FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Nightingale, SL AF Nightingale, SL TI New FDA web site for health care professionals SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 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 DEC 2 PY 1998 VL 280 IS 21 BP 1817 EP 1817 DI 10.1001/jama.280.21.1817 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 141ZZ UT WOS:000077176600005 PM 9846762 ER PT J AU Nightingale, SL AF Nightingale, SL TI New alcohol warning required for OTC analgesic/antipyretic products SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 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 DEC 2 PY 1998 VL 280 IS 21 BP 1817 EP 1817 DI 10.1001/jama.280.21.1817 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 141ZZ UT WOS:000077176600004 PM 9846762 ER PT J AU Nightingale, SL AF Nightingale, SL TI Jurisdiction over cloning technology to create human beings SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 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 DEC 2 PY 1998 VL 280 IS 21 BP 1817 EP 1817 DI 10.1001/jama.280.21.1817 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 141ZZ UT WOS:000077176600007 PM 9846762 ER PT J AU Kessler, L Brenner, RJ AF Kessler, L Brenner, RJ TI Serendipitous breast lesions on magnetic resonance imaging: Why is this lesion different from all other lesions? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material C1 US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. Univ Calif Los Angeles, Tower Breast Imaging Ctr, Los Angeles, CA USA. RP Kessler, L (reprint author), US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, 1350 Piccard Dr, Rockville, MD 20852 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 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 DEC 2 PY 1998 VL 90 IS 23 BP 1760 EP 1761 DI 10.1093/jnci/90.23.1760 PG 2 WC Oncology SC Oncology GA 144CV UT WOS:000077296900001 PM 9839510 ER PT J AU Roberts, T Golan, E Williams, R Messonnier, M Ready, R AF Roberts, T Golan, E Williams, R Messonnier, M Ready, R TI The adequacy of cost of illness for valuing health risk reductions: Applications to microbial food safety. SO AMERICAN JOURNAL OF AGRICULTURAL ECONOMICS LA English DT Meeting Abstract C1 US ERS, USDA, Washington, DC 20250 USA. US FDA, Rockville, MD 20857 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Agr Univ Norway, N-1432 As Nlh, Norway. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER AGRICULTURAL ECONOMICS ASSOC PI AMES PA 415 SOUTH DUFF AVE, STE C, AMES, IA 50010-6600 USA SN 0002-9092 J9 AM J AGR ECON JI Am. J. Agr. Econ. PD DEC PY 1998 VL 80 IS 5 BP 1165 EP 1165 PG 1 WC Agricultural Economics & Policy; Economics SC Agriculture; Business & Economics GA 163CZ UT WOS:000078386300100 ER PT J AU Levy, A Roe, B Teisl, MF Russell, M Moskovitz, D Austin, T AF Levy, A Roe, B Teisl, MF Russell, M Moskovitz, D Austin, T TI Electricity deregulation: What's in store for the environment? SO AMERICAN JOURNAL OF AGRICULTURAL ECONOMICS LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Univ Maine, Orono, ME 04469 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER AGRICULTURAL ECONOMICS ASSOC PI AMES PA 415 SOUTH DUFF AVE, STE C, AMES, IA 50010-6600 USA SN 0002-9092 J9 AM J AGR ECON JI Am. J. Agr. Econ. PD DEC PY 1998 VL 80 IS 5 BP 1183 EP 1183 PG 1 WC Agricultural Economics & Policy; Economics SC Agriculture; Business & Economics GA 163CZ UT WOS:000078386300249 ER PT J AU Fein, S Roe, B Whittington, L AF Fein, S Roe, B Whittington, L TI Successful coping strategies for balancing postpartum employment and breastfeeding. SO AMERICAN JOURNAL OF AGRICULTURAL ECONOMICS LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Georgetown Univ, Washington, DC 20057 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER AGRICULTURAL ECONOMICS ASSOC PI AMES PA 415 SOUTH DUFF AVE, STE C, AMES, IA 50010-6600 USA SN 0002-9092 J9 AM J AGR ECON JI Am. J. Agr. Econ. PD DEC PY 1998 VL 80 IS 5 BP 1201 EP 1201 PG 1 WC Agricultural Economics & Policy; Economics SC Agriculture; Business & Economics GA 163CZ UT WOS:000078386300406 ER PT J AU Teisl, MF Levy, A Bockstael, NE AF Teisl, MF Levy, A Bockstael, NE TI Nutrition labeling: Does the message reach the consumer? SO AMERICAN JOURNAL OF AGRICULTURAL ECONOMICS LA English DT Meeting Abstract C1 Univ Maine, Orono, ME 04469 USA. US FDA, Rockville, MD 20857 USA. Univ Maryland, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER AGRICULTURAL ECONOMICS ASSOC PI AMES PA 415 SOUTH DUFF AVE, STE C, AMES, IA 50010-6600 