; blanching; vehicle influence; ultraviolet filter substances; lateral spreading AB Tape-stripping and optical spectroscopy are used as a suitable combined method to determine the horny layer profile. Firstly, typical ultraviolet filter substances are used as active substances which are fixed inside the horny layer. Secondly, clobetasol propionate was applied topically in two formulations, Temovate (R) Cream and Temovate epsilon Emollient (R). The measured changes in the local distribution of the drug inside stratum corneum reflect the observed differences in the biological response visualized as blanching. The concentration of the drug in deeper parts of the horny layer proposes the existence of a small channel available for the percutaneous absorption. The observed low intensity blanching is correlated to the follicle orifices of the skin. After application of Temovate epsilon Emollient (R), a lateral spreading of the drug must be taken into account. Copyright (C) 2001 S. Karger AG, Basel. C1 Humboldt Univ, Med Fac Charite, Dermatol Clin, Ctr Expt & Appl Cutaneous Physiol, Berlin, Germany. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Lademann, J (reprint author), Humboldt Univ, Charite, Klin Dermatol Venerol & Allergol, CCP, D-10098 Berlin, Germany. NR 8 TC 48 Z9 49 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-2868 J9 SKIN PHARMACOL APPL JI Skin Pharmacol. Appl. Skin Physiol. PY 2001 VL 14 SU 1 BP 98 EP 102 DI 10.1159/000056397 PG 5 WC Dermatology; Pharmacology & Pharmacy SC Dermatology; Pharmacology & Pharmacy GA 467VM UT WOS:000170724500017 PM 11509914 ER PT S AU Ilev, IK Waynant, RW AF Ilev, IK Waynant, RW BE Conchello, JA Cogswell, CJ Wilson, T TI A high-resolution fiber-optic confocal microscope SO THREE-DIMENSIONAL AND MULTIDIMENSIONAL MICROSCOPY: IMAGE ACQUISITION AND PROCESSING VIII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on 3-Dimensional and Multidimensional Microscopy - Image Acquisition and Processing VIII CY JAN 21-22, 2001 CL SAN JOSE, CA SP SPIE DE Confocal laser microscope; multimode optical fiber; graded-index fiber; high numerical aperture; Gaussian mode distribution ID OUTPUT; LASER AB A novel design of a simple reflection confocal microscope with a multimode graded-index fiber output as an effective way for improving the dynamic range of the resolving power and achieving a submicron spatial resolution is presented. The basic idea for obtaining high spatial resolution involves the following advanced scheme properties. (1) It is an apertureless confocal arrangement in which the input laser emission with its maximum power is launched directly to the test object. (2) It uses a high-numerical-aperture focusing objective (NA>0.8) that provides high depth and spatial discriminations and thus, high axial and lateral resolutions are obtained. (3) It uses a graded-index multimode fiber (50-mum-core diameter) for signal detection rather than a conventional pinhole or single-mode fiber. The graded-index fiber ensures efficient launching and maintenance of high laser powers, and high sensitivity of signal detection. Moreover, according to the equivalent-Gaussian-mode model, the intensity mode distribution into the graded-index fiber can be presented as an equivalent Gaussian mode distribution. As a result, a significant reduction of the mode noise of the intensity distribution and of signal fluctuations is obtained. Thus, a regime of high-output power is achieved that provides high resolving power and a submicron axial resolution of 0.4 mum. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP US FDA, Ctr Devices & Radiol Hlth, HFZ-134, Rockville, MD 20857 USA. NR 12 TC 2 Z9 2 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3939-8 J9 PROC SPIE PY 2001 VL 4261 BP 7 EP 13 DI 10.1117/12.424531 PG 7 WC Microscopy; Radiology, Nuclear Medicine & Medical Imaging SC Microscopy; Radiology, Nuclear Medicine & Medical Imaging GA BS45X UT WOS:000169896200002 ER PT S AU Hellman, KB Solomon, RR Gaffey, C Durfor, CN Bishop, JG AF Hellman, KB Solomon, RR Gaffey, C Durfor, CN Bishop, JG BE Ikada, Y TI Regulatory considerations SO TISSUE ENGINEERING FOR THERAPEUTIC USE 5 SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 5th International Symposium on Tissue Engineering for Therapeutic Use CY NOV 16-17, 2000 CL TSUKUBA, JAPAN SP Japan Soc Promot Sci ID TISSUE C1 US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Rockville, MD 20850 USA. RP Hellman, KB (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, 12709 Twinbrook Pkwy, Rockville, MD 20850 USA. NR 9 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 0-444-50554-7 J9 INT CONGR SER PY 2001 VL 1222 BP 203 EP 222 PG 20 WC Engineering, Biomedical; Medicine, Research & Experimental SC Engineering; Research & Experimental Medicine GA BS31G UT WOS:000169429900020 ER PT J AU Barry, C Cole, S Fourie, B Geiter, L Gosey, L Grosset, J Kanyok, T Laughon, B Mitchison, D Nunn, P O'Brien, R Robinson, T Annick-Mouries, M Cynamon, M Duncan, K Goldberger, M Gutteridege, W Kioy, D Pablos-Mendez, A Orme, I Rieder, H Roscigno, G Vernon, A AF Barry, C Cole, S Fourie, B Geiter, L Gosey, L Grosset, J Kanyok, T Laughon, B Mitchison, D Nunn, P O'Brien, R Robinson, T Annick-Mouries, M Cynamon, M Duncan, K Goldberger, M Gutteridege, W Kioy, D Pablos-Mendez, A Orme, I Rieder, H Roscigno, G Vernon, A TI Scientific blueprint for tuberculosis drug development - Global alliance for TB drug development SO TUBERCULOSIS LA English DT Review ID SHORT-COURSE CHEMOTHERAPY; MULTIDRUG-RESISTANT TUBERCULOSIS; TREATING PULMONARY TUBERCULOSIS; SCINTILLATION PROXIMITY ASSAY; EARLY BACTERICIDAL ACTIVITY; AEROSOL INFECTION MODEL; MYCOBACTERIUM-BOVIS BCG; STRUCTURE-BASED DESIGN; ALAMAR-BLUE ASSAY; PREVENTIVE THERAPY C1 Ctr Dis Control & Prevent, Div TB Eliminat, Res & Evaluat Branch E10, Atlanta, GA 30333 USA. NIAID, NIH, Bethesda, MD USA. Inst Pasteur, Paris, France. S African MRC, Pretoria, South Africa. Sequella Fdn, Rockville, MD USA. US FDA, Bethesda, MD 20014 USA. Univ Paris 06, Paris, France. WHO, Special Programme Res & Training Trop Dis, CH-1211 Geneva, Switzerland. St George Hosp, Sch Med, London, England. Boston Consulting Grp Inc, Boston, MA USA. Vet Adm Med Ctr, Syracuse, NY 13210 USA. GlaxoSmithKline Inc, Stevenage, Herts, England. US FDA, Bethesda, MD 20014 USA. Rockefeller Fdn, New York, NY USA. Colorado State Univ, Ft Collins, CO 80523 USA. Int Union TB & Lung Dis, Bern, Switzerland. Global Alliance TB Drug Dev, New York, NY USA. CDC, Atlanta, GA 30333 USA. RP O'Brien, R (reprint author), Ctr Dis Control & Prevent, Div TB Eliminat, Res & Evaluat Branch E10, Atlanta, GA 30333 USA. EM rjo1@cdcede.gov RI Barry, III, Clifton/H-3839-2012 NR 209 TC 3 Z9 3 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1472-9792 J9 TUBERCULOSIS JI Tuberculosis PY 2001 VL 81 SU 1 BP 1 EP 52 PG 52 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 449LW UT WOS:000169686900001 ER PT J AU Dannenberg, AM Collins, FM AF Dannenberg, AM Collins, FM TI Progressive pulmonary tuberculosis is not due to increasing numbers of viable bacilli in rabbits, mice and guinea pigs, but is due to a continuous host response to mycobacterial products SO TUBERCULOSIS LA English DT Review ID EXPERIMENTAL AIRBORNE TUBERCULOSIS; DELAYED-TYPE HYPERSENSITIVITY; CELL-MEDIATED-IMMUNITY; PARASITE RELATIONSHIPS; RESPIRATORY ROUTE; GRANULOMA-FORMATION; TUBERCLE-BACILLI; INTERFERON-GAMMA; BCG LESIONS; INFECTION AB Tuberculosis (TB) kills more people in the world today than any other infectious disease. A better vaccine to prevent clinical tuberculosis is greatly needed. Candidate vaccines are often evaluated by infecting rabbits, mice and guinea pigs by an aerosol of virulent tubercle bacilli and culturing their lungs for viable bacilli at various times thereafter. In all three species, however, the number of viable bacilli usually does not continuously increase until the host succumbs. The number of viable bacilli increases logarithmically for only about 3 weeks. Then, the host develops delayed-type hypersensitivity (DTH) and cell-mediated immunity (CMI), which keep the number of viable bacilli rather constant during the subsequent weeks. In the immunized host, DTH and CMI stop the logarithmic increase sooner than in the unimmunized controls, so that the stationary bacillary levels that follow are lower. This review analyzes host-parasite interactions in the lungs of rabbits, mice and guinea pigs. All three species cannot prevent inhaled fully virulent tubercle bacilli from establishing an infection, but they differ markedly in the type of the disease produced once it is established. (C) 2001 Harcourt Publishers Ltd. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis, Bethesda, MD USA. RP Dannenberg, AM (reprint author), Johns Hopkins Univ, Sch Hyg, 615 N Wolfe St, Baltimore, MD 21205 USA. FU NIAID NIH HHS [AI-35195]; NIEHS NIH HHS [ES-03819] NR 106 TC 52 Z9 52 U1 0 U2 5 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1472-9792 J9 TUBERCULOSIS JI Tuberculosis PY 2001 VL 81 IS 3 BP 229 EP 242 DI 10.1054/tube.2001.0287 PG 14 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 449GK UT WOS:000169675800006 PM 11466035 ER PT J AU Mohan, KVK Atreya, CD AF Mohan, KVK Atreya, CD TI Nucleotide sequence analysis of rotavirus gene 11 from two tissue culture-adapted ATCC strains, RRV and Wa SO VIRUS GENES LA English DT Article DE OP-ORF; ns26; NSP5; NSP6; phosphoprotein; phylogeny ID IN-VIVO; NSP5; PHOSPHORYLATION; EXPRESSION; MUTATIONS; PROTEINS; DOMAIN; NS26 AB We report here nucleotide sequence and characterization of gene 11 from two tissue culture-adapted ATCC(1) rhesus (RRV) and human (Wa) strains of rotavirus. Gene 11 sequence encodes a nonstructural protein, NSP5 and also encodes NSP6, from an out of phase open reading frame. Sequence of RRVATCC gene 11 represents the first report from a rhesus rotavirus which has more than 90% homology at the nucleotide and deduced amino acid sequence level with that of its closely related simian SA11 strain. The Wa(ATCC) gene sequence differed from that of published Wa (Wa(Pub)) at three nucleotide positions, one at 264 (G(Wa-Pub) to A(ATCC-Wa)), another a nucleotide insertion (A) at position 388 and the third, a deletion (A) at 416. The latter two changes in Wa(ATCC) NSP5 resulted in drastic amino acid changes within a 10-residue region (123-132) from VHVYQFQLTN in Wa(Pub) to DSCVSISTNH in Wa(ATCC) NSP5 protein. In this region, Wa(ATCC) NSP5 is closer to published sequences from other strains, suggesting the authenticity of the present sequence. The nucleotide difference between Wa(Pub) and Wa(ATCC) NSP5 sequences, however, did not affect the NSP6 deduced amino acid sequence, which is overall highly conserved among all the strains compared. Sequence-based phylogenetic analysis of gene 11 identified a high degree of conservation within the Group A rotaviruses. In addition, it also separated RRVATCC and Wa(ATCC), suggesting rotavirus segregation by genogroup. An anti-NSP5 monoclonal antibody of SA11 recognized RRV NSP5 protein but not Wa(ATCC) NSP5 from the infected cells, further supporting the phylogenetic segregation of RRVATCC and Wa(ATCC) strains based on their NSP5 coding sequence. C1 US FDA, Sect Viral Pathogenesis & Adverse React, Lab Pediat & Resp Viral Dis, CBER, Bethesda, MD 20892 USA. RP Atreya, CD (reprint author), US FDA, Sect Viral Pathogenesis & Adverse React, Lab Pediat & Resp Viral Dis, CBER, Bldg 29A,Room 2C-11,HFM-460,NIH Campus,8800 Rockv, Bethesda, MD 20892 USA. NR 22 TC 14 Z9 18 U1 0 U2 0 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 PY 2001 VL 23 IS 3 BP 321 EP 329 PG 9 WC Genetics & Heredity; Virology SC Genetics & Heredity; Virology GA 490BZ UT WOS:000172031600009 PM 11778700 ER PT J AU Artlett, CM Ramos, R Jiminez, SA Patterson, K Miller, FW Rider, LG AF Artlett, CM Ramos, R Jiminez, SA Patterson, K Miller, FW Rider, LG CA Childhood Myositis Heterogeneity C TI Chimeric cells of maternal origin in juvenile idiopathic inflammatory myopathies SO LANCET LA English DT Article ID IDENTIFICATION; POLYMYOSITIS AB We identified maternal microchimerism by fluorescence in-situ hybridisation in magnetically-separated CD4 or CD8 peripheral blood cells of eight of nine male patients with juvenile idiopathic inflammatory myopathy, compared with two of nine healthy male controls. We also found maternal microchimerism in inflammatory lesions (one skin sample and nine muscle biopsy samples) of all ten patients examined, compared with two of ten biopsy samples from patients with other muscle disorders. These results suggest that maternal cells may be involved in the pathogenesis of juvenile idiopathic inflammatory myopathy. C1 Thomas Jefferson Univ, Div Rheumatol, Philadelphia, PA 19107 USA. Childrens Hosp & Reg Med Ctr, Dept Pathol, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD USA. NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Artlett, CM (reprint author), Thomas Jefferson Univ, Div Rheumatol, Philadelphia, PA 19107 USA. OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU NIAMS NIH HHS [R01 AR19616, R29 AR45399] NR 5 TC 103 Z9 105 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD DEC 23 PY 2000 VL 356 IS 9248 BP 2155 EP 2156 DI 10.1016/S0140-6736(00)03499-1 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 385HD UT WOS:000165997300016 PM 11191545 ER PT J AU Colman, EG AF Colman, EG TI Hippocrates ridens: a 17th century medico-political journal SO LANCET LA English DT Editorial Material C1 US FDA, Div Metab & Endocrine Drug Prod, Rockville, MD 20857 USA. RP Colman, EG (reprint author), US FDA, Div Metab & Endocrine Drug Prod, Rockville, MD 20857 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD DEC 23 PY 2000 VL 356 IS 9248 BP 2184 EP 2186 DI 10.1016/S0140-6736(00)03509-1 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 385HD UT WOS:000165997300041 PM 11191560 ER PT J AU Slotkin, TA Ferguson, SA Cada, AM McCook, EC Seidler, FJ AF Slotkin, TA Ferguson, SA Cada, AM McCook, EC Seidler, FJ TI Neonatal polyamine depletion by alpha-difluoromethylornithine: effects on adenylyl cyclase cell signaling are separable from effects on brain region growth SO BRAIN RESEARCH LA English DT Article DE adenylyl cyclase; beta-adrenergic receptor; alpha-difluoromethylornithine; G protein; ornithine decarboxylase ID DEVELOPING RAT-BRAIN; ORNITHINE DECARBOXYLASE; IRREVERSIBLE INHIBITOR; IMPAIRED DEVELOPMENT; CEREBELLAR CORTEX; AGED RATS; ONTOGENY; CHLORPYRIFOS; MECHANISMS; PROTEINS AB Ornithine decarboxylase (ODC) and the polyamines play an essential role in brain cell replication and differentiation. We administered alpha -difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, to neonatal rats on postnatal days 5-12, during the mitotic peak of the cerebellum, a treatment regimen that leads to selective growth inhibition and dysmorphology. In adulthood, cell signaling responses mediated through the adenylyl cyclase pathway were evaluated in order to determine if synaptic dysfunction extends to regions that appear to be otherwise unaffected by DFMO. Total adenylyl cyclase catalytic activity, evaluated with the direct enzymatic stimulant, Mn2+, was significantly elevated in male rats both in the cerebellum and in brain regions showing no growth retardation (cerebral cortex, brainstem); there were no significant effects in females. In contrast, signaling mediated through the G proteins that couple neurotransmitter receptors to adenylyl cyclase showed a deficit in the DFMO group, as evaluated with the response to fluoride; in males, there was no corresponding increase in activity as would have been expected solely from the enhancement of adenylyl cyclase, and in females, there was actually a significant decrease in the response to fluoride. Again, the deficits were not restricted to the cerebellum. Stimulation of adenylyl cyclase by isoproterenol, a beta -adrenergic receptor agonist that acts through G(s), likewise displayed deficits in both males and females, and without distinction by brain region. These results indicate that the ODC/polyamine pathway plays a role in the development of cell signaling, and hence in neurotransmission, above and beyond its role in cell replication and differentiation. Given the fact that numerous drugs and environmental contaminants have been shown to alter ODC and the polyamines in the developing brain, our findings suggest that changes in brain region growth or structure are inadequate to predict the targeting of specific neurotransmitter or signaling pathways, and that gender-selective functional defects may be present despite the absence of morphological differences. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Slotkin, TA (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Box 3813, Durham, NC 27710 USA. FU NICHD NIH HHS [HD-09713] NR 29 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 22 PY 2000 VL 887 IS 1 BP 16 EP 22 DI 10.1016/S0006-8993(00)02961-9 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 387HH UT WOS:000166116800003 PM 11134585 ER PT J AU Bai, RL Covell, DG Pei, XF Ewell, JB Nguyen, NY Brossi, A Hamel, E AF Bai, RL Covell, DG Pei, XF Ewell, JB Nguyen, NY Brossi, A Hamel, E TI Mapping the binding site of colchicinoids on beta-tubulin - 2-chloroacetyl-2-demethylthiocolchicine covalently reacts predominantly with cysteine 239 and secondarily with cysteine 354 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BOVINE BRAIN; BIOLOGICAL PROPERTIES; NUCLEOCAPSID PROTEIN; INHIBITOR BINDING; THIOCOLCHICINE; AGENTS; IDENTIFICATION; SEPARATION; KINETICS; RESIDUE AB 2-Chloroacetyl-2-demethylthiocolchicine (2CTC) and 3-chloroacetyl-3-demethylthiocolchicine (3CTC) resemble colchicine in binding to tubulin and react covalently with beta -tubulin, forming adducts with cysteine residues 239 and 354. The adducts at Cys-239 are less stable than those at Cys-354 during formic acid digestion. Extrapolating to zero time, the Cys-239 to Cys-354 adduct ratio is 77:23 for 2CTC and 27:73 for 3CTC. Using energy minimization modeling to dock colchicinoids into the electron crystallographic model of P-tubulin in protofilaments (Nogales, E., Wolf, S. G., and Downing, K. H. (1998) Nature 391, 199-203), we found two potential binding sites. At one, entirely encompassed within beta -tubulin, the C2- and CS-oxygen atoms of 2CTC and 3CTC overlapped poorly with those of colchicine and thiocolchicine, but distances from the reactive carbon atoms of the analogs to the sulfur atoms of the cysteine residues were qualitatively consistent with reactivity. The other potential binding site was located at the alpha/beta interface. Here, the oxygen atoms of the analogs overlapped well with those of colchicine, but relative distances of the reactive carbons to the cysteine sulfur atoms did not correlate with the observed reactivity. A significant conformational change must occur in the colchicine binding site of tubulin in the transition from the unpolymerized to the polymerized state. C1 NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,Frederick Canc Res & De, Frederick, MD 21702 USA. NCI, Lab Expt & Computat Biol, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. NIDDK, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Facil Biotechnol Resources, Bethesda, MD 20892 USA. RP Hamel, E (reprint author), NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,Frederick Canc Res & De, Bldg 469,Rm 104,POB B, Frederick, MD 21702 USA. FU NCI NIH HHS [N01CO56000] NR 38 TC 72 Z9 78 U1 0 U2 2 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 DEC 22 PY 2000 VL 275 IS 51 BP 40443 EP 40452 DI 10.1074/jbc.M005299200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 386BD UT WOS:000166039500087 PM 11005811 ER PT J AU Elliot, EL Kvenberg, JE AF Elliot, EL Kvenberg, JE TI Risk assessment used to evaluate the US position on Listeria monocytogenes in seafood SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Listeria monocytogenes; seafood; risk assessment; regulatory policy ID FIELD GEL-ELECTROPHORESIS; SPORADIC LISTERIOSIS; RAINBOW-TROUT; OUTBREAK; FOODS AB Human listeriosis has been associated with consumption of food including seafood. Surveillance information on the presence of Listeria monocytogenes in seafood products is presented as a background for steps that are being taken to inform risk managers of risks associated with particular food products. United States policy for L. monocytogenes in food has been shaped by our increasing knowledge of the epidemiology of outbreaks and sporadic cases of human listeriosis, the potentially severe public health consequences, and the characteristics of the organism. A quantitative risk assessment of the scientific knowledge we have about the organism and the epidemiology of listeriosis should be the basis for changes in this policy. Risk assessment uses quantitative scientific and epidemiological information in a structured format to determine the risks associated with particular hazards. A quantitative risk assessment is being performed using currently available data by the US Food and Drug Administration, in collaboration with the US Food Safety and Inspection Service, to determine the risk of listeriosis from various foods, including seafood, for specific intervention methods, and for general and at-risk population groups. The questions being considered include those on level of consumption, epidemiology, dose response, and the virulence, biology, and ecology of the organism. Risk managers can use the resulting information to form a defendable science-based policy on L. monocytogenes in food. (C) Published by Elsevier Science B.V. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Elliot, EL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-615,200 C St SW, Washington, DC 20204 USA. NR 30 TC 21 Z9 22 U1 2 U2 8 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 DEC 20 PY 2000 VL 62 IS 3 SI SI BP 253 EP 260 DI 10.1016/S0168-1605(00)00344-5 PG 8 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 387WF UT WOS:000166144300012 PM 11156269 ER PT J AU Smalley, W Shatin, D Wysowski, DK Gurwitz, J Andrade, SE Goodman, M Chan, KA Platt, R Schech, SD Ray, WA AF Smalley, W Shatin, D Wysowski, DK Gurwitz, J Andrade, SE Goodman, M Chan, KA Platt, R Schech, SD Ray, WA TI Contraindicated use of cisapride - Impact of food and drug administration regulatory action SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID TORSADES-DE-POINTES; CLARITHROMYCIN AB Context Cisapride, a gastrointestinal tract promotility agent, can cause life-threatening cardiac arrhythmias in patients susceptible either because of concurrent use of medications that interfere with cisapride metabolism or prolong the QT interval or because of the presence of other diseases that predispose to such arrhythmias. In June 1998, the US Food and Drug Administration (FDA) determined that use of cisapride was contraindicated in such patients and informed practitioners through additions to the boxed warning in the label and a "Dear Health Care Professional" letter sent by the drug's manufacturer. Objective To evaluate the impact of the FDA's 1998 regulatory action regarding contraindicated use of cisapride. Design and Setting Analysis of data for the 1-year periods before (July 1997-June 1998) and after (July 1998-June 1999) the regulatory action from the population-based, pharmacoepidemiology research databases of 2 managed care organizations (sites A and B) and a state Medicaid program (site C). Participants Patients with at least 180 days of prior enrollment in 1 of the 3 sites who were prescribed cisapride at least once in the period before (n = 24840) or after (n = 22459) regulatory action. Patients could be included in both cohorts. Main Outcome Measures Proportion of cisapride users in each period for whom cisapride use was contraindicated by the product label, based on computerized patient medical encounter records. Results In the year prior to regulatory action, cisapride use was contraindicated for 26%, 30%, and 60% of users in study sites A, B, and C, respectively. In the year after regulatory action, use was contraindicated for 24%, 28%, and 58% of users, a reduction in contraindicated use of approximately 2 per 100 cisapride users at each site. When the analysis was restricted to new users of cisapride after regulatory action, only minor reductions in contraindicated use were found. Conclusion The FDA's 1998 regulatory action regarding cisapride use had no material effect on contraindicated cisapride use. More effective ways to communicate new information about drug safety are needed. C1 Vanderbilt Univ, Med Ctr, Sch Med, Dept Prevent Med, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. VA Med Ctr, Ctr Geriatr Res Educ & Clin, Nashville, TN USA. Unitedhlth Grp, Ctr Hlth Care Policy & Evaluat, Minnetonka, MN USA. US FDA, Off Postmkt Drug Risk Assessment, Rockville, MD 20857 USA. Univ Massachusetts, Sch Med, Fallon Healthcare Syst, Worcester, MA USA. Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Worcester, MA USA. Univ Rhode Isl, Coll Pharm, Kingston, RI 02881 USA. Healthpartners Res Fdn, Bloomington, MN USA. Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ray, WA (reprint author), Vanderbilt Univ, Med Ctr, Sch Med, Dept Prevent Med, Med Ctr N,A-1124, Nashville, TN 37232 USA. NR 12 TC 177 Z9 180 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 20 PY 2000 VL 284 IS 23 BP 3036 EP 3039 DI 10.1001/jama.284.23.3036 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 382VC UT WOS:000165847200029 PM 11122591 ER PT J AU Koch, WH de Henestrosa, ARF Woodgate, R AF Koch, WH de Henestrosa, ARF Woodgate, R TI Identification of mucAB-like homologs on two IncT plasmids, R394 and Rts-1 SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE SOS mutagenesis; UmuC; Tus; DinI; LexA; C. freundii ID DIFFERENT INCOMPATIBILITY GROUPS; 60-MEGADALTON CRYPTIC PLASMID; DNA-POLYMERASE-ETA; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; INDUCIBLE MUTAGENESIS; UV MUTAGENESIS; UMU OPERON; ULTRAVIOLET-LIGHT; SEQUENCE-ANALYSIS AB Recent phylogenetic analysis of the superfamily of lesion-replicating DNA polymerases suggest that they can be broadly divided into four sub-groups comprised of UmuC-like, DinB-like, Rev1-like and Rad30-like proteins. The UmuC-like sub-family is best characterized at the genetic level and sequence analysis of eleven umu orthologs, residing on bacterial chromosomes or on self-transmissible R-plasmids allows further subdivision into five sub-groups (UmuDC, MucAB, ImpAB, RumAB and RulAB) based on amino acid sequence conservation. Some of these orthologs are apparently inactive in situ, but may promote increased mutagenesis and survival when subcloned and expressed from high-copy number plasmids. We were, therefore, interested in devising an assay that would identify umuC-like genes in situ in the absence of a functional assay. To this end, degenerate primers directed towards conserved amino acid regions within the UmuC-like sub-family of DNA polymerases were designed and used to identify mucAB-like operons on the IncT plasmids, R394 and Rts-1. Interestingly, DNA sequence analysis of an similar to7 kb region of R394 identified two LexA-regulated genes immediately downstream of mucAB((R394)) that are similar to the chromosomally-encoded Escherichia coli tus gene and the IncI plasmid-encoded impC gene, respectively. Analysis of the R394 and Rts-1 mucB genes revealed that both contain insertions which result in the expression of a truncated inactive MucB protein. While R394 was unable to restore mutagenesis functions to a Delta umuDC E. coli strain, Rts-1 surprisingly promoted significant levels of MMS-induced SOS mutagenesis, raising the possibility that Rts-1 encodes another, yet unidentified, umu-like homolog. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. US FDA, Mol Biol Branch, Washington, DC 20204 USA. RP Woodgate, R (reprint author), NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bldg 6,Room 1A13,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 63 TC 9 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD DEC 20 PY 2000 VL 457 IS 1-2 BP 1 EP 13 DI 10.1016/S0027-5107(00)00134-2 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 385CB UT WOS:000165983100001 PM 11106794 ER PT J AU Bondy, SC Ali, SF Kleinman, MT AF Bondy, SC Ali, SF Kleinman, MT TI Exposure of mice to tobacco smoke attenuates the toxic effect of methamphetamine on dopamine systems SO TOXICOLOGY LETTERS LA English DT Article DE tobacco smoke; nicotine; methamphetamine; dopamine; cigarettes; Parkinson's disease ID EXPERIMENTAL PARKINSONISM; PHARMACOLOGICAL AGENTS; NEUROTROPHIC FACTORS; STRIATAL INCREASE; CIGARETTE-SMOKE; NICOTINE; DISEASE; RATS AB Methamphetamine treatment of mice rapidly and severely depleted levels of dopamine and its metabolites. homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) in the caudate nucleus. Exposure of mice to cigarette smoke by means of nose-only breathing apparatus for 20 min twice daily over 3 days prior to drug treatment significantly attenuated the neurotoxicity of methamphetamine as judged by a lesser depletion of dopamine. DOPAC and HVA. The lesser effect of methamphetamine upon content of serotonin level was unaltered by prior inhalation of smoke. Results suggest a specific protective effect of inhaled tobacco smoke upon the effects of methamphetamine upon dopaminergic circuitry. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Calif Irvine, Dept Community & Environm Med, Ctr Environm & Occupat Hlth, Irvine, CA 92697 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Bondy, SC (reprint author), Univ Calif Irvine, Dept Community & Environm Med, Ctr Environm & Occupat Hlth, Irvine, CA 92697 USA. FU NIEHS NIH HHS [ES7992] NR 15 TC 3 Z9 3 U1 0 U2 0 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 DEC 20 PY 2000 VL 118 IS 1-2 BP 43 EP 46 DI 10.1016/S0378-4274(00)00267-8 PG 4 WC Toxicology SC Toxicology GA 387UU UT WOS:000166140900005 PM 11137307 ER PT J AU Takeshita, S Takeshita, F Haddad, DE Ishii, KJ Klinman, DM AF Takeshita, S Takeshita, F Haddad, DE Ishii, KJ Klinman, DM TI CpG oligodeoxynucleotides induce murine macrophages to up-regulate chemokine mRNA expression SO CELLULAR IMMUNOLOGY LA English DT Article DE CpG; oligodeoxynucleotide; macrophage; chemokine; innate immunity; inflammation ID IMMUNOSTIMULATORY DNA-SEQUENCES; BACTERIAL-DNA; CC-CHEMOKINES; CUTTING EDGE; IN-VIVO; MOTIFS; INFLAMMATION; ACTIVATION; OLIGONUCLEOTIDES; LYMPHOCYTES AB Intramuscular injection of synthetic oligodeoxynucleotides (ODN) expressing unmethylated CpG motifs trigger the rapid development of a local inflammatory response. In vitro studies demonstrate that macrophages exposed to CpG ODN up-regulate expression of mRNA encoding the chemokines MIP-1 alpha, MIP-1 beta, MIP-2, RANTES, JE/MCP-1, and IP-10, Within 6 h of in vivo administration, CpG: ODN induce a significant increase in chemokine mRNA levels at the site of injection and draining lymph nodes. These chemokines may contribute to the migration and stimulation of inflammatory cells that contribute to the development of CpG ODN-induced immune responses, (C) 2000 Academic Press. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. USN, Med Res Inst, Malaria Program, Bethesda, MD 20889 USA. RP Takeshita, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. RI Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 34 TC 59 Z9 64 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD DEC 15 PY 2000 VL 206 IS 2 BP 101 EP 106 DI 10.1006/cimm.2000.1735 PG 6 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 399XY UT WOS:000166840600003 PM 11161441 ER PT J AU Hanna, GM Evans, FE AF Hanna, GM Evans, FE TI Optimization of enantiomeric separation for quantitative determination of the chiral drug propranolol by H-1-NMR spectroscopy utilizing a chiral solvating agent SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE propranolol; H-1-NMR spectroscopy; chiral solvating agent; enantiomers; dastereoimeric solvates; absolute configuration; optical purity ID PERFORMANCE LIQUID-CHROMATOGRAPHY; STATIONARY PHASE; HUMAN-PLASMA; BETA-BLOCKERS; DERIVATIVES; RESOLUTION; AMINES; (-)-PROPRANOLOL; (+)-PROPRANOLOL; COLUMN AB High-field H-1-NMR methodology for enantiomeric composition determination of the chiral drug propranolol utilizing a chiral solvating agent is reported, Optimal experimental conditions for the resolution of enantiomers were determined by studying the interaction of substrate concentration, chiral solvating agent concentration and temperature. The success of the method is based on the selection of a chiral solvating agent that has the following two characteristics. First, it possesses functional groups that are complimentary to those of the chiral substrate for significant interaction to occur. Second, it has a group of diamagnetic anisotropy near its stereogenic center for translating spatial environments of solute nuclei into different magnetic environments that are measurable by NMR spectroscopy. Optical purities were determined on the basis of the intensities of the methyl proton resonances. The analysis of synthetic enantiomeric mixtures of propranolol by the proposed NMR method resulted in assay values, which agreed closely with the known quantities of each enantiomer in the mixtures tested. The mean +/- SD recovery values for the (R)-(+)-enantiomer was 100.0 +/- 0.6% of added antipode (n = 7). (C) 2000 Elsevier Science B.V. All rights reserved. C1 US FDA, NE Reg Lab, Jamaica, NY 11433 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Hanna, GM (reprint author), US FDA, NE Reg Lab, 158-15 Liberty Ave, Jamaica, NY 11433 USA. NR 23 TC 15 Z9 15 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD DEC 15 PY 2000 VL 24 IS 2 BP 189 EP 196 DI 10.1016/S0731-7085(00)00386-1 PG 8 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 380TR UT WOS:000165720000003 PM 11130198 ER PT J AU Marano, NN Rossiter, S Stamey, K Joyce, K Barrett, TJ Tollefson, LK Angulo, FJ AF Marano, NN Rossiter, S Stamey, K Joyce, K Barrett, TJ Tollefson, LK Angulo, FJ TI The National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria, 1996-1999: surveillance for action SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT Symposium on Public Health in the New Millennium held during the 137th American-Veterinary-Medical-Association Annual Convention CY JUN 23, 2000 CL SALT LAKE CITY, UTAH SP Amer Vet Med Assoc C1 Ctr Dis Control & Prevent, Foodborne & Diarrheal Dis Branch, Atlanta, GA 30333 USA. US FDA, Off Surveillance & Compliance, Ctr Vet Med, Rockville, MD 20855 USA. RP Marano, NN (reprint author), Ctr Dis Control & Prevent, Meningitis & Special Pathogens Branch, MS C-O9,1600 Clifton Rd, Atlanta, GA 30333 USA. NR 2 TC 27 Z9 28 U1 1 U2 1 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD DEC 15 PY 2000 VL 217 IS 12 BP 1829 EP 1830 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA 382QC UT WOS:000165832900030 PM 11132885 ER PT J AU Singer, SJ Tiernan, R Sullivan, EJ AF Singer, SJ Tiernan, R Sullivan, EJ TI Interstitial pneumonitis associated with sirolimus therapy in renal-transplant recipients. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Singer, SJ (reprint author), US FDA, Rockville, MD 20857 USA. NR 2 TC 76 Z9 77 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 14 PY 2000 VL 343 IS 24 BP 1815 EP 1816 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 382FH UT WOS:000165812000025 PM 11185606 ER PT J AU Averbuch, M Katzper, M AF Averbuch, M Katzper, M TI A search for sex differences in response to analgesia SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 101st Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 15-17, 2000 CL LOS ANGELES, CALIFORNIA SP Amer Soc Clin Pharmacol & Therapeut ID GENDER DIFFERENCES; GENERAL-POPULATION; EXPERIMENTAL PAIN; THRESHOLD; STIMULI; WOMEN; MICE AB Background: It is generally accepted that males and females respond differently to painful conditions. With few exceptions, according to the published literature, females demonstrate a lower pain threshold and a lower tolerance of painful stimuli. There is some support in the literature that females experience greater analgesic efficacy than do males after the administration of narcotic analgesics. We compared the analgesic response of females and males to ibuprofen in a post-third-molar extraction dental pain model. Methods: We performed a meta-analysis of 314 subjects included in the ibuprofen treatment arm of 7 double-blind, post-third-molar extraction dental pain (moderate to severe) studies, which were submitted to the agency electronically. The inclusion and exclusion criteria were practically identical in all studies. Pain relief and pain intensity measurements used the same metrics in all studies and were recorded just before and at least at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, and 6.0 hours after drug administration. Results: The study included 195 female subjects and 119 male subjects (mean age, 21 years). Other than requiring dental extractions, the subjects were all healthy. Postoperative baseline pain was greater in females than males to a statistically significant degree (P=.006). Both pain intensity and pain relief scores demonstrated the well-established analgesic effect of ibugrofen in the pooled data set as well as in all the individual studies. Moreover, the mean pain intensity and pain relief scores over time for the female and male treatment groups were not noticeably different at any time point after drug administration, with no imputation for missing values. Analysis of the data using the "baseline observation carried forward" technique for remedicated subjects (the technique recommended by the Food and Drug Administration for efficacy analysis of acute analgesic medications) produced the same results, which were confirmed by analysis of variance and t tests at each time point of the study. Conclusions: Our results demonstrated no sex effect on the analgesic response to ibuprofen. These results were obtained under the post-third-molar extraction setting, in which the least possible confounding factors are present. To fully establish the generality of this phenomenon, studies should be carried out in other pain models and using analgesic medications with different mechanisms of action. C1 US FDA, Ctr Drug Evaluat & Res, Div Analges Anti Inflammat & Ophthal Drug Prod, Rockville, MD 20854 USA. RP Katzper, M (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Analges Anti Inflammat & Ophthal Drug Prod, HFD 550,2 Locks Pond Ct, Rockville, MD 20854 USA. NR 34 TC 34 Z9 37 U1 1 U2 2 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 DEC 11 PY 2000 VL 160 IS 22 BP 3424 EP 3428 DI 10.1001/archinte.160.22.3424 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 380RX UT WOS:000165718200010 PM 11112235 ER PT J AU Bowyer, JF AF Bowyer, JF TI Neuronal degeneration in the limbic system of weanling rats exposed to saline, hyperthermia or d-amphetamine SO BRAIN RESEARCH LA English DT Article DE amphetamine; limbic system; seizures; neurodegeneration; weanlings ID STRIATAL DOPAMINE; FLUORO-JADE; METHAMPHETAMINE; NEUROTOXICITY; INJURY; DISSOCIATION; DAMAGE; USERS AB Neuronal degeneration was detected in the tenia tecta and other regions of the anterior limbic system of male weanling rats 3 days after four doses of 5 mg/kg d-amphetamine (4x5 mg/kg AMPH) when seizures occurred during AMPH exposure. Neurodegeneration in the parietal cortex, loss of tyrosine hydroxylase immunoreactivity in the caudate-putamen (CPu) and decreases in CPu tissue dopamine levels in weanlings was much less than those previously observed in adults. The neurotoxicity seen in the parietal cortex and CPu of the weanlings was much less than previously seen in adults even though severe hyperthermia and the behavior of retrograde propulsion occurred during AMPH exposure. Neurodegeneration was not detected in any of the previously mentioned brain regions in controls and weanlings made hyperthermic by a warm environment. However, signs of spontaneous neurodegeneration were seen in the posterior piriform cortex (Pir), posteriolateral cortical amygdaloid nucleus (PLCo), and the amygdalopiriform transition area (APir) of control weanlings. The doses of AMPH and the degree of hyperthermia necessary to induce seizures were substantially lower in weanlings compared to those previously observed in adult rats. Further studies will be necessary to determine if the susceptibility of weanlings to AMPH-induced seizures is related to or dependent on the same processes involved in producing degeneration in the posterior limbic system of saline controls. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Bowyer, JF (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 32 TC 15 Z9 15 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 8 PY 2000 VL 885 IS 2 BP 166 EP 171 DI 10.1016/S0006-8993(00)02925-5 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 385VX UT WOS:000166026800003 PM 11102570 ER PT J AU Vryheid, RE Kane, MA Muller, N Schatz, GC Bezabeh, S AF Vryheid, RE Kane, MA Muller, N Schatz, GC Bezabeh, S TI Infant and adolescent hepatitis B immunization up to 1999: a global overview SO VACCINE LA English DT Review DE hepatitis B; vaccination; immunization; infants; adolescents ID LONG-TERM EFFICACY; VACCINATION PROGRAM; COST-EFFECTIVENESS; VIRUS-INFECTION; SURFACE-ANTIGEN; FOLLOW-UP; HEPATOCELLULAR-CARCINOMA; DEVELOPING-COUNTRIES; EXPANDED PROGRAM; CHILDREN AB This article presents a global overview of hepatitis B infant and adolescent immunization programmes. The 108 reported universal infant or adolescent immunization programmes and 87 reported national infant coverage rates fit a pattern, explained by hepatitis B endemicity, prosperity, policy emphasis, and immunization programme strength. Most East and Southeast Asian, Pacific, and Middle Eastern countries have intermediate to highly endemic hepatitis B. Most have achieved 65-100% coverage. South and Central Asia and sub-Saharan Africa have intermediate to high endemicity, with some countries having hepatitis B immunization programmes. Some Southern and Eastern European countries, with intermediate endemicity, have high coverage. Low endemic Northern European countries vaccinate higher risk groups; some have universal infant or adolescent programmes. Caribbean and Latin American countries have varying endemicity, and most started programmes. Low endemic North American countries have universal vaccination programmes. Universal immunization strategies have greatly reduced incidence and prevalence, and are cost-effective for many countries, but many have difficulties affording this vaccine. Globally, most infants are not being immunized against hepatitis B virus infection. Increasing coverage, and decreasing the numbers of people diseased and dying from this virus, may require delivering heat-stable vaccine beyond cold chains, creative financing to reduce prices, and multivalent vaccines. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Program Appropriate Technol Hlth, Seattle, WA USA. Plexus Hlth Grp, St Simons Isl, GA USA. US FDA, Ctr Drug & Radiol Hlth, Washington, DC 20204 USA. RP Vryheid, RE (reprint author), POB 1115, Lemon Grove, CA 91946 USA. NR 131 TC 37 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 DEC 8 PY 2000 VL 19 IS 9-10 BP 1026 EP 1037 DI 10.1016/S0264-410X(00)00239-5 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 383QW UT WOS:000165894700008 PM 11137236 ER PT J AU Rados, WM AF Rados, WM TI Online information for health care professionals SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Rados, WM (reprint author), US FDA, Rockville, MD 20857 USA. NR 1 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 DEC 1 PY 2000 VL 62 IS 11 BP 2528 EP 2530 PG 3 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 381GQ UT WOS:000165754300011 PM 11130236 ER PT J AU Hoff, PM Ellerton, JA Dakhil, SR Winn, RJ Abbruzzese, JL Pazdur, R AF Hoff, PM Ellerton, JA Dakhil, SR Winn, RJ Abbruzzese, JL Pazdur, R TI Phase II study of intravenous CI-958 in metastatic colorectal adenocarcinoma SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE colorectal cancer; metastases; CI-958; investigational chemotherapy; phase II trial ID ANTICANCER AGENTS AB In a multicenter, phase II trial, CI-958, a benzothiopyranoindazole DNA intercalator, was administered to Is patients who had nor received prior chemotherapy for metastatic colorectal cancer. The drug was given by intravenous infusion at a dose of 700 mg/m(2) every 21 days. There were no objective responses. Grades III and TV toxic effects were limited to granulocytopenia in 42% of courses and anemia in 5% of courses. There was one case of grade III increase in transaminases. Our results show that at this dose and schedule, CI-958 lacks activity against colorectal cancer. C1 Univ Texas, MD Anderson Canc Ctr, Div Med, Dept Gastrointestinal Oncol & Digest Dis, Houston, TX 77030 USA. So Nevada Community Clin Oncol Program, Las Vegas, NV USA. Wichita Community Clin Oncol Program, Wichita, KS USA. US FDA, Div Oncol Drug Prod, Rockville, MD 20857 USA. RP Hoff, PM (reprint author), Univ Texas, MD Anderson Canc Ctr, Div Med, Dept Gastrointestinal Oncol & Digest Dis, 1515 Holcombe Blvd,Box 78, Houston, TX 77030 USA. FU NCI NIH HHS [CA 45809, CA 70172] NR 8 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD DEC PY 2000 VL 23 IS 6 BP 602 EP 604 DI 10.1097/00000421-200012000-00015 PG 3 WC Oncology SC Oncology GA 383XT UT WOS:000165910500015 PM 11202806 ER PT J AU Astor, BC Kaczmarek, RG Hefflin, B Daley, WR AF Astor, BC Kaczmarek, RG Hefflin, B Daley, WR TI Mortality after aortic valve replacement: Results from a nationally representative database SO ANNALS OF THORACIC SURGERY LA English DT Article ID BYPASS GRAFT-SURGERY; OPERATIVE MORTALITY; HEART-VALVE; LATE RISK; VOLUME; DETERMINANTS; EXPERIENCE; GENDER; IMPACT; OLDER AB Background. Nationally representative estimates of in-hospital mortality after aortic valve replacement are needed to evaluate whether results from The Society of Thoracic Surgeons National Cardiac Surgery Database are applicable to other institutions in the United States performing these procedures. Methods. Data from the 1994 Nationwide Inpatient Sample were used to estimate the patient characteristics and in-hospital mortality rates associated with aortic valve replacements performed in nonfederal hospitals in the United States. Procedural and hospital characteristics were examined for possible associations with in-hospital mortality. Results. An estimated 46,397 aortic valve replacements were performed. In-hospital mortality occurred in 4.3% of first-time isolated aortic valve replacements and 6.4% overall. The highest quartile of procedure-specific hospital volume, compared with the lowest quartile, was associated with lower in-hospital mortality (adjusted odds ratio, 0.58; 95% confidence interval, 0.42 to 0.81). Conclusions. The in-hospital mortality rates observed in this study are very similar to those reported from The Society of Thoracic Surgeons database. These data provide substantial evidence that results from The Society of Thoracic Surgeons database are representative of those achieved at other institutions. However, procedure-specific hospital volume must be considered in applying these results to individual institutions. (Ann Thorac Surg 2000;70:1939-45) (C) 2000 by The Society of Thoracic Surgeons. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Astor, BC (reprint author), Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, 2024 E Monument St, Baltimore, MD 21205 USA. NR 31 TC 70 Z9 77 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2000 VL 70 IS 6 BP 1939 EP 1945 DI 10.1016/S0003-4975(00)01670-2 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 385UT UT WOS:000166022900040 PM 11156099 ER PT J AU Guo, X Chen, J Beuchat, LR Brackett, RE AF Guo, X Chen, J Beuchat, LR Brackett, RE TI PCR detection of Salmonella enterica serotype Montevideo in and on raw tomatoes using primers derived from hilA SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; TYPHIMURIUM INVASION GENES; REGULATOR; SEQUENCE; OUTBREAK; SPROUTS; MEMBER; CELLS; ASSAY AB Salmonellae have been some of the most frequently reported etiological agents in fresh-produce-associated outbreaks of human infections in recent years. PCR assays using four innovative pairs of primers derived from hilA and sirA, positive regulators of Salmonella invasive genes, were developed to identify Salmonella enterica serotype Montevideo on and in tomatoes. Based on examination of 83 Salmonella strains and 22 non-Salmonella strains, we concluded that a pair of hilA primers detects Salmonella specifically. The detection limits of the PCR assay were 10(1) and 10(0) CFU/ml after enrichment at 37 degreesC for 6 and 9 h, respectively. When the assay was validated by detecting S. enterica serotype Montevideo in and on artificially inoculated tomatoes, 10(2) and 10(1) CFU/g were detected, respectively, after enrichment for 6 h at 37 degreesC. Our results suggest that the hili-based PCR assay is sensitive and specific, and can be used for rapid detection of Salmonellae in or on fresh produce. C1 Univ Georgia, Dept Food Sci & Technol, Ctr Food Safety & Qual Enhancement, Griffin, GA 30223 USA. US FDA, Off Plant Dairy Foods & Beverages, Washington, DC 20204 USA. RP Beuchat, LR (reprint author), Univ Georgia, Dept Food Sci & Technol, Ctr Food Safety & Qual Enhancement, 1109 Expt Rd, Griffin, GA 30223 USA. NR 32 TC 42 Z9 55 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD DEC PY 2000 VL 66 IS 12 BP 5248 EP 5252 DI 10.1128/AEM.66.12.5248-5252.2000 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 404QP UT WOS:000167112400024 PM 11097898 ER PT J AU Hur, HG Lay, JO Beger, RD Freeman, JP Rafii, F AF Hur, HG Lay, JO Beger, RD Freeman, JP Rafii, F TI Isolation of human intestinal bacteria metabolizing the natural isoflavone glycosides daidzin and genistin SO ARCHIVES OF MICROBIOLOGY LA English DT Article DE isoflavonoid; phytoestrogen; intestinal bacteria; biotransformation; reduction ID DIETARY ISOFLAVONES; IN-VITRO; PHYTOESTROGENS; ANGIOGENESIS; INHIBITION; MECHANISMS; RECEPTORS AB Fecal bacteria from a healthy individual were screened for the specific bacteria involved in the metabolism of dietary isoflavonoids. Two strains of bacteria capable of producing primary and secondary metabolites from the natural isoflavone glycosides daidzin and genistin were detected. The metabolites were identified by comparison of their HPLC/mass, H-1 NMR and UV spectra with those of standard and synthetic compounds. Both Escherichia coli HGH21 and the gram-positive strain HGH6 converted daidzin and genistin to the their respective aglycones daidzein and genistein. Under anoxic conditions, strain HGH6 further metabolized the isoflavones daidzein and genistein to dihydrodaidzein and dihydrogenistein. respectively. The reduction of a double bond between C-2 and C-3 to a single bond was isoflavonoid-specific by strain HGH6, which did not reduce a similar bond in the flavonoids apigenin and chrysin. Strain HGH6 did not further metabolize dihydrodaidzein and dihydrogenistein. This is the first study in which specific colonic bacteria that are involved in the metabolism of daidzin and genistin have been detected. 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 Rafii, F (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 NR 30 TC 156 Z9 175 U1 2 U2 25 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-8933 J9 ARCH MICROBIOL JI Arch. Microbiol. PD DEC PY 2000 VL 174 IS 6 BP 422 EP 428 DI 10.1007/s002030000222 PG 7 WC Microbiology SC Microbiology GA 389RR UT WOS:000166252000007 PM 11195098 ER PT J AU Gershon, S Wise, RP Niu, M Siegel, J AF Gershon, S Wise, RP Niu, M Siegel, J TI Postlicensure reports of infection during use of etanercept and infliximab. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20852 USA. NR 0 TC 10 Z9 10 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 DEC PY 2000 VL 43 IS 12 BP 2857 EP 2857 PG 1 WC Rheumatology SC Rheumatology GA 383ET UT WOS:000165870700034 ER PT J AU Lee, SJ AF Lee, SJ TI On estimators of scale and dispersion in neighbourhoods of parametric families SO AUSTRALIAN & NEW ZEALAND JOURNAL OF STATISTICS LA English DT Article DE contaminated distribution; mixed distribution; relative efficiency; standardized variance; trimmed mean; trimmed standard deviation; truncated distribution; Tukey models ID STATISTICS AB This paper investigates two estimators under the non-parametric neighbourhoods of an exponential scale parametric family. It uses the relative efficiency approach and shows that the tighter lower bounds on the relative efficiency of the upper trimmed mean to mean can be obtained under a sufficient condition. This condition gives the relationship between the possible positive lower bound and the degree of asymmetry of some related distributions. Similar arguments can be applied to the comparison of dispersion estimators under the neighbourhoods of a normal distribution. C1 Univ W Florida, Pensacola, FL 32514 USA. RP Lee, SJ (reprint author), US FDA, 9201 Corp Blvd,HFD-725,Rm N228, Rockville, MD 20850 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 1369-1473 J9 AUST NZ J STAT JI Aust. N. Z. J. Stat. PD DEC PY 2000 VL 42 IS 4 BP 393 EP 405 DI 10.1111/1467-842X.00137 PG 13 WC Statistics & Probability SC Mathematics GA 382XE UT WOS:000165852000002 ER PT J AU Lee, JH Klein, HG AF Lee, JH Klein, HG TI From leukocyte reduction to leukocyte transfusion: the immunological effects of transfused leukocytes SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Review DE leukocyte reduction; leukocyte transfusion; immunomodulation; transfusion-associated graft-versus-host disease; donor lymphocyte infusion; graft-versus-leukaemia effect ID BONE-MARROW TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; GRAFT-VERSUS-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL DEPLETION; MINOR HISTOCOMPATIBILITY ANTIGEN; RECURRENT SPONTANEOUS-ABORTIONS; PERIPHERAL-BLOOD LYMPHOCYTES; ACTIVATED KILLER CELLS AB In transfusion medicine, mononuclear leukocytes have been studied more often as contaminants of red blood cells or platelets responsible for adverse transfusion outcomes than as therapeutic cells; leukocyte transfusion has been effective in augmenting recipient immunity only in limited clinical situations. Studies in leukocyte reduction and leukocyte transfusion have progressed separately as if the leukocytes' adverse and therapeutic effects result from different immunological mechanisms. With growing clinical experience, however, it is increasingly clear that some adverse immune effects may be exploited for therapeutic benefit. Advances in clinical immunology, understanding of the variety of cells and functions in the leukocyte fraction of blood, and blood component preparation technology may lead to new ways of deriving immunological benefit from transfused blood leukocytes while minimizing their adverse effects. This chapter reviews the current uses of leukocyte reduction and mononuclear leukocyte transfusion, with an emphasis on the relationship between transfusion-associated graft-versus-host disease and donor lymphocyte infusion in controlling relapsed leukaemias. C1 US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Div Blood Applicat,Blood & Plasma Branch, Rockville, MD 20852 USA. NIH, Warren G Magnuson Clin Ctr, Div Transfus Med, Bethesda, MD 20892 USA. RP Lee, JH (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Div Blood Applicat,Blood & Plasma Branch, HFM-375,1401 Rockville Pike, Rockville, MD 20852 USA. NR 105 TC 7 Z9 7 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD DEC PY 2000 VL 13 IS 4 BP 585 EP 600 DI 10.1053/beha.2000.0101 PG 16 WC Hematology SC Hematology GA 383JC UT WOS:000165878500007 PM 11102278 ER PT J AU Lynch, TJ AF Lynch, TJ TI Biotechnology: alternatives to human plasma-derived therapeutic proteins SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Review DE biotechnology; blood proteins; gene expression; gene therapy; human; protein engineering; recombinant proteins; transgenes; transgenics ID VON-WILLEBRAND-FACTOR; HUMAN FACTOR-VIII; RECOMBINANT FACTOR-VIII; HUMAN-SERUM-ALBUMIN; HEMOPHILIA-A PATIENTS; PORCINE FACTOR-VIII; HUMAN FACTOR-IX; ACTIVE HUMAN ALPHA-1-ANTITRYPSIN; ADENOASSOCIATED VIRAL VECTOR; MEDIATED GENE-TRANSFER AB Proteins derived from human plasma have become critically important therapeutic products since their introduction in the 1940s. In the last 20 years, the tools of molecular biology have provided alternatives to the administration of the natural products. Recombinant analogues of Factor VIII and Factor IX are commercially available, and recombinant forms of other plasma proteins are under development. Genetic engineering also provides the opportunity to modify a natural protein to improve the efficiency with which it can be produced in vitro, or to change its therapeutic profile. More efficient production systems, such as transgenic plants or animals, may yield less costly therapies and a wider availability of products that are now in limited supply. Finally, gene therapy offers the prospect of permanently correcting conditions arising from deficiencies in any one of several plasma proteins, freeing individuals from the need to undergo periodic treatments with exogenous proteins. C1 US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Div Hematol, Rockville, MD 20857 USA. RP Lynch, TJ (reprint author), 14915 Broschart Rd,Suite 102, Rockville, MD 20850 USA. NR 136 TC 2 Z9 2 U1 0 U2 2 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD DEC PY 2000 VL 13 IS 4 BP 669 EP 688 DI 10.1053/beha.2000.0100 PG 20 WC Hematology SC Hematology GA 383JC UT WOS:000165878500012 PM 11102283 ER PT J AU Swartz, LA Progar, JJ May, JC AF Swartz, LA Progar, JJ May, JC TI The determination of phosphorus in Haemophilus influenzae type b conjugate vaccines by inductively coupled plasma-atomic emission spectrometry SO BIOLOGICALS LA English DT Article ID INFANTS AB This study describes a method for the determination of phosphorus in lyophilized Haemophilus influenzae type b conjugate vaccines by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The concentration of polysaccharide is directly related to the concentration of phosphorus as measured in the laboratory. Phosphorus is present in the polyribosyl-ribitol phosphate (PRP) group of the Haemophilus influenzae type b conjugate vaccine. The repeating unit of PRP is 3-B-D ribose[1-1]ribitoi-5-phosphate. Phosphorus in the final container is measured in mug per dose. The amount of PRP is calculated from this and reported in mug per dose. The Haemophilus influenzae type b conjugate vaccine was analyzed for phosphorus content within the range of 1.34 to 2.02 mug phosphorus per mi. The relative difference of phosphorus concentrations determined by the ICP-AES method from the phosphorus concentrations determined by the traditional colorimetric molybdate method ranged from 2.2 to 10.6%. Phosphorus spike recovery for the vaccine ranged from 93 to 99% (1.93+/-0.13 mug P/ml). The phosphorus determination of NIST SRM 3139 phosphorus spectrometric solution differed by 30% from the certified phosphorus value (1000 mg P/ml). C1 USDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Swartz, LA (reprint author), USDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 16 TC 4 Z9 4 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD DEC PY 2000 VL 28 IS 4 BP 227 EP 231 DI 10.1006/biol.2000.0261 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 411UH UT WOS:000167517300004 PM 11237358 ER PT J AU Cannon, JM Kostoryz, E Russo, KA Smith, RE Yourtee, DM AF Cannon, JM Kostoryz, E Russo, KA Smith, RE Yourtee, DM TI Bisphenol A and its biomaterial monomer derivatives alteration of in vitro cytochrome P450 metabolism in rat, minipig, and human SO BIOMACROMOLECULES LA English DT Article ID HUMAN LIVER-MICROSOMES; ENVIRONMENTAL ESTROGEN; LAURIC ACID; CHEMICALS; ISOFORMS; COATINGS; CAFFEINE; ENZYMES; 2E1 AB Bisphenol A (BPA) is a common structural component in a wide variety of biomaterial monomers. The effects of BPA and the following derivatives: bisphenol A glycidyl methacrylate (BisGMA), bisphenol A glycidyl diacrylate (BAGDA), bisphenol A ethoxylate dimethacrylate (BAEDM), bisphenol A dimethacrylate (BADM), and bisphenol A diglycidyl ether (BADGE) on mixed function oxidases (MFOs) are reported in this study. The rate of formation of metabolites from isoform-specific substrates for the MFOs (or cytochromes) CYP 1A, 2A, 2C, 2E, 3A, and 4A in the absence (control) and presence of BPA and derivatives was used to assess inhibition or stimulation of human, rat (male and female) liver, and minipig liver microsomal MFO activity. For human preparations the strongest inhibition by BPA was observed for CYP 2C. The inhibition was most prominent when a lower dose of BPA was used on the complete post-mitochondrial fraction. BPA inhibited rat microsomal CYP 1A isoform-specific metabolite production to 29 +/- 3% of control levels (100%). Biomaterial monomers exhibited mixed effects. For example, BPA stimulated CYP 4A in pooled human S9 to 129 +/- 1% of control. Also, BADM and BAGDA stimulated CYP 4A to 141% and 142% of control values, respectively. C1 Univ Missouri, Sch Pharm, Div Pharmacol, Toxicore Lab, Kansas City, MO 64108 USA. US FDA, Off Regulatory Affairs, Lenexa, KS 66214 USA. RP Yourtee, DM (reprint author), Univ Missouri, Sch Pharm, Div Pharmacol, Toxicore Lab, Kansas City, MO 64108 USA. NR 30 TC 14 Z9 15 U1 2 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 J9 BIOMACROMOLECULES JI Biomacromolecules PD WIN PY 2000 VL 1 IS 4 BP 656 EP 664 DI 10.1021/bm005564+ PG 9 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 433JD UT WOS:000168755500023 PM 11710196 ER PT J AU Kapley, A Lampel, K Purohit, HJ AF Kapley, A Lampel, K Purohit, HJ TI Thermocycling steps and optimization of multiplex PCR SO BIOTECHNOLOGY LETTERS LA English DT Article DE enteropathogens; multiplex PCR; multi-step PCR; thermocycling steps ID POLYMERASE CHAIN-REACTION; ESCHERICHIA-COLI; SALMONELLA; AMPLIFICATION; PROTEIN; WATER; INVA AB Multiplex PCR (M-PCR), a method that detects more than two target loci in a single reaction, relies on the variables which influence single template specific PCR. We describe here the role of temperature cycles in ensuring the efficiency of detection. We have designed a multi-step protocol, which uses gradients between the temperature steps. This has facilitated the target specific annealing in the developed M-PCR. We have examined various thermocycling steps and optimized the M-PCR protocol using 10(5) to 10(1) cells of Escherichia coli, Salmonella typhi, and Vibrio cholera as template in a single reaction. The sensitivity of the detection observed was 10(2) cells of each pathogen used in the study. 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 17 TC 17 Z9 17 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0141-5492 J9 BIOTECHNOL LETT JI Biotechnol. Lett. PD DEC PY 2000 VL 22 IS 24 BP 1913 EP 1918 DI 10.1023/A:1026748202071 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 379FF UT WOS:000165630600002 ER PT J AU Mandavilli, BS Ali, SF Van Houten, B AF Mandavilli, BS Ali, SF Van Houten, B TI DNA damage in brain mitochondria caused by aging and MPTP treatment SO BRAIN RESEARCH LA English DT Article DE aging; dopamine; MPTP; oxidative stress; DNA damage; mitochondria ID PARKINSONS-DISEASE; OXIDATIVE DAMAGE; SUBSTANTIA-NIGRA; HYDROGEN-PEROXIDE; MOUSE-BRAIN; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; STRIATAL DOPAMINE; NUCLEAR-DNA; COMPLEX-I; ATP LOSS AB 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyrine (MPTP) treatment leads to marked depletion of dopamine (DA) levels in the nigrostriatal pathway and dopaminergic neuronal degeneration in caudate-putamen and substantia nigra. MPTP is believed to inhibit complex I of the electron transport system leading to the generation of reactive oxygen species. We sought to test the hypotheses that MPTP treatment: (1) leads to dopamine depletion; (2) causes extensive mitochondrial DNA damage, and (3) that these effects would be age dependent. The levels of dopamine and its metabolites, DOPAC and HVA were analyzed by HPLC equipped with electrochemical detection. DNA damage was measured by quantitative PCR in both mitochondrial and nuclear (beta -polymerase) targets from the caudate-putamen, substantia nigra and cerebellum regions of control and MPTP-treated mice. The age groups studied were 22 days and 12 months. MPTP produced no significant effect on the levels of dopamine and its metabolites in young mice whereas in old, there was a significant decrease in this neurotransmitter system after MPTP administration. These 12-month-old mice, when compared to the young mice, showed a significant increase in mitochondrial DNA damage in the caudate-putamen and cerebellum. The latter region also displayed a significant increase in DNA damage in a nuclear gene. After treatment with MPTP, there was an age-dependent increase in DNA damage in mitochondria of the caudate-putamen while there was no significant DNA damage in the nuclear target. MPTP treatment led to damage in both mitochondrial and nuclear DNA of the substantia nigra, while there was no damage in either mitochondria or nucleus in cerebellum which was used as a negative control. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Van Houten, B (reprint author), NIEHS, Mol Genet Lab, NIH, 111 Alexander Dr,Box 12233, Res Triangle Pk, NC 27709 USA. FU NIA NIH HHS [2PO1AG10514] NR 63 TC 51 Z9 51 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 DEC 1 PY 2000 VL 885 IS 1 BP 45 EP 52 DI 10.1016/S0006-8993(00)02926-7 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 380TE UT WOS:000165718900006 PM 11121528 ER PT J AU Doerge, DR Churchwell, MI Fang, JL Beland, FA AF Doerge, DR Churchwell, MI Fang, JL Beland, FA TI Quantification of Etheno-DNA adducts using liquid chromatography, on-line sample processing, and electrospray tandem mass spectrometry SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID ETHYL CARBAMATE URETHANE; VINYL-CHLORIDE; QUANTITATIVE-ANALYSIS; RISK ASSESSMENT; LIVER DNA; 1,N-6-ETHENODEOXYADENOSINE; RATS; 3,N-4-ETHENODEOXYCYTIDINE; PYRIMIDOPURINONE; OXIDATION AB Etheno-DNA adducts are promutagenic lesions present in normal animal and human tissues that are believed to be important in the etiology of cancer related to diet and lifestyle. A method has been developed for the quantification of trace levels of etheno-DNA adducts using on-line sample preparation coupled with liquid chromatography and electrospray tandem mass spectrometry. The use of automat ed solid-phase extraction and stable labeled internal standards permitted the robust determination of ethenodeoxyadenosine contained in crude DNA hydrolysates from untreated rodent and human tissues at levels on the order of one adduct in 10(8) normal nucleotides from 100 mug of DNA. Inherent analyte response and matrix interference made sensitivity for simultaneous determination of ethenodeoxycytidine approximately 5-fold lower. The method was applied to the analysis of liver DNA from untreated and urethane-treated B6C3F1 mice, untreated rat liver, human placenta, and several commercial DNA preparations. Some sources of potential artifactual formation of etheno-DNA adducts were investigated. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 30 TC 66 Z9 68 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2000 VL 13 IS 12 BP 1259 EP 1264 DI 10.1021/tx0001575 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 386EX UT WOS:000166048600010 PM 11123967 ER PT J AU Fang, GC Chang, CN Wang, NP Wu, YS Wang, V Fu, PPC Cheng, CD Chen, SC Lin, DY AF Fang, GC Chang, CN Wang, NP Wu, YS Wang, V Fu, PPC Cheng, CD Chen, SC Lin, DY TI The study of TSP, PM2.5-10 and PM2.5 during Taiwan Chi-Chi Earthquake in the traffic site of central Taiwan, Taichung SO CHEMOSPHERE LA English DT Article DE PM2.5; PM2.5-10; TSP; earthquake; particulate matter AB Ambient particle concentration was taken on the traffic sampling sire over;the Chung-Chi Road over bridge (CCROB) in front of Hungkuang Institute of Technology (HKIT). The sampling time was from August 1999 to December 1999. During the sampling period, Taiwan's biggest earthquake in more than a century registered 7.3 on the Richter scale (Taiwan Chi-Chi Earthquake). Besides, there were more than 20,000 aftershocks that followed the Taiwan Chi-Chi Earthquake within three months. Thus, the PM2.5, PM2.5-10 particle concentrations were also collected then and compared with total suspended particle (TSP) in this study. The average PM2.5-10, PM2.5 and TSP concentrations are 24.6, 58.0 and 106 mu g/m(3), respectively, after the Taiwan Chi-Chi Earthquake. The average TSP concentrations before and after Taiwan Chi-Chi Earthquake were 70 and 127 mu g/m(3), respectively. It is clearly shown that the average concentration of TSP after Taiwan Chi-Chi Earthquake was about 1.8 times as that of TSP concentration before Taiwan Chi-Chi Earthquake in the traffic site of central Taiwan. And the ratios of PM2.5/PM2.5-10, PM2.5/PM10 and PM2.5/TSP are 2.2%, 67.2%, 38.9%, respectively. The results also indicated about Chi-Chi fine particle concentration (PM2.5) and the TSP increases in the traffic site of central Taiwan after Taiwan Chi-Chi Earthquake. (C) 2000 Elsevier Science Ltd All rights reserved. C1 Hungkuang Inst Technol, Air Tox & Environm Anal, Taichung 433, Taiwan. Tunghai Univ, Dept Environm Sci, Taichung 407, Taiwan. Hungkuang Inst Technol, Dept Hlth Care Adm, Taichung 433, Taiwan. Hungkuang Inst Technol, Off Secretary, Taichung 433, Taiwan. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Fang, GC (reprint author), Hungkuang Inst Technol, Air Tox & Environm Anal, Taichung 433, Taiwan. NR 8 TC 7 Z9 9 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD DEC PY 2000 VL 41 IS 11 BP 1727 EP 1731 DI 10.1016/S0045-6535(00)00055-2 PG 5 WC Environmental Sciences SC Environmental Sciences & Ecology GA 345WV UT WOS:000088838900003 PM 11057611 ER PT J AU Gergen, PJ Turkeltaub, PC Sempos, CT AF Gergen, PJ Turkeltaub, PC Sempos, CT TI Is allergen skin test reactivity a predictor of mortality? Findings from a national cohort SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article DE atopy; survival; allergen skin test reactivity ID DEATH-INDEX; CANCER INCIDENCE; UNITED-STATES; ASTHMA; DISEASE; POPULATION; HEALTH; IGE AB Background The importance of atopy on subsequent mortality is controversial. A clearer understanding is important as atopy is increasing worldwide. Objective To determine the influence of allergen skin test reactivity on observed mortality of a national cohort. Methods Baseline health status and atopic status (allergen skin testing) was measured as part of the second National Health and Nutrition Examination Survey (NHANES II), a representative sample of the US population, during the years 1976-80. Vital status and cause of death were assessed through December 31, 1992 for all examinees 30 years of age or older at baseline (n = 9252) as part of the NHANES II Mortality Study (NH2MS). The analytic sample contained 8179 men and women after excluding missing data. Allergen skin test reactivity was defined as weal greater than or equal to 3 mm to one of eight 1 : 20 (w/v), 50% glycerinated ('No US Standard of Potency') allergens licensed by the FDA: house dust, cat, dog, Alternaria, mixed giant/short ragweed, oak, perennial rye grass, and Bermuda grass. Survival analyses were conducted using multivariate adjusted Cox regression models to evaluate the association between atopy and all-cause, cardiovascular, and cancer mortality. Results There was no association between allergen skin test reactivity and all cause mortality: 30-44 years RR = 1.07 (95% CI 0.63-1.84); 45-59 years RR = 1.10 (0.78-1.55); 60-75 years RR = 1.07 (0.91-1.25). Results were unchanged when cancer or heart disease mortality were examined separately. The presence or absence of allergic symptoms, using the flare to define skin test reactivity, eliminating deaths in the first 5 years of follow-up, or eliminating individuals with pre-existing conditions did not alter the findings. Conclusions Atopy, defined by allergen skin test reactivity, with or without symptoms, is not a predictor of subsequent mortality. C1 Agcy Healthcare Res & Qual, Ctr Primary Care & Res, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. RP Gergen, PJ (reprint author), Agcy Healthcare Res & Qual, Ctr Primary Care & Res, Suite 201,6010 Execut Blvd, Rockville, MD 20852 USA. NR 38 TC 26 Z9 28 U1 2 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD DEC PY 2000 VL 30 IS 12 BP 1717 EP 1723 DI 10.1046/j.1365-2222.2000.00971.x PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 392FR UT WOS:000166401100008 PM 11122209 ER PT J AU Hein, DW McQueen, CA Grant, DM Goodfellow, GH Kadlubar, FF Weber, WW AF Hein, DW McQueen, CA Grant, DM Goodfellow, GH Kadlubar, FF Weber, WW TI Pharmacogenetics of the arylamine N-acetyltransferases: A Symposium in Honor of Wendell W. Weber SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID 4-AMINOBIPHENYL HEMOGLOBIN ADDUCTS; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; ESCHERICHIA-COLI; ACETYLATION POLYMORPHISM; CATALYTIC MECHANISM; HETEROCYCLIC AMINES; CANCER RISK; HUMAN NAT2; CARCINOGEN; MOUSE AB This article is a report on a symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics presented at the joint meeting of the American Society for Biochemistry and Molecular Biology and the American Society for Pharmacology and Experimental Therapeutics, June 4-8, Boston, Massachusetts. The presentations focused on the pharmacogenetics of the NAT1 and NAT2 arylamine N-acetyltransferases, including developmental regulation, structure-function relationships, and their possible role in susceptibility to breast, colon, and pancreatic cancers. The symposium honored Wendell W. Weber for over 35 years of leadership and scientific advancement in pharmacogenetics and was highlighted by his overview of the historical development of the field. C1 Univ Louisville, Hlth Sci Ctr, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA. Univ Toronto, Dept Pharmacol, Toronto, ON, Canada. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. RP Hein, DW (reprint author), Univ Louisville, Hlth Sci Ctr, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. RI Hein, David/A-9707-2008 FU NCI NIH HHS [CA-34627, R01 CA034627, R01 CA034627-15]; NIEHS NIH HHS [ES09812, ES10047] NR 66 TC 71 Z9 73 U1 0 U2 3 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 DEC PY 2000 VL 28 IS 12 BP 1425 EP 1432 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 377HR UT WOS:000165508600008 PM 11095579 ER PT J AU Joshi, BH Husain, SR Puri, RK AF Joshi, BH Husain, SR Puri, RK TI Preclinical studies with IL-13PE38QQR for therapy of malignant glioma SO DRUG NEWS & PERSPECTIVES LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; HUMAN B-CELLS; PSEUDOMONAS EXOTOXIN; INTERLEUKIN-13 RECEPTOR; CHIMERIC PROTEIN; BINDING SUBUNIT; IL-13 RECEPTOR; UP-REGULATION; GAMMA-CHAIN; EXPRESSION AB To develop novel therapeutic agents for the treatment of brain tumors, we have been investigating the expression of unique tumor-associated receptors or antigens on the tumor cell surface. About six years ago, we discovered that human solid tumor cell lines, including human malignant glioma, express high- to intermediate-affinity receptors (R) for a Th2 cell-derived cytokine, interleukin-13 (IL-13). Analysis of the subunit composition of IL-13R in primary explants of malignant glioma cells has demonstrated that IL-13R is composed of three different chains (IL-13R alpha1, IL-13R alpha2 and IL-4R alpha, also known as IL-13R alpha', alpha and IL-4R beta respectively) and that IL-13R alpha2 chain is overexpressed on these cells. Normal brain tissues express IL-13R alpha1 and IL-4R alpha chains, but show only marginal expression of IL-13R alpha2 chain. Thus IL-13R alpha2 chain appears to be overex pressed on glioma cells and may serve as a novel tumor biomarker or a target for receptor-directed therapeutic agents for brain tumors. To target IL-13 receptors, we have produced a recombinant fusion protein composed of IL-13 and a mutated form of Pseudomonas exotoxin (PE). This cytotoxin, termed IL-13PE38QQR or IL-13 cytotoxin, is highly and specifically cytotoxic to a spectrum of human glioma cell lines. In preclinical models of human glioblastoma tumors growing subcutaneously in immunodeficient mice, IL-13 cytotoxin has been found to have remarkable antitumor activity. The data that emerged from these studies reveal that localized or systemic administration of IL-13 cytotoxin can produce nontoxic drug levels and that IL-13 cytotoxin is potently effective against established glioblastoma tumors. On the basis of these and other preclinical studies, we have begun a phase I clinical trial using IL-13PE38QQR for therapy of recurrent malignant glioma. (C) 2000 Prous Science. All rights reserved. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, Bethesda, MD 20892 USA. US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, Bethesda, MD 20892 USA. NR 56 TC 10 Z9 10 U1 0 U2 1 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 DEC PY 2000 VL 13 IS 10 BP 599 EP 605 DI 10.1358/dnp.2000.13.10.858450 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 412PY UT WOS:000167564600004 PM 12879131 ER PT J AU Dufault, R Abelquist, E Crooks, S Demers, D DiBerardinis, L Franklin, T Horowitz, M Petullo, C Sturchio, G AF Dufault, R Abelquist, E Crooks, S Demers, D DiBerardinis, L Franklin, T Horowitz, M Petullo, C Sturchio, G TI Reducing environmental risk associated with laboratory decommissioning and property transfer SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Leadership Conference on Biomedical Research and the Environment CY NOV 01-02, 1999 CL BETHESDA, MARYLAND SP Natl Assoc Physicians Environm, Assoc Higher Educ Facil Officers, US Natl Inst Environm Hlth Sci, W Alton Jones Fdn, Mitchell Kapor Fdn, Shulsky Fdn, Hahn Family Fdn, Baxter Int Inc DE assessment; characterization; decommissioning; decontamination; demolition; environmental; laboratory; liability; remediation; renovation AB The need for more or less space is a common laboratory problem. Solutions may include renovating existing space, leaving or demolishing old space, or acquiring new space or property for building. All of these options carry potential environmental risk. Such risk can be the result of activities related to the laboratory facility or property (e.g., asbestos, underground storage tanks, lead paint), or the research associated with it (e.g., radioactive, microbiological, and chemical contamination). Regardless of the option chosen to solve the space problem, the potential environmental risk must be mitigated and the laboratory space and/or property must be decommissioned or rendered safe prior to any renovation, demolition, or property transfer activities. Not mitigating the environmental risk through a decommissioning process can incur significant financial liability for any costs associated with future decommissioning cleanup activities. Out of necessity, a functioning system, environmental due diligence auditing, has evolved over time to assess environmental risk and reduce associated financial liability. This system involves a 4-phase approach to identify, document, manage, and clean up areas of environmental concern or liability, including contamination. Environmental due diligence auditing includes a) historical site assessment, b) characterization assessment, c) remedial effort and d) final status survey. General practice standards from the American Society for Testing and Materials are available for conducting the first two phases. However, standards have not yet been developed for conducting the third and final phases of the environmental due diligence auditing process. Individuals involved in laboratory decommissioning work in the biomedical research industry consider this a key weakness. C1 US FDA, Div Facilities Planning Engn & Safety, Rockville, MD 20857 USA. Oak Ridge Inst Sci & Educ, Oak Ridge, TN USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. MIT, Cambridge, MA 02139 USA. USDA, Beltsville, MD USA. Analog Devices Inc, Cambridge, MA USA. US EPA, Las Vegas, NV 89193 USA. Merck Res Labs, Rahway, NJ USA. RP Dufault, R (reprint author), US FDA, Div Facilities Planning Engn & Safety, HFA-34,5630 Fishers Lane, Rockville, MD 20857 USA. NR 18 TC 1 Z9 1 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 2000 VL 108 SU 6 BP 1015 EP 1022 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 386TP UT WOS:000166077900010 PM 11121365 ER PT J AU Ikonomi, P Rivera, CE Riordan, M Washington, G Schechter, AN Noguchi, CT AF Ikonomi, P Rivera, CE Riordan, M Washington, G Schechter, AN Noguchi, CT TI Overexpression of GATA-2 inhibits erythroid and promotes megakaryocyte differentiation SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE GATA-2; erythroid progenitors; K562; megakaryocyte; differentiation ID TRANSCRIPTION FACTOR; MEGAKARYOBLASTIC DIFFERENTIATION; HEMATOPOIETIC DEFECT; BINDING PROTEINS; GENE-EXPRESSION; MESSENGER-RNA; CELL-LINES; STEM-CELLS; LEUKEMIA; EOSINOPHILS AB Objective. GATA-1 and GATA-2 transcription factors are required for effective hematopoiesis. These regulatory proteins present overlapping yet distinct patterns of expression in hematopoietic cells. Absence of GATA-2 leads to defective hematopoiesis and an embryonic lethal phenotype. Disruption of GATA-1 results in a compensatory increase in GATA-2 in early erythroid cells and incomplete erythropoiesis with embryos dying at 11.5 days. We examine the specific role of GATA-2 later in hematopoiesis, during erythroid differentiation. Materials and Methods. Stable K562 cell lines expressing various levels of GATA-2 were generated using a GATA-2 expression plasmid, Overexpression of GATA-2 transcripts was determined by quantitative polymerase chain reaction (PCR). Cytospin smears, growth curve analysis, PCR, and flow cytometry were used to examine the effects of increased levels of GATA-2 in altering cell phenotype and activation of megakaryocytic markers. Human progenitor erythroid cells also were transfected with a GATA-2 expression vector. Growth curve analysis, benzidine staining, and high-performance liquid chromatographic analysis were used to study the effects of GATA-2 on erythroid maturation and proliferation. Results. K562/GATA-2 cell lines expressing high levels of GATA-2 mRNA showed a marked decrease in proliferation and a shift in phenotype toward the megakaryocyte lineage. Ploidy analyses showed that these cell lines developed a multinuclear phenotype, including tetraploids and octaploids. PCR analysis showed activation of megakaryocyte-specific genes including thrombopoietin receptor (c-mpl). Surface expression of platelet glycoprotein receptors Ib/IX (CD42b/CD42a) and IIb/IIIa (CD41/CD61) also was demonstrated by flow cytometry. In primary human adult erythroid cultures transfected with a GATA-2 expression vector, production of total hemoglobin and cell proliferation decreased in a dose-dependent manner. Conclusions. GATA-2 plays an important role in deciding cell lineage throughout hematopoiesis, and increased expression of GATA-2 determines megakaryocytic differentiation. Downregulation of GATA-2 is required for erythroid differentiation. (C) 2000 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NIH, Hematol Serv, Dept Clin Pathol, Ctr Clin, Bethesda, MD USA. US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Noguchi, CT (reprint author), NIDDK, Biol Chem Lab, NIH, Bldg 10,Room 9N-307,10 Ctr Dr,MSC 1822, Bethesda, MD 20892 USA. OI Schechter, Alan N/0000-0002-5235-9408 NR 34 TC 64 Z9 71 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD DEC PY 2000 VL 28 IS 12 BP 1423 EP 1431 DI 10.1016/S0301-472X(00)00553-1 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 385XB UT WOS:000166029500016 PM 11146164 ER PT J AU Freni, SC Lewis, SM Mayhugh, MA Jairaj, K Arani, RB Turturro, A Hart, RW AF Freni, SC Lewis, SM Mayhugh, MA Jairaj, K Arani, RB Turturro, A Hart, RW TI Improved equations for estimating the resting metabolic rate SO HUMAN AND ECOLOGICAL RISK ASSESSMENT LA English DT Article DE resting metabolic rate (RMR); basal metabolic rate (BMR); RMR estimation; calorimetry ID ENERGY-EXPENDITURE; BODY-COMPOSITION; CALORIC REQUIREMENTS; PREDICTION EQUATION; MODERATELY OBESE; UNITED-STATES; OVERESTIMATION; REAPPRAISAL; NICOTINE; WEIGHT AB New models were developed for predicting the resting metabolic rate (RMR) with sufficient accuracy for use in epidemiologic studies and for weight control of individuals. For this purpose, the RMR of 213 women and 76 men was measured, and physical measurements were taken. The RMR was regressed on correlates of RMR, avoiding harmful degrees of collinearity by rejecting interregressor correlations exceeding r = 0.5. For women, the best model (R-2 = 0.71) included the regressors age, race, weight, pulse rate, smoking, and body temperature. The best model for males (R-2 = 0.81) included age, race, weight, blood pressure, smoking, time (of day the RMR was measured), and whether subjects had a meal prior to calorimetry. The models were cross validated internally and also validated using an external database. In both cases, die mean estimated RMR did not differ significantly from the measured RMR. The accuracy of the models was compared with four models reported in the literature, three of which overestimated the RMR by up to 17%. In conclusion, improved RMR prediction models have been developed, more accurate than existing models, rendering them suitable for application to epidemiological databases and for individual weight control programs. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Bionet Corp, Jefferson, AR 72079 USA. Univ Arkansas, Pine Bluff, AR 71601 USA. Univ Alabama, Birmingham, AL 35294 USA. RP Lewis, SM (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Bionet Corp, NCTR Rd, Jefferson, AR 72079 USA. NR 28 TC 2 Z9 2 U1 0 U2 2 PU CRC PRESS LLC 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 DEC PY 2000 VL 6 IS 6 BP 1039 EP 1054 DI 10.1080/10807030091124275 PG 16 WC Biodiversity Conservation; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 392FF UT WOS:000166399800010 ER PT J AU Van de Walle, R Barrett, HH Myers, KJ Altbach, MI Desplanques, B Gmitro, AF Cornelis, J Lemahieu, I AF Van de Walle, R Barrett, HH Myers, KJ Altbach, MI Desplanques, B Gmitro, AF Cornelis, J Lemahieu, I TI Reconstruction of MR images from data acquired on a general nonregular grid by pseudoinverse calculation SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE generalized reconstruction; magnetic resonance imaging; medical imaging; pseudoinverse image reconstruction ID LINEAR INVERSE PROBLEMS; K-SPACE; ROSETTE TRAJECTORIES; MOTION-DETECTION; DISCRETE-DATA; RESONANCE; ALGORITHM; DECOMPOSITION AB A minimum-norm least-squares image-reconstruction method for the reconstruction of magnetic resonance images from non-Cartesian sampled data is proposed, The method is based on a general formalism for continuous-to-discrete mapping and pseudoinverse calculation. It does not involve any regridding or interpolation of the data and therefore the methodology differs fundamentally from existing regridding-based methods. Moreover, the method uses a continuous representation of objects in the image domain instead of a discretized representation. Simulations and experiments show the possibilities of the method in both radial and spiral imaging. Simulations revealed that minimum-norm least-squares image reconstruction can result in a drastic decrease of artifacts compared with regridding-based reconstruction. Besides, both in vivo and phantom experiments showed that minimum-norm least-squares image reconstruction leads to contrast improvement and increased signal-to-noise ratio compared with image reconstruction based on regridding. As an appendix, an analytical calculation of the raw data corresponding to the well-known Shepp and Logan software head phantom is presented. C1 State Univ Ghent, Dept Elect & Informat Syst, B-9000 Ghent, Belgium. Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA. Univ Arizona, Ctr Opt Sci, Tucson, AZ 85724 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Free Univ Brussels, Dept Elect & Informat Proc, Brussels, Belgium. RP Van de Walle, R (reprint author), State Univ Ghent, Dept Elect & Informat Syst, B-9000 Ghent, Belgium. RI Lemahieu, Ignace/G-8625-2012 OI Lemahieu, Ignace/0000-0002-0894-9988 FU NCI NIH HHS [CA52643B]; NHLBI NIH HHS [HL03528] NR 43 TC 40 Z9 41 U1 1 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD DEC PY 2000 VL 19 IS 12 BP 1160 EP 1167 DI 10.1109/42.897806 PG 8 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 400CC UT WOS:000166850200002 PM 11212364 ER PT J AU Song, YS Park, HJ Komolprasert, V AF Song, YS Park, HJ Komolprasert, V TI Analytical procedure for quantifying five compounds suspected as possible contaminants in recycled paper/paperboard for food packaging SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE benzophenone; pentachlorophenol; anthracene; dimethyl phthalate; methyl stearate; analytical methods; ultrasonication; recycled paper ID PENTACHLOROPHENOL; SOLVENT; WOOD AB Because contaminants in recycled paper intended for food packaging could be a risk to public health, analytical methods are needed to identify and quantify residues of concern in paper/paperboard, The U.S. Food and Drug Administration is considering development of a guidance document for testing levels of contaminants that might be retained through paper recycling processes. An analytical procedure was developed using paper spiked with suspected contaminants at concentrations of 1-50 ppm in the paper. Benzophenone, dimethyl phthalate, anthracene, methyl stearate, and pentachlorophenol were introduced by soaking the paper in a solution in acetone at 25 degreesC for 24 h; the paper was removed and dried by evaporating the solvent with nitrogen. The model contaminant residues were extracted from the paper using ultrasonication and quantified by GC with flame ionization and electron capture detectors. Recoveries from the spiked paper were 80-109% with a repeatability of +/- 4%. The method was also used to analyze commercial recycled paperboard to validate its applicability. C1 US FDA, Natl Ctr Food Safety & Technol, Div Food Proc & Packaging, Summit Argo, IL 60501 USA. Rural Living Sci Inst, Suwon, South Korea. RP Song, YS (reprint author), US FDA, Natl Ctr Food Safety & Technol, Div Food Proc & Packaging, 6502 S Archer Rd, Summit Argo, IL 60501 USA. FU FDA HHS [FD-U-000431] NR 7 TC 31 Z9 36 U1 1 U2 5 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 DEC PY 2000 VL 48 IS 12 BP 5856 EP 5859 DI 10.1021/jf000512x PG 4 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 386MV UT WOS:000166066900012 PM 11141258 ER PT J AU Heller, DN Kaplan, DA Rummel, NG von Bredow, J AF Heller, DN Kaplan, DA Rummel, NG von Bredow, J TI Identification of cephapirin metabolites and degradants in bovine milk by electrospray ionization-ion trap tandem mass spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE cephapirin; desacetylcephapirin; ion trap mass spectrometry; beta-lactam antibiotics; metabolism; milk; liquid chromatagraphy-mass spectrometry; electrospray ionization ID LIQUID-CHROMATOGRAPHY; CONFIRMATION; CEFTIOFUR AB Liquid chromatography-ion trap tandem mass spectrometry (LC-MS/MS) with electrospray ionization was used to identify cephapirin metabolites and degradants in milk from cows dosed with cephapirin. The milk was extracted according to a previously published procedure. Structures for various components were tentatively identified by their molecular weight, product ion mass spectra, and/or correspondence to standard mass spectra. These components may have occurred as metabolites or as degradants that occurred on storage or during extraction. Compounds identified in the milk included cephapirin, desacetylcephapirin, cephapirin lactone, hydrolyzed cephapirin, and a reduced cephapirin lactone that has not previously been reported. Methylcephapirin was also identified, possibly as a trace contaminant in the formulation. Analysis of incurred milk extracts showed that cephapirin and desacetylcephapirin are the major residues in milk. Desacetylcephapirin residues persisted about as long as the parent drug. The detection limit for both residues by LC-MS/MS was similar to1 ng/mL in milk. These results have implications for microbiological methods or rapid test kits, if such methods or kits respond to cephapirin metabolites and degradants present in the milk. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Heller, DN (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 20 TC 13 Z9 15 U1 2 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD DEC PY 2000 VL 48 IS 12 BP 6030 EP 6035 DI 10.1021/jf000046b PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 386MV UT WOS:000166066900038 PM 11141270 ER PT J AU Pothuluri, JV Freeman, JP Heinze, TM Beger, RD Cerniglia, CE AF Pothuluri, JV Freeman, JP Heinze, TM Beger, RD Cerniglia, CE TI Biotransformation of vinclozolin by the fungus Cunninghamella elegans SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE vinclozolin; dicarboximide fungicide; fungal biotransformation; Cunninghamella elegans ID DICARBOXIMIDE FUNGICIDE VINCLOZOLIN; POLYCYCLIC AROMATIC-HYDROCARBONS; ENHANCED DEGRADATION; MALE-RAT; SOIL; METABOLISM; IPRODIONE; BIODEGRADATION; TRANSFORMATION; METOLACHLOR AB This study investigated the biotransformation of the dicarboximide fungicide vinclozolin [3-(3,5-dichlorophenyl)-5-methyl-5-vinyl-1,3-oxazolidine-2,4-dione] by the fungus Cunninghamella elegans. Experiments with phenyl-[U-ring-(14)C]vinclozolin showed that after 96 h incubation, 93% had been transformed to four major metabolites. Metabolites were separated by HPLC and characterized by mass and NMR spectroscopy. Biotransformation occurred predominantly on the oxazolidine-2,4-dione portion of vinclozolin. The metabolites were identified as the 3R- and 3S- isomers of 3',5'-dichloro-2,3,4-trihydroxy-2- methylbutyranilide, N-(2-hydroxy-2-methyl-1-oxobuten-3-yl)-3,5-dichlo-rophenyl-1-carbamic acid, and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide. The enanilide compound has been reported previously as a plant and mammalian metabolite and is implicated to contain antiandrogenic activity. The 3R- and 3S- isomers of 3',5'-dichloro-2,3,4-trihydroxy-2-methylbutyranilide are novel metabolites. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Pothuluri, JV (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, HFT-250,3900 NCTR Rd, Jefferson, AR 72079 USA. EM JPothuluri@nctr.fda.gov NR 51 TC 32 Z9 33 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD DEC PY 2000 VL 48 IS 12 BP 6138 EP 6148 DI 10.1021/jf0008543 PG 11 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 386MV UT WOS:000166066900054 PM 11312787 ER PT J AU Shaikh, B Chu, PS AF Shaikh, B Chu, PS TI Distribution of total C-14 residue in egg yolk, albumen, and tissues following oral [C-14]sulfamethazine administration to hens SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article; Proceedings Paper CT Symposium on Agrochemical Residues in Eggs held during the Fall 1999 National Meeting of the American-Chemical-Society CY 1999 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc, Agrochem Div DE sulfa drugs; sulfamethazine; total residue; eggs ID LIQUID-CHROMATOGRAPHY; METABOLITES; SULFAMETHAZINE; IDENTIFICATION AB The distribution of total C-14 residues was studied in egg yolk and albumen after administration of either single or multiple oral dosages of [C-14]sulfamethazine (SMZ). One day after a single dose of [C-14]SMZ (121 mg of sulfamethazine, 2.42 x 10(7) dpm), the 14C residue concentration peaked in egg albumen and egg yolk with the concentration in the former > 4-fold greater than in the latter. Three days postdose, the C-14 residue concentration in the yolk was similar to7-fold higher than in the egg albumen. A multiple dose of [C-14]SMZ containing sulfamethazine mass equivalent of an average therapeutic dose (282 mg, 2.9 x 10(7) dpm) for chickens was also administered orally for six consecutive days to hens. A significantly reduced level of egg production was observed during the medication, and most of the hens stopped laying eggs after the last dose. The C-14 residue concentrations peaked on the last day (sixth) of medication in egg albumen and yolk. The C-14 residue concentrations were also measured in liver, muscle, blood, and plasma of chickens sacrificed at 1, 24, 48, and 72 h after the last dose. Highest concentrations of C-14 residue were accumulated in Liver followed by, in decreasing order, blood, plasma, and muscle. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Shaikh, B (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 8 TC 9 Z9 9 U1 2 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD DEC PY 2000 VL 48 IS 12 BP 6404 EP 6408 DI 10.1021/jf000519e PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 386MV UT WOS:000166066900098 PM 11141292 ER PT J AU Chu, PS Donoghue, DJ Sheikh, B AF Chu, PS Donoghue, DJ Sheikh, B TI Determination of total C-14 residues of sarafloxacin in eggs of laying hens SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article; Proceedings Paper CT Symposium on Agrochemical Residues in Eggs held during the Fall 1999 National Meeting of the American-Chemical-Society CY 1999 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc, Agrochem Div DE fluoroquinolone; sarafloxacin; residues; egg ID PROGRAMMABLE FLUORESCENCE DETECTION; PERFORMANCE LIQUID-CHROMATOGRAPHY; ONLINE MICRODIALYSIS; MASS-SPECTROMETRY; FLUOROQUINOLONES; CONFIRMATION; YOLKS; FISH AB [C-14]Sarafloxacin was orally administered to six laying hens for five consecutive days. Eggs were collected for 15 days after the initial drug treatment. Egg yolk and egg albumen were separated and assayed for total radioactive residues (TRR) using a combustion oxidizer and scintillation counting techniques. Radioactivity was detected in egg yolk and egg albumen on the second day of dosing and reached a maximum at 24 h after drug withdrawal. Thereafter, the sarafloxacin TRR levels in egg albumen declined rapidly and were undetectable 2 days after the last dose, whereas the levels in egg yolk declined at a much slower rate and were undetectable 7 days after drug withdrawal. In both the egg albumen and yolk, HPLC analysis indicated that the parent sarafloxacin was the major component. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Chu, PS (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 15 TC 13 Z9 13 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 DEC PY 2000 VL 48 IS 12 BP 6409 EP 6411 DI 10.1021/jf000518m PG 3 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 386MV UT WOS:000166066900099 PM 11141293 ER PT J AU Schenck, FJ Donoghue, DJ AF Schenck, FJ Donoghue, DJ TI Determination of organochlorine and organophosphorus pesticide residues in eggs using a solid phase extraction cleanup SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article; Proceedings Paper CT Symposium on Agrochemical Residues in Eggs held during the Fall 1999 National Meeting of the American-Chemical-Society CY 1999 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc, Agrochem Div DE eggs; organochlorine pesticides; organophosphorus pesticides; solid phase extraction ID MULTIRESIDUE METHOD; FOODS AB A multiresidue solid phase extraction (SPE) method for the isolation and subsequent gas chromatographic determination of nonpolar organochloline and polar organophosphorus pesticide residues in eggs is described. The method uses an acetonitrile extraction followed by an SPE cleanup using graphitized carbon black and aminopropyl SPE columns. Organophosphorus pesticides are determined by gas chromatography with flame photometric detection. After further cleanup of the extract using Florisil SPE columns, organochlorine pesticides are determined by gas chromatography with electron capture detection. Studies were performed using eggs containing both fortified and incurred pesticide residues. The average recoveries were 86-108% for 8 fortified organochlorine pesticide residues and 61-149% for 28 fortified organophosphorus pesticide residues. C1 US FDA, SE Reg Lab, Atlanta, GA 30309 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Schenck, FJ (reprint author), US FDA, SE Reg Lab, 60 Eighth St NE, Atlanta, GA 30309 USA. NR 12 TC 44 Z9 51 U1 4 U2 14 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 DEC PY 2000 VL 48 IS 12 BP 6412 EP 6415 DI 10.1021/jf000142c PG 4 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 386MV UT WOS:000166066900100 PM 11141294 ER PT J AU Donoghue, DJ Myers, K AF Donoghue, DJ Myers, K TI Imaging residue transfer into egg yolks SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article; Proceedings Paper CT Symposium on Agrochemical Residues in Eggs held during the Fall 1999 National Meeting of the American-Chemical-Society CY 1999 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc, Agrochem Div DE imaging; MRI; residues; yolk; food safety ID AMPICILLIN AB Predict-ion models for residue transfer into eggs are being developed. Recent results indicate that the developing egg yolk serves as an important storage depot for chemical residues. The current study was conducted to visualize incorporation and potential compartmentalization of drug residues in developing egg yolks. To this end, the drug magnevist was injected into hens to evaluate drug transfer into either early- or rate-developing yolks. High-resolution magnetic resonance images (MRI) of drug residues in eggs were acquired using a 1.5 T Siemens Magnetom clinical scanner. A 10-cm circular surface coil was used for receiving the magnetic resonance signal. The eggs were positioned inside the coil cavity for an improved signal to noise ratio (SNR). Gradient-echo images were used to locate the centers of the eggs and to prescribe the position of the high-resolution image slab. The images were recorded using an inversion time (T1) weighted magnetization-prepared, rapid acquisition, gradient-recalled-echo (MPRAGE) pulse sequence. The sequence parameters used were as follows: repetition time (TR) equals 12 ms, echo time (TE) equals 5 ms, field of view (FOV) equals 200, TI = 10 ms, 1.25-mm slice thickness, and a matrix of 200 x 256. Following dosing, images of drug residues in eggs indicate that drugs can be incorporated and compartmentalized into ring structures within individual developing egg yolks. These results have significant human food safety implications because even after only a single dose, sequestered drug residues may be stored and later released to contaminate eggs for days to weeks after dosing. C1 US FDA, Ctr Vet Med, Div Anim Res, Laurel, MD 20708 USA. US FDA, Ctr Devices & Radiol Hlth, Div Elect & Comp Sci, Rockville, MD 20850 USA. RP Donoghue, DJ (reprint author), Univ Arkansas, Ctr Excellence Poultry Sci, Poultry Sci Ctr, O-408, Fayetteville, AR 72701 USA. NR 9 TC 9 Z9 9 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 DEC PY 2000 VL 48 IS 12 BP 6428 EP 6430 DI 10.1021/jf000146h PG 3 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 386MV UT WOS:000166066900103 PM 11141297 ER PT J AU Hinck, AP Walker, KP Martin, NR Deep, S Hinck, CS Freedberg, DI AF Hinck, AP Walker, KP Martin, NR Deep, S Hinck, CS Freedberg, DI TI Letter to the Editor: Sequential resonance assignments of the extracellular ligand binding domain of the human TGF-beta type II receptor SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE ligand; NMR assignments; receptor; TGF; transforming growth factor-beta; type II receptor ID KINASE C1 Univ Texas, Hlth Sci Ctr, Dept Biochem, Ctr Biomol Struct Anal, San Antonio, TX 78229 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Hinck, AP (reprint author), Univ Texas, Hlth Sci Ctr, Dept Biochem, Ctr Biomol Struct Anal, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIGMS NIH HHS [GM58670] NR 7 TC 19 Z9 19 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD DEC PY 2000 VL 18 IS 4 BP 369 EP 370 DI 10.1023/A:1026775321886 PG 2 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 381XN UT WOS:000165789500013 PM 11200535 ER PT J AU White, DG Hudson, C Maurer, JJ Ayers, S Zhao, SH Lee, MD Bolton, L Foley, T Sherwood, J AF White, DG Hudson, C Maurer, JJ Ayers, S Zhao, SH Lee, MD Bolton, L Foley, T Sherwood, J TI Characterization of chloramphenicol and florfenicol resistance in Escherichia coli associated with bovine diarrhea SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SALMONELLA-TYPHIMURIUM DT104; FIELD GEL-ELECTROPHORESIS; FOOD-BORNE OUTBREAK; FLUORINATED ANALOGS; POLYMORPHIC DNA; GENE; THIAMPHENICOL; INTEGRON AB Florfenicol, a veterinary fluorinated analog of thiamphenicol, is approved for treatment of bovine respiratory pathogens in the United States. However, florfenicol resistance has recently emerged among veterinary Escherichia coli isolates incriminated in bovine diarrhea. The flo gene, which confers resistance to florfenicol and chloramphenicol, has previously been identified in Photobacterium piscicida and Salmonella enterica serovar Typhimurium DT104. The flo gene product is closely related to the CmIA protein identified in Pseudomonas aeruginosa. The cmlA gene confers nonenzymatic chloramphenicol resistance via an efflux mechanism. Forty-eight E. coli isolates recovered from calves with diarrhea, including 41 that were both chloramphenicol and florfenicol resistant, were assayed for the presence of both flo and cmlA genes. Forty-two of the 44 isolates for which florfenicol MICs were greater than or equal to 16 mug/ml were positive via PCR for the flo gene. All E. coli isolates for which florfenicol MICs were less than or equal to8 mug/ml were negative for the flo gene (n = 4). Twelve E. coli isolates were positive for cmlA, and chloramphenicol MICs for all 12 were greater than or equal to 32 mug/ml. Additionally, eight isolates were positive for both flo and cmlA, and both florfenicol and chloramphenicol MICs for these isolates were > 64 mug/ml. DNA sequence analysis of the E. coli flo gene demonstrated 98% identity to the published GenBank sequences of both serovar Typhimurium flo(St) and P. piscicida pp-flo. The flo gene was identified on high-molecular-weight plasmids of approximately 225 kb among the majority of florfenicol-resistant E. coli isolates. However, not all of the Borfenicol-resistant E. coli isolates tested contained the large flo-positive plasmids. This suggests that several of the E. coli isolates may possess a chromosomal flo gene. The E. coli flo gene specifies nonenzymatic cross-resistance to both florfenicol and chloramphenicol, and its presence among bovine E. coli isolates of diverse genetic backgrounds indicates a distribution much wider than previously thought. C1 US FDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. N Dakota State Univ, Fargo, ND 58105 USA. Univ Georgia, Athens, GA 30602 USA. USDA ARS, Russell Res Ctr, Athens, GA 30613 USA. RP White, DG (reprint author), US FDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. FU NIAID NIH HHS [AI22383, R01 AI022383, R56 AI022383] NR 37 TC 105 Z9 114 U1 2 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 2000 VL 38 IS 12 BP 4593 EP 4598 PG 6 WC Microbiology SC Microbiology GA 399ND UT WOS:000166818500047 PM 11101601 ER PT J AU Derendorf, H Lesko, LJ Chaikin, P Colburn, WA Lee, P Miller, R Powell, R Rhodes, G Stanski, D Venitz, J AF Derendorf, H Lesko, LJ Chaikin, P Colburn, WA Lee, P Miller, R Powell, R Rhodes, G Stanski, D Venitz, J TI Pharmacokinetic/pharmacodynamic modeling in drug research and development SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID PHARMACOKINETIC-PHARMACODYNAMIC ANALYSIS; POPULATION PHARMACODYNAMICS; LIFE-TABLES; RESPONSES; INTEGRATION; PRINCIPLES; KINETICS; MARKERS; TIME; RAT AB The two domains in clinical pharmacology dealing with optimizing dosing recommendations are pharmacokinetics and pharmacodynamics. However, the usefulness of these disciplines is limited if viewed in isolation. Pharmacokinetic/pharmacodynamic (PK/PD) relationships and modeling builds the bridge between these two classical disciplines of clinical pharmacology. It links the concentration-time profile as assessed by pharmacokinetics to the in tensity of observed response as quantified by pharmacodynamics. Thus, the resulting so-called integrated PK/PD-models allow the description of the complete time course of the desired and/or undesired effects in response to a drug therapy. PK/PD-modeling can elucidate the causative relationship between drug exposure and response and provide a better understanding of the sequence of events that result in the observed drug effect. This information can then be used to streamline the drug development process and dose optimization. This consensus paper presents an update on the current state of PK/PD-modeling from an academic, industrial and regulatory perspective. (C)2000 the American College of Clinical Pharmacology. C1 Univ Florida, JHMHC, Dept Pharmaceut, Gainesville, FL 32610 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Rhone Poulenc, Collegeville, PA USA. MDS Harris, Phoenix, AZ USA. Warner Lambert Co, Ann Arbor, MI USA. Pharsight, Mt View, CA USA. Virginia Commonwealth Univ, Richmond, VA USA. RP Derendorf, H (reprint author), Univ Florida, JHMHC, Dept Pharmaceut, POB 100494, Gainesville, FL 32610 USA. RI Derendorf, Hartmut/B-4628-2012 OI Derendorf, Hartmut/0000-0003-4016-1370 NR 68 TC 86 Z9 95 U1 0 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD DEC PY 2000 VL 40 IS 12 BP 1399 EP 1418 PN 2 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 374MZ UT WOS:000165350100001 PM 11185661 ER PT J AU Mahmood, I AF Mahmood, I TI Interspecies scaling: Role of protein binding in the prediction of clearance from animals to humans SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID IN-VITRO DATA; PHARMACOKINETIC PARAMETERS; METABOLIC-CLEARANCE; PLASMA BINDING; DOG; RAT; MOUSE; DRUGS; INTEGRATION; RABBIT AB The objective of this study is to evaluate whether unbound clearance of a drug can be predicted more accurately than total clearance using the allometric approach and if there is any real advantage of predicting unbound clearance over total clearance. The total and unbound clearance of 20 randomly selected drugs were scaled up from the animal data (at least three animal species) obtained from the literature. Three methods were used to generate plots to scale up the clearance values: (I) total or unbound clearance versus body weight (simple allometric equation), (2) the product of total or unbound clearance and maximum life span potential (MLP) versus body weight, and (3) the product of total or unbound clearance and brain weight versus body weight. The results of this study indicate that there will be instances when unbound clearance can be predicted better than total clearance or vice versa. In conclusion, unbound clearance cannot be predicted any better than total clearance. (C)2000 the American College of Clinical Pharmacology. C1 US FDA, Woodmont Off Ctr 2, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Woodmont Off Ctr 2, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1, HFD-860,1451 Rockville Pike, Rockville, MD 20852 USA. NR 34 TC 20 Z9 20 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD DEC PY 2000 VL 40 IS 12 BP 1439 EP 1446 PN 2 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 374MZ UT WOS:000165350100004 PM 11185664 ER PT J AU McCarthy, SA DePaola, A Kaysner, CA Hill, WE Cook, DW AF McCarthy, SA DePaola, A Kaysner, CA Hill, WE Cook, DW TI Evaluation of nonisotopic DNA hybridization methods for detection of the tdh gene of Vibrio parahaemolyticus SO JOURNAL OF FOOD PROTECTION LA English DT Article ID THERMOSTABLE DIRECT HEMOLYSIN; POLYMERASE CHAIN-REACTION; THERMOLABILE HEMOLYSIN; TRH; STRAINS; PROBES; IDENTIFICATION; SEQUENCES; HOLLISAE AB Production of the thermostable direct hemolysin (TDH) by Vibrio parahaemolyticus is associated with pathogenicity of the organism and is encoded by the tdh gene. The timely resolution of seafood-associated outbreaks requires rapid and accurate detection of pathogenic V. parahaemolyticus. The specificity of alkaline phosphatase- and digoxigenin-labeled tdh gene probes was evaluated against 61 strains of V. parahaemolyticus (including isolates from recent outbreaks involving oysters from the Pacific Northwest, Texas, and New York), 85 strains of other vibrios, and 7 strains of non-vibrio species from clinical and environmental sources. The probes were specific for detection of the V. parahaemolyticus tdh gene. C1 US FDA, Gulf Coast Res Lab, Dauphin Island, AL 36528 USA. US FDA, Seafood Prod Res Ctr, Bothell, WA 98021 USA. RP McCarthy, SA (reprint author), US FDA, Gulf Coast Res Lab, Dauphin Isl, Dauphin Island, AL 36528 USA. NR 28 TC 37 Z9 39 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 DEC PY 2000 VL 63 IS 12 BP 1660 EP 1664 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 381YG UT WOS:000165791200006 PM 11131887 ER PT J AU Koo, J DePaola, A Marshall, DL AF Koo, J DePaola, A Marshall, DL TI Effect of simulated gastric fluid and bile on survival of Vibrio vulnificus and Vibrio vulnificus phage SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ESCHERICHIA-COLI O157-H7; OYSTERS CRASSOSTREA-VIRGINICA; ACID TOLERANCE RESPONSE; LISTERIA-MONOCYTOGENES; LACTIC-ACID; GULF-COAST; BACTERIA; PH; BACTERIOPHAGES; INACTIVATION AB Bacteria and phages may be exposed to acid conditions in the stomach and to bile in the intestine. Survival of three strains of Vibrio vulnificus and three strains of its phages was examined at 37 degreesC after exposure to simulated gastric fluid at pH 3 to 4 or to 0, 1, and 2% bile in broth or buffer. Mean D-values (decimal reduction times) at pH 4 and 3 were 3.3 and 1.3 min for V. vulnificus and 97.8 and 0.7 min far its phages. No V. vulnificus survivors were found at pH 2.0. There were few survival differences among strains of V. vulnificus or its phages. Numbers of V. vulnificus increased 1 log in tryptic soy broth containing 1 or 2% bile after 3 h. Numbers of V. vulnificus and its phages remained constant in phosphate-buffered saline regardless of bile concentrations up to 3 h. Those V. vulnificus bacteria and phages that survive stomach acidity may proliferate in the small intestine, since they are resistant to bile. C1 Mississippi State Univ, Mississippi Agr & Forestry Expt Stn, Dept Food Sci & Technol, Mississippi State, MS 39762 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. RP Marshall, DL (reprint author), Mississippi State Univ, Mississippi Agr & Forestry Expt Stn, Dept Food Sci & Technol, Box 9805, Mississippi State, MS 39762 USA. NR 41 TC 17 Z9 19 U1 0 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 DEC PY 2000 VL 63 IS 12 BP 1665 EP 1669 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 381YG UT WOS:000165791200007 PM 11131888 ER PT J AU Katsoudas, E Abdelmesseh, HH AF Katsoudas, E Abdelmesseh, HH TI Enzyme inhibition and enzyme-linked immunosorbent assay methods for carbamate pesticide residue analysis in fresh produce SO JOURNAL OF FOOD PROTECTION LA English DT Article ID IONIZATION MASS-SPECTROMETRY; PHASE EXTRACTION CLEANUP; PARTICLE-BASED ELISA; CHROMATOGRAPHIC DETERMINATION; INSECTICIDES; VALIDATION; VEGETABLES; FRUITS; WATER AB An acetylcholinesterase inhibition method was employed for detection of 21 carbamate pesticides in bananas, peaches, strawberries, and tomatoes. Each of these four agricultural commodities was spiked with 0.1 to 10 ppm of each of the 21 carbamates and individual detection levels were determined. Similar responses and detection limits were observed for all four produce when tested for a given carbamate. The detection levels ranged from 0.1 ppm for carbofuran and 3-hydroxycarbofuran to 6 ppm for promecarb and aldicarb sulfoxide. These results are generally at or below the tolerances established by the Environmental Protection Agency for these commodities. Positive samples from the enzyme inhibition screening were also analyzed with the carbaryl-specific enzyme-linked immunosorbent assay (ELISA) kit. The detection limits for carbaryl and carbofuran were 2.0 ppb and 8.0 ppb, respectively. The other carbamates did not exhibit cross-reactivity even at high ppb levels. Thus, the enzyme inhibition assay and ELISA are simple and fast screening procedures for the detection of carbamate pesticide residues in food commodities. C1 US FDA, NE Reg Lab, Jamaica, NY 11433 USA. RP Katsoudas, E (reprint author), US FDA, NE Reg Lab, 158-15 Liberty Ave, Jamaica, NY 11433 USA. NR 18 TC 3 Z9 8 U1 0 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 DEC PY 2000 VL 63 IS 12 BP 1758 EP 1760 PG 3 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 381YG UT WOS:000165791200023 PM 11131904 ER PT J AU Dixon, AM Widmalm, G Bull, TE AF Dixon, AM Widmalm, G Bull, TE TI Modified GOESY in the analysis of disaccharide conformation SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE NMR; disaccharide; conformation; 1-D NOE; spin-diffusion ID NUCLEAR-MAGNETIC-RESONANCE; MOLECULAR-DYNAMICS SIMULATION; SPIN-COUPLING CONSTANTS; PULSED-FIELD GRADIENTS; NOE SPECTROSCOPY; TEMPERATURE-DEPENDENCE; GLYCOSIDIC LINKAGE; NATURAL ABUNDANCE; NMR EXPERIMENTS; DIFFUSION AB One-dimensional nuclear magnetic resonance techniques were applied to the conformational investigation of a disaccharide. More specifically, nuclear Overhauser enhancements (NOEs) of protons on either side of the glycosidic bond have been used to determine the conformation of the disaccharide alpha -L-Rhap-(1 --> 2)-alpha -L-Rhap-OMe. A modified GOESY sequence, incorporating selective excitation and pulsed field gradient enhancement, was developed and used to accurately measure small NOE signals of interest. These experiments were named M-GOESY, for modified GOESY, and the data they provided were used to calculate internuclear distances in the disaccharide molecule. The accuracy of the M-GOESY measurements was enhanced by elimination of indirect effects, or spin diffusion, by selective inversion(s) of either the intermediate magnetization or the source and target magnetization during the mixing time. Results of this study indicate that the alpha -L-Rhap-(1 --> 2)-alpha -L-Rhap-OMe disaccharide molecule exists primarily in one conformation, with the glycosidic torsion angle psi approximate to -30 degrees based on past molecular dynamics simulations. (C) 2000 Academic Press. C1 US FDA, Biophys Lab, Off Vaccine Res & Review, Ctr Biol Evaluat & Res,HFM, Rockville, MD 20852 USA. Univ Stockholm, Arrhenius Lab, Dept Organ Chem, S-10691 Stockholm, Sweden. RP Bull, TE (reprint author), US FDA, Biophys Lab, Off Vaccine Res & Review, Ctr Biol Evaluat & Res,HFM, 1401 Rockville Pike, Rockville, MD 20852 USA. RI Dixon, Ann/I-3696-2012 OI Dixon, Ann/0000-0002-5261-304X NR 43 TC 30 Z9 31 U1 1 U2 8 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD DEC PY 2000 VL 147 IS 2 BP 266 EP 272 DI 10.1006/jmre.2000.2211 PG 7 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 383XH UT WOS:000165909600012 PM 11097818 ER PT J AU Matthews, EJ Benz, RD Contrera, JF AF Matthews, EJ Benz, RD Contrera, JF TI Use of toxicological information in drug design SO JOURNAL OF MOLECULAR GRAPHICS & MODELLING LA English DT Article ID CARCINOGENICITY; PHARMACEUTICALS; HAZARD AB This paper is an extension of the keynote address and another talk at the Symposium on the Use of Toxiciological Information in Drug Design. The symposium was organized by American Chemical Society's Chemical Information Division at the 220th National Meeting of the American Chemical Society in Washington, DC, August 20-24, 2000. We outline an approach for meeting the scientific information needs of the U.S. Food and Drug Administration (FDA). Ready access to scientific information is critical to support safety-related regulatory decisions and is especially valuable in situations where available experimental information from in vivo/in vitro studies are inadequate or unavailable. This approach also has applications for lead selection in drug discovery. A pilot electronic toxicology/safety knowledge base and computational toxicology initiative is underway in the FDA Center for Drug Evaluation and Research (CDER) that may be a prototype for an FDA knowledge base. The objectives of this effort are: (i) to strengthen and broaden the scientific basis of regulatory decisions, (ii) to provide the Agency with an electronic scientific institutional memory, (iii) to create a scientific resource for regulatory and applied research, and (iv) to establish an internal Web-based support service that can provide decision support information for regulators that will facilitate the review process and improve consistency and uniformity. An essential component of this scientific knowledge base is the creation of a comprehensive electronic inventory of CDER-regulated substances that permit identification of clusters of substances having similar chemical, pharmacological or toxicological activities, and molecular structure/substructures. Furthermore, the inventory acts as a pointer and link to other databases and critical non-clinical and clinical pharmacology/toxicology studies and reviews in FDA archives. Clusters of related substances are identified through the use of: (i) an extensive index of alternative names for each substance, (ii) a molecular structure key field consisting of a rudimentary or core structure represented as an ISIS(TM).mol-file, (iii) global search terms (molecular group, chemical class, clinical indication, or pharmacologic activity), and (iv) molecular clustering using structure/substructure similarity indices. The information contained in a toxicology knowledge database has limited value unless means are available to extract information, identify relationships, and create and test hypotheses. One such means is computational toxicology, also called in silico toxicology, ComTox, or e-TOX. Computational toxicology is the application of computer technology and information processing (informatics) to analyze, model, and estimate chemical toxicity based upon structure activity relationships (SAR). A computational toxicology software package, MCASE, has been evaluated and successfully improved by CDER through the incorporation of data from FDA archives and concomitant alterations of the logic used in the interpretation of the results to reflect the data analysis and hazard identification practices and priorities of the Center. Our modifications and uses of the MCASE program are discussed in detail. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Matthews, EJ (reprint author), US FDA, Ctr Drug Evaluat & Res, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 21 TC 21 Z9 22 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1093-3263 J9 J MOL GRAPH MODEL JI J. Mol. Graph. PD DEC PY 2000 VL 18 IS 6 BP 605 EP 615 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Crystallography; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Crystallography; Mathematical & Computational Biology GA 387KX UT WOS:000166122700004 PM 11155316 ER PT J AU Ibrahim, S Peggins, J Knapton, A Licht, T Aszalos, A AF Ibrahim, S Peggins, J Knapton, A Licht, T Aszalos, A TI Influence of antipsychotic, antiemetic, and Ca2+ channel blocker drugs on the cellular accumulation of the anticancer drug daunorubicin: P-glycoprotein modulation SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID BLOOD-BRAIN-BARRIER; MULTIDRUG-RESISTANCE; EXPRESSION; PHARMACOKINETICS; PLASMA; CELLS; LINE; DOXORUBICIN; MONOLAYERS; INHIBITION AB We investigated the effect of antiemetic, antipsychotic, and Ca2+ blocker drugs on the function of P-glycoprotein (Pgp) in vitro and compared inhibitory concentrations with therapeutic blood levels. Human colon adenocarcinoma (Caco-2) and human blood-brain barrier endothelial cells were transfected or transduced to express Pgp, and the uptake of rhodamine123, calcein AM, or daunorubicin was measured by flow cytometry in the presence of the drugs. NIH3T3/MDR1 cells were used for reference testing. Results of the flow cytometric studies were supported by cell proliferation and monolayer permeability studies. Thirty-five drugs are included in this study, of which 13 modulate the function of Pgp at the therapeutic blood concentration and 8 at a concentration 2 to 4 times higher. Two drugs, which block the function of Pgp only partially at therapeutic blood concentrations, blocked the function of Pgp completely if used concomitantly. Based on these in vitro experiments, we conclude that administration of several drugs that modulate the function of Pgp simultaneously may adversely affect the natural function of this efflux pump and may cause drug-induced side effects in patients. C1 US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. US FDA, Ctr Vet Med, Laurel, MD USA. US FDA, Div Appl Pharmacol Res, Laurel, MD USA. NCI, NIH, Bethesda, MD 20892 USA. RP Ibrahim, S (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, HFD-860,5600 Fishers Ln, Rockville, MD 20857 USA. NR 52 TC 25 Z9 25 U1 1 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 2000 VL 295 IS 3 BP 1276 EP 1283 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 374HD UT WOS:000165339000049 PM 11082465 ER PT J AU Feng, P Monday, SR AF Feng, P Monday, SR TI Multiplex PCR for detection of trait and virulence factors in enterohemorrhagic Escherichia coli serotypes SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE enterohemorrhagic E. coli; virulence factors; PCR; detection ID HEMOLYSIN; O157-H7; IDENTIFICATION; STRAINS; STX(2); HLYA; EAEA AB A multiplex PCR assay was developed which allowed the simultaneous detection of five trait genes or virulence markers in enterohemorrhagic Escherichia coli (EHEC) serotypes. A primer pair, designed to detect a single base-pair mutation in the uidA gene, is specific only for the prototypic EHEC of O157:H7 serotype and its toxigenic, non-motile variants. In a similar way, primers to the eaeA gene of the gamma -intimin derivative specifically detects strains in the EHEC 1 clonal group, which consists mostly of O157:H7 and some O55:H7 serotypes. The other three primer pairs, specific for stx1, stx2 and both variants of ehxA genes, will detect the presence of these virulence genes in all EHEC serotypes. Analysis of 34 strains, including various serotypes of EHEC, Shiga toxin-producing E. coli and enteropathogenic E. coli, confirmed that the multiplex PCR assay detected the presence of these genes in a manner consistent with the known genotype of each respective strains. (C) 2000 Academic Press. C1 US FDA, Div Microbiol Studies, Washington, DC 20204 USA. RP Feng, P (reprint author), US FDA, Div Microbiol Studies, HFS-516,200 C St SW, Washington, DC 20204 USA. EM pfeng@cfsan.fda.gov NR 17 TC 50 Z9 52 U1 2 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD DEC PY 2000 VL 14 IS 6 BP 333 EP 337 DI 10.1006/mcpr.2000.323 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 378LT UT WOS:000165586400002 PM 11090262 ER PT J AU Thompson, WE Branch, A Whittaker, J Stiles, J Zilberstein, M AF Thompson, WE Branch, A Whittaker, J Stiles, J Zilberstein, M TI Forskolin and phorbol ester modulate prohibitin gene products in conditionally immortalized rat granulosa cell SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Morehouse Sch Med, Atlanta, GA 30310 USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 280 BP 54A EP 54A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900281 ER PT J AU Hiltbold, EM Anderson, HA Roche, PA AF Hiltbold, EM Anderson, HA Roche, PA TI Membrane lipid rafts facilitate class II-restricted antigen presentation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, DBS, EIB, NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 599 BP 115A EP 115A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900601 ER PT J AU Bai, R Covell, DG Kepler, JA Li, AQ Ewell, JB Pettit, GR Nguyen, NY Fisher, RJ Hamel, E AF Bai, R Covell, DG Kepler, JA Li, AQ Ewell, JB Pettit, GR Nguyen, NY Fisher, RJ Hamel, E TI Direct photoaffinity labeling of tubulin by [H-3]dolastatin SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Screening Technol Branch, DTP, DCTD, Frederick, MD 21702 USA. NCI, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NCI, Prot Chem Lab, Frederick, MD 21702 USA. US FDA, Facil Biotechnol Resources, Rockville, MD 20857 USA. Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. NCI, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 986 BP 189A EP 189A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900990 ER PT J AU Simone, NL Paweletz, CP Charboneau, L Petricoin, EF Liotta, LA AF Simone, NL Paweletz, CP Charboneau, L Petricoin, EF Liotta, LA TI Laser capture microdissection: Beyond functional genomics to proteomics SO MOLECULAR DIAGNOSIS LA English DT Article DE surface-enhanced laser desorption spectrometry; matrix-assisted laser desorption-ionization time-of-flight spectrometry; immunoassays; microdissection; proteomics ID PROSTATE-SPECIFIC ANTIGEN; BREAST CANCERS; GENE; RNA AB Proteomics will drive biology and medicine beyond genomics, and can have a profound impact on molecular diagnostics. The posttranslational modifications of cellular proteins that govern physiology and become deranged in disease cannot be accurately portrayed by gene expression alone. Consequently, new technology is being developed to discover, and quantitatively monitor, proteomic changes that are associated with disease etiology and progression. In the past, proteomic technologies were restricted to tumor cell lines or homogenized bulk tissue specimens. This source material may not accurately reflect molecular events taking place in the specific cells of the tissue itself. This article describes a completely new class of proteomic-based approaches aimed at the identification and investigation of protein markers in the actual histologically defined cell populations that an immersed in heterogeneous diseased tissue, it is envisioned that these investigations will eventually lead to novel diagnostic, prognostic, or therapeutic markers that can be applied to monitor therapeutic toxicity or efficacy. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Tissue Proteom Unit, Div Therapeut Prot, Washington, DC 20204 USA. Georgetown Univ, Dept Chem, Washington, DC 20057 USA. RP Liotta, LA (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A33,10 Ctr Dr, Bethesda, MD 20892 USA. NR 28 TC 67 Z9 71 U1 0 U2 3 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1084-8592 J9 MOL DIAGN JI Mol. Diagn. PD DEC PY 2000 VL 5 IS 4 BP 301 EP 307 DI 10.1054/modi.2000.19808a PG 7 WC Biotechnology & Applied Microbiology; Medical Laboratory Technology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Medical Laboratory Technology; Research & Experimental Medicine GA 389DA UT WOS:000166222300007 PM 11172494 ER PT J AU Hutchins, B Sajjadi, N Seaver, S Shepherd, A Bauer, SR Simek, S Carson, K Aguilar-Cordova, E AF Hutchins, B Sajjadi, N Seaver, S Shepherd, A Bauer, SR Simek, S Carson, K Aguilar-Cordova, E TI Working toward an adenoviral vector testing standard SO MOLECULAR THERAPY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Canji Inc, San Diego, CA 92121 USA. Seaver Associates, US Pharmacopeia Cell Therapy Gene Therapy & Tissu, Concord, MA 01742 USA. Q One Biotech, Worcester, MA 01605 USA. US FDA, CBER, Rockville, MD 20852 USA. Williamsburg Bioproc Fdn, Norfolk, VA 23508 USA. RP Aguilar-Cordova, E (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RI Bauer, Steven/G-5559-2012 NR 0 TC 15 Z9 17 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD DEC PY 2000 VL 2 IS 6 BP 532 EP 534 DI 10.1006/mthe.2000.0217 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 389EF UT WOS:000166225100002 PM 11124052 ER PT J AU Krause, PR Klinman, DM AF Krause, PR Klinman, DM TI Varicella vaccine revisited - Reply SO NATURE MEDICINE LA English DT Letter ID HEALTHY-CHILDREN; ZOSTER VIRUS; EFFICACY; CHICKENPOX; LEUKEMIA C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Krause, PR (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bldg 29A,Rm 1 C 18, Bethesda, MD 20892 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2000 VL 6 IS 12 BP 1300 EP 1300 DI 10.1038/82072 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 380LV UT WOS:000165704100006 ER PT J AU Ferguson, SA Scallet, AC Flynn, KM Meredith, JM Schwetz, BA AF Ferguson, SA Scallet, AC Flynn, KM Meredith, JM Schwetz, BA TI Developmental neurotoxicity of endocrine disrupters: Focus on estrogens SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 17th International Neurotoxicology Conference CY OCT 17-20, 1999 CL LITTLE ROCK, ARKANSAS SP Natl Ctr Environm Assessment, USEPA, Agcy Toxic Substances & Dis Registry, NICHHD, Natl Inst Environm Hlth Sci, Natl Ctr Environm Health/CDC, Neurotoxicol Div/NHEERL/US EPA DE development; endocrine disrupter; estrogen ID SEXUALLY DIMORPHIC NUCLEUS; MEDIAL PREOPTIC AREA; FEMALE RATS; RECEPTOR-ALPHA; PITUITARY-RESPONSIVENESS; TESTOSTERONE PROPIONATE; ALKYLPHENOL ETHOXYLATES; MOLECULAR MECHANISMS; POSTNATAL INFLUENCE; PERINATAL TREATMENT AB A number of different environmental compounds are proposed to interact with the endocrine system (i.e., endocrine disrupters). Many of these have estrogenic effects in vitro and/or in vivo. Recent reviews have focused attention on the need for assessing the neurotoxicity of these compounds following developmental exposure. This attention comes in part from the literature on the effects of developmental exposure to exogenous estrogen on later behavioral and neuropathological alterations. A review of the ongoing neurobehavioral and neuropathological studies at the National Center for Toxicological Research on four such estrogen mimics (genistein, methoxychlor, nonylphenol, and ethinyl estradiol) is presented with results indicating that intake of a sodium solution is sensitive to these estrogen mimics. Developmental dietary exposure in male and female rats resulted in increased consumption of the sodium solution. Volume of the sexually dimorphic nucleus of the medial preoptic area was reduced by genistein, nonylphenol, and ethinyl estradiol exposure in males. The regulatory impact of these data and the directions for future research are discussed. (C) 2000 Inter Press, Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. US FDA, Rockville, MD 20857 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd,HFT-132, Jefferson, AR 72079 USA. NR 85 TC 27 Z9 31 U1 0 U2 4 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 USA SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2000 VL 21 IS 6 BP 947 EP 956 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 405TQ UT WOS:000167177000004 PM 11233764 ER PT J AU Flynn, KM Ferguson, SA Delclos, KB Newbold, RR AF Flynn, KM Ferguson, SA Delclos, KB Newbold, RR TI Multigenerational exposure to dietary genistein has no severe effects on nursing behavior in rats SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 17th International Neurotoxicology Conference CY OCT 17-20, 1999 CL LITTLE ROCK, ARKANSAS SP Natl Ctr Environm Assessment, USEPA, Agcy Toxic Substances & Dis Registry, NICHHD, Natl Inst Environm Hlth Sci, Natl Ctr Environm Health/CDC, Neurotoxicol Div/NHEERL/US EPA DE phytoestrogen; endocrine disrupter; estrogen ID MATERNAL-BEHAVIOR; SHR RATS; PHYTOESTROGENS; ISOFLAVONES; DAIDZEIN; ONSET; CARE; BETA AB The phytoestrogen and principal isoflavone in soy, genistein, has adverse effects on reproductive physiology in rodents. Since physiology and behavior are both sensitive to perturbations by estrogens, genistein may produce behavioral alterations as well. This paper reports one aspect of a study in wh ich several adult rodent behaviors will be assessed following long term multigenerational dietary exposure to genistein. Since maternal care may affect offspring behaviors in adulthood, it is important to determine the potential for genistein to affect maternal behavior. Here, rats (FU generation) were fed soy-free diets containing 0, 5, 100, or 500 ppm genistein (approx. 0, 0.4, 8, and 40 mg/kg/day for an adult) beginning on postnatal day (PND) 42. Two generations of offspring (F1 and F2) were continued on these diets and all treatment groups of the F3 generation were returned to 0 ppm at weaning (PND 22). In the first 3 weeks after parturition (for each generation), darns were assessed on 6 occasions for the presence of the arched back posture with at least one pup nursing. Data were analyzed by 3 way repeated measures analysis of variance (ANOVA) with generation, treatment, and postnatal day as factors, and p<0.05 required for significance There were no significant interactions among treatment, generation, or day, and no overall effects of treatment or generation. As expected, there was a significant overall effect of day, with animals nursing less on later days (p<0.0001). As assessed here, these results suggest that lifelong and multigenerational exposure to dietary genistein has no severe effects on nursing behavior in rodents. (C) 2000 Inter Press Inc. 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. Natl Inst Environm Hlth Sci, Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC USA. RP Flynn, KM (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd,HFT-132, Jefferson, AR 72079 USA. NR 24 TC 19 Z9 20 U1 0 U2 0 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 USA SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2000 VL 21 IS 6 BP 997 EP 1001 PG 5 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 405TQ UT WOS:000167177000009 PM 11233769 ER PT J AU Lu, MH Tang, N Ali, SF AF Lu, MH Tang, N Ali, SF TI Effects of single injection of methylazoxymethanol at postnatal day one on cell proliferation in different brain regions of male rats SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 17th International Neurotoxicology Conference CY OCT 17-20, 1999 CL LITTLE ROCK, AR SP Natl Ctr Environm Assessment, USEPA, Agcy Tox Subst & Dis Registry, NICHHD, Natl Inst Environm Hlth Sci, Natl Ctr Environm Health/CDC, Neurotoxicol Div/NHEERL/US EPA DE methylazoxymethanol; cell proliferation; S-phase cells; brain regions; microencephaly; rat ID EXTERNAL GRANULAR LAYER; MOUSE CEREBELLUM; NUCLEIC ACIDS; N-MYC; DNA; CYCASIN; NEUROBLASTOMA; HISTOGENESIS; METHYLATION; HYPOPLASIA AB Methylazoxymethanol (MAM) an aglycone of cycasin extracted from Cycad seed, is reported to induce microencephaly in rats after prenatal or postnatal administration. Forty postnatal day (PND) I rats derived from 8 timed-pregnant rats were used to evaluate the effect of a single subcutaneous injection of MAM on PND I on cell proliferation in rat brain. All darns were fed NIH-31 diet. In the MAM-treated group, each pup received a single injection of MAM at 10 mg/kg body weight. In the control group, pups were injected with saline solution. Body weight of pups was recorded on PNDs 1, 7, 14, 21, 28, and 60. One male pup in each litter was removed for sacrifice by decapitation on PNDs 7, 14, 27, 28, and 60. The brain was removed and dissected to obtain the brain stem, caudate nucleus, cerebellum, frontal cortex, hippocampus, hypothalamus, and olfactory bulb. The percentage (%) of S-phase cells in the cell cycle for each region was measured as index of cell proliferation. A significant (p<0.05) reduction in body weight was detected on PND 7. The % S-phase cells in cerebellum on PND 7 and olfactory bulb on PND 14 initially increased and then later decreased. There were significant decreases in the % S-phase cells in both cerebellum and caudate nucleus on PND 27 and olfactory bulb on PND 28. No significant changes were found in other br ain regions in cell proliferation activity between the control and MAM-treated groups. The % of S-phase cells in cerebellum decreased 65% on PND 60 but lacked statistical significance due to small number of animals used in each group. The results indicated that a single injection of MAM at 10 mg/kg/body weight on PND I inhibited cell proliferation in the cerebellum in a manner that could lead to microencephaly. (C) 2000 Inter Press, Inc. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Coll Med, Dept Pediat, Little Rock, AR 72205 USA. RP Lu, MH (reprint author), Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM mlu@nctr.fda.gov NR 39 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2000 VL 21 IS 6 BP 1145 EP 1151 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 405TQ UT WOS:000167177000023 PM 11233761 ER PT J AU La Grenade, L Vega, A Luke, MC AF La Grenade, L Vega, A Luke, MC TI Adverse effects of Lotrisone cream used in infants SO PEDIATRICS LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP La Grenade, L (reprint author), US FDA, Rockville, MD 20857 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 2000 VL 106 IS 6 BP 1519 EP 1520 PG 2 WC Pediatrics SC Pediatrics GA 383ZP UT WOS:000165914800052 ER PT J AU Boykins, RA Ardans, JA Wahl, LM Lal, RB Yamada, KM Dhawan, S AF Boykins, RA Ardans, JA Wahl, LM Lal, RB Yamada, KM Dhawan, S TI Immunization with a novel HIV-1-Tat multiple-peptide conjugate induces effective immune response in mice SO PEPTIDES LA English DT Article DE monocytes; macrophages; HIV-1-Tat; HIV; AIDS; pathogenesis; vaccine ID IMMUNODEFICIENCY-VIRUS TYPE-1; TAT PROTEIN; ENDOTHELIAL-CELLS; AIDS VACCINE; INFECTION; DOMAIN; PATHOGENESIS; MONOCYTES; IDENTIFICATION; CORECEPTORS AB We report here a novel, highly immunogenic synthetic, multiple-peptide conjugate comprising functional domains Tat(21-40) and Tat(53-68) from HIV-I group M plus Tat(9-20) from HIV-I group O of the HIV-Tat protein (HIV-1-Tat-MPC). Vaccination of mice with HIV-I-Tat-MPC induced an effective immune response to all three functional domains. The anti-HTV-1-Tat-MPC antibodies efficiently inhibited Tar-induced viral activation in monocytes infected with HIV(Ba-L) as well as with various clinical HIV-l isolates, and reduced Tat-mediated cytopathicity in infected cells by 60-75%. Our results indicate that anti-HIV-l-Tat-MPC antibodies inhibit viral pathogenesis, possibly by blocking functional determinants of Tar and disrupting autocrine and paracrine actions of secreted Tat protein. This epitope-specific, synthetic Tat construct may, therefore, provide a subunit AIDS vaccine candidate for inducing an effective immunoprophylaxis response to reduce progression of HIV infection. (C) 2000 Elsevier Science Inc. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Immunopathogenesis Sect, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Immunopathogenesis Lab, Atlanta, GA 30333 USA. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Immunopathol Sect, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Parasit Biol & Biochem, Bethesda, MD 20892 USA. RP Dhawan, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Immunopathogenesis Sect, Bethesda, MD 20892 USA. EM dhawan@cber.fda.gov OI Yamada, Kenneth/0000-0003-1512-6805 NR 38 TC 10 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD DEC PY 2000 VL 21 IS 12 BP 1839 EP 1847 DI 10.1016/S0196-9781(00)00334-X PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 394TA UT WOS:000166538300010 PM 11150644 ER PT J AU Tang, YM Green, BL Chen, GF Thompson, PA Lang, NP Shinde, A Lin, DX Tan, W Lyn-Cook, BD Hammons, GJ Kadlubar, FF AF Tang, YM Green, BL Chen, GF Thompson, PA Lang, NP Shinde, A Lin, DX Tan, W Lyn-Cook, BD Hammons, GJ Kadlubar, FF TI Human CYP1B1 Leu(432)Val gene polymorphism: ethnic distribution in African-Americans, Caucasians and Chinese; oestradiol hydroxylase activity; and distribution in prostate cancer cases and control SO PHARMACOGENETICS LA English DT Article DE human CYP1B1; genetic polymorphisms; oestradiol hydroxylase activity; prostate cancer susceptibility ID PRIMARY CONGENITAL GLAUCOMA; CYTOCHROME P4501B1; EXPRESSION; MUTATIONS; ESTRADIOL; CDNA; 4-HYDROXYLATION; ACTIVATION; MICROSOMES; CARCINOMA AB Cytochrome P4501B1 (CYP1B1) is involved in the activation of many carcinogens and in the metabolism of steroid hormones, including 17 beta -oestradiol (E-2) and testosterone. We report a significant difference in the allele frequencies of two point mutations in the coding region of the CYP1B1 gene among Caucasian (n = 189), African-American (n = 52) and Chinese (Linxian) (n = 109) populations, A (C to G) transversion at position 1666 in exon 3, which results in an amino acid substitution of Leu(432) to Val, was present in African-Americans with an allele frequency for Val(432) Of 0.75, in Caucasians of 0.43, and in Chinese of 0.17. A (C to T) transition at position 1719 in exon 3, with no amino acid change (Asp(449)), appeared to be closely linked with the Val(432) variant. Results using human lung microsomal preparations from individuals with the CYP1B1(Val/Val) and CYP1B1(Leu/Leu) genotypes indicate that Val(432) variant may be a high activity allele and thus may contribute to the interindividual differences in CYP1B1 activity. Because CYP1B1 is involved in hormone and carcinogen metabolism, and given the disparate rates of prostate cancer among ethnic groups, we also evaluated the association of the CYP1B1 Leu(432)Val polymorphism with prostate cancer risk in a pilot case-control study, Among Caucasians, 34% of men with cancer (n = 50) were homozygous for the Val(432) polymorphism, while only 12% of matched control subjects (n = 50) had this genotype. These preliminary data indicate that genetic polymorphisms in CYP1B1 might play an important role in human prostate carcinogenesis. Pharmacogenetics 10:761-766 (C) 2000 Lippincott Williams & Wilkins. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Surg Oncol, Little Rock, AR 72205 USA. Chinese Acad Med Sci, Inst Canc, Div Tumor Etiol & Carcinogenesis, Beijing 100021, Peoples R China. Beijing Union Med Coll, Beijing, Peoples R China. RP Kadlubar, FF (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, HFT-100,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 35 TC 90 Z9 91 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD DEC PY 2000 VL 10 IS 9 BP 761 EP 766 DI 10.1097/00008571-200012000-00001 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 387PY UT WOS:000166132000001 PM 11221602 ER PT J AU Nowell, S Ambrosone, CB Ozawa, S MacLeod, SL Mrackova, G Williams, S Plaxco, J Kadlubar, FF Lang, NP AF Nowell, S Ambrosone, CB Ozawa, S MacLeod, SL Mrackova, G Williams, S Plaxco, J Kadlubar, FF Lang, NP TI Relationship of phenol sulfotransferase activity (SULT1A1) genotype to sulfotransferase phenotype in platelet cytosol SO PHARMACOGENETICS LA English DT Article DE sulfotransferase; interindividual variability; phenotype; genotype; chemical carcinogenesis ID N-HYDROXY ARYLAMINES; METABOLIC-ACTIVATION; HUMAN LIVER; ESTROGEN SULFOTRANSFERASE; GENETIC-POLYMORPHISM; HETEROCYCLIC AMINES; AROMATIC-AMINES; DRUG-METABOLISM; PST ACTIVITY; LOCALIZATION AB Sulfation catalysed by human cytosolic sulfotransferases is generally considered to be a detoxification mechanism, Recently, it has been demonstrated that sulfation of heterocyclic aromatic amines by human phenol sulfotransferase (SULT1A1) can result in a DNA binding species. Therefore, sulfation capacity has the potential to influence chemical carcinogenesis in humans, To date, one genetic polymorphism (Arg(213)His) has been identified that is associated with reduced platelet sulfotransferase activity. In this study, data on age, race, gender, SULT1A1 genotype and platelet SULT1A1 activity were available for 279 individuals. A simple colorimetric phenotyping assay, in conjunction with genotyping, was employed to demonstrate a significant correlation (r = 0.23, P < 0.01) of SULT1A1 genotype and platelet sulfotransferase activity towards 2-naphthol, a marker substrate for this enzyme. There was also a difference in mean sulfotransferase activity based on gender (1.28 nmol/min/mg, females; 0.94 nmol/min/mg, males, P=0.001). DNA binding studies using recombinant SULT1A1*1 and SULT1A1*2 revealed that SULT1A1*1 catalysed N-hydroxy-aminobiphenyl (N-OH-ABP) DNA adduct formation with substantially greater efficiency (5.4 versus 0.4 pmol bound/mg DNA/20 min) than the SULT1A1*2 variant. A similar pattern was observed with 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5b]pyridine (N-OH-PhIP) (4.6 versus 1.8 pmol bound/mg DNA/20 min). Pharmacogenetics 10:789-797 (C) 2000 Lippincott Williams & Wilkins. C1 Univ Arkansas Med Sci, Dept Surg Oncol, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Cent Arkansas Vet Hlth Care Syst, Little Rock, AR USA. Natl Inst Hlth Sci, Div Pharmacol, Tokyo 158, Japan. RP Nowell, S (reprint author), Univ Arkansas Med Sci, Dept Surg Oncol, VA Res Slot 151,4300 W 7th St, Little Rock, AR 72205 USA. FU NCI NIH HHS [CA55751, CA58697]; NIA NIH HHS [AG15722] NR 60 TC 65 Z9 66 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 DEC PY 2000 VL 10 IS 9 BP 789 EP 797 DI 10.1097/00008571-200012000-00004 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 387PY UT WOS:000166132000004 PM 11191883 ER PT J AU Gardner, JS Blough, D Drinkard, CR Shatin, D Anderson, G Graham, D Alderfer, R AF Gardner, JS Blough, D Drinkard, CR Shatin, D Anderson, G Graham, D Alderfer, R TI Tramadol and seizures: A surveillance study in a managed care population SO PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT 13th International Congress of Pharmacology CY JUL 26-31, 1998 CL MUNICH, GERMANY ID POSTMARKETING SURVEILLANCE; DRUG; CONVULSIONS AB Study Objective. To investigate the occurrence of tramadol-associated seizures. Design. Retrospective cohort and case-control studies. Setting. UnitedHealth Group-affiliated independent practice model health plans, from different regions of the United States, contracting with large networks of physicians. Intervention. Analysis of administrative data from a large U.S. managed care population. Patients. A cohort of 9218 adult tramadol users and 37,232 concurrent nonusers. Measurements and Main Results. Fewer than 1% of users (80) had a presumed incident seizure claim after the first tramadol prescription. Risk of seizure claim was increased 2- to 6-fold among users adjusted for selected comorbidities and concomitant drugs. Risk was highest among those aged 25-54 years, those with more than four tramadol prescriptions, and those with history of alcohol abuse, stroke, or head injury. A case-control study among users was conducted to validate incident seizure outcomes from medical records. Only eight cases were confirmed, and all had cofactors associated with increased seizure risk. Conclusion. In a general population, risk of seizure may be associated with long-term therapy with tramadol or the presence of cofactors, or confined to a small sensitive population subset. C1 Univ Washington, Dept Pharm, Seattle, WA 98195 USA. Univ Washington, Pharmaceut Outcomes Res & Policy Program, Seattle, WA 98195 USA. UnitedHlth Grp, Ctr Hlth Care Policy & Evaluat, Minnetonka, MN USA. US FDA, Rockville, MD 20857 USA. VAMC, Roanoke Salem Program, UVA Psychiat Med Residency, Salem, VA USA. RP Gardner, JS (reprint author), Univ Washington, Dept Pharm, Box 357630, Seattle, WA 98195 USA. NR 26 TC 61 Z9 64 U1 0 U2 1 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD DEC PY 2000 VL 20 IS 12 BP 1423 EP 1431 DI 10.1592/phco.20.19.1423.34854 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 380CL UT WOS:000165680700003 PM 11130214 ER PT J AU Minai, OA Sullivan, EJ Stoller, JK AF Minai, OA Sullivan, EJ Stoller, JK TI Pulmonary involvement in Niemann-Pick disease: Case report and literature review SO RESPIRATORY MEDICINE LA English DT Editorial Material DE Niemann-Pick disease; sea-blue histiocytosis; interstitial lung disease ID SEA-BLUE HISTIOCYTE; FOLLOW-UP AB Niemann-Pick disease (NPD) is a rare, inherited, autosomal recessive, lipid storage disease. The pathognomonic intracellular accumulation of sphingomyelin results in the production and accumulation of 'foam cells'. Interstitial lung disease is a rare manifestation of NPD. We present the case of a 48-year-old white female with NPD involving the lungs, liver and spleen. The chest radiograph showed bilateral, predominantly basal reticulonodular infiltrates and serial pulmonary function tests over a period of years showed preserved expiratory airflow and a severely decreased diffusion capacity for carbon monoxide (DLCO). In view of her visceral involvement, lack of neurological symptoms and survival into adulthood, we believe our patient represents a case of type B NPD. In this type of NPD, aside from prominent hepatosplenomegaly and sexual immaturity, significant pulmonary infiltration with 'Pick cells' has been reported. To date, no therapeutic modality has been shown to alter the natural history of this disease, which results in progressive debilitation and death. This case is unique in that it provides the longest physiological follow-up in the literature, and provides data on the natural history of pulmonary involvement in NPD. C1 Cleveland Clin Fdn, Dept Pulm & Crit Care Med, Cleveland, OH 44195 USA. US FDA, Div Pulm & Allergy Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Minai, OA (reprint author), Cleveland Clin Fdn, Dept Pulm & Crit Care Med, 9500 Euclid Ave,Desk A-90, Cleveland, OH 44195 USA. NR 41 TC 46 Z9 47 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD DEC PY 2000 VL 94 IS 12 BP 1241 EP 1251 DI 10.1053/rmed.2000.0942 PG 11 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 488PH UT WOS:000171944500015 PM 11192962 ER PT J AU Horwitz, W AF Horwitz, W TI Reporting low-level analytical data SO SOUTH AFRICAN JOURNAL OF CHEMISTRY-SUID-AFRIKAANSE TYDSKRIF VIR CHEMIE LA English DT Article AB Low level measurements - those near, at, or below limits of measurements (specification, quantification, detection) - should be reported as they appear: positive, negative, or zero, as the best estimate of the measured characteristic, usually concentration. The long-term mean of such poor estimates will often provide a surprisingly good estimate of the true value" from the operation of the law of large numbers. This manner of reporting data near the limits of measurement can be independent of, and adaptable to, any set of agreed-upon definitions and parameters for the concept, including its uncertainty. This proposal is intended to help to standardize the method of reporting low-level analytical data, not to legitimize the data or any conclusions or actions resulting from their use or interpretation. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20240 USA. RP Horwitz, W (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-500, Washington, DC 20240 USA. EM wxhor@aol.com NR 7 TC 0 Z9 0 U1 1 U2 1 PU BUREAU SCIENTIFIC PUBL PI PRETORIA PA P O BOX 1758, PRETORIA 0001, SOUTH AFRICA SN 0379-4350 J9 S AFR J CHEM-S-AFR T JI South Afr. J. Chem.-Suid-Afr. Tydskr. Chem. PD DEC PY 2000 VL 53 AR 4 PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA 518XV UT WOS:000173694200003 ER PT J AU Slikker, W Beck, BD Cory-Slechta, DA Paule, MG Anger, WK Bellinger, D AF Slikker, W Beck, BD Cory-Slechta, DA Paule, MG Anger, WK Bellinger, D TI Cognitive tests: Interpretation for neurotoxicity? (Workshop summary) SO TOXICOLOGICAL SCIENCES LA English DT Article DE cognitive tests; behavioral neurotoxicology; metals; solvents; neurobehavioral test battery ID REPEATED ACQUISITION; RHESUS-MONKEYS; SUSTAINED ATTENTION; RESPONSE SEQUENCES; SAMPLE PERFORMANCE; CHILD-DEVELOPMENT; LEAD-EXPOSURE; DELAYED MATCH; TEST BATTERY; RATS AB The appropriate use and interpretation of cognitive tests presents important challenges to the toxicologist and to the risk assessor. For example, intelligence cannot be measured directly; rather intelligence is quantified indirectly by scoring responses (i.e., behaviors) to specific situations (problems), This workshop, "Cognitive Tests: Interpretation for Neurotoxicity?" provided an overview on the types of cognitive tests available and described approaches by which the validity of such tests can be assessed. Unlike many tools available to the toxicologist, cognitive tests have a particular advantage. Being noninvasive and species-neutral, the same test can be performed in different mammalian species. This enhances one's ability to assess the validity of test results. Criteria for test validity include comparable responses across species as well as similar disruption by the same neurotoxicant across species, Test batteries, such as the Operant Test Battery, have indicated remarkable similarity between monkeys and children with respect to performance of certain tasks involving, for example, short-term memory. Still, there is a need for caution in interpretation of such tests, In particular, cognitive tests, especially when performed in humans, are subject to confounding by a range of factors, including age, gender, and, in particular, education. Moreover, the ability of such tests to reflect intelligence must be considered. Certain aspects of intelligence, such as the ability to plan or carry out specific tasks, are not well reflected by many of the standard tests of cognition. Nonetheless, although still under development, cognitive tests do hold promise for reliably predicting neurotoxicity in humans. C1 Gradient Corp, Cambridge, MA 02142 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Rochester, Sch Med, Dept Environm Med, Rochester, NY 14642 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Behav Toxicol Lab, Jefferson, AR 72079 USA. Oregon Hlth Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97201 USA. Childrens Hosp, Neuroepidemiol Unit, Boston, MA 02115 USA. RP Beck, BD (reprint author), Gradient Corp, 238 Main St, Cambridge, MA 02142 USA. FU NIEHS NIH HHS [5R21 ES08707-02] NR 71 TC 11 Z9 12 U1 2 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 DEC PY 2000 VL 58 IS 2 BP 222 EP 234 DI 10.1093/toxsci/58.2.222 PG 13 WC Toxicology SC Toxicology GA 394ZG UT WOS:000166553800004 PM 11099635 ER PT J AU Fanning, MM Wassel, R Piazza-Hepp, T AF Fanning, MM Wassel, R Piazza-Hepp, T TI Pyrogenic reactions to gentamicin therapy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID AMINOGLYCOSIDES; METAANALYSIS C1 US FDA, Rockville, MD 20855 USA. RP Fanning, MM (reprint author), US FDA, Rockville, MD 20855 USA. NR 5 TC 8 Z9 8 U1 1 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 NOV 30 PY 2000 VL 343 IS 22 BP 1658 EP 1659 DI 10.1056/NEJM200011303432218 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 377JT UT WOS:000165511000031 PM 11184991 ER PT J AU MacGregor, JT Casciano, D Muller, L AF MacGregor, JT Casciano, D Muller, L TI Strategies and testing methods for identifying mutagenic risks SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE mutagenicity; carcinogenicity; testing guidelines; harmonization ID BIG BLUE(R) RATS; ENDOGENOUS HPRT GENE; LACI TRANSGENIC MICE; DNA ADDUCT FORMATION; ETHYL-N-NITROSOUREA; GENOTOXICITY TEST PROCEDURES; GENOTYPIC SELECTION METHODS; IN-VIVO MUTAGENICITY; HAMSTER OVARY CELLS; CHO-HGPRT SYSTEM AB The evolution of testing strategies and methods for identification of mutagenic agents is discussed, beginning with the concern over potential health and population effects of chemical mutagens in the late 1940s that led to the development of regulatory guidelines for mutagenicity testing in the 1970s and 1980s. Efforts to achieve international harmonization of mutagenicity testing guidelines are summarized, and current issues and needs in the field are discussed, including the need for quantitative methods of mutagenic risk assessment, dose-response thresholds, indirect mechanisms of mutagenicity, and the predictivity of mutagenicity assays for carcinogenicity in vivo. Speculation is offered about the future of mutagenicity testing, including possible near-term changes in standard test batteries and the longer-term roles of expression profiling of damage-response genes, in vivo mutagenicity testing methods, and models that better account for differences in metabolism between humans and laboratory model systems. Published by Elsevier Science B.V. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Fed Inst Drugs & Med Devices, Berlin, Germany. RP MacGregor, JT (reprint author), US FDA, Ctr Drug Evaluat & Res, 5600 Fishers Lane, Rockville, MD 20857 USA. EM macgregorj@cder.fda.gov NR 161 TC 23 Z9 27 U1 2 U2 3 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 NOV 20 PY 2000 VL 455 IS 1-2 BP 3 EP 20 DI 10.1016/S0027-5107(00)00116-0 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 385CX UT WOS:000165985200002 PM 11113464 ER PT J AU Holada, K Simak, J Vostal, JG AF Holada, K Simak, J Vostal, JG TI Transmission of BSE by blood transfusion SO LANCET LA English DT Letter ID SPONGIFORM ENCEPHALOPATHY; DISEASE C1 US FDA, Lab Cellular Hematol, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Holada, K (reprint author), US FDA, Lab Cellular Hematol, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. RI Simak, Jan/C-1153-2011 NR 5 TC 15 Z9 15 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 18 PY 2000 VL 356 IS 9243 BP 1772 EP 1772 DI 10.1016/S0140-6736(05)71968-1 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 376MX UT WOS:000165462300059 PM 11095289 ER PT J AU Simak, J Holada, K Vostal, JG AF Simak, J Holada, K Vostal, JG TI Prion protein is present on microparticles released by apoptotic endothelial cells. SO BLOOD LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD USA. RI Simak, Jan/C-1153-2011 NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 251 BP 60A EP 60A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100252 ER PT J AU Murata, T Kurokawa, K Sasaki, A Yoshimura, A Puri, RK Kobayashi, N AF Murata, T Kurokawa, K Sasaki, A Yoshimura, A Puri, RK Kobayashi, N TI Molecular cloning and characterization of interleukin 13 receptor binding protein. SO BLOOD LA English DT Meeting Abstract C1 Nagasaki Univ, Nagasaki 852, Japan. Kurume Univ, Kurume, Fukuoka 830, Japan. DCGT, CBER, Bethesda, MD USA. RI Yoshimura, Akihiko/K-5515-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 4300 BP 140B EP 140B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200640 ER PT J AU Oshima, Y Puri, RK AF Oshima, Y Puri, RK TI Development of a novel interleukin-13 antagonist that suppresses interleukin-13 induced signal transduction and cell proliferation. SO BLOOD LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1479 BP 342A EP 342A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101480 ER PT J AU Mondoro, TH Lozier, JN Vostal, JG AF Mondoro, TH Lozier, JN Vostal, JG TI An adenoviral vector increases platelet leukocyte association through the upregulation of the leukocyte integrin CD11b/18. SO BLOOD LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD USA. NIH, NHGRI, Clin Gene Therapy Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 5397 BP 380B EP 380B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201737 ER PT J AU Holada, K Simak, J D'Agnillo, F Vostal, JG AF Holada, K Simak, J D'Agnillo, F Vostal, JG TI Expression of prion protein on endothelial cells. SO BLOOD LA English DT Meeting Abstract C1 US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD USA. RI Simak, Jan/C-1153-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3540 BP 819A EP 819A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103539 ER PT J AU Rawat, R Rainey, GJ Thompson, CD Frazier-Jessen, MR Brown, RT Nordan, RP AF Rawat, R Rainey, GJ Thompson, CD Frazier-Jessen, MR Brown, RT Nordan, RP TI Constitutive activation of STAT3 is associated with the acquisition of an interleukin 6-independent phenotype by murine plasmacytomas and hybridomas SO BLOOD LA English DT Article ID PERIPHERAL-BLOOD CELLS; PHASE RESPONSE FACTOR; CYTOKINE RECEPTORS; GROWTH-FACTOR; TRANSCRIPTIONAL ACTIVATION; JAK/STAT PROTEINS; TYROSINE KINASE; ONCOSTATIN-M; V-SRC; PROLIFERATION AB Interleukin 6 (IL-6), the major growth factor for myeloma cells, signals through the activation of signal transducers and activators of transcription (STAT) proteins. An important step in the malignant progression of murine plasmacytomas is the transition from dependence on IL-6 to a state of IL-6 independence. To elucidate the mechanism whereby IL-6 independence occurs, intracellular signaling events elicited by IL-6 in both IL-6-dependent and -independent plasmacytomas and hybridomas were compared. It was found that STAT3, a key molecule involved in IL-6 signaling, was constitutively activated and phosphorylated in IL-6-independent cell lines compared to the IL-6-dependent cells. Further comparison of up stream signaling pathways revealed that JAK-1 was constitutively present in antiphosphotyrosine immunoprecipitates of IL-6-independent cells; gp180 was constitutively phosphorylated in a subset of IL-6 independent plasmacytomas, whereas other IL-6-independent lines showed no detectable gp130 phosphorylation in the absence of exogenous IL-6, Secretion of a factor capable of supporting the growth of IL-6-dependent cells was observed in one of the IL-6-independent plasmacytomas, but not in others, making an autocrine mechanism an unlikely explanation for IL-6 independence. These findings provide evidence that the constitutive activation of STAT3, either in the absence of detectable receptor-proximal events or associated with the concomitant activation of gp130, can contribute to the process of IL-6 independence. (C) 2000 by The American Society of Hematology. C1 Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Immunobiol Lab, Bethesda, MD 20892 USA. RP Rawat, R (reprint author), Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Immunobiol Lab, Bldg 29B,Room 4G07,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 51 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2000 VL 96 IS 10 BP 3514 EP 3521 PG 8 WC Hematology SC Hematology GA 372HA UT WOS:000165227200030 PM 11071649 ER PT J AU Paweletz, CP Ornstein, DK Roth, MJ Bichsel, VE Gillespie, JW Calvert, VS Vocke, CD Hewitt, SM Duray, PH Herring, J Wang, QH Hu, N Linehan, WM Taylor, PR Liotta, LA Emmert-Buck, MR Petricoin, EF AF Paweletz, CP Ornstein, DK Roth, MJ Bichsel, VE Gillespie, JW Calvert, VS Vocke, CD Hewitt, SM Duray, PH Herring, J Wang, QH Hu, N Linehan, WM Taylor, PR Liotta, LA Emmert-Buck, MR Petricoin, EF TI Loss of annexin 1 correlates with early onset of tumorigenesis in esophageal and prostate carcinoma SO CANCER RESEARCH LA English DT Article ID LASER-CAPTURE MICRODISSECTION; GENE-EXPRESSION; LIPOCORTIN-I; CANCER; DIFFERENTIATION; INDUCTION; CELLS AB Annexin I protein expression was evaluated in patient-matched longitudinal study sets of laser capture microdissected normal, premalignant, and invasive epithelium from human esophageal squamous cell cancer and prostatic adenocarcinoma, In 25 esophageal cases (20 by Western blot and 5 by immunohtstochemistry) and 17 prostate cases (3 by Western blot and 14 by immunohistochemistry), both tumor types showed either complete loss or a dramatic reduction in the level of annexin I protein expression compared with patient-matched normal epithelium (P less than or equal to 0,05), Moreover, by using Western blot analysis of laser capture microdissected, patient-matched longitudinal study sets of both tumor types, the loss of protein expression occurred in premalignant lesions. Concordance of this result with immunohistochemical analysis suggests that annexin I may be an essential component for maintenance of the normal epithelial phenotype. Additional studies investigating the mechanism(s) and functional consequences of annexin I protein loss in tumor cells are warranted. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prod, Bethesda, MD 20892 USA. Georgetown Univ, Dept Chem, Washington, DC 20057 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathogenet Unit, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Canc Prevent Studies Branch, NIH, Bethesda, MD 20892 USA. NCI, Canc Genome Anat Project, Off Director, NIH, Bethesda, MD 20892 USA. Natl Naval Med Ctr, Bethesda, MD 20892 USA. Shanxi Canc Hosp, Pathol Lab, Taiyuan 030013, Peoples R China. RP Petricoin, EF (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prod, Bethesda, MD 20892 USA. OI Hewitt, Stephen/0000-0001-8283-1788 NR 20 TC 162 Z9 184 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 NOV 15 PY 2000 VL 60 IS 22 BP 6293 EP 6297 PG 5 WC Oncology SC Oncology GA 375ZD UT WOS:000165432600015 PM 11103786 ER PT J AU Alper, O De Santis, ML Strombreg, K Hacker, NF Cho-Chung, YS Salomon, DS AF Alper, O De Santis, ML Strombreg, K Hacker, NF Cho-Chung, YS Salomon, DS TI Anti-sense suppression of epidermal growth factor receptor expression alters cellular proliferation, cell-adhesion and tumorigenicity in ovarian cancer cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID E-CADHERIN EXPRESSION; PROSTATE CARCINOMA-CELLS; EGF SUPERGENE FAMILY; BETA-CATENIN; PROTEIN INTERACTIONS; SIGNAL-TRANSDUCTION; MEDIATED ADHESION; EPITHELIAL-CELLS; BREAST-CANCER; IN-VIVO AB Over-expression of epidermal growth factor receptor (EGFR) in ovarian cancer has been well documented. Human NIH:OVCAR-8 ovarian carcinoma cells were transfected with an expression vector containing the anti-sense orientation of truncated human EGFR cDNA. EGFR anti-sense overexpression resulted in decreased EGFR protein and mRNA expression, cell proliferation and tumor formation in nude mice. In accordance with the reduced levels of EGFR in EGFR anti-sense-expressing cells, tyrosine phosphorylation of EGFR was decreased compared to untransfected parental cells treated with EGF. In EGFR anti-sense-transfected cells, expression of erbB-3, but not erbB-2, was increased. In addition, basal and heregulin-beta I-stimulated tyrosine phosphorylation of erbB-3 was higher in EGFR anti-sense vector-transfected cells. A morphological alteration in EGFR anti-sense gene-expressing cells was correlated with a decrease in the expression of E-cadherin, alpha -catenin and, to a lesser extent, beta -catenin. Changes in the expression of these proteins were associated with a reduction in complex formation among E-cadherin, beta -catenin and alpha -catenin and between beta -catenin and EGFR in EGFR anti-sense-expressing cells compared to sense-transfected control cells. These results demonstrate that EGFR expression in ovarian carcinoma cells regulates expression of cell adhesion proteins that may enhance cell growth and invasiveness. Published 2000 Wiley-Liss, Inc.(dagger). C1 NCI, Tumor Immunol & Biol Lab, Tumor Growth Factor Sect, NIH, Bethesda, MD 20892 USA. NCI, Tumor Immunol & Biol Lab, Cellular Biochem Sect, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD USA. Royal Hosp Women, Gynaecol Canc Ctr, Randwick, NSW, Australia. Walter Reed Army Inst Res, Dept Mol Pathol, Silver Spring, MD USA. RP NCI, Tumor Immunol & Biol Lab, Tumor Growth Factor Sect, NIH, 9200 Rockville Pike,Bldg 10,Room 5B39, Bethesda, MD 20892 USA. EM davetgfa@helix.nih.gov NR 52 TC 45 Z9 48 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD NOV 15 PY 2000 VL 88 IS 4 BP 566 EP 574 DI 10.1002/1097-0215(20001115)88:4<566::AID-IJC8>3.0.CO;2-D PG 9 WC Oncology SC Oncology GA 368TW UT WOS:000090134500008 PM 11058872 ER PT J AU Beger, RD Freeman, JP Lay, JO Wilkes, JG Miller, DW AF Beger, RD Freeman, JP Lay, JO Wilkes, JG Miller, DW TI C-13 NMR and electron ionization mass spectrometric data-activity relationship model of estrogen receptor binding SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID AUTOMATED STRUCTURE EVALUATION; MOLECULAR-FIELD ANALYSIS; CHEMICAL-SHIFTS; CHROMATOGRAPHIC RETENTION; ORGANIC-MOLECULES; NEURAL-NETWORK; 3D STRUCTURE; PREDICTION; SPECTRA; TOOL AB Two Spectroscopic Data-Activity Relationship (SDAR) models based on C-13 nuclear magnetic resonance (NMR) and electron ionization mass spectra (EI MS) data were developed for 108 compounds whose relative binding affinities (RBA) to the estrogen receptor are known. The C-13 NMR and EI MS data were used as spectrometric digital fingerprints to reflect the electronic and structural characteristics of the compounds. Both SDAR models segregated the 108 compounds into 20 strong, 15 medium, and 73 weak relative binding classifications. The first SDAR model, based on C-13 NMR data alone, gave a leave-one-out (LOO) cross-validation of 75.0%. The second SDAR model, based on a composite of C-13 NMR and EI MS data, gave a LOO cross-validation of 82.4%. Many of the misidentifications from the cross-validations were between medium and weak classifications, where there were fewer specific spectrometric characteristics to identify the relationship of spectra to estrogen receptor binding. Real and predicted C-13 NMR chemical shifts were used to test the predictive behavior of both SDAR models. The ease of use and speed of SDAR modeling may facilitate their use with other toxicological endpoints. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Beger, RD (reprint author), 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 37 TC 20 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC 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 NOV 15 PY 2000 VL 169 IS 1 BP 17 EP 25 DI 10.1006/taap.2000.9043 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 379EH UT WOS:000165627600003 PM 11076692 ER PT J AU Razzaque, A Dye, E Puri, RK AF Razzaque, A Dye, E Puri, RK TI Characterization of tumor vaccines during product development SO VACCINE LA English DT Article; Proceedings Paper CT 2nd Annual Conference on Vaccine Research CY MAR 27-30, 1999 CL BETHESDA, MARYLAND DE tumor vaccines; product development; regulatory issues ID DENDRITIC CELLS; MALIGNANT GLIOMAS; IN-VITRO; IMMUNOTHERAPY; ANTIGEN; IMMUNIZATION; PEPTIDES; IMMUNITY; VECTOR; RNA AB The term tumor vaccines encompasses a wide variety of diverse agents capable of interacting with the imune system to product local inflammation. delayed type hypersensitivity reaction and/or tumor regression and, hopefully, a therapeutic effect. These vaccines may be grouped into the following general areas: (1) Cell-based vaccines such as manipulated tumor cells, activated peripheral blood or bone marrow-derived lymphocytes, dendritic cells or other antigen presenting cells (APC) and gene-modified tumor cells or other cells engineered to express cytokines, growth factors or tumor antigens. (2) Antigen preparations, such as synthetic peptides. purified antigens and tumor cell lysates. (3) Viral and plasmid vectors expressing therapeutic genes. (4) Liposome containing antigen, peptides, plasmids encoding tumor antigens. While no tumor vaccine has been licensed by the FDA, numerous clinical trials are ongoing and some products have advanced to Phase III pivotal stages of development. However, as with many novel products, major regulatory and scientific issues associated with clinical use of tumor vaccines remain to be addressed. In this paper, we address issues associated with different types of tumor Vaccines and provide recommendations for the characterization of these vaccines at various stages of development. Published by Elsevier Science Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. RP Razzaque, A (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, HFM-530,NIH Bldg 29B,Room 2NN10, Bethesda, MD 20892 USA. NR 26 TC 6 Z9 7 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 NOV 8 PY 2000 VL 19 IS 6 BP 644 EP 647 DI 10.1016/S0264-410X(00)00251-6 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 375LL UT WOS:000165400800008 PM 11090716 ER PT J AU Gutman, S AF Gutman, S TI Labeling liquid-based systems: FDA clarification SO ACTA CYTOLOGICA LA English DT Letter DE cervix neoplasms; cervical smears; Papanicolaou smear; mass screening; AutoCyte PREP; ThinPrep (R) C1 US FDA, Div Clin Lab Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Gutman, S (reprint author), US FDA, Div Clin Lab Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD NOV-DEC PY 2000 VL 44 IS 6 BP 1120 EP 1120 PG 1 WC Pathology SC Pathology GA 378CX UT WOS:000165568400033 PM 11127746 ER PT J AU Piddock, LJV White, DG Gensberg, K Pumbwe, L Griggs, DJ AF Piddock, LJV White, DG Gensberg, K Pumbwe, L Griggs, DJ TI Evidence for an efflux pump mediating multiple antibiotic resistance in Salmonella enterica serovar Typhimurium SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ORGANIC-SOLVENT TOLERANCE; ESCHERICHIA-COLI; QUINOLONE RESISTANCE; CIPROFLOXACIN RESISTANCE; PSEUDOMONAS-AERUGINOSA; ACRAB EFFLUX; ACTIVATION; PROTEIN; MUTANTS; MARA AB The mechanism of multiple antibiotic resistance in six isolates of Salmonella enterica serovar Typhimurium recovered from a patient treated with ciprofloxacin was studied to investigate the role of efflux in the resistance phenotype. Compared to the patient's pretherapy isolate (L3), five of six isolates accumulated less ciprofloxacin, three of six isolates accumulated less chloramphenicol, and all six accumulated less tetracycline. The accumulation of one or more antibiotics was increased by carbonyl cyanide m-chlorophenylhydrazone to concentrations similar to those accumulated by L3 for all isolates except one, in which accumulation of all three agents remained approximately half that of L3, All isolates had the published wild-type sequences of marO and marR, No increased expression of marA, tolC, or soxS was observed by Northern blotting; however, three isolates showed increased expression of acrB, which was confirmed by quantitative competitive reverse transcription-PCR. However, there were no mutations within acrR or the promoter region of acrAB in any of the isolates. C1 Univ Birmingham, Div Infect & Immun, Antimicrobial Agents Res Grp, Birmingham B15 2TT, W Midlands, England. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Piddock, LJV (reprint author), Univ Birmingham, Div Infect & Immun, Antimicrobial Agents Res Grp, Birmingham B15 2TT, W Midlands, England. RI Griggs, Deborah/L-3903-2016 OI Griggs, Deborah/0000-0002-7039-6616 NR 33 TC 87 Z9 96 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 2000 VL 44 IS 11 BP 3118 EP 3121 DI 10.1128/AAC.44.11.3118-3121.2000 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 366WL UT WOS:000090029200032 PM 11036033 ER PT J AU DePaola, A Kaysner, CA Bowers, J Cook, DW AF DePaola, A Kaysner, CA Bowers, J Cook, DW TI Environmental investigations of Vibrio parahaemolyticus in oysters after outbreaks in Washington, Texas, and New York (1997 and 1998) SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID THERMOLABILE HEMOLYSIN; ENUMERATION; INFECTIONS; STRAINS; FLORIDA; PROBES; BAY AB Total Vibrio parahaemolyticus densities and the occurrence of pathogenic strains in shellfish were determined following outbreaks in Washington, Texas, and New York Recently developed nonradioactive DNA probes were utilized for the first time for direct enumeration of V. parahaemolyticus in environmental shellfish samples, V. parahaemolyticus was prevalent in oysters from Puget Sound, Wash.; Galveston Bay, Tex,; and Long Island Sound, N.Y., in the weeks following shellfish-associated outbreaks linked to these areas. However, only two samples (one each from Washington and Texas) were found to harbor total V. parahaemolyticus densities exceeding the level of concern of 10,000 g(-1). Pathogenic strains, defined as those hybridizing with tdh and/or trh probes, were detected in a few samples, mostly Puget Sound oysters, and at low densities (usually <10 g(-1)). Intensive sampling in Galveston Bay demonstrated relatively constant water temperature (27.8 to 31.7C) and V. parahaemolyticus levels (100 to 1,000 g(-1)) during the summer, Salinity varied from 14.9 to 29.3 ppt, A slight but significant (P < 0.05) negative correlation (-0.25) was observed between V. parahaemolyticus density and salinity. Based on our data, findings of more than 10,000 g-l total V. parahaemolyticus or >10 g(-1) tdh- and/or trh-positive V: parahaemolyticus in environmental oysters should be considered extraordinary. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. US FDA, Seafood Prod Res Ctr, Bothell, WA 98021 USA. US FDA, Div Math & Stat, Washington, DC 20204 USA. RP DePaola, A (reprint author), US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. NR 28 TC 186 Z9 199 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD NOV PY 2000 VL 66 IS 11 BP 4649 EP 4654 DI 10.1128/AEM.66.11.4649-4654.2000 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 369FM UT WOS:000165055300008 PM 11055906 ER PT J AU Lee, LH Pichichero, ME AF Lee, LH Pichichero, ME TI Costs of illness due to Bordetella pertussis in families SO ARCHIVES OF FAMILY MEDICINE LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Infectious-Diseases-Society-of-America CY NOV 18-21, 1999 CL PHILADELPHIA, PENNSYLVANIA SP Infect Dis Soc Amer ID CLINICAL CASE DEFINITIONS; INFECTION; VACCINE; DIAGNOSIS; DIPHTHERIA; CHILDREN; ADULTS; COUGH AB Objective: To assess costs of pertussis morbidity among families in a community setting. Design: Prospective survey. Results: Sixty-nine families (87 individuals) were studied. Twelve of 14 families with household contacts included an ill adolescent or parent. This individual was the first identified pertussis case within the household in 8 families. A family member required an average of 1.6 visits before (range, 0-7 visits) and after (range, 0-9 visits) pertussis was diagnosed; children younger than 1 year needed 2.5 and 2 visits, respectively. Symptomatic improvement occurred after a mean of 31 days (range, 4-134 days) after pertussis diagnosis and full recovery after a mean of 66 days (range, 5-383 days). Adults experienced the longest recovery time (median, 93 days) compared with other age groups. The average medical costs for an infant, child, adolescent, and adult were $2822, $308, $254, and $181, respectively. Parents lost an average of 6 workdays (range, 1-35 days) to care for an ill child; for these parents, costs associated with work loss averaged $767 per family. An average of 1.7 and 0.7 lost workdays accrued to bring an ill child to a physician's office and the emergency department, respectively. A majority (58%) of parents working while family members were ill with pertussis reported decreased work productivity ranging from 25% to 99%. Work-related costs contributed more than 60% of the overall costs of pertussis. Conclusions: The adverse financial effect of pertussis on 69 families in Monroe County, New York, was $145903 ($2115 per family) and supports the need for booster immunizations in adolescents and adults. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA. RP Lee, LH (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM 475,Suite 370N,1401 Rockville Pike, Rockville, MD 20852 USA. FU NIAID NIH HHS [AI05049] NR 34 TC 43 Z9 44 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1063-3987 J9 ARCH FAM MED JI Arch. Fam. Med. PD NOV-DEC PY 2000 VL 9 IS 10 BP 989 EP 996 DI 10.1001/archfami.9.10.989 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 384GL UT WOS:000165934400007 PM 11115197 ER PT J AU Sietmann, R Hammer, E Moody, J Cerniglia, CE Schauer, F AF Sietmann, R Hammer, E Moody, J Cerniglia, CE Schauer, F TI Hydroxylation of biphenyl by the yeast Trichosporon mucoides SO ARCHIVES OF MICROBIOLOGY LA English DT Article DE biphenyl; hydroxylation; Trichosporon; cytochrome P450 ID AROMATIC-HYDROCARBONS; FUNGAL METABOLISM; DEGRADATION; OXIDATION AB Hydroxylation of biphenyl by the dibenzofuran-degrading yeast Trichosporon mucoides SBUG 801 was studied. Glucose-grown cells degraded 40% of the biphenyl added within the first 24 h of incubation. The first step in the biotransformation pathway was the mono-hydroxylation of the biaryl compound to produce 2-, 3-, and 4-hydroxybiphenyl. Further oxidation produced seven dihydroxylated intermediates; the second hydroxyl group was added either on the aromatic ring already hydroxylated or on the second ring. Of all metabolites, 2,5-dihydroxybiphenyl accumulated in the supernatant in the highest concentration. The initial hydroxylation favors the 4-position to produce 4-hydroxybiphenyl, which is subsequently hydroxylated to form 3,4-dihydroxybiphenyl. When biphenyl was replaced as a substrate by 4-hydroxybiphenyl, further hydroxylation of the intermediate 3,4-dihydroxybiphenyl resulted in 3,4,4'-trihydroxybiphenyl. Incubation of T. mucoides with biphenyl and O-18(2) indicated a monooxygenase-catalyzed reaction in the oxidation of biphenyl. The hydroxylation was inhibited by 1-aminobenzotriazole and metyrapone, known cytochrome P450 inhibitors. These results are very similar to those observed in the biotransformation of biphenyl in mammals. C1 Univ Greifswald, Inst Mikrobiol & Mol Biol, D-17489 Greifswald, Germany. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Sietmann, R (reprint author), Univ Greifswald, Inst Mikrobiol & Mol Biol, F-L-Jahn-Str 15, D-17489 Greifswald, Germany. NR 25 TC 16 Z9 17 U1 0 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-8933 J9 ARCH MICROBIOL JI Arch. Microbiol. PD NOV PY 2000 VL 174 IS 5 BP 353 EP 361 DI 10.1007/s002030000219 PG 9 WC Microbiology SC Microbiology GA 380FC UT WOS:000165688200008 PM 11131026 ER PT J AU Lee, LH Ayoub, E Pichichero, ME AF Lee, LH Ayoub, E Pichichero, ME TI Fewer symptoms occur in same-serotype recurrent streptococcal tonsillopharyngitis SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID ACUTE RHEUMATIC-FEVER; UNITED-STATES; PHARYNGITIS; INFECTIONS; RESURGENCE; OUTBREAK; CARRIER; OHIO; AREA AB Background: Most patients with acute rheumatic fever report no antecedent pharyngitis. Objective: To determine the clinical and microbiological characteristics of recurrent group A P-hemolytic streptococcal (GABHS) tonsillopharyngitis. Design: Prospective randomized trial. Subjects: Symptoms were recorded and throat cultures were obtained at 4 to 6, 18 to 21, and 32 to 35 days following the start of treatment. A subset of 60 patients with subsequent GABHS episodes occurring were evaluated for a 0.2-or greater log rise in either antistreptolysin O or anti-deoxyribonuclease B titer to confirm a bona fide recurrence. Results: Sixteen (27%) of 60 patients had recurrent GABHS tonsillopharyngitis of the same serotype that occurred 21 days or longer following the onset of the initial GABHS infection and was associated with a 0.2- or greater log rise in either antistreptolysin O or antideoxyribonuclease B titer, indicating bona fide recurrent infection; these recurrences all occurred within 55 days. Fewer patients with recurrent GABHS pharyngitis of the same serotype had headache (P=.02), sore throat (P=.006), fever (P=.008), pharyngeal erythema (P<.001), pharyngeal edema (P<.001), pharyngeal exudate (P=.04), and adenitis (P=.03) compared with the initial episode. Chills, stomachache, scarlatina, tonsillar enlargement, and palatal petechiae were similar for both episodes. Conclusions: Fewer symptoms occur during recurrent GABHS pharyngitis of the same serotype compared with the initial infection. These patients may be less likely to seek physician attention, yet their infections put them at risk for sequelae. C1 US FDA, Div Vaccines & Related Prod Applicat, Rockville, MD 20852 USA. Univ Florida, Dept Pediat, Gainesville, FL USA. Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA. RP Lee, LH (reprint author), US FDA, Div Vaccines & Related Prod Applicat, HFM 475,Suite 370N,1401 Rockville Pike, Rockville, MD 20852 USA. NR 24 TC 11 Z9 11 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD NOV PY 2000 VL 126 IS 11 BP 1359 EP 1362 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 373HQ UT WOS:000165283600008 PM 11074833 ER PT J AU Matsui, K Riemenschneider, WK Hilbert, SL Yu, ZX Takeda, K Travis, WD Moss, J Ferrans, VJ AF Matsui, K Riemenschneider, WK Hilbert, SL Yu, ZX Takeda, K Travis, WD Moss, J Ferrans, VJ TI Hyperplasia of type II pneumocytes in pulmonary lymphangioleiomyomatosis - Immunohistochemical and electron microscopic study SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID THYROID TRANSCRIPTION FACTOR-1; KERATINOCYTE GROWTH-FACTOR; TRANSBRONCHIAL BIOPSY; MONOCLONAL-ANTIBODIES; LUNG; LYMPHANGIOMYOMATOSIS; EXPRESSION; EMPHYSEMA; DIAGNOSIS; ANTIGEN AB Background.-Little is known of the morphology of the pneumocytes lining the parenchymal cysts in lymphangioleiomyomatosis (LAM), Objective.-To evaluate the structural characteristics of the alveolar epithelial cells in LAM. Methods-Immunohistochemical and electron microscopic studies were performed on lung tissue from 22 women with pulmonary LAM. Results.-Epithelial cells that reacted with PE-10 (a mouse monoclonal antibody that recognizes the surfactant apoprotein A in type II pneumocytes) and TTF-1 tan antibody that identifies nuclear transcription factor found in type II pneumocytes) were the predominant cell type lining the surfaces of lesions of LAM and normal areas of lung. Scanning and transmission electron microscopic studies confirmed that these cells were type II pneumocytes as demonstrated by (1) apical microvilli, (2) electron-dense lamellar bodies, and (3) cytoplasmic projections that extended from the basal surfaces into the underlying connective tissue, where they made extensive contact with interstitial connective tissue cells. A few cells had morphologic characteristics of type I pneumocytes, including large flat surfaces lacking microvilli. Cells that appeared intermediate between type I and type II pneumocytes were observed occasionally. Conclusions,These observations and the reactivity of these cells with antibody to proliferating cell nuclear antigen demonstrate that extensive hyperplasia of type II pneumocytes is a major characteristic of LAM. C1 NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Ferrans, VJ (reprint author), NHLBI, Pathol Sect, NIH, Bldg 10-2N240,10 Ctr Dr MSC-1518, Bethesda, MD 20892 USA. NR 39 TC 23 Z9 24 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD NOV PY 2000 VL 124 IS 11 BP 1642 EP 1648 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 374KQ UT WOS:000165344700016 PM 11079017 ER PT J AU Zaitseva, M Lee, S Lapham, C Taffs, R King, L Romantseva, T Manischewitz, J Golding, H AF Zaitseva, M Lee, S Lapham, C Taffs, R King, L Romantseva, T Manischewitz, J Golding, H TI Interferon gamma and interleukin 6 modulate the susceptibility of macrophages to human immunodeficiency virus type 1 infection SO BLOOD LA English DT Article ID TUMOR-NECROSIS-FACTOR; CD4(+) T-CELLS; TROPIC HIV-1; SIGNAL-TRANSDUCTION; FUNCTIONAL CORECEPTOR; PRODUCTIVE INFECTION; DISEASE PROGRESSION; BETA-CHEMOKINES; IFN-GAMMA; CXCR4 AB The effect of interferon gamma (IFN-gamma) and interleukin 6 (IL-6) on infection of macrophages with human immunodeficiency virus type 1 (HIV-1) was investigated. By using a polymerase chain reaction-based viral entry assay and viral infectivity assay, it was demonstrated that IL-6 and IFN-gamma augmented susceptibility of monocyte-derived macrophages (MDMs) to infection with T-cell tropic CXCR4-utilizing (X4) HIV-I strains. Consistent with this finding, IFN-gamma and IL-6 augmented fusion of MDMs with T-tropic envelope-expressing cells. The enhanced fusion of cytokine-treated MDMs with T-tropic envelopes was inhibited by the CXCR4 ligand, SDF-1, and by T22 peptide. IFN-gamma and IL-6 did not affect expression of surface CXCR4 or SDF-1-induced Ca++ flux in MDMs, In contrast to the effect of IFN-gamma on the infection of MDMs with X4 strains, IFN-gamma inhibited viral entry and productive infection of MDMs with macrophage-tropic (M-tropic) HIV-1, Consistent with this finding, IFN-gamma induced a decrease in fusion with M-tropic envelopes that correlated with a modest reduction in surface CCR5 and CD4 on MDMs, It was further demonstrated that macrophage inflammatory protein (MIP)-1 alpha and MIP-beta secreted by cytokine-treated MDMs augmented their fusion with T-tropic-expressing cells and inhibited their fusion with M-tropic envelope-expressing cells. These data indicate that proinflammatory cytokines, which are produced during opportunistic infections or sexually transmitted diseases, may predispose macrophages to infection with X4 strains that, in turn, could accelerate disease progression. (C) 2000 by The American Society of Hematology. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Zaitseva, M (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bldg 29B,Rm 3G21, Bethesda, MD 20892 USA. NR 62 TC 36 Z9 37 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2000 VL 96 IS 9 BP 3109 EP 3117 PG 9 WC Hematology SC Hematology GA 367RA UT WOS:000090074200025 PM 11049991 ER PT J AU Brinton, LA Lubin, JH Burich, MC Colton, T Brown, SL Hoover, RN AF Brinton, LA Lubin, JH Burich, MC Colton, T Brown, SL Hoover, RN TI Breast cancer following augmentation mammoplasty (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE breast cancer; breast implants; incidence; mortality; prognosis; silicone ID IMPLANTS; WOMEN; RISK; DIAGNOSIS; CARCINOMA; SURVIVAL; SILICONE; MAMMAPLASTY; MASS AB Objective: Although clinical reports have raised concern that breast implants may either increase the risk of breast cancer or delay its diagnosis, epidemiologic studies have generally shown implant recipients to be at a reduced risk of subsequent breast cancer. A large retrospective cohort study was undertaken to clarify effects of cosmetic breast implantation. Methods: Medical records of 13,488 women receiving cosmetic implants at 18 plastic surgery practices and a group of 3936 patients who received other types of plastic surgery at the same practices were reviewed and information abstracted. Questionnaires were sent to all subjects located as alive, with 71% being completed. Attempts were made to obtain medical verification for all reported cancers and to obtain death certificates for deceased subjects. Results: A total of 136 breast cancers were observed among the breast implant patients. External analyses, using general population rates from the Surveillance, Epidemiology and End Results (SEER) program, resulted in 152.2 cases expected and a standardized incidence ratio (SIR) of 0.9 (95% CI 0.8-1.1). A comparable SIR was found for the other plastic surgery patients (SIR = 1.0, 95% CI 0.7-1.2). Internal analyses, directly comparing the implant patients with the other plastic surgery patients, showed a RR of 0.8 (95% CI 0.6-1.1). In neither the external nor internal analyses was there any systematic variation in risk by age or calendar year of initial implant. Risk also did not vary by years of follow-up or by type of implant. Risk was not affected by exclusion of patients who received their implants following surgery for benign breast disease. Although breast tumors tended to be detected at a somewhat later stage among the breast implant than the comparison patients, the difference was not statistically significant, nor was there any significant difference in breast cancer mortality between the two groups. Conclusions: Breast implants do not appear to alter the risk of subsequent breast cancer. C1 NCI, Epidemiol & Biostat Program, Bethesda, MD 20892 USA. NCI, Environm Epidemiol Branch, Bethesda, MD 20892 USA. ABT Associates Inc, Chicago, IL USA. Boston Univ, Dept Epidemiol & Biostat, Boston, MA 02215 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Brinton, LA (reprint author), NCI, Epidemiol & Biostat Program, Bethesda, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 38 TC 74 Z9 75 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 2000 VL 11 IS 9 BP 819 EP 827 DI 10.1023/A:1008941110816 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 359EB UT WOS:000089597600007 PM 11075871 ER PT J AU Fang, GC Chang, CN Wu, YS Wang, NP Wang, V Fu, PPC Yang, DG Chen, SC AF Fang, GC Chang, CN Wu, YS Wang, NP Wang, V Fu, PPC Yang, DG Chen, SC TI Comparison of particulate mass, chemical species for urban, suburban and rural areas in central Taiwan, Taichung SO CHEMOSPHERE LA English DT Article DE PM2.5; PM2.5-10; TSP; metallic element; acidic anion ID DRY DEPOSITION; AEROSOLS; PM10; AIR; NETHERLANDS; POLLUTANTS; ACIDITY; SULFATE; NITRATE; PM2.5 AB Aerosol samples for PM2.5, PM2.5-10 and TSP were collected from June to September 1998 and from February to March 1999 in central Taiwan, Ion chromatography was used to analyze the acidic anions: sulfate, nitrate and chloride in the Universal samples. The ratios of fine particle concentrations to coarse particle concentrations displayed that the fine particle concentrations are almost greater than that of coarse particle concentrations in Taichung area. The average concentrations of PM2.5, PM2.5-10 and TSP in urban sites are higher than in suburban and rural sites at both daytime and night-time. Chloride dominated in the coarse mode in daytime and in fine mode in night-time. Nitrate can be found in both the coarse and fine modes. Sulfate dominated in fine mode in both daytime and night-time, (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Hungkuang Inst Technol, Air Tox & Environm Lab, Taichung 43307, Taiwan. Tunghai Univ, Dept Environm Sci, Taichung 407, Taiwan. Hungkuang Inst Technol, Off Secretary, Taichung 433, Taiwan. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Fang, GC (reprint author), Hungkuang Inst Technol, Air Tox & Environm Lab, Taichung 43307, Taiwan. NR 17 TC 16 Z9 16 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD NOV PY 2000 VL 41 IS 9 BP 1349 EP 1359 DI 10.1016/S0045-6535(00)00003-5 PG 11 WC Environmental Sciences SC Environmental Sciences & Ecology GA 332MX UT WOS:000088079000006 PM 11057571 ER PT J AU Rosario, LA O'Brien, ML Schow, SR Henderson, CJ Wolf, CR Tew, KD AF Rosario, LA O'Brien, ML Schow, SR Henderson, CJ Wolf, CR Tew, KD TI Preclinical studies with a glutathione S-transferase P1-1 (GSTP1-1) activated prodrug. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Fox Chase Canc Ctr, Dept Pharmacol, Philadelphia, PA 19111 USA. US FDA, Rockville, MD 20857 USA. New York Med Coll, Valhalla, NY 10595 USA. Telik Inc, S San Francisco, CA USA. Univ Dundee, Imperial Canc Res Fund, Edinburgh, Midlothian, Scotland. NR 0 TC 0 Z9 0 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 NOV PY 2000 VL 6 SU S MA 114 BP 4489S EP 4489S PG 1 WC Oncology SC Oncology GA 375NW UT WOS:000165409000074 ER PT J AU Chen, ML Lee, SC Ng, MJ Schuirmann, DJ Lesko, LJ Williams, RL AF Chen, ML Lee, SC Ng, MJ Schuirmann, DJ Lesko, LJ Williams, RL TI Pharmacokinetic analysis of bioequivalence trials: Implications for sex-related issues in clinical pharmacology and biopharmaceutics SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID ASSESSING INDIVIDUAL BIOEQUIVALENCE; MENSTRUAL-CYCLE; PHARMACODYNAMICS; ELIMINATION AB Objectives: To address the questions of whether women should be included in bioequivalence trials and whether dosage adjustment may be needed in women relative to men. Methods: Sex-related analysis was conducted for 26 bioequivalence studies involving both sexes. A total of 94 data sets [47 each for the areas under the plasma concentration-time curve (AUC) and maximum concentration (C-max)] were used. ANOVA was performed. Three statistical models were used to estimate population means and intrasubject variability between sexes, as well as sex-by-formulation interactions. Comparisons mere made by use of confidence intervals, magnitude of observed differences, and statistical significance (alpha = .05). Results: With some exceptions, intrasubject variabilities were similar for men and women. In about 10% of the data sets (AUC or C-max), women had significantly higher variability. Although fewer, there were examples with higher variability in men. With a 20 percentage point difference used in the test-over-reference mean ratios between sexes as a signal of sex-by-formulation interaction, the frequency of this interaction (AUC or C-max) is similar to 13% and similar to 35%, counting by data sets and studies, respectively. Mean sex-related differences of greater than or equal to 20% in the pharmacokinetic parameters for the reference product were observed in 39% of the data sets (AUC or C-max). In similar to 28% of the data sets, these differences were statistically significant. The frequency was similar to 15% after body weight correction. Conclusions: In general, men and women have similar intrasubject variability. Where variability differs between sexes, there is a suggestion that higher variability in women may be more frequent. The data also suggest that a sex-based subject-by-formulation interaction can occur, although the frequency may be low Sex-related differences in pharmacokinetics are apparent in many drugs studied. Dosage adjustment with body weight may be warranted for drugs that exhibit a steep dose-response curve. Although exploratory, the results of this study support recommendations of the 1993 Food and Drug Administration gender guideline that women not be excluded from bioequivalence trials. (Clin Pharmacol Ther 2000;68:510-21.). C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci HFD 350, Rockville, MD 20857 USA. RP Chen, ML (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci HFD 350, 5600 Fishers Ln, Rockville, MD 20857 USA. NR 32 TC 54 Z9 57 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD NOV PY 2000 VL 68 IS 5 BP 510 EP 521 DI 10.1067/mcp.2000.111184 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 377TY UT WOS:000165543400007 PM 11103754 ER PT J AU Shamim, EA Rider, LG Miller, FW AF Shamim, EA Rider, LG Miller, FW TI Update on the genetics of the idiopathic inflammatory myopathies SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review ID INCLUSION-BODY MYOSITIS; MAJOR HISTOCOMPATIBILITY COMPLEX; PENICILLAMINE-INDUCED MYOSITIS; JUVENILE RHEUMATOID-ARTHRITIS; SYSTEMIC LUPUS-ERYTHEMATOSUS; NECROSIS-FACTOR-ALPHA; CLASS-II ALLELES; ANTIGEN PM-SCL; AUTOIMMUNE-DISEASES; IMMUNOGENETIC FEATURES AB A number of lines of investigation suggest that, as is likely the case for other autoimmune diseases, the idiopathic inflammatory myopathies (IIM) develop as a result of specific environmental exposures in genetically susceptible individuals. Current data imply that multiple genes are involved in the etiology of these complex disorders. Targeted gene studies and whole genome approaches have begun to identify several genetic risk factors for autoimmune diseases, but the rarity and heterogeneity of the IIM have limited our knowledge of their associated genes. Current findings suggest that human leukocyte antigen (HLA) genes on chromosome 6, particularly HLA DRB1*0301 and the linked allele DQA1*0501, have the strongest associations with all clinical forms of IIM in white patients. Different HLA alleles, however, may confer risk or protection for myositis in distinct ethnic, serologic, and environmental exposure groups. Non-HLA genetic risk factors, which have been documented for other autoimmune diseases, are now being identified for the IIM. These include polymorphic genes encoding immunoglobulin heavy chains (defined by serologic markers known as Gm allotypes), cytokines and their receptors, and certain proteins that accumulate in the myocyte vacuoles of inclusion body myositis patients. Selected allelic polymorphisms of interleukin-1 receptor antagonist variable number tandem repeats and genes for tumor necrosis factor alpha and interleukin-l alpha also have recently been associated with IIM. The pathogenic bases for the differences among the many clinically, pathologically and immunologically defined syndromes known as the IIM will be elucidated through a better understanding of the multiple genes that define risks for their development, as well as through investigations of gene-gene and gene-environment interactions. (C) 2000 Lippincott Williams & Wilkins. Inc. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Lab Mol & Dev Immunol, Bethesda, MD 20892 USA. RP Shamim, EA (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Lab Mol & Dev Immunol, NIH Bldg 29B,Room 2G11,HFM 561,8800 Rockville Pik, Bethesda, MD 20892 USA. OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 NR 87 TC 59 Z9 60 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD NOV PY 2000 VL 12 IS 6 BP 482 EP 491 DI 10.1097/00002281-200011000-00002 PG 10 WC Rheumatology SC Rheumatology GA 367GW UT WOS:000090054200002 PM 11092196 ER PT J AU Banfalvi, G Littlefield, N Hass, B Mikhailova, M Csuka, I Szepessy, E Chou, MW AF Banfalvi, G Littlefield, N Hass, B Mikhailova, M Csuka, I Szepessy, E Chou, MW TI Effect of cadmium on the relationship between replicative and repair DNA synthesis in synchronized CHO cells SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE 8-oxodeoxyguanosine; elutriation; permeable cells; strand breaks; synchronization ID OXIDATIVE DAMAGE; CYCLE; CARCINOGENESIS; ANTIOXIDANTS; CHECKPOINTS; APOPTOSIS; OXYGEN AB Repair and replicative DNA synthesis were measured at different stages of the cell cycle in control and cadmium-treated Chinese hamster ovary (CHO-K1) cells. Cells were synchronized by counterflow centrifugal elutriation. Elutriation resulted in five repair and four replication subphases. On Cd treatment, repair synthesis was elevated in certain subphases. Replicative subphases were suppressed by Cd treatment, with some of the peaks almost invisible. The number of spontaneous strand breaks measured by random oligonucleotide primed synthesis assay showed a cell-cycle-dependent fluctuation in control cells and was greatly increased after Cd treatment throughout the S phase. Elevated levels of the oxidative DNA damage product, 8-oxodeoxyguanosine, were observed after Cd treatment, with the highest level in early S phase, which gradually declined as damaged cells progressed through the cell cycle. C1 Semmelweis Univ, Sch Med, Dept Med Chem Mol Biol & Pathobiochem, Budapest, Hungary. Univ Debrecen, Dept Anim Anat & Physiol, Debrecen, Hungary. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Banfalvi, G (reprint author), Univ Debrecen, Dept Anim Physiol, 1 Egyet Ter, H-4010 Debrecen, Hungary. EM bgaspar@delfin.klte.hu NR 28 TC 18 Z9 21 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD NOV PY 2000 VL 267 IS 22 BP 6580 EP 6585 DI 10.1046/j.1432-1327.2000.01751.x PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 376KK UT WOS:000165456600008 PM 11054109 ER PT J AU Goldstein, JS Chen, T Gubina, E Pastor, RW Kozlowski, S AF Goldstein, JS Chen, T Gubina, E Pastor, RW Kozlowski, S TI ICAM-1 enhances MHC-peptide activation of CD8(+) T cells without an organized immunological synapse SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE T lymphocyte; adhesion molecule; MHC; cellular activation ID FUNCTION-ASSOCIATED ANTIGEN-1; CLASS-I; ADHESION MOLECULE-1; RECEPTOR; CD4(+); COSTIMULATION; SPECIFICITY; COMPLEXES; AFFINITY; LFA-1 AB In addition to the TCR-ligand interaction, other receptor-ligand pairs, such as LFA-1 and ICAM-1, play a major role in the activation of T cells. Recent studies of T cell activation suggest a coordinated movement of LFA-1 and ICAM-1 in forming a defined zone in the immunological synapse. It is unclear from these studies whether the organized molecular geometry of the immunological synapse is necessary for ICAM-1 enhancement of T cell activation. In this report, we demonstrate that ICAM-1 can enhance the activation of CD8(+) T cells by MHC-peptide in the absence of an organized immunologic synapse. Therefore, although the molecular organization of the immunologic synapse may amplify stimuli, it is not an absolute requirement for either CD8(+) T cell activation or the ICAIW-1 enhancement of TCR activation. C1 US FDA, Div Monoclonal Ab, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Bacterial & Allergen Prod & Parasitol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Kozlowski, S (reprint author), US FDA, Div Monoclonal Ab, Ctr Biol Evaluat & Res, 8800 Rockville Pike,Bldg 29B-3NN08,HFM-561, Bethesda, MD 20892 USA. NR 21 TC 9 Z9 9 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 2000 VL 30 IS 11 BP 3266 EP 3270 DI 10.1002/1521-4141(200011)30:11<3266::AID-IMMU3266>3.0.CO;2-F PG 5 WC Immunology SC Immunology GA 372UU UT WOS:000165253100023 PM 11093142 ER PT J AU Fritsche, J Fritsche, S Solomon, MB Mossoba, MM Yurawecz, MP Morehouse, K Ku, Y AF Fritsche, J Fritsche, S Solomon, MB Mossoba, MM Yurawecz, MP Morehouse, K Ku, Y TI Quantitative determination of conjugated linoleic acid isomers in beef fat SO EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY LA English DT Article DE conjugated linoleic acid; Ag+-HPLC; GC; beef; CLA ID PERFORMANCE LIQUID-CHROMATOGRAPHY; METHYL-ESTERS; ADIPOSE-TISSUE; MILK; SEPARATION; FOODS; CLA AB The amounts of 14 conjugated linoleic acid (CLA) isomers (t12t14, t11t13, t10t12, t9t11, t8t10, t7t9, t6t8; 12,14 c/t, t11c13, c11t13, t10c12, 9,11 c/t, t8c10, t7c9-18:2) in 20 beef samples were determined by triple-column silver-ion high-performance liquid chromatography (Ag+-HPLC). Quantitation was performed using an external CLA reference standard consisting of cis9, trans11-18:2, trans9, trans11-18:2 and cis9,cis11-18:2. Linearity was checked as being r > 0.9999 between 0.02 x 10(-3) to 2 mg/ml. The determination limit (5-fold signal/noise ratio) of the CLA reference was estimated to be 0.25, 0.50, 1.0 ng/injection for the cis/trans, trans,trans and cis,cis isomers, respectively. As expected, cis9,trans11-18:2 was the predominant isomer (1.95 +/- 0.54 mg/g fat) in beef, followed by trans7,cis9-18:2 (0.19 +/- 0.04 mg/g fat); cis,cis isomers were below the determination limit in most beef samples. Total CLA amounts determined by Ag+-HPLC were compared to total CLAs determined by gas chromatography (GC, 100 m CPSil(TM) 88 column). The amounts obtained by GC were generally higher than those determined by Ag+-HPLC due to co-eluting compounds. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Food Labeling, Washington, DC 20204 USA. ARS, USDA, Beltsville Agr Res Ctr, Meat Sci Res Lab, Beltsville, MD USA. RP Fritsche, J (reprint author), Unilever Res Labs Vlaardingen, Oil Based Prod Technol, Olivier van Noortlaan 120, NL-3133 AT Vlaardingen, Netherlands. NR 29 TC 66 Z9 69 U1 1 U2 6 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 1438-7697 J9 EUR J LIPID SCI TECH JI Eur. J. Lipid Sci. Technol. PD NOV PY 2000 VL 102 IS 11 BP 667 EP 672 DI 10.1002/1438-9312(200011)102:11<667::AID-EJLT667>3.3.CO;2-E PG 6 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 378AD UT WOS:000165558100002 ER PT J AU Bash, MC Lynn, F Concepcion, NF Tappero, JW Carlone, GM Frasch, CE AF Bash, MC Lynn, F Concepcion, NF Tappero, JW Carlone, GM Frasch, CE TI Genetic and immunologic characterization of a novel serotype 4, 15 strain of Neisseria meningitidis SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE Neisseria meningitidis; porin; genotype; meningococcal vaccine ID OUTER-MEMBRANE PROTEIN; B MENINGOCOCCAL DISEASE; VESICLE VACCINE; MOLECULAR VARIATION; VARIABLE REGIONS; ANTIBODY-BINDING; SAO-PAULO; PORA; IMMUNOGENICITY; SPECIFICITY AB The porin proteins of Neisseria meningitidis are important components of outer membrane protein (OMP) vaccines. The class 3 porin gene, porB, of a novel serogroup B, serotype 3, 15 isolate from Chile (Ch501) was found to be VR1-4, VR2-15, VR3-15 and VR4-15 by pol B variable region (VR) typing. Rabbit immunization studies using outer membrane vesicles revealed immunodominance of individual PorB (class 3) VR epitopes, The predominant anti-Ch501 PorB response was directed to the VRI epitope. Anti-PorB VR1 mediated killing was suggested by the bactericidal activity of Ch501 anti-sera against a type 4 strain not expressing PorA or class 5 OMPs. Studies that examine the molecular epidemiology of individual porB VRs, and the immune responses to PorB epitopes, may contribute co the development of broadly protective group B meningococcal vaccines. (C) 2000 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. C1 Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Div Bacterial Parasit & Allergen Prod, Rockville, MD 20852 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Bacterial & Mycot Dis, Meningitis & Special Pathogen Branch, Atlanta, GA USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Bacterial & Mycot Dis, Resp Dis Branch, Atlanta, GA USA. RP Bash, MC (reprint author), Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Div Bacterial Parasit & Allergen Prod, HFM-428,1401 Rockville Pike, Rockville, MD 20852 USA. NR 40 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD NOV PY 2000 VL 29 IS 3 BP 169 EP 176 DI 10.1016/S0928-8244(00)00201-7 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 374BZ UT WOS:000165325700001 PM 11064262 ER PT J AU Hur, HG Rafii, F AF Hur, HG Rafii, F TI Biotransformation of the isoflavonoids biochanin A, formononetin, and glycitein by Eubacterium limosum SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE O-demethylation; phytoestrogen; isoflavonoid; anaerobic bacterium; Eubacterium limosum ID NATURALLY-OCCURRING ESTROGENS; METHOXYLATED AROMATIC-ACIDS; DIETARY PHYTOESTROGENS; O-DEMETHYLATION; CANCER RISK; METABOLISM; BACTERIA; GROWTH; PHENYLMETHYLETHERS; ATHEROSCLEROSIS AB Eubacterium limosum (ATCC 8486), a strict anaerobe from the human intestinal tract that is capable of O-demethylation of several compounds, was tested for the ability to metabolize three methoxylated isoflavonoids, biochanin A, formononetin, and glycitein. Highperformance liquid chromatography elution profiles of metabolites produced from biochanin A, formononetin, and glycitein showed peaks that had identical retention times to authentic genistein, daidzein, and 6,7,4'-trihydroxyisoflavone, respectively. The metabolites were identified, using an on line liquid chromatography-electrospray mass spectrometer. E. limosum produced 61.4 muM of genistein and 13.2 muM of daidzein from 100 muM of biochanin A and formononetin, after 26 days incubation. O-demethylase activity is cell-associated and was not detected in the extracellular fraction of bacterial culture. This is the first study in which conversion of biochanin A, and formononetin to more potent phytoestrogens by a bacterium has been shown. (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. Seoul Natl Univ, Sch Agr Biotechnol, Suwon, South Korea. RP Rafii, F (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 36 TC 72 Z9 79 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD NOV 1 PY 2000 VL 192 IS 1 BP 21 EP 25 DI 10.1111/j.1574-6968.2000.tb09353.x PG 5 WC Microbiology SC Microbiology GA 367DV UT WOS:000090047200004 PM 11040423 ER PT J AU Ross, IA Johnson, W Sapienza, PP Kim, CS AF Ross, IA Johnson, W Sapienza, PP Kim, CS TI Effects of the seafood toxin domoic acid on glutamate uptake by rat astrocytes SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-Neuroscience CY OCT 25-30, 1997 CL NEW ORLEANS, LOUISIANA SP Soc Neurosci DE domoic acid; neurotoxicity; glutamate; astrocytes ID NMDA RECEPTOR ACTIVATION; HIGH AFFINITY UPTAKE; ASPARTIC-ACID; AMINO-ACIDS; CULTURED ASTROCYTES; NMR-SPECTROSCOPY; NERVOUS-SYSTEM; SPINAL-CORD; C-13 NMR; NEURONS AB Pronounced glutamic acid uptake was observed after only 15 min with glutamate concentrations of 60 nmol/mg protein when astrocytes were incubated with 1 mM glutamic acid. The uptake increased with time to a steady-state glutamate level of above 160 nmol/mg protein by 45 min. The uptake was energy dependent. Reduced temperature (0 degreesC) and ouabain (100 muM) inhibited uptake by 86.7% (P < 0.001; n = 18) and 84.4% (P < 0.001; n = 18), respectively, when compared with controls. After exposure of astrocytes to glutamate (1 mM) in the incubation medium, in the presence of domoic acid (10 and 100 muM) at 5 and 60 min, domoic acid (10 muM) elevated glutamate uptake by 64.0% (P < 0.05; n = 34) at 5 min but decreased glutamate uptake by 47.8% (P < 0.01; n = 19) at 60 min compared with controls. ri higher dose of domoic acid (100 muM) decreased glutamate uptake by 49.6% (P < 0.01; n = 20) and 61.3% (P < 0.001; n = 20) at 5 and 60 min, respectively, compared with controls. This study suggests that domoic acid may induce neurotoxicity because of the failure of astrocytes to remove extracellular glutamate. This may contribute to excitotoxic injury. Published by Elsevier Science Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Toxicol Res, Washington, DC 20204 USA. RP Kim, CS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Toxicol Res, HFS-506, Washington, DC 20204 USA. NR 48 TC 11 Z9 14 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD NOV PY 2000 VL 38 IS 11 BP 1005 EP 1011 DI 10.1016/S0278-6915(00)00083-1 PG 7 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 369JB UT WOS:000165061200007 PM 11038238 ER PT J AU Waynant, RW Ilev, IK AF Waynant, RW Ilev, IK TI Toward practical coherent X-ray sources: Potential medical applications SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article DE compton scattering; free electron lasers; frequency conversion; gamma ray lasers; hard X-rays; harmonic generation; medical applications; monochromatic X-rays; X-ray; X-ray applications; X-ray lasers ID LASER; PULSES AB This paper looks at several methods of producing coherent monochromatic X-rays for medical applications and evaluates their current progress and potential for becoming practical medical devices. C1 US FDA, Rockville, MD 20857 USA. RP Waynant, RW (reprint author), US FDA, Rockville, MD 20857 USA. NR 12 TC 3 Z9 3 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD NOV-DEC PY 2000 VL 6 IS 6 BP 1465 EP 1469 DI 10.1109/2944.902202 PG 5 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 407MP UT WOS:000167275600072 ER PT J AU Caputa, K Stuchly, MA Skopec, M Bassen, HI Ruggera, P Kanda, M AF Caputa, K Stuchly, MA Skopec, M Bassen, HI Ruggera, P Kanda, M TI Evaluation of electromagnetic interference from a cellular telephone with a hearing aid SO IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES LA English DT Article DE cellular telephone; EMI; hearing aid AB In a collaborative effort, electromagnetic interference (EMI) is evaluated from a global system For mobile communication telephone with one model of a hearing aid used in the ear canal. Since the electromagnetic fields cannot be measured in the ear canal, a reliable method of their modeling with the finite-difference time-domain method is established. Very good agreement has been achieved between the measured and computed electric and magnetic fields in free space in very close proximity to the telephone, Subsequently, electric and magnetic fields in the ear canal are computed for two models of the ear, and three positions of the telephone. The computed fields are compared with the acoustic measurements for a small number of humans subjected to the EMI test. C1 Univ Victoria, Dept Elect & Comp Engn, Victoria, BC V8W 3P6, Canada. US FDA, Rockville, MD 20852 USA. RP Caputa, K (reprint author), Univ Victoria, Dept Elect & Comp Engn, Victoria, BC V8W 3P6, Canada. NR 10 TC 14 Z9 14 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0018-9480 J9 IEEE T MICROW THEORY JI IEEE Trans. Microw. Theory Tech. PD NOV PY 2000 VL 48 IS 11 BP 2148 EP 2154 PN 2 PG 7 WC Engineering, Electrical & Electronic SC Engineering GA 375GE UT WOS:000165390500023 ER PT J AU Harris, GR Preston, RC DeReggi, AS AF Harris, GR Preston, RC DeReggi, AS TI The impact of piezoelectric PVDF on medical ultrasound exposure measurements, standards, and regulations SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Review ID MEMBRANE HYDROPHONE PERFORMANCE; SHOCK-WAVE LITHOTRIPTER; POLYMER FILM HYDROPHONE; BROAD-BAND PIEZO; POLARIZATION DISTRIBUTION; POLYVINYLIDENE FLUORIDE; PRESSURE DETERMINATION; DIAGNOSTIC ULTRASOUND; FREQUENCY-RESPONSE; ACOUSTIC FIELDS AB This paper describes the development of PVDF hydrophones for characterizing medical ultrasound fields. The polymer hydrophone approaches that have re suited from this work are discussed, with emphasis given to the spot-poled membrane design that has become the de facto reference device for these measurements. The various national and international standards and regulations that have followed from the successful use of PVDF hydrophones also are summarized. The works discussed encompass polymer-based hydrophones designed primarily for diagnostic and lithotripsy exposure measurements, both in water and in vivo. The advent of these hydrophones has made possible accurate and reliable measurements of exposure levels encountered in medical ultrasound and, thus, has allowed questions of ultrasound bioeffects and device safety to be addressed in a consistent and scientifically sound manner. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. Natl Phys Lab, Ctr Mech & Acoust Metrol, Teddington TW11 0LW, Middx, England. Natl Inst Stand & Technol, Div Polymers, Gaithersburg, MD 20899 USA. RP Harris, GR (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NR 188 TC 25 Z9 26 U1 4 U2 22 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 NOV PY 2000 VL 47 IS 6 BP 1321 EP 1335 DI 10.1109/58.883521 PG 15 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 371HE UT WOS:000165172200008 PM 18238678 ER PT J AU Brown, EW Davis, RM Gouk, C van der Zwet, T AF Brown, EW Davis, RM Gouk, C van der Zwet, T TI Phylogenetic relationships of necrogenic Erwinia and Brenneria species as revealed by glyceraldehyde-3-phosphate dehydrogenase gene sequences SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article DE Erwinia; Brenneria; gapDH; molecular evolution; differentiation; phylogeny ID BACTERIA; ENTEROBACTERIACEAE; EVOLUTION AB Recent examination of the relationships of the dry necrosis-inducing (necrogenic) erwinias using 16S rDNA sequences demonstrated that these bacteria comprise a polyphyletic group and, therefore, have been subdivided into three distinct genera, Erwinia, Brenneria and Pectobacterium, with the classical 'amylovora' group species now being distributed nearly evenly among the first two. To further assess the molecular evolutionary relationships between current necrogenic Erwinia and Brenneria species, as well as between these genera and the exclusively soft-rotting genus Pectobacterium, the glyceraldehyde-3-phosphate dehydrogenase (gapDH) genes from 57 Erwinia and Brenneria isolates along with Pectobacterium type strains were PCR-amplified, sequenced and subjected to phylogenetic analysis. Pairwise alignments of cloned gapDH genes revealed remarkably high interspecies genetic diversity among necrogenic isolates, Four evolutionary clades of necrogenic species were described that assorted more closely to known soft-rotting species than to each other. Interclade comparisons of gapDH nucleotide sequences revealed as much genetic divergence between these four necrogenic clades as existed between necrogenic and soft-rotting clades, An examination of the phylogenetic utility of the gapDH gene in light of current 16S rDNA clustering of these species revealed varying levels of taxonomic congruence between these genes for the structure of Erwinia, Brenneria and Pectobacterium. These analyses suggest that, while gapDH possesses sufficient genetic variation to fully differentiate Erwinia and Brenneria species, the gene may not accurately reflect interspecies taxonomic relatedness among all three phytopathogenic genera. C1 Loyola Univ, Dept Biol Sci, Chicago, IL 60626 USA. HortRes, Ruakura Res Ctr, Hamilton, New Zealand. ARS, USDA, Appalachian Fruit Res Ctr, Kearneysville, WV 25430 USA. RP Brown, EW (reprint author), US FDA, Mol Biol Branch, DMBRE OPA, Ctr Food Safety & Appl Nutr, Mailstop HFS-237,200 C St SW, Washington, DC 20204 USA. NR 47 TC 32 Z9 34 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AE, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD NOV PY 2000 VL 50 BP 2057 EP 2068 PN 6 PG 12 WC Microbiology SC Microbiology GA 388BC UT WOS:000166156700013 PM 11155980 ER PT J AU Pazdur, R AF Pazdur, R TI Introduction SO INVESTIGATIONAL NEW DRUGS LA English DT Editorial Material C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. RP Pazdur, R (reprint author), US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, 1451 Rockville Pike, Rockville, MD 20852 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD NOV PY 2000 VL 18 IS 4 BP 297 EP 298 DI 10.1023/A:1006442324310 PG 2 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 354UT UT WOS:000089348600001 ER PT J AU Henney, JE AF Henney, JE TI New drug for HIV infection SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Rockville, MD 20857 USA. RP Henney, JE (reprint author), US FDA, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 3 Z9 3 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 NOV 1 PY 2000 VL 284 IS 17 BP 2178 EP 2178 DI 10.1001/jama.284.17.2178 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 367GD UT WOS:000090052600006 PM 11056574 ER PT J AU Henney, JE AF Henney, JE TI New treatment for leukemia SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Rockville, MD 20857 USA. RP Henney, JE (reprint author), US FDA, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 3 Z9 3 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 NOV 1 PY 2000 VL 284 IS 17 BP 2178 EP 2178 DI 10.1001/jama.284.17.2178 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 367GD UT WOS:000090052600007 PM 11056574 ER PT J AU Henney, JE AF Henney, JE TI Clarification on buprenorphine SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Rockville, MD 20857 USA. RP Henney, JE (reprint author), US FDA, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 3 Z9 3 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 NOV 1 PY 2000 VL 284 IS 17 BP 2178 EP 2178 DI 10.1001/jama.284.17.2178 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 367GD UT WOS:000090052600005 PM 11056574 ER PT J AU Honig, P Phillips, J Woodcock, J AF Honig, P Phillips, J Woodcock, J TI How many deaths are due to medical errors? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID HOSPITALIZED-PATIENTS; ADVERSE EVENTS C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Honig, P (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 5 TC 9 Z9 9 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 NOV 1 PY 2000 VL 284 IS 17 BP 2187 EP 2188 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 367GD UT WOS:000090052600021 PM 11056584 ER PT J AU Henney, JE AF Henney, JE TI Challenges in regulating direct-to-consumer advertising SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article C1 US FDA, Washington, DC 20204 USA. RP Henney, JE (reprint author), US FDA, Washington, DC 20204 USA. NR 6 TC 7 Z9 7 U1 1 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 NOV 1 PY 2000 VL 284 IS 17 BP 2242 EP 2242 DI 10.1001/jama.284.17.2242 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 367GD UT WOS:000090052600037 PM 11056601 ER PT J AU Bulterys, M Burchett, SK Culnane, M Cunningham-Schrader, B Dominguez, K Dunkle, L Draper, L Fowler, MG Hanson, C Kpamegan, E Lindegren, ML Martin-Carpenter, L McIntosh, K McNamara, J McSherry, G Mitchell, WG Mofenson, LM Oleske, JM Rhodes, P Shapiro, DE Smith, ME Styrt, B AF Bulterys, M Burchett, SK Culnane, M Cunningham-Schrader, B Dominguez, K Dunkle, L Draper, L Fowler, MG Hanson, C Kpamegan, E Lindegren, ML Martin-Carpenter, L McIntosh, K McNamara, J McSherry, G Mitchell, WG Mofenson, LM Oleske, JM Rhodes, P Shapiro, DE Smith, ME Styrt, B CA Perinatal Safety Review Working Gr TI Nucleoside exposure in the children of HIV-infected women receiving antiretroviral drugs: Absence of clear evidence for mitochondrial disease in children who died before 5 years of age in five United States cohorts SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; mothers; infants; mitochondrial dysfunction; antiretroviral drugs ID INFANT-DEATH-SYNDROME; PERINATAL TRANSMISSION; ZIDOVUDINE TREATMENT; MUSCLE MITOCHONDRIA; LACTIC-ACIDOSIS; RISK-FACTORS; TOXICITY; ANALOGS; SKELETAL; IMPACT AB Background: Nucleoside reverse transcriptase inhibitors (NRTIs) have been associated with mitochondrial toxicity in individuals receiving treatment. A report of two deaths in Europe attributed to mitochondrial dysfunction in HIV-uninfected infants with perinatal NRTI exposure prompted a review of five U.S. cohorts. Methods: Deaths in HIV-exposed children <60 months of age and HIV-uninfected or indeterminate were reviewed. Review included birth history; perinatal antiretroviral drug exposure; hospital, laboratory, and clinic records; death reports; autopsy results; and local physician queries. Deaths were classified as unrelated (Class 1), unlikely related (Class 2), possibly related (Class 3), or highly suggestive or proven relationship (Class 4), to mitochondrial dysfunction; sudden infant death syndrome (SIDS) was categorized separately. Results and Conclusions: Among over 20,000 children of HIV-infected women, over half of whom had been exposed to NRTIs, 223 died. In HIV-uninfected children, 26 deaths were attributed to Class 1, and 4 were attributed to SIDS. In HIV-indeterminate children, 141, 10, 3, and 0 were Classes 1, 2, 3, and 4, respectively; 33 were due to SIDS and 6 could not be classified. There was no indication that antiretroviral exposure was associated with Class 2 or 3 deaths, or deaths from SIDS. A. search for mitochondrial dysfunction among living children in these cohorts is ongoing. C1 Harvard Univ, Childrens Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA. US Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Epidemiol Branch, Atlanta, GA USA. NIAID, Div Aids, Pediat Med Branch, NIH, Bethesda, MD 20892 USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. Bristol Myers Squibb Co, Pharmaceut Res Inst, Wallingford, CT 06492 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Clin Trials & Surveys Corp, Baltimore, MD USA. CDC, Div HIV AIDS Prevent Surveillance & Epidemiol, Surveillance Branch, Atlanta, GA 30333 USA. Glaxo Wellcome Res & Dev Ltd, Res Triangle Pk, NC USA. Univ Med & Dent New Jersey, Sch Med, Dept Pediat, Newark, NJ 07103 USA. Univ So Calif, Sch Med, Keck Sch Med, Los Angeles, CA USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. NICHHD, Pediat Adolescent & Mat AIDS Branch, NIH, Bethesda, MD 20892 USA. CDC, Div HIV AIDS Prevent, Stat & Data Management Branch, Atlanta, GA 30333 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. US FDA, CDER, Div Antiviral Drug Prod, Rockville, MD 20857 USA. RP McIntosh, K (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Div Infect Dis, Enders 609,300 Longwood Ave, Boston, MA 02115 USA. RI Oleske, James/C-1951-2016; OI Oleske, James/0000-0003-2305-5605; Mofenson, Lynne/0000-0002-2818-9808 NR 36 TC 86 Z9 88 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD NOV 1 PY 2000 VL 25 IS 3 BP 261 EP 268 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 381DE UT WOS:000165746400008 ER PT J AU Rodriguez-Saona, LE Fry, FS Calvey, EM AF Rodriguez-Saona, LE Fry, FS Calvey, EM TI Use of Fourier transform near-infrared reflectance spectroscopy for rapid quantification of castor bean meal in a selection of flour-based products SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE FT-NIR spectroscopy; food contaminants; castor bean meal ID MULTIPLICATIVE SCATTER CORRECTION; TOTAL DIETARY FIBER; CALIBRATION METHODS; BICINCHONINIC ACID; NIR SPECTROSCOPY; CEREAL PRODUCTS; PROTEIN; SPECTRA; RICIN; IDENTIFICATION AB Methodology was developed and evaluated for the rapid detection of castor bean meal (CBM) containing the toxic protein ricin by using Fourier transform near-infrared (FT-NIR) spectroscopy and multivariate techniques. The method is intended to be a prototype to develop a more general approach to detect food tampering. Measurements were made on an FT-NIR system using a diffuse reflection-integrating sphere. Flours spiked with caffeine, crystalline sugar, and corn meal, 1-20% w/w, were used as test articles to evaluate the methodologies. Food matrices (bleached flour, wheat flour, and blueberry pancake mix) spiked with CBM (0.5-8% w/w) were analyzed. Multiplicative scatter correction transformed partial least-squares regression models, using a specific NIR spectral region, predicted CBM contamination in foods with a standard error of cross-validation of <0.6% and a coefficient of determination (R-2) of 94%. Models discriminated between flour samples contaminated with CBM and other protein sources (egg white, soybean meal, tofu, and infant formula). CBM had loading spectra with bands characteristic of amide groups (4880 and 4555 cm(-1)) and lipids (5800, 5685, 4340, and 4261 cm(-1)). C1 US FDA, Washington, DC 20204 USA. Univ Maryland, Dept Chem, JIFSAN, Washington, DC 20204 USA. RP Calvey, EM (reprint author), US FDA, 200 C St SW, Washington, DC 20204 USA. RI Rodriguez-Saona, Luis/A-8557-2013 NR 51 TC 13 Z9 15 U1 2 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD NOV PY 2000 VL 48 IS 11 BP 5169 EP 5177 DI 10.1021/jf000604m PG 9 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 377AP UT WOS:000165490000012 PM 11087454 ER PT J AU Schneider, MJ Donoghue, DJ AF Schneider, MJ Donoghue, DJ TI Multiresidue determination of fluoroquinolones in eggs SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; RESIDUES; HPLC; ENROFLOXACIN; COMBINATION; DIALYSIS; MILK AB A multiresidue method was developed for the determination of fluoroquinolones in eggs. Extraction of eggs with ammoniacal acetonitrile was followed by liquid-liquid defatting, solvent evaporation, and redissolution in a small volume of buffer. The fluoroquinolones were further purified by on-line microdialysis, concentrated on a trace enrichment column, and separated by reversed-phase liquid chromatography with fluorescence detection. Norfloxacin (NOR), ciprofloxacin (CIP), and sarafloxacin (SAR) were extracted from fortified eggs over a range of 2-200 mug/kg, with recoveries of 65.7-78.9%, 65.6-77.1%, and 67.6-110%, respectively. Enrofloxacin (ENRO) was extracted over a range of 1-100 mug/kg, with recoveries of 71.5-86.7%, whereas desethylene ciprofloxacin (DCIP) and danofloxacin (DANO) were extracted over a range of 0.2-20 mug/kg, with recoveries of 68.7-90.7% and 76.0-93.8%, respectively. The limits of quantitation for the 6 fluoroquinolones were as follows: DCIP and DaNO, 0.3 mug/kg; ENRO, 1 mug/kg; NOR and CIP, 2 mug/kg; and SAR, 3 mug/kg. Both SAR and ENRO incurred eggs were also successfully analyzed using this method. C1 ARS, USDA, Eastern Reg Res Ctr, Wyndmoor, PA 19038 USA. US FDA, Ctr Vet Med, Div Anim Res, Laurel, MD 20708 USA. RP Schneider, MJ (reprint author), ARS, USDA, Eastern Reg Res Ctr, 600 E Mermaid Ln, Wyndmoor, PA 19038 USA. NR 12 TC 23 Z9 24 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 NOV-DEC PY 2000 VL 83 IS 6 BP 1306 EP 1312 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 379BF UT WOS:000165620500003 PM 11128131 ER PT J AU Ware, GM Price, G Carter, L Eitenmiller, RR AF Ware, GM Price, G Carter, L Eitenmiller, RR TI Liquid chromatographic preparative method for isolating ergot alkaloids, using a particle-loaded membrane extracting disk SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID WHEAT AB A liquid chromatographic method is described for the determination of ergot alkaloids in wheat. Ergonovine, ergotamine, ergocornine, alpha -ergocryptine, and ergocristine are extracted from wheat with methanol-0.25% concentrated H3PO4 (40 + 60) pH 2.2, cleaned up by using a solid-phase extraction (SPE) disk, and separated by reversed-phase liquid chromatography with fluorescence detection. Ergot alkaloids are basic compounds that form water-soluble salts in acidic aqueous solution. Because ergot alkaloid salts are positively charged, they can be easily and selectively trapped on a negatively charged strong cation-exchange SPE disk. A strong wash solvent, methanol-0.25% concentrated H3PO4 (40 + 60) was used to remove matrix Interferences not bonded by ionic interactions with the cation-exchange column, The ergot alkaloids were eluted from the ion-exchange column by adjusting the pH of the elution solvents to slightly basic conditions (pH 9). The SPE disk concentrated and cleanly separated the ergot alkaloids from matrix interferences. Standard calibration curves for ergot alkaloids for the concentration range 0.1-2.0 mug/mL were linear. The SPE disk had a column capacity equivalent to about 1 g extracted wheat. At spiking levels of 2.3-46 ng/g for ergonovine and 20-400 ng/g for ergotamine, ergocornine, alpha -ergocryptine, and ergocristine, the mean recovery was 88.1% with a coefficient of variation (CV) of 5.33%. The recovery data ranged from 79.1 to 95.9%. Ergonovine had the lowest overall recovery and the largest CV. The method has an estimated reliable limit of detection and limit of quantitation of <5 and <20 ng/g, respectively, for each ergot alkaloid tested. C1 US FDA, SE Reg Lab, Atlanta, GA 30309 USA. Univ Georgia, Dept Food Sci & Technol, Athens, GA 30602 USA. RP Ware, GM (reprint author), US FDA, SE Reg Lab, 60 8th St, Atlanta, GA 30309 USA. NR 10 TC 18 Z9 19 U1 3 U2 4 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2000 VL 83 IS 6 BP 1395 EP 1399 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 379BF UT WOS:000165620500015 PM 11128143 ER PT J AU Sagripanti, JL Bonifacino, A AF Sagripanti, JL Bonifacino, A TI Resistance of Pseudomonas aeruginosa to liquid disinfectants on contaminated surfaces before formation of biofilms SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID CHEMICAL GERMICIDES; OUTBREAK; SPORES AB A comparison was made of the effectiveness of popular disinfectants (Cavicide, Cidexplus, Clorox, Exspor, Lysol, Renalin, and Wavicide) under conditions prescribed for disinfection in the respective product labels on Pseudomonas aeruginosa either in suspension or deposited onto surfaces of metallic or polymeric plastic devices. The testing also included 7 nonformulated germicidal agents (glutaraldehyde, formaldehyde, peracetic acid, hydrogen peroxide, sodium hypochlorite, phenol, and cupric ascorbate) commonly used in disinfection and decontamination. Results showed that P. aeruginosa is on average 300-fold more resistant when present on contaminated surfaces than in suspension. This increase in resistance agrees with results reported in studies of biofilms, but unexpectedly, it precedes biofilm formation. The surface to which bacteria are attached can influence the effectiveness of disinfectants. Viable bacteria attached to devices may require dislodging through more than a one-step method for detection. The data, obtained with a sensitive and quantitative test, suggest that disinfectants are less effective on contaminated surfaces than generally acknowledged. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Div Life Sci,Mol Biol Branch HF2 113, Rockville, MD 20852 USA. RP Sagripanti, JL (reprint author), USA, SBCCOM, AMSSB, RRT, 5183 Blackhawk Rd, Aberdeen Proving Ground, MD 21010 USA. NR 29 TC 25 Z9 26 U1 1 U2 10 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2000 VL 83 IS 6 BP 1415 EP 1422 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 379BF UT WOS:000165620500018 PM 11128146 ER PT J AU Blodgett, RJ Hitchins, AD AF Blodgett, RJ Hitchins, AD TI Evaluating presence/absence of target microbes in microbiological tests SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LISTERIA-MONOCYTOGENES; DAIRY-PRODUCTS; IMMUNOASSAY; FOODS; SEAFOODS; MEATS AB A typical qualitative microbiological method performance (collaborative) study gathers a data set of responses about a test for the presence or absence of a target microbe. We developed 2 models that estimate false-positive and false-negative rates. One model assumes a constant probability that the tests will indicate the target microbe is present for any positive concentration in the test portion. The other model assumes that this probability follows a logistic curve. Test results from several method performance studies illustrate these estimates. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Blodgett, RJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 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 NOV-DEC PY 2000 VL 83 IS 6 BP 1429 EP 1433 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 379BF UT WOS:000165620500020 PM 11128148 ER PT J AU Beger, RD Freeman, JP Lay, JO Wilkes, JG Miller, DW AF Beger, RD Freeman, JP Lay, JO Wilkes, JG Miller, DW TI Producing C-13 NMR, infrared absorption, and electron ionization mass spectrometric data models of the monodechlorination of chlorobenzenes, chlorophenols, and chloroanilines SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article ID ANAEROBIC ESTUARINE SEDIMENT; AUTOMATED STRUCTURE EVALUATION; MOLECULAR-FIELD ANALYSIS; CHEMICAL-SHIFTS; CHROMATOGRAPHIC RETENTION; ORGANIC-MOLECULES; 3D STRUCTURE; DECHLORINATION; PREDICTION; SPECTRA AB We have developed four spectroscopic data-activity relationship (SDAR) models of monodechlorination of 32 chlorinated benzene compounds-in anaerobic estuarine sediment. The SDAR models were based on combinations-of C-13 nuclear magnetic resonance (NMR),infrared-absorption (IR), and electron ionization mass spectrometric (EI:MS) data. The SDAR models segregated the 32 compounds into 17 readily monodechlorinated compounds and 15 not readily monodechlorinated compounds. The SDAR model-based on C-13 NMR, IR; and EI MS data gave a leave-one-out cross-validation of 93.8%. The SDAR model based on a composite of C-13 NMR and IR data gave a leave-one-out cross-validation of 90.6%. The SDAR model based on a composite of IR and Fl MS data gave a leave-one-out cross-validation of 84.4%. The SDAR model based on a composite of C-13 NMR and BI MS data gave a leave-one-out cross-validation of 84.4%. These reliable SDAR models provide a rapid and simple way to predict whether a chlorinated benzene compound will readily go through monodechlorination. The FDA has filed a patent application on methods of using any combination of spectral data (NMR, MS, W-vis, IR, and fluorescence; phosphorescence) to model a chemical, physical, or biological endpoint. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Beger, RD (reprint author), 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 28 TC 10 Z9 10 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD NOV-DEC PY 2000 VL 40 IS 6 BP 1449 EP 1455 DI 10.1021/ci000331v PG 7 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 378PX UT WOS:000165593700018 PM 11128104 ER PT J AU Israel, E Attie, KM Bengtsson, BA Blethen, SL Blum, W Cameron, F Carel, JC Carlsson, L Chipman, JJ Christiansen, JS Clayton, P Clemmons, DR Cohen, P Drop, S Fujieda, K Ghigo, E Hintz, RL Ho, K Ilondo, MM Jasper, H Jesussek, B Kappelgaard, AM Laron, Z Lippe, BM Malozowski, S Mullis, PE de Munick-Keizer-Schrama, S Nishi, Y Parks, JS Phelps, C Ranke, M Robinson, I Rosenfeld, RG Rose, S Saenger, P Saggese, G Savage, M Shalet, S Sizonenko, PC Strasburger, C Tachibana, K Tanaka, T Thorner, MO Wikland, KA Zadik, Z AF Israel, E Attie, KM Bengtsson, BA Blethen, SL Blum, W Cameron, F Carel, JC Carlsson, L Chipman, JJ Christiansen, JS Clayton, P Clemmons, DR Cohen, P Drop, S Fujieda, K Ghigo, E Hintz, RL Ho, K Ilondo, MM Jasper, H Jesussek, B Kappelgaard, AM Laron, Z Lippe, BM Malozowski, S Mullis, PE de Munick-Keizer-Schrama, S Nishi, Y Parks, JS Phelps, C Ranke, M Robinson, I Rosenfeld, RG Rose, S Saenger, P Saggese, G Savage, M Shalet, S Sizonenko, PC Strasburger, C Tachibana, K Tanaka, T Thorner, MO Wikland, KA Zadik, Z CA GH Res Soc TI Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: Summary statement of the GH Research Society SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article C1 Aarhus Kommune Hosp, Med Dept M, DK-8000 Aarhus C, Denmark. Genentech Inc, S San Francisco, CA 94080 USA. Univ Gothenburg, Sahlgrenska Hosp, Gothenburg, Sweden. Eli Lilly & Co, Bad Homburg, Germany. Royal Childrens Hosp, Parkville, Vic 3052, Australia. Hop St Vincent de Paul, F-75674 Paris, France. Eli Lilly & Co, Indianapolis, IN 46285 USA. Manchester Childrens Hosp, Manchester, Lancs, England. Univ N Carolina, Chapel Hill, NC USA. Mattell Childrens Hosp, Los Angeles, CA USA. Sophia Childrens Hosp, Rotterdam, Netherlands. Hokkaido Univ, Sch Med, Sapporo, Hokkaido 060, Japan. Univ Turin, Turin, Italy. Stanford Univ, Stanford, CA 94305 USA. Garvan Inst Med Res, Sydney, NSW, Australia. Novo Nordisk AS, DK-2880 Bagsvaerd, Denmark. CONICET, CEDIE, RA-1033 Buenos Aires, DF, Argentina. Ferring Pharmaceut Ltd, Kiel, Germany. Schneider Childrens Med Ctr Israel, Petah Tiqwa, Israel. Pharmacia & Upjohn Inc, Los Angeles, CA USA. US FDA, Rockville, MD 20857 USA. Univ Bern, Inselspital, CH-3010 Bern, Switzerland. Sophia Kinderziekenhuls, Rotterdam, Netherlands. Hiroshima Red Cross Hosp, Hiroshima, Japan. Emory Univ, Sch Med, Atlanta, GA USA. Ferring Pharmaceut Ltd, Copenhagen, Denmark. Univ Tubingen, Tubingen, Germany. Natl Inst Med Res, London NW7 1AA, England. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ Tennessee, Memphis, TN USA. Albert Einstein Coll Med, New York, NY USA. Univ Pisa, Pisa, Italy. St Bartholomews Hosp, Sch Med, London, England. Christie Hosp, Manchester, Lancs, England. Hop Univ Cantonal Enfants, Geneva, Switzerland. Univ Munich, Munich, Germany. Kanagawa Childrens Ctr, Yokohama, Kanagawa, Japan. Natl Childrens Med Res Ctr, Tokyo 154, Japan. Univ Virginia, Hlth Sci Ctr, Charlottesville, VA USA. Pediat Growth Ctr, Gothenburg, Sweden. Kaplan Hosp, IL-76100 Rehovot, Israel. RP Israel, E (reprint author), Aarhus Kommune Hosp, Med Dept M, DK-8000 Aarhus C, Denmark. RI Parks, John/F-8570-2011; Ho, Ken/E-5832-2011; Albertsson-Wikland, Kerstin/D-3843-2012; Cameron, Fergus/N-9535-2015; OI Clayton, Peter/0000-0003-1225-4537; Carlsson Ekander, Lena/0000-0003-4145-6242 NR 4 TC 326 Z9 339 U1 2 U2 11 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2000 VL 85 IS 11 BP 3990 EP 3993 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 402ML UT WOS:000166992000008 ER PT J AU Cutler, NR Sramek, JJ Greenblatt, DJ Chaikin, P Collins, J AF Cutler, NR Sramek, JJ Greenblatt, DJ Chaikin, P Collins, J TI Defining the maximum tolerated dose: An update SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Editorial Material C1 Calif Clin Trials, Beverly Hills, CA 90211 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Rhone Poulenc Rorer, Collegeville, PA USA. Food & Drug Adm, Rockville, MD USA. RP Cutler, NR (reprint author), Calif Clin Trials, 8501 Wilshire Blvd, Beverly Hills, CA 90211 USA. NR 0 TC 6 Z9 6 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD NOV PY 2000 VL 40 IS 11 BP 1183 EP 1183 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 364ZZ UT WOS:000089925100001 ER PT J AU Wang, D Miller, R Zheng, J Hu, CP AF Wang, D Miller, R Zheng, J Hu, CP TI Comparative population pharmacokinetic-pharmacodynamic analysis for piroxicam-beta-cyclodextrin and piroxicam SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article AB Piroxicam (Feldene(C)) is indicated for osteoarthritis and rheumatoid arthritis but not analgesia due to its delayed onset of pain relief. Piroxicam-P-cyclodextrin (PBCD) was developed for pain indication by virtue of the increased absorption rate of piroxicam. Forty-eight patients received a single dose of PBCD or Feldene (10, 20 and 40 mg) in a randomized study, and piroxicam plasma concentration and pain relief were measured. The purpose of the study was to investigate the PK-PD relationship of piroxicam, determine the optimal dose, and evaluate the effect of increased absorption rate on analgesic effect of piroxicam for the pain model studied. The pharmacokinetic data were best described by a two-compartment model with first-order absorption. The absorption rate of PBCD (5/h) was faster than Feldene (1.41/h). Pain relief was found to be increasing with drug concentration in a hypothetical effect compartment (E-max model). The estimated half-life of the equilibration between plasma and effect site was about 2.34 hours. Monte Carlo simulation showed that the time when at least 50% of the patients have a 75% probability of achieving meaningful pain relief (pain intensity difference (PID greater than or equal to 1)for PBCD and Feldene at a dose of 20 mg was about 0.5 and 1.5 hours, respectively. PBCD demonstrated an advantage with an onset of pain relief 1 hour earlier than Feldene. (C)2000 the American College of Clinical Pharmacology. C1 US FDA, CDER, OCPB, DPEIII, Rockville, MD 20850 USA. Warner Lambert Parke Davis, Parke Davis Pharmaceut Res, Ann Arbor, MI 48105 USA. Pharsight Corp, Cary, NC USA. RP Wang, D (reprint author), US FDA, CDER, OCPB, DPEIII, HFD-880,RM N363,9201 Corp Blvd, Rockville, MD 20850 USA. NR 4 TC 8 Z9 9 U1 1 U2 2 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 NOV PY 2000 VL 40 IS 11 BP 1257 EP 1266 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 364ZZ UT WOS:000089925100011 PM 11075311 ER PT J AU Momcilovic, D Rasooly, A AF Momcilovic, D Rasooly, A TI Detection and analysis of animal materials in food and feed SO JOURNAL OF FOOD PROTECTION LA English DT Review ID BOVINE SPONGIFORM ENCEPHALOPATHY; STAPHYLOCOCCAL-ENTEROTOXIN-A; POLYMERASE CHAIN-REACTION; HEATED MEAT-PRODUCTS; SPECIES IDENTIFICATION; DNA HYBRIDIZATION; PRION PROTEIN; SCRAPIE; DIFFERENTIATION; ELECTROPHORESIS AB Bovine spongiform encephalopathy (BSE) belongs to a group of progressively degenerative neurological diseases known as transmissible spongiform encephalopathies (TSEs) associated with a variant form of Creutzfeldt-Jakob disease in humans. TSEs are fatal diseases caused by prions (proteinaceous infectious particle) and are characterized by an incubation period that may range from several months to several years, depending on the host. Because BSE is spread through animal feed, the main strategy for preventing the establishment and spread of BSE is to prohibit the use of proteins derived from mammalian tissue in feed for ruminant animals. Enforcement of these regulations relies on the ability to identify the presence of prohibited proteins in ruminant feed. The methods to detect bovine products in rendered and cooked materials are based on analyses of DNA, bone, or protein, in this article, we discuss the current methodology as well as other potentially useful methods of analysis of animal material in food. While methods are generally useful, none specifically distinguish between prohibited bovine material and allowable bovine products, such as milk or blood. Furthermore, all these methods are hampered by the fact that the rendering process involves heat treatment that denatures and degrades proteins and DNA. There is a need for improving existing methods and developing new methods to overcome these two limitations. C1 US FDA, Ctr Vet Med, Rockville, MD 20857 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Rasooly, A (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20857 USA. NR 48 TC 47 Z9 57 U1 1 U2 6 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 NOV PY 2000 VL 63 IS 11 BP 1602 EP 1609 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 370QJ UT WOS:000165133500025 PM 11079709 ER PT J AU Zimmerman, ML Friedman, SL AF Zimmerman, ML Friedman, SL TI Identification of rodent filth exhibits SO JOURNAL OF FOOD SCIENCE LA English DT Article DE identification; rodent; excreta; gnawing; nesting material AB Three main types of rodent filth (rodent excreta pellets, gnawing, and nesting material) are described and identification procedures are listed. Suspect excreta pellets that may be encountered in foods from various animals are described In detail and presented in a dichotomous key for comparison and identification. The physical features associated with the excreta pellets (color, shape, size, weight, surface, and matrix composition) are listed for the insects and animals found in the key. Rodent gnawing and rodent nesting materials are defined and the importance of the paired Incisor marks, scalloping along edges and the appearance of the building materials are described. The importance of urine, rodent excreta, hairs and/or parasites when defining nesting material, are discussed, along with the key elements used to recognize the gnawing direction by the rodents. Historical data on rodents and health/safety concerns when handling rodent filth exhibits are addressed. C1 US FDA, Ctr Vet Med, Baltimore, MD 21201 USA. RP Zimmerman, ML (reprint author), US FDA, Ctr Vet Med, 900 Madison Ave, Baltimore, MD 21201 USA. EM mzimmerm@ora.fda.gov NR 26 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-1147 EI 1750-3841 J9 J FOOD SCI JI J. Food Sci. PD NOV-DEC PY 2000 VL 65 IS 8 BP 1391 EP 1394 DI 10.1111/j.1365-2621.2000.tb10618.x PG 4 WC Food Science & Technology SC Food Science & Technology GA 391WB UT WOS:000166378300023 ER PT J AU Muthukkumar, S Goldstein, J Stein, KE AF Muthukkumar, S Goldstein, J Stein, KE TI The ability of B cells and dendritic cells to present antigen increases during ontogeny SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFLUENZAE TYPE-B; C CAPSULAR POLYSACCHARIDE; CD4(+) T-CELLS; HEMOPHILUS-INFLUENZAE; CONJUGATE VACCINE; NEISSERIA-MENINGITIDIS; GROUP-A; IMMUNE-RESPONSE; IN-VIVO; CLINICAL-EVALUATION AB The immune response to polysaccharide (PS) Ags in mice is delayed during ontogeny even when administered in a thymus-dependent (TD) form. In this study, Neisseria meningitidis group C IS-tetanus toroid conjugate (MCPS-TT) vaccine was used to examine whether the delay in the development of Ab responses to TD PS conjugate vaccines in neonatal mice is due to defective Ag presentation. The results show that B cells and dendritic cells (DC) from 3- and 7-day-old mice were severely defective in presenting TT and MCPS-TT to Ag-specific T cell clones. The ability of these cells to present Ag reaches adult levels by 4 wk, The development of anti-MCPS and anti-TT Abs in neonatal mice parallels the functional ability of their APC to present Ag. DC from neonatal mice expressed very low levels of MHC class II, costimulatory molecules B7.1, B7.2, and CD11c but high levels of monocyte-specific markers F4/80 and CD11b and granulocyte marker, Ly6G, Significant changes in the expression of these markers were observed as the age of the mice increased. MHC class II, B7.1 and B7.2, and CD11c all increased with age, reaching adult levels between 3 and 3 wk, concurrent with the function of APC, These results demonstrate that one reason neonates fail to produce high titers of anti-PS Abs even when immunized in a TD form is that their B cells and DC are not fully functional. C1 NIH, US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. RP Stein, KE (reprint author), NIH, US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bldg 29B Room 3NN16,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 67 TC 61 Z9 61 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2000 VL 165 IS 9 BP 4803 EP 4813 PG 11 WC Immunology SC Immunology GA 367RV UT WOS:000090076000007 PM 11046003 ER PT J AU Gutman, S AF Gutman, S TI Labeling liquid-based systems: FDA clarification SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Letter DE Pay smear; cervical smears; mass screening; computer-assisted diagnosis; AutoCyte PREP; ThinPrep C1 US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Clin Lab Devices, Rockville, MD 20857 USA. RP Gutman, S (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Clin Lab Devices, Rockville, MD 20857 USA. NR 2 TC 4 Z9 4 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD NOV PY 2000 VL 45 IS 11 BP 969 EP 970 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 379AN UT WOS:000165618900026 PM 11127121 ER PT J AU Smith, CC Nelson, J Aurelian, L Gober, M Goswami, BB AF Smith, CC Nelson, J Aurelian, L Gober, M Goswami, BB TI Ras-GAP binding and phosphorylation by herpes simplex virus type 2 RR1 PK (ICP10) and activation of the Ras/MEK/MAPK mitogenic pathway are required for timely onset of virus growth SO JOURNAL OF VIROLOGY LA English DT Article ID RIBONUCLEOTIDE REDUCTASE ICP10; PROTEIN-KINASE ACTIVITY; CIS-RESPONSE ELEMENTS; PHOSPHOTYROSINE-DEPENDENT MANNER; HUMAN-IMMUNODEFICIENCY-VIRUS; NUCLEOTIDE EXCHANGE FACTOR; NF-KAPPA-B; LARGE SUBUNIT; SH2 DOMAINS; SIGNALING PATHWAYS AB We used a herpes simplex virus type 2 (HSV-2) mutant with a deletion in the RR1 (ICP10) PK domain (ICP10 Delta PK) and an MEK inhibitor (PD98059) to examine the role of ICP10 PK in virus growth. In HSV-2-infected cells, ICP10 PK binds and phosphorylates the GTPase activating protein Pas-CAP. In vitro binding and peptide competition assays indicated that Ras-GAP N-SH2 and PH domains, respectively, bind ICP10 at phosphothreonines 117 and 141 and a WD40-like motif at positions 160 to 173. Binding and phosphorylation did not occur in cells infected with ICP10 Delta PK GTPase activity was significantly lower in HSV-2 than in ICP10 Delta PK-infected cells. Conversely, the levels of activated Pas and mitogen-activated protein kinase (MAPK), and the expression and stabilization of the transcription factor c-Fos were significantly increased in cells infected with HSV-2 or a revertant virus [HSV-2(R)] but not with ICP10 Delta PK. PD98059 inhibited MAPK activation and induction-stabilization of c-Pos. Expression from the ICP10 promoter was increased in cells infected with HSV-2 but not with ICP10 Delta PK, and increased expression was ablated by PD98059. ICP10 DNA formed a complex with nuclear extracts from HSV-2-infected cells which was supershifted by c-Fos antibody and was not seen,vith extracts from ICP10 Delta PK-infected cells. Complex formation was abrogated by PD98059. Onset of HSV-2 replication was significantly delayed by PD98059 (14 h versus 2 h in untreated cells), a delay similar to that seen for ICP10 Delta PK. The data indicate that Pas-CAP phosphorylation by ICP10 PK is involved in the activation of the Ras/MEK/MAPK mitogenic pathway and c-Fos induction and stabilization. This results in increased ICP10 expression and the timely onset of HSV-2 growth. C1 Univ Maryland, Sch Med, Virol Immunol Labs, Dept Pharmacol & Expt Therapeut, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Microbiol, Baltimore, MD 21201 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Aurelian, L (reprint author), Univ Maryland, Sch Med, Virol Immunol Labs, Dept Pharmacol & Expt Therapeut, 10 S Pine St,Room 500-F, Baltimore, MD 21201 USA. NR 90 TC 60 Z9 66 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2000 VL 74 IS 22 BP 10417 EP 10429 DI 10.1128/JVI.74.22.10417-10429.2000 PG 13 WC Virology SC Virology GA 367WE UT WOS:000090083800017 PM 11044086 ER PT J AU Carbone, KM Pletnikov, M AF Carbone, KM Pletnikov, M TI Borna again, starting from the beginning SO MOLECULAR PSYCHIATRY LA English DT Editorial Material ID DISEASE VIRUS-INFECTION; RATS; ABNORMALITIES; PERSISTENT; DAMAGE C1 Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. US FDA, Ctr Biol Evaluat & Res, DVP, OVRR,Lab Pediat & Resp Viral Dis, Bethesda, MD USA. RP Carbone, KM (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat, Ross 618,720 Rutland Ave, Baltimore, MD 21205 USA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 2000 VL 5 IS 6 BP 577 EP 577 DI 10.1038/sj.mp.4000810 PG 1 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 372MC UT WOS:000165236600004 PM 11126388 ER PT J AU Lesko, LJ Rowland, M Peck, CC Blaschke, TF AF Lesko, LJ Rowland, M Peck, CC Blaschke, TF TI Optimizing the science of drug development: Opportunities for better candidate selection and accelerated evaluation in humans SO PHARMACEUTICAL RESEARCH LA English DT Editorial Material ID REMIFENTANIL GI87084B; PHARMACOKINETICS; PHARMACODYNAMICS; INTEGRATION AB This report is a distillation of two tandem conferences, the first entitled "AAPS, ACCP, ASCPT, FDA Symposium on Clinical Pharmacology: Optimizing the Science of Drug Development," held in September, 1998 in Arlington, Virginia, USA, and the second entitled "5(th) EUFEPS Conference on Optimizing Drug Development: Fast Tracking into Human," held in December, 1998 in Wiesbaden, Germany. The collective aims of these conferences were: To identify critical issues which currently limit drug candidate selection and the early phases of human drug development. To explore those modern scientific and technological innovations which could further improve preclinical and clinical development. To assess the impact of using modern approaches of clinical pharmacology in the early stages of drug development on the time, cost, quality, and regulatory decisions associated with this process. To assess the implications of the new standards for the definition of evidence of efficacy in the US as they relate to International Conference on Harmonisation (ICH) and US regulatory guidances, with special emphasis on the characteristics of confirmatory evidence. To generate recommendations for the design and analysis of early phase, state-of the-art clinical studies in healthy volunteers and patients that allow bridging of information from nonclinical to late-phase clinical studies designed to demonstrate safety and efficacy. To prepare a combined summary of the two conferences to facilitate communication of these new ideas for optimizing drug candidate selection and early-phase clinical development, as well as to provide a rationale for the development of future regulatory guidances. C1 Stanford Univ, Dept Med, Sch Med, Div Clin Pharmacol,Stanford Med Ctr S009, Stanford, CA 94305 USA. US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20851 USA. Univ Manchester, Sch Pharm & Pharmaceut Sci, Manchester M13 9PL, Lancs, England. Georgetown Univ, Ctr Drug Dev Sci, Washington, DC 20007 USA. RP Blaschke, TF (reprint author), Stanford Univ, Dept Med, Sch Med, Div Clin Pharmacol,Stanford Med Ctr S009, Stanford, CA 94305 USA. NR 13 TC 56 Z9 58 U1 0 U2 0 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 NOV PY 2000 VL 17 IS 11 BP 1335 EP 1344 DI 10.1023/A:1007574217260 PG 10 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 393UY UT WOS:000166489100001 PM 11205725 ER PT J AU Jackson, AJ AF Jackson, AJ TI The role of metabolites in bioequivalency assessment. III. Highly variable drugs with linear kinetics and first-pass effect SO PHARMACEUTICAL RESEARCH LA English DT Article DE intrinsic clearance; metabolites; bioequivalence ID SIMULATIONS; PHARMACOKINETICS; SINGLE; CMAX AB Purpose. Simulated pharmacokinetic (PK) studies were done to determine the effect of intrinsic clearance (CLINT) on the probability of meeting bioequivalence criteria for extent (AUC) and rate (Cmax) of drug absorption when the absorption rate and fraction absorbed (F) were formulated either to be equivalent or to differ by 25%. Methods. Simulated PK studies were done using a linear first-pass model with CLINT values ranging from 15 L/HR to 900 L/HR. Test/ Reference absorption rate constants (Ka) and fraction absorbed (Fa) ratios of 1.0 or 1.25 were used for all simulations. The impact of the value of CLINT and its intrasubject variation upon the probability of concluding bioequivalence at the two different Ka and F ratios was studied. Additionally, the effect of fraction metabolized i.v., (Fm) on the probabilities of concluding equivalence was studied at values of 0.25 and 0.75. Results. When CLINT values were raised above those for liver blood flow, the frequency of trials in which bioequivalence was correctly declared decreased when parent AUC was used as a bioequivalence criterion. Only when CLINT exceeded liver blood flow did the metabolite become important in assessing extent of absorption. Conclusions. The Cmax for the parent drug provided the most accurate assessment of bioequivalence. The Cmax for the metabolite was insensitive to changes related to rate of input, and when CLINT exceeded liver blood flow, evaluation of the metabolite Cmax data may lead to a conclusion of bioequivalence for products that were not. C1 US FDA, Ctr Drug Evaluat & Res, Div Bioequivalence, Rockville, MD 20857 USA. RP Jackson, AJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Bioequivalence, Rockville, MD 20857 USA. NR 14 TC 22 Z9 23 U1 0 U2 0 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 NOV PY 2000 VL 17 IS 11 BP 1432 EP 1436 DI 10.1023/A:1007581016352 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 393UY UT WOS:000166489100015 PM 11205739 ER PT J AU Ilev, IK Waynant, RW AF Ilev, IK Waynant, RW TI A simple submicron confocal microscope with a fiberoptic output SO REVIEW OF SCIENTIFIC INSTRUMENTS LA English DT Article ID OPTICAL MICROSCOPY; 2-PHOTON; FIBERS; LASER AB We present a simple design of a reflection-type confocal microscope with a multimode graded-index fiber output. Due to the use of an apertureless confocal arrangement, a high-aperture focusing objective and a large-core graded-index multimode fiber for signal detection, a regime of high-output power is achieved that provides high resolving power and submicron spatial resolution. The graded-index multimode fiber ensures an efficient launching and maintenance of high laser powers, a high sensitivity to spatial displacements of the focusing backreflectance emission, and a low mode noise and signal fluctuations. At axial scanning of the test object, a submicron resolution of 0.4 mum is obtained. (C) 2000 American Institute of Physics. [S0034-6748(00)03912-5]. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-134,12725 Twinbrook Pkwy, Rockville, MD 20857 USA. NR 25 TC 11 Z9 11 U1 0 U2 1 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0034-6748 J9 REV SCI INSTRUM JI Rev. Sci. Instrum. PD NOV PY 2000 VL 71 IS 11 BP 4161 EP 4164 AR PII [S0034-6748(00)03912-5] DI 10.1063/1.1322589 PG 4 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 369TY UT WOS:000165084100026 ER PT J AU Chang, HC Doerge, DR AF Chang, HC Doerge, DR TI Dietary genistein inactivates rat thyroid peroxidase in vivo without an apparent hypothyroid effect SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE genistein; soy; thyroid peroxidase; mass spectrometry ID SOY ISOFLAVONES; MASS-SPECTROMETRY; FORMULA; PROPYLTHIOURACIL; MECHANISM; INFANTS; PLASMA; WOMEN AB Biological effects of genistein are currently under investigation by the National Toxicology Program because of widespread and increasing soy consumption by humans and evidence for modulation of endocrine function. Rats were exposed to genistein aglycone in soy-free feed fortified at 0, 5, 100, and 500 ppm starting in utero through 20 weeks. Thyroid glands and serum were analyzed for total genistein (aglycone + conjugates) using HPLC with electrospray mass spectrometric detection. Microsomal thyroid peroxidase (TPO) activity was measured spectrophotometrically. The total genistein content in rat serum was as high as 8 muM, and significant dose-dependent increases of genistein in thyroid tissue up to 1 pmol/mg were found in male and female rats. The activity of TPO in male and female rats was found to be reduced by up to 80% in a dose-dependent manner. Male and female rats consuming a standard soy-based rodent diet (NIH 31) had TPO activity approximately 50% lower than rats consuming a soy-free diet and this loss was commensurate with measured serum levels of isoflavones. Suicide inactivation of rat, porcine, and human TPO was observed in vitro at concentrations of genistein aglycone comparable to those measured in rat thyroids, Thyroid hormone levels (T3, T4, TSH) in serum, thyroid weights, and histopathology showed no differences between treated and untreated groups. These findings suggest that, even though substantial amounts of TPO activity are lost concomitant to soy isoflavone consumption by normal rats, the remaining enzymatic activity is sufficient to maintain thyroid homeostasis in the absence of additional perturbations. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 44 TC 67 Z9 70 U1 1 U2 7 PU ACADEMIC PRESS INC 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 NOV 1 PY 2000 VL 168 IS 3 BP 244 EP 252 DI 10.1006/taap.2000.9019 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 400WB UT WOS:000166893700009 PM 11042097 ER PT J AU Post, LO Keller, WC AF Post, LO Keller, WC TI Current status of food animal antidotes SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article AB The availability of antidotes in veterinary medicine has been an issue for more than a decade. Antidotes are available for food animals through extralabel use, regulatory discretion, and compounding. There is little economic incentive for pharmaceutical companies to pursue approval of antidotes and other drug products that have a small market. in addition human food safety concerns must be addressed when approving antidotes for use in food animals. This article provides a brief history of antidote availability, current mechanisms for procuring food animal antidotes, and availability of specific antidotes for use in food animals. C1 US FDA, Div Surveillance, Off Surveillance & Compliance, Ctr Vet Med, Rockville, MD 20857 USA. RP Post, LO (reprint author), HFV-216,7500 Standish Pl, Rockville, MD 20855 USA. NR 0 TC 2 Z9 3 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0720 J9 VET CLIN N AM-FOOD A JI Vet. Clin. N. Am.-Food Anim. Pract. PD NOV PY 2000 VL 16 IS 3 BP 445 EP + PG 10 WC Veterinary Sciences SC Veterinary Sciences GA 371YE UT WOS:000165206200004 PM 11084985 ER PT J AU Chen, ML Patnaik, R Hauck, WW Schuirmann, DJ Hyslop, T Williams, R AF Chen, ML Patnaik, R Hauck, WW Schuirmann, DJ Hyslop, T Williams, R CA FDA Individual Population Bioequiv TI An individual bioequivalence criterion: regulatory considerations SO STATISTICS IN MEDICINE LA English DT Article ID EQUIVALENCE; POPULATION; DRUGS; BIOAVAILABILITY; INTERVALS AB Over the years, concerns have been raised regarding the appropriateness of using the average bioequivalence approach for evaluation of comparability between formulations. In lieu of average bioequivalence, scientists from academia, industry and regulatory agencies have spent considerable effort and time in exploring the concepts of population and individual bioequivalence, and developing the statistical methods to assess the bioavailability metrics using these approaches. Recently, the Food and Drug Administration (FDA) has published a preliminary draft guidance entitled 'In vivo bioequivalence studies based on population and individual bioequivalence equivalence approaches'. The concept of prescribability and switchability underscores the difference between the population and individual bioequivalence approaches. The most important consideration for individual bioequivalence, the focus of this paper, rests on the assurance that products deemed bioequivalent can be used interchangeably in the target population (switchability). In addition to the comparison of averages, the individual bioequivalence approach compares within-subject variabilities and assesses subject-by-formulation interaction. The proposed criterion represents substantial departure from the current practice and thus has resulted in extensive public discussion. In contrast to the current average bioequivalence procedure, the proposed individual bioequivalence approach offers flexible equivalence criteria based on the individual therapeutic window and variability of the reference drug product. The proposed criterion rewards manufacture of less variable drug products, allows scaling criteria for highly variable/narrow therapeutic range drugs, and promotes the use of subjects from the general population in bioequivalence studies. The FDA is currently considering various approaches for resolution of issues raised from the public debate on the subject-by-formulation interaction term, statistical methods and resource implications. Published in 2000 by John Wiley & Sons, Ltd. C1 US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Evaluat 2 HFD870, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. RP Chen, ML (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci HFD350, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 43 TC 27 Z9 32 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD OCT 30 PY 2000 VL 19 IS 20 BP 2821 EP 2842 PG 22 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 365DF UT WOS:000089932600009 PM 11033578 ER PT J AU Beasley, VR Lovell, RA Holmes, KR Walcott, HE Schaeffer, DJ Hoffmann, WE Carmichael, WW AF Beasley, VR Lovell, RA Holmes, KR Walcott, HE Schaeffer, DJ Hoffmann, WE Carmichael, WW TI Microcystin-LR decreases hepatic and renal perfusion, and causes circulatory shock, severe hypoglycemia, and terminal hyperkalemia in intravascularly dosed swine SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A LA English DT Article ID BLUE-GREEN-ALGA; ISOLATED RAT HEPATOCYTES; PROTEIN PHOSPHATASES; PEPTIDE HEPATOTOXIN; BLOOD PERFUSION; AERUGINOSA; TOXICITY; TOXIN; INHIBITION; SYSTEM AB Cross-bred, anesthetized female swine were given intravascularly a lethal (72 mug/kg; n = 6) or toxic-sublethal (25 mug/kg; n = 6) dose of microcystin-LR (MCLR), from Microcystis aeruginosa, or the vehicle (n = 4). At the high dose, from 12 to 18 min after administration , central venous pressure and hepatic perfusion were significantly lower, and shortly thereafter, portal venous pressure was significantly higher and aortic mean pressure was significantly lower than controls. By 45 min postdosing, serum bile acids, lactate, potassium , and total bilirubin, as well as blood pO(2),were significantly higher, while hematocrit, platelet count, and blood bicarbonate, pCO(2), and base excess were significantly lower than controls. By 90 min, serum arginase, urea nitrogen, inorganic phosphorus, and creatinine were significantly higher, while glucose and blood pH were significantly lower than in controls. By 150 min, serum alanine and aspartate aminotransferases, alkaline phosphatase, lactate dehydrogenase, and creatinine phosphokinase activities were significantly higher than controls. At the low dose, significant differences from controls occurred in hemodynamic, organ perfusion, and serum chemistry parameters, but such changes generally took longer to occur and were of a lesser magnitude than at the high dose. Livers of the high-dose swine were swollen and dark red-purple, and exuded excessive blood on the cut surface. Based on increases in liver weight and liver hemoglobin, 38% of the total blood volume was lost into the liver. Terminally, all high-dose swine experienced hyperkalemia, and most had severe hypoglycemia. Death due to acute MCLR toxicosis in intravascularly dosed swine appears to result from severe intrahepatic hemorrhage, partial obstruction of blood flow through the liver, circulatory shock, severe hypoglycemia, and/or terminal hyperkalemia. C1 Univ Illinois, Coll Vet Med, Dept Vet Biosci, Urbana, IL 61802 USA. US FDA, Ctr Vet Med, Div Anim Feeds, Rockville, MD 20857 USA. Univ Illinois, Coll Vet Med, Dept Pathobiol, Urbana, IL 61801 USA. Wright State Univ, Dept Biol Sci, Dayton, OH 45435 USA. RP Beasley, VR (reprint author), Univ Illinois, Coll Vet Med, Dept Vet Biosci, 2001 S Lincoln Ave, Urbana, IL 61802 USA. FU NHLBI NIH HHS [HL-27011] NR 66 TC 38 Z9 47 U1 5 U2 10 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. TOXICOL. ENV. HEALTH PT A PD OCT 27 PY 2000 VL 61 IS 4 BP 281 EP 303 DI 10.1080/00984100050136599 PG 23 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 368RZ UT WOS:000090132500005 PM 11071321 ER PT J AU Mauck, CK Baker, JM Birnkrant, DB Rowe, PJ Gabelnick, HL AF Mauck, CK Baker, JM Birnkrant, DB Rowe, PJ Gabelnick, HL TI The use of colposcopy in assessing vaginal irritation in research SO AIDS LA English DT Review DE vagina; colposcopy; microbicide; contraceptive; irritation; genital; epithelium ID RANDOMIZED CLINICAL-TRIAL; CERVICAL MUCOSA; NONOXYNOL-9; GEL; EPITHELIUM; EXPRESSION; HEALTHY; SAFETY; FILMS AB Since the early 1990s, colposcopy of the vagina and cervix has been used in the development of vaginal products in order to detect epithelial changes that may increase the likelihood of HIV or acquisition of other sexually transmitted diseases. As part of a continued effort to examine and define the role of colposcopy in a research setting, the Contraceptive Research and Development Program (CONRAD) and the International Working Group on Microbicides (IWGM), in association with the United Nations Program for AIDS (UNAIDS) sponsored a conference entitled, 'The Use of Colposcopy in Assessing Vaginal Irritation in Research', held in Washington, DC in January 1999. This is a report of that conference. The World Health Organization's colposcopy procedure and nomenclature, published in 1995, were reviewed and changes were recommended. The revised procedure involves colposcopic examination of the external genitalia, naked eye examination of the cervix, fornices, and vaginal walls, followed by lavage and colposcopic examination of those areas, and sampling as appropriate for microscopic examination. Revised nomenclature replaces the terms used for findings with descriptions of what is actually seen. Digital video imaging and testing for inflammatory markers may be adjuncts to colposcopy and should be further studied. Other areas requiring additional research include the natural history of colposcopic changes, factors other than product use that may affect colposcopic findings, the clinical significance of findings, and the procedure which best assesses these findings. (C) 2000 Lippincott Williams & Wilkins. C1 Contracept Res & Dev Program, Arlington, VA 22209 USA. US FDA, Ctr Drug Evaluat & Res, Div Antiviral Drug Prod, Rockville, MD 20857 USA. WHO, Special Programme Res Dev & Res Training Human Re, CH-1211 Geneva, Switzerland. RP Mauck, CK (reprint author), Contracept Res & Dev Program, 1611 N Kent St,Suite 806, Arlington, VA 22209 USA. NR 23 TC 19 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD OCT 20 PY 2000 VL 14 IS 15 BP 2221 EP 2227 DI 10.1097/00002030-200010200-00002 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 371AL UT WOS:000165155400001 PM 11089609 ER PT J AU Trontell, AE Honig, PK AF Trontell, AE Honig, PK TI Clopidogrel and thrombotic thrombocytopenic purpura. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Trontell, AE (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 OCT 19 PY 2000 VL 343 IS 16 BP 1191 EP 1192 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 364FY UT WOS:000089882800013 PM 11041753 ER PT J AU Bever, RJ Couch, LH Sutherland, JB Williams, AJ Beger, RD Churchwell, MI Doerge, DR Howard, PC AF Bever, RJ Couch, LH Sutherland, JB Williams, AJ Beger, RD Churchwell, MI Doerge, DR Howard, PC TI DNA adduct formation by Fusarium culture extracts: lack of role of fusarin C SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE Fusarium fungi; DNA adducts; HPLC; fusarin C; P-32-postlabeling ID MUTAGENIC METABOLITE; ESOPHAGEAL CANCER; MONILIFORME; MAIZE; RATS; CORN; CARCINOGENICITY; CHINA; AREAS; RISK AB Fusarium fungi have been shown to infect corn and other crops worldwide, and have a significant impact on human health through loss of crops or contamination of food with mycotoxins. Isolates of Fusarium fungi from an area of South Africa with high incidence of esophageal cancer have been shown to induce esophageal and liver cancer in rats. Several isolates of Fusarium fungi were grown on corn to determine if genotoxic products were produced. We report the incubation of methanol extracts of Fusarium verticillioides cultures with DNA in the presence of rat liver fractions (S9) resulted in the formation of a unique DNA adduct that was detected by P-32-postlabeling. Fusarin C was purified from cultures of Fusarium verticillioides RRC 415, and was not responsible for the formation of the DNA adduct. Treatment of the methanolic extracts with ultraviolet B radiation reduced the fusarin C content in the extract; however, this had no effect on the formation of the DNA adduct following incubation of the extract with DNA and S9. The unique DNA adduct was formed following the incubation of several Fusarium verticillioidess isolates from the US and South Africa, while extracts of cultures of Fusarium graminearium and Fusarium sacchari isolates formed very little of the DNA adduct when incubated with DNA and S9. These data suggest that neither fusarin C nor any of its metabolites an responsible for formation of the DNA adduct, and that an unidentified compound is prevent in F. verticillioides cultures that forms a DNA adduct, and may be important in the etiology of human esophageal cancer. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, US Publ Hlth Serv, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Chem & Microbiol, US Publ Hlth Serv, Jefferson, AR 72079 USA. RP Howard, PC (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, US Publ Hlth Serv, HFT-110,3900 NCTR Rd, Jefferson, AR 72079 USA. FU NIA NIH HHS [IAG 224-93-0001] NR 36 TC 17 Z9 17 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD OCT 16 PY 2000 VL 128 IS 2 BP 141 EP 157 DI 10.1016/S0009-2797(00)00195-2 PG 17 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 368XD UT WOS:000090142000004 PM 11024453 ER PT J AU Sweeney, C McClure, GY Fares, MY Stone, A Coles, BF Thompson, PA Korourian, S Hutchins, LF Kadlubar, FF Ambrosone, CB AF Sweeney, C McClure, GY Fares, MY Stone, A Coles, BF Thompson, PA Korourian, S Hutchins, LF Kadlubar, FF Ambrosone, CB TI Association between survival after treatment for breast cancer and glutathione S-transferase P1 Ile(105)Val polymorphism SO CANCER RESEARCH LA English DT Article ID GENETIC POLYMORPHISMS; EXPRESSION; PI; CHEMOTHERAPY; CYTOCHROME-P450; SUSCEPTIBILITY; CONJUGATION; ISOENZYMES; RESISTANCE; VARIANTS AB A glutathione S-transferase (GST) P1 polymorphism results in an amino acid substitution, Ile(105)Val; the Val-containing enzyme has reduced activity toward alkylating agents. Cancer patients with the variant enzyme may differ in removal of treatment agents and in outcomes of therapy, We evaluated survival according to GSTP1 genotype among women (a = 240) treated Pur breast cancer. Women with the low-activity Val/Val genotype had better survival. Compared with Ile/Ile, hazard ratios for overall survival were 0.8 (95% confidence interval, 0.5-1.3) for Ile/Val and 0.3 (95% confidence interval, 0.1-1.0) for Val/Val (P for trend = 0.04). Inherited metabolic variability may influence treatment outcomes. C1 Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. RP Sweeney, C (reprint author), Univ Arkansas Med Sci, Arkansas Canc Res Ctr, 4301 W Markham St,Slot 795, Little Rock, AR 72205 USA. OI Sweeney, Carol/0000-0003-1113-7160 NR 19 TC 116 Z9 129 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 OCT 15 PY 2000 VL 60 IS 20 BP 5621 EP 5624 PG 4 WC Oncology SC Oncology GA 367HC UT WOS:000090054800007 PM 11059750 ER PT J AU Marti, GE Gaigalas, A Vogt, RF AF Marti, GE Gaigalas, A Vogt, RF TI Recent developments in quantitative fluorescence calibration for analyzing cells and microarrays SO CYTOMETRY LA English DT Editorial Material ID CYTOMETRY C1 US FDA, Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Div Cell & Gene Therapy, Bethesda, MD USA. NIST, Chem Sci & Technol Lab, Div Biotechnol, Gaithersburg, MD 20899 USA. Ctr Dis Control & Prevent, Natl Diabet Lab, Atlanta, GA USA. RP Vogt, RF (reprint author), CDC, Mailstop F19, Atlanta, GA 30341 USA. NR 9 TC 9 Z9 10 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOMETRY JI Cytometry PD OCT 15 PY 2000 VL 42 IS 5 BP 263 EP 263 DI 10.1002/1097-0320(20001015)42:5<263::AID-CYTO1>3.0.CO;2-Q PG 1 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 366DG UT WOS:000089989100001 PM 11025482 ER PT J AU Stephen, P Brown, AE Dolan, MJ Michael, NL Zhou, S Perfetto, HC Robb, M Lane, J Mayers, D McNeil, JG Malone, JD Garner, R Birx, DL AF Stephen, P Brown, AE Dolan, MJ Michael, NL Zhou, S Perfetto, HC Robb, M Lane, J Mayers, D McNeil, JG Malone, JD Garner, R Birx, DL TI Clinical prognosis of patients with early-stage HIV disease: Contribution of HIV-1 RNA and T-lymphocyte subset quantitation and expression SO CYTOMETRY LA English DT Meeting Abstract C1 Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Washington, DC 20307 USA. Wilford Hall Med Ctr, Lackland AFB, TX USA. Henry M Jackson Fdn, Rockville, MD USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. SRA Technol, Gaithersburg, MD USA. Natl Naval Med Ctr, Bethesda, MD USA. US FDA, Ctr Devices & Radiol Hlth, OSB, DBS, Rockville, MD 20857 USA. Henry Ford Hosp, Div Infect Dis, Detroit, MI USA. USN, Med Ctr, San Diego, CA 92152 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOMETRY JI Cytometry PD OCT 15 PY 2000 VL 42 IS 5 MA 32 BP 321 EP 322 PG 2 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 366DG UT WOS:000089989100040 ER PT J AU Hoff, PM Janjan, N Saad, ED Skibber, J Crane, C Lassere, Y Cleary, KR Benner, S Randolph, J Abbruzzese, JL Pazdur, R AF Hoff, PM Janjan, N Saad, ED Skibber, J Crane, C Lassere, Y Cleary, KR Benner, S Randolph, J Abbruzzese, JL Pazdur, R TI Phase I study of preoperative oral uracil and tegafur plus leucovorin and radiation therapy in rectal cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADJUVANT THERAPY; CHEMORADIATION; CHEMOTHERAPY; FLUOROURACIL; COMBINATION; CARCINOMA; INFUSION; UFT AB Purpose: preoperative combined-modality therapy for rectal cancer may allow for sphincter preservation, while decreasing recurrence rates and improving the overall prognosis. Oral chemotherapy with uracil and tegafur (UFT) plus leucovorin (LV) may reduce costs and complications associated with protracted infusions of fluorouracil. Our goal was to evaluate the safety of UFT plus LV combined with preoperative radiation and determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of UFT plus LV in this setting. Patients and Methods: patients with tumor-node-metastasis stage II or III rectal cancer received escalating doses of UFT (starting at 250 mg/m(2)/d, with 50-mg/m(2)/d increments between consecutive cohorts) and fixed doses of LV (90 mg/d). The UFT and LV combination was given 5 days per week concurrently with ct 5-week course of preoperative radiation totaling 45 Gy (1.8 Gy/fraction). Surgery was performed 4 to 6 weeks after radiation and was followed by four 35-day cycles of fixed doses of UFT and LV (28 days of therapy each cycle). Results: Fifteen patients were treated, and 13 received the full preoperative chemotherapy. All planned radiation was delivered successfully. The MTD of UFT with radiation was 350 mg/m(2)/d with 90 mg/d of LV. Diarrhea was the DLT. Sphincter-preserving surgery was performed in 12 of 14 patients. One patient had progressive disease before surgery. Pathologic evolvation of 14 resected specimens showed a complete response in three cases. Conclusion: Preoperative chemoradiation with oral UFT plus LV is feasible and well tolerated and should be further investigated. (C) 2000 by American Society of Clinical Oncology. C1 Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol & Digest Dis, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA. US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20857 USA. RP Hoff, PM (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol & Digest Dis, Box 78,1515 Holcombe Blvd, Houston, TX 77030 USA. NR 21 TC 37 Z9 38 U1 0 U2 2 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 OCT 15 PY 2000 VL 18 IS 20 BP 3529 EP 3534 PG 6 WC Oncology SC Oncology GA 367TG UT WOS:000090077100012 PM 11032595 ER PT J AU Markovic-Housley, Z Miglierini, G Soldatova, L Rizkallah, PJ Muller, U Schirmer, T AF Markovic-Housley, Z Miglierini, G Soldatova, L Rizkallah, PJ Muller, U Schirmer, T TI Crystal structure of hyaluronidase, a major allergen of bee venom SO STRUCTURE LA English DT Article DE allergen; bee venom; crystallography; glycosidase family 56; hyaluronidase ID N-ACETYLGLUCOSAMINIDASE-H; ACTIVE-SITE RESIDUES; GLYCOSYL HYDROLASES; 3-DIMENSIONAL STRUCTURE; TRICHODERMA-REESEI; CROSS-REACTIVITY; CRYSTALLOGRAPHIC EVIDENCE; TESTICULAR HYALURONIDASE; SUBSTRATE RECOGNITION; CATALYTIC DOMAIN AB Background: Hyaluronic acid (HA) is the most abundant glycosaminoglycan of vertebrate extracellular spaces and is specifically degraded by a beta -1,4 glycosidase. Bee venom hyaluronidase (Hya) shares 30% sequence identity with human hyaluronidases, which are involved in fertilization and the turnover of HA. On the basis of sequence similarity, mammalian enzymes and Hya are assigned to glycosidase family 56 for which no structure has been reported yet. Results: The crystal structure of recombinant (Baculovirus) Hya was determined at 1.6 Angstrom resolution. The overall topology resembles a classical (beta/alpha)(8) TIM barrel except that the barrel is composed of only seven strands. A long substrate binding groove extends across the C-terminal end of the barrel. Cocrystallization with a substrate analog revealed the presence of a HA tetramer bound to subsites -4 to -1 and distortion of the -1 sugar. Conclusions: The structure of the complex strongly suggest an acid-base catalytic mechanism, in which Glu113 acts as the proton donor and the N-acetyl group of the substrate is the nucleophile. The location of the catalytic residues shows striking similarity to bacterial chitinase which also operates via a substrate-assisted mechanism. C1 Univ Basel, Biozentrum, Div Biol Struct, CH-4056 Basel, Switzerland. Polytech SCRL, I-34012 Trieste, Italy. US FDA, Lab Immunochem, Rockville, MD 20852 USA. SERC, Daresbury Lab, CCLRC, Warrington WA4 4AD, Cheshire, England. Ziegler Hosp Bern, Med Clin, CH-3001 Bern, Switzerland. RP Markovic-Housley, Z (reprint author), Univ Basel, Biozentrum, Div Biol Struct, CH-4056 Basel, Switzerland. NR 74 TC 168 Z9 180 U1 2 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD OCT 15 PY 2000 VL 8 IS 10 BP 1025 EP 1035 DI 10.1016/S0969-2126(00)00511-6 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 420TW UT WOS:000168022200003 PM 11080624 ER PT J AU Chen, ZG Eggerman, TL Potosky, D Arborati, M Patterson, AP AF Chen, ZG Eggerman, TL Potosky, D Arborati, M Patterson, AP TI Calcium increases apolipoprotein B mRNA editing SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; CULTURED RAT HEPATOCYTES; MESSENGER-RNA; INDUCED APOPTOSIS; BINDING PROTEIN; CACO-2 CELLS; SECRETION; INHIBITION; APOBEC-1; BIOSYNTHESIS AB ApoB-100 and apoB-48 are major components of chylomicrons, very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL), The two proteins are generated from a single apoB mRNA by apoB mRNA editing which induces an in-frame stop codon in apoB mRNA Apolipoprotein B (apoB) mRNA editing is an important determinant of the proportion of full-length (apoB-100) and truncated (apoB-48) proteins in total apoB metabolism. Calcium is involved in the regulation of secretion and synthesis of VLDL and apoB. In this paper, we demonstrate for the first time that the amount of edited apoB mRNA in the cultured cells Caco-2 and McA7777 is markedly increased by calcium. Increasing extracellular calcium concentration, calcium ionophore (A23187 and ionomycin) treatment, and depleting calcium stores and raising cytoplasmic calcium concentration by thapsigargin increase apoB mRNA editing up to threefold in a dose dependent manner. Calcium has no direct stimulative effect on apoB mRNA editing in an in vitro editing system. The editing increase by extracellular calcium is not related to alterations of APOBEC-1 mRNA expression. These data suggest that calcium is not only involved in the regulation of apolipoprotein metabolism but also apoB mRNA editing. (C) 2000 Academic Press. C1 NHLBI, NIH, Bethesda, MD 20892 USA. US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Patterson, AP (reprint author), NHLBI, NIH, 6000 Execut Blvd,Suite 302, Bethesda, MD 20892 USA. NR 40 TC 8 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 14 PY 2000 VL 277 IS 1 BP 221 EP 227 DI 10.1006/bbrc.2000.3668 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 367PJ UT WOS:000090070400038 PM 11027667 ER PT J AU Bocharov, AV Vishnyakova, TG Baranova, IN Remaley, AT Patterson, AP Eggerman, TL AF Bocharov, AV Vishnyakova, TG Baranova, IN Remaley, AT Patterson, AP Eggerman, TL TI Heat shock protein 60 is a high-affinity high-density lipoprotein binding protein SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE high-density lipoprotein-binding protein; heat shock protein 60 ID CELLULAR CHOLESTEROL EFFLUX; HIGH-TEMPERATURE; SR-BI; APOLIPOPROTEIN; HSP60; RECEPTOR; CELLS; ASSOCIATION; CHAPERONIN; CLONING AB A new 55-kDa HDL/apolipoprotein binding protein was demonstrated in plasma membrane preparations of the human cell lines and primary cultured hepatocytes, Analysis of specific binding by ligand immunoblots of HDL, apoA-I, and apoA-II to a partially purified S5-kDa PA-I plasma membrane preparation demonstrated a K-d,K-HDL = 50 nM (10 mug/ml), K-d,K-apoA-II = 20 nM (0.4 mug/ml), and K-d,K-apoA-I = 330 nM (10 mug/ml). Following preparative SDS-PAGF electrophoresis of a plasma membrane preparation isolated from human PA-I cells, fractions with apoA-II binding activity were collected, concentrated, and subjected to two-dimensional electrophoresis. Internal microprotein sequencing of the 55-kDa protein band revealed the binding protein as being heat shock protein 60 (hsp60), The hsp60 monoclonal antibody LK-1 blocked apoA-II binding to the 55-kDa HBP preparation. In summary, these results provide a potential mechanism to explain the known association between immunity developed against hsp60 and the development of atherosclerosis, (C) 2000 Academic Press. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, OTRR, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NIH, Dept Clin Pathol, Bethesda, MD 20892 USA. RP Eggerman, TL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, OTRR, 8800 Rockville Pike,NIH Campus Bldg 29B,Room 2NN1, Bethesda, MD 20892 USA. NR 52 TC 14 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 14 PY 2000 VL 277 IS 1 BP 228 EP 235 DI 10.1006/bbrc.2000.3663 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 367PJ UT WOS:000090070400039 PM 11027668 ER PT J AU Cisar, JO Xu, DQ Thompson, J Swaim, W Hu, L Kopecko, DJ AF Cisar, JO Xu, DQ Thompson, J Swaim, W Hu, L Kopecko, DJ TI An alternative interpretation of nanobacteria-induced biomineralization SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CALCIUM PHOSPHATE; STONE FORMATION; CALCIFICATION; NANNOBACTERIA; LIPIDS; ROCKS AB The reported isolation of nanobacteria from human kidney stones raises the intriguing possibility that these microorganisms are etiological agents of pathological extraskeletal calcification [Kajander, E. O. & Ciftcioglu. N. (1998) Proc. Natl. Acad. Sci. USA 95, 8274-8279]. Nanobacteria were previously isolated from FBS after prolonged incubation in DMEM. These bacteria initiated biomineralization of the culture medium and were identified in calcified particles and biofilms by nucleic acid stains, 16S rDNA sequencing, electron microscopy. and the demonstration of a transferable biomineralization activity. We have now identified putative nanobacteria, not only from FBS, but also from human saliva and dental plaque after the incubation of 0.45-mu m membrane-filtered samples in DMEM. Although biomineralization in our "cultures" was transferable to fresh DMEM. molecular examination of decalcified biofilms failed to detect nucleic acid or protein that would be expected from growth of a living entity. In addition, biomineralization was not inhibited by sodium azide. Furthermore, the 169 rDNA sequences previously ascribed to Nanobacterium sangoineum and Nanobacterium sp. were found to be indistinguishable from those of an environmental microorganism, Phyllobacterium mysinacearum, that has been previously detected as a contaminant in PCR. Thus. these data do not provide plausible support for the existence of a previously undiscovered bacterial genus. Instead, we provide evidence that biomineralization previously attributed to nanobacteria may be initiated by nonliving macromolecules and transferred on "subculture" by self-propagating microcrystalline apatite. C1 NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NIDCR, Cellular Imaging Core, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Enter & Sexually Transmitted Dis, Bethesda, MD 20892 USA. RP Cisar, JO (reprint author), NIDCR, Oral Infect & Immun Branch, NIH, Bldg 30,Room 302, Bethesda, MD 20892 USA. EM john.cisar@nih.gov NR 27 TC 148 Z9 162 U1 2 U2 21 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 OCT 10 PY 2000 VL 97 IS 21 BP 11511 EP 11515 DI 10.1073/pnas.97.21.11511 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363GA UT WOS:000089825700071 PM 11027350 ER PT J AU Slotkin, TA Seidler, FJ Ali, SF AF Slotkin, TA Seidler, FJ Ali, SF TI Cellular determinants of reduced adaptability of the aging brain: neurotransmitter utilization and cell signaling responses after MDMA lesions SO BRAIN RESEARCH LA English DT Article DE adenylyl cyclase; aging brain; dopamine; methylenedioxymethamphetamine (MDMA); serotonin (5-HT) ID ADENYLYL-CYCLASE; SEROTONIN TRANSPORTER; AGED RATS; SUBSTITUTED AMPHETAMINES; INCREASED EXPRESSION; MESSENGER-RNA; YOUNG; HEART; NEUROTOXICITY; RECEPTORS AB Senescence is accompanied by the loss of neurons and synapses, and the maintenance of function depends on adaptive change at the levels of synaptic activity and cellular responsiveness. In the current study, we administered the neurotoxin MDMA, to young and aged mice and assessed the effects on indices of neuronal activity and cell signaling mediated through adenylyl cyclase. Young mice given MDMA showed 80% depletion of dopamine in the caudate and 30% depletion in the cerebral cortex; measurements of dopamine turnover indicated a compensatory upregulation of the activity of the remaining neurons in the caudate but downregulation in the cerebral cortex, Serotonin levels were comparatively less affected but serotonin turnover was decreased significantly in both regions. At the level of cell signaling, the young mice showed heterologous upregulation of adenylyl cyclase activity and a consequent enhancement of responses mediated through neurotransmitter receptors. In aged mice, MDMA treatment produced the same degree of lesioning but substantially different changes in neuronal activity and cell signaling. In the cerebral cortex, dopamine turnover was increased, and serotonin turnover decreased, effects opposite in direction to those seen in young mice. In the aged group, MDMA elicited heterologous loss of adenylyl cyclase responses instead of displaying the supersensitivity that had been seen in the young group. The aging brain thus displays maladaptation to the loss of monoaminergic input, effects that may augment the functional impairment associated with neurodegenerative disorders or stroke. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Slotkin, TA (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. EM t.slotkin@duke.edu FU NICHD NIH HHS [HD09713] NR 42 TC 24 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD OCT 6 PY 2000 VL 879 IS 1-2 BP 163 EP 173 DI 10.1016/S0006-8993(00)02767-0 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 362DG UT WOS:000089762900021 PM 11011018 ER PT J AU Pazdur, R AF Pazdur, R TI Response rates, survival, and chemotherapy trials SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20857 USA. RP Pazdur, R (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, 5600 Fishers Lane,HFD 150, Rockville, MD 20857 USA. NR 6 TC 37 Z9 38 U1 0 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 4 PY 2000 VL 92 IS 19 BP 1552 EP 1553 DI 10.1093/jnci/92.19.1552 PG 2 WC Oncology SC Oncology GA 358NC UT WOS:000089563300002 PM 11018082 ER PT J AU Lamb, NE Yi, P Rozen, R Hobbs, C James, SJ AF Lamb, NE Yi, P Rozen, R Hobbs, C James, SJ TI Folate metabolism and meiotic recombination: Interlocking pieces of the nondisjunction puzzle. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Emory Univ, Atlanta, GA 30322 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. McGill Univ, Montreal Childrens Hosp, Res Inst, Montreal, PQ H3H 1P3, Canada. Arkansas Ctr Birth Defects Res, Little Rock, AR USA. NR 0 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 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1412 BP 259 EP 259 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701413 ER PT J AU Astrinidis, A Strizheva, GD Carsillo, T Kruger, W Sullivan, EJ Ryu, JH Henske, EP AF Astrinidis, A Strizheva, GD Carsillo, T Kruger, W Sullivan, EJ Ryu, JH Henske, EP TI Evidence of a correlation between germline mutations in the carboxy-terminus of tuberin (TSC2) and pulmonary lymphangiomyomatosis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. US FDA, Rockville, MD 20857 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. RI Astrinidis, Aristotelis/A-1396-2010 NR 0 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 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2240 BP 399 EP 399 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702241 ER PT J AU D'Agnillo, F Alayash, AI AF D'Agnillo, F Alayash, AI TI Interactions of hemoglobin with hydrogen peroxide alters thiol levels and course of endothelial cell death SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE glutathione; hemoprotein; ferryl intermediate; apoptosis ID RED-BLOOD-CELLS; OXIDATIVE STRESS; LIPID-PEROXIDATION; NITRIC-OXIDE; GLUTATHIONE DEPLETION; HEMORRHAGIC-SHOCK; RENAL-FAILURE; APOPTOSIS; INJURY; MYOGLOBIN AB We investigated cellular injury and death induced by ultrapure human Hb (HbA(0)) and its diaspirin cross-linked derivative DBBF-Hb in normal and glutathione (GSH)-depleted bovine aortic endothelial cells subjected to hydrogen peroxide (H2O2). HbA(0) underwent extensive degradation and heme loss, whereas DBBF-Hb persisted longer in its ferryl (Fe4+) form. The formation of ferryl HbA(0) or ferryl DBBF-Hb was associated with a significant decrease in endothelial cell GSH compared with the addition of H2O2 or Hbs alone. This effect was inhibited by catalase, but not by superoxide dismutase or deferoxamine mesylate. The presence of HbA(0) and DBBF-Hb reduced H2O2-induced apoptosis, as measured by cell morphology, annexin V binding assay, and caspase inhibition, consistent with the ability to consume H2O2 in an enzyme-like fashion. However, the pattern of cell death and injury produced by HbA(0) and DBBF-Hb appeared to be distinctly different among proteins as well as among cells with and without GSH. These findings may have important implications for the use of cell-free Hb as oxygen therapeutics in patients with coexisting pathologies who may lack antioxidant protective mechanisms. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Plasma Derivat, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Plasma Derivat, 8800 Rockville Pike,Bldg 29,Rm 112, Bethesda, MD 20892 USA. NR 64 TC 23 Z9 23 U1 2 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 2000 VL 279 IS 4 BP H1880 EP H1889 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 358FK UT WOS:000089547600050 PM 11009476 ER PT J AU Brown, SL Middleton, MS Berg, WA Soo, MS Pennello, G AF Brown, SL Middleton, MS Berg, WA Soo, MS Pennello, G TI Prevalence of rupture of silicone gel breast implants revealed on MR imaging in a population of women in Birmingham, Alabama SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CONNECTIVE-TISSUE DISEASES; COMPLICATIONS; MAMMOGRAPHY; SONOGRAPHY; DIAGNOSIS AB OBJECTIVE. Silicone gel breast implants have been reported to rupture, but the prevalence of implant rupture in an unreferred population of women is not known. The objective of this study was to assess the prevalence of implant rupture and the presence of extracapsular silicone gel in an unreferred population of women without regard to the absence or presence of any local or systemic symptoms. SUBJECTS AND METHODS. Women identified as part of a National Cancer Institute cohort study on breast implants, living in the Birmingham, AL, area were invited to undergo MR imaging of their current silicone gel breast implants at the Kirl;lin Clinic at the University of Alabama at Birmingham. Three radiologists independently examined and rated all MR images for signs of implant rupture and extracapsular silicone. RESULTS. A total of 344 women with silicone gel boast implants underwent MR imaging. Breast implant rupture was reported by at least two of three radiologists for 378 (55.0%) of the 687 implants in this study. Another 50 implants (7.2%) were rated as indeterminate (suspicious) for rupture. A majority of women in this study, 265 (77.0%) of 344, had at least one breast implant that was rated as ruptured or indeterminate. Radiologists also agreed that silicone gel could be seen outside the fibrous capsule that forms around the: implant in 85 (12.4%) of the 687 implants affecting 73 women (21.2%). Factors that affected implant rupture were implant age and location (submuscular or subglandular). The median implant age at rupture was estimated to be 10.8 years with a 95% confidence interval of 8.4-13.9 years. CONCLUSION. The prevalence of silent or occult silicone gel boast implant rupture is higher than was previously suspected. Most women in this study had MR imaging evidence of at least one ruptured silicone gel breast implant. C1 Ctr Devices Radiol Hlth Food & Drug Adm, Off Surveillance & Biometr, Rockville, MD 20850 USA. Univ Calif San Diego, Sch Med, Dept Radiol, San Diego, CA 92103 USA. Univ Maryland, Sch Med, Dept Radiol, Div Breast Imaging, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Greenbaum Canc Ctr, Baltimore, MD 21201 USA. Duke Univ, Duke S Hosp, Med Ctr, Dept Radiol, Durham, NC 27710 USA. RP Brown, SL (reprint author), Ctr Devices Radiol Hlth Food & Drug Adm, Off Surveillance & Biometr, 1350 Piccard Dr,HFZ-541, Rockville, MD 20850 USA. RI Soo, Mary/B-1580-2017 NR 34 TC 73 Z9 73 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2000 VL 175 IS 4 BP 1057 EP 1064 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 357GQ UT WOS:000089490500025 PM 11000165 ER PT J AU White, DG Piddock, LJV Maurer, JJ Zhao, SH Ricci, V Thayer, SG AF White, DG Piddock, LJV Maurer, JJ Zhao, SH Ricci, V Thayer, SG TI Characterization of fluoroquinolone resistance among veterinary isolates of avian Escherichia coli SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID QUINOLONE RESISTANCE; ANTIMICROBIAL AGENTS; DNA GYRASE; CHICKENS; MUTATION; MEDICINE; BACTERIA; POULTRY; ANIMALS; GENE AB Fluoroquinolone-resistant avian Escherichia coli isolates from northern Georgia were investigated for gyrA and parC mutations. All isolates contained a mutation in GgrA replacing Ser83 with Leu; seven isolates also contained mutations replacing Asp87 with either Gly or Tyr. Random amplified polymorphic DNA analysis revealed that quinolone-resistant E. coli isolates were genetically diverse. C1 US FDA, Ctr Vet Med, Res Off, Div Anim & Food Microbiol, Laurel, MD 20708 USA. Univ Georgia, Dept Avian Med, Athens, GA 30602 USA. Univ Birmingham, Div Immun & Infect, Birmingham, W Midlands, England. N Dakota State Univ, Dept Vet & Microbiol Sci, Fargo, ND 58105 USA. RP White, DG (reprint author), US FDA, Ctr Vet Med, Res Off, Div Anim & Food Microbiol, Laurel, MD 20708 USA. NR 25 TC 48 Z9 49 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2000 VL 44 IS 10 BP 2897 EP 2899 DI 10.1128/AAC.44.10.2897-2899.2000 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 355TK UT WOS:000089402300056 PM 10991884 ER PT J AU Walsh, TJ Jackson, AJ Lee, JW Amantea, M Sein, T Bacher, J Zech, L AF Walsh, TJ Jackson, AJ Lee, JW Amantea, M Sein, T Bacher, J Zech, L TI Dose-dependent pharmacokinetics of amphotericin B lipid complex in rabbits (vol 44, pg 2068, 2000) SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Correction C1 NCI, Mycol Unit, NIH, Bethesda, MD 20892 USA. NCI, Immunocompromised Host Sect, NIH, Bethesda, MD 20892 USA. NCI, Math Biol Lab, NIH, Bethesda, MD 20892 USA. NIH, Vet Resource Program, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Div Bioequivalence, Rockville, MD 20857 USA. RP Walsh, TJ (reprint author), NCI, Mycol Unit, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2000 VL 44 IS 10 BP 2924 EP 2924 DI 10.1128/AAC.44.10.2924-2924.2000 PG 1 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 355TK UT WOS:000089402300065 ER PT J AU Wang, RF Wennerstrom, D Cao, WW Khan, AA Cerniglia, CE AF Wang, RF Wennerstrom, D Cao, WW Khan, AA Cerniglia, CE TI Cloning, expression, and characterization of the katG gene, encoding catalase-peroxidase, from the polycyclic aromatic hydrocarbon-degrading bacterium Mycobacterium sp strain PYR-1 SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID HYDROGEN-PEROXIDE; PYRENE; DEGRADATION; IDENTIFICATION; FLUORANTHENE; INACTIVATION; DIOXYGENASE AB A 81-kDa protein from Mycobacterium sp. strain PYR-1 was expressed in response to exposure of the strain to the polycyclic aromatic hydrocarbon pyrene and recovered by two-dimensional gel electrophoresis. The N-terminal sequence of the protein indicated that it was similar to catalase-peroxidase. An oligonucleotide probe designed from this sequence was used to screen a genomic library of Mycobacterium sp, strain PYR-1, and a positive clone, containing a part of the gene encoding the 81-kDa protein, was isolated. A gene-walking technique was used to sequence the entire gene, which was identified as katG for catalase-peroxidase. The deduced KatG protein sequence showed significant homology to KatGII of Mycobacterium fortuitum and clustered with catalase-peroxidase proteins from other Mycobacterium species in a phylogenetic tree. The katG gene was expressed in Escherichia coli to produce a protein with catalase-peroxidase activity. Since the induction of this catalase-peroxidase occurred in pyrene-induced cultures and the exposure of these cultures to hydrogen peroxide reduced pyrene metabolism, our data suggest that this enzyme plays a role in polycyclic aromatic hydrocarbon metabolism by strain PYR-1. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM CCerniglia@nctr.fda.gov NR 26 TC 38 Z9 46 U1 0 U2 9 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 OCT PY 2000 VL 66 IS 10 BP 4300 EP 4304 DI 10.1128/AEM.66.10.4300-4304.2000 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 360CW UT WOS:000089649700018 PM 11010873 ER PT J AU Miller, AJ Bayles, DO Eblen, BS AF Miller, AJ Bayles, DO Eblen, BS TI Cold shock induction of thermal sensitivity in Listeria monocytogenes SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID SUBLETHAL HEAT-SHOCK; ESCHERICHIA-COLI; SCOTT-A; SALMONELLA-TYPHIMURIUM; ENVIRONMENTAL STRESSES; GROWTH TEMPERATURE; GROUND-BEEF; RESISTANCE; ADAPTATION; THERMOTOLERANCE AB Cold shock at 0 to 15 degrees C for 1 to 3 h increased the thermal sensitivity of Listeria monocytogenes. In a model broth system, thermal death time at 60 degrees C was reduced by up to 45% after L. monocytogenes Scott A was cold shocked for 3 h, The duration of the cold shock affected thermal tolerance more than did the magnitude of the temperature downshift. The Z values were 8.8 degrees C for controls and 7.7 degrees C for cold-shocked cells. The D values of cold-shocked cells did not return to control levels after incubation for 3 h at 28 degrees C followed by heating at 60 degrees C, Nine L. monocytogenes strains that were cold shocked for 3 h exhibited D,, values that were reduced by 13 to 37%. The D-value reduction was greatest in cold-shocked stationary-phase cells compared to cells from cultures in either the lag or exponential phases of growth. In addition, cold-shocked cells were more likely to be inactivated by a given heat treatment than nonshocked cells, which were more likely to experience sublethal injury. The D values of chloramphenicol-treated control cells and chloramphenicol-treated cold-shocked cells were no different from those of untreated cold-shocked cells, suggesting that cold shock suppresses synthesis of proteins responsible for heat protection. In related experiments, the D values of L. monocytogenes Scott A were decreased 25% on frankfurter skins and 15% in ultra-high temperature milk if the inoculated products were first cold shocked, Induction of increased thermal sensitivity in L. monocytogenes by thermal flux shows potential to become a practical and efficacious preventative control method. C1 USDA ARS, Eastern Reg Res Ctr, Microbial Food Safety Res Unit, Wyndmoor, PA 19038 USA. RP Miller, AJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Mail Stop HFS-32,200 C St SW, Washington, DC 20204 USA. NR 47 TC 27 Z9 28 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD OCT PY 2000 VL 66 IS 10 BP 4345 EP 4350 DI 10.1128/AEM.66.10.4345-4350.2000 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 360CW UT WOS:000089649700025 PM 11010880 ER PT J AU Lampel, KA Orlandi, PA Kornegay, L AF Lampel, KA Orlandi, PA Kornegay, L TI Improved template preparation for PCR-based assays for detection of food-borne bacterial pathogens SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; LISTERIA-MONOCYTOGENES; AMPLIFICATION; GENE; DNA; MICROORGANISMS; SALMONELLA; PRODUCTS AB Shigella flexneri, Salmonella enterica serotype Typhimurium, and Listeria monocytogenes were applied to FTA filters, and the filters were used directly as templates to demonstrate their sensitivity and applicability in PCR-based detection assays. With pure cultures, the sensitivities of detection by FTA filter-based PCR were 30 to 50 and 200 CFU for the gram-negative enterics and Listeria, respectively. Different numbers of S. flexneri cells were used in controlled contamination experiments with several different foods (produce, beef, and apple cider). Aliquots from concentrated food washes subsequently spotted onto FTA filters and assayed by PCR gave consistently positive results and detection limits similar to those observed with pure-culture dilutions. This universal method for PCR template preparation from bacterial cells is rapid and highly sensitive and reduces interference from food-associated inhibitors of PCR In addition, its broad applicability eliminates the need for multiple methods for analysis of food matrices. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Lampel, KA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-237,200 C St SW, Washington, DC 20204 USA. NR 21 TC 98 Z9 104 U1 0 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD OCT PY 2000 VL 66 IS 10 BP 4539 EP 4542 DI 10.1128/AEM.66.10.4539-4542.2000 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 360CW UT WOS:000089649700058 PM 11010913 ER PT J AU Dalu, A Blaydes, BS Lomax, LG Delclos, KB AF Dalu, A Blaydes, BS Lomax, LG Delclos, KB TI A comparison of the inflammatory response to a polydimethylsiloxane implant in male and female Balb/c mice SO BIOMATERIALS LA English DT Article DE biomaterials; sexual dimorphism; inflammatory response; cytokines ID TUMOR-NECROSIS-FACTOR; BLOOD MONONUCLEAR-CELLS; FOREIGN-BODY REACTION; SOFT-TISSUE RESPONSE; RAT ANIMAL-MODEL; BIOMEDICAL POLYMERS; RECEPTOR ANTAGONIST; ESTROGEN-RECEPTORS; SILICONE IMPLANTS; CYTOKINE RELEASE AB The implantation of biomaterials elicits a host response that influences the long-term behavior of implanted medical devices. This foreign body response is governed by cells of the immune system. Because sexual dimorphism in the immune system is well-established, a comparative study of the foreign body response in male and female mice was initiated. Eight-week-old male and female Balb/c mice received two subcutaneous implants in the interscapular region of a smooth peroxide-catalyzed polydimethylsiloxane (PDMS) and were sacrificed at 2, 14, 42, 70, and 105 days after implantation (n = 6 per sex per time point). Controls for each time point underwent the surgical procedure but received no implant. Tissue from the implant or surgical site was fixed, processed, and paraffin-embedded for histopathological evaluation and immunohistochemical (IHC) staining for tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). In control animals, an inflammatory response was observed at 2 days that was decreased by 14 days and absent after 42 days. At 2 and 14 days after PDMS implantation, a mild to moderate inflammatory reaction was observed around implants. The peak response was seen at 14 days, and granulation tissue, composed primarily of fibroblasts, macrophages, and neutrophils, was first observed at this time. After 105 days, the implantation site was surrounded by mature connective tissue, which had minimal numbers of macrophages and neutrophils, with severity scores that did not differ significantly in males and females. The immunostaining for TNF-alpha and IL-1 beta followed similar temporal patterns, with both reaching a peak at the two week time point and remaining elevated, compared to level of expression in the controls, throughout the 105 day observation period. Staining for both cytokines in the implanted animals was generally higher in females than in males, although this difference was significant only for IL-1 beta. These results suggest subtle differences between males and females in the activity of peri-implant inflammatory cells. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Pathol Associates Int Corp, Jefferson, AR 72079 USA. RP Delclos, KB (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd,HFT-110, Jefferson, AR 72079 USA. NR 60 TC 15 Z9 16 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD OCT PY 2000 VL 21 IS 19 BP 1947 EP 1957 DI 10.1016/S0142-9612(00)00078-8 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 337YA UT WOS:000088389900004 PM 10941916 ER PT J AU Mondoro, TH White, MM Jennings, LK AF Mondoro, TH White, MM Jennings, LK TI Active GPIIb-IIIa conformations that link ligand interaction with cytoskeletal reorganization SO BLOOD LA English DT Article ID GLYCOPROTEIN-IIB; CLOT RETRACTION; TYROSINE PHOSPHORYLATION; MONOCLONAL-ANTIBODIES; PLATELET CYTOSKELETON; FIBRINOGEN RECEPTOR; INTEGRIN; AGGREGATION; ACTIVATION; COMPLEX AB Glycoprotein (GP) IIb-IIIa plays a critical role in platelet aggregation and platelet-mediated clot retraction. This study examined the intramolecular relationship between GPIIb-IIIa activation and fibrinogen binding, platelet aggregation, and platelet-mediated clot retraction. To distinguish between different high-affinity activation states of GPIIb-IIIa, the properties of an antibody (D3) specific for GPIIIa that induces GPIIb-IIIa binding to adhesive protein molecules and yet completely inhibits clot retraction were used. Clot retraction inhibition by D3 was not due to altered platelet-fibrin interaction; however, combination treatments of D3 and adenosine diphosphate (ADP) inhibited full-scale aggregation and decreased the amounts of GPIIb-IIIa and talin incorporated into the core cytoskeletons. Morphologic evaluation of the D3/ADP aggregates showed platelets that were activated but to a lesser extent when compared to ADP only. ADR addition to platelets caused an increase in the number of D3 binding sites indicating that ligand had bound to the GPIIb-IIIa receptor. These data suggest that high-affinity GPIIb-IIIa-mediated ligand binding can be separated mechanistically from GPIIb-IIIa-mediated clot retraction and that clot retraction requires additional signaling through GPIIb-IIIa after ligand binding. The conformation recognized by D3 represents the expression of a GPIIb-IIIa activation state that participates in full-scale platelet aggregation, cytoskeletal reorganization, and clot retraction.(Blood. 2000; 96:2487-2495) (C) 2000 by The American Society of Hematology. C1 Univ Tennessee, Vasc Biol Program, Memphis, TN 38163 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Jennings, LK (reprint author), Univ Tennessee, Vasc Biol Program, Rm H300,Coleman Bldg,956 Court Ave, Memphis, TN 38163 USA. FU NHLBI NIH HHS [HL53514] NR 40 TC 11 Z9 11 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 OCT 1 PY 2000 VL 96 IS 7 BP 2487 EP 2495 PG 9 WC Hematology SC Hematology GA 358HL UT WOS:000089552500025 PM 11001901 ER PT J AU Yang, ZJ Faustino, PJ Andrews, PA Monastra, R Rasmussen, AA Ellison, CD Cullen, KJ AF Yang, ZJ Faustino, PJ Andrews, PA Monastra, R Rasmussen, AA Ellison, CD Cullen, KJ TI Decreased cisplatin/DNA adduct formation is associated with cisplatin resistance in human head and neck cancer cell lines SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE head and neck cancer; cisplatin; glutathione; apoptosis ID PLATINUM-BASED CHEMOTHERAPY; S-TRANSFERASE-PI; OVARIAN-CANCER; INDUCED APOPTOSIS; BCL-2 EXPRESSION; GLUTATHIONE; CARCINOMA; CYTOTOXICITY; SENSITIVITY; CIS-DIAMMINEDICHLOROPLATINUM(II) AB Purpose: To evaluate the correlation between cisplatin sensitivity, intracellular glutathione, and platinum/DNA adduct formation (measured by atomic absorption spectroscopy) in a series of seven head and neck cancer cell lines, and to evaluate the effect of biochemical modulation of glutathione on platinum/DNA adduct formation and repair. Methods: Cisplatin/DNA adducts were measured by atomic absorption spectroscopy. Glutathione content was measured by enzymatic assay and was modulated with buthionine sulfoximine. Apoptosis was measured by double-labeled flow cytometry. Results: Intracellular glutathione concentration was strongly correlated with cisplatin resistance (P = 0.002, R-2 = 0.7). There was also a statistically significant inverse correlation between cisplatin/DNA adduct formation and the IC50 for cisplatin in these cell lines. (P = 0.0004, R-2 = 0.67). In addition, resistant cells were able to repair approximately 70% of cisplatin/DNA adducts at 24 h, while sensitive cells repaired less than 28% of adducts in the same period. However, despite the positive correlation between cellular glutathione and cisplatin resistance, there was no direct correlation between intracellular glutathione concentration and platinum/DNA adduct formation. Further, depletion of intracellular glutathione by buthionine sulfoximine did not dramatically alter formation of cisplatin/DNA adducts even though it resulted in marked increase in cisplatin cytotoxicity and was associated with increased apoptosis. Conclusions: These results suggest that glutathione has multiple effects not directly related to formation of cisplatin/DNA adducts, but may also be an important determinant of the cell's ability to repair cisplatin-induced DNA damage and resist apoptosis. C1 Georgetown Univ, Med Ctr, Div Hematol Oncol, Washington, DC 20007 USA. Georgetown Univ, Lombardi Canc Ctr, Washington, DC 20007 USA. US FDA, Laurel, MD 20708 USA. RP Cullen, KJ (reprint author), Georgetown Univ, Med Ctr, Div Hematol Oncol, 3800 Reservoir Rd NW, Washington, DC 20007 USA. FU NCI NIH HHS [R21CA73866] NR 30 TC 38 Z9 38 U1 2 U2 8 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 OCT PY 2000 VL 46 IS 4 BP 255 EP 262 DI 10.1007/s002800000167 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 361RY UT WOS:000089738400001 PM 11052622 ER PT J AU Collins, JM AF Collins, JM TI Innovations in Phase 1 trial design: Where do we go next? SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID I CLINICAL-TRIALS C1 US FDA, Lab Clin Pharmacol, Rockville, MD 20850 USA. RP Collins, JM (reprint author), US FDA, Lab Clin Pharmacol, Room 314,4 Res Court, Rockville, MD 20850 USA. NR 15 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 OCT PY 2000 VL 6 IS 10 BP 3801 EP 3802 PG 2 WC Oncology SC Oncology GA 365CV UT WOS:000089931600001 PM 11051221 ER PT J AU Ranstam, J Buyse, M George, SL Evans, S Geller, NL Scherrer, B Lesaffre, E Murray, G Edler, L Hutton, JL Colton, T Lachenbruch, P AF Ranstam, J Buyse, M George, SL Evans, S Geller, NL Scherrer, B Lesaffre, E Murray, G Edler, L Hutton, JL Colton, T Lachenbruch, P CA ISCB Subcomm Fraud TI Fraud in medical research: An international survey of biostatisticians SO CONTROLLED CLINICAL TRIALS LA English DT Article AB The characteristics of scientific fraud and its impact on medical research are in general not well known. However, the interest in the phenomenon has increased steadily during the last decade. Biostatisticians routinely work closely with physicians and scientists in many branches of medical research and have therefore unique insight into data. In addition, they have methodological competence to detect fraud and could be expected to have a professional interest in valid results. Biostatisticians therefore are likely to provide reliable information on the characteristics of fraud in medical research. The objective of this survey of biostatisticians, who were members of the International Society for Clinical Biostatistics, was to assess the characteristics of fraud in medical research. The survey was performed between April and July 1998. The participation rate was only 37%. We report the results because a majority (51%) of the participants knew about fraudulent projects, and many did not know whether the organization they work for has a formal system for handling suspected fraud or not. Different forms of fraud (e.g., fabrication and falsification of data, deceptive reporting of results, suppression of data, and deceptive design or analysis) had been observed in fairly similar numbers. We conclude that fraud is not a negligible phenomenon in medical research, and that increased awareness of the forms in which it is expressed seems appropriate. C1 Malmo Univ, Sch Hlth & Soc, SE-20506 Malmo, Sweden. Int Inst Drug Dev, Brussels, Belgium. Duke Univ, Durham, NC 27706 USA. Med Control Agcy, London, England. NHLBI, Bethesda, MD 20892 USA. Inst Rech Jouvenail, Paris, France. Ctr Biostat, Louvain, Belgium. Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland. German Canc Res Ctr, D-6900 Heidelberg, Germany. Univ Newcastle Upon Tyne, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Boston Univ, Boston, MA 02215 USA. US FDA, Rockville, MD 20857 USA. RP Ranstam, J (reprint author), Malmo Univ, Sch Hlth & Soc, SE-20506 Malmo, Sweden. RI Ranstam, Jonas/A-4386-2009 OI Ranstam, Jonas/0000-0002-8287-7273 NR 9 TC 35 Z9 37 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD OCT PY 2000 VL 21 IS 5 BP 415 EP 427 DI 10.1016/S0197-2456(00)00069-6 PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 361AH UT WOS:000089699200001 PM 11018560 ER PT J AU Ellenberg, SS AF Ellenberg, SS TI Fraud is bad, studying fraud is hard SO CONTROLLED CLINICAL TRIALS LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Ellenberg, SS (reprint author), US FDA, Rockville, MD 20857 USA. NR 6 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD OCT PY 2000 VL 21 IS 5 BP 498 EP 500 DI 10.1016/S0197-2456(00)00089-1 PG 3 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 361AH UT WOS:000089699200007 PM 11018566 ER PT J AU Pollock, ML Fazio, A AF Pollock, ML Fazio, A TI Medical center clinical rotation for pharmaceutical drug information professionals SO DRUG INFORMATION JOURNAL LA English DT Article DE drug information; rotation; medical center AB Drug information practitioners can be at a disadvantage in that they do not work directly in patient-care environments. This article describes a clinical rotation program developed to enable Parke-Davis drug information colleagues to experience a contemporary patient care environment at a local medical center. In March 2000, 13 Parke-Davis drug information professionals completed one-day rotations at Morristown Memorial Hospital. The general medicine clinical rotation provided meaningful experience in observing state-of the-art health care, helped drug information colleagues better relate to the situations that health professional customers face, fostered more effective communication with health care professionals and patients, and provided a better appreciation of patient-care literature and in preparing drug information-medical communications that refer to and discuss patient care situations. Morristown Memorial Hospital has been invited to participate in a rotation program at Parke-Davis. C1 Parke Davis, Drug Informat Serv, Morris Plains, NJ USA. Morristown Mem Hosp, Dept Pharm, Morristown, NJ USA. RP Pollock, ML (reprint author), US FDA, CDER, Off Post Mkt Drug Risk Assessment, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 2 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 OCT-DEC PY 2000 VL 34 IS 4 BP 1129 EP 1132 PG 4 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 374JZ UT WOS:000165343200019 ER PT J AU Sprando, RL Collins, TFX Wiesenfeld, P Babu, US Rees, C Black, T Olejnik, N Rorie, J AF Sprando, RL Collins, TFX Wiesenfeld, P Babu, US Rees, C Black, T Olejnik, N Rorie, J TI Testing the potential of flaxseed to affect spermatogenesis: morphometry SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE morphology; testis; flaxseed; lignans; male rat; phytoestrogens ID LEYDIG-CELLS; PHYTOESTROGENS AB Quantitative information was collected on male reproductive effects of maternal and postnatal dietary exposure to flaxseed (20 or 40%), flaxmeal (13 or 26%) or standard NIH AIN-93 feed (0% flaxseed control). Measurements were made on the testes of Fl generation males rats (1) whose mothers were exposed to the diets designated above, and (2) who, after weaning, were placed on the same diet as their mothers for an additional 70 days. The seminiferous tubules comprised 86%, 84%, 84%, 84% and 85% of the total testis volume while the interstitial space comprised 12%, 14%, 14%, 14%, 13% of the total testis volume for the 0% flaxseed/flaxmeal, 20% flaxseed, 13% flaxmeal, 40% flaxseed and 26% flaxmeal groups, respectively. Statistically significant decreases in the absolute volume of the seminiferous tubules were observed in the 20% and 40% flaxseed-treated groups when these groups were compared to controls. Borderline statistically significant differences were also observed when Sertoli cell nucleolar number per tubular cross-section were compared in the 13% flaxmeal and 20% flaxseed treatment groups. These effects were not considered biologically significant because other parameters of male reproductive function appeared normal, Overall, the quantitative information obtained suggests that exposure to flaxseed/flaxmeal at the doses used in the present study does not adversely affect testis structure or spermatogenesis in the rat. Published by Elsevier Science Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Toxicol Res, Beltsville, MD 20708 USA. RP Sprando, RL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Toxicol Res, 8301 Muirkirk Rd, Beltsville, MD 20708 USA. NR 26 TC 9 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD OCT PY 2000 VL 38 IS 10 BP 887 EP 892 DI 10.1016/S0278-6915(00)00080-6 PG 6 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 359WV UT WOS:000089635800005 PM 11039322 ER PT J AU Kvenberg, J Stolfa, P Stringfellow, D Garrett, ES AF Kvenberg, J Stolfa, P Stringfellow, D Garrett, ES TI HACCP development and regulatory assessment in the United States of America SO FOOD CONTROL LA English DT Article DE HACCP; food safety; critical control points; critical limits; pathogen reduction; regulatory; risk; verification; validation AB Hazard Analysis Critical Control Point (HACCP) is internationally recognized as the best method of assuring product safety by controlling foodborne safety hazards. Currently, within the USA, the FDA has mandated HACCP for fish and fishery products and is proposing mandating HACCP for fruit and vegetable juices. The USDA has mandated Pathogen Reduction/HACCP requirements for meat and poultry processing, and the NMFS Seafood Inspection Program operates a voluntary HACCP program for seafood plants. The requirements for mandatory implementation and proposed regulations represent a significant change in the manner in which foods are regulated for food safety and necessitate a new understanding of the different roles and responsibilities between the food industries and the regulatory agencies within the USA. Each agency will approach the evaluation process differently given their unique legislative authorities and programmatic operations. Nevertheless, each agency agrees that HACCP is the best food control system of choice and is committed to improve food safety requirements. (C) 2000 Published by Elsevier Science Ltd. All rights reserved. C1 US FDA, Div HACCP Programs, HFS 615, Washington, DC 20204 USA. USDA, FSIS, Washington, DC 20250 USA. Natl Marine Fisheries Serv, Natl Seafood Inspect Lab, Pascagoula, MS 39568 USA. RP Kvenberg, J (reprint author), US FDA, Div HACCP Programs, HFS 615, 200 St SW, Washington, DC 20204 USA. NR 30 TC 15 Z9 18 U1 1 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-7135 J9 FOOD CONTROL JI Food Control PD OCT PY 2000 VL 11 IS 5 BP 387 EP 401 DI 10.1016/S0956-7135(99)00090-0 PG 15 WC Food Science & Technology SC Food Science & Technology GA 314BL UT WOS:000087034200010 ER PT J AU Lee, YJ Shacter, E AF Lee, YJ Shacter, E TI Hydrogen peroxide inhibits activation, not activity, of cellular caspase-3 in vivo SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; CYTOCHROME-C; POLY(ADP-RIBOSE) POLYMERASE; NEUTROPHIL APOPTOSIS; OXIDATIVE STRESS; LYMPHOMA-CELLS; DEATH; NECROSIS; INDUCTION; CLEAVAGE AB Oxidants such as H2O2 can induce a low level of apoptosis at low concentrations but at higher concentrations cause necrosis. Higher concentrations of H2O2 also inhibit the induction of apoptosis by chemotherapy drugs. One theory is that, at higher concentrations, H2O2 causes direct oxidative inactivation of caspase-3 activity, thus preventing the apoptotic pathway from being used. We find that treatment of recombinant caspase-3 with H2O2 can partially reduce its enzymatic activity: However, the following findings show that this does not occur in the cell. (1) The inhibition by H2O2 of VP-16-induced apoptosis and cellular caspase-3 activity can be overcome by adding inhibitors of poly(ADP-ribose) polymerase (PARP) at sub-stoichiometric concentrations. (2) Delayed addition of H2O2 to VP-16-treated cells prevents additional caspase induction but does not inhibit the caspase activity that has already been generated. (3) H2O2 is a poor inhibitor of caspase-3 activity in cell lysates. (4) Addition of H2O2 to cells inhibits activation of caspase-9, which is required for activation of caspase-3. We conclude that inhibition of caspase-3 activity in the cell occurs indirectly at a step located upstream of caspase-3 activation. H2O2 acts in part by inducing DNA strand breaks and activating PARP, thus depleting the cells of ATP. When this pathway is blocked, even high concentrations of H2O2 can induce caspase-9 and -3 activation and cause apoptosis. (C) 2000 Elsevier Science Inc. C1 US FDA, Ctr Biol Evaluat & Res, Immunol Lab, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Shacter, E (reprint author), US FDA, Ctr Biol Evaluat & Res, Immunol Lab, Div Therapeut Prot, HFM-538,Bldg 29A,Room 2A-11,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 38 TC 69 Z9 71 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD OCT 1 PY 2000 VL 29 IS 7 BP 684 EP 692 DI 10.1016/S0891-5849(00)00366-X PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 367VR UT WOS:000090082600012 PM 11033421 ER PT J AU Gallagher, G Dickensheets, H Eskdale, J Izotova, LS Mirochnitchenko, OV Peat, JD Vazquez, N Pestka, S Donnelly, RP Kotenko, SV AF Gallagher, G Dickensheets, H Eskdale, J Izotova, LS Mirochnitchenko, OV Peat, JD Vazquez, N Pestka, S Donnelly, RP Kotenko, SV TI Cloning, expression and initial characterisation of interleukin-19 (IL-19), a novel homologue of human interleukin-10 (IL-10) SO GENES AND IMMUNITY LA English DT Article DE interleukin-10; interleukin-19; homologue; expression; monocyte; chromosome one; cloning ID SYSTEMIC LUPUS-ERYTHEMATOSUS; NECROSIS-FACTOR-ALPHA; B-LYMPHOCYTE HYPERACTIVITY; INTERFERON-GAMMA RECEPTOR; RHEUMATOID-ARTHRITIS; CRYSTAL-STRUCTURE; HUMAN MONOCYTES; T-CELLS; CYTOKINE SYNTHESIS; MOLECULAR-CLONING AB Interleukin-10 (IL-10) is a pleiotropic cytokine with important immunoregulatory functions whose actions influence activities of many of the cell-types in the immune system. We report here identification and cloning of a gene and corresponding cDNAs encoding a novel homologue of IL-IO, designated IL-19. IL-19 shares 21% amino acid identity with IL-10. The exon/intron structure of IL-19 is similar to that of the human IL-IO gene, comprising five exons and four introns within the coding region of the IL-19 cDNA. There are at least two distinct IL-19 mRNA species that differ in their 5'-sequences, suggesting the existence of an intron in the 5'-sequences of coding portion of the IL-19 gene. The longer 5'-sequence contains an alternative initiating ATG codon that is in-frame with the rest of the coding sequence. The expression of IL-19 mRNA can be induced in monocytes by LPS-treatment. The appearance of IL-19 mRNA in LPS-stimulated monocytes was slightly delayed compared to expression of IL-10 mRNA: significant levels of IL-10 mRNA were detectable at 2 h post-stimulation, whereas IL-19 mRNA was not detectable until 4 h. Treatment of monocytes with IL-4 or IL-13 did not induce de novo expression of IL-19, but these cytokines did potentiate IL-19 gene expression in LPS-stimulated monocytes. In addition, GM-CSF was capable of directly inducing IL-19 gene expression in monocytes. IL-19 does nor bind or signal through the canonical IL-10 receptor complex, suggesting existence of an IL-19 specific receptor complex, the identity of which remains to be discovered. C1 Univ Glasgow, Glasgow Royal Infirm, Dept Surg, Glasgow G31 2ER, Lanark, Scotland. US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet & Microbiol, Piscataway, NJ 08854 USA. RP Gallagher, G (reprint author), Univ Glasgow, Glasgow Royal Infirm, Dept Surg, Queen Elizabeth Bldg,10 Alexandra Parade, Glasgow G31 2ER, Lanark, Scotland. FU NCI NIH HHS [1P30-CA72720, R01-CA46465]; NIAID NIH HHS [R01 AI43369, R01 AI36450] NR 63 TC 195 Z9 211 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD OCT PY 2000 VL 1 IS 7 BP 442 EP 450 DI 10.1038/sj.gene.6363714 PG 9 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 362GM UT WOS:000089770300006 PM 11196675 ER PT J AU Lawrence, SM Huddleston, KA Tomiya, N Pitts, LR Nguyen, N Lee, YC Vann, WF Coleman, TA Betenbaugh, MJ AF Lawrence, SM Huddleston, KA Tomiya, N Pitts, LR Nguyen, N Lee, YC Vann, WF Coleman, TA Betenbaugh, MJ TI Cloning and expression of human genes involved in sialic acid metabolism SO GLYCOBIOLOGY 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, Dept Prot Dev, Rockville, MD USA. US FDA, Lab Bacterial Polysaccharides, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 2000 VL 10 IS 10 MA 143 BP 1116 EP 1116 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 360JN UT WOS:000089664300155 ER PT J AU Louch, HA Buczko, ES Venable, RM Vann, WF AF Louch, HA Buczko, ES Venable, RM Vann, WF TI Site-directed mutagenesis of the ganglioside binding domain of tetanus toxin SO GLYCOBIOLOGY 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 OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 2000 VL 10 IS 10 MA 183 BP 1127 EP 1127 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 360JN UT WOS:000089664300195 ER PT J AU Dahari, H Major, M Mihalik, J Feinstone, S Neumann, AU AF Dahari, H Major, M Mihalik, J Feinstone, S Neumann, AU TI Lack of virus cytopathicity but strong IFN and cellular immune response during primary HCV infection in chimpanzees. SO HEPATOLOGY LA English DT Meeting Abstract C1 Bar Ilan Univ, Ramat Gan, Israel. US FDA, Washington, DC 20204 USA. NR 0 TC 2 Z9 2 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2000 VL 32 IS 4 MA 572 BP 302A EP 302A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400559 ER PT J AU Arichi, T Major, ME Saito, T Nishioka, M Engelhard, VH Feinstone, SM Berzolsky, JA AF Arichi, T Major, ME Saito, T Nishioka, M Engelhard, VH Feinstone, SM Berzolsky, JA TI Application of epitope enhancement to a prophylactic DNA vaccine for hepatitis C virus (HCV) in an HLA-A2.1 transgenic mouse model: Enhanced HCV specific CTL induction and protection from HCV-recombinant vaccinia infection. SO HEPATOLOGY LA English DT Meeting Abstract C1 Kagawa Med Univ, Kagawa, Japan. US FDA, Bethesda, MD 20014 USA. Yamagata Univ, Sch Med, Yamagata 99023, Japan. Univ Virginia, Charlottesville, VA 22903 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2000 VL 32 IS 4 MA 853 BP 373A EP 373A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400840 ER PT J AU Wedemeyer, H Cagneten, S Davis, AR Feinstone, SM Rehermann, B AF Wedemeyer, H Cagneten, S Davis, AR Feinstone, SM Rehermann, B TI Oral immunization with HCV-NS3 encoding salmonella: Long-lasting induction of HCV-specific CTL in an HLA-A2 transgenic mouse model. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2000 VL 32 IS 4 MA 905 BP 386A EP 386A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400892 ER PT J AU Momosaki, S Umemura, T Scudamore, CH Kojiro, M Alter, HJ Tabor, E AF Momosaki, S Umemura, T Scudamore, CH Kojiro, M Alter, HJ Tabor, E TI The prevalence of SEN-V infection in patients with hepatocellular carcinoma. SO HEPATOLOGY LA English DT Meeting Abstract C1 US FDA, Bethesda, MD 20014 USA. NIH, Bethesda, MD 20892 USA. Univ British Columbia, Dept Surg, Vancouver, BC V6T 1W5, Canada. Kurume Univ, Dept Pathol, Kurume, Fukuoka 830, Japan. NR 0 TC 4 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2000 VL 32 IS 4 MA 1155 BP 448A EP 448A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622401140 ER PT J AU Momosaki, S Hsia, CC Yamaguchi, R Scudamore, CH Kojiro, M Tabor, E AF Momosaki, S Hsia, CC Yamaguchi, R Scudamore, CH Kojiro, M Tabor, E TI Use of the Alu-PCR method to evaluate hepatitis B virus integration in hepatocellular carcinomas from patients with HBsAg-seronegative HBV infections. SO HEPATOLOGY LA English DT Meeting Abstract C1 US FDA, Bethesda, MD 20014 USA. Univ British Columbia, Dept Surg, Vancouver, BC V6T 1W5, Canada. Kurume Univ, Dept Pathol, Kurume, Fukuoka 830, Japan. US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2000 VL 32 IS 4 MA 1165 BP 451A EP 451A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622401151 ER PT J AU Sathyamoorthy, V Hall, RH McCardell, BA Kothary, MH Ahn, SJ Ratnayake, S AF Sathyamoorthy, V Hall, RH McCardell, BA Kothary, MH Ahn, SJ Ratnayake, S TI Purification and characterization of a cytotonic protein expressed in vitro by the live cholera vaccine candidate CVD 103-HgR SO INFECTION AND IMMUNITY LA English DT Article ID BIOTYPE EL-TOR; VIBRIO-CHOLERAE; FLUID ACCUMULATION; ESCHERICHIA-COLI; UNITED-STATES; INFANT MICE; TOXIN; ENTEROTOXINS; CVD-111; SAFETY AB Cholera vaccines developed by the deletion of CTX genes from Vibrio cholerae induce a residual reactogenicity in up to 10% of vaccinees. A novel cytotonic agent named secreted CHO cell elongating protein (S-CEP) was purified from culture supernatants of CVD 103-HgR (Levine et al,, Lancet ii:467-170, 1988). Five fractionation steps yielded electrophoretically pure S-CEP with an M-r of 79,000, A partially purified preparation caused fluid accumulation in the sealed infant mouse model. The amino terminus bore a unique sequence with strong homology to a cytotonic toxin of El Tor V. cholerae. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Virulence Assessment, HFS 327, Washington, DC 20204 USA. RP Hall, RH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Virulence Assessment, HFS 327, Washington, DC 20204 USA. NR 27 TC 4 Z9 8 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 2000 VL 68 IS 10 BP 6062 EP 6065 DI 10.1128/IAI.68.10.6062-6065.2000 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 355QE UT WOS:000089395700082 PM 10992523 ER PT J AU Evans, ME Jordan, CT Chang, SMW Conrad, C Gerberding, JL Kaufman, HL Mayhall, CG Nolta, JA Pilaro, AM Sullivan, S Weber, DJ Wivel, NA AF Evans, ME Jordan, CT Chang, SMW Conrad, C Gerberding, JL Kaufman, HL Mayhall, CG Nolta, JA Pilaro, AM Sullivan, S Weber, DJ Wivel, NA TI Clinical infection control in gene therapy: A multidisciplinary conference SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article AB Gene therapy is being studied for the treatment of a variety of acquired and inherited disorders. Retroviruses, adenoviruses, poxviruses, adeno-associated viruses, herpesviruses, and others are being engineered to transfer genes into humans. Treatment protocols using recombinant viruses are being introduced into clinical settings. Infection control professionals will be involved in reviewing the safety of these agents in their clinics and hospitals. To date, only a limited number of articles have been written on infection control in gene therapy,(1.2) and no widely available recommendations exist from federal or private organizations to guide infection control professionals. The goals of the conference were to provide a forum where gene therapy experts could share their perspectives and experience with infection control in gene therapy and to provide an opportunity for newcomers to the field to learn about issues specific to infection control in gene therapy. Recommendations for infection control in gene therapy were proposed (Infect Control Hosp Epidemiol 2000;21:659-673). C1 Univ Kentucky, Coll Med, Albert B Chandler Med Ctr, Div Infect Dis, Lexington, KY 40536 USA. Univ Kentucky, Coll Med, Albert B Chandler Med Ctr, Dept Internal Med, Lexington, KY 40536 USA. Schering Plough Res Inst, San Diego, CA USA. Canji Inc, San Diego, CA USA. Stanford Univ, Lucile Packard Childrens Hosp, Div Pediat Pulmonol, Palo Alto, CA USA. Ctr Dis Control & Prevent, Hosp Infect Program, Atlanta, GA USA. Yeshiva Univ, Albert Einstein Coll Med, Bronx, NY USA. Univ Texas, Med Branch Hosp, Dept Internal Med, Div Infect Dis, Galveston, TX 77555 USA. Childrens Hosp, Div Immunol Res BMT, Los Angeles, CA 90027 USA. US FDA, CBER, Rockville, MD 20857 USA. Valentis Inc, The Woodlands, TX USA. Univ N Carolina Hosp, Dept Hosp Epidemiol, Chapel Hill, NC USA. Univ N Carolina Hosp, Dept Occupat Hlth, Chapel Hill, NC USA. Univ Penn, Sch Med, Inst Gene Therapy, Philadelphia, PA 19104 USA. RP Evans, ME (reprint author), Univ Kentucky, Med Ctr, Room HG608,800 Rose St, Lexington, KY 40536 USA. OI Nolta, Jan/0000-0003-4576-8542 FU NCI NIH HHS [CA 84929-01]; NIDDK NIH HHS [R01 DK053041, R01 DK053041-04] NR 10 TC 3 Z9 3 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD OCT PY 2000 VL 21 IS 10 BP 659 EP 673 DI 10.1086/501711 PG 17 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 364BV UT WOS:000089872900011 PM 11083185 ER PT J AU Balaban, N Rasooly, A AF Balaban, N Rasooly, A TI Staphylococcal enterotoxins SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Review DE Staphylococcus aureus; enterotoxin; human pathogen ID T-CELL-RECEPTOR; MULTIPLE SEQUENCE ALIGNMENT; AUREUS TOXIN SUPERANTIGENS; GENE SEA EXPRESSION; CLASS-II MOLECULES; COMPLEX CLASS-II; CRYSTAL-STRUCTURE; NUCLEOTIDE-SEQUENCE; BINDING-SITES; BIOLOGICAL-ACTIVITIES AB Staphylococcus aureus is a major human pathogen that produces a wide array of toxins, thus causing various types of disease symptoms. Staphylococcal enterotoxins (SEs), a family of nine major serological types of heat stable enterotoxins, are a leading cause of gastroenteritis resulting from consumption of contaminated food. In addition, SEs are powerful superantigens that stimulate non-specific T-cell proliferation. SEs share close phylogenetic relationships, with similar structures and activities. Here we review the structure and function of each known enterotoxin. (C) 2000 Elsevier Science B.V. All rights reserved. C1 US FDA, Ctr Vet Med, Washington, DC 20204 USA. Univ Calif Davis, Dept Med Pathol, Davis, CA 95616 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Rasooly, A (reprint author), US FDA, Ctr Vet Med, Washington, DC 20204 USA. NR 84 TC 426 Z9 464 U1 9 U2 48 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 OCT 1 PY 2000 VL 61 IS 1 BP 1 EP 10 DI 10.1016/S0168-1605(00)00377-9 PG 10 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 358RQ UT WOS:000089571300001 PM 11028954 ER PT J AU Lucas, AD Kalson, JA Nutter, JC Wallis, RR AF Lucas, AD Kalson, JA Nutter, JC Wallis, RR TI Identifying toxic degradation products in cellulose acetate dialyzers SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article DE cellulose acetate; dialyzers; hemodialysis; degradation; conjunctivitis ID DIALYSIS CENTER; FLOW-CYTOMETRY; CELL-DEATH; INTOXICATION; MECHANISMS; APOPTOSIS; OXIDATION; MEMBRANES; IMMEDIATE AB In September 1996, seven patients at Hospital A suffered conjunctivitis, hearing loss, diminished vision, and headaches 7-24 h after hemodialysis treatment. Eleven-year-old dialysis modules were identified as a common link between these patients. Degradation of the cellulose acetate (CA) material was identified as the cause of this incident. Degradation products were characterized from retrieved CA dialysis membranes. A series of synthesized CA degradation products was tested in vitro to assess toxicity. Based on the toxicity of the material preparations to the cells, animal tests were performed on selected CA degradation extracts and compared to extracts from actual dialysis membranes. Rabbits were IV-injected with extracts from a 13-year-old dialyzer, synthesized model compounds, and compared to controls. Ophthamological evaluation of the rabbits showed eye injury (iritis/ciliary flush) when the animals were treated with the old dialyzer or synthesized model compounds. Isolation and characterization of a toxic fraction from both of these extracts strongly indicated that oxidative stress at some point in the storage or manufacture of CA dialyzers created degradation products that reproduced some of the patient symptoms identified at Hospital A, (C) 2000 John Wiley & Sons, Inc.* J Biomed Mater Res (Appl Biomater) 53: 449-456, 2000. C1 US FDA, CDRH, OST, Rockville, MD 20852 USA. RP Lucas, AD (reprint author), US FDA, CDRH, OST, HFZ 112,12709 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 24 TC 5 Z9 6 U1 0 U2 3 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 OCT PY 2000 VL 53 IS 5 BP 449 EP 456 DI 10.1002/1097-4636(200009)53:5<449::AID-JBM2>3.0.CO;2-0 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 356XK UT WOS:000089469300002 PM 10984691 ER PT J AU Nemunaitis, J Eager, R Twaddell, T Corey, A Sekar, K Tkaczuk, K Thompson, J Hoff, PM Pazdur, R AF Nemunaitis, J Eager, R Twaddell, T Corey, A Sekar, K Tkaczuk, K Thompson, J Hoff, PM Pazdur, R TI Phase I assessment of the pharmacokinetics, metabolism, and safety of emitefur in patients with refractory solid tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADVANCED COLORECTAL-CANCER; CONTINUOUS VENOUS INFUSION; DIHYDROPYRIMIDINE DEHYDROGENASE; 5-FLUOROURACIL LEVELS; ANTITUMOR-ACTIVITY; BREAST-CANCER; CAPECITABINE; BOF-A2; FLUOROURACIL; CARCINOMA AB Purpose: To determine the toxicities, dose-limiting toxicities (DLT), maximum-tolerated dose, and pharmacokinetic profile of emitefur (BOF-A2) in patients with advanced solid tumors. Methods: This was a phase I dose-escalating trial in which cohorts of patients received BOF-A2 (cohort 1, 300 mg/m(2) orally [PO] tid; cohort 2, 200 mg/m(2) PO tid; cohort 3, 200 mg/m(2) bid; and cohort 4, 250 mg/m(2) bid) for 14 consecutive days followed by 1 week of rest (cycle 1). Pharmacokinetics, toxicity, and tumor response were monitored. Results: Nineteen patients received 110 cycles (three patients in cohort 1, three patients in cohort 2, 10 patients in cohort 3, and three patients in cohort 4), DLT (grade 3 stomatitis, diarrhea, leukopenia) wets observed in cohorts 1, 2, and 4, pharmacokinetics indicated that prolonged systemic expression of fluorouracil (5-FU) is maintained after administration of BOF-A2 at a dose of 200 mg bid for 14 days. The mean steady-state concentration of plasma 5-FU was greater than or equal to 24 ng/mL, which wets 184-fold greater than the minimum effective cytotoxic concentration in vitro. Lack of variation of 5-FU trough levels within a day at steady-state indicates suppression of circadian variation. One patient in cohort 3 achieved a partial response and five patients maintained stable disease in excess of 6 months. Conclusion: BOF-A2 at a dose of 200 mg PO bid for 14 days followed by 7 days of rest is well tolerated. Prolonged exposure to 5-FU above the predicted preclinical minimum effective concentration is maintained, without evidence of circadian variation. Furthermore, evidence of antitumor activity is suggested. J Clin Oncol 18:3423-3434. (C) 2000 by American Society of Clinical Oncology. C1 US Oncol, Dallas, TX 75246 USA. Baylor Univ, Med Ctr, Houston, TX 77030 USA. Mary Crowley Med Res Ctr, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Otsuka Amer Pharmaceut Inc, Palo Alto, CA USA. US FDA, Div Oncol Drug Prod, Rockville, MD 20857 USA. Univ Maryland, Greenbaum Canc Ctr, Baltimore, MD 21201 USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. RP Nemunaitis, J (reprint author), US Oncol, 3535 Worth St,Collins Bldg,5th Floor, Dallas, TX 75246 USA. NR 46 TC 11 Z9 11 U1 1 U2 7 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 OCT 1 PY 2000 VL 18 IS 19 BP 3423 EP 3434 PG 12 WC Oncology SC Oncology GA 361BA UT WOS:000089700800014 PM 11013283 ER PT J AU Cohen, MH AF Cohen, MH TI Thalidomide in the treatment of high-grade gliomas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID TRIALS C1 US FDA, Rockville, MD 20857 USA. RP Cohen, MH (reprint author), US FDA, Rockville, MD 20857 USA. NR 5 TC 4 Z9 4 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 OCT 1 PY 2000 VL 18 IS 19 BP 3453 EP 3453 PG 1 WC Oncology SC Oncology GA 361BA UT WOS:000089700800027 PM 11013292 ER PT J AU Ajayi, FO Sun, H Perry, J AF Ajayi, FO Sun, H Perry, J TI Adverse drug reactions: A review of relevant factors SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article AB We examined some of the factors that contribute to the development of adverse drug reactions (ADRs) and analyzed post-marketing ADR reports for 22 drugs. The role of metabolic based drug-drug interaction in the development of ADRs can not be overstated. Assessment of the postmarketing ADR data for 22 drugs revealed that drugs with high potential for eliciting clinically significant ADRs are usually detected and either with drawn from the market or placed on restricted use within the first year or two of marketing. Postmarketing data could be a useful tool for understanding the ADR profile of drugs if reporting can be adequately monitored and verified. It is hoped that early evaluation of the clinically meaningful factors such as metabolism, pharmacogenetics, and effect of physiologic and pathophysiologic states on the clinical effect of a drug during drug development would significantly reduce the incidence and severity of post-marketing ADRs. C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. RP Ajayi, FO (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Off Clin Pharmacol & Biopharmaceut, 5600 Fishers Lane,HFD-880, Rockville, MD 20857 USA. NR 20 TC 30 Z9 33 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD OCT PY 2000 VL 40 IS 10 BP 1093 EP 1101 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 356LA UT WOS:000089443700003 PM 11028248 ER PT J AU Yang, S Angulo, FJ Altekruse, SF AF Yang, S Angulo, FJ Altekruse, SF TI Evaluation of safe food-handling instructions on raw meat and poultry products SO JOURNAL OF FOOD PROTECTION LA English DT Article AB Every year in the United States, millions of people become ill, thousands of people die, and substantial economic costs are incurred from foodborne diseases. As a measure to prevent foodborne diseases, since July 1994, the U.S. Department of Agriculture has required that safe food-handling labels be placed on retail packages of raw or partially cooked meat and poultry products. Through selected stares' Behavioral Risk Factor Surveillance System (BRFSS) interviews, survey data were collected to determine the proportion of adults aware of the label and adults who reported changing their raw meat-handling practices because of the label. Fifty-one percent of the 14,262 respondents reported that they had seen the label. Of these, 79% remembered reading the label, and 37% of persons who reported that they had seen and read the label reported changing their raw meat preparation methods because of the label. Women were more Likely than men to have read the label, as were persons who are at least 30 years of age compared to younger adults (P < 0.05). Both label awareness and risky food-handling behaviors increased with education and income, suggesting that safe food-handling labels have limited influence on consumer practices. Our results also suggest that the labels might be more effective in discouraging cross-contamination than in promoting thorough cooking practices. We suggest that the label is only one component among many food safety education programs that are needed to inform consumers about proper food-handling and preparation practices and to motivate persons who have risky food-handling and preparation behaviors to change these behaviors. C1 Ctr Dis Control & Prevent, Foodborne Diarrheal Dis Branch, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Sci Assessment & Suuport, Div Market Studies,Epidemiol Branch, Washington, DC 20204 USA. RP Angulo, FJ (reprint author), Ctr Dis Control & Prevent, Foodborne Diarrheal Dis Branch, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, 1600 Clifton Rd NE M-S A-38, Atlanta, GA 30333 USA. NR 17 TC 19 Z9 22 U1 1 U2 5 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 OCT PY 2000 VL 63 IS 10 BP 1321 EP 1325 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 361NW UT WOS:000089730000002 PM 11041129 ER PT J AU Skinner, GE Gendel, SM Fingerhut, GA Solomon, HA Ulaszek, J AF Skinner, GE Gendel, SM Fingerhut, GA Solomon, HA Ulaszek, J TI Differentiation between types and strains of Clostridium botulinum by riboprinting SO JOURNAL OF FOOD PROTECTION LA English DT Article ID FIELD GEL-ELECTROPHORESIS; RIBOSOMAL-RNA SEQUENCES; LISTERIA-MONOCYTOGENES; ECORI FRAGMENTS; FOOD; IDENTIFICATION; OUTBREAKS AB The ability of automated ribotyping to differentiate between major types and individual strains of Clostridium botulinum was tested using the Qualicon Riboprinter Microbial Characterization System. Pure spores of C. botulinum type A, proteolytic type B, nonproteolytic type B, and type E strains were inoculated onto modified anaerobic egg yolk agar and incubated 24 h at 35 degrees C. Plates were rinsed with buffer (2 mM Tris + 20 mM EDTA) to remove vegetative cells that were heated for 10 min at 80 degrees C, treated with a lysing agent, and ribotyped in the Qualicon Riboprinter utilizing the enzyme EcoRI. Riboprint patterns were obtained for 30 strains of the four major types of C. botulinum most commonly involved in human foodborne botulism. Proteolytic strains yielded the best and most consistent results. Fifteen ribogroups were identified among the 31 strains tested. Interestingly, in two cases, a single ribogroup contained patterns from isolates belonging to evolutionarily distinct Clostridium lineages. This degree of differentiation between strains of C. botulinum may be useful in hazard analysis and identification, hazard analysis and critical control point monitoring and validation, environmental monitoring, and in inoculation studies. C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. US FDA, Washington, DC 20204 USA. RP Skinner, GE (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. NR 15 TC 17 Z9 18 U1 0 U2 0 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 OCT PY 2000 VL 63 IS 10 BP 1347 EP 1352 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 361NW UT WOS:000089730000006 PM 11041133 ER PT J AU Dickensheets, HL Freeman, SL Donnelly, RP AF Dickensheets, HL Freeman, SL Donnelly, RP TI Interleukin-12 differentially regulates expression of IFN-gamma and interleukin-2 in human T lymphoblasts SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID CELL STIMULATORY FACTOR; TUMOR-NECROSIS-FACTOR; INTERFERON-GAMMA; HUMAN MONOCYTES; TYROSINE PHOSPHORYLATION; CYTOKINE PRODUCTION; IMMUNE-RESPONSES; IL-12 RECEPTOR; HUMAN-LYMPHOCYTES; TH1 CELLS AB Interleukin-12 (IL-12) is known to upregulate expression of interferon-gamma (IFN-gamma) by activated T cells. However, the effects of IL-12 on production of other Th1-type cytokines are less well defined. In this study, we examined the effects of IL-12 on expression of several cytokines, including IFN-gamma, IL-2, tumor necrosis factor-a (TNF-alpha), and IL-10, by primary human CD3(+) T cells. Although purified resting T cells were largely nonresponsive to IL-12 stimulation, anti-CD3-activated T cell blasts were strongly responsive, as demonstrated by the ability of IL-12 to induce Stat4 DNA-binding activity. Restimulation of T lymphoblasts on immobilized anti-CD3 monoclonal antibodies (mAb) induced rapid expression of TNF-alpha mRNA and more gradual increases in mRNA levels for IL-2, IFN-gamma, and IL-10. IL-12 markedly upregulated expression of IFN-gamma and IL-10 but downregulated expression of IL-2 in a dose-dependent and time-dependent manner. The levels of IL-2 produced by IL-12-treated T cells correlated inversely with the levels of IL-10. Moreover, neutralization of IL-10 activity with anti-IL-10 antibodies normalized IL-2 production by IL-12-treated T cells, confirming that the inhibition of IL-2 production by IL-12 was IL-10 mediated. Thus, IL-12 amplified expression of IFN-gamma and IL-10 and, via its ability to upregulate production of IL-10, inhibited expression of IL-2. These findings demonstrate that IL-12 differentially regulates expression of the Th1-type lymphokines, IFN-gamma and IL-2, in T lymphoblasts. C1 US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Rockville, MD 20852 USA. RP Donnelly, RP (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, HFM-538,1401 Rockville Pike, Rockville, MD 20852 USA. NR 58 TC 9 Z9 11 U1 0 U2 0 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 OCT PY 2000 VL 20 IS 10 BP 897 EP 905 DI 10.1089/10799900050163271 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 365GY UT WOS:000089944300014 PM 11054278 ER PT J AU Piperova, LS Teter, BB Bruckental, I Sampugna, J Mills, SE Yurawecz, MP Fritsche, J Ku, K Erdman, RA AF Piperova, LS Teter, BB Bruckental, I Sampugna, J Mills, SE Yurawecz, MP Fritsche, J Ku, K Erdman, RA TI Mammary lipogenic enzyme activity, trans fatty acids and conjugated linoleic acids are altered in lactating dairy cows fed a milk fat-depressing diet SO JOURNAL OF NUTRITION LA English DT Article DE acetyl-CoA carboxylase; fatty acid synthase; trans fatty acids; conjugated linoleic acid; lactating dairy cows ID GENE-EXPRESSION; BOVINE-MILK; ABOMASAL INFUSION; ADIPOSE-TISSUE; HOLSTEIN COWS; DUODENAL FLOW; ISOMERS; YIELD; BIOHYDROGENATION; IDENTIFICATION AB The objectives of the present study were to examine the effect of a milk fat-depressing (MFD) diet on: 1) the activity of mammary acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), 2) ACC mRNA relative abundance and 3) distributions of conjugated linoleic acids (CLA) and trans-18:1 fatty acids (tFA) in milk fat. Twelve lactating Holstein cows were used in a single reversal design. Two diets were fed: a control diet (60:40% forage/concentrate) and an MFD diet (25:70% forage/concentrate, supplemented with 5% soybean oil). The MFD diet decreased (P < 0 0.001) milk fat by 43% and ACC and FAS activity by 61 and 44%, respectively. A reduced ACC mRNA relative abundance (P < 0.001) corresponded with the lower ACC activity. The fatty acids synthesized de novo were decreased (P < 0.002), whereas tFA were increased from 1.9 to 15.6% due predominantly to a change in trans-10-18:1 isomer (P < 0.001). With the MFD diet, the trans-7, cis-9 and trans-10, cis-12 CLA isomers were elevated (P < 0.001), in contrast to the decrease in trans-11-18:1 (P < 0.001) and cis-g, trans-11-18:2. The data were consistent with a dietary effect on mammary de novo FA synthesis mediated through a reduction in ACC and FAS activity and in ACC mRNA abundance. The results were compatible with a role of trans-10, cis-12 CLA in milk fat depression, but alterations noted in tFA and other CLA isomers suggest that they also may be important during diet-induced milk fat depression. C1 Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. Univ Maryland, Dept Biochem & Chem, College Pk, MD 20742 USA. Volcani Inst, IL-50250 Bet Dagan, Israel. Purdue Univ, Dept Anim Sci, W Lafayette, IN 47907 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Erdman, RA (reprint author), Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. NR 52 TC 170 Z9 178 U1 0 U2 7 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD OCT PY 2000 VL 130 IS 10 BP 2568 EP 2574 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 361NB UT WOS:000089728200027 PM 11015491 ER PT J AU Mahayni, H Rekhi, GS Uppoor, RS Marroum, P Hussain, AS Augsburger, LL Eddington, ND AF Mahayni, H Rekhi, GS Uppoor, RS Marroum, P Hussain, AS Augsburger, LL Eddington, ND TI Evaluation of "external" predictability of an in vitro-in vivo correlation for an extended-release formulation containing metoprolol tartrate SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE metoprolol; in vitro; in vivo; correlation; extended-release; drug release; mechanism ID GASTROINTESTINAL TRANSIT AB The purpose of this study was to examine the external predictability of an in vitro-in vivo correlation (IVIVC) for a metoprolol hydrophilic matrix extended-release formulation, with an acceptable internal predictability, in the presence of a range of formulation manufacturing changes. Tn addition, this report evaluated the predictability of the IVIVC for another formulation of metoprolol tartrate differing in its release mechanism. Study 1 examined the scale up of a matrix extended-release tablet from a 3-kg small batch (I) to a 50-kg large batch (II). The second study examined the influence of scale and processing changes [3-kg small batch with fluid bed granulation and drying (III); 80-kg large batch with high shear granulation and microwave drying (IV), and a formulation with an alternate release mechanism formulated as a multiparticulate capsule (V)]. In vitro dissolution of all formulations (I-V) was conducted with a USP apparatus I at pH 6.8 and 150 rpm. Subjects received the metoprolol formulations, and serial blood samples were collected over 48 h and analyzed by a validated HPLC assay using fluorescence detection. A previously developed IVIVC was used to predict plasma profiles. Prediction errors (PE) were <10% for C-max and area under the curve (AUC) of concentration versus time for I, II, and TV. The C-max for III was slightly underestimated (11.7%); however, the PE of the AUC was <10%. Formulation V displayed a PE for C-max > 20% and an AUC within 5% of observed values. The low PEs for C-max and AUC observed for I-TV strongly suggest that the metoprolol IVIVC is externally valid, predictive of alternate processing methods (IV), scale-up (II, III), and allows the in vitro dissolution data to be used as a surrogate for validation studies. However, the lack of predictability for V supports the contention that IVIVCs are formulation specific. (C) 2000 Wiley-Liss, Tnc. and the American Pharmaceutical Association. C1 Univ Maryland, Sch Pharm, Pharmacokinet Biopharmaceut Lab, Baltimore, MD 21201 USA. US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20857 USA. Elan Pharma Inc, Gainesville, GA 30504 USA. Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. RP Eddington, ND (reprint author), Univ Maryland, Sch Pharm, Pharmacokinet Biopharmaceut Lab, 100 Penn St,AHB, Baltimore, MD 21201 USA. NR 12 TC 24 Z9 25 U1 1 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD OCT PY 2000 VL 89 IS 10 BP 1354 EP 1361 DI 10.1002/1520-6017(200010)89:10<1354::AID-JPS13>3.0.CO;2-P PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 362VJ UT WOS:000089798700013 PM 10980510 ER PT J AU Walker, LM Walker, PD Imam, SZ Ali, SF Mayeux, PR AF Walker, LM Walker, PD Imam, SZ Ali, SF Mayeux, PR TI Evidence for peroxynitrite formation in renal ischemia-reperfusion injury: Studies with the inducible nitric oxide synthase inhibitor L-N-6-(1-iminoethyl)lysine SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID IN-VIVO; NO SYNTHASE; RAT-KIDNEY; FAILURE; NITROTYROSINE; MICE; REOXYGENATION; INFLAMMATION; EXPRESSION; PROTECTS AB Reactive oxygen species are suggested to participate in ischemia-reperfusion (I-R) injury. However, induction of inducible nitric oxide synthase (iNOS) and production of high levels of nitric oxide (NO) also contribute to this injury. NO can combine with superoxide to form the potent oxidant peroxynitrite (ONOO-). NO and ONOO- were investigated in a rat model of renal I-R injury using the selective iNOS inhibitor L-N-6-(1-iminoethyl) lysine (L-NIL). Sprague-Dawley rats were subjected to 40 min of bilateral renal ischemia followed by 6 h of reperfusion with or without L-NIL administration. Control animals received a sham surgery and had plasma creatinine values of 0.4 +/- 0.1 mg/dl. I-R surgery significantly increased plasma creatinine levels to 1.9 +/- 0.3 mg/dl (P < .05) and caused renal cortical necrosis. L-NIL administration (3 mg/kg) in animals subjected to I-R significantly decreased plasma creatinine levels to 1.2 +/- 0.10 mg/dl (P < .05 compared with I-R) and reduced tubular damage. ONOO- formation was evaluated by detecting 3-nitrotyrosine-protein adducts, a stable biomarker of ONOO- formation. Immunohistochemistry and HPLC revealed that the kidneys from I-R animals had increased levels of 3-nitrotyrosine-protein adducts compared with control animals. L-NIL-treated rats (3 mg/kg) subjected to I-R showed decreased levels of 3-nitrotyrosine-protein adducts. These results support the hypothesis that iNOS-generated NO mediates damage in I-R injury possibly through ONOO- formation. C1 Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Mayeux, PR (reprint author), Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. FU NIDDK NIH HHS [DK44716] NR 36 TC 102 Z9 103 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 2000 VL 295 IS 1 BP 417 EP 422 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 354AA UT WOS:000089306600057 PM 10992009 ER PT J AU Freidlin, V Ko, HS Wilkin, JK AF Freidlin, V Ko, HS Wilkin, JK TI Re: Chronic treatment with finasteride daily does not affect spermatogenesis or semen production in young men SO JOURNAL OF UROLOGY LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Freidlin, V (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 2000 VL 164 IS 4 BP 1319 EP 1320 DI 10.1016/S0022-5347(05)67180-7 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 352QR UT WOS:000089229800063 PM 10992402 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 (vol 74, pg 5368, 2000) SO JOURNAL OF VIROLOGY LA English DT Correction C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIAMSD, Struct Biol Res Lab, Bethesda, MD 20892 USA. RP Weng, YK (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RI Weiss, Carol/F-6438-2011 OI Weiss, Carol/0000-0002-9965-1289 NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2000 VL 74 IS 20 BP 9811 EP 9811 DI 10.1128/JVI.74.20.9811-9811.2000 PG 1 WC Virology SC Virology GA 357LP UT WOS:000089503400060 ER PT J AU Max, EE Mitchell, M Mills, FC AF Max, EE Mitchell, M Mills, FC TI Multiple recombination events near the 3 ' boundary of the human IgH locus duplication SO MAMMALIAN GENOME LA English DT Article ID HOMOLOGY-DIRECTED REPAIR; CONSTANT-REGION; MAMMALIAN-CELLS; ALPHA-GENES C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Max, EE (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-541,Bldg 29A,2B09,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 14 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD OCT PY 2000 VL 11 IS 10 BP 938 EP 940 DI 10.1007/s003350010192 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 358RZ UT WOS:000089572100022 PM 11003713 ER PT J AU Beard, BB Mirotznik, MS Chang, IA AF Beard, BB Mirotznik, MS Chang, IA TI High spatial resolution measurements of specific absorption rate around ICD leads SO MEDICAL ENGINEERING & PHYSICS LA English DT Article DE defibrillation; Specific Absorption Rate (SAR); measurement techniques ID ELECTRIC SHOCKS; DEFIBRILLATION AB Introduction: It has been shown that strong electric shocks can cause local refractoriness in the heart. This is of particular concern if the region of refractoriness is the area sensed by an implant to determine cardiac rhythm, as is the case with many Implantable Cardioverter Defibrillator (ICD) leads which use the same electrodes for shocking and sensing. Failure to sense the true cardiac rhythm can cause application of unnecessary shocks and potential induction of arrhythmias. We developed a system to accurately map the areas where local refractoriness is most probable. We measured the Specific Absorption Rate (SAR) around typical ICD leads. Current density (J), a parameter that determines defibrillation effectiveness, is proportional to the square root of SAR. Methods and results: SAR measurements were performed in a homogeneous saline media using a variety of ICD leads. Gated 60 Hz shocks were used to produce heating, which was measured by thermistor probes. The temperature-rate-of-change is directly proportional to the SAR, Measurement techniques were developed that produced accurate SAR results at high spatial resolutions. Multiple polarities and configurations of ICD leads were tested. Conclusions: We confirmed the spatial distribution of the SAR and corresponding current density possessed sharp peaks and were highly localized around the leads' electrodes. Scans with a resolution of 1 mm or less are required in the area of peak SAR in order to capture the peak's value. Published by Elsevier Science Ltd on behalf of IPEM. C1 US FDA, Ctr Devices & Radiol Hlth, Electrophys Branch, Rockville, MD 20850 USA. Catholic Univ Amer, Dept Elect Engn, Washington, DC 20064 USA. RP Beard, BB (reprint author), US FDA, Ctr Devices & Radiol Hlth, Electrophys Branch, HFZ-133,9200 Corp Blvd, Rockville, MD 20850 USA. OI Beard, Brian/0000-0001-6480-0857 NR 7 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1350-4533 J9 MED ENG PHYS JI Med. Eng. Phys. PD OCT PY 2000 VL 22 IS 8 BP 587 EP 592 DI 10.1016/S1350-4533(00)00073-4 PG 6 WC Engineering, Biomedical SC Engineering GA 409BV UT WOS:000167365400008 PM 11182583 ER PT J AU Nawaz, MS Khan, SA Khan, AA Khambaty, FM Cerniglia, CE AF Nawaz, MS Khan, SA Khan, AA Khambaty, FM Cerniglia, CE TI Comparative molecular analysis of erythromycin-resistance determinants in staphylococcal isolates of poultry and human origin SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE multiplex-PCR; erythromycin rRNA methylase gene; ermA; ermB; ermC; efflux pump; msrA/msrB; S. aureus ID COAGULASE-NEGATIVE STAPHYLOCOCCI; STREPTOGRAMIN-B RESISTANCE; ENTEROBACTERIACEAE HIGHLY RESISTANT; ANTIBIOTIC-RESISTANCE; ENTEROCOCCUS-FAECALIS; METHYLASE GENES; CLINICAL STRAIN; AUREUS; PLASMID; MACROLIDES AB The ermA, ermB, ermC and msrA/msrB genes were detected in multidrug-resistant Staphylococcus spp. strains by PCR. Among 25 human clinical staphylococcal isolates the ermA, ermB, ermC and the msrA/msrB genes were detected in 88, 72, 4 and 100% of the strains, respectively. Among 24 poultry isolates the ermA, ermB, ermC and the msrA/msrB genes were detected in 100, 16.6, 50 and 12.5% of the strains, respectively. The ermA gene was found exclusively on the chromosome, whereas the ermC gene was found on 2.4-4.2 kb plasmids. Restriction fragment length poly morphism (RFLP) analysis of the ermA gene with EcoRI revealed five patterns (25.0, 21.0, 10.5, 6.2 and 4.8 kb) for the clinical strains and two (8.0 and 6.2 kb) for the poultry strains. The 6.2 kb RFLP pattern, in both the poultry and human clinical isolates, indicates a common lineage for the ermA gene. (C) 2000 Academic Press. C1 Natl Ctr Toxicol Res, Div Microbiol, FDA, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Nutr, Div Microbiol Studies, Washington, DC 20204 USA. RP Nawaz, MS (reprint author), Natl Ctr Toxicol Res, Div Microbiol, FDA, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 39 TC 26 Z9 28 U1 0 U2 3 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 OCT PY 2000 VL 14 IS 5 BP 311 EP 319 DI 10.1006/mcpr.2000.0320 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 371PU UT WOS:000165188000006 PM 11040095 ER PT J AU Liotta, L Petricoin, E AF Liotta, L Petricoin, E TI Molecular profiling of human cancer SO NATURE REVIEWS GENETICS LA English DT Review ID LASER-CAPTURE MICRODISSECTION; GENE-EXPRESSION PATTERNS; IMMUNOSENSOR; MICROARRAYS; CELLS; ARRAY; IMMUNOASSAY; FABRICATION; SYSTEMS; TISSUE AB Traditionally, tumours have been categorized on the basis of histology. However, the staining pattern of cancer cells viewed under the microscope is insufficient to reflect the complicated underlying molecular events that drive the neoplastic process. By surveying thousands of genes at once, using DNA arrays, it is now possible to read the molecular signature of an individual patient's tumour. When the signature is analysed with clustering algorithms, new classes of cancer emerge that transcend distinctions based on histological appearance alone. Using DNA arrays, protein arrays and appropriate experimental models, the ultimate goal is to move beyond correlation and classification to achieve new insights into disease mechanisms and treatment targets. C1 NCI, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Liotta, L (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 51 TC 328 Z9 338 U1 1 U2 25 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD OCT PY 2000 VL 1 IS 1 BP 48 EP 56 DI 10.1038/35049567 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 381KY UT WOS:000165763000017 PM 11262874 ER PT J AU Cowan, GSM Li, J Desai, V Buffington, CK Feuers, R AF Cowan, GSM Li, J Desai, V Buffington, CK Feuers, R TI High oxidative stress via the electron transport system in liver and muscle of the morbidly obese. SO OBESITY RESEARCH LA English DT Meeting Abstract C1 Univ Tennessee, Memphis, TN USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA O140 BP 48S EP 48S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100192 ER PT J AU Buffington, CK Li, J Desai, V Cowan, GSM Feuers, RJ AF Buffington, CK Li, J Desai, V Cowan, GSM Feuers, RJ TI Defects in anti-oxidant potential in liver and muscle of the morbidly obese. SO OBESITY RESEARCH LA English DT Meeting Abstract C1 Univ Tennessee, Memphis, TN 38163 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA PF25 BP 122S EP 122S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100478 ER PT J AU Hoff, PM Saad, ED Janjan, N Skibber, J Pazdur, R AF Hoff, PM Saad, ED Janjan, N Skibber, J Pazdur, R TI A phase I study - Preoperative UFT/leucovorin and radiation therapy in rectal cancer SO ONCOLOGY-NEW YORK LA English DT Article; Proceedings Paper CT Orzel/UFT Investigators Meeting and Consensus Conference CY OCT 07-10, 1999 CL VANCOUVER, CANADA SP Univ Alabama Birmingham, Comprehens Canc Ctr ID COLOANAL ANASTOMOSIS; ADJUVANT THERAPY; LEUCOVORIN; URACIL; CHEMOTHERAPY; FLUOROURACIL; COMBINATION; CARCINOMA; INFUSION; UFT AB The use of combined modality regimens has been wed established irt the treatment of stages II and III rectal cancer. The most common chemotherapy regimens used include continuous-infusion 5-FU delivered with the help of a central venous catheter and the use of portable pumps. These regimens are expensive and cart potentially develop line problems. The availability of the oral agent UFT in combination with oral leucovorin prompted the development of an all-oral chemotherapy regimen that could be combined with radiotherapy. At The University of Texas M. D. Anderson Cancer Center, we routinely use combined chemotherapy and radiotherapy preoperatively for the treatment of rectal cancers, and decided to conduct a phase I trial irt which UFT and leucovorin was used instead of the conventional 5-FU. The preliminary results are encouraging and seem to demonstrate the feasibility of this approach. C1 Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol & Digest Dis, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20857 USA. RP Hoff, PM (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol & Digest Dis, 1515 Holcombe Blvd,Box 78, Houston, TX 77030 USA. NR 18 TC 4 Z9 4 U1 0 U2 1 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD OCT PY 2000 VL 14 IS 10 SU 9 BP 56 EP 58 PG 3 WC Oncology SC Oncology GA 371KT UT WOS:000165178700012 PM 11098495 ER PT J AU Cote, CJ Karl, HW Notterman, DA Weinberg, JA McCloskey, C AF Cote, CJ Karl, HW Notterman, DA Weinberg, JA McCloskey, C TI Adverse sedation events in pediatrics: Analysis of medications used for sedation SO PEDIATRICS LA English DT Review DE sedation; adverse events; critical incident; medication errors; monitoring; guidelines; procedures; systems errors; drug overdose; drug-drug interactions; critical incident analysis ID CHLORAL HYDRATE SEDATION; INTENSIVE-CARE UNIT; DRUG EVENTS; NITROUS-OXIDE; CLINICAL PHARMACOKINETICS; INTRAMUSCULAR MEPERIDINE; YOUNG-CHILDREN; ORAL MIDAZOLAM; DISPOSITION; FENTANYL AB Objectives. To perform a systematic investigation of medications associated with adverse sedation events in pediatric patients using critical incident analysis of case reports. Methods. One hundred eighteen case reports from the adverse drug reporting system of the Food and Drug Administration, the US Pharmacopoeia, and the results of a survey of pediatric specialists were used. Outcome measures were death, permanent neurologic injury, prolonged hospitalization without injury, and no harm. The overall results of the critical incident analysis are reported elsewhere. The current investigation specifically examined the relationship between outcome and medications: individual and classes of drugs, routes of administration, drug combinations and interactions, medication errors and overdoses, patterns of drug use, practitioners, and venues of sedation. Results. Ninety-five incidents fulfilled study criteria and all 4 reviewers agreed on causation; 60 resulted in death or permanent neurologic injury. Review of adverse sedation events indicated that there was no relationship between outcome and drug class (opioids; benzodiazepines; barbiturates; sedatives; antihistamines; and local, intravenous, or inhalation anesthetics) or route of administration (oral, rectal, nasal, intramuscular, intravenous, local infiltration, and inhalation). Negative outcomes (death and permanent neurologic injury) were often associated with drug overdose (n = 28). Some drug overdoses were attributable to prescription/transcription errors, although none of 39 overdoses in 34 patients seemed to be a decimal point error. Negative outcomes were also associated with drug combinations and interactions. The use of 3 or more sedating medications compared with 1 or 2 medications was strongly associated with adverse outcomes (18/20 vs 7/70). Nitrous oxide in combination with any other class of sedating medication was frequently associated with adverse outcomes (9/10). Dental specialists had the greatest frequency of negative outcomes associated with the use of 3 or more sedating medications. Adverse events occurred despite drugs being administered within acceptable dosing limits. Negative outcomes were also associated with drugs administered by nonmedically trained personnel and drugs administered at home. Some injuries occurred on the way to a facility after administration of sedatives at home; some took place in automobiles or at home after discharge from medical supervision. Deaths and injuries after discharge from medical supervision were associated with the use of medications with long half-lives (chloral hydrate, pentobarbital, promazine, promethazine, and chlorpromazine). Conclusions. Adverse sedation events were frequently associated with drug overdoses and drug interactions, particularly when 3 or more drugs were used. Adverse outcome was associated with all routes of drug administration and all classes of medication, even those (such as chloral hydrate) thought to have minimal effect on respiration. Patients receiving medications with long plasma half-lives may benefit from a prolonged period of postsedation observation. Adverse events occurred when sedative medications were administered outside the safety net of medical supervision. Uniform monitoring and training standards should be instituted regardless of the subspecialty or venue of practice. Standards of care, scope of practice, resource management, and reimbursement for sedation should be based on the depth of sedation achieved (ie, the degree of vigilance and resuscitation skills required) rather than on the drug class, route of drug administration, practitioner, or venue. C1 Northwestern Univ, Sch Med, Childrens Mem Hosp, Dept Pediat Anesthesiol, Chicago, IL 60614 USA. Univ Washington, Sch Med, Childrens Hosp, Dept Pediat Anesthesiol, Seattle, WA USA. Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. New York Presbyterian Hosp, Div Crit Care Med, New York, NY USA. Lebonheur Childrens Med Ctr, Dept Emergency Serv, Memphis, TN USA. Univ Tennessee, Coll Med, Dept Pediat, Memphis, TN USA. US FDA, Ctr Drug Evaluat & Res, Off Post Mkt Drug Assessment, Div Drug Risk Evaluat 2, Washington, DC 20204 USA. RP Cote, CJ (reprint author), Northwestern Univ, Sch Med, Childrens Mem Hosp, Dept Pediat Anesthesiol, Chicago, IL 60614 USA. NR 121 TC 212 Z9 220 U1 3 U2 16 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 OCT PY 2000 VL 106 IS 4 BP 633 EP 644 DI 10.1542/peds.106.4.633 PG 12 WC Pediatrics SC Pediatrics GA 359QG UT WOS:000089623100018 PM 11015502 ER PT J AU Braun, MM Mootrey, GT Salive, ME Chen, RT Ellenberg, SS AF Braun, MM Mootrey, GT Salive, ME Chen, RT Ellenberg, SS CA VAERS Working Grp TI Infant immunization with acellular pertussis vaccines in the United States: Assessment of the first two years' data from the Vaccine Adverse Event Reporting System (VAERS) SO PEDIATRICS LA English DT Article DE vaccine; pertussis vaccine; acellular pertussis vaccine; vaccine safety; adverse effects ID CONTROLLED TRIAL; SAFETY; CHILDREN AB Objective. To evaluate the safety of infant immunization with acellular pertussis vaccines in the United States. Background. The US Food and Drug Administration approved the first acellular pertussis vaccine for use in infants in the United States on July 31, 1996. Outcome Measures. Adverse events in the United States after infant immunization with pertussis-containing vaccines, representing temporal (but not necessarily causal) associations between vaccinations and adverse events. Data Source. Reports to the Vaccine Adverse Event Reporting System (VAERS), a passive national surveillance system. Design. Reports concerning infant immunization against pertussis between January 1, 1995 (when whole-cell vaccine was in exclusive use) and June 30, 1998 (when acellular vaccine was in predominant use) were analyzed, if the reports were entered into the VAERS database by November 30, 1998. Results. During the study, there were 285 reports involving death, 971 nonfatal serious reports, and 4514 less serious reports after immunization with any pertussis-containing vaccine. For 1995 there were 2071 reports; in 1996 there were 1894 reports; in 1997 there were 1314 reports, and in the first half of 1998 there were 491 reports. Diphtheria-tetanus-pertussis vaccine (DTP) was cited in 1939 reports, diphtheria-tetanus-whole-cell pertussis-Haemophilus influenzae type b vaccine (DTPH) in 2918 reports, and diphtheria-tetanus-acellular pertussis vaccine (DTaP) in 913 reports. The annual number of deaths during the study was 85 in 1995, 82 in 1996, 77 in 1997, and 41 in the first half of 1998. The annual number of reported events categorized as nonfatal serious (defined as events involving initial hospitalization, prolongation of hospitalization, life-threatening illness, or permanent disability) to VAERS for all pertussis-containing vaccines declined: 334 in 1995, 311 in 1996, 233 in 1997, and 93 in the first half of 1998. Similarly, the annual number of less serious reports to VAERS for pertussis-containing vaccines declined: 1652 in 1995, 1501 in 1996, 1004 in 1997, and 357 in the first half of 1998. A comparison of the adverse event profiles (proportional distributions) for DTaP, DTP, and DTPH, as well as an analysis of specific adverse events considered in a 1991 Institute of Medicine report on the safety of diphtheria-tetanus-pertussis vaccine, did not identify any new, clear safety concerns. Conclusions. These findings reflect the administration of millions of doses of acellular pertussis vaccine and are reassuring with regard to the safety of marketed acellular pertussis vaccines. VAERS data, although subject to the limitations of passive surveillance, support the prelicensure data with regard to the safety of the US-licensed acellular pertussis vaccines that we evaluated. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Ctr Dis Control & Prevent, Natl Immunizat Program, Atlanta, GA 30333 USA. RP Braun, MM (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-220,Rockville Pike, Rockville, MD 20852 USA. NR 33 TC 28 Z9 29 U1 1 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2000 VL 106 IS 4 BP art. no. EP e51 DI 10.1542/peds.106.4.e51 PG 7 WC Pediatrics SC Pediatrics GA 359QG UT WOS:000089623100008 PM 11015546 ER PT J AU DuVernoy, TS Braun, MM AF DuVernoy, TS Braun, MM CA VAERS Working Grp TI Hypotonic-hyporesponsive episodes reported to the Vaccine Adverse Event Reporting System (VAERS), 1996-1998 SO PEDIATRICS LA English DT Article DE hypotonic-hyporesponsive episode; childhood immunization; adverse event; vaccine safety ID CELL PERTUSSIS-VACCINE; CHILDREN; IMMUNIZATION; INFANTS; SEIZURES; CONVULSIONS; SYNCOPE AB Background. A hypotonic-hyporesponsive episode (HHE) is the sudden onset of hypotonia, hyporesponsiveness, and pallor or cyanosis that occurs within 48 hours after childhood immunizations. This syndrome has been primarily associated with pertussis-containing vaccines administered to children <2 years of age, and has been estimated to occur once every 1750 diphtheria-tetanus-pertussis (DTwP) vaccinations. Previous studies of HHE were limited by small numbers of cases and, sometimes, by limited details of the event. Objectives. To characterize a large number of HHE cases reported to the Vaccine Adverse Event Reporting System (VAERS), to assist clinicians in identifying HHE, and to assist researchers in investigating the risk factors, cause, and pathogenesis of this syndrome. Methods. More than 40 000 VAERS reports received between 1996 and 1998 were screened for HHE by a computer algorithm and reviewed, and a telephone follow-up questionnaire was administered to the witness of HHE. Results. There were 215 HHE cases, all nonfatal. The median age of onset of HHE was 4.0 months (range: 1.1-107 months). Over half of the reports (53%) concerned females. The median birth weight was 3.36 kg (range: 1.27-4.96 kg); 4.7% had a birth weight <2500 g. The median interval between vaccination and HHE was 210 minutes (range: 1 minute-2 days). Among children with HHE who were <24 months of age, the episode occurred within 5 minutes in only 8.5%, compared with 66.7% of children with HHE >24 months of age. There were no relevant findings regarding family medical history or the mothers' gestational history. Nearly all of the children (98.6%) returned to their prevaccination state according to the telephone questionnaire; median time to return was 6 hours (range: 1 minute-4 months). The 3 children reported as not returning to their prevaccination state all had VAERS reports submitted after they developed conditions (autism, complex partial epilepsy, and developmental delays with infantile spasms) that are not known to be causally associated with immunization. The vast majority of children (93%) with HHE received a pertussis-containing vaccine, either diphtheria-tetanus-acellular pertussis (DTaP, 28%), DTwP (11%), or diphtheria-tetanus-pertussis-Haemophilus influenzae type b (DTwP-HIB, 61%). During the HHE episode, 90.1% of the children had pallor and 49% had cyanosis. Because of the HHE event, 6.8% of children had had all vaccines withheld as of the date of the interview. Of the remainder, 66.5% of children have had 1 or more subsequent vaccinations or vaccine components withheld, and 26.7% have not had any subsequent vaccinations withheld. Only 1 child was reported to have had a repeat episode of HHE, occurring after hepatitis B vaccination. From 1996 to 1998, the number of HHE reports decreased from 99 to 38, when the predominant pertussis vaccine administered to infants changed from whole-cell to acellular. Conclusion. This study represents the largest published case series of children with HHE and supports the generally benign, self-limited, nonrecurrent nature of this syndrome. Although HHE has been less frequently reported to VAERS after increased use of DTaP, HHE does occur after the administration of DTaP and other nonpertussis-containing vaccines. Although most parents and pediatricians withheld the pertussis component of subsequent vaccinations, many did not, with no reported adverse events occurring in the children after the subsequent immunizations. Restricting the definition of HHE to a more narrow age range (eg, <2 years of age) is also proposed because most of the older children probably experienced vasovagal syncope rather than HHE within 5 minutes of immunization. C1 US FDA, Ctr Biol Evaluat & Res, Off Biostat & epidemiol, Div Epidemiol, Rockville, MD 20852 USA. RP Braun, MM (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Biostat & epidemiol, Div Epidemiol, HFM-220,1401 Rockville Pike, Rockville, MD 20852 USA. NR 32 TC 33 Z9 34 U1 0 U2 1 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 OCT PY 2000 VL 106 IS 4 BP art. no. EP e52 DI 10.1542/peds.106.4.e52 PG 9 WC Pediatrics SC Pediatrics GA 359QG UT WOS:000089623100009 PM 11015547 ER PT J AU Popke, EJ Mayorga, AJ Fogle, CM Paule, MG AF Popke, EJ Mayorga, AJ Fogle, CM Paule, MG TI Comparison of drug effects on the performance of two timing tasks in rats SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE time; temporal; operant; behavior; clack; DRL; TRD ID RESPONSE DURATION DIFFERENTIATION; SCHEDULES; REINFORCEMENT; MEMORY AB Previous evidence suggests that different timing tasks are differentially sensitive to pharmacological manipulation, especially when different values for the temporal parameters are used. The present series of experiments compared the effects of physostigmine, caffeine, pentobarbital, morphine, and naloxone on the performance of a differential reinforcement of low rates with limited hold (DRL-LH) and a temporal response differentiation (TRD) task. In the DRL-LH task, rats were reinforced for responses that occurred 10-14 s from the end of the previous response. In the TRD task, rats were reinforced for responses with a duration of 10-14 s. The peak response time and peak spread of the initiation time distribution (for DRL-LH) or the response duration distribution (for TRD) were used as indices of temporal discrimination. Physostigmine, caffeine, and pentobarbital produced very similar effects on peak response time for both tasks, but the effects of morphine and naloxone were different for the two tasks. Effects on peak spread for the two tasks did not always correspond to changes in peak response time, suggesting that different processes may be measured by these two endpoints. Further, these effects were independent of changes in response rate suggesting that the effects were not due to gross disruptions in motivation or motor control. These results suggest that the effects of drugs on DRL-LH and TRD performance may differ, even when temporal parameters are identical. (C) 2000 Elsevier Science Inc. All rights reserved. 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 16 TC 9 Z9 9 U1 0 U2 0 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 OCT PY 2000 VL 67 IS 2 BP 377 EP 385 DI 10.1016/S0091-3057(00)00380-4 PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 386EB UT WOS:000166046200022 PM 11124404 ER PT J AU Kipshidze, N Keelan, MH Petersen, JR Bachutashvili, I Vossoughi, J Karanian, J Ghosh, C Iversen, P Roubin, GS Leon, MB Moses, JW AF Kipshidze, N Keelan, MH Petersen, JR Bachutashvili, I Vossoughi, J Karanian, J Ghosh, C Iversen, P Roubin, GS Leon, MB Moses, JW TI Photoactivation of vascular iNOS and elevation of cGMP in vivo: Possible mechanism for photovasorelaxation and inhibition restenosis in an atherosclerotic rabbit model SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID NITRIC-OXIDE; SMOOTH-MUSCLE; CYCLIC-GMP; ULTRAVIOLET-RADIATION; BALLOON ANGIOPLASTY; RELAXATION; TENSION; LASER AB Recently, intravascular low-power red laser light (LPRLL) therapy has been proposed for the prevention of postangioplasty restenosis due to the observed inhibition of experimental neointimal formation. The objective of this study was to determine the impact of endoluminal LPRLL on vascular levels of inducible nitric oxide synthase (iNOS) and cyclic guanosine monophosphate (cGMP) to help define the mechanism of this effect. Eight atherosclerotic male adult New Zealand White rabbits weighing 4-6 kg were used in these studies. The iliac arteries were treated in separate zones with: (1) balloon inflation only; (2) laser illumination only; and (3) balloon inflation + laser illumination. An uninjured zone of the iliac artery served as a control. Laser irradiation (630 nm) was delivered to the vessel wall via a Cold" laser Illuminator (Cook, Inc., Bloomington, ZN), with a 3 mm-diameter balloon. Experiments demonstrated that vascular cGMP levels obtained immediately following treatment in the balloon only group was the lowest (0.29 +/- 0.05 pmol/mg protein) and significantly lower compared with the uninjured controls (1.01 +/- 0.07 pmol/mg protein) (P < 0.001), In the laser only treated group cGMP levels were significantly increased (2.87 0.12 pmol/mg protein) compared with the uninjured control (P < 0.001) and the balloon only group (P < 0.001). Vascular cGMP levels in the balloon + laser group (2.09 +/- 0.07 pmol/mg protein) was also increased compared to the balloon only (P < 0.001) and control (P < 0.001) groups. Qualitative analysis of Western blot demonstrated that laser illumination induces iNOS. In contrast balloon dilatation did not induce iNOS, Balloon + laser treatment, however, tended to restore the expression of iNOS, Our study demonstrated that intravascular low dose laser irradiation induces iNOS and elevates vascular cGMP in an in vivo atherosclerotic rabbit model. C1 Lenox Hill Heart & Vasc Inst, New York, NY USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. SW Fdn Biomed Res, Washington, DC USA. US FDA, Washington, DC 20204 USA. AVI Biopharma, Portland, OR USA. RP Kipshidze, N (reprint author), Lenox Hill Hosp, 130 E 77th St, New York, NY 10021 USA. NR 22 TC 7 Z9 12 U1 0 U2 1 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD OCT PY 2000 VL 72 IS 4 BP 579 EP 582 DI 10.1562/0031-8655(2000)072<0579:POVIAE>2.0.CO;2 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 366VU UT WOS:000090027600024 PM 11045733 ER PT J AU Mahmood, I AF Mahmood, I TI Limited sampling model for the estimation of pharmacokinetic parameters in children SO THERAPEUTIC DRUG MONITORING LA English DT Article DE pharmacokinetics; pediatric patients; plasma concentration; multiple linear regression ID MAXIMUM PLASMA-CONCENTRATION; UNDER-THE-CURVE; C-MAX; AREA; CARBAMAZEPINE; POPULATION; DESIGN; AUC AB A limited sampling model (LSM) is proposed for the first-time assessment of pharmacokinetic parameters (area under the concentration-time curve (AUC), C-max, and T-1/2) in children after a single oral dose of drug. Three drugs were evaluated in this study. The LSM was developed for each drug from the data of 10 healthy adult volunteers. The relationship at selected time points between plasma concentration and the AUC or. C-max was evaluated by multiple linear regression. The multiple linear regression that gave the best correlation coefficient (r) for 3 sampling times versus AUC or C-max was chosen as the LSM. Pharmacokinetic parameters generated using sparse sampling (3 blood samples) were compared with pharmacokinetic parameters generated using extensive sampling (>7 blood samples). The results indicated that a limited sampling model can be developed from adult data to estimate pharmacokinetic parameters in children with fair degree of accuracy. C1 US FDA, Div Pharmaceut Evaluat 1, Off Clin Pharmacol & Biopharmaceut, Woodmont Off Ctr 2, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Div Pharmaceut Evaluat 1, Off Clin Pharmacol & Biopharmaceut, Woodmont Off Ctr 2, HFD-860,1451 Rockville Pike, Rockville, MD 20852 USA. NR 19 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD OCT PY 2000 VL 22 IS 5 BP 532 EP 536 DI 10.1097/00007691-200010000-00005 PG 5 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA 358ZZ UT WOS:000089588200005 PM 11034257 ER PT J AU Harvath, L Mondoro, TH Franke, PJ Aksamit, RR Lightfoot, T Leitman, SF Stroncek, DF AF Harvath, L Mondoro, TH Franke, PJ Aksamit, RR Lightfoot, T Leitman, SF Stroncek, DF TI Granulocyte concentrates: Chemotactic activity and platelet-granulocyte interactions are differentially affected by mobilization regimen and storage SO TRANSFUSION LA English DT Meeting Abstract C1 NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. US FDA, 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 OCT PY 2000 VL 40 IS 10 SU S BP 12S EP 12S PG 1 WC Hematology SC Hematology GA 364CN UT WOS:000089874600047 ER PT J AU Wear, KA Stuber, AP Reynolds, JC AF Wear, KA Stuber, AP Reynolds, JC TI Relationships of ultrasonic backscatter with ultrasonic attenuation, sound speed and bone mineral density in human calcaneus SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE calcaneus; trabecular bone; backscatter; ultrasound ID CANCELLOUS BONE; HIP FRACTURE; OS CALCIS; IN-VITRO; VELOCITY; WOMEN; COEFFICIENTS; PREDICTION; SIGNALS; LIVER AB Ultrasonic attenuation and sound speed have been investigated in trabecular bone by numerous authors. Ultrasonic backscatter has received much less attention, To investigate relationships among these three ultrasonic parameters and bone mineral density (BMD), 30 defatted human calcanei were investigated in vitro. Normalized broadband ultrasonic attenuation (nBUA), sound speed (SOS), and logarithm of ultrasonic back-scatter coefficient (LBC) were measured. Bone mineral density was assessed using single-beam dual energy x-ray absorptiometry (DEXA). The correlation coefficients of least squares linear regressions of the three individual ultrasound (US) parameters with BMD were 0.84 (nBUA), 0.84 (SOS) and 0.79 (LBC). The 95% confidence intervals for the correlation coefficients were 0.69-0.92 (nBUA), 0.68-0.92 (SOS) and 0.60-0.90 (LBC). The correlations among pairs of US variables ranged from 0.63-0.79. Variations in nBUA accounted for r(2) = 62% of the variations in LBC. Variations in SOS accounted for r(2) = 40% of the variations in LBC. These results suggest that ultrasonic backscattering properties may contain substantial information Rot already contained in nBUA and SOS. A multiple regression model including all three US variables was somewhat more predictive of BMD than a model including only nBUA and SOS. (C) 2000 World federation for Ultrasound in Medicine & Biology. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. NIH, Bethesda, MD 20892 USA. RP US FDA, Ctr Devices & Radiol Hlth, HFZ-142,122720 Twinbrook Pkwy, Rockville, MD 20852 USA. EM kaw@cdrh.fda.gov NR 42 TC 41 Z9 42 U1 0 U2 4 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 OCT PY 2000 VL 26 IS 8 BP 1311 EP 1316 DI 10.1016/S0301-5629(00)00267-2 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 385CA UT WOS:000165983000012 PM 11120369 ER PT J AU Wear, KA AF Wear, KA TI Candidate mechanisms to explain temperature dependence of ultrasonic attenuation in human calcaneus SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Letter 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 5 TC 0 Z9 0 U1 0 U2 1 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 OCT PY 2000 VL 26 IS 8 BP 1370 EP 1370 DI 10.1016/S0301-5629(00)00284-2 PG 1 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 385CA UT WOS:000165983000020 ER PT J AU Chen, RM Chou, MW Ueng, TH AF Chen, RM Chou, MW Ueng, TH TI Induction of cytochrome P450 1A1 in human hepatoma HepG2 cells by 6-nitrochrysene SO TOXICOLOGY LETTERS LA English DT Article DE 6-nitrochrysme; cytochrome P450 1A1; induction; HepG2 cells ID POLYCYCLIC AROMATIC-HYDROCARBONS; N-ACETYLTRANSFERASE; METABOLISM; RAT; MUTAGENICITY; LIVER; ACTIVATION; ENZYMES; MICE; RNA AB The present study has determined the effects of 6-nitrochrysene (6-NC) on human cytochrome P450-dependent monooxygenases in human hepatoma HepG2 cells. Treatment of HepG2 cells with 6-NC increased the activities of microsomal benzo[a]pyrene hydroxylase, 7-ethoxycoumarin and 7-ethoxyresorufin O-deethylases, cytosolic glutathione S-transferase and N-acetyltransferase, and S9 metabolic activation of 6-NC in the Ames mutagenicity test. Immunoblot and RNA blot analyses revealed that 6-NC induced CYP1A1 protein and mRNA levels in the hepatoma cells. Nuclear transcription assay demonstrated that 6-NC increased the transcription rate of CYP1A1 gene in HepG2 cells. Treatment of human lung carcinoma NCI-H322 cells with 6-NC increased benzo[a]pyrene hydroxylase activity and CYP1A1 protein and mRNA levels. These results demonstrate that 6-NC is an inducer of human CYP1A1 and the induction occurs at a transcriptional level in HepG2 cells. The ability of 6-NC to induce liver and lung CYP1A1 may be an important factor to consider in assessing 6-NC metabolism and toxicity in humans. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Natl Taiwan Univ, Coll Med, Inst Toxicol, Taipei, Taiwan. Natl Ctr Toxicol Res, Jefferson, AR USA. Taipei Med Coll, Wan Fang Hosp, Dept Anesthesia, Taipei, Taiwan. RP Ueng, TH (reprint author), Natl Taiwan Univ, Coll Med, Inst Toxicol, 1 Jen Ai Rd,Sect 1, Taipei, Taiwan. NR 35 TC 13 Z9 13 U1 0 U2 1 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 SEP 30 PY 2000 VL 117 IS 1-2 BP 69 EP 77 DI 10.1016/S0378-4274(00)00242-3 PG 9 WC Toxicology SC Toxicology GA 364LH UT WOS:000089893500008 PM 11033235 ER PT J AU Malozowski, S Sahlroot, JT AF Malozowski, S Sahlroot, JT TI Hemodynamic effects of sildenafil SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Malozowski, S (reprint author), US FDA, Rockville, MD 20857 USA. NR 2 TC 2 Z9 4 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 28 PY 2000 VL 343 IS 13 BP 967 EP 968 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 357KT UT WOS:000089501400014 PM 11012322 ER PT J AU Yi, P Melnyk, S Pogribna, M Pogribny, IP Hines, RJ James, SJ AF Yi, P Melnyk, S Pogribna, M Pogribny, IP Hines, RJ James, SJ TI Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocysteine and lymphocyte DNA hypomethylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADENOSYL-L-HOMOCYSTEINE; SMOOTH-MUSCLE CELLS; ISOLATED RAT-LIVER; METHYL-DEFICIENT; METHYLENETETRAHYDROFOLATE REDUCTASE; METHIONINE METABOLISM; POSTMENOPAUSAL WOMEN; FOLATE-DEFICIENCY; BIOGENIC-AMINES; TISSUE-LEVELS AB S-Adenosylmethionine and S-adenosylhomocysteine (SAH), as the substrate and product of essential cellular methyltransferase reactions, are important metabolic indicators of cellular methylation status. Chronic elevation of SAH, secondary to the homocysteine-mediated reversal of the SAH hydrolase reaction, reduces methylation of DNA, RNA, proteins, and phospholipids. High affinity binding of SAH to the active site of cellular methyltransferases results in product inhibition of the enzyme. Using a sensitive new high pressure liquid chromatography method with coulometric electrochemical detection, plasma SAH levels in healthy young women were found to increase linearly with mild elevation in homocysteine levels (r = 0.73; p < 0.001); however, S-adenosylmethionine levels were not affected, Plasma SAH levels were positively correlated with intracellular lymphocyte SAH levels (r = 0.81; p < 0.001) and also with lymphocyte DNA hypomethylation (r = 0.74, p < 0.001). These results suggest that chronic elevation in plasma homocysteine levels, such as those associated with nutritional deficiencies or genetic polymorphisms in the folate pathway, may have an indirect and negative effect on cellular methylation reactions through a concomitant increase in intracellular SAH levels. C1 US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72202 USA. Univ Arkansas Med Sci, Sch Hlth Related Profess, Little Rock, AR 72202 USA. RP James, SJ (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 70 TC 390 Z9 406 U1 4 U2 14 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 SEP 22 PY 2000 VL 275 IS 38 BP 29318 EP 29323 DI 10.1074/jbc.M002725200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 356JH UT WOS:000089439800020 PM 10884384 ER PT J AU Temple, R Ellenberg, SS AF Temple, R Ellenberg, SS TI Placebo-controlled trials and active-control trials in the evaluation of new treatments - Part 1: Ethical and scientific issues SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CLINICAL-TRIALS; EQUIVALENCE; ORTHODOXY; MYTHS AB In recent years, several authors have argued that placebo-controlled trials are invariably unethical when known effective therapy is available for the condition being studied, regardless of the condition or the consequences of deferring treatment. Some have also disputed the Value of placebo-controlled trials in such a setting, asserting that the comparison of new treatment with old treatment is sufficient to establish efficacy and is all that should be of interest. This article considers the ethical concerns about use of placebo controls and describes the limited ability of active-control equivalence (also known as noninferiority) trials to establish efficacy of new therapies in many medical contexts. The authors conclude that placebo-controlled trials are not uniformly unethical when known effective therapies are available; rather. their acceptability is determined by whether the patient will be harmed by deferral of therapy. If patients are not harmed, such trials can ethically be carried out. Furthermore, active-control trials, although valuable, informative, and appropriate in many circumstances, often cannot provide reliable evidence of the effectiveness of a new therapy. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Temple, R (reprint author), US FDA, Ctr Drug Evaluat & Res, 5600 Fishers Lane,HFD-101-WOC II-6014, Rockville, MD 20857 USA. NR 40 TC 463 Z9 475 U1 1 U2 18 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 19 PY 2000 VL 133 IS 6 BP 455 EP 463 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 354KM UT WOS:000089329700008 PM 10975964 ER PT J AU Ellenberg, SS Temple, R AF Ellenberg, SS Temple, R TI Placebo-controlled trials and active-control trials in the evaluation of new treatments - Part 2: Practical issues and specific cases SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MEDICATION-FREE RESEARCH; METASTATIC COLORECTAL-CANCER; ACUTE ISCHEMIC STROKE; CLINICAL RESEARCH; PERINATAL TRANSMISSION; FLUOROURACIL FAILURE; DEVELOPING-COUNTRIES; RANDOMIZED TRIAL; ETHICAL DILEMMAS AB Placebo controls are commonly used in clinical trials of investigational treatments because they have important advantages. In recent years, some have criticized the use of placebo-controlled trials when effective alternative therapy exists, regardless of the expected effect of the therapy. In part 1 of this paper, ethical arguments are addressed and the interpretive problems inherent in the use of active-control equivalence trials to establish efficacy of a new treatment are clarified. However, uncertainties may complicate decisions about appropriate use of placebo controls in some situations. Part 2 discusses more fully the ethical considerations for using placebo controls in particular medical settings. The value and relevance of placebo-controlled trials of new agents in situations in which proven effective therapy is available are also explored. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. RP Ellenberg, SS (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 44 TC 207 Z9 210 U1 2 U2 10 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 19 PY 2000 VL 133 IS 6 BP 464 EP 470 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 354KM UT WOS:000089329700009 PM 10975965 ER PT J AU Sommers, CL Dejarnette, JB Huang, K Lee, J El-Khoury, D Shores, EW Love, PE AF Sommers, CL Dejarnette, JB Huang, K Lee, J El-Khoury, D Shores, EW Love, PE TI Function of CD3 epsilon-mediated signals in T cell development SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE TCR; CD3epsilon; development; mice; cell survival ID RECEPTOR TRANSGENIC MICE; TCR ZETA-CHAIN; ANTIGEN RECEPTOR; ACTIVATION MOTIFS; ALPHA-BETA; SELECTION; GAMMA; SURVIVAL; COMPLEX; PHOSPHORYLATION AB The T cell antigen receptor (TCR) and pre-TCR complexes are composed of multiple signal-transducing subunits (CD3 gamma, CD3 delta, CD3 epsilon, and zeta) that each contain one or more copies of a semiconserved functional motif, the immunoreceptor tyrosine-based activation motif (ITAM). Although biochemical studies indicate that individual TCR-ITAMs may bind selectively or with different affinity to various effector molecules, data from other experiments suggest that at least some ITAMs are functionally equivalent. In this study, we examined the role of CD3 epsilon ITAM-mediated signals in T cell development by genetically reconstituting CD3 epsilon-deficient mice with transgenes encoding either wild-type or ITAM-mutant (signaling defective) forms of the protein. The results demonstrate that signals transduced by CD3 epsilon are not specifically required for T cell maturation but instead contribute quantitatively to TCR signaling in a manner similar to that previously observed for zeta chain. Unexpectedly, analysis of TCR-transgenic/CD3 epsilon-mutant mice reveals a potential role for CD3 epsilon signals in T cell survival. C1 NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. Ctr Biol Evaluat & Res Food & Drug Adm, Div Hematol Prod, Bethesda, MD 20892 USA. RP Love, PE (reprint author), NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NR 30 TC 37 Z9 38 U1 0 U2 2 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 SEP 18 PY 2000 VL 192 IS 6 BP 913 EP 919 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 356EM UT WOS:000089423300015 PM 10993922 ER PT J AU Nedelkov, D Rasooly, A Nelson, RW AF Nedelkov, D Rasooly, A Nelson, RW TI Multitoxin biosensor-mass spectrometry analysis: a new approach for rapid, real-time, sensitive analysis of staphylococcal toxins in food SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE biomolecular interaction analysis mass spectrometry; surface plasmon resonance; MALDI-TOF mass spectrometry; enterotoxin B; toxic-shock syndrome toxin-1; Staphylococcus aureus ID BIOMOLECULAR INTERACTION ANALYSIS; SURFACE-PLASMON RESONANCE; BIOSPECIFIC INTERACTION ANALYSIS; ASSAY KIT TECRA; ENTEROTOXIN-A; SHOCK-SYNDROME; T-CELLS; AUREUS; GENE; IDENTIFICATION AB Biomolecular interaction analysis mass spectrometry (BIA-MS) was applied to detection of bacterial toxins in food samples. This two-step approach utilizes surface plasmon resonance (SPR) to detect the binding of the toxin(s) to antibodies immobilized on a surface of a sensor chip. SPR detection is then followed by identification of the bound toxin(s) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Staphylococcal enterotoxin B (SEB) was readily detected in milk and mushroom samples at levels of 1 ng/ml. In addition, non-specific binding of food components to the immobilized antibody and to the sensor chip surface was detected. To evaluate the applicability of BIA-MS in the analysis of materials containing multiple toxic components, sample containing both SEE and toxic-shock syndrome toxin-l was analyzed. Both toxins were successfully and simultaneously detected through the utilization of multiaffinity sensor chip surfaces. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Intrins Bioprobes Inc, Tempe, AZ 85281 USA. US FDA, Div Microbiol Studies, OSRS, CFSAN, Washington, DC 20204 USA. RP Nedelkov, D (reprint author), Intrins Bioprobes Inc, 2009 E 5th St,Suite 11, Tempe, AZ 85281 USA. FU NCI NIH HHS [1 R43 CA82079-01] NR 49 TC 81 Z9 88 U1 2 U2 22 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 SEP 15 PY 2000 VL 60 IS 1 BP 1 EP 13 DI 10.1016/S0168-1605(00)00328-7 PG 13 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 356RH UT WOS:000089456200001 PM 11014517 ER PT J AU Love, PE Lee, J Shores, EW AF Love, PE Lee, J Shores, EW TI Critical relationship between TCR signaling potential and TCR affinity during thymocyte selection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL-RECEPTOR; ZETA-CHAIN; ANTIGEN RECEPTOR; TRANSGENIC MICE; NEGATIVE SELECTION; ACTIVATION MOTIFS; THYMIC SELECTION; LYMPHOCYTES-T; GAMMA-CHAIN; TRANSDUCTION AB Whether a developing thymocyte becomes positively or negatively selected is thought to be determined by the affinity/avidity of its TCR for MHC/peptide ligands expressed in the thymus, Presumably, differences in affinity translate into differences in the potency of the ensuing TCR-mediated signals, and these differences in signal strength determine the outcome of thymocyte selection. However, there is little direct evidence establishing a relationship between TCR-ligand affinity and signal strength during positive and negative selection. The TCR complex contains multiple signaling motifs, known as immunoreceptor tyrosine-based activation motifs (ITAMs) that are required for T cell activation. To examine the effects of TCR signal strength on selection, the signaling potential of the TCR was modified by substituting transgenic TCR 5-chains containing either three, one, or zero ITAMs for endogenous (3-ITAM) zeta -chain. These zeta -chain variants were then bred into different alpha beta TCR transgenic backgrounds. We report that reductions in TCR signaling potential have distinct effects on the selection of thymocytes expressing different TCRs, and that the requirement for zeta -chain ITAMs critically depends upon the specificity and apparently, affinity, of the TCR for its selecting ligand(s). C1 NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Shores, EW (reprint author), 1401 Rockville Pke,HFM-538, Rockville, MD 20852 USA. NR 37 TC 51 Z9 52 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2000 VL 165 IS 6 BP 3080 EP 3087 PG 8 WC Immunology SC Immunology GA 384JB UT WOS:000165938100023 PM 10975819 ER PT J AU Cho, BP Blankenship, LR Moody, JD Doerge, DR Beland, FA Culp, SJ AF Cho, BP Blankenship, LR Moody, JD Doerge, DR Beland, FA Culp, SJ TI Synthesis and characterization of 4 '-amino and 4 '-nitro derivatives of 4-N,N-dimethylaminotriphenylmethane as precursors for a proximate malachite green metabolite SO TETRAHEDRON LA English DT Article DE malachite green; nitration; nitro-dediazoniation; hydro-dediazonation; nitrosamines ID ICTALURUS-PUNCTATUS TISSUE; LIQUID-CHROMATOGRAPHY; LEUCOMALACHITE GREEN; ACID PYROLYSATE; GENTIAN-VIOLET; NITRATION AB This paper describes the preparation of 4'-amino (2) and 4'-nitro (3) derivatives of 4-N,N-dimethylaminotriphenylmethane as precursors for presumed DNA-binding metabolites of malachite green. The primary amine 2 was synthesized via a condensation of 4-lithiated bis-(N,N-trimethylsilyl)aniline and 4-(dimethylamino)benzophenone. A simple nitro-dediazoniation reaction of 2 failed to afford 3, but gave exclusively a mixture derived from hydro-dediazoniation followed by nitration and N-dealkylative-N-nitrosation. Direct nitration of N,N-dimethylaminotriphenylmethane, however, afforded 3 as well as other nitro isomers. Published by Elsevier Science Ltd. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Cho, BP (reprint author), Natl Ctr Toxicol Res, HFT-110,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 29 TC 10 Z9 10 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD SEP 15 PY 2000 VL 56 IS 38 BP 7379 EP 7388 DI 10.1016/S0040-4020(00)00649-9 PG 10 WC Chemistry, Organic SC Chemistry GA 354QJ UT WOS:000089340900003 ER PT J AU Levenbook, I Dragunsky, E Pervikov, Y AF Levenbook, I Dragunsky, E Pervikov, Y TI Development of a transgenic mouse neurovirulence test for oral poliovirus vaccine: international collaborative study 1993-1999 SO VACCINE LA English DT Article DE OPV; Tg mouse test; international collaborative study ID MICE; MODEL AB The neurovirulence safety of oral live poliovirus vaccine (OPV) has been tested in monkeys, because only primates are sensitive to all three types of poliovirus. The genetic engineering of transgenic mice susceptible to poliovirus led to studies on the suitability of these mice for a neurovirulence test of OPV. A WHO international collaborative study started with type-3 OPV in 1993 and was completed in 1999. The study produced a voluminous set of data proving that the TgPVR21 mice, inoculated with OPV samples into the lumbar cord, provided a test for neurovirulence of OPV as sensitive and reproducible as the monkey test. A statistical decision model for acceptance/rejection of type-3 vaccines using the transgenic mouse test has been developed. The mouse neurovirulence test showed a number of essential advantages over the monkey lest. This is the first example of a successful introduction of transgenic animals into control of biologicals. In October 1999, the WHO Expert Committee on Biological Standardization approved TgPVR21 mice as alternative to the monkey model for neurovirulence resting of OPV type 3, A final step of the collaborative study with OPV types 1 and 2 is in progress, and data obtained so far are promising. Two breeding stations for production of TgPVR21 mice are being established in Asia and Europe. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. WHO, Dept Vaccines & Biol, Geneva, Switzerland. RP Dragunsky, E (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 14 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD SEP 15 PY 2000 VL 19 IS 2-3 BP 163 EP 166 DI 10.1016/S0264-410X(00)00190-0 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 352UV UT WOS:000089237000003 PM 10930668 ER PT J AU Horne, AD Lachenbruch, PA Goldenthal, KL AF Horne, AD Lachenbruch, PA Goldenthal, KL TI Intent-to-treat analysis and preventive vaccine efficacy SO VACCINE LA English DT Article DE intent-to-treat; per-protocol; clinical trials ID RANDOMIZED CLINICAL-TRIALS; REQUIRING PROLONGED OBSERVATION; PLACEBO-CONTROLLED TRIAL; SIMPLEX VIRUS TYPE-2; GENITAL HERPES; GLYCOPROTEIN-D; HIV-INFECTION; IMMUNOTHERAPY; PERTUSSIS; EVENTS AB While the intent-to-treat (ITT) concept has often been discussed and debated in the literature with respect to randomized, placebo-controlled therapeutic trials, there has been little discussion of this issue in the context of preventive vaccine efficacy trials. ITT analysis has traditionally played a minor role (if any) in the latter trials. This paper discusses the ITT approach to analysis in randomized superiority trials of preventive vaccine efficacy, using clinical endpoints. Data are presented from published literature as well as from a simple mathematical model. The data suggest that when compliance and efficacy are high, both ITT and "per-protocol" approaches generally lead to similar conclusions regarding the acceptability of a vaccine for use in a population. However, when compliance is low, the ITT and per-protocol estimates of vaccine efficacy can be widely disparate. ITT and per-protocol analyses address unique and relevant scientific questions, and often both will be informative in evaluating preventive vaccines. Published by Elsevier Science Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Horne, AD (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 45 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD SEP 15 PY 2000 VL 19 IS 2-3 BP 319 EP 326 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 352UV UT WOS:000089237000022 PM 10930687 ER PT J AU Duncan, R Esmaili, A Law, LMJ Bertholet, S Hough, C Hobman, TC Nakhasi, HL AF Duncan, R Esmaili, A Law, LMJ Bertholet, S Hough, C Hobman, TC Nakhasi, HL TI Rubella virus capsid protein induces apoptosis in transfected RK13 cells SO VIROLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM; STRUCTURAL PROTEINS; GOLGI-COMPLEX; BCL-2; GLYCOPROTEINS; PARTICLES; SEQUENCE; DEATH; RNA; LYMPHOCYTES AB Rubella virus is an enveloped positive-strand RNA virus that can cause mild to severe birth defects or death in an infected fetus. RV induction of programmed cell death, demonstrated in cell culture, has been implicated in the pathogenesis. The timing of apoptosis, 48 h p.i., suggested that accumulation of RV structural proteins might induce cell death in infected cells. Expression of RV structural proteins, capsid, envelope glycoproteins El and E2, in transiently transfected RK13 cells was as potent an inducer of cell death as RV infection. Immunofluorescence microscopy revealed that RV structural protein transfected cells exhibited the condensed nuclei typical of apoptotic cell death. Transfection with the capsid protein construct, but not E2 and El, resulted in as much cell death as joint expression of all three RV structural proteins. Capsid required a membrane-anchoring domain to induce cell death, but a heterologous polypeptide fused to the capsid membrane anchor did not cause apoptosis. Deletion mutants demonstrated that the apoptosis-inducing activity resides In the N-terminal 170 amino acids of capsid. Though apoptosis-inducing capsid constructs appear to have an ER sub-cellular localization, disruption of the ER calcium storage capacity does not correlate with cell death. Mechanisms consistent with these results are discussed. (C) 2000 Academic Press. C1 US FDA, Ctr Biol Evaluat & Res, Lab Parasit Biol & Biochem, Bethesda, MD 20892 USA. Univ Alberta, Dept Cell Biol & Anat, Edmonton, AB T6G 2H7, Canada. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. RP Duncan, R (reprint author), US FDA, Lab Parasit Biol & Biochem, Ctr Biol Evaluat & Res, Bldg 29,Rm 425,1401 Rockville Pike HFM 310, Rockville, MD 20852 USA. RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 NR 41 TC 29 Z9 32 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 SEP 15 PY 2000 VL 275 IS 1 BP 20 EP 29 DI 10.1006/viro.2000.0467 PG 10 WC Virology SC Virology GA 356VY UT WOS:000089464600003 PM 11017784 ER PT J AU Mohan, KVK Dermody, TS Atreya, CD AF Mohan, KVK Dermody, TS Atreya, CD TI Mutations selected in rotavirus enterotoxin NSP4 depend on the context of its expression SO VIROLOGY LA English DT Article ID NONSTRUCTURAL GLYCOPROTEIN NSP4; PROTEIN; CELLS; IDENTIFICATION; INFECTION AB The rotavirus NSP4 protein is cytotoxic when transiently expressed in cells and is capable of inducing secretory diarrhea in neonatal mice. NSP4 consists of 175 amino acids, and sequences important for its toxic effects have been mapped to the carboxy-terminal half of the protein. In this report, we compared NSP4-enccding nucleotide sequences recovered from cell lines engineered to express NSP4 from human rotavirus strain Wa with NSP4 sequences recovered from cells persistently infected with either Wa or simian rotavirus strain SA11. In cells stably transfected with Wa NSP4, we found that proline(138) was changed to either serine or threonine. However, in cells persistently infected with SA11, we found that phenylalanine(33) was changed to leucine, and in cells persistently infected with Wa, no changes were observed in NSP4, Expression of Wa NSP4 in Caco-2 cells resulted in increased cell-doubling times and decreased cell viability in comparison to cells expressing NSP4-serine(138) or NSP4-threonine(138). This result suggests that sequence polymorphism at residue 138 in Wa NSP4 influences the cytotoxicity of the protein. Therefore, mutations in the carboxy-terminal half of NSP4 are selected when NSP4 is expressed in cells in the absence of other viral proteins, but not in the context of viral replication. These findings suggest that cytotoxic functions of NSP4 are not operant during natural rotavirus infection. (C) 2000 Academic Press. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Elizabeth B Lamb Ctr Pediat Res, Nashville, TN 37232 USA. RP Atreya, CD (reprint author), Bldg 29A,Room 2c-11,HFM-460,8800 Rockville Pike, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI32539] NR 19 TC 13 Z9 13 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 SEP 15 PY 2000 VL 275 IS 1 BP 125 EP 132 PG 8 WC Virology SC Virology GA 356VY UT WOS:000089464600013 PM 11017794 ER PT J AU Wise, RP Salive, ME Braun, MM Mootrey, GT Seward, JF Rider, LG Krause, PR AF Wise, RP Salive, ME Braun, MM Mootrey, GT Seward, JF Rider, LG Krause, PR TI Postlicensure safety surveillance for varicella vaccine SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID REPORTING-SYSTEM VAERS; POLYMERASE CHAIN-REACTION; PERIPHERAL FACIAL PALSY; ZOSTER VIRUS; HEALTHY-CHILDREN; FOLLOW-UP; THROMBOCYTOPENIA; IMMUNIZATION; CHICKENPOX; EFFICACY AB Context Since its licensure in 1995, the extensive use of varicella vaccine and close surveillance of the associated anecdotal reports of suspected adverse effects provide the opportunity to detect potential risks not observed before licensure because of the relatively small sample size and other limitations of clinical trials. Objectives To detect potential hazards, including rare events, associated with varicella vaccine, and to assess case reports for clinical and epidemiological implications. Design and Setting Postlicensure case-series study of suspected vaccine adverse events reported to the US Vaccine Adverse Event Reporting System (VAERS) from March 17, 1995, through July 25, 1998. Main Outcome Measures Numbers of reported adverse events, proportions, and reporting rates (reports per 100 000 doses distributed). Results VAERS received 6574 case reports of adverse events in recipients of varicella vaccine, a rate of 67.5 reports per 100 000 doses sold. Approximately 4% of reports described serious adverse events, including 14 deaths. The most frequently reported adverse events were rashes, possible vaccine failures, and injection site reactions. Misinterpretation of varicella serology after vaccination appeared to account for 17% of reports of possible vaccine failures. Among 251 patients with herpes tester, 14 had the vaccine strain of varicella tester virus (VZV), while 12 had the wild-type virus. None of 30 anaphylaxis cases was fatal, An immunodeficient patient with pneumonia had the vaccine strain of VZV in a lung biopsy, Pregnant women occasionally received varicella vaccine through confusion with varicella tester immunoglobulin. Although the role of varicella vaccine remained unproven in most serious adverse event reports, there were a few positive rechallenge reports and consistency of many cases with syndromes recognized as complications of natural varicella. Conclusion Most of the reported adverse events associated with varicella vaccine are minor, and serious risks appear to be rare. We could not confirm a vaccine etiology for most of the reported serious events; several will require further study to clarify whether varicella vaccine plays a role. Education is needed to ensure appropriate use of varicella serologic assays and to eliminate confusion between varicella vaccine and varicella zoster immunoglobulin. C1 US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Div Epidemiol, Rockville, MD 20857 USA. US FDA, Off Therapeut Res & Review & DNA Viruses, Div Monoclonal Antibodies, Labs Mol & Dev Immunol, Rockville, MD 20857 USA. US FDA, Off Vaccines Res & Review, Rockville, MD 20857 USA. Ctr Dis Control & Prevent, Branch Vaccine Safety & Dev, Div Epidemiol & Surveillance, Natl Immunizat Program, Atlanta, GA USA. Ctr Dis Control & Prevent, Branch Child Vaccine Preventable Dis, Div Epidemiol & Surveillance, Natl Immunizat Program, Atlanta, GA USA. RP Wise, RP (reprint author), 1401 rockville Pike,FDA CBER HFM-225, Rockville, MD 20852 USA. OI Rider, Lisa/0000-0002-6912-2458 NR 69 TC 121 Z9 123 U1 0 U2 4 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 SEP 13 PY 2000 VL 284 IS 10 BP 1271 EP 1279 DI 10.1001/jama.284.10.1271 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 350WL UT WOS:000089124600034 PM 10979114 ER PT J AU Itzhak, Y Martin, JL Ali, SF AF Itzhak, Y Martin, JL Ali, SF TI nNOS inhibitors attenuate methamphetamine-induced dopaminergic neurotoxicity but not hyperthermia in mice SO NEUROREPORT LA English DT Article DE 3-bromo-7-nitroindazole; dopaminergic neurotoxicity; hyperthermia; S-methylthiocitruline; nitric oxide (NO); 7-nitroindazole ID NITRIC-OXIDE SYNTHASE; BODY-TEMPERATURE; TYROSINE-HYDROXYLASE; FREE-RADICALS; 7-NITROINDAZOLE; OXIDATION; PROTECTS; STRESS AB Methamphetamine (METH)-induced dopaminergic neurotoxicity is associated with hyperthermia. We investigated the effect of several neuronal nitric oxide synthase (nNOS) inhibitors on METH-induced hyperthermia and striatal dopaminergic neurotoxicity. Administration of METH (5 mg/kg; q. 3 h X 3) to Swiss Webster mice produced marked hyperthermia and 50-60% depletion of striatal dopaminergic markers 72 h after METH administration. Pretreatment with the nNOS inhibitors S-methylthiocitrulline (SMTC; 10 mg/kg) or 3-bromo-7-nitroindazole (3-Br-7-NI; 20 mg/kg) before each METH injection did not affect the persistent hyperthermia produced by METH, but afforded protection against the depletion of dopaminergic markers. A low dose (25 mg/kg) of the nNOS inhibitor 7-nitroindazole (7-NI) did not affect METH-induced hyperthermia, but a high dose (50 mg/kg) produced significant hypothermia. These findings indicate that low dose of selective nNOS inhibitors protect against METH-induced neurotoxicity with no effect on body temperature and support the hypothesis that nitric oxide (NO) and peroxynitrite have a major role in METH-induced dopaminergic neurotoxicity. NeuroReport 11:2943-2946 (C) 2000 Lippincott Williams & Wilkins. C1 Univ Miami, Sch Med, Dept Psychiat & Behav Sci R629, Miami, FL 33136 USA. US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Jefferson, AR 72079 USA. RP Itzhak, Y (reprint author), Univ Miami, Sch Med, Dept Psychiat & Behav Sci R629, Gautier Bldg,1011 NW 15th St, Miami, FL 33136 USA. FU NIDA NIH HHS [DA 08584] NR 24 TC 51 Z9 53 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD SEP 11 PY 2000 VL 11 IS 13 BP 2943 EP 2946 DI 10.1097/00001756-200009110-00022 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 354ZC UT WOS:000089360300022 PM 11006970 ER PT J AU Mesmer, MZ Flurer, RA AF Mesmer, MZ Flurer, RA TI Determination of chlorophacinone and diphacinone in commercial rodenticides by liquid chromatography-UV detection and liquid chromatography-electrospray ionization mass spectrometry SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE rodenticides; chlorophacinone; diphacinone; indanediones ID BRODIFACOUM; SERUM AB This work describes a simple method for the determination and mass-spectrometric confirmation of the indanediones in commercial rodenticides. The sample is sonicated in methanol containing 2% formic acid and analyzed by liquid chromatography-UV detection. Once retention time and UV-Vis spectrum provide tentative identification, mass-spectrometric confirmation is obtained by analyzing a second aliquot by LC and electrospray ionization mass spectrometry (LC-ESI-MS). The extensive fragmentation of the indanedione molecule under MS/MS conditions provides sufficient structural information for positive identification on analyte levels as low as 20 ng on column. (C) 2000 Published by Elsevier Science B.V. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Mesmer, MZ (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. NR 10 TC 20 Z9 27 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD SEP 8 PY 2000 VL 891 IS 2 BP 249 EP 255 DI 10.1016/S0021-9673(00)00608-7 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 353QB UT WOS:000089286000005 PM 11043785 ER PT J AU Hrinczenko, BW Schechter, AN Wojtkowski, TL Pannell, LK Cashon, RE Alayash, AI AF Hrinczenko, BW Schechter, AN Wojtkowski, TL Pannell, LK Cashon, RE Alayash, AI TI Nitric oxide-mediated heme oxidation and selective beta-globin nitrosation of hemoglobin from normal and sickle erythrocytes SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE nitric oxide; hemoglobin; sickle cell anemia ID S-NITROSOHEMOGLOBIN; BIOCHEMICAL-CHARACTERIZATION; MASS-SPECTROMETRY; OXYGEN-AFFINITY; NO; MYOGLOBIN AB Nitric oxide (NO) has been reported to modulate the oxygen affinity of blood from sickle cell patients (SS), but not that of normal adult blood (AA), with little or no heme oxidation, However, we had found that the NO donor compounds 2-(N,N-diethylamino)-diazenolate-2-oxide (DEANO) and S-nitrosocysteine (CysNO) caused increased oxygen affinity of red cells from both AA and SS individuals and also caused significant methemoglobin (metHb) formation. Rapid kinetic experiments in which HbA(0), AA, or SS erythrocytes were mixed with CysNO or DEANO showed biphasic time courses indicative of initial heme oxidation followed by reductive heme nitrosylation, respectively. Hemolysates treated with CysNO showed by electrospray mass spectrometry a peak corresponding to a 29 mass unit increase (consistent with NO binding) of both the beta(A) and beta(S) chains but not of the alpha chains, Therapeutic use of NO in sickle cell disease may ultimately require further optimization of these competing reactions, i.e., heme reactivity (nitrosylation or oxidation) versus direct S-nitrosation of hemoglobin on the P-globin, (C) 2000 Academic Press. C1 US FDA, Ctr Biol Evaluat & Res, Lab Plasma Derivat, Bethesda, MD 20892 USA. NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Struct Mass Spect Grp, NIH, Bethesda, MD 20892 USA. Univ Maine, Dept Biochem Microbiol & Mol Biol, Orono, ME 04469 USA. RP Alayash, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Plasma Derivat, 8800 Rockville Pike,NIH Campus,Bldg 29,Room 112, Bethesda, MD 20892 USA. OI Schechter, Alan N/0000-0002-5235-9408 NR 18 TC 14 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 7 PY 2000 VL 275 IS 3 BP 962 EP 967 DI 10.1006/bbrc.2000.3413 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 353FV UT WOS:000089264900041 PM 10973828 ER PT J AU van der Laan, LJW Lockey, C Griffeth, BC Frasier, FS Wilson, CA Onions, DE Hering, BJ Long, ZF Otto, E Torbett, BE Salomon, DR AF van der Laan, LJW Lockey, C Griffeth, BC Frasier, FS Wilson, CA Onions, DE Hering, BJ Long, ZF Otto, E Torbett, BE Salomon, DR TI Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice SO NATURE LA English DT Article ID HUMAN-CELLS; ENGRAFTMENT; PIGS AB Animal donors such as pigs could provide an alternative source of organs for transplantation. However, the promise of xenotransplantation is offset by the possible public health risk of a cross-species infection(1,2). All pigs contain several copies of porcine endogenous retroviruses (PERV)(3,4), and at least three variants of PERV can infect human cell lines in vitro in co-culture, infectivity and pseudotyping experiments(3,5-7). Thus, if xenotransplantation of pig tissues results in PERV viral replication, there is a risk of spreading and adaptation of this retrovirus to the human host. C-type retroviruses related to PERV are associated with malignancies of haematopoietic lineage cells in their natural hosts(8). Here we show that pig pancreatic islets produce PERV and can infect human cells in culture. After transplantation into NOD/SCID (non-obese diabetic, severe combined immunodeficiency) mice, we detect ongoing viral expression and several tissue compartments become infected. This is the first evidence that PERV is transcriptionally active and infectious cross-species in vivo after transplantation of pig tissues. These results show that a concern for PERV infection risk associated with pig islet xenotransplantation in immunosuppressed human patients may be justified. C1 Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. Genet Therapy Inc, Gaithersburg, MD 20878 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Glasgow, Dept Vet Pathol, Glasgow G61 1QH, Lanark, Scotland. Q One Biotech Ltd, Glasgow G20 OXA, Lanark, Scotland. Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA. RP Salomon, DR (reprint author), Scripps Res Inst, Dept Mol & Expt Med, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. RI Salomon, Daniel/E-9380-2012; OI van der Laan, Luc/0000-0002-0651-5334 NR 22 TC 233 Z9 239 U1 1 U2 11 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 7 PY 2000 VL 407 IS 6800 BP 90 EP 94 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 350WE UT WOS:000089124000048 PM 10993079 ER PT J AU Li, YS Fu, PP Church, JS AF Li, YS Fu, PP Church, JS TI The conformation of some nitro-polycyclic aromatic hydrocarbons SO JOURNAL OF MOLECULAR STRUCTURE LA English DT Article DE nitro-polycyclic aromatic hydrocarbons; Raman spectra; depolarization ratio; conformation; structure and mutagenicity relationship ID RAT-LIVER MICROSOMES; METABOLISM; MUTAGENICITY; 9-NITROANTHRACENE AB The Raman spectra of some nitro-polycyclic aromatic hydrocarbons, including 2-nitroanthracene, 7-nitrobenz[a] anthracene, 6-nitrochrysene, 1-nitropyrene, 6-nitrobenzo[a]pyrene, and 6-nitro-7,8,9,10-tetrahydrobenzo[a]pyrene have been recorded in the frequency region 1100-1700 cm(-1). The stretching vibrational modes for the nitro group in each of these compounds were assigned based on group frequencies, the measured infrared and Raman spectra, the relative spectral intensities, and the Raman depolarization data. From the measured Raman depolarization data, the orientation of the nitro-substituent with respect to polycyclic aromatic hydrocarbon was determined for each of these compounds except 6-nitro-7,8,9, 10-tetrahydrobenzo[a]pyrene. The results were correlated with the direct-acting mutagenicity of the nitro compounds according to the hypothesis suggested by P.P. Fu and his co-workers. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Memphis, Dept Chem, Memphis, TN 38152 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. CSIRO, Text & Fibre Technol, Belmont, Vic 3216, Australia. RP Li, YS (reprint author), Univ Memphis, Dept Chem, Memphis, TN 38152 USA. NR 26 TC 28 Z9 28 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-2860 J9 J MOL STRUCT JI J. Mol. Struct. PD SEP 5 PY 2000 VL 550 SI SI BP 217 EP 223 DI 10.1016/S0022-2860(00)00519-6 PG 7 WC Chemistry, Physical SC Chemistry GA 355GZ UT WOS:000089379100017 ER PT J AU Houn, F Bright, RA Bushar, HF Croft, BY Finder, CA Gohagan, JK Jennings, RJ Keegan, P Kessler, LG Kramer, BS Martynec, LO Robinowitz, M Sacks, WM Schultz, DG Wagner, RF AF Houn, F Bright, RA Bushar, HF Croft, BY Finder, CA Gohagan, JK Jennings, RJ Keegan, P Kessler, LG Kramer, BS Martynec, LO Robinowitz, M Sacks, WM Schultz, DG Wagner, RF TI Study design in the evaluation of breast cancer imaging technologies SO ACADEMIC RADIOLOGY LA English DT Article DE breast cancer; diagnosis; efficacy; regulatory requirements; screening; technology evaluation ID DIAGNOSTIC-ACCURACY; ROC METHODOLOGY AB Rationale and Objectives. Bringing a new imaging technology to market is a complex process. Beyond conceptualization and proof of concept, obtaining U.S. Food and Drug Administration (FDA) approval for clinical use depends on the documented experimental establishment of safety and efficacy. In turn, safety and efficacy are evaluated in the context of the intended use of the technology. The purpose of this study was to examine a conceptual framework for technology development and evaluation, focusing on new breast imaging technologies as a highly visible and current case in point. Materials and Methods. The FDA views technology development in terms of a preclinical and four clinical phases of assessment. With a concept of research and development as a learning model, this phased-assessment concept of regulatory review against intended use was integrated with a five-level version of a hierarchy-of-efficacy framework for evaluating imaging technologies. Study design and analysis issues are presented in this context, as are approaches to supporting expanded clinical indications and new intended uses after a new technology is marketed. Conclusion, Boast imaging technologies may be intended for use as replacements for standard-of-care technologies, as adjuncts, or as complementary technologies. Study designs must be appropriate to establish claims of superiority or equivalence to the standard for the intended use. Screening technologies are ultimately judged on their demonstrated effectiveness in decreasing cause-specific mortality through early detection, but they may be brought to market for other uses on the basis of lesser standards of efficacy leg, sensitivity, specificity, positive and negative predictive value, and stage of disease detected). C1 US FDA, Rockville, MD 20852 USA. NCI, Bethesda, MD 20892 USA. RP Houn, F (reprint author), US FDA, 5600 Fishers Ln,HFD-103, Rockville, MD 20852 USA. RI Croft, Barbara/D-1248-2013; Bright, Roselie/D-2240-2016 OI Croft, Barbara/0000-0003-2544-150X; NR 41 TC 18 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD SEP PY 2000 VL 7 IS 9 BP 684 EP 692 DI 10.1016/S1076-6332(00)80524-3 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 351DU UT WOS:000089143200002 PM 10987329 ER PT J AU Myers, MR Lytle, D Routson, LB AF Myers, MR Lytle, D Routson, LB TI Virus adsorption within pores in latex: Assessment of reversibility effects SO AICHE JOURNAL LA English DT Article C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Myers, MR (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. NR 4 TC 3 Z9 3 U1 0 U2 1 PU AMER INST CHEMICAL ENGINEERS PI NEW YORK PA 3 PARK AVE, NEW YORK, NY 10016-5901 USA SN 0001-1541 J9 AICHE J JI AICHE J. PD SEP PY 2000 VL 46 IS 9 BP 1894 EP 1896 DI 10.1002/aic.690460917 PG 3 WC Engineering, Chemical SC Engineering GA 355JH UT WOS:000089382200016 ER PT J AU Hobbs, CA Sherman, SL Yi, P Hopkins, SE Torfs, CP Hine, RJ Pogribna, M Rozen, R James, SJ AF Hobbs, CA Sherman, SL Yi, P Hopkins, SE Torfs, CP Hine, RJ Pogribna, M Rozen, R James, SJ TI Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID NEURAL-TUBE DEFECTS; METHIONINE SYNTHASE REDUCTASE; FOLATE/METHYL-DEFICIENT RATS; DNA METHYLTRANSFERASE GENE; MAMMALIAN FEMALE MEIOSIS; METHYLENETETRAHYDROFOLATE REDUCTASE; CHROMOSOME SEGREGATION; HISTONE DEACETYLASE; IMMUNODEFICIENCY SYNDROME; POSTMENOPAUSAL WOMEN AB Down syndrome is a complex genetic and metabolic disorder attributed to the presence of three copies of chromosome 21. The extra chromosome derives from the mother in 93% of cases and is due to abnormal chromosome segregation during meiosis (nondisjunction). Except for advanced age at conception, maternal risk factors for meiotic nondisjunction are not well established. A recent preliminary study suggested that abnormal folate metabolism and the 677C-->T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene may be maternal risk factors for Down syndrome. The present study was undertaken with a larger sample size to determine whether the MTHFR 677C-->T polymorphism was associated with increased risk of having a child with Down syndrome. Methionine synthase reductase (MTRR) is another enzyme essential for normal folate metabolism. A common polymorphism in this gene was recently associated with increased risk of neural tube defects and might also contribute to increased risk for Down syndrome. The frequencies of the MTHFR 677C-->T and MTRR 66A-->G mutations were evaluated in DNA samples from 157 mothers of children with Down syndrome and 144 control mothers. Odds ratios were calculated for each genotype separately and for potential gene-gene interactions. The results are consistent with the preliminary observation that the MTHFR 677C-->T polymorphism is more prevalent among mothers of children with Down syndrome than among control mothers, with an odds ratio of 1.91 (95% confidence interval [CT] 1.19-3.05). In addition, the homozygous MTRR 66A-->G polymorphism was independently associated with a 2.57-fold increase in estimated risk (95% CI 1.33-4.99). The combined presence of both polymorphisms was associated with a greater risk of Down syndrome than was the presence of either alone, with an odds ratio of 4.08 (95% CI 1.94-8.56). The two polymorphisms appear to act without a multiplicative interaction. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Arkansas Childrens Hosp, Arkansas Ctr Birth Defects Res & Prevent, Little Rock, AR 72202 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Emory Univ, Sch Med, Dept Genet, Atlanta, GA USA. Calif Birth Defects Monitoring Program, Emeryville, CA USA. McGill Univ, Montreal Childrens Hosp, Res Inst, Montreal, PQ H3H 1P3, Canada. RP James, SJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. FU NHLBI NIH HHS [HL 58955-01, R01 HL058955]; NICHD NIH HHS [P01-HD32111]; PHS HHS [U50/CCU613236-02] NR 54 TC 215 Z9 232 U1 0 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 2000 VL 67 IS 3 BP 623 EP 630 DI 10.1086/303055 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 348TJ UT WOS:000089002300009 PM 10930360 ER PT J AU Khan, SA Nawaz, MS Khan, AA Steele, RS Cerniglia, CE AF Khan, SA Nawaz, MS Khan, AA Steele, RS Cerniglia, CE TI Characterization of erythromycin-resistant methylase genes from multiple antibiotic resistant Staphylococcus spp isolated from milk samples of lactating cows SO AMERICAN JOURNAL OF VETERINARY RESEARCH LA English DT Article ID COAGULASE-NEGATIVE STAPHYLOCOCCI; STREPTOGRAMIN-B RESISTANCE; BOVINE MAMMARY-GLAND; DAIRY HEIFERS; AUREUS; MASTITIS; LINCOSAMIDES; PREVALENCE; MACROLIDES; EPIDEMIOLOGY AB Objective-To isolate and characterize erythromycin-resistant methylase genes in multiple-antibiotic resistant staphylococci isolated from milk samples. Animals-300 lactating cows. Procedure-23 erythromycin-resistant staphylococci were isolated from milk samples of 300 lactating cows. The prevalence of erythromycin-resistant methylase (erm) genes, ermC and ermA genes, and the multicomponent macrolide efflux pump in staphylococci msrA genes were identified and characterized by use of multiplex polymerase chain reaction (PCR). Southern hybridization, restricted fragment length polymorphism (RFLP) analysis, and dot-blot hybridization. Results-Biochemical characterization indicated that 3 of 23 (13%) isolates were coagulase-positive Staphylococcus aureus, and the rest were coagulase-negative. Multiplex PCR resulted in amplification of a 520-base pair (bp) region of the ermC gene from the cell lysates of a strain of S simulans M-21 and S sciuri M-28. The ermC gene in both isolates was found on a 3-kilobase plasmid. The ermA gene was found on the chromosome of 21 isolates, and 6 RFLP patterns were observed. None of the isolates harbored the msrA gene. Conclusions-Erythromycin-resistant Staphylococcus spp isolated from milk samples of lactating cows may serve as reservoirs of erm genes homologous to those described in human isolates. However, the chromosomal insert patterns and prevalence of these genes, the sizes of plasmids harboring the genes, and the number of inserts of the genes (copy number) may differ from that of human isolates. C1 US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Nawaz, MS (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 22 TC 10 Z9 13 U1 1 U2 3 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0002-9645 J9 AM J VET RES JI Am. J. Vet. Res. PD SEP PY 2000 VL 61 IS 9 BP 1128 EP 1132 DI 10.2460/ajvr.2000.61.1128 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA 350AP UT WOS:000089078400022 PM 10976747 ER PT J AU Swee, W Klontz, KC Lambert, LA AF Swee, W Klontz, KC Lambert, LA TI A nationwide outbreak of alopecia associated with the use of a hair-relaxing formulation SO ARCHIVES OF DERMATOLOGY LA English DT Article ID GREEN HAIR AB Objective: To study the long-term outcome of adverse effects reported by persons who used a commercial hair-straightening product known as the Rio Hair Naturalizer System (World Rio Corporation). Design: Survey of individuals who contacted the Food and Drug Administration in 1994 and 1995 to report adverse effects linked to using the product. Setting: Persons residing in the United States. Patients: A total of 464 (59% of 790 eligible) patients who returned a completed questionnaire. Main Outcome Measures: Adverse effects associated with using the Rio Hair Naturalizer System products (neutral or color enhancer). Results: Ninety percent of respondents were African American women between the ages of 15 and 55 years. The most common complaints associated with the use of the products were hair breakage and/or hair loss, reported by 95% of respondents. Three quarters of those experiencing hair loss reported losing 40% or more of their original hair. The median time between the loss of original hair and the growth of new hair was 8 months; however, 40 (9%) respondents reported having no new growth at the time of completing the survey, some 2 years after using the product. When mixed according to package instructions, the mean pH of a sample of 20 neutral product kits tested was 1.39 (range, 1.1-3.15). For the 21 color-enhancer products tested, the mean pH was 2.82 (range, 2.29-3.08). Conclusion:: A nationwide outbreak of alopecia and scalp injuries involving tens of thousands of women land some men) occurred following the marketing of a chemical hair-relaxing product. Most of those affected reported substantial hair loss,with a majority indicating growth of new hair that was abnormal in both quantity and quality. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. George Washington Univ, Sch Publ Hlth, Washington, DC USA. RP Klontz, KC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-728,200 C St SW, Washington, DC 20204 USA. NR 19 TC 22 Z9 22 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD SEP PY 2000 VL 136 IS 9 BP 1104 EP 1108 DI 10.1001/archderm.136.9.1104 PG 5 WC Dermatology SC Dermatology GA 353NW UT WOS:000089283200004 PM 10987865 ER PT J AU Gallagher, G Dickensheets, H Eskdale, J Izotova, LS Mirochnitchenko, O Peat, J Pestka, S Vasquez, N Donnelly, RP Kotenko, SV AF Gallagher, G Dickensheets, H Eskdale, J Izotova, LS Mirochnitchenko, O Peat, J Pestka, S Vasquez, N Donnelly, RP Kotenko, SV TI Cloning, characterisation and expression of interleukin-19 (IL-19), a novel homologue of human interleukin-10 (IL-10). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Univ Glasgow, Glasgow, Lanark, Scotland. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. UMDNJ, New Brunswick, NJ 08903 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2000 VL 43 IS 9 SU S MA 16 BP S53 EP S53 PG 1 WC Rheumatology SC Rheumatology GA 357JU UT WOS:000089495800017 ER PT J AU Hu, YC Kaufman, J Cho, MW Golding, H Shiloach, J AF Hu, YC Kaufman, J Cho, MW Golding, H Shiloach, J TI Production of HIV-1 gp120 in packed-bed bioreactor using the vaccinia virus/T7 expression system SO BIOTECHNOLOGY PROGRESS LA English DT Article ID POLYMERASE SYSTEM; RNA-POLYMERASE; CELLS; TYPE-1 AB The HeLa cell-vaccinia virus system is an attractive method for producing recombinant mammalian proteins with proper post-translation modifications. This approach is especially important for the production of HIV-1 envelope glycoprotein, gp120, since more than half of its total mass is due to carbohydrates. A recombinant vaccinia virus/T7 RNA polymerase expression system was developed to express and produce large amounts of gp120 tagged with six histidine residues. In this system, the expressed T7 RNA polymerase from one virus drives the transcription of the gp120 encoded in the second virus. During the process development phase, the following parameters were studied: infection time, infection duration, multiplicity of infection, ratio of the two viruses, medium composition, and medium replacement strategy during the infection phase. The chosen production method was based on using the packed-bed bioreactor. The HeLa cells were immobilized on fibrous disks (Fibra-Cel) packed in an internal basket positioned in a vertically mixed bioreactor (Celligen Plus), and 25 g of carriers were packed in a 1.6-L (working volume) reactor. The process included a growth stage followed by a production stage. In the growth stage, the bed was perfused with a serum-containing medium, allowing the cells to grow to saturation, and in the production stage, done using serum-free medium, the cells were infected with the two recombinant viruses. The expressed protein was secreted, collected from the culture fluid, and purified. The specific production was found to be between 2 and 3 mu g of protein/10(6) cells, and the volumetric production was around 10 mg/50 g carriers. C1 NIDDK, Biotechnol Unit, LCDB, NIH, Bethesda, MD 20892 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Shiloach, J (reprint author), NIDDK, Biotechnol Unit, LCDB, NIH, Bldg 6,Rm B1-33, Bethesda, MD 20892 USA. NR 22 TC 16 Z9 19 U1 0 U2 1 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 SEP-OCT PY 2000 VL 16 IS 5 BP 744 EP 750 DI 10.1021/bp000112u PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 362UX UT WOS:000089797600011 PM 11027165 ER PT J AU Yao, L Pike, SE Setsuda, J Parekh, J Gupta, G Raffeld, M Jaffe, ES Tosato, G AF Yao, L Pike, SE Setsuda, J Parekh, J Gupta, G Raffeld, M Jaffe, ES Tosato, G TI Effective targeting of tumor vasculature by the angiogenesis inhibitors vasostatin and interleukin-12 SO BLOOD LA English DT Article ID CHEMOKINE RECEPTOR CXCR3; LEWIS-LUNG-CARCINOMA; ENDOTHELIAL-CELLS; MATRIX METALLOPROTEINASES; T-CELLS; B-CELLS; GROWTH; REGRESSION; MIG; ANGIOSTATIN AB Solid tumors are dependent on preexisting vasculature and neovascularization for their growth. Successful cancer therapies targeting the tumor vasculature would be expected to block the existing tumor blood supply and to prevent tumor neovascularization. We tested the antitumor activity of experimental therapy with 2 distinct antiangiogenic drugs. Vasostatin inhibits endothelial cell growth and neovascularization, and interleukin-12 (IL-12) targets the tumor vasculature acting through interferon-gamma (IFN-gamma) and the downstream chemokines interferon-inducible protein-10 (IP-10) and monokine induced by IFN-gamma. Individually, vasostatin and IL-12 produced distinct efficacy profiles in trials aimed at reducing tumor growth in athymic mice. In combination, these inhibitors halted the growth of human Burkitt lymphoma, colon carcinoma, and ovarian carcinoma. Thus, cancer therapy that combines distinct inhibitors of angiogenesis is a novel, effective strategy for the experimental treatment of cancer. (C) 2000 by The American Society of Hematology. C1 NCI, Med Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Ctr Biol Evaluat & Res, Rockville, MD USA. NCI, Pathol Lab, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Tosato, G (reprint author), NIH Bethesda Campus,Bldg 10,Rm 12N226,8800 Rockvi, Bethesda, MD 20892 USA. FU PHS HHS [IRA AWD-7] NR 49 TC 75 Z9 87 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2000 VL 96 IS 5 BP 1900 EP 1905 PG 6 WC Hematology SC Hematology GA 358VR UT WOS:000089578300041 PM 10961892 ER PT J AU Fang, GC Chang, CN Wu, YS Wang, V Fu, PPC Yang, DG Chen, SC Chu, CC AF Fang, GC Chang, CN Wu, YS Wang, V Fu, PPC Yang, DG Chen, SC Chu, CC TI The study of fine and coarse particles, and metallic elements for the daytime and night-time in a suburban area of central Taiwan, Taichung SO CHEMOSPHERE LA English DT Article DE metal analysis; fine particles; coarse particle; air sampling ID AEROSOL; AIR AB Daily average concentrations of fine and coarse particulates, and TSP samples have been measured simultaneously at daytime and night-time periods by using Universal and PS-1 sampler in a suburban area of central Taiwan from June to August 1998, The samples were analyzed by atomic absorption spectrometry to determine the fine and coarse particulate concentrations of metallic elements (Ca, Fe, Mn, Pb, Cu, Zn and Cr). The concentration of PM2.5 and TSP showed a decreased trend for the daytime period. The fine particle concentrations were about two times as that of coarse particulate concentrations. The averaged fine particulate concentrations at daytime are higher than at night-time. Ca and Fe were mostly in the coarse particulate mode. The correlation coefficients were 0.63 and 0.69 for elements Ca and Fe in the coarse particle mode for day and night periods, Pb showed a similar distribution ratio with Mn for the fine to coarse particle ratios at both day and night period, Pb and Mn are highly correlated for the day (R = 0.78) and night period (R = 0.61) at particle size <2.5 mu m. Cu and Zn were mainly in fine particles at both day and night period, Fe and Ca consist of the major parts of all the elements. Elemental Mn is the lowest among the rest of the heavy metals. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Hungkuang Inst Technol, Dept Environm Engn & Hlth, Taichung 433, Taiwan. Tunghai Univ, Dept Environm Sci, Taichung 407, Taiwan. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Chien Yu Hosp, Kaohsiung, Taiwan. Hungkuang Inst Technol, Off Secretary, Taichung 433, Taiwan. RP Fang, GC (reprint author), Hungkuang Inst Technol, Dept Environm Engn & Hlth, Taichung 433, Taiwan. NR 14 TC 50 Z9 51 U1 2 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD SEP PY 2000 VL 41 IS 5 BP 639 EP 644 DI 10.1016/S0045-6535(99)00507-X PG 6 WC Environmental Sciences SC Environmental Sciences & Ecology GA 313KF UT WOS:000086998300004 PM 10834362 ER PT J AU MacLeod, SL Nowell, S Massengill, J Jazieh, A McClure, G Plaxco, J Kadlubar, FF Lang, NP AF MacLeod, SL Nowell, S Massengill, J Jazieh, A McClure, G Plaxco, J Kadlubar, FF Lang, NP TI Cancer therapy and polymorphisms of cytochromes P450 SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE LA English DT Article; Proceedings Paper CT 2nd Joint IFCC-Roche Diagnostics Conference CY APR 16-19, 2000 CL KYOTO, JAPAN DE cytochrome P450; chemotherapeutic agents; pharmacogenetics; polymorphism ID CAFFEINE URINARY METABOLITES; GENETIC VARIANT; IN-VIVO; DOCETAXEL; CYP1A2; BIOTRANSFORMATION; PHARMACOKINETICS; POPULATION; PACLITAXEL; CYP3A4 AB Cytochrome P450 (CYP) enzymes are important in the metabolism of some endogenous compounds, environmental and dietary xenobiotics and many drugs. Many of these enzymes have genetic polymorphisms that produce significant changes in metabolic activity, however the function of other polymorphisms is unknown. Genetic polymorphisms have important influences on variability in human pharmacokinetics, including intra-individual differences in drug toxicity, drug interactions and response to chemotherapy. Other factors that influence drug metabolism include differences in enzyme expression due to differences in age, gender, smoking status, exposure to dietary or environmental xenobiotics or co-administration of other drugs. In addition, some xenobiotics and drugs can directly inhibit or induce the activity of CYPs. All of these factors can produce differences in metabolic capacities among individuals which can produce toxicity in some patients and sub-effective dosing in others. Maximum clinical benefit will require a more complete understanding of the influence of these polymorphisms on allele function and their interaction with inducers and inhibitors of enzyme expression or activity. This effort will permit the pharmacogenetic screening of patients before the administration of drugs and result in the identification of individuals who are prone to adverse reactions or poor response, resulting in more effective individualized therapy. C1 Cent Arkansas Vet Hlth Care Syst, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Little Rock, AR USA. RP Lang, NP (reprint author), Cent Arkansas Vet Hlth Care Syst, 4300 W 7th St 112-LR, Little Rock, AR 72205 USA. NR 23 TC 14 Z9 16 U1 0 U2 1 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1434-6621 J9 CLIN CHEM LAB MED JI Clin. Chem. Lab. Med. PD SEP PY 2000 VL 38 IS 9 BP 883 EP 887 DI 10.1515/CCLM.2000.128 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 380LQ UT WOS:000165703700015 PM 11097344 ER PT J AU Marroum, PJ Uppoor, RS Parmelee, T Ajayi, F Burnett, A Yuan, R Svadjian, R Lesko, LJ Balian, JD AF Marroum, PJ Uppoor, RS Parmelee, T Ajayi, F Burnett, A Yuan, R Svadjian, R Lesko, LJ Balian, JD TI In vivo drug-drug interaction studies - A survey of all new molecular entities approved from 1987 to 1997 SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID INHIBITION; METABOLISM AB Ninety-eight new molecular entities applications approved between 1987 to 1991 (period I) and 193 applications for new molecular entities between 1992 to 1997 (period II) were surveyed for drug-drug interaction studies. In period I (used as a comparator), 32 applications contained drug-drug interaction studies for a total of 117 studies. In period II, 106 applications reported drug-drug interaction studies, and the number of studies per new molecular entity ranged from 0 to 15. Most studies (77%) were performed in healthy subjects, with 44% using crossover designs, 7% using parallel designs, and the remaining using fixed sequence designs, The most common dosing scheme for new molecular entities/interacting drug was multiple dose (47%), whereas single dose/multiple dose was used in 31% of studies, and single dose/single dose was used in 18% of studies. Of the 540 drug-drug interaction studies submitted in period II, 80 (15%) resulted in clinically significant labeling statements, Submissions for new molecular entities to the Center for Drug Evaluation and Research divisions most likely to include drug-drug interaction studies were neuropharmacology, cardiorenal, antiviral, and antiinfective drugs, Some drug classes such as oncology drug products and radioimaging products were least likely to include drug-drug interaction studies in their submissions. We conclude that the use of drug-drug interaction studies in the drug development process has increased between the two periods. C1 US FDA, Ctr Drug Evaluat & Res, OPS, OCPB,DPE 1, Rockville, MD 20857 USA. RP Marroum, PJ (reprint author), US FDA, Ctr Drug Evaluat & Res, OPS, OCPB,DPE 1, 5600 Fishers Ln,Woodont-2 Bldg,Rm 5008, Rockville, MD 20857 USA. NR 11 TC 18 Z9 18 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 2000 VL 68 IS 3 BP 280 EP 285 DI 10.1067/mcp.2000.109366 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 358LR UT WOS:000089560000007 PM 11014409 ER PT J AU Frame, LT Ozawa, S Nowell, SA Chou, HC Delongchamp, RR Doerge, DR Lang, NP Kadlubar, FF AF Frame, LT Ozawa, S Nowell, SA Chou, HC Delongchamp, RR Doerge, DR Lang, NP Kadlubar, FF TI Simple colorimetric assay for phenotyping the major human thermostable phenol sulfotransferase (SULT1A1) using platelet cytosols SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID N-HYDROXY ARYLAMINES; HUMAN-LIVER; METABOLIC-ACTIVATION; HETEROCYCLIC AMINES; GENETIC POLYMORPHISMS; PARTIAL-PURIFICATION; FLUOROMETRIC ASSAY; MOLECULAR-CLONING; SULFATION; PHARMACOGENETICS AB A thermostable phenol sulfotransferase, SULT1A1, has been implicated in numerous detoxification and bioactivation pathways; however, little is known regarding its endogenous function or its putative role in mediating risk for human environmental disease. A simple endpoint colorimetric assay is described that can be used for rapid phenotyping of SULT1A1 activity in human populations. The assay utilizes a microtiter-plate format and relatively small amounts of platelet cytosol-derived enzyme. The enzyme catalyzes the synthesis of 2-naphthylsulfate from 2-naphthol and 5'-phosphoadenosine 3'-phosphosulfate (PAPS), whereas addition of p-nitrophenyl sulfate to the assay contributes to an effective PAPS-regenerating system. In contrast to other sulfotransferase assay methods, 3'-phosphoadenosine 5'-phosphate (PAP) does not accumulate during the incubation to interfere with enzyme activity, but instead serves as a cofactor to cause the removal of sulfate from p-nitrophenyl sulfate to regenerate PAPS. This reaction concomitantly results in generation of p-nitrophenol that can be quantified colorimetrically at 405 nm (epsilon = 18,200 M-1) to give an indirect measure of sulfotransferase activity. Using platelet enzyme preparations from adult human subjects, sulfation rates of two prototypical thermostable phenol sulfotransferase substrates (2-naphthol and p-nitrophenol) and one thermolabile phenol sulfotransferase substrate (dopamine) were determined using standard radiochemical protocols. These data were then compared with results from the colorimetric assay using 2-naphthol as substrate. There was a good correlation between the phenotyping assay and radiochemical assays for both 2-naphthol sulfotransferase and p-nitrophenol sulfotransferase activity (r = 0.85 and 0.69, respectively). However, SULT1A1 activity was approximately 10 to 20 times higher with the colorimetric determination. As anticipated, there was no correlation between SULT1A1 activity and dopamine sulfotransferase activity (r = 0.07) in these human platelet preparations. This inexpensive and rapid method for phenotyping SULT1A1 activity may help investigators assess a role for this enzyme in disease susceptibility. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biometry, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Cent Arkansas Vet Hlth Care Syst, Dept Surg, Little Rock, AR USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. RP Kadlubar, FF (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 39 TC 44 Z9 45 U1 3 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD SEP PY 2000 VL 28 IS 9 BP 1063 EP 1068 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 346FR UT WOS:000088860600010 PM 10950850 ER PT J AU Puri, RK AF Puri, RK TI IL-4 receptor-directed cytotoxin for therapy of AIDS-associated KS tumors SO DRUG NEWS & PERSPECTIVES LA English DT Article ID CIRCULARLY PERMUTED INTERLEUKIN-4; KAPOSIS-SARCOMA CELLS; COMMON GAMMA-CHAIN; PSEUDOMONAS EXOTOXIN; CARCINOMA-CELLS; FUNCTIONAL COMPONENT; CHIMERIC TOXIN; EXPRESSION; GROWTH; PHOSPHORYLATION AB AIDS-associated Kaposi's sarcoma (AIDS-KS) represents one of the most common malignancies associated with human immunodeficiency virus infection. To target effective therapeutic agents, we have discovered that AIDS-KS cells express high-affinity receptors for interleukin-4 (IL-4), a pleiotropic immune regulatory cytokine. Molecular studies have revealed that AIDS-KS cells express type II IL-4 receptors, in which IL-4 forms a productive complex with primary IL-4 binding protein (IL-4R beta, also known as IL-4R alpha) and a shared subunit between IL-4 and IL-13R systems (IL-13R alpha', also known as IL-13R alpha1). A recombinant fusion protein composed of IL-4 and a mutated form of a powerful bacterial toxin called Pseudomonas exotoxin (PE)-the fusion protein is termed IL4(38-37)-PE38KDEL or cpIL4-PE-was found to be highly and specifically cytotoxic to AIDS-KS cells in vitro. Normal human immune cells (e.g., resting T and B cells and monocytes) or endothelial cells, a possible precursor of AIDS-KS, expressed low numbers of IL-4R and showed little or no sensitivity to cpIL4-PE. Administration of cpIL4-PE in nude mice with established subcutaneously growing AIDS-KS tumors produced remarkable antitumor activity in a dose-dependent manner with the highest dose exhibiting complete responses without any visible toxicity. KS tumors produced metabolic changes including cachexia, hypoglycemia and lymphopenia, all of which were prevented by cpIL4-PE treatment. These studies indicate that cpIL4-PE is a promising experimental therapeutic agent for treatment of AIDS-KS. (C) 2000 Prous Science. Ail rights reserved. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, Bethesda, MD 20892 USA. NR 38 TC 3 Z9 4 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 SEP PY 2000 VL 13 IS 7 BP 395 EP 402 DI 10.1358/dnp.2000.13.7.858492 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 378JP UT WOS:000165581500002 PM 12937611 ER PT J AU Royce, ME Hoff, PM Pazdur, R AF Royce, ME Hoff, PM Pazdur, R TI Progress in colorectal cancer chemotherapy - How far have we come, how far to go? SO DRUGS & AGING LA English DT Review ID HIGH-DOSE LEUCOVORIN; PHASE-III TRIAL; THYMIDYLATE SYNTHASE INHIBITOR; ACTIVE SPECIFIC IMMUNOTHERAPY; 2 BIOCHEMICAL MODULATORS; RANDOMIZED TRIAL; CONTINUOUS-INFUSION; DIHYDROPYRIMIDINE DEHYDROGENASE; FLUOROURACIL FAILURE; INTERFERON ALPHA-2A AB Fluorouracil has been the mainstay of treatment for colorectal cancer (CRC) for almost 40 years. Various schedules and biochemical modulators have been investigated in an attempt to improve the therapeutic efficacy of fluorouracil. To date, fluorouracil plus folinic acid represents the standard therapy in CRC for the adjuvant treatment of patients at high risk for relapse and for the first-line treatment of metastatic disease. Combination chemotherapy regimens have not been developed due to the lack of other active agents. However, the availability of several novel agents now allows investigation of combination regimens in this disease. One group of such agents, the oral fluoropyrimidines (tegafur/uracil plus oral folinic acid, capecitabine, eniluracil plus oral fluorouracil, and tegafur/gimeracil/potassium oxonate), are convenient oral alternatives to intravenous fluorouracil. A particular advantage of these oral agents is the reduction in the incidence of febrile neutropenia and mucositis compared with fluorouracil given in an intravenous bolus schedule. To gain clinical acceptance, however, oral fluoropyrimidines must confer at least the same survival advantages associated with the optimal intravenous fluorouracil regimens. Irinotecan and oxaliplatin are 2 other novel agents that have mechanisms of action that are uniquely different from those of fluorouracil, with demonstrated activity in patients with fluorouracil-refractory disease. Recent randomised trials comparing fluorouracil plus folinic acid with combinations of either irinotecan or oxaliplatin and fluorouracil plus folinic acid have shown that response rates are improved and time to progression is increased in patients receiving the combination regimens. These regimens are being rapidly introduced in the adjuvant setting, and the role and acceptance of these combination regimens as first-line therapy needs to be defined. Other novel agents bring evaluated in the treatment of patients with advanced CRC include oral edrecolomab (monoclonal antibody 17-1A) and tumour vaccines. Future research is focused on enabling clinicians to individualise treatment strategies in patients with CRC, so as to improve clinical outcomes and reduce drug toxicity. C1 Univ Texas, MD Anderson Canc Ctr, Dept GI Oncol & Digest Dis, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Div Med, Houston, TX 77030 USA. US FDA, Ctr Drug Evaluat & Treatment, Div Oncol Prod, Rockville, MD 20857 USA. RP Hoff, PM (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept GI Oncol & Digest Dis, Box 78,1515 Holcombe Blvd, Houston, TX 77030 USA. NR 91 TC 9 Z9 9 U1 1 U2 2 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PD SEP PY 2000 VL 17 IS 3 BP 201 EP 216 DI 10.2165/00002512-200017030-00004 PG 16 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 356KA UT WOS:000089441400004 PM 11043819 ER PT J AU Flurer, CL AF Flurer, CL TI Characterization of galactomannans by capillary electrophoresis SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE capillary electrophoresis; tara; guar; cassia; locust bean; protein profiles AB Capillary electrophoresis (CE) was utilized in the characterization of various galactomannans. Standards of gums were extracted with 50% CH3CN to remove the residual proteins from the gum matrix. Separation buffers were optimized with respect to pH, buffer concentration and presence of sodium dodecyl sulphate, yielding protein profiles from which the desired information could be obtained. Examples are given of the profiles generated by various gums and gum blends to aid in the verification of component presence, and to demonstrate levels of adulteration detectable under the buffer conditions used. 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 2 TC 5 Z9 6 U1 0 U2 0 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 SEP PY 2000 VL 17 IS 9 BP 721 EP 731 DI 10.1080/026520300415255 PG 11 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 348RT UT WOS:000089000800001 PM 11091784 ER PT J AU Vanderveen, JE Bode, JW Bruhn, CM Campbell, E Harlander, SK Nelson, G Taylor, S AF Vanderveen, JE Bode, JW Bruhn, CM Campbell, E Harlander, SK Nelson, G Taylor, S TI Labeling of rDNA biotechnology-derived foods SO FOOD TECHNOLOGY LA English DT Article AB This section begins with an overview of the United States food labeling requirements directly relevant to the labeling of recombinant DNA biotechnology-derived foods, including constitutional limitations on the government's authority to regulate food labeling and specific case studies relevant to labeling rDNA biotechnology-derived foods. Next, the report discusses labeling policies for rDNA biotechnology-derived foods in the U.S. and internationally and the impact of labeling distinctions on food product distribution systems. Finally, consumer perceptions of various label statements are discussed. C1 US FDA, San Antonio, TX USA. Olsson Frank & Weeda PC, Washington, DC USA. Univ Calif Davis, Ctr Consumer Res, Davis, CA 95616 USA. AAC Consulting Grp, Bethesda, MD USA. Biorat Consultants Inc, New Brighton, MN 55112 USA. Univ Illinois, Dept Agr & Consumer Econ, Urbana, IL 61801 USA. Univ Nebraska, Dept Food Sci & Technol, Lincoln, NE 68583 USA. RP Vanderveen, JE (reprint author), US FDA, San Antonio, TX USA. NR 40 TC 0 Z9 1 U1 0 U2 0 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 SEP PY 2000 VL 54 IS 9 BP 62 EP 74 PG 13 WC Food Science & Technology SC Food Science & Technology GA 353HZ UT WOS:000089269900014 ER PT J AU Kawakami, K Joshi, BH Puri, RK AF Kawakami, K Joshi, BH Puri, RK TI Sensitization of cancer cells to interleukin 13-Pseudomonas exotoxin-induced cell death by gene transfer of interleukin 13 receptor alpha chain SO HUMAN GENE THERAPY LA English DT Article ID HUMAN GLIOMA-CELLS; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; SIGNAL-TRANSDUCTION; IL-13 RECEPTOR; RETROVIRAL VECTORS; (IL)-13 BINDING; CARCINOMA-CELLS; CLONING; TOXIN AB We have demonstrated that primary interleukin 13 (IL-13) binding protein IL-13 receptor (IL-13R) alpha chain plays an important role in IL-13 binding and internalization in the IL-13R system, Although IL-13R alpha chain is expressed on many cancer cell lines, some cancer types do not express or express low levels of this receptor chain. Consequently, these cells show no or low sensitivity to the cytotoxic effect of a recombinant chimeric protein composed of IL-13 and a mutated form of a Pseudomonas exotoxin, IL13-PE38QQR. Here we demonstrate that pancreatic cancer, renal cell carcinoma, head and neck cancer, and glioblastoma cell lines that were genetically altered to express high levels of IL-13R alpha chain increase their binding affinity for IL-13, and increase their sensitivity to IL13-PE38QQR by at least 6-fold to 1000-fold compared with mock-transfected control cells. This observation was made by protein synthesis inhibition assay and confirmed by clonogenic assay. Our studies provide a proof of principle for a novel strategy for cancer therapy that combines gene transfer and targeted cytotoxin therapy. C1 NIH, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,Food & Drug Adm, 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, Bldg 29B,Room 2NN10,29 Lincoln Dr MSC 4555, Bethesda, MD 20892 USA. NR 39 TC 39 Z9 42 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD SEP 1 PY 2000 VL 11 IS 13 BP 1829 EP 1835 DI 10.1089/10430340050129459 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 352AX UT WOS:000089193300002 PM 10986556 ER PT J AU Rahmoeller, G AF Rahmoeller, G TI Do medical device manufacturers care about patients? SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Editorial Material C1 US FDA, Div Cardiovasc Devices, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD SEP-OCT PY 2000 VL 19 IS 5 BP 116 EP 116 DI 10.1109/MEMB.2000.870239 PG 1 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 355QK UT WOS:000089396200018 PM 11191138 ER PT J AU Kossaczka, Z Shiloach, J Johnson, V Taylor, DN Finkelstein, RA Robbins, JB Szu, SC AF Kossaczka, Z Shiloach, J Johnson, V Taylor, DN Finkelstein, RA Robbins, JB Szu, SC TI Vibrio cholerae O139 conjugate vaccines: Synthesis and immunogenicity of V-cholerae O139 capsular polysaccharide conjugates with recombinant diphtheria toxin mutant in mice SO INFECTION AND IMMUNITY LA English DT Article ID NORTH-AMERICAN VOLUNTEERS; IMMUNOLOGICAL PROPERTIES; VIRULENCE DETERMINANTS; EXPERIMENTAL CHALLENGE; BENGAL; LIPOPOLYSACCHARIDE; PROTECTION; ANTIBODY; TETRAFLUOROBORATE; ANTIBACTERIAL AB Epidemiologic and experimental data provide evidence that a critical level of serum immunoglobulin G (IgG) antibodies to the surface polysaccharide of Vibrio cholerae O1 (lipopolysaccharide) and of Vibrio cholerae O139 (capsular polysaccharide [CPS]) is associated with immunity to the homologous pathogen. The immunogenicity of polysaccharides, especially in infants, may be enhanced by their covalent attachment to proteins (conjugates). Two synthetic schemes, involving 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) as activating agents, mere adapted to prepare four conjugates of V. cholerae O139 CPS with the recombinant diphtheria toxin mutant, CRMH21G. Adipic acid dihydrazide was used as a linker. When injected subcutaneously into young outbred mice by a clinically relevant dose and schedule, these conjugates elicited serum CPS antibodies of the IgG and IgM classes with vibriocidal activity to strains of capsulated V. cholerae O139. Treatment of these sera with 2-mercaptoethanol (2-ME) reduced, but did not eliminate, their vibriocidal activity, These results indicate that the conjugates elicited Ige with vibriocidal activity. Conjugates also elicited high levels of serum diphtheria toxin IgG. Convalescent sera from 20 cholera patients infected with V. cholerae O139 had vibriocidal titers ranging from 100 to 3,200: absorption with the CPS reduced the vibriocidal titer of all sera to less than or equal to 50. Treatment with 2-ME reduced the titers of 17 of 20 patients to less than or equal to 50. These data show that, like infection with V. cholerae O1, infection with V. cholerae O139 induces vibriocidal antibodies specific to the surface polysaccharide of this bacterium (CPS) that are mostly of IgM class. Based on these data, clinical trials with the V. cholerae O139 CPS conjugates with recombinant diphtheria toxin are planned. C1 NICHHD, NIH, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Washington, DC 20307 USA. Univ Missouri, Dept Mol Microbiol & Immunol, Columbia, MO 65212 USA. RP Kossaczka, Z (reprint author), NICHHD, NIH, Bldg 6,Rm 424, Bethesda, MD 20892 USA. NR 45 TC 38 Z9 40 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 SEP PY 2000 VL 68 IS 9 BP 5037 EP 5043 DI 10.1128/IAI.68.9.5037-5043.2000 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 346KM UT WOS:000088870200028 PM 10948122 ER PT J AU Yaes, RJ AF Yaes, RJ TI Defining a uniform biologically effective dose for organs with parallel architecture SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Letter ID LINEAR-QUADRATIC MODEL; DISTRIBUTIONS; RADIOTHERAPY C1 US FDA, Ctr Drug Evaluat & Res, Div Med Imaging & Radiopharmaceut Drug Prod, Rockville, MD 20857 USA. RP Yaes, RJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Med Imaging & Radiopharmaceut Drug Prod, HFD-160,5600 Fishers Lane, Rockville, MD 20857 USA. NR 10 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2000 VL 48 IS 2 BP 609 EP 611 DI 10.1016/S0360-3016(00)00752-5 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 349WT UT WOS:000089069100043 PM 11012307 ER PT J AU Junod, SW AF Junod, SW TI The politics of international health: The children's vaccine initiative and the struggle to develop vaccines for the third world. SO ISIS LA English DT Book Review RP Junod, SW (reprint author), US FDA, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0021-1753 J9 ISIS JI Isis PD SEP PY 2000 VL 91 IS 3 BP 634 EP 635 DI 10.1086/384933 PG 2 WC History & Philosophy Of Science SC History & Philosophy of Science GA 375EH UT WOS:000165386200089 ER PT J AU Anderson, DL Cunningham, WC AF Anderson, DL Cunningham, WC TI Revalidation and long-term stability of National Institute of Standards and Technology Standard Reference Materials 1566, 1567, 1568, and 1570 SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID RAY ACTIVATION-ANALYSIS; NEUTRON-SCATTERING; TRACE-ELEMENTS; TOTAL DIET; FOOD; BORON; SPECTROMETRY; LABORATORIES; HISTORY AB Multiple units of Standard Reference Materials (SRMs) 1566 Oyster Tissue, 1567 Wheat Flour, 1568 Rice Flour, and 1570 Trace Elements in Spinach, produced by the National Institute of Standards and Technology (NIST, then the National Bureau of Standards), were analyzed 17-20 years after the original certification dates and 12-15 years after the certificates became invalid. Instrumental neutron activation analysis and thermal neutron prompt gamma-ray activation analysis were used to measure mass fractions for 27 elements in these SRMs to revalidate them for use in quality assurance (QA) programs required for food analysis programs within the U.S. Food and Drug Administration. With the exception of Se in SRM 1567, all element mass fractions were in agreement with certified values and literature data. Some evidence of B loss from SRM 1568 was observed. These materials were judged to be suitable for continued use in QA programs. Findings showed that these matrixes exhibited stability of moisture, mass fraction, and weight basis for far longer (greater than or equal to 15 years) than was indicated by the 5-year validity statement on the NIST Certificates of Analysis. C1 US FDA, Elemental Res Branch HFS338, Washington, DC 20204 USA. RP Anderson, DL (reprint author), US FDA, Elemental Res Branch HFS338, Washington, DC 20204 USA. NR 20 TC 12 Z9 12 U1 0 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2000 VL 83 IS 5 BP 1121 EP 1134 PG 16 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 360KT UT WOS:000089667400013 PM 11048853 ER PT J AU Hight, SC AF Hight, SC TI Graphite furnace atomic absorption spectrometric determination of lead and cadmium extracted from ceramic foodware: Collaborative study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A modification of the official flame atomic absorption spectrometric (FAAS) method for determining lead and cadmium extracted from ceramic foodware was collaboratively studied. In the modified method, graphite furnace atomic absorption spectrometry (GFAAS) is substituted for FAAS, The modified method also includes mandatory quality control procedures to improve method performance, The extraction procedure of the official method (leaching with 4% acetic acid for 24 h at room temperature) remains unchanged. Seven laboratories analyzed blind duplicate portions of 3 ceramicware leach solutions containing Pb at concentrations of 0.0196, 0.403, and 3.73 mu g/mL and Cd at concentrations of 0.00236, 0.0456, and 0.544 mu g/mL. Performance of the modified method compared well with that of the official method. The repeatability relative standard deviation (RSDr) ranged from 0.87 to 6.7% for Pb and from 3.7 to 11% for Cd, The reproducibility relative standard deviation (RSDR) ranged from 4.5 to 12% for Pb and from 7.0 to 11% for Cd, Accuracy of collaborator results was 97-98% for Pb and 93-101% for Cd. Quality control results and quantitation limits were excellent, Method quantitation limits varied among laboratories from 0.005 to 0.019 mu g/mL for Pb and from 0.0004 to 0.0019 mu g/mL for Cd. The modified method was adopted First Action by AOAC INTERNATIONAL. C1 US FDA, Ctr Food Safety & Appl Nutr, Elemental Res Branch, Washington, DC 20204 USA. RP Hight, SC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Elemental Res Branch, HFS-338,200 C St SW, Washington, DC 20204 USA. NR 9 TC 2 Z9 4 U1 0 U2 5 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2000 VL 83 IS 5 BP 1174 EP 1188 PG 15 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 360KT UT WOS:000089667400019 PM 11048859 ER PT J AU Park, DL Whitaker, TB Giesbrecht, FG Njapau, H AF Park, DL Whitaker, TB Giesbrecht, FG Njapau, H TI Performance of three pneumatic probe samplers and four analytical methods used to estimate aflatoxins in bulk cottonseed SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB The requirement by the U.S. Food and Drug Administration that agricultural products susceptible to aflatoxin contamination contain aflatoxin at levels less than or equal to 20 parts per billion for consumer-ready products has led to the establishment of inspection programs by various industries. In Arizona, cottonseed samples from 100 ton piles are collected by an accumulation of 3 or more probings with a pneumatic probe. When sampling compacted cottonseed piles, the large official pneumatic probe (7.6 x 127 cm) decreases in efficiency, Two smaller probes (1.9 x 127 cm and 1.9 x 254 cm)were therefore developed and tested for their suitability for sampling cottonseed piles. Three rapid analytical methods (one thin-layer chromatographic and 2 immunochemical) were tested for suitability as on-site assay systems. An analysis of variance of the analytical test results showed no differences between the various probes tested. Of the rapid methods, however, only the AflaTest-P immunoaffinity column gave results similar to those of the official AOAC thin-layer chromatography method. In terms of safety, however, all methods prevent material contaminated above regulatory limits from reaching the consumer. C1 Univ Arizona, Dept Food Sci, Tucson, AZ 85721 USA. N Carolina State Univ, USDA ARS, Raleigh, NC 27695 USA. N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. Louisiana State Univ, Ctr Agr, Dept Food Sci, Baton Rouge, LA 70803 USA. RP Park, DL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Nat Prod, HFS-345,200 C St SW, Washington, DC 20204 USA. NR 10 TC 6 Z9 6 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2000 VL 83 IS 5 BP 1247 EP 1251 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 360KT UT WOS:000089667400028 PM 11048868 ER PT J AU Calvo, MS Gundberg, CM Barton, CN Park, YK AF Calvo, MS Gundberg, CM Barton, CN Park, YK TI Association of vitamin K-1 intake with femoral bone mass in older white women: Significant findings about supplement users from the Third National Health and Nutrition Examination Survey, 1988-94 (NHANES III). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Yale Univ, Dept Orthopaed, New Haven, CT USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA SU335 BP S412 EP S412 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898401108 ER PT J AU Carpenter, TO Barton, CN Park, YK AF Carpenter, TO Barton, CN Park, YK TI Usual dietary magnesium intake in NHANES III is associated with femoral bone mass. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Yale Univ, Sch Med, New Haven, CT 06520 USA. US FDA, Office Sci Anal Support, Washington, DC 20204 USA. US FDA, Office Nutr Prod Labeling Dietary Supplements, Washington, DC 20204 USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA SA311 BP S292 EP S292 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400615 ER PT J AU Wear, KA AF Wear, KA TI Sources of disparity for transit-time-based and frequency-domain-based sound speed measurements in trabecular bone. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA SU317 BP S408 EP S408 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898401090 ER PT J AU Wear, KA AF Wear, KA TI Fundamental mechanisms underlying broadband ultrasonic attenuation and backscattering in calcaneus. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA SA295 BP S289 EP S289 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400601 ER PT J AU Lathers, CM AF Lathers, CM TI Lessons learned from the past: A guide for the future of clinical pharmacology in the 21st century SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID POPULATION PHARMACOKINETICS; BASIC CONCEPTS; 1ST TIME; CONTROVERSY; DRUGS; SYSTEM; BIOEQUIVALENCE; INSTRUCTION AB This article is a documentary of the history of the American College of Clinical Pharmacology (ACCP) and the Journal of Clinical Pharmacology. The history of the college and of the journal is presented as summarized by a few of the many leaders who played key roles in the growth of the profession of Clinical Pharmacology. Together, the college, the journal, and all clinical pharmacologists working in academia, industry CROs, or government in many different subspecialty areas of the discipline contribute to the advancement of clinical pharmacology, the development of new drugs, and to an improved qualify of life for mankind. Achieving leadership in health care in an era of change requires actions to be dynamic and flexible. Leaders must be capable of self-development and self-education. Leaders must examine challenges from top to bottom and build on the leadership foundations of vision, courage, and knowledge. Strong leaders are needed for the future of clinical pharmacology to address the rapidly changing environment for health care givers and the challenges faced by those working in drug development or training new leaders. One lesson from the past, from the professional life of Harry Gold, is that it is very important to convey the excitement of the field of clinical pharmacology and to pass on this excitement and knowledge base to those currently leading the educational process necessary to keep clinical pharmacologists in the forefront of the medical arena of today and tomorrow The college became an instrument for change in the field of clinical pharmacology. Forward thinking efforts of the college did not allow stagnation. All founding leaders of the college were possessed of a dream of "what could be and what should be. " Two points should be emphasized: the importance of teaching teachers how to teach and the importance of forming national networks, such as the college, to concentrate on the role of teaching students. Today's students are the leaders of tomorrow The training of any given student in the field of clinical pharmacology continues over many years and requires the effort of many qualified mentors. The ACCP continues to prepare or the changing demands of a new millennium. The college responded to three challenges:(1) utilization of new technologies consistent with contemporary trends; (2) identification of new member services; and (3) dissemination of a position paper defining the philosophical foundations of the college. The basic tenant of the college remains the same today as it has been over the years: provide a multidisciplinary educational environment to have a broad appeal to the membership interested in clinical pharmacology. (C)2000 the American College of Clinical Pharmacology. C1 Amer Coll Clin Pharmacol, New York, NY USA. RP Lathers, CM (reprint author), US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, 7500 Standish Pl,HFV-100,Room 390, Rockville, MD 20855 USA. NR 37 TC 4 Z9 5 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2000 VL 40 IS 9 BP 946 EP 966 DI 10.1177/00912700022009684 PG 21 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 347DL UT WOS:000088912100006 PM 10975067 ER PT J AU Chang, HC Seng, JE Leakey, JEA Gandy, J AF Chang, HC Seng, JE Leakey, JEA Gandy, J TI Metabolism of flutamide in diet control Fischer 344 and Brown Norway x F 344 rats, and its hydroxylation and conjugation by human CYP450s and UDP-glucuronosyltransferases SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Article DE flutamide; diet restricted; non limited-fed; hydroxylation; glucuronidation; CYP450; UDP-glucuronosyltransferase ID HUMAN-LIVER; ANTIANDROGEN FLUTAMIDE; PROSTATE-CANCER; NONSTEROIDAL ANTIANDROGEN; ENZYME-ACTIVITIES; HYDROXYFLUTAMIDE; GLUCURONIDATION; EXPRESSION; CYTOCHROME-P450; IDENTIFICATION AB In our current report, flutamide (2-methyl-N-[4-nitro-3-(trifluoromethyl)-phenyl] propanamide) treated diet control and non limited-fed Fischer 344 (F344) and Brown Nora ay (BN) x F344 rats showed that diet control reduces spontaneous and flutamide-induced hyperplasia((1)). In this continued study, we found that serum concentrations of active metabolite of flutamide, 2-hydroxyflutamide (OH-flu), were 181 +/- 26.6 ng/mL and 68 +/- 8.0 ng/mL (p<0.05), in non-limited fed and diet control F344 rats. In BN x F344 rats, the serum concentrations of 2-OH-flutamide were 232 +/- 57 ng/mL and 57 +/- 6 ng/mL (p<0.05) in non-limited fed and diet control animals, in diet control groups, liver microsomes from flutamide-treated F344 rats showed high 7-ethoxyresorufin O-deethylase (EROD) activity, white 7-Benzoxyresorufin O-dealkylase (BROD) activity was not affected significantly. Both rat and human liver microsomes show ed flutamide oxidation activity. Human liver microsomes showed 10 times higher activity than rat liver microsomes (0.673 +/- 0.04 vs 0.063 +/- 0.008 nmol OH-flu/min/mg protein). Microsomes from human tissues such as colon, colon cancer, kidney, bladder, pancreas, prostate. prostate cancer, or ovarian cancer, showed no or non-detectable activity for flutamide hydroxylation. CYP450 1A1, 1A2, 1B1 and 2C19 from human lymphoblastoid cell lines, oxidized flutamide to OH-flu in vitro, with activities from 0.118 +/- 0.005 to 0.275 +/- 0.010 nmol/min/mg protein. Microsomes isolated from human kidney, colon, and liver showed UDP-glucuronosyltransferase (UGT) activity for glucuronidation of OH-flu. Human kidney showed the highest activity. Several human recombinant UGTs(1A1, 1A4, 1A6, 1A7. 1A9, and 1A10) also showed glucuronidation activity for OH-flu. It was found that UGT1A6 was more active than other human UGTs. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. NR 55 TC 2 Z9 2 U1 0 U2 0 PU NATL LABORATORIES FOODS DRUGS PI NANKANG, TAIPEI PA DEPT HEALTH, EXECUTIVE YUAN, 161-2 KUEN YANG ST DR. ERICK T. SUEN, DEPUTY DIR., NANKANG, TAIPEI, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD SEP PY 2000 VL 8 IS 3 BP 166 EP 173 PG 8 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA 360XA UT WOS:000089691600003 ER PT J AU Grehan, JF Hilbert, SL Ferrans, VJ Droel, JS Salerno, CT Bianco, RW AF Grehan, JF Hilbert, SL Ferrans, VJ Droel, JS Salerno, CT Bianco, RW TI Development and evaluation of a swine model to assess the preclinical safety of mechanical heart valves SO JOURNAL OF HEART VALVE DISEASE LA English DT Article; Proceedings Paper CT World Symposium on Heart Valve Disease CY JUN 11-14, 1999 CL LONDON, ENGLAND ID PROSTHESES; THERAPY; THROMBOGENICITY; STENTS; SHEEP; PIGS AB Background ann aim of the study: The current standard of in vitro and in vivo preclinical heart valve testing has recently been questioned because of its failure to reveal the thrombogenic potential of the Medtronic Parallel(TM) prosthetic valve. The aim of this study was to develop a swine model for the in vivo preclinical evaluation of mechanical heart valves, and to assess the ability of this model to identify mechanical heart valve design features that result in valve-related thrombosis. Methods: Twenty-two swine underwent mitral valve replacement (MVR) using three different bileaflet mechanical valve designs (St Jude Medical, CarboMedics, Medtronic Parallel). Each animal was placed in an anticoagulation protocol (group I, INR 3.0-3.5; group II, INR 2.0-2.5; group III, no anticoagulation) and followed for up to 20 weeks. Terminal studies were performed on all animals surviving for more than 30 days. Results: Twenty-one animals survived the immediate postoperative period. Four of six group I animals died from hemorrhagic (large wound hematoma; hemopericardium) complications early in the study. In the two long-term (61 and 89 days) survivors, INRs of 3.0 to 3.5 were never achieved (61-day survivor, mean INR 2.0 +/- 1.03; ranger 0.8-5.4; 89-day survivor, mean INR 1.92 +/- 1.34; range: 1.0-7.9). Pathological analysis of explants from group I survivors revealed minimally obstructive fibrous sheathing on the inflow orifice without restriction of bileaflet motion (61 and 89 days), and two large perivalvular defects (61 days). Six of seven group II animals died from early hemorrhagic complications (hemopericardium) (mean INR 2.32 +/- 1.84; range: 0.8-8.2). Vegetations resulting in obstruction of both sides of the valve orifice and restriction of bileaflet motion were observed in a group II survivor (mean INR 2.33 +/- 1.58; range: 0.9-7.0). Group III animals (n = 8) survived for a mean of 106 +/- 60 days (range: 1-177 days). In group III, fibrous sheathing was present on all explanted valves and organized thrombi in six valves; orifice obstruction (seven valves) and restriction of bileaflet motion (three valves) were also observed. Conclusion: The use of MVR in swine as a preclinical model to evaluate the safety and performance of mechanical heart valves is limited by: (i) difficulty in maintaining safe levels of anticoagulation with warfarin, resulting in a high incidence of hemorrhagic complications; (ii) marked fibrous sheath formation and associated thrombosis; and (iii) an increased incidence of perivalvular defects, believed to result from normal somatic growth occurring in young swine. C1 Univ Minnesota, Dept Surg, Div Expt Surg, Minneapolis, MN 55455 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NHLBI, NIH, Rockville, MD USA. RP Bianco, RW (reprint author), Univ Minnesota, Dept Surg, Div Expt Surg, Box 220 Mayo,420 Delaware St SE, Minneapolis, MN 55455 USA. NR 37 TC 19 Z9 24 U1 2 U2 2 PU I C R PUBLISHERS PI NORTHWOOD PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD, ENGLAND HA6 2ET SN 0966-8519 J9 J HEART VALVE DIS JI J. Heart Valve Dis. PD SEP PY 2000 VL 9 IS 5 BP 710 EP 719 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 358MB UT WOS:000089560900019 PM 11041189 ER PT J AU Hata, TR Scholz, TA Ermakov, IV McClane, RW Khachik, F Gellermann, W Pershing, LK AF Hata, TR Scholz, TA Ermakov, IV McClane, RW Khachik, F Gellermann, W Pershing, LK TI Non-invasive Raman spectroscopic detection of carotenoids in human skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE carotenoids; human; Ramon spectroscopy; skin ID BETA-CAROTENE; ALPHA-TOCOPHEROL; CANCER PATIENTS; HUMAN PLASMA; LYCOPENE; FLUORESCENCE; CARCINOMA; ISOMERS; SERUM; IDENTIFICATION AB Carotenoids are thought to play a significant part in the skin's anti-oxidant defense system, and may help prevent malignancy. Inability to measure skin carotenoid content readily has, however, made it difficult to establish the relationship between carotenoid concentration and the occurrence of cutaneous malignancy. We have measured in vivo carotenoid concentration using a noninvasive optical method, Raman spectroscopy. To validate our instrumentation, abdominoplasty skin was evaluated by both Raman spectroscopy and high-performance liquid chromatography determination for carotenoid content. Evaluation of the Raman signal in specific carotenoid solutions was also performed. Precision of Raman measurements within skin sites, within subjects, and between subjects was measured. Sensitivity of the method was evaluated as a function of anatomical region and the distribution of carotenoids within the stratum corneum, Lastly, we evaluated the Raman signal in actinic keratosis and basal cell carcinoma lesions and perilesional skin and compared this with region-matched sites in healthy subjects. Our results indicate that the Raman scattering method reflects the presence of carotenoids in human skin and is highly reproducible. Evaluation of five anatomical regions demonstrated significant differences in carotenoid concentration by body region with the highest carotenoid concentration noted in the palm. Comparison of carotenoid concentrations in basal cell carcinomas, actinic keratosis, and their perilesional skin demonstrate a significantly lower carotenoid concentration than in region-matched skin of healthy subjects. These results represent the first evidence that carotenoid concentration in the skin correlate with the presence or absence of skin cancer and precancerous lesions. C1 Univ Utah, Dept Dermatol, Salt Lake City, UT 84132 USA. Univ Utah, Dept Phys, Laser Inst, Salt Lake City, UT 84112 USA. Univ Maryland, Dept Chem & Biochem, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Hata, TR (reprint author), Univ Utah, Dept Dermatol, 50 N Med Dr,Rm 4B454, Salt Lake City, UT 84132 USA. RI Khachik, Frederick/C-5055-2009 NR 38 TC 198 Z9 201 U1 5 U2 29 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2000 VL 115 IS 3 BP 441 EP 448 DI 10.1046/j.1523-1747.2000.00060.x PG 8 WC Dermatology SC Dermatology GA 350KR UT WOS:000089100300016 PM 10951281 ER PT J AU Widemann, BC Sung, E Anderson, L Salzer, WL Balis, FM Monitjo, KS McCully, C Hawkins, M Adamson, PC AF Widemann, BC Sung, E Anderson, L Salzer, WL Balis, FM Monitjo, KS McCully, C Hawkins, M Adamson, PC TI Pharmacokinetics and metabolism of the methotrexate metabolite 2,4-diamino-N-10-methylpteroic acid SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID HIGH-DOSE METHOTREXATE; LEUCOVORIN RESCUE; RHESUS-MONKEYS; CARBOXYPEPTIDASE-G(2); THYMIDINE; TOXICITY; ASSAY; DRUG AB The novel methotrexate (MTX) rescue agent carboxypeptidase-G(2)(CPDG(2)) converts >98% of plasma MTX to 2,4-diamino-N-10-methylpteroic acid (DAMPA) and glutamate in patients with MTX-induced renal failure and delayed MTX excretion. DAMPA is eliminated more rapidly than MTX in these patients, suggesting nonrenal elimination. The pharmacokinetics and metabolism of DAMPA were studied in four nonhuman primates with reverse-phase HPLC with UV, photodiode array detection, and mass spectroscopy. The mean peak plasma DAMPA concentration was 51 mu M and the plasma disposition was described by a three-compartment open model with first order elimination. The mean clearance of DAMPA was 1.9 l/kg/h and the mean terminal half-life was 51 min. Forty-six percent of the dose was excreted in the urine as parent compound. Three DAMPA metabolites, hydroxy-DAMPA, DAMPA-glucuronide, and hydroxy-DAMPA-glucuronide, were identified in plasma and urine. These metabolites also were identified in plasma from patients who received CPDG(2) as an MTX rescue agent. The cytotoxicity of DAMPA and its effect on MTX cytotoxicity were assessed in the Molt-4 human leukemic cell line. DAMPA was not cytotoxic and did not significantly alter the cytotoxicity of MTX. In nonhuman primates metabolism of DAM PA is a major route of DAM PA elimination, and metabolism underlies the more rapid elimination of DAMPA versus MTX in patients with MTX-induced renal dysfunction after administration of CPDG(2). C1 NCI, Pharmacol & Expt Therapeut Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. RP Widemann, BC (reprint author), NCI, Pharmacol & Expt Therapeut Sect, Pediat Oncol Branch, NIH, Bldg 10,Room 13N240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 23 TC 36 Z9 43 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2000 VL 294 IS 3 BP 894 EP 901 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 347QH UT WOS:000088940300013 PM 10945838 ER PT J AU Gilbert, KM Wahid, R Fecher, NP Freeman, JP Fifer, EK AF Gilbert, KM Wahid, R Fecher, NP Freeman, JP Fifer, EK TI Potential clinical use of butyric acid derivatives to induce antigen-specific T cell inactivation SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; TH2 CLONES; LEUKEMIA; SODIUM; RATS AB Compounds with the capacity to induce antigen-specific unresponsiveness in CD4(+) T cells can in some clinical situations be more beneficial than general immune suppressants. Newly synthesized ester, ester/amide, and amide derivatives of butyrate with the capacity to induce antigen-specific T cell unresponsiveness in vivo and in vitro were tested here. The ester and ester/amide derivatives of butyrate were shown to block proliferation by interleukin-2-stimulated murine Th1 cells in vitro. A 3-day treatment with these same two derivatives also suppressed a primary antibody response to a thymus-dependent antigen in mice. In addition, even a single injection of the ester derivative of n-butyrate 2-(4-morpholinyl)ethyl butyrate hydrochloride (MEB) on day 2 or 3 after immunization suppressed the generation of memory T cells capable of proliferating to antigen or of promoting a secondary antigen-specific antibody response. MEB also induced antigen-specific unresponsiveness in antigen-activated, but not resting or interleukin-2-activated, T cells in vitro. DNA analysis showed that regardless of when MEB was added to the cultures, it induced the eventual G(1) sequestration of essentially all activated Th1 cells. Because G(1) blockade is associated with Th1 cell anergy, this finding suggests that MEB has the potential to induce anergy in already-activated CD4+ T cells. Taken together, the results presented here establish MEB as a novel means of inducing anergy in CD4(+) T cells both in vitro and in vivo and underscore the likelihood that MEB and/or other butyrate derivatives can be used as immunotherapeutic reagents. C1 Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pharmaceut Sci, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Gilbert, KM (reprint author), Univ Arkansas Med Sci, Dept Microbiol & Immunol, Mail Slot 511,4301 W Markham St, Little Rock, AR 72205 USA. NR 17 TC 13 Z9 15 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2000 VL 294 IS 3 BP 1146 EP 1153 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 347QH UT WOS:000088940300046 PM 10945871 ER PT J AU Woods, TO AF Woods, TO TI Cyclic loading and creep of intracranial aneurysm clips SO JOURNAL OF TESTING AND EVALUATION LA English DT Article DE intracranial aneurysm clips; cyclic loading; creep; mechanical testing; fatigue; corrosion AB Intracranial aneurysm clips are used to clamp closed a portion of a blood vessel in order to prevent the rupture of cerebrovascular aneurysms. After implantation, the clips are subjected to stress, produced by the clamped tissue, in a corrosive environment. Aneurysm clips can fail by fracture or by loosening and slippage, and a failure can result in death if the aneurysm ruptures. Previous research has shown that the force required to open an aneurysm clip may decrease with repeated openings. The influence of repeated loadings on the ultimate survivability of the clip is not known. Factors such as creep and stress relaxation, which may cause a clip to loosen or slip after implantation, have not been studied. Standard test methods do not address these performance characteristics. The objective of this research is to develop test methods to investigate the cyclic load-displacement and creep behavior of intracranial aneurysm clips in both air and a simulated physiologic environment. Results of testing aneurysm clips with three spring geometries are given. C1 US FDA, CDRH, Div Mech & Mat Sci, Rockville, MD 20850 USA. RP Woods, TO (reprint author), US FDA, CDRH, Div Mech & Mat Sci, HFZ-150,9200 Corp Blvd, Rockville, MD 20850 USA. NR 22 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0090-3973 J9 J TEST EVAL JI J. Test. Eval. PD SEP PY 2000 VL 28 IS 5 BP 337 EP 344 PG 8 WC Materials Science, Characterization & Testing SC Materials Science GA 356KY UT WOS:000089443500001 ER PT J AU Hine, RJ James, SJ AF Hine, RJ James, SJ TI Down syndrome and folic acid update SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Letter C1 Univ Arkansas Med Sci, Little Rock, AR 72205 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Hine, RJ (reprint author), Univ Arkansas Med Sci, Little Rock, AR 72205 USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD SEP PY 2000 VL 100 IS 9 BP 1004 EP 1004 DI 10.1016/S0002-8223(00)00289-3 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 460MM UT WOS:000170311400007 PM 11019341 ER PT J AU Brecher, SJ Bender, MM Wilkening, VL McCabe, NM Anderson, EM AF Brecher, SJ Bender, MM Wilkening, VL McCabe, NM Anderson, EM TI Status of nutrition labeling, health claims, and nutrient content claims fop processed foods: 1997 Food Label and Package Survey SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article AB The Food and Drug Administration (FDA) conducts studies of food labels as part of its ongoing monitoring of the nutritional status of the US population. In 1994 FDA nutrition labeling rules were implemented and in 1997 the Food Label and Package Survey characterized various aspects of the labeling of processed, packaged foods, including nutrition labeling, health claims, and nutrient content claims. For the survey, FDA selected a multistage, representative sample of food products from the SCAN-TRACK food sales database (AC Nielsen Co, Schaumburg, Ill). FDA identified 58 product groups and selected those product classes from the database that accounted for 80% of sales in each group. From each product class, FDA selected the 3 top-selling product brands and randomly selected follower brands. Based on label information from a final sample of 1,267 food products, FDA determined the percentage of products sold that bear Nutrition Facts labels, health claims, and nutrient content claims. The purpose of this article was to present FDA findings regarding the status of food labels 3 years after implementation of the nutrition labeling rules. Nutrition-labeled products accounted for an estimated 96.5% of the annual sales of processed, packaged foods. An additional 3.4% of products sold were exempt from labeling regulations. Nutrient content claims and health claims appeared on an estimated 39% and 4%, respectively, of the products sold. Dietitians and other health care professionals can use this survey information to identify food types with specific label information and to assist the US consumer in making more varied and healthful food choices in the marketplace. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Nutr Prod Labeling & Dietary Supplements, Washington, DC 20204 USA. RP Brecher, SJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Nutr Prod Labeling & Dietary Supplements, 200 C St SW, Washington, DC 20204 USA. NR 7 TC 25 Z9 25 U1 0 U2 5 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 SEP PY 2000 VL 100 IS 9 BP 1057 EP 1062 DI 10.1016/S0002-8223(00)00308-4 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 460MM UT WOS:000170311400025 PM 11019354 ER PT J AU Garnick, MB Fair, WR Bostwick, D Debruyne, F Fourcroy, J Grignon, D Porterfield, H Sufrin, G Thrasher, B Hart, C AF Garnick, MB Fair, WR Bostwick, D Debruyne, F Fourcroy, J Grignon, D Porterfield, H Sufrin, G Thrasher, B Hart, C TI Fifth International Conference on Neoadjuvant Hormonal Therapy for Prostate Cancer - Overview consensus statement SO MOLECULAR UROLOGY LA English DT Editorial Material C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Health, New York, NY USA. Bostwick Lab, Richmond, VA USA. Univ Nijmegen Hosp, NL-6500 HB Nijmegen, Netherlands. US FDA, Bethesda, MD 20014 USA. Wayne State Univ, Harper Hosp, Detroit, MI USA. UsTOO, Oakbrook, IL USA. Buffalo Gen Hosp, Buffalo, NY 14203 USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. RP Garnick, MB (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, 330 Brookline Ave, Boston, MA 02215 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1091-5362 J9 MOL UROL JI Mol. Urol. PD FAL PY 2000 VL 4 IS 3 BP 89 EP 92 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 364UY UT WOS:000089912400001 PM 11184767 ER PT J AU Obin, M Halbleib, M Lipman, R Carroll, K Taylor, A Bronson, R AF Obin, M Halbleib, M Lipman, R Carroll, K Taylor, A Bronson, R TI Calorie restriction increases light-dependent photoreceptor cell loss in the neural retina of Fischer 344 rats SO NEUROBIOLOGY OF AGING LA English DT Article DE retina; aging; calorie restriction; photoreceptors; light damage; rat ID NERVE-FIBER POPULATION; DIETARY RESTRICTION; LONG-TERM; FOOD RESTRICTION; DELAYS CATARACT; OPTIC-NERVE; AGE; DEGENERATION; DAMAGE; MOUSE AB We investigated the effect of greater than or equal to 8 months of 40% caloric restriction (CR) on photoreceptor cell loss in 12, 18, and 24 month-old Fischer 344 rats (N = 154). Rats: were reared at the NIA Biomarkers Program, National Center for Toxicological Research. Photoreceptor cell density, assessed histologically, declined with age in both the CR-fed and ad lib (AL)-fed cohorts (P < 0.000), but declines were more pronounced in the CR cohort (P < 0.0005). The deleterious effect of CR was most pronounced in the central as opposed to the peripheral retina (P = 0.008), suggesting a light-dependent mechanism. Photoreceptor cell density was inversely associated with rearing under bright light (300-750 lux) as compared with rearing under lower illuminance (less than or equal to 200lux) (P < 0.0005). However, the deleterious effect of bright light on photoreceptor cell density was more pronounced in the CR cohort (P = 0.04). Effects of CR on circadian activity are likely to increase the actual light exposure of the CR cohort and may explain the apparent inability of CR to delay retinal aging in albino rats. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Tufts Univ, Lab Nutr & Vis Res, JMUSDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Tufts Univ, Vet Pathol Program, JMUSDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Obin, M (reprint author), Tufts Univ, Lab Nutr & Vis Res, JMUSDA, Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA. FU NEI NIH HHS [EY11703]; NIA NIH HHS [R01-AG07747] NR 58 TC 10 Z9 11 U1 0 U2 0 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 SEP-OCT PY 2000 VL 21 IS 5 BP 639 EP 645 DI 10.1016/S0197-4580(00)00165-2 PG 7 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 353JN UT WOS:000089271200004 PM 11016532 ER PT J AU Uecker, A Gonzalez-Lima, F Cada, A Reiman, EM AF Uecker, A Gonzalez-Lima, F Cada, A Reiman, EM TI Behavior and brain uptake of fluorodeoxyglucose in mature and aged C57BL/6 mice SO NEUROBIOLOGY OF AGING LA English DT Article DE hypometabolism; aging; motor; water maze; inferior colliculus; flocculus; mammillary body; mouse ID CEREBRAL GLUCOSE-UTILIZATION; 2-DEOXYGLUCOSE UPTAKE PATTERNS; RADIAL MAZE PERFORMANCE; INFERIOR COLLICULUS; METABOLIC-RATE; CYTOCHROME-OXIDASE; ALZHEIMERS-DISEASE; INBRED STRAINS; OPEN-FIELD; NMRI MICE AB This paper describes regional brain energy metabolism, sensorimotor, and memory functions in mature (12 months) and old (24 months) C57BL/6 mice. Male mice were tested across a variety of sensorimotor procedures and in the Morris water maze before evaluating brain uptake of fluorodeoxyglucose (FDG) in the resting state. Mature mice outperformed older mice during the difficult sensorimotor and memory tasks, but not the easier tasks. This suggested that the greater sensorimotor and memory demands of a task compromised the performance of the older mice. This conclusion was consistent with the relative FDG uptake decreases found in regions mediating sensorimotor coordination (vestibular, cerebellar, ventral thalamic regions) and some limbic regions linked to memory (mammillary body, posterior cingulate, and piriform cortices). The inferior colliculus and flocculus had the greatest metabolism in mature mice, as shown by resting FDG uptake, and these regions showed the most marked hypometabolism in the older mice. The data also showed that the neurobehavioral correlative pattern in older mice was modified. In conclusion, brain regions with higher energy metabolism, and the behaviors to which they are related, were affected most greatly by aging in C57BL/6 mice-suggesting that these areas are more metabolically vulnerable to aging effects. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Univ Texas, Dept Psychol, Austin, TX 78712 USA. Univ Texas, Inst Neurosci, Austin, TX 78712 USA. Univ Arizona, Arizona Res Lab, Div Neural Syst Memory & Aging, Tucson, AZ 85724 USA. Harrington Arthritis Res Ctr, Arizona Biomed Consortium Div, Phoenix, AZ 85006 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72029 USA. Good Samaritan Reg Med Ctr, Phoenix, AZ 85006 USA. Univ Arizona, Dept Psychiat, Tucson, AZ 85724 USA. RP Gonzalez-Lima, F (reprint author), Univ Texas, Dept Psychol, Mezes Hall 330, Austin, TX 78712 USA. EM gonzalez-lima@psy.utexas.edu FU NIMH NIH HHS [T32MH18837]; NINDS NIH HHS [R01NS37755] NR 57 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD SEP-OCT PY 2000 VL 21 IS 5 BP 705 EP 718 DI 10.1016/S0197-4580(00)00099-3 PG 14 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 353JN UT WOS:000089271200012 PM 11016540 ER PT J AU Paule, MG Rowland, AS Ferguson, SA Chelonis, JJ Tannock, R Swanson, JM Castellanos, FX AF Paule, MG Rowland, AS Ferguson, SA Chelonis, JJ Tannock, R Swanson, JM Castellanos, FX TI Attention deficit/hyperactivity disorder: characteristics, interventions, and models SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Review DE attention deficit disorder; epidemiology; prevalence; rodent models; cerebellar stunting; short-term memory; cognitive markers; treatment; stimulant medication; multimodal interventions; neuroimaging; prefrontal cortex; dopaminergic dysfunction ID DEFICIT-HYPERACTIVITY DISORDER; SPONTANEOUSLY HYPERTENSIVE RATS; OPERANT TEST BATTERY; IV FIELD TRIALS; CEREBRAL GLUCOSE-METABOLISM; CORPUS-CALLOSUM MORPHOLOGY; OF-ONSET CRITERION; WISTAR-KYOTO RAT; MAGNETIC-RESONANCE; INHIBITORY CONTROL AB An epidemiological study of Attention Deficit/Hyperactivity Disorder (ADHD) suggests that the prevalence may be two to three times higher than the figure of 3-5% often cited. In addition, the data suggest that both underdiagnosis and overdiagnosis occur frequently. Rodent animal models of ADHD, like the Spontaneously Hypertensive Rat (SHR) and other rat models such as those with chemical and radiation-induced brain lesions and cerebellar stunting, and the Coloboma mouse model exhibit clear similarities with several aspects of the human disorder and should prove useful in studying specific traits. Operant behavioral tasks that model learning, short-term memory and simple discriminations are sensitive to ADHD and methylphenidate has been shown to normalize ADHD performance in a short-term memory task. Recent findings challenge not only the current postulate that response inhibition is a unique deficit in ADHD, but also the concepts of ADHD and its treatment, which presume intact perceptual abilities. Time perception deficits may account, in part, for the excessive variability in motor response times on speeded reaction time tasks, motor control problems and motor clumsiness associated with ADHD. The Multimodality Treatment Study of ADHD (MTA) provided data suggesting that pharmacological interventions that included systematic and frequent follow-up with parents and teachers, with or without psychosocial interventions, are superior to psychosocial interventions or standard community care alone. Additionally, the MTA was one of the first studies to demonstrate benefits of multimodal and pharmacological interventions lasting longer than 1 year. Imaging studies have demonstrated differences in brain areas in children with ADHD: anterior corpus callosum, right anterior white matter, and cerebellar volumes are all decreased in children with ADHD and there is less brain asymmetry in ADHD subjects. Additionally, functional imaging studies, coupled with pharmacological manipulations, suggest decreased blood flow and energy utilization in prefrontal cortex and striatum, and the dysregulation of catecholamine systems in persons with ADHD. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Beh Toxicol Lab, Jefferson, AR 72079 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ Arkansas, Dept Psychol, Little Rock, AR 72204 USA. Hosp Sick Children, Res Inst, Brain & Behav Res Programme Psychiat Res, Toronto, ON M5G 1X8, Canada. Univ Calif Irvine, Child Dev Ctr, Irvine, CA 92612 USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Paule, MG (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, Beh Toxicol Lab, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 240 TC 71 Z9 74 U1 9 U2 25 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 SEP-OCT PY 2000 VL 22 IS 5 BP 631 EP 651 DI 10.1016/S0892-0362(00)00095-7 PG 21 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 381NR UT WOS:000165769900003 PM 11106857 ER PT J AU Chelonis, JJ Daniels-Shaw, JL Blake, DJ Paule, MG AF Chelonis, JJ Daniels-Shaw, JL Blake, DJ Paule, MG TI Developmental aspects of delayed matching-to-sample task performance in children SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE short-term memory; recall; delayed matching-to-sample; age; sex; intelligence; children ID OPERANT TEST BATTERY; SHORT-TERM-MEMORY; INTELLIGENCE; MONKEYS AB The influence of age, sex, and intelligence (IQ) on performance of a delayed matching-to-sample (DMTS) task, commonly used with animals and adult human subjects to study aspects of short-term memory, was examined for 674 children, 5 to 13 years old. The data suggest that younger children were less accurate at short delays and displayed a greater decrease in accuracy as recall delay increased than older children. Children with lower IQs demonstrated consistent impairment in recall of information when compared to children with higher IQs. No significant differences in task performance were observed between boys and girls. These normative data provide insights into the developmental time course of behaviors thought to serve as metrics of short-term memory. These data will be critical for ongoing and future studies in determining whether specific clinical diagnoses, drug treatments, or other risk factors (e.g., perinatal drug exposure, pregnancy complications, exposure to toxicants) are associated with differences on specific aspects of task performance. The use of tasks that are also applicable to animal models provides great opportunities for the conduct of important comparative studies. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Pediat, Little Rock, AR 72202 USA. Univ Arkansas, Dept Psychol, Little Rock, AR 72204 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Chelonis, JJ (reprint author), Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Pediat, 800 Marshall St, Little Rock, AR 72202 USA. NR 26 TC 26 Z9 26 U1 2 U2 4 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 SEP-OCT PY 2000 VL 22 IS 5 BP 683 EP 694 DI 10.1016/S0892-0362(00)00090-8 PG 12 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 381NR UT WOS:000165769900007 PM 11106861 ER PT J AU Caner, C Hernandez, RJ Pascall, MA AF Caner, C Hernandez, RJ Pascall, MA TI Effect of high-pressure processing on the permeance of selected high-barrier laminated films SO PACKAGING TECHNOLOGY AND SCIENCE LA English DT Article DE permeability; films; high-pressure processing AB This study investigated the effects of high pressure processing (HPP) on the barrier properties of eight multilayer films. Pouches made from these films were filled with distilled water, sealed and then pressure processed at 600 and 800 MPa for 5, 10 and 20 min at 45 degreesC. Controls were similarly prepared but exposed to atmospheric pressure. After processing, all pouches were dried and their oxygen, carbon dioxide and water vapour permeance determined. Films used in this study were PET/SiO(x)/LDPE, PET/Al(2)O(3)/LDPE, PET/PVDC/nylon/HDPE/PE, PE/nylon/EVOH/PE, PE/nylon/PE, metallized-PET/EVA/LLDPE, PP/nylon/PP and PET/PVDC/EVA. Results showed that metallized PET was most severely affected by HPP, as its permeance values for oxygen, carbon dioxide and water increased as much as 150%. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 US FDA, NCFST, Summit Argo, IL 60501 USA. Michigan State Univ, Sch Packaging, E Lansing, MI 48824 USA. RP Pascall, MA (reprint author), US FDA, NCFST, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM rjhernan@msu.edu; mxp@cfsan.fda.gov RI Pascall, Melvin /A-5354-2013 NR 14 TC 29 Z9 33 U1 2 U2 21 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-3214 J9 PACKAG TECHNOL SCI JI Packag. Technol. Sci. PD SEP-OCT PY 2000 VL 13 IS 5 BP 183 EP 195 DI 10.1002/1099-1522(200009)13:5<183::AID-PTS514>3.0.CO;2-U PG 13 WC Engineering, Manufacturing; Food Science & Technology SC Engineering; Food Science & Technology GA 387PL UT WOS:000166130900002 ER PT J AU Bright, RA AF Bright, RA TI What is FDA doing about medical errors and adverse events related to medical devices? SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Editorial Material ID DRUG EVENTS C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Bright, RA (reprint author), 1350 Piccard Dr,HFZ-541, Rockville, MD 20855 USA. RI Bright, Roselie/D-2240-2016 NR 15 TC 0 Z9 0 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP-OCT PY 2000 VL 9 IS 5 BP 437 EP 440 DI 10.1002/1099-1557(200009/10)9:5<437::AID-PDS537>3.0.CO;2-G PG 4 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 368BA UT WOS:000090096600011 PM 19025851 ER PT J AU Thompson, KL Rosenzweig, BA Tsong, Y Sistare, FD AF Thompson, KL Rosenzweig, BA Tsong, Y Sistare, FD TI Evaluation of in vitro reporter gene induction assays for use in a rapid prescreen for compound selection to test specificity in the Tg.AC mouse short-term carcinogenicity assay SO TOXICOLOGICAL SCIENCES LA English DT Article DE stress response genes; Tg.AC; in vitro assay; gadd153; c-fos; zeta-globin; p53; K562; HepG2 ID DNA-DAMAGING AGENTS; MESSENGER-RNA LEVELS; ERYTHROID-DIFFERENTIATION; P53 ACTIVITY; CELL-LINE; TRANSCRIPTION; ACTIVATION; BIOASSAYS; K562 AB Under ICH guidelines, short-term carcinogenicity assays such as the Tg,AC assay are allowed alternatives for one species in the 2-year rodent bioassay. The Tg.AC transgenic mouse, which carries the v-Ha-ras oncogene under control of the zeta -globin promoter, develops skin papillomas in response to dermal application of carcinogens and tumor promoters. The appropriate specificity of the Tg,AC model for testing pharmaceuticals has not been systematically evaluated, The selection of candidate test compounds among noncarcinogenic pharmaceuticals would be aided by a high-throughput in vitro prescreen correlative of activity in the in vivo Tg.AC assay, Here we describe the development of a prescreen based on correct response to 24 compounds tested previously in Tg,AC mice. The in vitro prescreens, chosen to reflect molecular pathways possibly involved in Tg.AC papilloma formation, consisted of a zeta -globin promoter-luciferase construct stably expressed in K562 cells (Zeta-Luc) and three of the stress-response element-chloramphenicol acetyltransferase (CAT) fusion constructs stably expressed in HepG2 cells that are part of the CAT-Tox (L)iver assay, The stress response elements chosen were the c-fos promoter, the gadd153 promoter, and p53 response element repeats. Of the four assays, the gadd153-CAT assay showed the strongest concordance with activity in the Tg.AC assay, correctly classifying 78% of Tg.AC positive and 83% of Tg.AC negative compounds. The correlation was further improved by adding the Zeta-Luc assay as a second-stage screen. These cell-based assays will be used in a novel approach to selecting candidate compounds that challenge the specificity of the Tg,AC assay toward pharmaceuticals. C1 US FDA, Div Appl Pharmacol Res, OTR OPS, Laurel, MD 20708 USA. US FDA, Off Biostat, ORM, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. RP Sistare, FD (reprint author), US FDA, Div Appl Pharmacol Res, OTR OPS, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 37 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD SEP PY 2000 VL 57 IS 1 BP 43 EP 53 DI 10.1093/toxsci/57.1.43 PG 11 WC Toxicology SC Toxicology GA 377BU UT WOS:000165492700007 PM 10966510 ER PT J AU Xu, ZJ Chang, LW Slikker, W Ali, SF Rountree, RL Scallet, AC AF Xu, ZJ Chang, LW Slikker, W Ali, SF Rountree, RL Scallet, AC TI A dose-response study of Ibogaine-induced neuropathology in the rat cerebellum SO TOXICOLOGICAL SCIENCES LA English DT Article DE ibogaine; Purkinje neuron; Bergmann astrocyte; neurodegeneration; calbindin; GFAP; NOAEL; cerebellum ID PURKINJE-CELL LOSS; PARASAGITTAL ZONES; ASTROGLIOSIS; DEGENERATION; VERMIS; MOUSE AB Ibogaine (IBO) is an indole alkaloid from the West African shrub, Tabernanthe iboga. It is structurally related to harmaline, and both these compounds are rigid analogs of melatonin. IBO has both psychoactive and stimulant properties. In single-blind trials with humans, it ameliorated withdrawal symptoms and interrupted the addiction process. However, IBO also produced neurodegeneration of Purkinje cells and gliosis of Bergmann astrocytes in the cerebella of rats given even a single dose (100 mg/kg, ip). Here, we treated rats (n = 6 per group) with either a single ip injection of saline or with 25 mg/kg, 50 mg/kg, 75 mg/kg, or 100 mg/kg of IBO. As biomarkers of cerebellar neurotoxicity, we specifically labeled degenerating neurons and axons with silver, astrocytes with antisera to glial fibrillary acidic protein (GFAP), and Purkinje neurons with antisera to calbindin, All rats of the 100-mg/kg group showed the same pattern of cerebellar damage previously described: multiple bands of degenerating Purkinje neurons. All rats of the 75-mg/ kg group had neurodegeneration similar to the 100-mg/kg group, but the bands appeared to be narrower. Only 2 of 6 rats that received 50 mg/kg were affected; despite few degenerating neuronal perikarya, cerebella from these rats did contain patches of astrocytosis similar to those observed with 75 or 100 mg/kg IBO. These observations affirm the usefulness of GFAP immunohistochemistry as a sensitive biomarker of neurotoxicity. None of the sections from the 25-mg/kg rats, however stained, were distinguishable from saline controls, indicating that this dose level may be considered as a no-observable-adverse-effect level (NOAEL). C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. RP Scallet, AC (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Dr, Jefferson, AR 72079 USA. NR 25 TC 19 Z9 19 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 SEP PY 2000 VL 57 IS 1 BP 95 EP 101 DI 10.1093/toxsci/57.1.95 PG 7 WC Toxicology SC Toxicology GA 377BU UT WOS:000165492700012 PM 10966515 ER PT J AU Hung, HMJ AF Hung, HMJ TI Evaluation of a combination drug with multiple doses in unbalanced factorial design clinical trials SO STATISTICS IN MEDICINE LA English DT Article ID EXISTENCE; TESTS AB Flexibilities for sample size allocation are often demanded for achieving multiple study objectives in combination drug trials. The global tests of Hung, Chi and Lipicky are extended for analysis of unbalanced factorial design trials to test the hypothesis that at least one of the non-zero dose combinations of two drugs is more effective than the respective component doses, When the dose combinations have heterogeneous effect sizes, an unbalanced design may induce greater power than the balanced design, An adjusted p-value approach is proposed for testing the individual dose combinations under the condition that the maximum type I error probability is protected. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 US FDA, Off Biostat, Div Biometr 1, CDER, Rockville, MD 20852 USA. RP Hung, HMJ (reprint author), US FDA, Off Biostat, Div Biometr 1, CDER, HFD-710,Room 5062,Woodmont 2,1451 Rockville Pike, Rockville, MD 20852 USA. NR 8 TC 16 Z9 16 U1 2 U2 2 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 AUG 30 PY 2000 VL 19 IS 16 BP 2079 EP 2087 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 344NG UT WOS:000088765300001 PM 10931512 ER PT J AU Kang, SH Chen, JJ AF Kang, SH Chen, JJ TI An approximate unconditional test of non-inferiority between two proportions SO STATISTICS IN MEDICINE LA English DT Article ID ESTABLISH EQUIVALENCE; NULL HYPOTHESIS; TEST STATISTICS; EFFICACY; TRIAL; TABLES AB This paper investigates an approximate unconditional test for non-inferiority between two independent binomial proportions. The P-value of the approximate unconditional test is evaluated using the maximum likelihood estimate of the nuisance parameter. In this paper, we clarify some differences in defining the rejection regions between the approximate unconditional and conventional conditional or unconditional exact test. We compare the approximate unconditional test with the asymptotic test and unconditional exact test by Chan (Statistics in Medicine, 17, 1403-1413, 1998) with respect to the type I error and power. In general, the type I errors and powers are in the decreasing order of the asymptotic, approximate unconditional and unconditional exact tests. In many cases, the type I errors are above the nominal level from the asymptotic test, and are below the nominal level from the unconditional exact test. In summary, when the non-inferiority test is formulated in terms of the difference between two proportions, the approximate unconditional test is the most desirable, because it is easier to implement and generally more powerful than the unconditional exact test and its size rarely exceeds the nominal size. However, when a test between two proportions is formulated in terms of the ratio of two proportions, such as a test of efficacy, more caution should be made in selecting a test procedure. The performance of the tests depends on the sample size and the range of plausible values of the nuisance parameter. published in 2000 by John Wiley & Sons, Ltd. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Kang, SH (reprint author), Univ Texas, Sch Med, Dept Internal Med, Clin Epidemiol Sect, Houston, TX 77030 USA. NR 22 TC 19 Z9 19 U1 0 U2 0 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 AUG 30 PY 2000 VL 19 IS 16 BP 2089 EP 2100 DI 10.1002/1097-0258(20000830)19:16<2089::AID-SIM537>3.0.CO;2-B PG 12 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 344NG UT WOS:000088765300002 PM 10931513 ER PT J AU Schmued, LC Hopkins, KJ AF Schmued, LC Hopkins, KJ TI Fluoro-Jade B: a high affinity fluorescent marker for the localization of neuronal degeneration SO BRAIN RESEARCH LA English DT Article DE Fluoro-Jade B; neuronal degeneration; kainic acid; neuropathology AB Fluoro-Jade B, like its predecessor Fluoro-Jade, is an anionic fluorescein derivative useful for the histological staining of neurons undergoing degeneration. However, Fluoro-Jade B has an even greater specific affinity for degenerating neurons. This notion is supported by the conspicuous staining of degenerating neuronal elements with minimal background staining. This improved signal-to-noise ratio means that fine neuronal processes including distal dendrites, axons and axon terminals can be more readily detected and documented. Although the staining time and dye concentration are reduced, the method is as rapid, simple and reliable as the original Fluoro-Jade technique. Like Fluoro-Jade, Fluoro-Jade B is compatible with a number of other labeling procedures including immunofluorescent and fluorescent Nissl techniques, (C) 2000 Elsevier Science B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Schmued, LC (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 6 TC 850 Z9 878 U1 1 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 25 PY 2000 VL 874 IS 2 BP 123 EP 130 DI 10.1016/S0006-8993(00)02513-0 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 350NK UT WOS:000089107800004 PM 10960596 ER PT J AU Anderson, DL Mackey, EA Lamaze, GP Lindstrom, RM Chen-Mayer, HH Liposky, PJ AF Anderson, DL Mackey, EA Lamaze, GP Lindstrom, RM Chen-Mayer, HH Liposky, PJ TI Thermal neutron capture prompt gamma-ray activation analysis facility at the National Center for Neutron Research. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Elemental Res Branch HFS 338, Washington, DC 20204 USA. Natl Inst Stand & Technol, Div Analyt Chem, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 2000 VL 220 MA 132-NUCL BP U22 EP U22 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 386XV UT WOS:000166091300132 ER PT J AU Armstrong, DJ AF Armstrong, DJ TI Antimicrobials and the future. 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 AUG 20 PY 2000 VL 220 MA 147-AGFD BP U42 EP U42 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 386XU UT WOS:000166091200147 ER PT J AU Bolger, PM Carrington, C Humphreys, SH AF Bolger, PM Carrington, C Humphreys, SH TI Fumonisin toxicity and risk assessment. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 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 AUG 20 PY 2000 VL 220 MA 104-AGFD BP U36 EP U36 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 386XU UT WOS:000166091200105 ER PT J AU Brause, A Roach, JAG AF Brause, A Roach, JAG TI HPLC detection of patulin in apple juice with GC/MS confirmation of patulin identity. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Analyt Chem Serv Columbia Inc, Columbia, MD 21045 USA. US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 2000 VL 220 MA 83-AGFD BP U33 EP U33 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 386XU UT WOS:000166091200084 ER PT J AU Bullerman, LB Jackson, LS AF Bullerman, LB Jackson, LS TI Stability of fumonisins in food processing. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Nebraska, Dept Food Sci & Technol, Lincoln, NE 68583 USA. US FDA, NCFST, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 2000 VL 220 MA 94-AGFD BP U35 EP U35 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 386XU UT WOS:000166091200095 ER PT J AU Contrera, JF Matthews, EJ AF Contrera, JF Matthews, EJ TI Keynote address: Application of toxicology databases in drug development. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA OTR, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 2000 VL 220 MA 19-CINF BP U197 EP U198 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 386XU UT WOS:000166091200999 ER PT J AU Hansen, PA AF Hansen, PA TI Antimicrobial chemicals and other antimicrobial food treatments: FDA premarket considerations. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, 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 AUG 20 PY 2000 VL 220 MA 119-AGFD BP U38 EP U38 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 386XU UT WOS:000166091200119 ER PT J AU Henry, SH Bosch, FX Bowers, JC Portier, CJ AF Henry, SH Bosch, FX Bowers, JC Portier, CJ TI Aflatoxin, hepatitis, and worldwide liver cancer risks. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Inst Oncol, Lhospitalet De Llobregat, Spain. NIEHS, Res Triangle Pk, NC 27709 USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 2000 VL 220 MA 105-AGFD BP U36 EP U37 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 386XU UT WOS:000166091200106 ER PT J AU Keller, SE Merker, R AF Keller, SE Merker, R TI Approaches to developing appropriate microbial surrogates for field and in-plant testing of antimicrobials and other pathogen control measures. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 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 AUG 20 PY 2000 VL 220 MA 146-AGFD BP U42 EP U42 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 386XU UT WOS:000166091200146 ER PT J AU Kramer, JKG Zhou, JQJ Dugan, MER Aalhus, JL Sehat, N Mossoba, MM Yurawecz, MP AF Kramer, JKG Zhou, JQJ Dugan, MER Aalhus, JL Sehat, N Mossoba, MM Yurawecz, MP TI Comparison of CLA isomer incorporation into tissue lipids of pigs fed a mixture of either 4 or 2 major cis/trans CLA isomers. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Agr & Agri Food Canada, Food Res Ctr, So Crop Protect, Guelph, ON N1G 5C9, Canada. Agr & Agri Food Canada, Meats Sect, Lacombe Res Ctr, Lacombe, AB, Canada. US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 2000 VL 220 MA 6-AGFD BP U22 EP U22 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 386XU UT WOS:000166091200007 ER PT J AU LaVecchia, M AF LaVecchia, M TI Priority-based Assessment of Food Additives (PAFA): A toxicological database. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, Div Petit Control, 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 AUG 20 PY 2000 VL 220 MA 81-CINF BP U206 EP U206 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 386XU UT WOS:000166091201059 ER PT J AU Matthews, EJ Contrera, JF AF Matthews, EJ Contrera, JF TI Application of computational toxicology (ComTox) and Multicase (Mcase) software to the FDA mission. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA OTR, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 2000 VL 220 MA 21-CINF BP U198 EP U198 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 386XU UT WOS:000166091201001 ER PT J AU McCormack, JF AF McCormack, JF TI FDA'S electronic records and signatures regulation (21 CFR Part 11). SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Off Enforcement, Off Regulatory Affairs, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 2000 VL 220 MA 81-AGRO BP U59 EP U59 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 386XU UT WOS:000166091200234 ER PT J AU Moody, JD Heinze, TM Zhang, DL Cerniglia, CE AF Moody, JD Heinze, TM Zhang, DL Cerniglia, CE TI Metabolism of the tricyclic antidepressant drug amoxapine by Cunninghamella elegans. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR USA. Bristol Myers Squibb Co, Metab & Pharmacokinet, New York, NY 10154 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 2000 VL 220 MA 102-MEDI BP U554 EP U554 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 386XU UT WOS:000166091203010 ER PT J AU Mossoba, MM Kramer, JKG Fritsche, J Yurawecz, MP Eulitz, K Ku, Y Rader, JI AF Mossoba, MM Kramer, JKG Fritsche, J Yurawecz, MP Eulitz, K Ku, Y Rader, JI TI Application of standard addition to eliminate CLA and other interferences in the determination of trans fatty acids in selected food products by infrared spectroscopy. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, Office Sci Anal Support, Washington, DC 20204 USA. Agr & Agri Food Canada, Guelph, ON N1G 5C9, Canada. US FDA, Labeling & Dietary Supplements, Off Nutr Prod, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 2000 VL 220 MA 1-AGFD BP U21 EP U21 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 386XU UT WOS:000166091200002 ER PT J AU Musser, SM Eppley, RM Trucksess, MW AF Musser, SM Eppley, RM Trucksess, MW TI Analytical methods for fumonisins in foods. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 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 AUG 20 PY 2000 VL 220 MA 80-AGFD BP U33 EP U33 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 386XU UT WOS:000166091200081 ER PT J AU Park, D AF Park, D TI Effect of processing on aflatoxin. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Div Nat Prod, 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 AUG 20 PY 2000 VL 220 MA 92-AGFD BP U34 EP U35 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 386XU UT WOS:000166091200092 ER PT J AU Roach, JAG AF Roach, JAG TI Detection and identification of isomers of conjugated linoleic acid (CLA) and related compounds by electron ionization mass spectrometry. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, 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 AUG 20 PY 2000 VL 220 MA 2-AGFD BP U21 EP U21 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 386XU UT WOS:000166091200003 ER PT J AU Ryu, DJ Jackson, LS Bullerman, LB AF Ryu, DJ Jackson, LS Bullerman, LB TI Effects of processing on zearalenone. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Nebraska, Dept Food Sci & Technol, Lincoln, NE 68583 USA. US FDA, NCFST, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 2000 VL 220 MA 95-AGFD BP U35 EP U35 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 386XU UT WOS:000166091200096 ER PT J AU Sheinin, EB AF Sheinin, EB TI Career opportunities for chemists at FDA'S Center for Drug Evaluation and Research. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Off Pharmaceut Sci, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 2000 VL 220 MA 35-CHAL BP U219 EP U219 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 386XU UT WOS:000166091201121 ER PT J AU Troxell, TC AF Troxell, TC TI US perspective on mycotoxin regulatory issues. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, 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 AUG 20 PY 2000 VL 220 MA 110-AGFD BP U37 EP U37 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 386XU UT WOS:000166091200110 ER PT J AU Yurawecz, MP Roach, JAG Mossoba, MM Kramer, JKG Sehat, N Eulitz, K Fritsche, J Ku, Y AF Yurawecz, MP Roach, JAG Mossoba, MM Kramer, JKG Sehat, N Eulitz, K Fritsche, J Ku, Y TI Identification of conjugated linoleic acid (CLA) isomers in commercial products and foods. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, Labeling & Dietary Supplements, Off Nutr Prod, Washington, DC 20204 USA. Agr & Agri Food Canada, Ottawa, ON, Canada. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 2000 VL 220 MA 3-AGFD BP U21 EP U21 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 386XU UT WOS:000166091200004 ER PT J AU Jude, AR Little, JM Freeman, JP Evans, JE Radominska-Pandya, A Grant, DF AF Jude, AR Little, JM Freeman, JP Evans, JE Radominska-Pandya, A Grant, DF TI Linoleic acid diols are novel substrates for human UDP-glucuronosyltransferases SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE linoleic acid diols; glucuronidation; fatty acids; UGTs; human enzymes; enzyme kinetics ID DRUG-METABOLIZING-ENZYMES; EPOXIDE HYDROLASE; BILE-ACIDS; FATTY-ACIDS; HUMAN-LIVER; BURN TOXIN; GLUCURONIDATION; LEUKOTOXIN; RAT; ESTERS AB Linoleic acid diol glucuronides have been isolated previously from urine of patients suffering from generalized peroxisomal disorders. Glucuronidation of linoleic acid and linoleic acid diols by human liver microsomes was studied to investigate the role of glucuronide conjugation in the metabolism of linoleic acid diols. Glucuronide products were isolated and analyzed by TLC and HPLC-MS. HPLC-PUIS showed ions with (m/z) corresponding to singly glucuronidated linoleic acid diols while TLC revealed that the glucuronidation was at a hydroxyl position. Kinetic analysis gave apparent K-m values in the range of 50-200 mu M and V-max rates from 5 to 12 nmol/mg x min. These rates are substantially higher than activities seen for most endogenous hydroxylated substrates. Assays using each of the four individually purified linoleic acid diol enantiomers suggest that glucuronidation occurs at only one of the two hydroxyl groups of each enantiomer. These results show for the first time that hydroxylated fatty acids are actively glucuronidated by human liver microsomes and suggest that glucuronidation may play a significant role in the biotransformation of linoleic acid diols in humans. (C) 2000 Academic Press. C1 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. Univ Arkansas, Dept Chem, Little Rock, AR 72204 USA. Natl Ctr Toxicol Res, Mass Spectrometry Div, Jefferson, AR 72079 USA. Eunice Kennedy Shriver Ctr Mental Retardat Inc, Mass Spectrometry Facil, Waltham, MA 02452 USA. RP Radominska-Pandya, A (reprint author), Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, 4301 W Markham,Slot 516, Little Rock, AR 72205 USA. FU NIDDK NIH HHS [DK45123, DK51971, DK49715] NR 38 TC 22 Z9 23 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD AUG 15 PY 2000 VL 380 IS 2 BP 294 EP 302 DI 10.1006/abbi.2000.1933 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 347UZ UT WOS:000088948700010 PM 10933884 ER PT J AU Mochizuki, T Karavanov, AA Curtiss, PE Ault, KT Sugimoto, N Watabe, T Shiokawa, K Jamrich, M Cho, KWY Dawid, IB Taira, M AF Mochizuki, T Karavanov, AA Curtiss, PE Ault, KT Sugimoto, N Watabe, T Shiokawa, K Jamrich, M Cho, KWY Dawid, IB Taira, M TI Xlim-1 and LIM domain binding protein 1 cooperate with various transcription factors in the regulation of the goosecoid promoter SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Xenopus; head organizer; homeobox gene; goosecoid promoter; Xlim-1; Ldb1; Otx2; Gsc; PV.1; Xvent-1; Xbra; LIM domain ID ANTERIOR PRIMITIVE ENDODERM; HOMEOBOX GENE; XENOPUS-EMBRYOS; SPEMANNS ORGANIZER; HOMEODOMAIN PROTEINS; MOUSE GASTRULA; RETINOIC ACID; MESODERM; HEAD; DROSOPHILA AB The homeobox genes Xlim-1 and goosecoid (gsc) are coexpressed in the Spemann organizer and later in the prechordal plate that acts as head organizer. Based on our previous finding that gsc is a possible target gene for Xlim-1, we studied the regulation of gsc transcription by Xlim-1 and other regulatory genes expressed at gastrula stages, by using gsc-luciferase reporter constructs injected into animal explants. A 492-bp upstream region of the gsc promoter responds to Xlim-1/3m, an activated form of Xlim-1, and to a combination of wild-type Xlim-1 and Ldb1, a LIM domain binding protein, supporting the view that gsc is a direct target of Xlim-1. Footprint and electrophoretic mobility shift assays with GST-homeodomain fusion proteins and embryo extracts overexpressing FLAG-tagged full-length proteins showed that the Xlim-1 homeodomain or Xlim-1/Ldb1 complex recognize several TAATXY core elements in the 492-bp upstream region, where XY is TA, TG, CA, or GG. Some of these elements are also bound by the ventral factor PV.1, whereas a TAATCT element did not bind Xlim-1 or PV.1 but did bind the anterior factors Otx2 and Gsc. These proteins modulate the activity of the gsc reporter in animal caps: Otx2 activates the reporter synergistically with Xlim-1 plus Ldb1, whereas Gsc and PV.1 strongly repress reporter activity. We show further, using animal cap assays, that the endogenous gsc gene was synergistically activated by Xlim-1, Ldb1, and Otx2 and that the endogenous otx2 gene was activated by Xlim-1/3m, and this activation was suppressed by the posterior factor Xbra. Based on these data, we propose a model for gene interactions in the specification of dorsoventral and anteroposterior differences in the mesoderm during gastrulation. (C) 2000 Academic Press. C1 Univ Tokyo, Dept Biol Sci, Grad Sch Sci, Mol Embryol Lab,Bunkyo Ku, Tokyo 1130033, Japan. CREST, Japanese Sci & Technol Corp, Tokyo, Japan. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. US FDA, Dev Biol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Univ Calif Irvine, Dept Dev & Cell Biol, Ctr Dev Biol, Irvine, CA 92717 USA. RP Taira, M (reprint author), Univ Tokyo, Dept Biol Sci, Grad Sch Sci, Mol Embryol Lab,Bunkyo Ku, Tokyo 1130033, Japan. NR 56 TC 48 Z9 52 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 15 PY 2000 VL 224 IS 2 BP 470 EP 485 DI 10.1006/dbio.2000.9778 PG 16 WC Developmental Biology SC Developmental Biology GA 347XY UT WOS:000088955500029 PM 10926781 ER PT J AU Rader, JI Weaver, CM Angyal, G AF Rader, JI Weaver, CM Angyal, G TI Total folate in enriched cereal-grain products in the United States following fortification SO FOOD CHEMISTRY LA English DT Article DE folates; enriched cereal-grain products; fortification ID FOLIC-ACID; LIQUID-CHROMATOGRAPHY; EXTRACTION; AFFINITY AB The full compliance date for mandatory folic acid fortification of enriched cereal-grain products in the United States was 1 January, 1998. There is currently a great interest in determining the effectiveness of this measure, which was instituted to increase the folate intakes of women of child-bearing age to reduce their risk of having a pregnancy affected by a neural tube birth defect. We surveyed 83 enriched cereal-grain products that are required to be fortified with folic acid under the new regulations and an additional 79 foods that contain enriched cereal-grain ingredients or that are currently fortified with folic acid. Products were collected and analyzed between February 1998 and April 1999. Total folate was determined by microbiological assay using a tri-enzyme digestion. We compared analyzed values for total folate with amounts required by Federal regulations and/or with label declarations of folate content. For many enriched cereal-grain products, there were significant differences between amounts of folate found on analysis and amounts required by Federal regulations. In part because of this, label declarations of folate content were also in error. The high values found in some enriched cereal-grain products may represent manufacturers' averages as well as the presence of higher-than-expected levels of endogenous folates. These results indicate that reliable food composition databases cannot be developed without extensive new data on the actual concentrations of folate in recently fortified enriched cereal-grain products as well as in products containing enriched cereal-grain ingredients. Reliance on older data bases or on compositional information that has a weak analytical underpinning will lead to unsound estimates of folate intake, and hence, of the potential impact of the new fortification program. Published by Elsevier Science Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Food Labeling, Washington, DC 20204 USA. RP Rader, JI (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Food Labeling, 200 C St SW, Washington, DC 20204 USA. NR 30 TC 102 Z9 105 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0308-8146 J9 FOOD CHEM JI Food Chem. PD AUG 15 PY 2000 VL 70 IS 3 BP 275 EP 289 DI 10.1016/S0308-8146(00)00116-3 PG 15 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA 328PZ UT WOS:000087860400001 ER PT J AU Fitzsimmons, SP Clark, KC Wilkerson, R Shapiro, MA AF Fitzsimmons, SP Clark, KC Wilkerson, R Shapiro, MA TI Inhibition of tetanus toxin fragment C binding to ganglioside G(T1b) by monoclonal antibodies recognizing different epitopes SO VACCINE LA English DT Article DE tetanus toxin fragment C; monoclonal antibodies; ganglioside G(T1b) ID BOTULINUM TOXINS; POLYPEPTIDE FRAGMENTS; RECEPTOR; NEUROTOXINS; EXPRESSION; MEMBRANES; CELLS AB Anti-tetanus toroid monoclonal antibodies would be useful in exploring the relationship of tetanus toxin structure to its function. Tetanus toxin fragment C has been shown to be responsible for binding to neurons via gangliosides. Eleven new and two previously derived monoclonal antibodies specific for tetanus toxin fragment C were shown to recognize five different fragment C epitopes, two of which were overlapping. Three of these epitopes participate in the binding to ganglioside G(T1b) One epitope was defined by a monoclonal antibody that did not inhibit the interaction between fragment C and ganglioside. This antibody however, was blocked from binding to fragment C by antibodies that were able to inhibit the fragment C-ganglioside interaction. Published by Elsevier Science Ltd. 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, Rockville, MD 20852 USA. NR 21 TC 13 Z9 15 U1 2 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 AUG 15 PY 2000 VL 19 IS 1 BP 114 EP 121 DI 10.1016/S0264-410X(00)00115-8 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 351GR UT WOS:000089149900015 PM 10924793 ER PT J AU Gaylor, DW AF Gaylor, DW TI The use of Haber's Law in standard setting and risk assessment SO TOXICOLOGY LA English DT Article DE concentration; time; reference dose; cancer risk; safety factor; noncancer effects; risk assessment AB Haber's Law simply states that the incidence and/or severity of a toxic effect depends on the total exposure, i.e. exposure concentration (c) rate times the duration time (t) of exposure (c x t). This rule, within constraints, is often used in setting exposure guidelines for toxic substances. Establishing reference doses (acceptable daily intakes) for long-term exposures when only the results of short-term studies are available requires the use of an uncertainty (safety) factor. The value of this uncertainty factor often approximates a value comparable to Haber's Law for extrapolation from short-term to long-term exposure durations. As a default procedure, cancer risk estimates are generally based on the average lifetime daily dose which is derived from the total cumulative exposure, i.e. Haber's (c x t). This has been shown both theoretically and empirically to be valid within a factor of 20 for carcinogenesis. This provides some credence for the use of an additional safety factor of 10, in some instances, for exposures of children to carcinogens. Finally, a generalization of Haber's Law, exposure concentration raised to a power times exposure duration, is discussed. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. 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 9 TC 34 Z9 37 U1 3 U2 8 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 AUG 14 PY 2000 VL 149 IS 1 BP 17 EP 19 DI 10.1016/S0300-483X(00)00228-6 PG 3 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 349ZZ UT WOS:000089076700003 PM 10963857 ER PT J AU Coles, B Yang, MH Lang, NP Kadlubar, FF AF Coles, B Yang, MH Lang, NP Kadlubar, FF TI Expression of hGSTP1 alleles in human lung and catalytic activity of the native protein variants towards 1-chloro-2,4-dinitrobenzene, 4-vinylpyridine and (+)-anti benzo[a]pyrene-7,8-diol-9,10-oxide SO CANCER LETTERS LA English DT Article DE glutathione S-transferase P1; human lung; expression; catalysis; cancer susceptibility ID GLUTATHIONE-S-TRANSFERASE; POLYCYCLIC AROMATIC-HYDROCARBONS; ANTI-DIOL EPOXIDES; MOLECULAR EPIDEMIOLOGY; GENETIC POLYMORPHISMS; SUPERGENE FAMILY; CANCER RISK; PI; P1-1; SUSCEPTIBILITY AB The human glutathione S-transferase (GST) P1 alleles coding for Val(105) (hGSTP1*B and/or P1*C) are over- represented in lung cancer patients. However, the corresponding recombinant Va(105) protein variants tend to show higher catalytic activity than the Ile(105) variants towards bay-region diol epoxides that are thought to be etiological agents in lung cancer. We have examined 29 normal human lung samples with respect to several factors that could confound relationships between hGSTP1 allele type and cancer susceptibility, namely, inter-individual and allele-specific variation of hGSTP1 expression, and differ ences between the catalytic properties of the native and recombinant hGSTP1-1 variant protein products. hGSTP1 expression varied 7-fold among individuals but was independent of hGSTP1*A, P1*B or P1*C allele type. hGST subunits A1, A2, M1 and M3 were minor components, similarly variable in expression. Despite this variability of expression. the levels of hGSTP1 expression linearly correlated with those of the next most highly expressed GST, hGSTM3, even though the genes for these GSTs are on different chromosomes. Differences between the native protein variants, using 1-chloro-2,4-dinitrobenzene and (+)-anti-benzo[a]pyrene diolepoxide as substrates. were more marked than those between the recombinant variants. However, the order of differential catalytic specificity was the same for native and recombinant variants. Neither the expression of the hGSTP1 alleles nor the catalytic properties of the protein variants appears to provide a simple mechanistic rationale for the observed over-representation of the hGSTP1*B and/or I*C alleles in lung cancer. Published by Elsevier Science Ireland Ltd. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 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, B (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. FU NCI NIH HHS [R01-CA58697] NR 43 TC 26 Z9 28 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 AUG 11 PY 2000 VL 156 IS 2 BP 167 EP 175 DI 10.1016/S0304-3835(00)00458-4 PG 9 WC Oncology SC Oncology GA 396XD UT WOS:000166662500007 PM 10880766 ER PT J AU Clark, PI Natanblut, SL Schmitt, CL Wolters, C Iachan, R AF Clark, PI Natanblut, SL Schmitt, CL Wolters, C Iachan, R TI Factors associated with tobacco sales to minors - Lessons learned from the FDA compliance checks SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID YOUTH ACCESS; CIGARETTE SALES; UNDERAGE YOUTH; AVAILABILITY; COMMUNITIES; LAWS; AGE AB Context. Tobacco products continue to be widely accessible to miners. Between 1997 and 1999, the US Food and Drug Administration (FDA) conducted more than 150000 tobacco sales age-restriction compliance checks. Data obtained from these checks provide important guidance for curbing illegal sales. Objective To determine which elements of the compliance checks were most highly associated with illegal sales and thereby inform best practices for conducting efficient compliance check programs. Design and Setting Cross-sectional analysis of FDA compliance checks in 110062 unique establishments in 36 US states and the District of Columbia. Main Outcome Measure Illegal sales of tobacco to miners at compliance checks; association of illegal sales with variables such as age and sex of the minor. Results The rate of illegal sales for all first compliance checks in unique stores was 26.6%. Clerk failure to request proof of age was strongly associated with illegal sales (uncorrected sales rate, 10.5% compared with 89.5% sales when proof was not requested; multivariate-adjusted odds ratio [OR], 0.03; 95% confidence interval [CI], 0.03-0.04). Other factors associated with increased illegal sales were employment of older miners to make the purchase attempt (adjusted ORs for 16- and 17-year-old miners compared with 15-year-olds were 1.52 [95% CI, 1.46-1.63] and 2.43 [95% CI, 2.31-2.59], respectively), attempt to purchase smokeless tobacco (adjusted OR, 2.16 [95% CI, 1.90-2.45] vs cigarette purchase attempts), and performing checks at or after 5 PM (adjusted OR, 1.28 [95% CI, 1.21-1.35] vs before 5 PM). Female sex of clerk and minor, Saturday checks, type of store (convenience store selling gas, gas station, drugstore, supermarket and general merchandise), and rural store locations also were associated with increased illegal sales. Conclusions This analysis found that a request for age verification strongly predicted compliance with the law. The results suggest several ways in which the process of compliance checks might be optimized. C1 Battelle Mem Inst, Ctr Publ Hlth Res & Evaluat, Baltimore, MD 21209 USA. US FDA, Off Tobacco Programs, Rockville, MD 20857 USA. RP Clark, PI (reprint author), Battelle Mem Inst, Ctr Publ Hlth Res & Evaluat, 6115 Falls Rd,Suite 200, Baltimore, MD 21209 USA. NR 33 TC 42 Z9 43 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 AUG 9 PY 2000 VL 284 IS 6 BP 729 EP 734 DI 10.1001/jama.284.6.729 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 341JM UT WOS:000088587300032 PM 10927782 ER PT J AU Liu, FF Ang, CYW Heinze, TM Rankin, JD Beger, RD Freeman, JP Lay, JO AF Liu, FF Ang, CYW Heinze, TM Rankin, JD Beger, RD Freeman, JP Lay, JO TI Evaluation of major active components in St. John's Wort dietary supplements by high-performance liquid chromatography with photodiode array detection and electrospray mass spectrometric confirmation SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE food analysis; St. John's Wort; Hypericum peforatum; naphthodianthrones; flavonoids; phloroglucinols ID HYPERICUM-PERFORATUM L; HYPERFORIN; EXTRACTS AB A RP-HPLC method with photodiode array detection and LC-electrospray ionization (ESI) MS confirmation was established for the determination of major active components in St. John's Wort dietary supplement capsules. The samples alternatively were extracted with ethanol-acetone (2:3) using a 55 degrees C water-bath shaker or an ambient temperature ultrasonic bath. Extracts were separated by RP-C-18 chromatography using a 95-min water-methanol-acetonitrile-trifluoroacetic acid gradient. The major components were identified by photodiode array detection and-then confirmed by LC-ESI-MS. The quantification of components was performed using an internal standard (luteolin). This method may serve as a valuable tool for the quality evaluation of St, John's Wort dietary supplement products. (C) 2000 Published by Elsevier Science B.V. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Ang, CYW (reprint author), US FDA, Natl Ctr Toxicol Res, Div Chem, 3900 NCTR Rd, Jefferson, AR 72079 USA. RI Lay, Jackson/G-1007-2011 OI Lay, Jackson/0000-0003-3789-2527 NR 15 TC 60 Z9 66 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD AUG 4 PY 2000 VL 888 IS 1-2 BP 85 EP 92 DI 10.1016/S0021-9673(00)00555-0 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 338HV UT WOS:000088414100009 PM 10949475 ER PT J AU Koller, E Mann, M Malozowski, S Bacsanyi, J Gibert, C AF Koller, E Mann, M Malozowski, S Bacsanyi, J Gibert, C TI Aseptic necrosis in HIV seropositive patients: A possible etiologic role for megestrol acetate SO AIDS PATIENT CARE AND STDS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; AVASCULAR NECROSIS; FEMORAL-HEAD; GELATINOUS TRANSFORMATION; INFECTED PATIENTS; BONE-MARROW; THERAPY; OSTEONECROSIS; CACHEXIA; CANCER AB The association between pharmacologic doses of corticosteroids and the development of aseptic bone necrosis has been well documented. Recent reports have described the corticosteroid activity of megestrol acetate. A retrospective review of adverse events reported to the U.S. Food and Drug Administration identified three human immunodeficiency virus (HIV) seropositive patients who developed avascular necrosis of the femoral head during treatment with megestrol acetate. All were males, ages 34, 36, and 55 years, and were on therapy for 6, 1.5, and 18 months, respectively, when symptoms of aseptic necrosis occurred in the absence of antecedent trauma. Megestrol acetate doses were 640, 320, and 600-1200 mg/d, respectively. Two patients had no history of corticosteroid use whereas the third had taken an undisclosed dose and duration of corticosteroids concurrent with pentamidine administration. Notably, despite the predominant use of megestrol in women for hormone sensitive malignancies, none of the reports of aseptic necrosis occurred in this population. Megestrol acetate may be associated with the development of avascular necrosis via its glucocorticoid-like effects. Cachectic acquired immunodeficiency syndrome (AIDS) patients may have additional risk factors that predispose them to aseptic necrosis when receiving megestrol acetate. C1 US FDA, CDER, DMEDP, Rockville, MD 20857 USA. Vet Adm Med Ctr, Dept Infect Dis, Washington, DC 20422 USA. RP Koller, E (reprint author), US FDA, CDER, DMEDP, Parklawn Bldg,Room 14B04,HFD 510,5600 Fishers Lan, Rockville, MD 20857 USA. NR 36 TC 25 Z9 25 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD AUG PY 2000 VL 14 IS 8 BP 405 EP 410 DI 10.1089/108729100416614 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 348PF UT WOS:000088993300003 PM 10977969 ER PT J AU Sundlof, SF AF Sundlof, SF TI Protecting consumers by safeguarding animal health SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. NR 1 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 AUG 1 PY 2000 VL 62 IS 3 BP 659 EP 660 PG 2 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 343LX UT WOS:000088704800014 PM 10950218 ER PT J AU Dart, RC Goldfrank, LR Chyka, PA Lotzer, D Woolf, AD McNally, J Snodgrass, WR Olson, KR Scharman, E Geller, RJ Spyker, D Kraft, M Lipsy, M AF Dart, RC Goldfrank, LR Chyka, PA Lotzer, D Woolf, AD McNally, J Snodgrass, WR Olson, KR Scharman, E Geller, RJ Spyker, D Kraft, M Lipsy, M TI Combined evidence-based literature analysis and consensus guidelines for stocking of emergency antidotes in the United States SO ANNALS OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT American-College-of-Emergency-Physicians Research Forum CY OCT, 1999 CL LAS VEGAS, NEVADA SP Amer Coll Emergency Physicians ID AVAILABILITY AB Study objective: To develop guidelines for the stocking of antidotes at hospitals that accept emergency admissions using combined evidence-based and consensus methods. Methods: Study participants were 12 medical care providers from disciplines that are affected by insufficient stocking of emergency antidotes (clinical pharmacology, critical care, clinical pharmacy, emergency medicine, hospital pharmacy, internal medicine, managed care pharmacy, clinical toxicology, pediatrics, poison control centers, pulmonary medicine, regulatory medicine). Selection of individuals for the study panel was based on evidence of previous antidote research or perspective regarding the purchase and use of antidotes. The literature regarding each antidote was systematically amassed using pre-1966 literature files, current MEDLINE searches, the reference lists of major medical textbooks, and citations solicited from the consensus panel. Articles relevant to 4 defined core questions were included. These articles formed the basis of an evidence-based analysis performed by the principal investigator. After literature analysis, a literature summary and proposed guidelines for antidote stocking were submitted to the panel. Consensus was formed by electronic iterative presentation of alternatives to each panel member using a modified Delphi method. All panel members participated in 5 rounds of guideline analysis of 20 antidotes. Results: Of the 20 antidotes, 16 antidotes were ultimately recommended for stocking (N-acetylcysteine, atropine, Crotalid snake antivenin, calcium gluconate and chloride, cyanide antidote kit, deferoxamine, digoxin immune Fab, dimercaprol, ethanol, fomepizole, glucagon, methylene blue, naloxone, pralidoxime, physostigmine, sodium bicarbonate), 2 were not recommended for stocking (black widow antivenin, ethylenediamine tetraacetic acid), and consensus could not be reached for 2 antidotes (flumazenil, physostigmine). Conclusion: These guidelines provide a tool to be used in revising or creating policies and procedures with regard to the stocking of antidotes in hospitals that accept emergency patients. C1 Univ Colorado, Hlth Sci Ctr, Dept Surg,Rocky Mt Poison & Drug Ctr, Denver Hlth & Hosp Author, Denver, CO 80230 USA. NYU, Bellevue Hosp Ctr, Sch Med, Med Ctr,Dept Emergency Med, New York, NY 10016 USA. Univ Tennessee, Dept Pharm, So Poison Ctr, Memphis, TN 38104 USA. Univ Wisconsin Hosp, Poison Ctr, Madison, WI 53792 USA. Harvard Univ, Childrens Hosp, Sch Med,Dept Pediat,Program Clin Toxicol, Massachusetts Rhode Isl Poison Control Ctr,Dept M, Boston, MA 02115 USA. Univ Arizona, Arizone Poison & Drug Informat Ctr, Tucson, AZ USA. Univ Texas, Med Branch, Dept Pediat, SE Texas Poison Ctr, Galveston, TX 77550 USA. Calif Poison Control Syst, San Francisco Div, San Francisco, CA USA. W Virginia Poison Ctr, Charleston, WV USA. Emory Univ, Sch Med, Dept Pediat, Georgia Poison Ctr, Atlanta, GA USA. US FDA, Ctr Devices & Radiol Hlth, Div Cardiovasc & Resp Devices, Washington, DC 20204 USA. Univ Colorado, Hlth Sci Ctr, Natl Jewish Med & Res Ctr, Div Pulm & Crit Care Med, Denver, CO USA. Univ Arizona, Intergrp Arizona, Tucson, AZ USA. RP Dart, RC (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Surg,Rocky Mt Poison & Drug Ctr, Denver Hlth & Hosp Author, 1010 Yosemite Circle, Denver, CO 80230 USA. NR 19 TC 65 Z9 69 U1 0 U2 6 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD AUG PY 2000 VL 36 IS 2 BP 126 EP 132 DI 10.1067/mem.2000.108182 PG 7 WC Emergency Medicine SC Emergency Medicine GA 341HJ UT WOS:000088584700006 PM 10918103 ER PT J AU Walsh, TJ Jackson, AJ Lee, JW Amantea, M Sein, T Bacher, J Zech, L AF Walsh, TJ Jackson, AJ Lee, JW Amantea, M Sein, T Bacher, J Zech, L TI Dose-dependent pharmacokinetics of amphotericin B lipid complex in rabbits SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article AB Amphotericin B lipid complex (ABLC) was recently approved by the Food and Drug Administration for treatment of patients with invasive fungal infections who are intolerant of or refractory to conventional amphotericin B therapy. Little is known, however, about the pharmacokinetics of this new antifungal compound. We therefore investigated the pharmacokinetics of ABLC in comparison with those of conventional desoxycholate amphotericin B (DAmB) in rabbits. The pharmacokinetics of DAmB in a rabbit model were similar to those previously reported in humans. The pharmacokinetics of ABLC differed substantially from those of DAmB. Plasma amphotericin B levels following ABLC administration were 10 times lower than those following administration of an equal dosage of DAmB. The levels of ABLC in whole blood were approximately 40 times greater than those in plasma. The ABLC model differed from the DAmB model by (i) a dose- and time-dependent uptake and return between the plasma compartment and apparent cellular components of the blood-sediment compartment and (ii) time-dependent tissue uptake and return to plasma from serially connected compartments. Following infusion of ABLC, there was a nonlinear uptake into the apparent cellular components of the blood-sediment compartment. This uptake was related to the reciprocal of the integral of the total amount of drug infused (i.e., the more drug infused the greater the fractional uptake between 0.5 and 5 mg/kg of body weight for ABLC). The transfer of drug from plasma to the cellular components of the blood-sediment compartment resulted in initial uptake followed by rapid redistribution back to the plasma. The study describes a detailed model of the pharmacokinetics of ABLC and characterizes a potential role of the cellular components of the blood-sediment compartment in the distribution of this new antifungal compound in tissue. C1 NCI, Mycol Unit, NIH, Bethesda, MD 20892 USA. NCI, Immunocompromised Host Sect, NIH, Bethesda, MD 20892 USA. NCI, Math Biol Lab, NIH, Bethesda, MD 20892 USA. NIH, Vet Resource Program, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Div Bioequivalence, Rockville, MD 20857 USA. RP Walsh, TJ (reprint author), NCI, Mycol Unit, NIH, Bldg 10,Room BN240, Bethesda, MD 20892 USA. NR 18 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 2000 VL 44 IS 8 BP 2068 EP 2076 DI 10.1128/AAC.44.8.2068-2076.2000 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 336NB UT WOS:000088308200010 PM 10898677 ER PT J AU Moody, JD Zhang, DL Heinze, TM Cerniglia, CE AF Moody, JD Zhang, DL Heinze, TM Cerniglia, CE TI Transformation of amoxapine by Cunninghamella elegans SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID MAMMALIAN METABOLISM; ACTIVE METABOLITES; MICROBIAL MODELS; ANTI-DEPRESSANT; BIOTRANSFORMATION; FUNGUS; 7-HYDROXYAMOXAPINE; PHARMACOKINETICS AB We examined Cunninghamella elegans to determine its ability to transform amoxapine, a tricyclic antidepressant belonging to the dibenzoxazepine class of drugs. Approximately 57% of the exogenous amoxapine was metabolized to three metabolites that were isolated by high-performance liquid chromatography and were identified by nuclear magnetic resonance and mass spectrometry as 7-hydroxyamoxapine (48%), N-formyl-7-hydroxyamoxapine (31%), and N-formylamoxapine (21%). 7-Hydroxyamoxapine, a mammalian metabolite with biological activity, now can be produced in milligram quantities for toxicological evaluation. 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. Bristol Myers Squibb, Dept Metab & Pharmacokinet, Princeton, NJ 08502 USA. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 24 TC 25 Z9 29 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD AUG PY 2000 VL 66 IS 8 BP 3646 EP 3649 DI 10.1128/AEM.66.8.3646-3649.2000 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 340QP UT WOS:000088546300077 PM 10919836 ER PT J AU Kimball, AB Summers, RM Turner, M Dugan, EM Hicks, J Miller, FW Rider, LG AF Kimball, AB Summers, RM Turner, M Dugan, EM Hicks, J Miller, FW Rider, LG TI Magnetic resonance imaging detection of occult skin and subcutaneous abnormalities in juvenile dermatomyositis - Implications for diagnosis and therapy SO ARTHRITIS AND RHEUMATISM LA English DT Article ID IDIOPATHIC INFLAMMATORY MYOPATHIES; VALIDATED DISEASE-ACTIVITY; DAMAGE INDEXES; MUSCLE; PANNICULITIS; MYOSITIS; SUBCUTIS AB Objective. To assess the utility of magnetic resonance imaging (MRI) of skin, subcutaneous tissue, and fascia in evaluating disease activity in juvenile dermatomyositis (DM). Methods. Short tau inversion recovery (STIR) MRI of the proximal thighs and buttocks, cutaneous assessment, and other measures of disease activity were prospectively obtained in 26 children meeting criteria for probable or definite juvenile DM. Also undergoing STIR MRI assessment were 8 subjects who were being evaluated for muscle disorders and who were not diagnosed as having juvenile DM. Results. Skin, subcutaneous, or fascial edema of the thighs and buttocks were seen on STIR MRI in up to 85% of juvenile DM patients at baseline evaluation compared with no more than 38% of the comparison group without juvenile DM. In juvenile DM, STIR MRI skin and subcutaneous edema scores correlated (r(s) = 0.51, P = 0.008), as did fascial and muscle edema scores (r(s) = 0.58, P = 0.002). Skin global disease activity scores correlated with MRI skin edema scores (r(s) = 0.41, P = 0.04), and serum aldolase levels correlated with both MRI skin and subcutaneous edema scores (r = 0.44 and 0.40, P = 0.03 and 0.05 respectively). The extent and severity of STIR MRI changes in the skin, subcutaneous tissue, and fascia were not predicted by most other measures of juvenile DM disease activity. Five juvenile DM patients with thigh MRI subcutaneous edema developed clinically apparent calcinosis at the same location within 9 months. Conclusion. Edema or inflammation in the skin, subcutaneous tissue, and fascia, found on STIR MRI, is common in juvenile DM patients and is often undetected by standard assessments. These MRI changes can precede the development of calcinosis. STIR MRI may be a useful adjunct for assessing disease activity and guiding the treatment of juvenile DM. C1 Natl Canc Inst, NIH, Bethesda, MD USA. Washington Hosp Ctr, Washington, DC 20010 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20014 USA. RP Rider, LG (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, 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 24 TC 65 Z9 71 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 AUG PY 2000 VL 43 IS 8 BP 1866 EP 1873 DI 10.1002/1529-0131(200008)43:8<1866::AID-ANR24>3.0.CO;2-6 PG 8 WC Rheumatology SC Rheumatology GA 342RT UT WOS:000088659500024 PM 10943878 ER PT J AU Hrinczenko, BW Alayash, AI Wink, DA Gladwin, MT Rodgers, GP Schechter, AN AF Hrinczenko, BW Alayash, AI Wink, DA Gladwin, MT Rodgers, GP Schechter, AN TI Effect of nitric oxide and nitric oxide donors on red blood cell oxygen transport SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE nitric oxide; haemoglobin; methaemoglobin; oxygen affinity; sickle cell anaemia ID S-NITROSOHEMOGLOBIN; COVALENT BINDING; HEMOGLOBIN-S; DISEASE; NO; HYDROXYUREA; AFFINITY; ERYTHROCYTES; GLUTATHIONE; OXIDATION AB A mechanism has been proposed in which nitric oxide (NO) may bind to cysteine beta 93 and be transported B haemoglobin from the lungs to the tissues and modify vascular tone. In addition, it has been reported that treatment of sickle cell anaemia blood with 80 p.p.m. NO gas in air shifts the oxygen affinity as measured by P-50 to the left. We exposed normal and sickle cell anaemia blood to 80 p.p.m. NO in air for 1 h in vitro and found no change in P-50 of either normal or sickle cell blood, in addition, we exposed normal and sickle cell blood in buffer to aqueous NO (NO gas dissolved in buffer) at varying concentrations and found that the induced left shift in P-50 correlates strongly and linearly with methaemoglobin formation. We also treated normal and sickle cell blood with other nitric oxide donors, such as sodium 2-(N,N-diethylamino)-diazenolate-2-oxide (DEANO), S-nitrosocysteine (CysNO) and sodium trioxodinitrate (OXINO, or Angeli's salt). In all cases, we found a dose-dependent increase in methaemoglobin that was strongly correlated with the dose-dependent P-50 reduction. Our data do not support the report that low NO concentrations call selectively increase the oxygen affinity of sickle fell blood without affecting methaemoglobin levels significantly. NO, however map have benefit in sickle cell disease by other mechanisms. C1 NIDDK, NIH, Biol Chem Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Plasma Derivat, Bethesda, MD USA. NCI, NIH, Radiat Biol Branch, Div Clin Sci, Bethesda, MD USA. NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD USA. NIDDK, NIH, Mol & Clin Hematol Branch, Bethesda, MD 20892 USA. RP Schechter, AN (reprint author), NIDDK, NIH, Biol Chem Lab, Bldg 10,Rm 9N-307, Bethesda, MD 20892 USA. OI Schechter, Alan N/0000-0002-5235-9408 NR 40 TC 22 Z9 25 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD AUG PY 2000 VL 110 IS 2 BP 412 EP 419 DI 10.1046/j.1365-2141.2000.02203.x PG 8 WC Hematology SC Hematology GA 347PC UT WOS:000088937500022 PM 10971400 ER PT J AU Holada, K Vostal, JG AF Holada, K Vostal, JG TI Different levels of prion protein (PrPc) expression on hamster, mouse and human blood cells SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE prion protein; blood cells; flow cytometry; monoclonal antibody 6H4; comparison of expression ID CREUTZFELDT-JAKOB-DISEASE; LYMPHOCYTE-ACTIVATION; SCRAPIE; MICE; INFECTIVITY; TISSUE; BRAIN; PATHOGENESIS; REPLICATION; COMPONENTS AB The host prion protein, PrPc, and its conformationally changed isoform, PrPsc, play an essential role in the transmissible spongiform encephalopathy (TSE) infections. The prion hypothesis postulates that PrPsc is the TSE infectious agent and that it serves as a template to convert host PrPc to additional PrPsc. Blood of experimentally TSE-infected rodents has been shown to contain TSE infectivity. if blood-borne TSE infectivity requires association with PrPc. differences in the distribution of PrPc in blood could affect the amount and distribution of blood-borne infectivity in different hosts. We have compared the distribution of PrPc on the peripheral blood cells of humans, hamsters and mice using quantitative flow cytometry. Human lymphocytes, monocytes and platelets displayed much greater quantities of PrPc than corresponding mouse cells. Mouse platelets did not express any detectable PrPc. A similar low level of PrPc was found on both human and mouse red blood cells. None of the hamster peripheral blood cells displayed detectable amounts of PrPc. If PrPc contributes to the propagation or transport of TSE infectivity in blood, the species differences in PrPc distribution reported here need to be considered when extrapolating the results of rodent TSE transmission studies with blood and blood components to humans. C1 US FDA, Div Hematol, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD 20892 USA. RP Vostal, JG (reprint author), US FDA, Div Hematol, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bldg 29,Room 323,HFM-335,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 32 TC 65 Z9 66 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD AUG PY 2000 VL 110 IS 2 BP 472 EP 480 DI 10.1046/j.1365-2141.2000.02158.x PG 9 WC Hematology SC Hematology GA 347PC UT WOS:000088937500033 PM 10971411 ER PT J AU Ramljak, D Calvert, RJ Wiesenfeld, PW Diwan, BA Catipovic, B Marasas, WFO Victor, TC Anderson, LM Gelderblom, WCA AF Ramljak, D Calvert, RJ Wiesenfeld, PW Diwan, BA Catipovic, B Marasas, WFO Victor, TC Anderson, LM Gelderblom, WCA TI A potential mechanism for fumonisin B-1-mediated hepatocarcinogenesis: cyclin D1 stabilization associated with activation of Akt and inhibition of GSK-3 beta activity SO CARCINOGENESIS LA English DT Article ID HUMAN ESOPHAGEAL CANCER; PROTEIN-KINASE-B; CELL-CYCLE; FUSARIUM-MONILIFORME; RAT-LIVER; SPHINGOLIPID BIOSYNTHESIS; INCREASED EXPRESSION; RESTRICTION POINT; MAMMARY-TUMORS; B-1 AB Fumonisin B-1 (FB1) is a worldwide corn contaminant and has been epidemiologically linked to the high incidence of human esophageal cancer in South Africa and China. FB1 is hepatocarcinogenic in rats by an unknown mechanism. Inhibition of ceramide synthase and disruption of membrane phospholipids have been shown to be mechanisms of toxicity. Here we show overexpression of cyclin D1 protein in both preneoplastic and neoplastic liver specimens obtained from a long-term feeding study of FB1 in rats. In rats fed FB1 short-term, cyclin D1 protein levels in liver were increased up to five-fold in a dose-responsive manner. Northern blot analysis demonstrated no increase in mRNA levels of cyclin D1, 2D electrophoresis of cyclin D1 protein in FB1-treated samples showed a distinct pattern of migration (presence of less negatively charged form of the protein) that differed from controls. Recently, it has been shown that phosphorylation of cyclin D1 by glycogen synthase kinase 3 beta (GSK-3 beta) on a single threonine residue (Thr-286) positively regulates proteosomal degradation of cyclin D1, In FB1-treated samples we detected GSK-3 beta phosphorylated on serine 9; activated protein kinase B (Akt) appears to be responsible for this activity-inhibiting phosphorylation, These findings suggest that overexpression of cyclin D1 results from stabilization due to a lack of phosphorylation mediated by GSK-3 beta, We also observed an increase in cyclin dependent kinase 4 (Cdk4) complexes with cyclin D1 in FB1-treated samples; additionally, elevated Cdk4 activity was shown by increased phosphorylation of the retinoblastoma protein. In summary, the activation of Akt leads to increased survival, inhibition of GSK-3 beta activity and post-translational stabilization of cyclin D1, all events responsible for disruption of the cell cycle G(1)/S restriction point in hepatocytes, This is the first report suggesting the mechanism by which FB1 acts as a carcinogen. C1 NCI, Comparat Carcinogenesis Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Special Nutr, Div Sci & Appl Technol, Laurel, MD 20708 USA. NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Johns Hopkins Univ, Ctr Asthma & Allergy, Baltimore, MD 21224 USA. S African MRC, Nutr Dis Res Inst, ZA-7505 Tygerberg, South Africa. Univ Stellenbosch, MRC, Ctr Cellular & Mol Biol, ZA-7505 Tygerberg, South Africa. RP Ramljak, D (reprint author), NCI, Comparat Carcinogenesis Lab, Frederick Canc Res & Dev Ctr, Bldg 538,Room 205E, Frederick, MD 21702 USA. FU NCI NIH HHS [N01CO56000] NR 59 TC 47 Z9 47 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2000 VL 21 IS 8 BP 1537 EP 1546 DI 10.1093/carcin/21.8.1537 PG 10 WC Oncology SC Oncology GA 340XM UT WOS:000088561800012 PM 10910956 ER PT J AU Thonell, L Pendle, S Sacks, L AF Thonell, L Pendle, S Sacks, L TI Clinical and radiological features of South African patients with tuberculomas of the brain SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID IMMUNODEFICIENCY-VIRUS INFECTION; INTRACRANIAL TUBERCULOMAS; PARADOXICAL EXPANSION; MENINGITIS AB Intracranial tuberculomas are a rare complication of tuberculosis that typically occurs in immunocompromised patients not treated previously for tuberculosis. We identified tuberculomas in 12 patients (11 of whom were infected with human immunodeficiency virus) at a hospital in Johannesburg, South Africa. Responses to antituberculous therapy were good, often despite the presence of large lesions, and surgery was not considered necessary in any of the patients. C1 Sizwe Trop Dis Hosp, Johannesburg, South Africa. RP Sacks, L (reprint author), Ctr Drug Evaluat & Res, Div Special Pathogens, 9201 Corp Blvd,HFD 590, Rockville, MD 20850 USA. NR 9 TC 10 Z9 10 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 AUG PY 2000 VL 31 IS 2 BP 619 EP 620 DI 10.1086/313989 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 363MD UT WOS:000089838700040 PM 10987736 ER PT J AU Larsen, U Yan, S AF Larsen, U Yan, S TI Does female circumcision affect infertility and fertility? A study of the Central African Republic, Cote d'Ivoire, and Tanzania SO DEMOGRAPHY LA English DT Article; Proceedings Paper CT Annual Meeting of the Population-Association-of-America CY MAR, 1999 CL NEW YORK, NEW YORK SP Populat Assoc Amer ID SUB-SAHARAN AFRICA; STERILITY AB This study explores the association between female circumcision and infertility and fertility, using information from the Demographic and Health Surveys (DHS). In Cote d'Ivoire and Tanzania, circumcised women had lower childlessness, lower infertility by age, and higher total fertility rates than women who were not circumcised the reverse pattern prevailed in the Central African Republic. In all three countries, however circumcised women grouped by age at circumcision did not have significantly different odds of infertility nor of having a child than did uncircumcised women, when the effects of covariates were controlled Thus we find evidence suggesting that the practice of female circumcision does not have a statistically discernible effect on women's ability to reproduce. C1 Harvard Univ, Sch Publ Hlth, Dept Populat & Int Hlth, Boston, MA 02115 USA. US FDA, CDER, Rockville, MD 20857 USA. RP Larsen, U (reprint author), Harvard Univ, Sch Publ Hlth, Dept Populat & Int Hlth, 665 Huntington Ave, Boston, MA 02115 USA. NR 19 TC 18 Z9 18 U1 0 U2 1 PU POPULATION ASSN AMER PI WASHINGTON PA 1722 N ST NW, WASHINGTON, DC 20036 USA SN 0070-3370 J9 DEMOGRAPHY JI Demography PD AUG PY 2000 VL 37 IS 3 BP 313 EP 321 DI 10.2307/2648044 PG 9 WC Demography SC Demography GA 344UF UT WOS:000088776900005 PM 10953806 ER PT J AU Fang, H Tong, WD Perkins, R Soto, AM Prechtl, NV Sheehan, DM AF Fang, H Tong, WD Perkins, R Soto, AM Prechtl, NV Sheehan, DM TI Quantitative comparisons of in vitro assays for estrogenic activities SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE antiestrogens; chemical structure; data mining; endocrine disrupters; E-SCREEN assay; estrogens; estrogen receptor competitive binding assay; estrogen receptors; MCF-7 cell proliferation assay; species sensitivity; yeast-based reporter gene assay ID BREAST-CANCER-CELLS; IN-VITRO; RECEPTOR-BETA; ENVIRONMENTAL ESTROGENS; SERUM-ALBUMIN; TARGET-CELLS; MCF-7 CELLS; WILD-TYPE; BINDING; IDENTIFICATION AB Substances that may act as estrogens show a broad chemical structural diversity To thoroughly address the question of possible adverse estrogenic effects, reliable methods are needed to detect and identify the chemicals of these diverse structural classes. We compared three assays-in vitro estrogen receptor competitive binding assays (ER binding assays), yeast-based reporter gene assays (yeast assays), and the MCF-7 cell proliferation assay (E-SCREEN assay)-to determine their quantitative agreement in identifying structurally diverse estrogens. We examined assay performance for relative sensitivity, detection of active/inactive chemicals, and estrogen/antiestrogen activities. In this examination, we combined individual data sets in a specific, quantitative data mining exercise. Data sets for at least 29 chemicals from five laboratories were analyzed pair-wise by X-Y plots. The ER binding assay was a good predictor for the other two assay results when the antiestrogens were excluded (r(2) is 0.78 for the yeast assays and 0.85 for the E-SCREEN assays). Additionally, the examination strongly suggests that biologic information that is not apparent From any of the individual assays can be discovered by quantitative pair-wise comparisons among assays. Antiestrogens are identified as outliers in the ER binding/yeast assay, while complete antagonists are identified in the ER binding and E-SCREEN assays. Furthermore, the presence of outliers may be explained by different mechanisms that induce an endocrine response, different impurities in different batches of chemicals, different species sensitivity, or limitations of the assay techniques. Although these assays involve different level of biologic complexity, the major conclusion is that they generally provided consistent information in quantitatively determining estrogenic activity for the five data sets examined. The results should provide guidance for expanded data mining examinations and the selection of appropriate assays to screen estrogenic endocrine disrupters. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. ROW Sci Inc, Jefferson, AR USA. Tufts Univ, Sch Med, Dept Anat & Cellular Biol, Boston, MA 02111 USA. RP Fang, H (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. FU NIEHS NIH HHS [ES-08314] NR 56 TC 195 Z9 201 U1 0 U2 27 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 2000 VL 108 IS 8 BP 723 EP 729 DI 10.1289/ehp.00108723 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 353VU UT WOS:000089296800020 PM 10964792 ER PT J AU Sobel, J Hirshfeld, AB McTigue, K Burnett, CL Altekruse, S Brenner, F Malcolm, G Mottice, SL Nichols, CR Swerdlow, DL AF Sobel, J Hirshfeld, AB McTigue, K Burnett, CL Altekruse, S Brenner, F Malcolm, G Mottice, SL Nichols, CR Swerdlow, DL TI The pandemic of Salmonella Enteritidis phage type 4 reaches Utah: a complex investigation confirms the need for continuing rigorous control measures SO EPIDEMIOLOGY AND INFECTION LA English DT Article ID UNITED-STATES; INFECTIONS; OUTBREAKS AB In 1995, Salmonella Enteritidis (SE) cases in the state of Utah increased fivefold. Isolates were identified as phage type 4 (PT4). Risk factors and sources of infection were investigated in two case-control studies, a traceback of implicated foods, and environmental testing. Forty-three patients with sporadic infections and 86 controls were included in a case-control study of risk factors for infection. A follow-up case-control study of 25 case and 19 control restaurants patronized by case and control patients examined risks associated with restaurant practices. In the first case-control study, restaurant dining was associated with illness (P = 0.002). In the follow-up case-control study, case restaurants were likelier to use > 2000 eggs per week (P < 0.02), to pool eggs (P < 0.05), and to use eggs from cooperative 'A' (P < 0.009). Eggs implicated in separately investigated SE PT4 outbreaks were traced to cooperative 'A', and SE PT4 was cultured from one of the cooperative's five local farms. We conclude that SE PT4 transmitted by infected eggs from a single farm caused a fivefold increase in human infections in Utah. C1 Ctr Dis Control & Prevent, Food & Diarrheal Dis Branch, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. State Utah Dept Hlth, Bur Epidemiol, Salt Lake City, UT USA. US FDA, Ctr Food Safety & Appl Nutr, Off Sci Assessment & Support, Washington, DC 20204 USA. State Utah Dept Hlth, Div Epidemiol & Lab Serv, Salt Lake City, UT USA. RP Sobel, J (reprint author), Ctr Dis Control & Prevent, Food & Diarrheal Dis Branch, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, MS-A38,1600 Clifton Rd NE, Atlanta, GA 30333 USA. NR 20 TC 24 Z9 27 U1 1 U2 1 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 AUG PY 2000 VL 125 IS 1 BP 1 EP 8 DI 10.1017/S0950268899004057 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 368GH UT WOS:000090109000001 PM 11057952 ER PT J AU Schenck, FJ Friedman, SL AF Schenck, FJ Friedman, SL TI The effect of storage at 4 degrees C on the stability of ampicillin residues in raw milk SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE ampicillin; milk; stability ID LIQUID-CHROMATOGRAPHY; AMOXICILLIN AB Raw milk samples collected from tanker trucks are routinely screened for beta-lactam antibiotic drug residues using rapid screening tests. If drug residues are detected, the milk may be shipped on ice blocks to a laboratory for further analysis. A study was conducted to determine the stability of ampicillin in raw milk stored at +4 degrees C in order to predict if shipping the milk would result in the degradation of ampicillin residues. Milk samples were spiked with 20 ppb ampicillin, stored at +4 degrees C and 70 degrees C for 1-6 days, and then analysed by HPLC with fluorescence detection. No loss of ampicillin residues was found in milk stored at +4 degrees C for 1-6 days. 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 8 TC 8 Z9 8 U1 0 U2 4 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 AUG PY 2000 VL 17 IS 8 BP 675 EP 677 DI 10.1080/02652030050083196 PG 3 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 340WH UT WOS:000088558600003 PM 11027028 ER PT J AU Bufano, NS AF Bufano, NS TI Keeping eggs safe from farm to table SO FOOD TECHNOLOGY LA English DT Editorial Material C1 US FDA, Washington, DC 20204 USA. RP Bufano, NS (reprint author), US FDA, 200 C St SW, Washington, DC 20204 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 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 AUG PY 2000 VL 54 IS 8 BP 192 EP 192 PG 1 WC Food Science & Technology SC Food Science & Technology GA 346KG UT WOS:000088869500011 ER PT J AU Ilev, IK Waynant, RW Ediger, MN Bonaguidi, MA AF Ilev, IK Waynant, RW Ediger, MN Bonaguidi, MA TI Ultraviolet laser delivery using an uncoated hollow taper SO IEEE JOURNAL OF QUANTUM ELECTRONICS LA English DT Article DE laser beam focusing; laser biomedical applications; multimode transmission lines; optical fiber couple; optical materials; optical waveguide components; ultraviolet imaging ID FIBER AB We demonstrate a simple grazing-incidence-based method for ultraviolet (UV) laser delivery and direct laser-to-taper coupling using an uncoated glass hollow taper. The taper serves as a mode homogenizer that converts the strongly multimode distribution of the input laser emission into a high-quality smooth profile at the taper output. An uncoated pyrex-glass hollow taper is used for direct launching, without any intermediate focusing elements, of UV laser emission from the third harmonic (lambda = 355 nm) of a Q-switched Nd:YAG laser into the taper. The linear hollow taper provides a laser-to-taper coupling efficiency exceeding 70%. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Marquette Univ, Dept Biomed Engn, Milwaukee, WI 53201 USA. RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 14 TC 13 Z9 13 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0018-9197 J9 IEEE J QUANTUM ELECT JI IEEE J. Quantum Electron. PD AUG PY 2000 VL 36 IS 8 BP 944 EP 948 DI 10.1109/3.853551 PG 5 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 339YK UT WOS:000088505300007 ER PT J AU Bacon, DJ Alm, RA Burr, DH Hu, L Kopecko, DJ Ewing, CP Trust, TJ Guerry, P AF Bacon, DJ Alm, RA Burr, DH Hu, L Kopecko, DJ Ewing, CP Trust, TJ Guerry, P TI Involvement of a plasmid in virulence of Campylobacter jejuni 81-176 SO INFECTION AND IMMUNITY LA English DT Article ID AGROBACTERIUM-TUMEFACIENS VIRB; EPITHELIAL-CELL CULTURES; GUINEA-PIG MODEL; HELICOBACTER-PYLORI; LEGIONELLA-PNEUMOPHILA; INTRACELLULAR SURVIVAL; MOLECULAR CHARACTERIZATION; ANTIBIOTIC-RESISTANCE; PATHOGENICITY ISLAND; GENOME SEQUENCE AB Campylobacter jejuni strain 81-176 contains two, previously undescribed plasmids, each of which is approximately 35 kb in size. Although one of the plasmids, termed pTet, carries a tetO gene, conjugative transfer of tetracycline resistance to another strain of C.jejuni could not be demonstrated. Partial sequence analysis of the second plasmid, pVir, revealed the presence of four open reading frames which encode proteins with significant sequence similarity to Helicobacter pylori proteins, including one encoded by the cag pathogenicity island. All four of these plasmid-encoded proteins show some level of homology to components of type IV secretion systems. Mutation of one of these plasmid genes, comB3, reduced both adherence to and invasion of INT407 cells to approximately one-third that seen with wild-type strain 81-176. Mutation of comB3 also reduced the natural transformation frequency. A mutation in a second plasmid gene, a virB11 homolog, resulted in a 6-fold reduction in adherence and an 11-fold reduction in invasion compared to the wild type. The isogenic virB11 mutant of strain 81-176 also demonstrated significantly reduced virulence in the ferret diarrheal disease model. The virB11 homolog was detected on plasmids in 6 out of 58 fresh clinical isolates of C. jejuni, suggesting that plasmids are involved in the virulence of a subset of C. jejuni pathogens. C1 USN, Med Res Ctr, Enter Dis Dept, Silver Spring, MD 20910 USA. Astra Zeneca, Infect Discovery, Cambridge, MA 02139 USA. US FDA, Beltsville, MD 20708 USA. US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Guerry, P (reprint author), USN, Med Res Ctr, Enter Dis Dept, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. RI Guerry, Patricia/A-8024-2011 NR 69 TC 208 Z9 216 U1 1 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2000 VL 68 IS 8 BP 4384 EP 4390 DI 10.1128/IAI.68.8.4384-4390.2000 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 337AY UT WOS:000088336200003 PM 10899834 ER PT J AU Liu, FF Ang, CYW Springer, D AF Liu, FF Ang, CYW Springer, D TI Optimization of extraction conditions for active components in Hypericum perforatum using response surface methodology SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Hypericum perforatum; extraction; response surface methodology; optimization ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; CONSTITUENTS; WORT AB Optimal conditions for extraction of Hypericum perforatum were determined using response surface methodology. A 3 x 4 x 4 full factorial design representing three extraction temperatures, four extraction times, and four solvent concentrations was executed. The overall extraction efficiency was defined by comparing either the total extractable material weight or the individual component peak area to the peak area of luteolin as internal standard. Of the tested variables, the extraction temperature most significantly affected extraction efficiency. Higher temperatures gave better extraction efficiencies, but high temperature also caused decomposition of hypericin. Within the test range, responses for most variables had local maxima. Optimum ranges of time and concentration for individual variables were overlaid. Considering all variables, optimum ranges for extraction time and extraction solvent concentration (percent ethanol in acetone) were 5.0-6.7 h and 44-74% at 23 degrees C, 5.4-6.9 h and 45-72% at 40 degrees C, and 5.3-5.9 h and 44-69% ethanol in acetone at 55 degrees C, respectively. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Ang, CYW (reprint author), US FDA, Natl Ctr Toxicol Res, Div Chem, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 20 TC 53 Z9 55 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD AUG PY 2000 VL 48 IS 8 BP 3364 EP 3371 DI 10.1021/jf991086m PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 347VU UT WOS:000088950500049 PM 10956117 ER PT J AU Lesko, LJ Rowland, M Peck, CC Blaschke, TF AF Lesko, LJ Rowland, M Peck, CC Blaschke, TF TI Optimizing the science of drug development: Opportunities for better candidate selection and accelerated evaluation in humans SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID REMIFENTANIL GI87084B; PHARMACOKINETICS; PHARMACODYNAMICS; INTEGRATION AB Two international meetings were convened in 1998 to review the current science of drug development and the potential opportunities to optimize the evaluation of new drugs in humans. This report represents a synopsis of these meetings, and focuses on the current state of knowledge pertaining to drug development, future scientific and technical needs, and the relative merits of various strategies intended to accelerate the clinical development of drugs. (C) 2000 the American College of Clinical pharmacology. C1 US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20851 USA. Univ Manchester, Sch Pharm & Pharmaceut Sci, Manchester, Lancs, England. Georgetown Univ, Ctr Drug Dev Sci, Washington, DC 20057 USA. Stanford Univ, Sch Med, Dept Med, Div Clin Pharmacol, Stanford, CA 94305 USA. RP Lesko, LJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, 1451 Rockville Pike,HFD-850, Rockville, MD 20851 USA. NR 11 TC 20 Z9 22 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 AUG PY 2000 VL 40 IS 8 BP 803 EP 814 DI 10.1177/00912700022009530 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 336NE UT WOS:000088308500001 PM 10934664 ER PT J AU Koo, J DePaola, A Marshall, DL AF Koo, J DePaola, A Marshall, DL TI Impact of acid on survival of Vibrio vulnificus and Vibrio vulnificus phage SO JOURNAL OF FOOD PROTECTION LA English DT Article ID OYSTERS CRASSOSTREA-VIRGINICA; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; TOLERANCE RESPONSE; GRAS COMPOUNDS; GULF-COAST; BACTERIOPHAGES; INFECTIONS; BIOCIDES; INACTIVATION AB Three strains of Vibrio vulnificus and V. vulnificus phages were tested for acid sensitivity at 21 degrees C. V. vulnificus strain 304 was more resistant to pH 4.0 than strains CVD-l and A-9, whereas acid sensitivities of V. vulnificus strains at pH 3.0 and 2.0 were similar. V. vulnificus phage strain 110A-7 was more resistant to pH 4.0 than strain 153A-7, whereas acid sensitivities of phage strains at pH 3.5 and 3.0 were similar. Numbers of V. vulnificus and its phage were close to the limit of detection after 100 s at pH 2.0 and after 24 min at pH 3.0. Acid D-values at 21 degrees C decreased as pH decreased for both V. vulnificus and phages. D-values of phage strains at pH 3.5 were 10-fold greater than those of host strain at pH 4.0. D-values of phage strains were slightly greater than those of host strain at pH 3.0. These results suggest that V. vulnificus and its phage were very sensitive to pH of less than 3.0, although V. vulnificus phages were more resistant to acid than their host. C1 Mississippi State Univ, Mississippi Agr & Forestry Expt Stn, Dept Food Sci & Technol, Mississippi State, MS 39762 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. RP Marshall, DL (reprint author), Mississippi State Univ, Mississippi Agr & Forestry Expt Stn, Dept Food Sci & Technol, Box 9805, Mississippi State, MS 39762 USA. NR 34 TC 5 Z9 6 U1 1 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 AUG PY 2000 VL 63 IS 8 BP 1049 EP 1052 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 342KB UT WOS:000088642800007 PM 10945579 ER PT J AU Hitchins, AD Duvall, RE AF Hitchins, AD Duvall, RE TI Feasibility of a defined microflora challenge method for evaluating the efficacy of foodborne Listeria monocytogenes selective enrichments SO JOURNAL OF FOOD PROTECTION LA English DT Article ID MEDIA; FOODS AB Comparison of isolation methods for microbial pathogens is complicated by the variable interference caused by the competitive microflora present in test samples such as foods. In principle, using measured amounts of a standard competitor in a defined surrogate food matrix might control the effect of variable interference. This possibility was investigated using Listeria monocytogenes and enrichment broths belonging to the acriflavine-nalidixate selective agent class. Triplicate test sample sets were prepared. Each set consisted of suspensions of variable levels of the standard competitor, Enterococcus faecium strain 111 (approximate to 10 to 10(9) CFU/25 g), mixed with a low constant level (10 to 100 CFU/25 g) of L, monocytogenes. These test samples were enriched at 30 degrees C for 48 h in different selective media and streaked onto selective isolation agars. The input CFU ratio (E. faecium/L. monocytogenes) that permitted a 50% end point L, monocytogenes recovery was 2,2 x 10(6) or higher for the Food and Drug Administration one-step enrichments and 0.8 x 10(6) for the International Standards Organization (ISO) two-step enrichment. These and other results show that this evaluation method is feasible with this class of enrichments. Interestingly, L. monocytogenes could be detected in enrichment cultures at high-input E, faecium/L. monocytogenes ratios even when the enriched samples were plated onto nonselective media. The pinpoint colonies of L, monocytogenes embedded in a confluent lawn of E. faecium 111 were detectable by their contrasting coloration in Henry obliquely transmitted illumination. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Hitchins, AD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 16 TC 4 Z9 4 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 AUG PY 2000 VL 63 IS 8 BP 1064 EP 1070 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 342KB UT WOS:000088642800010 PM 10945582 ER PT J AU Wong, S Street, D Delgado, SI Klontz, KC AF Wong, S Street, D Delgado, SI Klontz, KC TI Recalls of foods and cosmetics due to microbial contamination reported to the US Food and Drug Administration SO JOURNAL OF FOOD PROTECTION LA English DT Article ID EPIDEMIC LISTERIOSIS; OUTBREAK; INFECTIONS AB In the U.S., food product recalls serve as an important intervention in stemming the consumption of food products contaminated with infectious disease agents. We summarize the number and nature of foods and cosmetics recalled as a result of microbial contamination reported to the U.S. Food and Drug Administration (FDA) for the period I October 1993 through 30 September 1998. During this period, microbial contamination of food and cosmetic products was the leading cause for recalls, accounting for a total of 1,370 recalls (36% of all products recalled). Listeria monocytogenes accounted for the greatest number of food products recalled because of microbial contamination, whereas Pseudomonas aeruginosa was the most common microbe associated with recalls of cosmetic products. Dairy products, followed by seafood and pastry items, were the types of products most often associated with recalls due to microbial contamination. The FDA was the entity most often responsible for detecting microbial contamination of foods and cosmetics (33% of all such recalls), followed by state regulatory agencies (24%), and manufacturers/retailers (21%). Nineteen percent of recalls were associated with at least one reported case of illness. Salmonella was the pathogen most often implicated in reports of illness associated with these recalled products. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Klontz, KC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 16 TC 54 Z9 58 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 AUG PY 2000 VL 63 IS 8 BP 1113 EP 1116 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 342KB UT WOS:000088642800017 PM 10945589 ER PT J AU Fogelman, I Davey, V Ochs, HD Elashoff, M Feinberg, MB Mican, J Siegel, JP Sneller, M Lane, HC AF Fogelman, I Davey, V Ochs, HD Elashoff, M Feinberg, MB Mican, J Siegel, JP Sneller, M Lane, HC TI Evaluation of CD4(+) T cell function in vivo in HIV-infected patients as measured by bacteriophage phiX174 immunization SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 12th World AIDS Conference CY JUN 28-JUL 03, 1998 CL GENEVA, SWITZERLAND ID ACTIVE ANTIRETROVIRAL THERAPY; DEFECTIVE HUMORAL IMMUNITY; ANTIBODY-RESPONSES; CD40 LIGAND; HYPER-IGM; IMMUNODEFICIENCY; DEFICIENCY; EXPRESSION; DISEASE; ABNORMALITIES AB Bacteriophage phiX174 immunization was used to measure CD4(+) T cell function in vivo in human immunodeficiency virus (HIV)-infected patients across all disease stages. Function was evaluated by measuring the ability of T cells to provide help to B cells in antibody production, amplification, and isotype switching. A total of 33 patients and 10 controls received 3 bacteriophage phiX174 immunizations 6 weeks apart. The patients' responses regarding bacteriophage-specific total antibody titers and IgG titers were quantitatively and qualitatively inferior to the controls' responses. Overall, 7 of 33 patients had normal T cell function. Baseline CD4 counts provided the strongest correlation with total antibody and IgG titers. HIV RNA had a weaker association with responses but had some predictive power among patients with a CD4 count >200 cells/mu L. Bacteriophage phiX174 immunization seems to be a useful tool for measuring immune function in vivo, which suggests that most HIV-infected patients may have abnormal CD4(+) T cell function despite adequate antiretroviral treatment. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. Emory Univ, Vaccine Res Ctr, Atlanta, GA 30322 USA. RP Fogelman, I (reprint author), 3962 Germantown Rd, Edgewater, MD 21037 USA. NR 24 TC 39 Z9 40 U1 0 U2 2 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 AUG PY 2000 VL 182 IS 2 BP 435 EP 441 DI 10.1086/315739 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 347WJ UT WOS:000088951900008 PM 10915073 ER PT J AU Chang, HC Churchwell, MI Delclos, KB Newbold, RR Doerge, DR AF Chang, HC Churchwell, MI Delclos, KB Newbold, RR Doerge, DR TI Mass spectrometric determination of genistein tissue distribution in diet-exposed Sprague-Dawley rats SO JOURNAL OF NUTRITION LA English DT Article DE genistein; isoflavones; mass spectrometry; rats; pharmacokinetics ID ESTROGEN-RECEPTOR-BETA; SOY ISOFLAVONES; QUANTITATIVE-ANALYSIS; FEMALE RATS; IN-VITRO; PHYTOESTROGENS; EXCRETION; DAIDZEIN; METABOLISM; PLASMA AB Genistein, the principal soy isoflavone, was administered in the diet to male and female Sprague-Dawley rats as part of a multigeneration study of potential endocrine modulation. The rats were exposed to genistein in utero, through maternal milk, and as adults through postnatal d 140 via essentially isoflavone-free feed (similar to 0.5 mu g/g) fortified at 5, 100 and 500 mu g/g with genistein aglycone. Analytical methods based on liquid chromatography, mass spectrometry and the use of deuterated genistein were developed and validated for use in measuring genistein in serum and tissues. Pharmacokinetic analysis of serum genistein showed a significant difference (P < 0.001) in the elimination half-life and area under the concentration-time curve between male [2.97 +/- 0.14 h and 22.3 +/- 1.2 mu mol/(L . h), respectively] and female rats [4.26 +/- 0.29 h and 45.6 +/- 3.1 mu mol/(L . h), respectively, +/- SEM]. Endocrine-responsive tissues including brain, liver, mammary, ovary, prostate, testis, thyroid and uterus showed significant dose-dependent increases in total genistein concentration. Female liver contained the highest amount of genistein (7.3 pmol/mg tissue) and male whole brain contained the least (0.04 pmol/mg). The physiologically active aglycone form was present in tissues at fractions up to 100%, and the concentration was always greater than that observed in serum in which conjugated forms predominated (95-99%). These results for measured amounts of genistein, present as aglycone and conjugates, in putative target tissues provide a link with other studies in which blood concentrations and physiologic effects of genistein are measured. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NIEHS, Dev Endocrinol Sect, Reprod Toxicol Grp, Lab Toxicol,Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 30 TC 195 Z9 203 U1 0 U2 12 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD AUG PY 2000 VL 130 IS 8 BP 1963 EP 1970 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 339TA UT WOS:000088492900015 PM 10917909 ER PT J AU Lee, S Tiffany, HL King, L Murphy, PM Golding, H Zaitseva, MB AF Lee, S Tiffany, HL King, L Murphy, PM Golding, H Zaitseva, MB TI CCR8 on human thymocytes functions as a human immunodeficiency virus type 1 coreceptor SO JOURNAL OF VIROLOGY LA English DT Article ID CHEMOKINE RECEPTOR CCR8; HUMAN THYMIC IMPLANTS; CELLS IN-VITRO; SCID-HU MICE; HIV-1 INFECTION; DIFFERENTIAL TROPISM; FUSION COFACTOR; GP120 BINDING; CXCR4; VIVO AB To determine whether human immunodeficiency virus type 1 (HIV-1) coreceptors besides CXCR4 and CCR5 are involved in HIV-1 infection of the thymus, we focused on CCR8, a receptor for the chemokine I-309, because of its high expression in the thymus. Similar levels of CCR8 mRNA were detected in immature and mature primary human thymocytes. Consistent with this, [I-125]I-309 was shown to bind specifically and with similar affinity to the surface of immature and mature human thymocytes. Fusion of human thymocytes with cells expressing HIV-1 X4 or X 4R5 envelope glycoprotein was inhibited by I-309 in a dose-dependent manner. In addition, I-309 partially inhibited productive infection of human thymocytes by X4, R5, and X4R5 HIV-1 strains. Our data provide the first evidence that CCR8 functions as an HIV-1 coreceptor on primary human cells and suggest that CCR8 may contribute to HIV-l-induced thymic pathogenesis. C1 CBER, FDA, Div Viral Prod, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Zaitseva, MB (reprint author), CBER, FDA, Div Viral Prod, Bldg 29B,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 46 TC 36 Z9 36 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2000 VL 74 IS 15 BP 6946 EP 6952 DI 10.1128/JVI.74.15.6946-6952.2000 PG 7 WC Virology SC Virology GA 333AE UT WOS:000088105900027 PM 10888633 ER PT J AU Chango, A Emery-Fillon, N de Courcy, GP Lambert, D Pfister, M Rosenblatt, DS Nicolas, JP AF Chango, A Emery-Fillon, N de Courcy, GP Lambert, D Pfister, M Rosenblatt, DS Nicolas, JP TI A polymorphism (80G-> A) in the reduced folate carrier gene and its associations with folate status and homocysteinemia SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE folate status; homocysteine; methylenetetrahydrofolate reductase; polymorphism; reduced-folate carrier ID METHYLENETETRAHYDROFOLATE REDUCTASE; COMMON MUTATION; NEURAL-TUBE; TRANSPORT; CELLS; EXPRESSION; RECEPTORS; DEFECTS; CLONING; CANCER AB 5-Methyltetrahydrofolate is the predominant form of folate in plasma. It may be the preferred substrate for transport via the reduced-folate carrier (RFC). We isolated a cDNA for the reduced folate carrier (RFC-1) from human skin fibroblasts, A common polymorphism at position 80 in exon 2 of RFC-1 was identified. This polymorphism changes a guanine (G) to an adenine (A), abolishing a CfoI restriction site. Using genomic DNA samples from 169 healthy subjects, we identified 27.1% GG homozygotes, 21.9% AA homozygotes, and 50.9% GA heterozygotes. We explored the impact of this polymorphism, separately and in combination with the 677C->T polymorphism in the methylenetetrahydrofolate reductase gene, on folate status and total homocysteine levels. We found a moderate, but significant, increase in total homocysteine levels in doubly homozygous 80GG/677TT subjects as compared to 80GG/677CC (P = 0.01) or 80GG/677CT (P = 0.04) subjects. In addition, individuals who mere 80AA/677CT had higher plasma folate levels than those who were 80GG/677CT (P = 0.02). (C) 2000 Academic Press. C1 Fac Med Vandoeuvre Nancy, INSERM, U308, Lab Biochim Med, F-54505 Vandoeuvre Les Nancy, France. Conservatoire Natl Arts & Metiers, Inst Sci & Tech Nutr & Alimentat, F-75003 Paris, France. McGill Univ, Dept Med, Div Med Genet, Montreal, PQ, Canada. RP US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT-140,3900 NCTR Rd, Jefferson, AR 72079 USA. EM achango@nctr.fda.gov NR 29 TC 225 Z9 243 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD AUG PY 2000 VL 70 IS 4 BP 310 EP 315 DI 10.1006/mgme.2000.3034 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 394JJ UT WOS:000166520000008 PM 10993718 ER PT J AU Meyer, MC Straughn, AB Mhatre, RM Hussain, A Shah, VP Bottom, CB Cole, ET Lesko, LL Mallinowski, H Williams, RL AF Meyer, MC Straughn, AB Mhatre, RM Hussain, A Shah, VP Bottom, CB Cole, ET Lesko, LL Mallinowski, H Williams, RL TI The effect of gelatin cross-linking on the bioequivalence of hard and soft gelatin acetaminophen capsules SO PHARMACEUTICAL RESEARCH LA English DT Article DE gelatin capsules; acetaminophen; crosslinking; dissolution; human bioequivalence ID DISSOLUTION; PARACETAMOL; ABSORPTION AB Purpose. To determine if changes in the in vitro dissolution of hard and soft gelatin acetaminophen capsules, which result from gelatin crosslinking, are predictive of changes in the bioavailability of the capsules in humans. Methods. Both hard and soft gelatin capsules were "stressed" by a controlled exposure to formaldehyde, resulting in unstressed, moderately stressed and highly stressed capsules. In vitro dissolution studies were conducted using water or SGF with and without pepsin as the media. Separate 24-subject, 3-way crossover human bioequivalence studies were performed on the unstressed and stressed acetaminophen capsules. Plasma acetaminophen was determined by high performance liquid chromatography (HPLC) for 12 hr after each dose. Results. The in vitro rate of dissolution of hard and soft gelatin capsules was decreased by crosslinking. The bioequivalence studies showed that both hard and soft gelatin capsules, which failed to meet the USP dissolution specification in water, but complied when tested in SGF containing pepsin, were bioequivalent to the unstressed control capsules. The capsules that were cross-linked to the greatest extent were not bioequivalent to the unstressed control capsules, based on Cmax. A trend toward an increase in Cmax with increased level of crosslinking was observed, but this was only significant for the severely stressed capsules. Conclusions. On the basis of this study a two-tier in vitro dissolution test was developed using enzymes to distinguish between bioequivalent and bioinequivalent gelatin capsules. C1 Univ Tennessee, Coll Pharm, Dept Pharmaceut Sci, Memphis, TN 38163 USA. US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. LDS Technol Inc, Boothwyn, PA 19061 USA. Warner Lambert Co, Capsugel Div, CH-4144 Arlesheim Basel, Switzerland. RP Meyer, MC (reprint author), Univ Tennessee, Coll Pharm, Dept Pharmaceut Sci, Memphis, TN 38163 USA. NR 13 TC 24 Z9 25 U1 1 U2 14 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 AUG PY 2000 VL 17 IS 8 BP 962 EP 966 DI 10.1023/A:1007579221726 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 356ZM UT WOS:000089474100011 PM 11028942 ER PT J AU Popke, EJ Fogle, CM Paule, MG AF Popke, EJ Fogle, CM Paule, MG TI Ethanol enhances nicotine's effects on DRL performance in rats SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE nicotine; ethanol; operant behavior; rats; DRL ID DIFFERENTIAL-REINFORCEMENT; ACETYLCHOLINE-RECEPTORS; NUCLEUS-ACCUMBENS; CIGARETTE-SMOKING; CORTICAL-NEURONS; DOPAMINE RELEASE; TIMING BEHAVIOR; ALCOHOL; DRUGS; MODULATION AB The present experiment examined effects of nicotine (0.0, 0.3, 0.56, and 1.0 mg/kg; IP) and ethanol (0.0, 0.5, 1.5, and 3.0 g/kg; IG) on operant behavior using a differential reinforcement of low response rate (DRL) schedule in rats. DRL schedules are sensitive to effects of nicotine and provide an assessment of the subject's ability to accurately estimate time and to inhibit schedule-controlled responding. When administered alone, nicotine shifted the mode of the interresponse time distribution to the left and reduced the percentage of reinforced responses. Nicotine also had an inverted U-shaped dose effect on the number of "bursting" responses. When administered after pretreatment with ethanol, nicotine's effects on the distribution of interresponse times and bursting were potentiated. These effects are consistent with previous reports and with the suggestion that ethanol pretreatment can potentiate effects of subsequently administered nicotine. Published by Elsevier Science Inc. C1 US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Popke, EJ (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 63 TC 6 Z9 7 U1 0 U2 0 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 AUG PY 2000 VL 66 IS 4 BP 819 EP 826 DI 10.1016/S0091-3057(00)00275-6 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 354CZ UT WOS:000089313400020 PM 10973521 ER PT J AU Nagaraju, K Raben, N Loeffler, L Parker, T Rochon, PJ Lee, E Danning, C Wada, R Thompson, C Bahtiyar, G Craft, J van Huijsduijnen, RH Plotz, P AF Nagaraju, K Raben, N Loeffler, L Parker, T Rochon, PJ Lee, E Danning, C Wada, R Thompson, C Bahtiyar, G Craft, J van Huijsduijnen, RH Plotz, P TI Conditional up-regulation of MHC class I in skeletal muscle leads to self-sustaining autoimmune myositis and myositis-specific autoantibodies SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IDIOPATHIC INFLAMMATORY MYOPATHY; ANTIGEN-PRESENTING CELLS; TRANSFER-RNA SYNTHETASE; MEDIATED CYTO-TOXICITY; T-CELLS; HISTOCOMPATIBILITY MOLECULES; SYSTEMIC AUTOIMMUNITY; MICROVASCULAR CHANGES; ABERRANT EXPRESSION; MONONUCLEAR-CELLS AB In the human inflammatory myopathies (polymyositis and dermatomyositis), the early, widespread appearance of MHC class I on the surface of muscle cells and the occurrence of certain myositis-specific autoantibodies are striking features. We have used a controllable muscle-specific promoter system to up-regulate MHC class I in the skeletal muscles of young mice. These mice develop clinical, biochemical, histological, and immunological features very similar to human myositis. The disease is inflammatory, limited to skeletal muscles, self-sustaining, more severe in females, and often accompanied by autoantibodies, including, in some mice, autoantibodies to histidyl-tRNA synthetase, the most common specificity found in the spontaneous human disease, anti-Jo-1. This model suggests that an autoimmune disease may unfold in a highly specific pattern as the consequence of an apparently nonspecific event-the sustained up-regulation of MHC class I in a tissue-and that the specificity of the autoantibodies derives not from the specificity of the stimulus, but from the context, location, and probably the duration of the stimulus. This model further suggests that the presumed order of events as an autoimmune disease develops needs to be reconsidered. C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. Serono Pharmaceut Res Inst, CH-1228 Geneva, Switzerland. RP Plotz, P (reprint author), NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NR 47 TC 165 Z9 180 U1 0 U2 4 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 AUG 1 PY 2000 VL 97 IS 16 BP 9209 EP 9214 DI 10.1073/pnas.97.16.9209 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 341UL UT WOS:000088608000081 PM 10922072 ER PT J AU Kang, SH Kodell, RL Chen, JJ AF Kang, SH Kodell, RL Chen, JJ TI Incorporating model uncertainties along with data uncertainties in microbial risk assessment SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE food safety; low-dose extrapolation; Akaike's information criterion; nonlinear programming; GAMS AB Much research on food safety has been conducted since the National Food Safety Initiative of 1997. Risk assessment plays an important role in food safety practices and programs, and various dose-response models for estimating microbial risks have been investigated. Several dose-response models can provide reasonably good fits to the data in the experimental dose range, but yield risk estimates that differ by orders of magnitude in the low-dose range. Hence, model uncertainty can be just important as data uncertainty (experimental variation) in risk assessment. Although it is common in risk assessment to account for data uncertainty, it is uncommon to account for model uncertainties. In this paper we incorporate data uncertainties with confidence limits and model uncertainties with a weighted average of an estimate from each of various models. A numerical tool to compute the maximum likelihood estimates and confidence limits is addressed. The proposed method for incorporating model uncertainties is illustrated with real data sets. (C) 2000 Academic Press. C1 Univ Texas, Sch Med, Clin Epidemiol Sect, Houston, TX 77030 USA. US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Kang, SH (reprint author), Univ Texas, Sch Med, Clin Epidemiol Sect, Houston, TX 77030 USA. NR 19 TC 42 Z9 42 U1 0 U2 2 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 AUG PY 2000 VL 32 IS 1 BP 68 EP 72 DI 10.1006/rtph.2000.1404 PG 5 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 368YM UT WOS:000090145100008 PM 11029270 ER PT J AU Biles, PV Ziobro, GC AF Biles, PV Ziobro, GC TI Regulatory action criteria for filth and other extraneous materials IV. Visual detection of hair in food SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article AB Under Section 402(a)(3) of the Food, Drug and Cosmetic Act the distribution of foods which may contain repulsive or offensive matter, considered as filth, is prohibited. Filth includes contaminants such as rat, mouse, and other animal hairs and excreta; whole insects, insect parts, and excreta; and other extraneous materials which, because of their repulsiveness, would not knowingly be eaten or used. The presence of such filth renders food adulterated. Some foods, even when produced under good manufacturing practice, contain low level of natural or unavoidable defects such as dirt, insect parts, and hair that are not hazardous to health. Although the health hazard is eliminated, most consumers find the presence of "any" visible filth contaminant such as hair in a food product objectionable. The objective of this study was to determine when a defect (hair) in a food (mushrooms) is visible to a consumer by testing the visual acuity of a consumer panel under controlled laboratory conditions. Of the panelists participating in the study, when presented with a single hair on a flat surface with a solid-colored background, 27% were able to detect a l-mm hair, 58% were able to detect a 3-mm hair, and 75% were able to detect a 10-mm hair. Twenty-five percent of the panelists surveyed were able to detect a 5- or 10-mm hair on sliced, canned mushrooms. The experimental design and results of this study are discussed. C1 US FDA, Microanalyt Branch, Washington, DC 20204 USA. RP Biles, PV (reprint author), US FDA, Microanalyt Branch, HFS-315,200 C St SW, Washington, DC 20204 USA. NR 11 TC 5 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 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD AUG PY 2000 VL 32 IS 1 BP 73 EP 77 DI 10.1006/rtph.2000.1403 PG 5 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 368YM UT WOS:000090145100009 PM 11029271 ER PT J AU Ponce, RA Bartell, SM Wong, EY LaFlamme, D Carrington, C Lee, RC Patrick, DL Faustman, EM Bolger, M AF Ponce, RA Bartell, SM Wong, EY LaFlamme, D Carrington, C Lee, RC Patrick, DL Faustman, EM Bolger, M TI Use of quality-adjusted life year weights with dose-response models for public health decisions: A case study of the risks and benefits of fish consumption SO RISK ANALYSIS LA English DT Article DE risk-benefit analysis; fish; risk analysis; methylmercury; quality of life ID CORONARY HEART-DISEASE; POLYUNSATURATED FATTY-ACIDS; DEVELOPMENTAL NEUROTOXICITY; POLYCHLORINATED-BIPHENYLS; CARDIOVASCULAR-DISEASE; METHYLMERCURY EXPOSURE; MYOCARDIAL-INFARCTION; DIETARY-INTAKE; FOOD; PCBS AB Risks associated with toxicants in food are often controlled by exposure reduction. When exposure recommendations are developed for foods with both harmful and beneficial qualities. however, they must balance the associated risks and benefits to maximize public health. Although quantitative methods are commonly used to evaluate health risks, such methods have not been generally applied to evaluating the health benefits associated with environmental exposures. A quantitative method for risk-benefit analysis is presented that allows for consideration of diverse health endpoints that differ in their impact (i.e., duration and severity) using dose-response modeling weighted by quality-adjusted life years saved. To demonstrate the usefulness of this method, the risks and benefits of fish consumption are evaluated using a single health risk and health benefit endpoint. Benefits are defined as the decrease in myocardial infarction mortality resulting from fish consumption, and risks are defined as the increase in neurodevelopmental delay (i.e., talking) resulting from prenatal methylmercury exposure. Fish consumption rates are based on information from Washington State. Using the proposed framework, the net health impact of eating fish is estimated in either a whole population or a population consisting of women of childbearing age and their children. It is demonstrated that across a range of fish methylmercury concentrations (0-1 ppm) and intake levels (0-25 g/day), individuals would have to weight the neurodevelopmental effects 6 times more (in the whole population) or 250 times less (among women of child-bearing age and their children) than the myocardial infarction benefits in order to be ambivalent about whether or not to consume fish. These methods can be generalized to evaluate the merits of other public health and risk management programs that involve trade-offs between risks and benefits. C1 Univ Washington, Dept Environm Hlth, Seattle, WA 98105 USA. Washington Dept Hlth, Olympia, WA USA. US FDA, Contaminants Branch, Washington, DC 20204 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Inst Neurotoxicol & Neurodev Disorders, Redmond, WA USA. RP Ponce, RA (reprint author), Univ Washington, Dept Environm Hlth, 4225 Roosevelt Way NE 300, Seattle, WA 98105 USA. RI Bartell, Scott/M-8919-2013 OI Bartell, Scott/0000-0001-7797-2906 NR 84 TC 45 Z9 45 U1 1 U2 5 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 AUG PY 2000 VL 20 IS 4 BP 529 EP 542 DI 10.1111/0272-4332.204050 PG 14 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 361VL UT WOS:000089744900011 PM 11051076 ER PT J AU Varricchio, F AF Varricchio, F TI Another type of medication error: Dilution/reconstitution SO SOUTHERN MEDICAL JOURNAL LA English DT Article C1 US FDA, Ctr Biol Evaluat & Res, Div Biostat & Epidemiol, Rockville, MD 20852 USA. RP Varricchio, F (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Biostat & Epidemiol, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 USA SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD AUG PY 2000 VL 93 IS 8 BP 834 EP 834 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 344UQ UT WOS:000088777800024 PM 10963525 ER PT J AU Patterson, TA Binienda, ZK Newport, GD Lipe, GW Gillam, MP Slikker, W Sandberg, JK AF Patterson, TA Binienda, ZK Newport, GD Lipe, GW Gillam, MP Slikker, W Sandberg, JK TI Transplacental pharmacokinetics and fetal distribution of 2 ',3 '-didehydro-3 '-deoxythymidine (d4T) and its metabolites in late-term rhesus macaques SO TERATOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-RELATED COMPLEX; STAVUDINE 2',3'-DIDEHYDRO-3'-DEOXYTHYMIDINE; CELLULAR PHARMACOLOGY; MACACA-NEMESTRINA; HUMAN PLACENTA; 3'-DEOXY-2',3'-DIDEHYDROTHYMIDINE; 3'-AZIDO-3'-DEOXYTHYMIDINE; DISPOSITION; MONKEYS AB Background: The overall goal of human immunodeficiency virus (HIV) therapy during pregnancy is to maintain maternal health and reduce the probability of vertical transmission during gestation and delivery, while keeping toxicity risks low. Azidothymidine (AZT) is currently recommended for pregnant women infected with HIV; however, many pregnant women are unable to tolerate AZT because of toxicity. In the present study, the placental transfer and fetal accumulation of the anti-HIV compound 2',3'-didehydro-3'-deoxythymidine (d4T) and its active (triphosphorylated) and inactive (thymine and beta-aminoisobutyric acid) metabolites were examined at steady state in late-term rhesus macaques. Methods: On the day of the hysterotomy, the mother was administered an intravenous loading dose of d4T, followed by a 3-hr steady-state intravenous infusion that also included [H-3]d4T as a tracer. After 3 hr of infusion, the fetus was delivered by cesarean section under halothane/N2O anesthesia. Plasma, amniotic fluid, and tissues were analyzed for d4T and its inactive metabolites by HPLC; tissue samples were analyzed for d4T and active (phosphorylated) metabolites by strong anion-exchange HPLC, Results: Maternal steady-state plasma concentrations of d4T were 1-2 mu g/ml, with a fetal-to-maternal plasma ratio of 0.85 +/- 0.09. The fetal tissue distribution of radioactivity was highest in the kidney and lowest in the brain. D4T, thymine, and beta-aminoisobutyric acid were detected in all fetal tissues examined. Conclusions: Our data indicate that d4T readily crosses the placenta and is present in the fetus as parent compound or its inactive metabolites after maternal infusion. Although fetal plasma concentrations of d4T were similar to clinical d4T concentrations, no phosphorylated metabolites were detected. Teratology 62:93-99, 2000. Published 2000 Wiley-Liss, Inc.dagger. C1 US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Patterson, TA (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. FU NIEHS NIH HHS [IAG Y01-ES-10187] NR 21 TC 13 Z9 14 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 AUG PY 2000 VL 62 IS 2 BP 93 EP 99 DI 10.1002/1096-9926(200008)62:2<93::AID-TERA5>3.0.CO;2-M PG 7 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 340JG UT WOS:000088528900005 PM 10931506 ER PT J AU Papaconstantinou, AD Umbreit, TH Fisher, BR Goering, PL Lappas, NT Brown, KM AF Papaconstantinou, AD Umbreit, TH Fisher, BR Goering, PL Lappas, NT Brown, KM TI Bisphenol A-induced increase in uterine weight and alterations in uterine morphology in ovariectomized B6G3F1 mice: Role of the estrogen receptor SO TOXICOLOGICAL SCIENCES LA English DT Article DE bisphenol A (BPA); ICI 182,780 (ICI); beta-estradiol (E-2); estrogen receptor (ER); uterotrophic effects; uterine weight; myometrium; stroma; luminal epithelium; B6C3F1 mouse ID ENVIRONMENTAL ESTROGEN; IN-VIVO; MESSENGER-RNA; RABBIT UTERUS; RAT; ENDOCRINE; ANTIESTROGEN; ALPHA; GENE; GROWTH AB The ability of the environmental xenoestrogen bisphenol A (BPA) to increase uterine wet weight in the rodent remains controversial, and few studies have previously examined the effects of BPA on uterine morphology. Furthermore, it is not known whether BPA-induced uterotrophic effects are, similarly to beta-estradiol (E-2), mediated through the estrogen receptor (ER). In this study, we compared the effects of BPA on uterine wet weight and morphology to those of E-2 in the B6C3F1 ovariectomized mouse. To examine whether these effects were mediated through the ER, the antiestrogen ICI 182,780 (ICI) was co-administered with BPA or E-2. We report that subcutaneous administration of BPA at doses between 0.8 and 8 mg/day over 4 days significantly increased mean uterine wet weights above those of vehicle (corn oil)-treated mice. The uterine weight data suggest that BPA acts as a partial agonist with an EC50 of 0.72 mg/day compared to 19.4 ng/day for E-2. BPA (2 mg/day) and E-2 (40 ng/day) induced a significant increase in luminal epithelial height and in the thickness of both the stromal and myometrial layers of the uterus. The effects of 40 ng E-2/day on all endpoints studied were reversed by 20 pg ICU day. ICI at 200, but not 20 mu g/day, was able to reverse the BPA (2 mg/day)-induced increase in both uterine wet weight and luminal epithelial height. ICI alone at 200 mu g/day stimulated an increase in thickness of both the stroma and myometrium and did not reverse the effects of BPA (2 mg/day) on these layers. These results suggest that the BPA-induced increase in uterine wet weight and in luminal epithelial height in the ovariectomized B6C3F1 mouse are mediated by the ER. C1 George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA. George Washington Univ, Dept Forens Sci, Washington, DC 20052 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Brown, KM (reprint author), George Washington Univ, Dept Biol Sci, 332 Lisner Hall,2023 G St NW, Washington, DC 20052 USA. NR 50 TC 76 Z9 80 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD AUG PY 2000 VL 56 IS 2 BP 332 EP 339 DI 10.1093/toxsci/56.2.332 PG 8 WC Toxicology SC Toxicology GA 343GP UT WOS:000088693600013 PM 10910991 ER PT J AU Chung, KT Chen, SC Wong, TY Li, YS Wei, CI Chou, MW AF Chung, KT Chen, SC Wong, TY Li, YS Wei, CI Chou, MW TI Mutagenicity studies of benzidine and its analogs: Structure-activity relationships SO TOXICOLOGICAL SCIENCES LA English DT Article DE mutagenicity; oxidation potential; physicochemical properties ID AROMATIC-AMINES; BLADDER-CANCER; AZO DYES; WORKERS; REDUCTION; EXPOSURE; MODELS; TUMORS AB The Ames Salmonella/microsome assay was employed to test the mutagenicity of benzidine and its analogs using strains TA98 and TA100 in the presence and absence of Aroclor 1254-induced rat S9 mix. 3,3'-Dichlorobenzidine-2HCl and 4,4'-dinitro-2-biphenylamine were directly mutagenic to TA98, while 4,4'-dinitro-2biphenylamine was directly mutagenic to both TA98 and TA100 in the absence of S9 mix. 2-Aminobiphenyl, 3-aminobiphenyl, and 3,3'-5,5'-tetramethylbenzidine were not mutagenic in either strains in the presence or absence of So. In the presence of S9 mix, 4-aminobiphenyl, benzidine, 3,3'-dichlorobenzidine-2HCl, 3,3'-dimethoxybenzidine, 3,3'-4,4'-tetraaminobiphenyl, o-tolidine, N, N-N', N'-tetramethylbenzidine, and 4,4'-dinitro-2-biphenylamine were mutagenic to TA98; 4-aminobiphenyl, 3,3'-dichlorobenzidine-2HCl, 3,3'-dimethoxybenzidine, and 4,4'-dinitro-2-biphenylamine were mutagenic to TA100. Physicochemical parameters of these compounds including oxidation potentials, the energy difference between the lowest unoccupied molecular orbital and the highest occupied molecular orbital, ionization potentials, dipole moment, relative partition coefficient, and basicity did not correlate with their bacterial mutagenic activities. C1 Univ Memphis, Dept Microbiol & Mol Sci, Memphis, TN 38152 USA. Univ Memphis, Dept Chem, Memphis, TN 38152 USA. Auburn Univ, Dept Nutr & Food Sci, Auburn, AL 36849 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chung, KT (reprint author), Univ Memphis, Dept Microbiol & Mol Sci, Memphis, TN 38152 USA. NR 40 TC 35 Z9 38 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD AUG PY 2000 VL 56 IS 2 BP 351 EP 356 DI 10.1093/toxsci/56.2.351 PG 6 WC Toxicology SC Toxicology GA 343GP UT WOS:000088693600015 PM 10910993 ER PT J AU Lay, JO AF Lay, JO TI MALDI-TOF mass spectrometry and bacterial taxonomy SO TRAC-TRENDS IN ANALYTICAL CHEMISTRY LA English DT Article DE bacterium; chemotaxonomy; proteins; biomarker; matrix-assisted laser desorption ionization; time of flight; mass spectrometry ID FAST-ATOM-BOMBARDMENT; ASSISTED LASER DESORPTION/IONIZATION; WHOLE CELLS; RAPID IDENTIFICATION; PROTEINS AB In the few years since the first reports that characteristic proteins could be desorbed directly from bacterial cells using MALDI, the use of mass spectrometry to investigate bacteria, bacterial proteins and the bacterial proteome has advanced rapidly. The effects of experimental parameters are understood sufficiently that reproducible spectra can be obtained in different laboratories and bacteria can be characterized by genus, species or strain. Specific biomarker proteins have been identified and the feasibility of using reference spectra, reference cultures or protein databases for taxonomic identification of bacteria by MALDI-MS has been demonstrated. (C) 2000 Elsevier Science B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Lay, JO (reprint author), US FDA, Natl Ctr Toxicol Res, Div Chem, 2900 NCTR Rd, Jefferson, AR 72079 USA. RI Lay, Jackson/G-1007-2011 OI Lay, Jackson/0000-0003-3789-2527 NR 23 TC 72 Z9 78 U1 1 U2 5 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-9936 J9 TRAC-TREND ANAL CHEM JI Trac-Trends Anal. Chem. PD AUG PY 2000 VL 19 IS 8 BP 507 EP 516 DI 10.1016/S0165-9936(00)00027-3 PG 10 WC Chemistry, Analytical SC Chemistry GA 340JH UT WOS:000088529000010 ER PT J AU Henderson, IR Nataro, JP Kaper, JB Meyer, TF Farrand, SK Burns, DL Finlay, BB St Gene, JW AF Henderson, IR Nataro, JP Kaper, JB Meyer, TF Farrand, SK Burns, DL Finlay, BB St Gene, JW TI Renaming protein secretion in the Gram-negative bacteria SO TRENDS IN MICROBIOLOGY LA English DT Letter ID OUTER-MEMBRANE PROTEIN; ESCHERICHIA-COLI; IV SECRETION C1 Queens Univ Belfast, Sch Med, Dept Microbiol & Immunobiol, Belfast BT12 6BN, Antrim, North Ireland. Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. Max Planck Inst Infekt Biol, Mol Biol Abt, D-10117 Berlin, Germany. Univ Illinois, Dept Microbiol, Urbana, IL 61801 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ British Columbia, Biotechnol Lab, Vancouver, BC V6T 1Z3, Canada. Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. RP Henderson, IR (reprint author), Queens Univ Belfast, Sch Med, Dept Microbiol & Immunobiol, Grosvenor Rd, Belfast BT12 6BN, Antrim, North Ireland. RI Meyer, Thomas F./J-2485-2013 OI Meyer, Thomas F./0000-0002-6120-8679 NR 11 TC 36 Z9 38 U1 0 U2 5 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD AUG PY 2000 VL 8 IS 8 BP 352 EP 352 DI 10.1016/S0966-842X(00)01814-X PG 1 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 346PP UT WOS:000088880500007 PM 11041650 ER PT J AU Purucker, M Malozowski, S AF Purucker, M Malozowski, S TI Inhaled corticosteroids and bone density SO LANCET LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Div Pulm & Allergy Drug Prod, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Div Metab & Endocrine Drug Prod, Rockville, MD 20857 USA. RP Purucker, M (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Pulm & Allergy Drug Prod, Rockville, MD 20857 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUL 29 PY 2000 VL 356 IS 9227 BP 427 EP 427 DI 10.1016/S0140-6736(05)73571-6 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 339NZ UT WOS:000088486000044 PM 10972393 ER PT J AU Johnson, JR Robinson, BL Ali, SF Binienda, Z AF Johnson, JR Robinson, BL Ali, SF Binienda, Z TI Dopamine toxicity following long term exposure to low doses of 3-nitropropionic acid (3-NPA) in rats SO TOXICOLOGY LETTERS LA English DT Article DE 3-nitropropionic acid (3-NPA); dopamine; neurotoxicity; oxidative stress; brain; rat ID BLOOD-BRAIN-BARRIER; ENERGY-LEVELS; LESIONS; DAMAGE; DYSFUNCTION; STRIATUM; TOXIN AB A toxin produced by legumes of the genus Astragalus and Arthrinium fungi, 3-NPA is a suicide inhibitor of succinate dehydrogenase and causes acute encephalopathy and late onset dystonia. It has been suggested that dopamine (DA) toxicity plays a role in 3-NPA induced brain damage. In order to simulate natural conditions of toxicant intake, adult, male, Sprague-Dawley rats were exposed to 3-NPA weekly for 24-h periods at 10 and 20 mg/40 mi in drinking water. This dosing regimen continued for 3 months with animals from both high and low dose groups sacrificed at the end of each month. Dopamine and its metabolites, 3,4-dihydroxylphenylacetic acid (DOPAC) and homovanillic acid (HVA), were assessed by HPLC-EC in the frontal cortex (FC) and caudate nucleus (CN). Increases of DA. concentration were seen in both low and high dose groups in the CN after 1 and 3 months of dosing and in the FC after 2 months of exposure. An increase in DA turnover was observed in the CN of the high; dose group following 2 months of dosing. Data suggest an activation of the dopaminergic system after long-term, intermittent exposure to 3-NPA. The production of radical oxygen species associated with DA metabolism may contribute to 3-NPA-induced neurotoxicity. (C) 2000 Published by Elsevier Science Ireland Ltd. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Binienda, Z (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 21 TC 17 Z9 18 U1 0 U2 1 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 JUL 27 PY 2000 VL 116 IS 1-2 BP 113 EP 118 DI 10.1016/S0378-4274(00)00214-9 PG 6 WC Toxicology SC Toxicology GA 341XB UT WOS:000088615300013 PM 10906428 ER PT J AU LeClerc, JE Cebula, TA AF LeClerc, JE Cebula, TA TI Pseudomonas survival strategies in cystic fibrosis SO SCIENCE LA English DT Letter C1 US FDA, Mol Biol Branch HFS235, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP LeClerc, JE (reprint author), US FDA, Mol Biol Branch HFS235, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 5 TC 17 Z9 18 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 21 PY 2000 VL 289 IS 5478 BP 391 EP 392 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 336ME UT WOS:000088305500018 PM 10939947 ER PT J AU O'Bryan, E AF O'Bryan, E TI Add harmony to your system SO EDN LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP O'Bryan, E (reprint author), US FDA, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU CAHNERS-DENVER PUBLISHING CO PI OAK BROOK PA 2000 CLEARWATER DR, OAK BROOK, IL 60523-8809 USA SN 0012-7515 J9 EDN JI EDN PD JUL 20 PY 2000 VL 45 IS 15 BP 148 EP + PG 2 WC Engineering, Electrical & Electronic SC Engineering GA 334YK UT WOS:000088213900032 ER PT J AU Buchanan, RL Smith, JL Long, W AF Buchanan, RL Smith, JL Long, W TI Microbial risk assessment: dose-response relations and risk characterization SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article; Proceedings Paper CT 17th International Conference of the International Committee on food Microbiology and Hygiene - Food Micro 99 CY SEP 13-17, 1999 CL VELDHOVEN, NETHERLANDS SP Int Life Sci Inst, Europe DE dose-response; foodborne pathogens; mathematical models; pathogenicity ID LISTERIA-MONOCYTOGENES; EXPRESSION; FOOD; AGE AB Characterizations of the risks associated with foodborne pathogens are dependent on the availability of information on the population's Exposure to the biological agents. However, by itself, exposure data are insufficient to assess the public health impact of pathogenic microorganisms. This requires the availability of effective dose-response models. Successful development of models that describe dose-response relations for enteric pathogens is dependent on a sound understanding of the mechanisms of pathogenicity associated with individual pathogens. This includes knowledge of how the various pathogen, host, and food matrix factors influence pathogenicity. Currently, a group of sigmoidal mathematical equations are used to empirically describe dose-response relations. While these have proven to be highly useful, advances in microbial food safety risk assessment will likely require the development of mechanistic models that more effectively consider the range of factors that influence the frequency and severity of foodborne infections in a population. (C) 2000 Elsevier Science B.V. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. USDA ARS, Eastern Reg Res Ctr, Wyndmoor, PA 19038 USA. RP Buchanan, RL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 26 TC 75 Z9 77 U1 0 U2 20 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 JUL 15 PY 2000 VL 58 IS 3 BP 159 EP 172 DI 10.1016/S0168-1605(00)00270-1 PG 14 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 338GU UT WOS:000088411400004 PM 10939266 ER PT J AU Fitzsimmons, SP Clark, KJ Mostowski, HS Shapiro, MA AF Fitzsimmons, SP Clark, KJ Mostowski, HS Shapiro, MA TI Underutilization of the V kappa 10C gene in the B cell repertoire is due to the loss of productive VJ rearrangements during B cell development SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNOGLOBULIN-KAPPA LOCUS; L-CHAIN; BINDING ACTIVITY; MOUSE; SELECTION; RECEPTOR; TRANSCRIPTION; ANTIBODIES; RECOMBINATION; TOLERANCE AB The V kappa 10 family of murine light chain Ig genes is composed of three members, two of which (V kappa 10A and V kappa 10B) are well used. V kappa 10C, the third member of this family, is not detected in any expressed Abs, Our previous work showed that V kappa 10C is structurally functional and can recombine, but mRNA levels in spleen were extremely low relative to thole of V kappa 10A and V kappa 10B, Furthermore, while the V kappa 10C promoter was efficient in Il cells, it was shown to work inefficiently in pre-B cell lines. Here, we extend our analysis of the V kappa 10 family and examine V kappa 10 gene accessibility, their representation in V kappa cDNA phage libraries, and the frequency and nature of rearrangements during different stages of B cell development. We demonstrate that V kappa 10C is under-represented in V kappa cDNA libraries, but that the frequency of its sterile transcripts in pre-B cells surpasses both V kappa 10A and V kappa 10B, indicating that the gene is as accessible as V kappa 10A and V kappa 10B to the recombination machinery. We also demonstrate that V kappa 10C recombines at a frequency equal to that of V kappa 10A in pre-B cells and has a normal nonproductive to productive recombination ratio. As B cells develop, however, both the frequency of V kappa 10C rearrangements and the presence of productive rearrangements decline, indicating that these cells are in some fashion being eliminated. C1 US FDA, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Fitzsimmons, SP (reprint author), US FDA, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, 1401 Rockville Pike,Bldg 29B,Room 5E12, Rockville, MD 20852 USA. NR 44 TC 4 Z9 4 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 JUL 15 PY 2000 VL 165 IS 2 BP 852 EP 859 PG 8 WC Immunology SC Immunology GA 332QU UT WOS:000088085600030 PM 10878359 ER PT J AU Knudson, JF Kortepeter, C Dubitsky, GM Ahmad, SR Chen, M AF Knudson, JF Kortepeter, C Dubitsky, GM Ahmad, SR Chen, M TI Antipsychotic drugs and venous thromboembolism SO LANCET LA English DT Letter C1 US FDA, Div Drug Prod HFD 120, Rockville, MD 20852 USA. US FDA, OPDRA HFD 430, Rockville, MD 20852 USA. RP Knudson, JF (reprint author), US FDA, Div Drug Prod HFD 120, Rockville, MD 20852 USA. NR 1 TC 32 Z9 33 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUL 15 PY 2000 VL 356 IS 9225 BP 252 EP 253 DI 10.1016/S0140-6736(05)74504-9 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 334GQ UT WOS:000088179100052 PM 10963226 ER PT J AU Wang, T Fontenot, RD Soni, MG Bucci, TJ Mehendale, HM AF Wang, T Fontenot, RD Soni, MG Bucci, TJ Mehendale, HM TI Enhanced hepatotoxicity and toxic outcome of thioacetamide in streptozotocin-induced diabetic rats SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Society-of-Toxicology CY MAR 01-05, 1998 CL SEATTLE, WASHINGTON SP Soc Toxicol DE hepatotoxicity; diabetes; bioactivation; tissue repair; DNA synthesis ID LIVER-REGENERATION; HEPATIC REGENERATION; HEPATOTROPHIC FACTORS; PARTIAL-HEPATECTOMY; TISSUE-REPAIR; DNA-SYNTHESIS; INSULIN; INJURY; NECROSIS; EXPRESSION AB Diabetes is known to potentiate thioacetamide (TA)-induced liver injury via enhanced bioactivation. Little attention has been given to the role of compensatory tissue repair on ultimate outcome of hepatic injury in diabetes. The objective of this study was to investigate the effect of diabetes on TA-induced liver injury and lethality and to investigate the underlying mechanisms. We hypothesized that hepatotoxicity of TA in diabetic rats would increase due to enhanced bioactivation-mediated liver injury and also due to compromised compensatory tissue repair, consequently making a nonlethal dose of TA lethal. On day 0, male Sprague-Dawley rats (250-300 g) were injected with streptozotocin (STZ, 60 mg/kg ip) to induce diabetes. On day 10 the STZ-induced diabetic rats and the nondiabetic rats received a single dose of TA (300 mg/kg ip). This normally nonlethal dose of TA caused 90% mortality in the STZ-induced diabetic rats. At various times (0-60 h) after TA administration, liver injury was assessed by plasma alanine aminotransferase (ALT), sorbitol dehydrogenase (SDH), and liver histopathology. Liver function was evaluated by plasma bilirubin. Cell proliferation and tissue repair were evaluated by [H-3]thymidine (H-3-T) incorporation and proliferating cell nuclear antigen (PCNA) assays. In the nondiabetic rat, liver necrosis peaked at 24 h and declined thereafter toward normal by 60 h. In the STZ-induced diabetic rat, however, liver necrosis was significantly increased from 12 h onward and progressed, culminating in liver failure and death. Liver tissue repair studies showed that, in the liver of nondiabetic rats, S-phase DNA synthesis was increased at 36 h and peaked at 48 h following TA administration. However, DNA synthesis was approximately 50% inhibited in the liver of diabetic rats. PCNA study showed a corresponding decrease of cell-cycle progression, indicating that the compensatory tissue repair was sluggish in the diabetic rats. Further investigation of tissue repair by employing equitoxic doses (300 mg TA/kg in the non-diabetic rats; 30 mg TA/kg in the diabetic rats) revealed that, despite equal injury up to 24 h following injection, the tissue repair response in the diabetic rats was much delayed. The compromised tissue repair prolonged liver injury in the diabetic rats. These studies suggest that the increased TA hepatotoxicity in the diabetic rat is due to combined effects of increased bioactivation-mediated liver injury of TA and compromised compensatory tissue repair. (C) 2000 Academic Press. C1 Univ Louisiana, Coll Pharm, Dept 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, Dept Toxicol, Monroe, LA 71209 USA. FU NIEHS NIH HHS [ES-08604, ES-9870] NR 31 TC 42 Z9 42 U1 0 U2 0 PU ACADEMIC PRESS INC 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 15 PY 2000 VL 166 IS 2 BP 92 EP 100 DI 10.1006/taap.2000.8952 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 340GX UT WOS:000088525700003 PM 10896850 ER PT J AU Carson, MC AF Carson, MC TI Ion-pair solid-phase extraction SO JOURNAL OF CHROMATOGRAPHY A LA English DT Review DE reviews; ion-pair solid-phase extraction; solid-phase extraction ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SUPERCRITICAL-FLUID CHROMATOGRAPHY; MASS-SPECTROMETRY; POSTCOLUMN DERIVATIZATION; SAMPLE PREPARATION; QUANTITATIVE-DETERMINATION; FLUORESCENCE DETECTION; ULTRAVIOLET DETECTION; PHENOLIC-COMPOUNDS; BIOGENIC-AMINES AB Solid-phase extraction (SPE) is a technique widely employed by analytical chemists. SPE cartridges are available in a wide variety of formats containing media with diverse chemistries. This paper will review ion-pair SPE, one of the less frequently applied, and presumably less well-known techniques. Advantages of this technique over more conventional reversed-phase or ion-exchange SPE include selectivity, compatibility with rapid evaporative concentration, and potential application to multiclass multiresidue analysis. (C) 2000 Published by Elsevier Science B.V. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Carson, MC (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 48 TC 24 Z9 25 U1 1 U2 22 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 JUL 14 PY 2000 VL 885 IS 1-2 BP 343 EP 350 DI 10.1016/S0021-9673(00)00471-4 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 334NF UT WOS:000088192000019 PM 10941681 ER PT J AU Plakas, SM El Said, KR Musser, SM AF Plakas, SM El Said, KR Musser, SM TI Pharmacokinetics, tissue distribution, and metabolism of flumequine in channel catfish (Ictalurus punctatus) SO AQUACULTURE LA English DT Article DE flumequine; pharmacokinetics; metabolism; channel catfish ID SALMON SALMO-SALAR; HALIBUT HIPPOGLOSSUS-HIPPOGLOSSUS; EEL ANGUILLA-ANGUILLA; ATLANTIC SALMON; OXOLINIC ACID; ANTIBACTERIAL AGENTS; DISPOSITION; QUINOLONES; SEAWATER; FISH AB The pharmacokinetics and metabolism of the fluoroquinolone drug flumequine (FLU) were examined after intravascular (1 mg/kg) or oral (5 mg/kg) dosing in channel catfish. Parent FLU concentrations in plasma declined slowly after intravascular dosing, with a half-life of 25 h. After oral dosing, FLU concentrations in plasma were highest (3.1 mu g/ml) at 14 h after dosing; absorption and elimination half-lives were 4.9 and 22 h, respectively. The oral bioavailability of FLU was 44%, based on normalized plasma data. Plasma protein binding of parent FLU was extensive, but saturable (88%-55% bound at 0.125-8.0 mu g/ml). After oral dosing with C-14-labeled FLU, radioactive residues were evenly distributed among the major tissues analyzed, with peak concentrations occurring at 12-24 h. Residue concentrations were highest in liver (6.2 mu g/g) and lowest in muscle (1.8 mu g/g) at 24 h. Only parent FLU was found in muscle and was eliminated with a half-life of 26 h. FLU and its metabolites were recovered in urine and bile. Residues in bile consisted almost entirely of a taurine conjugate of FLU. In urine, the taurine conjugate and hydroxy-FLU metabolites were found, in addition to the parent compound. Published by Elsevier Science B.V. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. US FDA, Instrumentat & Biophys Branch, Washington, DC 20204 USA. RP Plakas, SM (reprint author), US FDA, Gulf Coast Seafood Lab, POB 158, Dauphin Island, AL 36528 USA. NR 29 TC 22 Z9 28 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0044-8486 J9 AQUACULTURE JI Aquaculture PD JUL 5 PY 2000 VL 187 IS 1-2 BP 1 EP 14 DI 10.1016/S0044-8486(00)00303-3 PG 14 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA 318JQ UT WOS:000087280900001 ER PT J AU Vela, NP Caruso, JA AF Vela, NP Caruso, JA TI Element selective detection for supercritical-fluid chromatography SO JOURNAL OF BIOCHEMICAL AND BIOPHYSICAL METHODS LA English DT Review DE supercritical-fluid chromatography; inductively coupled plasma-atomic emission spectrometry; inductively coupled plasma-mass spectrometry; speciation; organometallics ID PLASMA-MASS-SPECTROMETRY; ATOMIC EMISSION; MULTIELEMENT DETECTION; ENVIRONMENTAL-SAMPLES; ORGANOTIN COMPOUNDS; FLAME IONIZATION; ICP-MS; SPECIATION AB This manuscript describes the use of Supercritical-Fluid Chromatography (SFC) with plasma spectrometric detection for the analysis of oganometallics. An introduction on the principles and characteristics of Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES) and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) is included, along with a discussion about requirements for coupling SFC to plasma detection and the different approaches for interfacing SFC to ICP. The last part of this review paper provides a comprehensive description of SFC-ICP applications for the analysis of oganometallics containing iron, silicon, tin, chromium, arsenic, lead, mercury and antimony. (C) 2000 Published by Elsevier Science B.V. All rights reserved. C1 Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Caruso, JA (reprint author), Univ Cincinnati, Dept Chem, Room 137,McMicken Hall, Cincinnati, OH 45221 USA. NR 33 TC 12 Z9 15 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-022X J9 J BIOCHEM BIOPH METH JI J. Biochem. Biophys. Methods PD JUL 5 PY 2000 VL 43 IS 1-3 BP 45 EP 58 DI 10.1016/S0165-022X(00)00091-9 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 333YM UT WOS:000088158400004 PM 10869666 ER PT J AU Mandelson, MT Oestreicher, N Porter, PL White, D Finder, CA Taplin, SH White, E AF Mandelson, MT Oestreicher, N Porter, PL White, D Finder, CA Taplin, SH White, E TI Breast density as a predictor of mammographic detection: Comparison of interval- and screen-detected cancers SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PARENCHYMAL PATTERNS; REPLACEMENT THERAPY; RISK-FACTORS; AGE; CARCINOMAS; PROGRAM; TRIAL; CLASSIFICATION; SPECIFICITY; SENSITIVITY AB Background: Screening mammography is the best method to reduce mortality from breast cancer, yet some breast cancers cannot be detected by mammography, Cancers diagnosed after a negative mammogram are known as interval cancers. This study investigated whether mammographic breast density is related to the risk of interval cancer. Methods: Subjects were selected from women participating in mammographic screening from 1988 through 1993 in a large health maintenance organization based in Seattle, WA, Women were eligible for the study if they had been diagnosed with a first primary invasive breast cancer within 24 months of a screening mammogram and before a subsequent one. Interval cancer case subjects (n = 149) were women whose breast cancer occurred after a negative or benign mammographic assessment. Screen-detected control subjects (n = 388) were diagnosed after a positive screening mammogram, One radiologist, who was blinded to cancer status, assessed breast density by use of the American College of Radiology Breast Imaging Reporting and Data System. Results: Mammographic sensitivity (i.e., the ability of mammography to detect a cancer) was 80% among women with predominantly fatty breasts but just 30% in women with extremely dense breasts. The odds ratio (OR) for interval cancer among women with extremely dense breasts was 6.14 (95% confidence interval [CI] = 1.95-19.4), compared with women with extremely fatty breasts, after adjustment for age at index mammogram, menopausal status, use of hormone replacement therapy, and body mass index. When only those interval cancer cases confirmed by retrospective review of index mammograms were considered, the OR increased to 9.47 (95% CI = 2.78-32.3), Conclusion: Mammographic breast density appears to be a major risk factor for interval cancer. C1 Grp Hlth Cooperat, Ctr Hlth Studies, Seattle, WA 98101 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Canc Prevent Res, Seattle, WA 98195 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Program Canc Biol, Div Human Biol, Seattle, WA 98195 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Program Canc Biol, Div Publ Hlth Sci, Seattle, WA 98195 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. US FDA, Div Mammog Qual, Rockville, MD 20857 USA. US FDA, Radiat Programs, Rockville, MD 20857 USA. Univ Washington, Dept Family Med, Seattle, WA 98195 USA. RP Mandelson, MT (reprint author), Grp Hlth Cooperat, Ctr Hlth Studies, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. FU NCI NIH HHS [K07CA71869, U01CA63731] NR 39 TC 437 Z9 450 U1 1 U2 15 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 5 PY 2000 VL 92 IS 13 BP 1081 EP 1087 DI 10.1093/jnci/92.13.1081 PG 7 WC Oncology SC Oncology GA 330ZW UT WOS:000087993000014 PM 10880551 ER PT J AU Yui, K Ali, SF AF Yui, K Ali, SF TI Collegium Internationale Neuro-Psychopharmacologium (CINP) Symposium: Neurobiological base of stimulant-induced sensitization: from animals to man - Preface: Recent advances of neurobiological basis of stimulant-induced sensitization SO ADDICTION BIOLOGY LA English DT Editorial Material ID MEDIAL PREFRONTAL CORTEX; VENTRAL TEGMENTAL AREA; BEHAVIORAL SENSITIZATION; NUCLEUS-ACCUMBENS; COCAINE SENSITIZATION; AMPHETAMINE; DOPAMINE; RAT; EXPRESSION; STRIATUM C1 US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Yui, K (reprint author), Takasago 3-16-34-31, Urawa, Saitama 3360011, Japan. NR 30 TC 0 Z9 0 U1 0 U2 0 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD JUL PY 2000 VL 5 IS 3 BP 321 EP 324 DI 10.1111/j.1369-1600.2000.tb00198.x PG 4 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 339TB UT WOS:000088493000010 PM 20575848 ER PT J AU Ali, SF Haung, P Itzhak, Y AF Ali, SF Haung, P Itzhak, Y TI Role of peroxynitrite in methamphetamine-induced dopaminergic neurotoxicity and sensitization in mice SO ADDICTION BIOLOGY LA English DT Article; Proceedings Paper CT XXI Collegium-Internationale-Neuropsycho-Pharmacologium Meeting CY JUL, 1998 CL GLASGOW, SCOTLAND SP Collegium Int Neuropsycho Pharmacologium ID NITRIC-OXIDE SYNTHASE; INDUCED BEHAVIORAL SENSITIZATION; HEAT-SHOCK-PROTEIN; SEROTONERGIC NEUROTOXICITY; ENVIRONMENTAL-TEMPERATURE; PHARMACOLOGICAL AGENTS; INDUCED HYPERTHERMIA; LIPID-PEROXIDATION; STRIATAL DOPAMINE; DEFICIENT MICE AB Methamphetamine (METH)-induced dopaminergic neurotoxicity is thought to be associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Recently, we have reported that copper/zinc(CuZn)-superoxide dismutase transgenic mice are resistant to METH-induced neurotoxicity. In the present study, we examined the role of the neuronal nitric oxide synthase (nNOS), susceptibility of nNOS knockout (KO) mice and sensitization to psychostimulants after neurotoxic doses of METH. Male Swiss Webster mice were treated with or without 7-nitroindazole (7-NI) along with METH (5 mg/kg,ip,q 3 h x 3) and were sacrificed 72 h after the last METH injection. Dopamine (DA) and dopamine transporter (DAT) binding sites were determined in striatum from saline and METH-treated animals. 7-NI completely protected against the depletion of DA, and DAT in striatum. In follow-up experiments nNOS KO mice along with appropriate control (C57BL/6N, SV129 and B6FSV129) mice were treated with METH (5 mg/kg,ip, q 3 h x 3) and were sacrificed 72 h after dosing. This schedule of METH administrations resulted in only 10-20% decrease in tissue content of DA and no apparent change in the number of DAT binding sites in nNOS KO mice. However, this regime of METH resulted in a significant decrease in the content of DA as well as DAT binding sires in the wild-type animals. Pre-exposure to single or multiple doses of METH resulted in a marked locomotion sensitization in response to METH. However, the nNOS KO mice show no sensitization in response to METH after single or multiple injections of METH. Therefore, these studies strongly suggest the role of peroxynitrite, nNOS and DA system in METH-induced neurotoxicity and behavioral sensitization. C1 US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charleston, MA USA. Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL USA. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, HFT-132, Jefferson, AR 72079 USA. NR 62 TC 3 Z9 3 U1 0 U2 0 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD JUL PY 2000 VL 5 IS 3 BP 331 EP 341 DI 10.1111/j.1369-1600.2000.tb00200.x PG 11 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 339TB UT WOS:000088493000012 PM 20575850 ER PT J AU Scott, WL Kondratovich, M Blum, D AF Scott, WL Kondratovich, M Blum, D TI Central venous catheter tip placement and catheter occlusion SO AMERICAN JOURNAL OF SURGERY LA English DT Letter ID SUPERIOR VENA-CAVA; CARDIAC-TAMPONADE; PATIENT C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Scott, WL (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 14 TC 1 Z9 1 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD JUL PY 2000 VL 180 IS 1 BP 78 EP 79 DI 10.1016/S0002-9610(00)00483-9 PG 2 WC Surgery SC Surgery GA 362AU UT WOS:000089757100019 PM 11184784 ER PT J AU Heller, DN AF Heller, DN TI Liquid chromatography/mass spectrometry for timely response in regulatory analyses: Identification of pentobarbital in dog food SO ANALYTICAL CHEMISTRY LA English DT Article ID MASS-SPECTROMETRY; ANTIBIOTICS; IONIZATION; RESIDUES AB A limited liquid chromatography/mass spectrometry (LC/MS) data set was acquired under conditions which called for timely response without benefit of a fully developed method. Quality assurance elements verified that an LC/MS procedure developed in a short time was sufficiently under control to meet its purpose. LC/MS was used to rule out a potential problem with a gas chromatography (GC)/MS method that had been developed for regulatory purposes. The LC/MS data set showed that signals identified by GC/MS as diagnostic of pentobarbital (PB) were not artifacts of derivatization or GC analysis, Samples of dry dog food identified by GC/MS as containing PB were also shown by LC/MS to contain PB. The LC/MS method would not he recommended as a substitute for GC/MS, primarily because of poorer sensitivity. Although the data set is limited, and justifiably represents only the starting point for conventional method development, the purpose at hand was served adequately. This work demonstrates the utility of LC/MS for rapid regulatory response, provided there is a framework of quality assurance checks. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Heller, DN (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 11 TC 10 Z9 10 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JUL 1 PY 2000 VL 72 IS 13 BP 2711 EP 2716 DI 10.1021/ac9913053 PG 6 WC Chemistry, Analytical SC Chemistry GA 329YW UT WOS:000087936900020 PM 10905297 ER PT J AU Ilev, IK Waynant, RW Bonaguidi, MA AF Ilev, IK Waynant, RW Bonaguidi, MA TI Attenuation measurement of infrared optical fibers by use of a hollow-taper-based coupling method SO APPLIED OPTICS LA English DT Article ID GLASS WAVE-GUIDES; DELIVERY AB An alternative method for attenuation measurement of infrared (IR) fibers is described. The method includes a simple technique for direct laser-to-fiber coupling with an uncoated glass hollow taper. The operating principle of the hollow taper is based on the grazing-incidence effect of light reflection. The hollow taper forms a smooth Gaussian-shaped profile of the output laser emission and provides the proper conditions for equilibrium-mode distribution of optical power within the test IR fibers. The experimental hollow-taper-based coupling method is used for measurement of attenuation and bending losses of various kinds of IR fiber, including solid-core (fluoride, chalcogenide, and germanium-doped) and hollow fibers. (C) 2000 Optical Society of America. OCIS codes: 060.2340, 060.2310, 060.2280. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Univ Wisconsin, Dept Biomed Engn, Milwaukee, WI 53201 USA. RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-134, Rockville, MD 20857 USA. EM ilko@eob.cdrh.fda.gov NR 16 TC 6 Z9 6 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD JUL 1 PY 2000 VL 39 IS 19 BP 3192 EP 3196 DI 10.1364/AO.39.003192 PG 5 WC Optics SC Optics GA 331YE UT WOS:000088045600002 PM 18349883 ER PT J AU Shacter, E Williams, JA Hinson, RM Senturker, S Lee, Y AF Shacter, E Williams, JA Hinson, RM Senturker, S Lee, Y TI Oxidative stress interferes with cancer chemotherapy: inhibition of lymphoma cell apoptosis and phagocytosis SO BLOOD LA English DT Article ID HYDROGEN-PEROXIDE; BREAST-CANCER; DNA; NECROSIS; DAMAGE; RECOGNITION; TISSUE; AGENTS AB Many antineoplastic drugs kill tumor cells by inducing apoptosis. This highly controlled mechanism of cell death is thought to be physiologically advantageous because apoptotic cells are removed by phagocytosis before they lose their permeability barrier, thus preventing induction of an inflammatory response to the dying cells. In contrast, necrotic cells lyse and release their contents into the extracellular space, thus inducing inflammation. In this report, we examine the effects of oxidative stress on chemotherapy-induced cell killing. We find that H2O2 inhibits the ability of 4 different chemotherapy drugs (VP-16, doxorubicin, cisplatin, and AraC) to induce apoptosis in human Burkitt lymphoma cells, H2O2 shifts the form of cell death from apoptosis to pyknosis/necrosis, which occurs after a significant delay compared with chemotherapy-induced apoptosis. It can also lower the degree of cell killing by these drugs. These effects of H2O2 can be prevented by the antioxidant agents Desferal, Tempol, and dimethylsulfoxide. Phagocytosis by monocyte-derived macrophages of VP-16-treated lymphoma cells is also inhibited by H2O2. Cells killed with H2O2 (with Or without VP-16) do ultimately undergo phagocytosis, but this occurs only after they have lost their permeability barrier. Thus, membrane-intact apoptotic cells are recognized and phagocytosed by monocyte-derived macrophages, but membrane-intact pyknotic/necrotic cells are not. The results suggest that chemotherapy-induced apoptosis and phagocytosis of cancer cells may be enhanced by including certain antioxidant agents in the treatment protocol. (Blood. 2000;96:307-313) (C) 2000 by The American Society of Hematology. C1 US FDA, Immunol Lab, Div Therapeut Prot, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Shacter, E (reprint author), Bldg 29A,Rm 2A-11,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 33 TC 105 Z9 109 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 2000 VL 96 IS 1 BP 307 EP 313 PG 7 WC Hematology SC Hematology GA 327UX UT WOS:000087813200045 PM 10891466 ER PT J AU Gorski, JP Apone, S Shaffer, KA Batchelder, A Jean, W Williams, JA Shacter, E Eyre, DR AF Gorski, JP Apone, S Shaffer, KA Batchelder, A Jean, W Williams, JA Shacter, E Eyre, DR TI Hypercalcemia during the osteogenic phase after rat marrow ablation coincides with increased bone resorption assessed by the NTx marker SO BONE LA English DT Article DE crosslinked alpha(2)(I) N-telopeptide; osteoclasts; bone resorption; hypercalcemia; fracture healing ID OSTEOCLAST-LIKE CELLS; TRANSFORMING GROWTH-FACTOR; LINKED N-TELOPEPTIDES; CROSS-LINKS; I COLLAGEN; BIOCHEMICAL MARKERS; EXCRETION; CALCIUM; DIFFERENTIATION; TURNOVER AB Marrow ablation is a model of bone turnover in which the excavated tibial intramedullary cavity is rapidly and reproducibly filled by osteoblasts with new woven bone (days 6-8), which is then rapidly resorbed by osteoclasts (days 10-15), We showed previously (Magnuson et al,, 1997) that marrow ablation induces a-dramatic hypercalcemia and hypercalciuria in rats that unexpectedly peaked at the time of maximal osteogenesis and continued throughout the subsequent resorption phase, Based upon the amount of calcium mobilized and a peak of urinary hydroxyproline, we suggested that the hypercalcemia and hypercalciuria were due to increased systemic osteoclastic bone resorption induced by marrow ablation, We now apply a new enzyme-linked immunosorbent assay for rodent alpha(2)(I) N-telopeptide (NTx), a marker of bone resorption, to the marrow ablation model to demonstrate that excretion of NTx parallels that of calcium release in the operated control group, Specifically, maximal NTx/ creatinine excretion coincides with the onset of hypercalcemia on days 7-8, A peak of NTx was also observed in methylprednisolone- and deflazacort-treated ablated animals. Analyses for urinary free deoxypyridinoline crosslink failed to detect a significant ablation-induced change in excretion. Interleukin 6 activity was increased in all operated control and glucocorticoid-treated groups after marrow ablation, whereas serum parathyroid hormone remained at presurgical levels in operated controls throughout. the 15-day study period. The NTx results confirm that bilateral tibial marrow ablation induces a burst of extratibial bone resorption and hypercalcemia 7-8 days later, We have estimated that the osteogenic phase of the ablation model deposits 40 mg of calcium as hydroxyapatite crystals within the intramedullary cavity on days 6-8; this represents 33%-50% of the total blood calcium content of a young rat. We hypothesize that the size and rapidity of this demand for ionized calcium is met through an extratibial bone resorption pathway of osteoclast formation and activation that anticipates and fulfills this need, and that is initiated at the time of marrow ablation, (Bone 27:103-110; 2000) (C) 2000 by Elsevier Science Inc. All rights reserved. C1 Univ Missouri, Sch Biol Sci, Div Mol Biol & Biochem, Kansas City, MO 64110 USA. Ostex Int Inc, Seattle, WA USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Univ Washington, Sch Med, Dept Orthoped, Seattle, WA USA. RP Gorski, JP (reprint author), Univ Missouri, Sch Biol Sci, Div Mol Biol & Biochem, Room B109,BSB Bldg,5007 Rockhill Rd, Kansas City, MO 64110 USA. FU NIAMS NIH HHS [R37 AR037318, R01 AR036794]; NIDCR NIH HHS [DE-11197] NR 46 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 8756-3282 J9 BONE JI Bone PD JUL PY 2000 VL 27 IS 1 BP 103 EP 110 DI 10.1016/S8756-3282(00)00295-7 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337TF UT WOS:000088377200015 PM 10865216 ER PT J AU Yoon, S Hirata, RDC Nguyen, NY Curi, R Russo, M Hirata, MH AF Yoon, S Hirata, RDC Nguyen, NY Curi, R Russo, M Hirata, MH TI Expression and biological activity of two recombinant polypeptides related to subunit 1 of the interferon-alpha receptor SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article DE interferon alpha; interferon-alpha receptor; inhibitor of interferon-alpha; autoimmune diseases; graft-versus-host disease; recombinant protein ID BONE-MARROW TRANSPLANTATION; VERSUS-HOST DISEASE; BETA RECEPTOR; IFN-ALPHA; THERAPY; BINDING; ANTIBODIES; OMEGA; ASSAY; FORM AB Abnormal production of interferon alpha (IFN-alpha) has been found in certain autoimmune diseases and can be also observed after prolonged therapy with IFN-alpha, IFN-alpha can contribute to the pathogenesis of allograft rejection in bone marrow transplants. Therefore, the development of IFN-alpha inhibitors as a soluble receptor protein may be valuable for the therapeutic control of these diseases. We have expressed two polypeptides encoding amino acids 93-260 (P1) and 261-410 (P2) of the extracellular domain of subunit 1 of the interferon-alpha receptor (IFNAR 1-EC) in E. coli. The activities of the recombinant polypeptides and of their respective antibodies were evaluated using antiproliferative and antiviral assays. Expression of P1 and P2 polypeptides was achieved by transformation of cloned plasmid pRSET A into E. coli BL21(DE3)pLysS and by IPTG induction. P1 and P2 were purified by serial sonication steps and by gel filtration chromatography with 8 M urea and refolded by dialysis. Under reducing SDS-PAGE conditions, the molecular weight of P1 and P2 was 22 and 17 kDa, respectively, Polyclonal anti-P1 and anti-P2 antibodies were produced in mice. Pi and P2 and their respective polyclonal antibodies were able to block the antiproliferative activity of 6.25 nM IFN-alpha beta on Daudi cells, but did not block IFN-alpha beta activity at higher concentrations (>6.25 nM). On the other hand, the polypeptides and their respective antibodies did not inhibit the antiviral activity of IFN-alpha beta on Hep 2/c cells challenged with encephalomyocarditis virus. C1 Univ Sao Paulo, Dept Anal Clin & Toxicol, Fac Ciencias Farmaceut, BR-05508900 Sao Paulo, Brazil. US FDA, Fac Biotechnol Resources, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Univ Sao Paulo, Inst Ciencias Biomed, Sao Paulo, Brazil. RP Yoon, S (reprint author), Univ Sao Paulo, Dept Anal Clin & Toxicol, Fac Ciencias Farmaceut, Av Lineau Prestes,580,Bloco 17, BR-05508900 Sao Paulo, Brazil. RI Hirata, Rosario/A-7284-2011; Russo, Momtchilo/D-8614-2012; Hirata, Mario/C-9718-2013 NR 33 TC 1 Z9 1 U1 1 U2 1 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PD JUL PY 2000 VL 33 IS 7 BP 771 EP 778 PG 8 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA 335GQ UT WOS:000088236100007 PM 10881052 ER PT J AU Hansen, LA Sigman, CC Andreola, F Ross, SA Kelloff, GJ De Luca, LM AF Hansen, LA Sigman, CC Andreola, F Ross, SA Kelloff, GJ De Luca, LM TI Retinoids in chemoprevention and differentiation therapy SO CARCINOGENESIS LA English DT Review ID ACUTE PROMYELOCYTIC LEUKEMIA; ACID RECEPTOR-ALPHA; PML-RAR-ALPHA; ARYL-HYDROCARBON RECEPTOR; FEMALE SENCAR MICE; GROWTH-FACTOR-BETA; BREAST-CANCER; VITAMIN-A; MALIGNANT CONVERSION; 9-CIS-RETINOIC ACID AB Retinoids are essential for the maintenance of epithelial differentiation. As such, they play a fundamental role in chemoprevention of epithelial carcinogenesis and in differentiation therapy. Physiological retinoic acid is obtained through two oxidation steps from dietary retinol, i.e. retinol-->retinal-->retinoic acid. The latter retinal-->retinoic acid step is irreversible and eventually marks disposal of this essential nutrient, through cytochrome P450-dependent oxidative steps. Mutant mice deficient in aryl hydrocarbon receptor (AHR) accumulate retinyl palmitate, retinol and retinoic acid. This suggests a direct connection between the AHR and retinoid homeostasis. Retinoids control gene expression through the nuclear retinoic acid receptors (RARs) alpha, beta and gamma and 9-cis-retinoic acid receptors alpha, beta and gamma, which bind with high affinity the natural ligands all-trans-retinoic acid and 9-cis-retinoic acid, respectively. Retinoids are effective chemopreventive agents against skin, head and neck, breast, liver and other forms of cancer. Differentiation therapy of acute promyelocytic leukemia (APL) is based on the ability of retinoic acid to induce differentiation of leukemic promyelocytes. Patients with relapsed, retinoid-resistant APL are now being treated with arsenic oxide, which results in apoptosis of the leukemic cells. Interestingly, induction of differentiation in promyelocytes and consequent remission of APL following retinoid therapy depends on expression of a chimeric PML-RAR alpha fusion protein resulting from a t(15;17) chromosomal translocation, This protein functions as a dominant negative against the function of both PML and RARs and its overexpression is able to recreate the phenotypes of the disease in transgenic mice. The development of new more effective and less toxic retinoids, alone or in combination with other drugs, may provide additional avenues for cancer chemoprevention and differentiation therapy. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Chemoprevent Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Food Safety & Appl Nutr, OSN, Washington, DC 20204 USA. RP De Luca, LM (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 115 TC 199 Z9 212 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 2000 VL 21 IS 7 BP 1271 EP 1279 DI 10.1093/carcin/21.7.1271 PG 9 WC Oncology SC Oncology GA 336QD UT WOS:000088313700001 PM 10874003 ER PT J AU King, RS Teitel, CH Kadlubar, FF AF King, RS Teitel, CH Kadlubar, FF TI In vitro bio activation of N-hydroxy-2-amino-alpha-carboline SO CARCINOGENESIS LA English DT Article ID ARYLAMINE N-ACETYLTRANSFERASE; HETEROCYCLIC AMINE CARCINOGENS; METABOLIC-ACTIVATION; COLORECTAL-CANCER; AROMATIC-AMINES; CYTOCHROME P4501A2; ALPHA-CARBOLINES; GAMMA-CARBOLINES; PERIPHERAL LUNG; TRANSGENIC MICE AB 2-Amino-alpha-carboline (A alpha C) is a mutagenic and carcinogenic heterocyclic amine present in foods cooked at high temperature and in cigarette smoke. The mutagenic activity of A alpha C is dependent upon metabolic activation to N-hydroxy-A alpha C (N-OH-A alpha C); however, the metabolism of N-OH-A alpha C has not been studied. We have synthesized 2-nitro-alpha-carboline and N-OH-A alpha C and have examined in vitro bioactivation of N-OH-A alpha C by human and rodent liver cytosolic sulfotransferase(s) and acetyltransferase(s) and by recombinant human N-acetyltransferases, NAT1 and NAT2, The sulfotransferase-dependent bioactivation of N-OH-A alpha C by human liver cytosol exhibited large interindividual variation (0.5-75, n = 14) and was significantly higher than bioactivation of N-hydroxy-2-amino-1-methyl-6- phenylimidazo[4,5-b]pyridine (N-OH-PhIP), Correlation and inhibition studies suggested that the isoform of sulfotransferase primarily responsible for bioactivation of N-OH-A alpha C in human liver cytosol is SULT1A1. O-Acetyltransferase-dependent bioactivation of N-OH-A alpha C by human liver cytosol also exhibited large inter-individual variation (16-192, n = 18). In contrast to other N-hydroxy heterocyclic amines, which are primarily substrates only for NAT2, both NAT1 and NAT2 catalyzed bioactivation of N-OH-A alpha C. The rate of bioactivation of N-OH-A alpha C by both NATL and NAT2 was significantly higher than that for N-OH-PhIP. In rat and mouse liver cytosols, the level of sulfotransferase-dependent bioactivation of N-OH-A alpha C was similar to the level in the high sulfotransferase activity human liver cytosol, The level of O-acetyltransferase-dependent bioactivation of N-OH-A alpha C in rat liver cytosol was also comparable with that in the high acetyltransferase activity human liver cytosol, However, the level of O-acetyltransferase-dependent bioactivation of N-OH-A alpha C in mouse liver cytosol was comparable with that in the low acetyltransferase activity human liver cytosol, In contrast to N-OH-PhIP, bioactivation of N-OH-A alpha C was not inhibited by glutathione S-transferase activity; however, DNA binding of N-acetoxy-A alpha C was inhibited 20% in the presence of GSH. These results suggest that bioactivation of N-OH-A alpha C may be a significant source of DNA damage in human tissues after dietary exposure to A alpha C and that the relative contribution of each pathway to bioactivation or detoxification of N-OH-A alpha C differs significantly from other N-hydroxy heterocyclic or aromatic amines. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Kadlubar, FF (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. RI King, Roberta/A-1749-2010; yang, min/G-3030-2011 OI King, Roberta/0000-0002-3550-4255; NR 53 TC 61 Z9 62 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 2000 VL 21 IS 7 BP 1347 EP 1354 DI 10.1093/carcin/21.7.1347 PG 8 WC Oncology SC Oncology GA 336QD UT WOS:000088313700011 PM 10874013 ER PT J AU Culp, SJ Warbritton, AR Smith, BA Li, EE Beland, FA AF Culp, SJ Warbritton, AR Smith, BA Li, EE Beland, FA TI DNA adduct measurements, cell proliferation and tumor mutation induction in relation to tumor formation in B6C3F1 mice fed coal tar or benzo[a]pyrene SO CARCINOGENESIS LA English DT Article ID MOUSE FORESTOMACH TUMORS; IN-VIVO; SMALL-INTESTINE; RODENT LIVER; LUNG-TUMORS; H-RAS; APOPTOSIS; GENE; 2-ACETYLAMINOFLUORENE; CARCINOGENICITY AB Coal tar is a complex mixture containing hundreds of compounds, at least 30 of which are polycyclic aromatic hydrocarbons, including the carcinogen benzo[a]pyrene (BaP), Although humans are exposed to complex mixtures on a daily basis, the synergistic or individual effects of components within a mixture on the carcinogenic process remain unclear, We have compared DNA adduct formation and cell proliferation in mice fed coal tar or BaP for 4 weeks with tumor formation in a 2 year chronic feeding study. Additionally, we have analyzed tumor DNA for mutations in the K-ras, H-ras and p53 genes, In the forestomach of mice fed either coal tar or BaP an adduct indicative of BaP was detected, with adduct levels increasing in a dose-responsive manner, K-ms mutations were detected in the forestomach tumors, with the incidence being similar in mice fed coal tar or BaP, These results suggest that the BaP within coal tar is associated with forestomach tumor induction in coal tarfed mice. DNA adduct levels in the small intestine were not predictive of tumor incidence in this tissue; instead, the tumors appeared to result from compound-induced cell proliferation at high doses of coal tar. K-rns mutations were detected in lung tumors. Since lung tumors were not increased by BaP, coal tar components other than BaP appear to be responsible for the tumors induced in this tissue. N-ras mutations, primarily occurring at codon 61, were the most common mutation observed in liver tumors induced by coal tar. Since this mutation profile is observed in spontaneous hepatic tumors, components in the coal tar may be promoting the expansion of pre-existing lesions. C1 Natl Ctr Toxicol Res, HFT 110, Jefferson, AR 72079 USA. Pathol Assoc Int, Jefferson, AR 72079 USA. RP Culp, SJ (reprint author), Natl Ctr Toxicol Res, HFT 110, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 39 TC 45 Z9 47 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 2000 VL 21 IS 7 BP 1433 EP 1440 DI 10.1093/carcin/21.7.1433 PG 8 WC Oncology SC Oncology GA 336QD UT WOS:000088313700021 PM 10874023 ER PT J AU Rider, LG Artlett, CM Foster, CB Ahmed, A Neeman, T Chanock, SJ Jimenez, SA Miller, FW AF Rider, LG Artlett, CM Foster, CB Ahmed, A Neeman, T Chanock, SJ Jimenez, SA Miller, FW CA Childhood Myositis Heterogeneity C TI Polymorphisms in the IL-1 receptor antagonist gene VNTR are possible risk factors for juvenile idiopathic inflammatory myopathies SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE IL-1 receptors (genetics); polymorphism; genetic risk factor; myositis; juvenile dermatomyositis ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASES; GRAVES-DISEASE; BOWEL-DISEASE; INTERLEUKIN-1; DERMATOMYOSITIS; ASSOCIATION; SUSCEPTIBILITY; SEVERITY AB Although HLA-DRB1 and -DQA1 alleles have been associated with adult and juvenile idiopathic inflammatory myopathies (JIIM), they only partially account for the genetic risk for these autoimmune disorders. Because IL-1 alpha and IL-1 beta, and the anti-inflammatory competitive inhibitor, IL-1 receptor antagonist (IL-1Ra), have been implicated in the pathogenesis of myositis, we assessed the role of variable number tandem repeat (VNTR) polymorphisms of the IL-1Ra gene (IL-1RN) in the aetiology of JIIM: IL-1RN VNTR polymorphisms were performed on 250 JIIM patients and 471 race-matched controls and were correlated with clinical characteristics. The IL-1RN A1 allele, associated with increased proinflammatory activity, was found to be a risk factor for Caucasians with JIIM (96.0% carriage rate versus 90.2% in race-matched controls, P-corr = 0.037, odds ratio (OR) = 2.5, confidence interval (CI) = 1.1-5.8), but not for African-Americans, in whom the A3 allele was a possible risk factor (7.0% versus 1.1% in race-matched controls, P-corr = 0.07, OR = 6.5, CI = 1.1-40.3). IL-1RN genotypes did not correlate with circulating levels of IL-1Ra, which were higher in patients than in controls. The polymorphic IL-1RN locus could be the first non-MHC genetic risk factor identified for JIIM, and different alleles may confer susceptibility for different ethnic groups. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Div Rheumatol, Philadelphia, PA 19107 USA. NCI, Paediat Oncol Branch, Bethesda, MD 20892 USA. Specialty Labs, Santa Monica, CA USA. US FDA, Div Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Rider, LG (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, 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 34 TC 41 Z9 49 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JUL PY 2000 VL 121 IS 1 BP 47 EP 52 DI 10.1046/j.1365-2249.2000.01266.x PG 6 WC Immunology SC Immunology GA 328NH UT WOS:000087856600008 PM 10886238 ER PT J AU Gans, HA Maldonado, Y Yasukawa, LL Beeler, J Audet, S Forghani, B Rinki, MM Dehovitz, R Hammer, L Arvin, AM AF Gans, HA Maldonado, Y Yasukawa, LL Beeler, J Audet, S Forghani, B Rinki, MM Dehovitz, R Hammer, L Arvin, AM TI Developmental maturation of the immune response to measles and mumps live viral vaccines. SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 CA Dept Hlth, Berkeley, CA USA. US FDA, Rockville, MD 20857 USA. Palo Alto Med Fdn, Palo Alto, CA USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. NR 0 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 JUL PY 2000 VL 31 IS 1 MA 57 BP 223 EP 223 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 347VY UT WOS:000088950900107 ER PT J AU Miele, PS Doan, NM Levy, CS Jolson, HM Smith, MA Lucey, DR AF Miele, PS Doan, NM Levy, CS Jolson, HM Smith, MA Lucey, DR TI Nocardiosis: 13 cases illustrating the broad clinical spectrum SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Washington Hosp Ctr, Washington, DC 20010 USA. NR 0 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 JUL PY 2000 VL 31 IS 1 MA 197 BP 247 EP 247 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 347VY UT WOS:000088950900247 ER PT J AU Evans, MC Gomez, TM Altekruse, SA Tauxe, RV Swerdlow, DL AF Evans, MC Gomez, TM Altekruse, SA Tauxe, RV Swerdlow, DL TI Declines in Salmonella serotype Enteritidis infections in the United States, 1980-1998: A triumph of prevention efforts SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 Ctr Dis Control & Prevent, Atlanta, GA USA. US FDA, Rockville, MD 20857 USA. USDA, Atlanta, GA USA. NR 0 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 JUL PY 2000 VL 31 IS 1 MA 504 BP 300 EP 300 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 347VY UT WOS:000088950900554 ER PT J AU Spiguel, CP AF Spiguel, CP TI The pharmaceutical industry in the 21(st) century: Surviving in the e-business environment SO DRUG INFORMATION JOURNAL LA English DT Article DE pharmaceutical industry; e-business; Internet; information management; information technology AB e- . . . the electronically enabled exchange and management of information to execute (. . .), is at the core of the most impactful societal change in history, the so called "Information Age." The pharmaceutical industry likes to think of itself as an innovator and rightly so in its life science disciplines (so we do not address these areas in this article). However the story is a little different in the core competency of information management (IM). In IM, the pharmaceutical industry has been conservative at best, if not recalcitrant in adapting to the changes that have already reshaped other industries such as finance, automobile, and aerospace, all of which share with pharmaceuticals some key IM characteristics. Hence the challenger How does the pharmaceutical industry survive the exhilarating pace of change that is bringing about the e-business imperatives of the Information Age marking the beginning of this new century? This pager introduces seven trends which are major drivers in determining the way that global markets are taking shape in the Information Age, and outlines some CEO strategic imperatives to address those drivers in various industries, including some of those mentioned above. It then attempts to suggest what could be pharmaceuticals CEOs' concerns in terms of their organizations' core competencies, to bring the industry into the new century, given its very historically conservative approach to information management. Finally, it concludes with an account of how the industry's highly regulated environment has reflected the coming of the Information Age, exemplified by the Food and Drug Administration Modernization Act of 1997, and how the Pharmaceutical Research and Manufacturers of America has positioned itself to partner in this transition. A model outlining the various phases to be undertaken is offered in closing. C1 AstraZeneca, Commercial Informat Management, Wilmington, DE 19850 USA. Pharmaceut Res & Manufacturers Amer, Informat Management Liaison Food & Drug Adm, Washington, DC USA. RP Spiguel, CP (reprint author), AstraZeneca, Commercial Informat Management, 1800 Concord Pike,POB 15437, Wilmington, DE 19850 USA. NR 12 TC 2 Z9 2 U1 1 U2 3 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 JUL-SEP PY 2000 VL 34 IS 3 BP 709 EP 723 PG 15 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 344YC UT WOS:000088787800007 ER PT J AU Tabacova, S AF Tabacova, S TI Exposures of current interest in reproductive and developmental health: Emerging or understudied problems SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 US FDA, NCTR, Rockville, MD 20857 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2000 VL 11 IS 4 MA 702 BP S149 EP S149 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 326CD UT WOS:000087713600400 ER PT J AU Tabacova, S Balabaeva, L Little, R Baird, D AF Tabacova, S Balabaeva, L Little, R Baird, D TI Adverse pregnancy outcomes associated with oxidized nitrogen exposures and oxidative stress: Human cancer research man and animal evidence SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 US FDA, NCTR, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 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 JUL PY 2000 VL 11 IS 4 MA 670 BP S143 EP S143 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 326CD UT WOS:000087713600376 ER PT J AU Fadiran, EO Jones, CD Ette, EI AF Fadiran, EO Jones, CD Ette, EI TI Designing population pharmacokinetic studies: Performance of mixed designs SO EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS LA English DT Article DE population pharmacokinetics ID PARAMETER-ESTIMATION; PHARMACODYNAMICS AB The interplay of the following factors: population design (PDN), the cost function in terms of maximum cost (Max. C) (i.e., maximum number of samples / sample size), sample size, and intersubject variability [restricted (30%) to moderate (60%)] on the estimation of pharmacokinetic parameters from population pharmacokinetic data sets obtained using mixed designs was investigated in a simulation study. A two compartment model with multiple bolus intravenous inputs was assumed, and the residual variability was set at 15%. The sample size (N) investigated ranged from 30 to 200 with the associated cost function varying accordingly with the five individual and sixteen population designs studied. Accurate and precise estimates of structural model parameters were obtained for N greater than or equal to 50 (Max.C greater than or equal to 150) irrespective of the intersubject variability (ITV) and PDN investigated. When ITV was 30%, all structural model parameters were well estimated irrespective of the PDN. Robust estimates of clearance and its variability were obtained for all N at all levels of ITV with Max. C greater than or equal to 90 (PDN greater than or equal to 4). Imprecise estimates of ITV in V1, V2, and Q were obtained at 60% ITV irrespective of N, PDN, or Max. C. Positive bias was associated with the estimation of variability in V1, V2, and Q with PDN less than or equal to 4 (Max. C less than or equal to 150). This was due in part to a greater proportion of subjects sampled only once. Correspondingly, residual variability was underestimated. It is of utmost importance to avoid this artifact by ensuring that at least a moderate subset of subjects contributing data to a population pharmacokinetic study contribute data more than once. Given a sample size and ITV, the cost function must be considered in designing a population pharmacokinetic study using mixed designs. C1 Solvay Pharmaceut Inc, Clarksburg, MD 20871 USA. US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. Vertex Pharmaceut, Cambridge, MA USA. RP Ette, EI (reprint author), Ventex Pharmacokinet Inc, 130 Werely St, Cambridge, MA 02139 USA. NR 19 TC 3 Z9 3 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 JUL-DEC PY 2000 VL 25 IS 3-4 BP 231 EP 239 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 440TD UT WOS:000169189600014 PM 11420896 ER PT J AU Takeshita, F Klinman, DM AF Takeshita, F Klinman, DM TI CPG ODN-mediated regulation of IL-12 p40 transcription SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE bacterial DNA; CpG motif; immunomodulator; IL-12; gene regulation ID NF-KAPPA-B; BACTERIAL-DNA; IMMUNOSTIMULATORY OLIGODEOXYNUCLEOTIDES; INTERFERON-GAMMA; CUTTING EDGE; INTERLEUKIN-12; MOTIFS; CELLS; ACTIVATION; MURINE AB Oligodeoxynucleotides (ODN) containing CpG motifs activate RAW 264.7 mouse macrophages and RPMI 8226 human myeloma cells to produce IL-12 p40. Using deletion and site-directed mutagenesis, the nuclear factor (NF)-kappa B half-site and the CCAAT/enhancer binding protein (C/EBP) recognition site were identified as potent cis-acting elements in CpG ODN-mediated IL-12 p40 promoter activation. Several NF-kappa B/Rel proteins competed for binding to the NF-kappa B half-site. The p65/c-Rel and p65/p50 heterodimer occupied this site shortly after CpG ODN administration (0.5-2 h), while the p50/c-Rel heterodimer dominated binding in the late stage (8-12 h). The induction of p50/c-Rel heterodimer was associated with a significant expression of IL-12 p40 mRNA. C/EBP beta also contributed to CpG ODN-mediated IL-12 p40 promoter activation. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bldg 29A,Rm 3 D 10, Bethesda, MD 20892 USA. NR 28 TC 32 Z9 33 U1 2 U2 2 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 JUL PY 2000 VL 30 IS 7 BP 1967 EP 1976 DI 10.1002/1521-4141(200007)30:7<1967::AID-IMMU1967>3.0.CO;2-5 PG 10 WC Immunology SC Immunology GA 335UC UT WOS:000088262300019 PM 10940886 ER PT J AU Wang, RF Cao, WW Khan, AA Cerniglia, CE AF Wang, RF Cao, WW Khan, AA Cerniglia, CE TI Cloning, sequencing, and expression in Escherichia coli of a cytochrome P450 gene from Cunninghamella elegans SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE P450; cloning; expression; Cunninghamella elegans ID BIOTRANSFORMATION; METABOLISM; FUNGUS; IDENTIFICATION AB A polyclonal antibody against microsomes of a fungus, Cunninghamella elegans, was used to screen a C. elegans cDNA library. A cDNA clone, containing an open reading frame (ORF) encoding a protein of 389 amino acids (aa), was obtained. GenBank comparison (BLAST) showed that the protein was closely related to P450 because a heme-binding region, which is highly conserved in all P450 sequences, was found in the ORF protein. Using an oligo probe designed from this CI. elegans heme-binding region to rescreen the cDNA library, we obtained three new clones. Sequence comparison showed that the three clones, with different length cDNA inserts, were from the same mRNA of the C. elegans P450 gene. One clone had the full C, elegans P450 gene, encoding 473 aa with a molecular mass of 54958.60, whereas the 389 was a part of the 473 aa without the N-terminal. The entire C. elegans P450 gene was successfully subcloned and overexpressed in a plasmid-Escherichia coli system (pQE30). Immunostaining with three antibodies (CYP1A1, CYP2E1, and CYP3A1) against mammalian P450 enzymes and benzidine staining for hemoproteins showed positive results for the recombinant protein expressed in E. coli. A phylogenetic tree was constructed by comparison of other fungal P450s to the C. elegans sequence. The C. elegans P450 clustered close to the cyp51 family and was named cyp509A1 by the International Committee on the Nomenclature for Cytochrome P450 Enzymes. (C) 2000 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. C1 US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Cerniglia, CE (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 23 TC 18 Z9 20 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD JUL 1 PY 2000 VL 188 IS 1 BP 55 EP 61 DI 10.1111/j.1574-6968.2000.tb09168.x PG 7 WC Microbiology SC Microbiology GA 329WN UT WOS:000087931600010 PM 10867234 ER PT J AU Green, MD Schultz, WB AF Green, MD Schultz, WB TI Tort law deference to FDA regulation of medical devices SO GEORGETOWN LAW JOURNAL LA English DT Review ID GOVERNMENT-REGULATION; PRESCRIPTION DRUGS; FEDERAL PREEMPTION; PRODUCTS-LIABILITY; PREMARKET APPROVAL; AMENDMENTS; ARCHITECTURE; STANDARD; JOURNALS; CLAIMS C1 Univ Iowa, Iowa City, IA 52242 USA. US Dept Justice, Washington, DC 20530 USA. US FDA, Rockville, MD 20857 USA. RP Green, MD (reprint author), Univ Iowa, Iowa City, IA 52242 USA. NR 148 TC 14 Z9 14 U1 0 U2 6 PU GEORGETOWN LAW JOURNAL ASSN PI WASHINGTON PA 600 NEW JERSEY AVE N W, WASHINGTON, DC 20001 USA SN 0016-8092 J9 GEORGETOWN LAW J JI Georget. Law J. PD JUL PY 2000 VL 88 IS 7 BP 2119 EP 2145 PG 27 WC Law SC Government & Law GA 337AH UT WOS:000088334800004 PM 11503660 ER PT J AU Adelman, N Chester, L Slack, K AF Adelman, N Chester, L Slack, K TI The HSRProj database: Update on health services research in progress SO HEALTH AFFAIRS LA English DT Article C1 US FDA, Rockville, MD 20857 USA. US Dept HHS, Parklawn Hlth Lib, Rockville, MD USA. RI Slack, Kathy/D-4733-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JUL-AUG PY 2000 VL 19 IS 4 BP 257 EP 258 DI 10.1377/hlthaff.19.4.257 PG 2 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 335KM UT WOS:000088242700028 PM 10916981 ER PT J AU Wear, KA Armstrong, DW AF Wear, KA Armstrong, DW TI The relationship between ultrasonic backscatter and bone mineral density in human calcaneus SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Letter ID CANCELLOUS BONE; HIP FRACTURE; IN-VITRO; ATTENUATION; VELOCITY; WOMEN; PREDICTION; LIVER; MASS AB Backscatter and attenuation coefficients were measured from 24 human calcanei in vitro. The logarithm of the backscatter coefficient at 500 kHz showed moderate correlations with bone mineral density (r = 0.81, 95% confidence interval: 0.59-0.91) and attenuation (r = 0.79, 95% CI: 0.58-0.91). These results suggest that backscatter measurements may be useful in the diagnosis of osteoporosis. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. USN, Natl Res Ctr, Bethesda, MD 20889 USA. RP US FDA, Ctr Devices & Radiol Hlth, HFZ-142,12720 Twinbrook Pkwy, Rockville, MD 20852 USA. EM kaw@cdrh.fda.gov NR 32 TC 24 Z9 25 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0885-3010 EI 1525-8955 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD JUL PY 2000 VL 47 IS 4 BP 777 EP 780 DI 10.1109/58.852057 PG 4 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 334FK UT WOS:000088175800002 PM 18238608 ER PT J AU Verthelyi, D Klinman, DM AF Verthelyi, D Klinman, DM TI Sex hormone levels correlate with the activity of cytokine-secreting cells in vivo SO IMMUNOLOGY LA English DT Article ID MULTIPLE-SCLEROSIS PATIENTS; MENSTRUAL-CYCLE; T-CELLS; PERIPHERAL-BLOOD; IMMUNE-RESPONSE; ANDROGEN RECEPTORS; GONADAL-STEROIDS; ESTROGEN; DEHYDROEPIANDROSTERONE; DISEASES AB This work examines the correlation between serum levels of oestrogen, progesterone and dehydroepiandrosterone sulphate (DHEA-S) and the number of human peripheral blood cells actively secreting interleukin (IL)-2, IL-4, IL-6, IL-10, tumour necrosis factor-alpha (TNF-alpha) or interferon-gamma (IFN-gamma) in vivo. Simultaneous assessment of serum hormone levels and cytokine-secreting cell activity throughout the menstrual cycle showed that the number of peripheral blood mononuclear cells (PBMC) able to secrete IL-4 in response to stimulation correlated significantly (P < 0.0001) with oestrogen levels and fluctuated with the menstrual cycle in pre-menopausal women. The activity of IFN-gamma-secreting cells, on the other hand, varied as a function of serum DHEA-S levels in pre-menopausal women (P < 0.0001). Similarly, the number of cells secreting IFN-gamma in men correlated with serum DHEA-S levels (P < 0.001). In contrast, post-menopausal women had fewer cells actively secreting cytokines and the activity of these cells did not correlate with sex hormone levels. These results suggest that sex hormones may modulate cytokine production in vivo and contribute to gender-related differences in normal and pathological immune responses. C1 US FDA, Retroviral Immunol Sect, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Retroviral Immunol Sect, Ctr Biol Evaluat & Res, Bldg 29A Rm 3D10, Bethesda, MD 20892 USA. NR 41 TC 90 Z9 99 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD JUL PY 2000 VL 100 IS 3 BP 384 EP 390 DI 10.1046/j.1365-2567.2000.00047.x PG 7 WC Immunology SC Immunology GA 336LT UT WOS:000088304100015 PM 10929062 ER PT J AU Farizo, KM Huang, T Burns, DL AF Farizo, KM Huang, T Burns, DL TI Importance of holotoxin assembly in Ptl-mediated secretion of pertussis toxin from Bordetella pertussis SO INFECTION AND IMMUNITY LA English DT Article ID ISLET-ACTIVATING PROTEIN; GRAM-NEGATIVE BACTERIA; MONOCLONAL-ANTIBODIES; SUBCELLULAR-LOCALIZATION; ADP-RIBOSYLATION; MEMBRANE-PROTEIN; S1 SUBUNIT; SYSTEM; GENES; CLONING AB We examined the structural components of pertussis toxin that are required for efficient export from Bordetella pertussis via the Ptl system, a member of the type IV family of macromolecular transporters. First, we constructed a strain of B. pertussis that contains a functional Ptl system but does not produce pertussis toxin. Plasmids which express either the S1 subunit or the B oligomer were then introduced into this strain. We found that the B oligomer of the toxin is not secreted in the absence of the S1 subunit. Conversely, the S1 subunit is also not secreted by a Ptl-mediated mechanism in the absence of the B oligomer. Thus, an assembled holotoxin is required for Ptl-mediated export of pertussis toxin from B. pertussis. C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. RP Farizo, KM (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, HFM-434,Bldg 29,room 418,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 32 TC 29 Z9 31 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 JUL PY 2000 VL 68 IS 7 BP 4049 EP 4054 DI 10.1128/IAI.68.7.4049-4054.2000 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 326AT UT WOS:000087710200036 PM 10858221 ER PT J AU Thompson, RD Carlson, M AF Thompson, RD Carlson, M TI Liquid chromatographic determination of dehydroepiandrosterone (DHEA) in dietary supplement products SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MASS-SPECTROMETRY; INTERNAL STANDARD; SULFATE AB A liquid chromatographic (LC) method was developed to assess the potency of products that contain dehydroepiandrosterone (DHEA), a precursor hormone synthesized from cholesterol by the human adrenal cortex and converted to potent androgens and/or estrogens in peripheral tissues, Forty-five commercial products (both single and multi-ingredient) were subjected to analysis by the proposed method. A Zorbax R-X C-18 column with a mobile phase containing acetonitrile-0.025M phosphate buffer (60 + 40), pH 3.50, and UV detection at 292 nm was used for 87% of the products. An alternative mobile phase containing methanol-0.025M phosphate (75 + 25), pH 3.50, was used to isolate DHEA from more complex product mixtures. Assay values varied from 0 to 109.5% of the declared amount with an overall mean value of 91.1%. The recoveries based on fortified products ranged from 96.4 to 101.2%, and the intraday precision (RSD, n = 5) varied from 0.50 to 1.66%. C1 US FDA, Minneapolis, MN 55401 USA. RP Thompson, RD (reprint author), 1425 W 28th St,611, Minneapolis, MN 55408 USA. NR 22 TC 18 Z9 18 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 JUL-AUG PY 2000 VL 83 IS 4 BP 847 EP 857 PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 343FG UT WOS:000088690600010 PM 10995111 ER PT J AU Ware, GM Chase, GW Eitenmiller, RR Long, AR AF Ware, GM Chase, GW Eitenmiller, RR Long, AR TI Determination of vitamin K-1 in medical foods by liquid chromatography with postcolumn reduction and fluorometric detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PHYLLOQUINONE CONTENT; INFANT FORMULAS; PLASMA; MILK AB A liquid chromatographic (LC) method is described for the determination of vitamin K-1 in medical foods, The sample is enzymatically digested with lipase and alpha-amylase and extracted with 1% sodium bicarbonate solution-isopropanol (1 + 1), After C-18 solid-phase extraction, vitamin K1 is separated by nonaqueous reversed-phase LC, converted to the hydroquinone by postcolumn zinc reduction, and quantitated by fluorescence detection. The limit of detection is 8 pg (3 sigma), and the limit of quantitation is 27 pg (10 sigma) on column. Linear response ranged from 0.1 to 1.0 ng vitamin K1 (r = 0.9999), The mean recovery (n = 38) for all spiking levels was 101.6 +/- 2.85%. Analysis of Standard Reference Material 1846, Infant Formula, gave a mean value of 0.95 +/- 0.088 mg vitamin K/kg (K or K1?)(n = 31) with a coefficient of variation of 9.26. C1 US FDA, SE Reg Lab, Atlanta, GA 30309 USA. Univ Georgia, Dept Food Sci & Technol, Athens, GA 30602 USA. RP Ware, GM (reprint author), US FDA, SE Reg Lab, 60 Eighth St NE, Atlanta, GA 30309 USA. NR 18 TC 5 Z9 5 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 2000 VL 83 IS 4 BP 957 EP 962 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 343FG UT WOS:000088690600020 PM 10995121 ER PT J AU Hansen, R Koller, EA Malozowski, S AF Hansen, R Koller, EA Malozowski, S TI Full remission of growth hormone (GH)-induced retinopathy after GH treatment discontinuation: Long-term follow-up SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Div Metab & Endocrine Drug Prod, Rockville, MD 20857 USA. RP Koller, EA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Metab & Endocrine Drug Prod, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 2 TC 12 Z9 12 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 JUL PY 2000 VL 85 IS 7 BP 2627 EP 2627 DI 10.1210/jc.85.7.2627 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337XB UT WOS:000088387500042 PM 10902819 ER PT J AU Little, RF Wyvill, KM Pluda, JM Welles, L Marshall, V Figg, WD Newcomb, FM Tosato, G Feigal, E Steinberg, SM Whitby, D Goedert, JJ Yarchoan, R AF Little, RF Wyvill, KM Pluda, JM Welles, L Marshall, V Figg, WD Newcomb, FM Tosato, G Feigal, E Steinberg, SM Whitby, D Goedert, JJ Yarchoan, R TI Activity of thalidomide in AIDS-related Kaposis's sarcoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ACQUIRED IMMUNODEFICIENCY SYNDROME; NECROSIS-FACTOR-ALPHA; II CLINICAL-TRIALS; PHASE-II; DNA-SEQUENCES; INFLAMMATORY CYTOKINES; PENTOSAN POLYSULFATE; NATURAL-HISTORY; SPINDLE CELLS AB Purpose: To assess the toxicity and activity of oral thalidomide in Kaposi's sarcoma (KS) in a phase II dose-escalation study. Patients and Methods: Human immunodeficiency virus (HIV)-seropositive patients with biopsy-confirmed KS that progressed over the 2 months before enrollment received an initial dose of 200 mg/d of oral thalidomide in a phase II study. The dose was increased to a maximum of 1,000 mg/d for up to 1 year. Anti-HIV therapy was maintained during the study period. Toxicity, tumor response, immunologic and angiogenic factors, and virologic parameters were assessed. Results: Twenty patients aged 29 to 49 years with a median CD4 count of 246 cells/mm(3) (range, 14 to 646 cells/mm(3)) were enrolled, All patients were assessable for toxicity, and 17 for response, Drowsiness in nine and depression in seven patients were the most frequent toxicities observed. Eight (47%; 95% confidence interval [CI], 23% to 72%) of the 17 assessable patients achieved a partial response, and an additional two patients had stable disease, Based on all 20 patients treated, the response rate was 40% (95% CI, 19% to 64%). The median thalidomide dose at the time of response wets 500 mg/d (range, 400 to 1,000 mg/d). The median duration of drug treatment was 6.3 months, and the median time to progression was 7.3 months. Conclusion: Oral thalidomide was tolerated in this population at doses up to 1,000 mg/d for as long as 12 months and was found to induce clinically meaningful anti-KS responses in a sizable subset of the patients. Additional studies of this agent in KS are warranted. C1 NCI, Div Clin Sci, HIV AIDS Malignancy Branch, Med Branch, Bethesda, MD 20892 USA. NCI, Div Clin Sci, Biostat & Data Management Sect, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD USA. Sci Applicat Int Corp, Frederick, MD USA. RP Yarchoan, R (reprint author), Bldg 10,Room 12N226,MSC 1906,10 Ctr Dr, Bethesda, MD 20892 USA. RI Ain, Kenneth/A-5179-2012; Figg Sr, William/M-2411-2016 OI Ain, Kenneth/0000-0002-2668-934X; NR 67 TC 194 Z9 202 U1 1 U2 3 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 JUL PY 2000 VL 18 IS 13 BP 2593 EP 2602 PG 10 WC Oncology SC Oncology GA 330AL UT WOS:000087940600013 PM 10893291 ER PT J AU Olsen, AR Hammack, TS AF Olsen, AR Hammack, TS TI Isolation of Salmonella spp. from the housefly, Musca domestica L., and the dump fly, Hydrotaea aenescens (Wiedemann) (Diptera : Muscidae), at caged-layer houses SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ENTERITIDIS INFECTIONS; EGGS AB Flies, especially houseflies, are widely recognized as potential reservoirs and vectors of foodborne Salmonella pathogens. In this study, flies were collected at caged-layer facilities that had produced eggs that were implicated as the food vehicle in two recent outbreaks of Salmonella Enteritidis infections. The flies were separated by species into pools for microbiological testing. A total of 15 species pools of houseflies, Musca domestica L., and 7 species pools of bronze dump flies, Hydrotaea aenescens (Wiedemann) (Diptera: Muscidae), were analyzed. Salmonella Enteritidis was isolated from 2 of the 15 pools of houseflies. Other species of Salmonella were isolated from three pools of flies, including Salmonella Infantis from houseflies and from dump flies and Salmonella Heidelberg from houseflies. Salmonella Mbandaka was isolated from a lesser mealworm, Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae). C1 US FDA, Washington, DC 20204 USA. RP Olsen, AR (reprint author), US FDA, HFS-315,200 C St SW, Washington, DC 20204 USA. NR 15 TC 68 Z9 71 U1 3 U2 6 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 JUL PY 2000 VL 63 IS 7 BP 958 EP 960 PG 3 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 333YL UT WOS:000088158300020 PM 10914668 ER PT J AU Whitting, RC Hogue, A Schlosser, WD Ebel, ED Morales, RA Baker, A McDowell, RM AF Whitting, RC Hogue, A Schlosser, WD Ebel, ED Morales, RA Baker, A McDowell, RM TI A quantitative process model for Salmonella enteritidis in shell eggs SO JOURNAL OF FOOD SCIENCE LA English DT Article DE microbial pathogen; food safety; risk assessment ID RISK ASSESSMENT; GROWTH; HENS; CONTAMINATION; STRAINS AB A stochastic model estimating growth of Salmonella Enteritidis during egg collection, processing, storage, and transportation is described. The model contains equations for internal egg temperature, yolk membrane integrity, and exponential growth rate of S. Enteritidis, Monte Carlo simulations determined that no growth was likely to occur during the average 4.5 d of the egg's progression from lay through transportation. However, various time-temperature combinations affected the subsequent abuse an egg can withstand before S. Enteritidis growth begins. Scenarios demonstrated the relative importance of ambient air temperature and indicated the greatest safety improvements in this phase for shell eggs would result from preventing unrefrigerated storage or hastening cooling immediately after lay. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. FSIS, USDA, Washington, DC USA. FSIS, USDA, College Stn, TX USA. FSIS, USDA, Ft Collins, CO USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. APHIS, USDA, Riverdale, MD USA. RP Whitting, RC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 26 TC 16 Z9 16 U1 0 U2 3 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA SUITE 300 221 N LASALLE ST, CHICAGO, IL 60601-1291 USA SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD JUL-AUG PY 2000 VL 65 IS 5 BP 864 EP 869 DI 10.1111/j.1365-2621.2000.tb13601.x PG 6 WC Food Science & Technology SC Food Science & Technology GA 353ZT UT WOS:000089305900023 ER PT J AU Offringa, DP Tyson-Medlock, V Ye, ZP Levandowski, RA AF Offringa, DP Tyson-Medlock, V Ye, ZP Levandowski, RA TI A comprehensive systematic approach to identification of influenza A virus genotype using RT-PCR and RFLP SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE influenza virus; influenza vaccine reassortants; RT-PCR; RFLP; genotype 1 ID NUCLEOTIDE-SEQUENCES; RECOMBINANTS; VACCINES; SEGMENTS AB Amplification of influenza A virus gene segments by reverse transcription-polymerase chain reaction (RT-PCR) can be combined with enzymatic digestion to reveal unique restriction fragment length polymorphisms specific for H1N1 and H3N2 subtype viruses. We have used the method to provide a rapid, specific and reproducible identification of the genotype of high-growth influenza reassortants derived from A/Puerto Rico/8/34 (PR8). Digestion of the gene segments amplified from wild-type viruses, PR8 and reassortants at sites unique to either the wild-type strain or to PR8 provided positive, unambiguous identification of the origin of each of the internal genes, and distinguished the internal genes of both H1N1 and H3N2 strains from those of PR8. This method has also permitted us to quickly confirm that reasserting has occurred and to optimize the selection of reassortant clones with maximum number of PR8 internal genes. Since the method can detect 1-10% of a second strain in a mixed population, the method can also be used to detect samples containing more than one viral subtype and to assess the purity of influenza viruses used for manufacturing vaccines. (C) 2000 Elsevier Science B.V. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Rockville, MD 20852 USA. RP Offringa, DP (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, 1401 Rockville Pike HFM 463, Rockville, MD 20852 USA. NR 19 TC 24 Z9 26 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD JUL PY 2000 VL 88 IS 1 BP 15 EP 24 DI 10.1016/S0166-0934(00)00180-4 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 333TW UT WOS:000088147700003 PM 10921838 ER PT J AU Feldman, SA Audet, S Beeler, JA AF Feldman, SA Audet, S Beeler, JA TI The fusion glycoprotein of human respiratory syncytial virus facilitates virus attachment and infectivity via an interaction with cellular heparan sulfate SO JOURNAL OF VIROLOGY LA English DT Article ID RECOMBINANT VACCINIA VIRUS; SUBGROUP-B; F-GLYCOPROTEIN; BINDING DOMAIN; PROTEINS; RSV; IDENTIFICATION; SUPERIORITY; CLEAVAGE; SEQUENCE AB Human respiratory syncytial virus (RSV) F glycoprotein (RSV-F) can independently interact with immobilized heparin and facilitate both attachment to and infection of cells via an interaction with cellular heparan sulfate. RSV-glycosaminoglycan (GAG) interactions were evaluated using heparin agarose affinity chromatography. RSV-F from A2- and B1/cp-52 (cp-52)-infected cell lysates, RSV F derived from a recombinant vaccinia virus, and affinity-purified F protein all bound to and were specifically eluted from heparin columns. In infectivity inhibition studies, soluble GAGs decreased the infectivity of RSV A2 and cp-52, with bovine lung heparin exhibiting the highest specific activity against both A2 (50% effective dose [ED50] = 0.28 +/- 0.11 mu g/ml) and cp-52 (ED50 = 0.55 +/- 0.14 mu g/ml). Furthermore, enzymatic digestion of cell surface GAGs by heparin lyase I and heparin lyase III but not chondroitinase ABC resulted in a significant reduction in cp-52 infectivity. Moreover, bovine lung heparin inhibited radiolabeled A2 and cp-52 virus binding up to 30%. Taken together, these data suggest that RSV-F independently interacts with heparin/heparan sulfate and this type of interaction facilitates virus attachment and infectivity. C1 US FDA, Lab Pediat & Resp Virus Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Feldman, SA (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29A,3B-05,HFM 463,1401 Rockville Pike, Rockville, MD 20852 USA. NR 28 TC 132 Z9 138 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2000 VL 74 IS 14 BP 6442 EP 6447 DI 10.1128/JVI.74.14.6442-6447.2000 PG 6 WC Virology SC Virology GA 327WU UT WOS:000087817900025 PM 10864656 ER PT J AU Roach, JAG Yurawecz, MP Kramer, JKG Mossoba, MM Eulitz, K Ku, Y AF Roach, JAG Yurawecz, MP Kramer, JKG Mossoba, MM Eulitz, K Ku, Y TI Gas chromatography-high resolution selected-ion mass spectrometric identification of trace 21 : 0 and 20 : 2 fatty acids eluting with conjugated linoleic acid isomers SO LIPIDS LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; CONFIRMATION; SEPARATION AB High-resolution selected-ion recording (SIR) of the exact molecular ion mass was used to confirm unambiguously the presence of conjugated linoleic acid (CLA) derivatives in biological matrices and standard mixtures and to differentiate non-CLA derivatives from CLA derivatives in the CLA region of the gas chromatogram. The success of this method was based on the selectivity of the SIR technique and its sensitivity, which was comparable to that of flame-ionization detection. A minor fatty acid methyl ester (FAME) was identified as methyl heneicosanoate (21:0), and six isomers of 20:2 FAME were found to elute in the CLA region. Isomerization of a standard CLA mixture resulted in a non-CLA flame-ionization response eluting in the CLA region of the gas chromatogram. it is therefore recommended that the identification of minor CLA isomers in natural products or biological matrices should include their direct confirmation by mass spectrometry. C1 US FDA, Washington, DC 20204 USA. Agr & Agri Food Canada, Food Res Ctr, So Crop Protect, Guelph, ON N1G 5C9, Canada. RP Roach, JAG (reprint author), US FDA, 200 C St SW, Washington, DC 20204 USA. NR 16 TC 27 Z9 29 U1 0 U2 7 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PD JUL PY 2000 VL 35 IS 7 BP 797 EP 802 DI 10.1007/s11745-000-0588-9 PG 6 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 339WG UT WOS:000088500400013 PM 10941882 ER PT J AU Kane, AS Dykstra, MJ Noga, EJ Reimschuessel, R Baya, A Driscoll, C Paerl, HW Landsberg, J AF Kane, AS Dykstra, MJ Noga, EJ Reimschuessel, R Baya, A Driscoll, C Paerl, HW Landsberg, J TI Etiologies, observations and reporting of estuarine finfish lesions SO MARINE ENVIRONMENTAL RESEARCH LA English DT Article; Proceedings Paper CT 10th international Symposium on Pollutant Responses in Marine Organisms (PRIMO 10) CY APR 25-29, 1999 CL COLL WILLIAM & MARY, WILLIAMSBURG, VIRGINIA HO COLL WILLIAM & MARY DE fish pathology; ulcers; lesions; Pfiesteria; HABs ID FISH KILLS; RED SPOT; DISEASE; DINOFLAGELLATE; AUSTRALIA; FLORIDA; RIVER AB Lesions in estuarine finfish are associated with a variety of organisms including parasites and bacterial, viral, and fungal infectious agents. In addition, trauma, suboptimal water quality, and other abiotic stress factors may result in the loss of homeostasis. We have observed solitary ulcerative lesions on menhaden sampled from the Chesapeake Bay, Maryland, the Pamlico River, North Carolina, and the St. Johns River, Florida. Histologically, the lesions demonstrated a marked chronic inflammatory infiltrate and granulomas in response to fungal hyphae throughout large areas of exposed necrotic muscle. Gram-negative rod-shaped bacteria were also observed in the lesions, a common finding in ulcers of aquatic organisms. Similar observations in menhaden and other species have been described previously in the literature as ulcerative mycosis, mycotic granulomatosis, red spot disease, and epizootic ulcerative syndrome. Despite the many different known causes of fish lesions, the popular press and the scientific literature have recently emphasized Pfiesteria in piscicida and other Pfiesteria-like dinoflagellates (and their bioactive compounds) as the primary causative agent for finfish lesions, particularly mycotic granulomatous ulcers in Atlantic menhaden. While some laboratory data suggest that Pfiesteria may play a role in field-observed lesions, much more cause-and-effect evidence is needed to determine the importance of other risk factors, both alone or and in combination with Pfiesteria. In order to better understand the etiology of lesion initiation and progression in estuarine finfish, accurate assessments of environmental conditions collected on appropriate temporal and spatial scales, and fish morphological indicators consistent with gross and histological pathologic terminology, should be used for reporting fish lesion observations and kills. Further, this outlook will help to avoid bias and may foster a broader perspective for examining the health of estuarine systems in general. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Univ Maryland, Aquat Pathobiol Ctr, Dept Vet Med, College Pk, MD 20742 USA. N Carolina State Univ, Coll Vet Med, Raleigh, NC 27606 USA. US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20740 USA. Maryland Dept Nat Resources, Sarbanes Cooperat Oxford Lab, Oxford, MD 21654 USA. Univ N Carolina, Inst Marine Sci, Morehead City, NC 28557 USA. Florida Marine Res Inst, Florida Dept Environmm Protect, St Petersburg, FL 33701 USA. RP Kane, AS (reprint author), Univ Maryland, Aquat Pathobiol Ctr, Dept Vet Med, 8075 Greenmead Dr, College Pk, MD 20742 USA. NR 16 TC 8 Z9 9 U1 2 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0141-1136 J9 MAR ENVIRON RES JI Mar. Environ. Res. PD JUL-DEC PY 2000 VL 50 IS 1-5 BP 473 EP 477 DI 10.1016/S0141-1136(00)00117-3 PG 5 WC Environmental Sciences; Marine & Freshwater Biology; Toxicology SC Environmental Sciences & Ecology; Marine & Freshwater Biology; Toxicology GA 376ZG UT WOS:000165486700073 PM 11460735 ER PT J AU Weaver, JL AF Weaver, JL TI Flow cytometry: measuring cell populations and studying cell physiology - Introduction to flow cytometry SO METHODS-A COMPANION TO METHODS IN ENZYMOLOGY LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Laurel, MD 20708 USA. RP Weaver, JL (reprint author), CDER MOD-1,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 2 TC 5 Z9 5 U1 1 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD JUL PY 2000 VL 21 IS 3 BP 199 EP 201 DI 10.1006/meth.2000.1000 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 332RC UT WOS:000088086400001 PM 10873474 ER PT J AU Weaver, JL Torous, D AF Weaver, JL Torous, D TI Flow cytometry assay for counting micronucleated erythrocytes: Development process SO METHODS-A COMPANION TO METHODS IN ENZYMOLOGY LA English DT Article ID PERIPHERAL-BLOOD; RETICULOCYTES; MOUSE AB Development of any new assay proceeds in several phases. When an assay is intended for regular use to support regulatory decision-making there are significant additional stages in the development process beyond the initial description of the method. In this paper we discuss some of the studies related to the development of a flow cytometric method for counting micronuclei in rodent erythrocytes. Studies related to fixation methods and conditions, standardization of DNA staining, and antibody staining are discussed. These studies, while not part of the formal description of the method, are needed as part of the preparation for the formal validation of the method. In addition, the lessons learned in transferring the method to other laboratories are briefly discussed in relation to defining the final protocol. (C) 2000 Academic Press. C1 US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Laurel, MD USA. Litron Labs Inc, Rochester, NY 14620 USA. RP Weaver, JL (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Laurel, MD USA. NR 10 TC 3 Z9 10 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD JUL PY 2000 VL 21 IS 3 BP 281 EP 287 DI 10.1006/meth.2000.1008 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 332RC UT WOS:000088086400009 PM 10873482 ER PT J AU McCardell, BA Kothary, MH Hall, RH Sathyamoorthy, V AF McCardell, BA Kothary, MH Hall, RH Sathyamoorthy, V TI Identification of a CHO cell-elongating factor produced by Vibrio cholerae O1 SO MICROBIAL PATHOGENESIS LA English DT Article DE Vibrio cholerae; enterotoxin; CHO cell elongation ID ESCHERICHIA-COLI; EL-TOR; ENTERO-TOXIN; VACCINE; PURIFICATION; GM1; ACE AB Vibrio cholerae strains with all known toxin genes deleted or inactivated still cause diarrhoea in some volunteers, suggesting the presence of an unknown virulence factor or factors. Lysozyme-EDTA treated cells of JBK70, a genetically manipulated cholera toxin negative strain of Vibrio cholerae O1,biotype El Tor, release a factor that causes elongation of Chinese hamster ovary (CHO) cells. CHO cell-elongating toxin (Cef) was purified by FPLC chromatography (anion exchange; Q Sepharose High Performance) followed by 2D electrophoresis (isoelectric focusing gel, IEF; pH 3-9 and SDS-PAGE, 8-25% gradient gel). Partly purified toxin (anion exchange or IEF-eluted concentrate) caused fluid accumulation in sealed infant mice suggesting that Cef shows some properties of an enterotoxin. On SDS-PAGE (8-25%) and]EF (pH 2.5-5.0) gels, CHO cell activity was associated with a single band at 85 kDa and a pI of 3.8, respectively. A unique amino terminal sequence, XGDETNSSGASTEVVYESYIQQ, was determined by automated Edman degradation of gel-purified protein. The unique molecular mass, N-terminal sequence and activity on CHO cells indicate that this factor is not zonula occludens toxin (Zot) or accessory cholera enterotoxin (Ace) or the Hly A haemolysin. Partly purified Cef did not increase cyclic AMP or prostaglandin E-2 levels in CHO cells which suggests that its mechanism of action differs from that of cholera toxin. C1 US FDA, Div Virulence Assessment, Washington, DC 20204 USA. RP McCardell, BA (reprint author), US FDA, Div Virulence Assessment, 200 C St SW, Washington, DC 20204 USA. NR 25 TC 8 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD JUL PY 2000 VL 29 IS 1 BP 1 EP 8 DI 10.1006/mpat.2000.0361 PG 8 WC Immunology; Microbiology SC Immunology; Microbiology GA 333LX UT WOS:000088132500001 PM 10873485 ER PT J AU Holson, RR Adams, J Ferguson, SA Scalzo, FM AF Holson, RR Adams, J Ferguson, SA Scalzo, FM TI Retinoic acid exposure on gestational days 11 to 13 impairs swallowing in rat offspring SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE retinoids; all-trans-retinoic acid; swallowing; cranial nerves ID ABNORMAL-DEVELOPMENT; OLFACTORY PATHWAY; NUCLEUS AMBIGUUS; HINDBRAIN; TRANSFORMATION; ORGANIZATION; BEHAVIOR; MIDBRAIN; IDENTITY; NEURONS AB We have previously reported that exposure to 10 mg/kg of all-trans-retinoic acid (RA) daily on the 11th, 12th, and 13th days of rat gestation is lethal to all fetuses so exposed, due to an inability to suckle [R.R. Holson et al., Neurotoxicol Teratol 19 (1997) 347-3531. Because this lethal RA effect could be due to any of a variety of causes, from olfactory problems in locating the nipple to a motor problem in sucking or swallowing, we performed the following experiment. Albino dams were exposed to 10-mg/kg RA or vehicle daily over gestational days (GDs) 11 to 13. On the afternoon of GD 21 all pups were delivered by c-section. Tongue cannulae were inserted into the oral cavity of these offspring, and used to infuse a solution of condensed milk directly into the mouth. During and after each of four infusions, the behavioral response to the infusion (typically rolling and curling) was recorded. Controls responded well to this procedure, typically swallowing all milk so infused. In contrast, almost no RA-exposed neonates were able to swallow milk infused into the oral cavity. In such cases the milk simply dribbled out of the mouth, while the stomach was found to be empty at autopsy. However, the RA-treated animals did seem aware that milk was entering their mouths, because they showed a normal behavioral response to milk infusion. We conclude that GD 11-13 retinoid lethality is due to motor not sensory problems in the control of swallowing. (C) 2000 Elsevier Science Inc. All rights reserved. C1 New Mexico Tech, Dept Psychol, Socorro, NM 87801 USA. Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Arkansas Childrens Hosp, Res Inst, Dept Pediat, Little Rock, AR 72202 USA. RP Holson, RR (reprint author), New Mexico Tech, Dept Psychol, Socorro, NM 87801 USA. NR 37 TC 3 Z9 3 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-AUG PY 2000 VL 22 IS 4 BP 541 EP 545 DI 10.1016/S0892-0362(00)00072-6 PG 5 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 350RX UT WOS:000089115900006 PM 10974592 ER PT J AU Kwon, OS Slikker, W Davies, DL AF Kwon, OS Slikker, W Davies, DL TI Biochemical and morphological effects of fumonisin B-1 on primary cultures of rat cerebrum SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE fumonisin B-1; glia; leukoencephalomalacia; mycotoxin; oligodendrocyte; sphinganine; sphingosine ID 2',3'-CYCLIC NUCLEOTIDE 3'-PHOSPHODIESTERASE; PERFORMANCE LIQUID-CHROMATOGRAPHY; FUSARIUM-MONILIFORME; SPHINGOLIPID BIOSYNTHESIS; NERVOUS-SYSTEM; MESSENGER-RNA; CALF BRAIN; IN-VITRO; INHIBITION; SPHINGANINE AB Chronic dietary consumption of the mycotoxin fumonisin B-1 (FB1) is associated with leukoencephalomalacia and neuronal degeneration, but identification of the cellular mechanisms underlying this neurotoxicity is difficult due to concurrent adverse systemic changes. For this reason, the present investigation used an in vitro approach to assess the short-term consequences of direct FB1 (0.5-75 mu M) exposure on astrocytes and oligodendrocytes in primary cultures of rat cerebrum. Beginning at 5 days in vitro, the cultures were exposed to FB1 at five concentrations (0.5-75 mu M), and the cultures were evaluated at 10 and 15 days in vitro. The levels of the sphingolipid-associated constituents sphingosine and sphinganine were determined with a high-performance liquid chromatography. Relative to untreated cultures, exposure to FB1 diminished the levels of sphingosine at 15 days in vitro, whereas FB1-exposed cultures showed significantly increased sphinganine levels and sphinganine/sphingosine ratios. In addition to these changes in sphingolipid constituents, FB1-exposed (0.5-75 mu M) cultures exhibited a two-fold increase in the number of process-bearing cells by 15 days in vitro. Also, the activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase, an enzyme associated with myelin and oligodendrocytes, was increased in FB1-treated cultures. This study suggests that shortterm exposure to FB1 may modify the proliferation or differentiation of glial cells. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Anat, Little Rock, AR 72205 USA. RP Kwon, OS (reprint author), Korea Inst Sci & Technol, Bioanal & Biotransformat Res Ctr, Sungbuk Gu, 39-1 Kawolgok Dong, Seoul 136791, South Korea. NR 38 TC 13 Z9 13 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-AUG PY 2000 VL 22 IS 4 BP 565 EP 572 DI 10.1016/S0892-0362(00)00082-9 PG 8 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 350RX UT WOS:000089115900009 PM 10974595 ER PT J AU Ferguson, SA Flynn, KM Delclos, KB Newbold, RR AF Ferguson, SA Flynn, KM Delclos, KB Newbold, RR TI Maternal and offspring toxicity but few sexually dimorphic behavioral alterations result from nonylphenol exposure SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE nonylphenol; endocrine disrupter; sodium intake; activity ID OPEN-FIELD BEHAVIOR; ENDOCRINE DISRUPTORS; SEX-DIFFERENCES; MALE-RATS; RESEARCH NEEDS; P-NONYLPHENOL; FEMALE RATS; ESTROGEN; ANDROGENS; TESTOSTERONE AB Nonylphenol ethoxylates are used in the production of surfactants and are found in numerous manufactured substances, para-Nonylphenol (NP) is a suspected endocrine disrupter, exhibiting estrogen-like activity and might cause alterations with developmental exposure. To evaluate such effects, pregnant Sprague-Dawley rats consumed diets containing 0 (n = 11), 25 (n = 10), 500 (n = 10), or 2,000 (n = 9) ppm NP beginning on gestational day (GD) 7. At postnatal day (PND) 21, offspring continued on the same maternal diets until PND 77 and were evaluated for behavioral alterations (open-field activity at PNDs 22-24, 43-45, 64-66, play behavior at PND 35, running wheel activity at PND 63-77, flavored solution intake at PND 69-75). During pregnancy and lactation, darns in the 25-, 500-, and 2,000-ppm groups consumed 9 to 25% less food, which was associated with a 17% less weight gain during GDs 1 to 21 in dams of the 2,000-ppm group, although this effect was not statistically significant. Gestation duration, birth weight, sex ratio of live pups, and number of live or dead pups per litter did not differ between treatment groups. Offspring body weight and food consumption were decreased in the ?,000ppm group beginning at PNP 28; however, an effect of feed aversion could not be eliminated. Behavioral assessments of offspring indicated no consistent NP-related effects in open-field activity at PNDs 22-24, 43-45, and 65-67 nor in running wheel activity at PNDs 63-75. Play behavior at PND 35 and intake of a 0.3% saccharin-flavored solution at PNDs 69-71 did not differ with respect to treatment groups. However, intake of a 3% sodium-flavored solution at PNDs 73-75 was significantly increased in offspring of the 2,000-ppm group and intake of regular water during this same time was also significantly increased. These results indicate that developmental NP treatment results in maternal and offspring toxicity as evidenced by decreased food intake and weight gain. However, behavioral alterations were evident only in increased intake of a sodium solution. (C) 2000 Elsevier Science Inc. All rights reserved. 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, Environm Toxicol Program, Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. FU PHS HHS [224-93-0001] NR 45 TC 40 Z9 40 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-AUG PY 2000 VL 22 IS 4 BP 583 EP 591 DI 10.1016/S0892-0362(00)00071-4 PG 9 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 350RX UT WOS:000089115900011 PM 10974597 ER PT J AU Calvo, MS AF Calvo, MS TI Dietary considerations to prevent loss of bone and renal function SO NUTRITION LA English DT Article ID PARATHYROID-HORMONE SECRETION; VITAMIN-D SUPPLEMENTATION; SOFT DRINK CONSUMPTION; HIGH PHOSPHORUS; BLOOD-PRESSURE; CALCIUM; WOMEN; DENSITY; TRIAL; GIRLS C1 US FDA, Ctr Food Safety & Appl Nutr, Off Special Nutr, Clin Res & Review Staff, Washington, DC 20204 USA. RP Calvo, MS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Special Nutr, Clin Res & Review Staff, HFS-452,200 C St SW, Washington, DC 20204 USA. NR 28 TC 26 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0899-9007 J9 NUTRITION JI Nutrition PD JUL-AUG PY 2000 VL 16 IS 7-8 BP 564 EP 566 DI 10.1016/S0899-9007(00)00313-0 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 337RF UT WOS:000088374900034 PM 10906557 ER PT J CA Sinus Allergy Hlth Partnership TI Antimicrobial treatment guidelines for acute bacterial rhinosinusitis - Executive summary SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID RESISTANT STREPTOCOCCUS-PNEUMONIAE; ACUTE MAXILLARY SINUSITIS; COMMUNITY-ACQUIRED SINUSITIS; RESPIRATORY-TRACT PATHOGENS; ACUTE OTITIS-MEDIA; NASOPHARYNGEAL COLONIZATION; COMMON COLD; HAEMOPHILUS-INFLUENZAE; MORAXELLA-CATARRHALIS; INVASIVE DISEASE C1 Sinus & Allergy Hlth Partnership, Washington, DC 20036 USA. Univ Pacific, Stockton, CA 95211 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 USA. Henry Ford Hosp, Dept Otolaryngol Head & Neck Surg, Detroit, MI 48202 USA. SUNY Buffalo, Buffalo, NY 14260 USA. CDC, Natl Ctr Infect Dis, Resp Dis Branch, Atlanta, GA 30333 USA. Univ Wisconsin, Madison, WI 53706 USA. Albany Med Coll, Dept Med, Albany, NY 12208 USA. Albany Med Coll, Dept Pharmacol, Albany, NY 12208 USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Univ Iowa, Coll Pharm, Iowa City, IA 52242 USA. Univ Nebraska, Dept Otolaryngol Head & Neck Surg, Lincoln, NE 68583 USA. Univ Texas, Hlth Sci Ctr, Sch Med, Houston, TX 77030 USA. US FDA, Div Anti Infect Drug Prod, Rockville, MD 20857 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Childrens Hosp, Pittsburgh, PA 15213 USA. Tufts Univ, Sch Med, New England Med Ctr, Medford, MA 02155 USA. RP Sinus & Allergy Hlth Partnership, 1990 M St NW,Suite 680, Washington, DC 20036 USA. NR 95 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JUL PY 2000 VL 123 IS 1 SU S BP S1 EP S32 DI 10.1067/mhn.2000.107873 PN 2 PG 32 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 338RK UT WOS:000088432900001 ER EF