USA SN 0002-9092 J9 AM J AGR ECON JI Am. J. Agr. Econ. PD DEC PY 1998 VL 80 IS 5 BP 1201 EP 1201 PG 1 WC Agricultural Economics & Policy; Economics SC Agriculture; Business & Economics GA 163CZ UT WOS:000078386300403 ER PT J AU Sheehan, DM AF Sheehan, DM TI The developmental toxicity of phytoestrogens in experimental animals: are there concerns for humans? SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 1998 VL 68 IS 6 SU S BP 1543S EP 1543S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 145VM UT WOS:000077392300107 ER PT J AU Sheehan, DM Medlock, KL Burroughs, CD AF Sheehan, DM Medlock, KL Burroughs, CD TI Permanent effects of neonatal coumestrol and equol treatment in rats SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 1998 VL 68 IS 6 SU S BP 1543S EP 1544S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 145VM UT WOS:000077392300108 ER PT J AU Jones, CA McQuillan, GM Kusek, JW Eberhardt, MS Herman, WH Coresh, J Salive, M Jones, CP Agodoa, LY AF Jones, CA McQuillan, GM Kusek, JW Eberhardt, MS Herman, WH Coresh, J Salive, M Jones, CP Agodoa, LY TI Serum creatinine levels in the US population: Third National Health and Nutrition Examination Survey SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE NHANES III; cross-sectional population survey; serum creatinine; ethnicity/race; sex; age; kidney; renal function ID STAGE RENAL-DISEASE; UNITED-STATES POPULATION; NON-HISPANIC WHITES; MEXICAN-AMERICANS; EXCESS INCIDENCE; BLOOD-PRESSURE; HYPERTENSION; NIDDM; COMPLICATIONS; PREVALENCE AB This report describes the distribution of serum creatinine levels by sex, age, and ethnic group in a representative sample of the US population. Serum creatinine level was evaluated in the third National Health and Nutrition Examination Survey (NHANES III) in 18,723 participants aged 12 years and older who were examined between 1988 and 1994. Differences in mean serum creatinine levels were compared for subgroups defined by sex, age, and ethnicity (non-Hispanic white, non-Hispanic black, and Mexican-American). The mean serum creatinine value was 0.96 mg/dL for women in the United States and 1.16 mg/dL for men. Overall mean creatinine levels were highest in non-Hispanic blacks (women, 1.01 mg/dL; men, 1.25 mg/dL), lower in non-Hispanic whites (women, 0.97 mg/dL; men, 1.16 mg/dL), and lowest in Mexican-Americans (women, 0.86 mg/dL; men, 1.07 mg/dL). Mean serum creatinine levels increased with age among both men and women in all three ethnic groups, with total US mean levels ranging from 0.88 to 1.10 mg/dL in women and 1.00 to 1.29 mg/dL in men. The highest mean creatinine level was seen in non-Hispanic black men aged 60+ years. In the total US population, creatinine levels of 1.5 mg/dL or greater were seen in 9.74% of men and 1.78% of women. Overall, among the US noninstitutionalized population, 10.9 million people are estimated to have creatinine values of 1.5 mg/dL or greater, 3.0 million have values of 1.7 mg/dL or greater, and 0.8 million have serum creatinine levels of 2.0 mg/dL or greater. Mean serum creatinine values are higher in men, non-Hispanic blacks, and older persons and are lower in Mexican-Americans. In the absence of information on glomerular filtration rate (GFR) or lean body mass, it is not clear to what extent the variability by sex, ethnicity, and age reflects normal physiological differences rather than the presence of kidney disease. Until this information is known, the use of a single cutpoint to define elevated serum creatinine values may be misleading. (C) 1998 by the National Kidney Foundation, Inc. C1 NIDDKD, Program Epidemiol, NIH, DKUHD, Bethesda, MD 20892 USA. NIDDKD, Clin Trials Program, NIH, DKUHD, Bethesda, MD 20892 USA. NIDDKD, End Stage Renal Dis Program, NIH, DKUHD, Bethesda, MD 20892 USA. NIDDKD, Minor Hlth Program, NIH, DKUHD, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth Examinat Stat, Hyattsville, MD 20782 USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. US FDA, Ctr Biol Evaluat & Res, Div Biostat & Epidemiol, Rockville, MD 20857 USA. Univ Michigan, Med Ctr, Dept Internal Med, Div Endocrinol & Metab, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Jones, CP (reprint author), NIDDKD, Program Epidemiol, NIH, DKUHD, Natcher Bldg,Room 6AS-13K,45 Ctr Dr,MSC 6600, Bethesda, MD 20892 USA. NR 33 TC 365 Z9 377 U1 0 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD DEC PY 1998 VL 32 IS 6 BP 992 EP 999 DI 10.1016/S0272-6386(98)70074-5 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 145QY UT WOS:000077383900011 PM 9856515 ER PT J AU Hoi, L Dalsgaard, I DePaola, A Siebeling, RJ Dalsgaard, A AF Hoi, L Dalsgaard, I DePaola, A Siebeling, RJ Dalsgaard, A TI Heterogeneity among isolates of Vibrio vulnificus recovered from eels (Anguilla anguilla) in Denmark SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID EUROPEAN EEL; BIOTYPE-2; VIRULENCE; DNA; IDENTIFICATION; CAPSULE; EPIDEMIOLOGY; PHAGOCYTOSIS; INFECTIONS; SEROGROUP AB The findings of this study demonstrate that Vibrio vulnificus isolates recovered from diseased eels in Denmark are heterogeneous as shown by O serovars, capsule types, ribotyping, phage typing, and plasmid profiling, The study: includes 85 V. vulnificus isolates isolated from the gills, intestinal contents, mucus, spleen, and kidneys of eels during five disease outbreaks on two Danish eel farms from 1995 to 1997, along with a collection of 12 V. vulnificus reference strains, The results showed that more than one serovar may be capable of causing disease in eels and that these isolates are genetically heterogenous as shown by ribotyping, Ribotyping also showed that the same isolates map persist in an eel farm and cause recurrent outbreaks, Phage typing did not correlate with ribotyping or serotyping. However, we observed that 26 of 28 isolates, which mere not susceptible to any of the phages, showed the same ribotype, O serovar, and capsule type, This suggests that these Isolates mag possess features that make them resistant to lysis by the phages used in this study. Ninety-three of 97 isolates harbored between one and three high-molecular-weight plasmids which previously had been suggested to be associated with eel virulence, The subdivision of V. vulnificus into two biotypes based on the indole reaction can no longer be supported, since 82 of 97 isolates in this study mere indole positive, and a subdivision into serovars appears to he more correct. C1 Royal Vet & Agr Univ, Dept Vet Microbiol, DK-1870 Frederiksberg C, Denmark. Royal Vet & Agr Univ, Danish Inst Fisheries Res, DK-1870 Frederiksberg, Denmark. US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL USA. Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA. RP Hoi, L (reprint author), Royal Vet & Agr Univ, Dept Vet Microbiol, Stigboljen 4, DK-1870 Frederiksberg C, Denmark. NR 39 TC 38 Z9 39 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD DEC PY 1998 VL 64 IS 12 BP 4676 EP 4682 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 145XB UT WOS:000077396700008 PM 9835548 ER PT J AU Calci, KR Burkhardt, W Watkins, WD Rippey, SR AF Calci, KR Burkhardt, W Watkins, WD Rippey, SR TI Occurrence of male-specific bacteriophage in feral and domestic animal wastes, human feces, and human-associated wastewaters SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID RNA BACTERIOPHAGES; ESCHERICHIA-COLI; WATER; INACTIVATION; COLIPHAGES; INDICATORS; ENVIRONMENT; ORGANISMS; POLLUTION; VIRUS AB Male-specific bacteriophage (MSB) densities were determined in animal and human fecal wastes to assess their potential impact on aquatic environments. Fecal samples (1,031) from cattle, chickens, dairy cows, dogs, ducks, geese, goats, hogs, horses, seagulls, sheep, and humans as well as 64 sewerage samples were examined for MSB. All animal species were found to harbor MSB, although the great majority excreted these viruses at very low levels. The results from this study demonstrate that in areas affected by both human and animal wastes, wastewater treatment plants are the principal contributors of MSB to fresh, estuarine, and marine waters. C1 US FDA, Gulf Coast Seafodd Lab, US Publ Hlth Serv, Dauphin Island, AL 36528 USA. US FDA, US Publ Hlth Serv, Washington, DC 20204 USA. Univ Rhode Isl, Dept Microbiol, Kingston, RI 02881 USA. RP Calci, KR (reprint author), US FDA, Gulf Coast Seafodd Lab, US Publ Hlth Serv, POB 158, Dauphin Island, AL 36528 USA. EM KRC@VM.CFSAN.FDA.Gov NR 24 TC 83 Z9 87 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD DEC PY 1998 VL 64 IS 12 BP 5027 EP 5029 PG 3 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 145XB UT WOS:000077396700062 PM 9835602 ER PT J AU Krause, PR Lewis, AM AF Krause, PR Lewis, AM TI Safety of viral DNA in biological products SO BIOLOGICALS LA English DT Article ID CELLS AB Data from studies of the infectivity of DNA injected directly into laboratory animals are used to estimate the potential infectivity risk of residual DNA in biological products. The potential for some novel products to contain infectious quantities of residual cellular DNA is discussed, and further study of this subject is suggested. (C) 1998 The International Association of Biological Standardization. C1 US FDA, Off Vaccines Res & Rev, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Krause, PR (reprint author), US FDA, Off Vaccines Res & Rev, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 11 TC 8 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD DEC PY 1998 VL 26 IS 4 BP 317 EP 320 DI 10.1006/biol.1998.0161 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 202WB UT WOS:000080674200008 PM 10403035 ER PT J AU Berger, VW Permutt, T Ivanova, A AF Berger, VW Permutt, T Ivanova, A TI Convex hull test for ordered categorical data SO BIOMETRICS LA English DT Article DE data peeling; exact conditional test; margin-based test; Smirnov test; stochastic order ID CONTINGENCY-TABLES; ORDINAL DATA; INDEPENDENCE AB When testing for stochastic order in ordered 2 x J contingency tables, it is common to select the cutoff required to declare significance so as to ensure that the size of the test is exactly ct conditionally on the margins. It is valid, however, to use the margins to select not only the cutoff but also the form of the test. Linear rank tests, which are locally most powerful and frequently used in practice, suffer from the drawback that they may have power as low as zero to detect some alternatives of interest when the margins satisfy certain conditions. The Smirnov and convex hull tests are shown, through exact conditional power calculations and simulations, to avoid this drawback. The convex hull test is also admissible and palindromic invariant and minimizes the required significance level to have limiting power of one as the alternative moves away from the null in any direction. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Univ Maryland Baltimore Cty, Dept Math & Stat, Baltimore, MD 21250 USA. RP Berger, VW (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike 200S,HFM-215, Rockville, MD 20852 USA. NR 22 TC 18 Z9 18 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 1998 VL 54 IS 4 BP 1541 EP 1550 DI 10.2307/2533678 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 154PZ UT WOS:000077898700028 PM 9988542 ER PT J AU Flyer, PA AF Flyer, PA TI A comparison of conditional and unconditional randomization tests for highly stratified designs SO BIOMETRICS LA English DT Article DE conditional; permuted block; randomization; stratification; unconditional AB An unconditional randomization procedure is proposed for use in highly stratified randomized experiments where the sample size assigned to each treatment cannot be fixed in advance. This procedure is contrasted to the usual conditional randomization procedure in which sample sizes assigned within randomization units are treated as fixed and randomization units without both treatments assigned are deleted. The unconditional procedure is shown to have superior power for the populations studied. C1 US FDA, Div Biometr 4, Rockville, MD 20857 USA. RP Flyer, PA (reprint author), US FDA, Div Biometr 4, HFD-725,5600 Fishers Lane, Rockville, MD 20857 USA. NR 10 TC 0 Z9 0 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 1998 VL 54 IS 4 BP 1551 EP 1559 DI 10.2307/2533679 PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 154PZ UT WOS:000077898700029 PM 9883551 ER PT J AU Maudru, T Peden, K AF Maudru, T Peden, K TI Adaptation of the fluorogenic 5 '-nuclease chemistry to a PCR-based reverse transcriptase assay SO BIOTECHNIQUES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PRODUCT; SIGNALS C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Peden, K (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29A,Room 3D08,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 16 TC 35 Z9 35 U1 0 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD DEC PY 1998 VL 25 IS 6 BP 972 EP 975 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 147KV UT WOS:000077511300012 PM 9863050 ER PT J AU Swann, JP AF Swann, JP TI Networks of innovation: Vaccine development at Merck, Sharp & Dohme, and Mulford, 1895-1995. SO BULLETIN OF THE HISTORY OF MEDICINE LA English DT Book Review C1 US FDA, Hist Off, Rockville, MD 20857 USA. RP Swann, JP (reprint author), US FDA, Hist Off, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 0007-5140 J9 B HIST MED JI Bull. Hist. Med. PD WIN PY 1998 VL 72 IS 4 BP 786 EP 788 DI 10.1353/bhm.1998.0178 PG 3 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 149BJ UT WOS:000077585000032 ER PT J AU D'Agostino, RB Weintraub, M Russell, HK Stepanians, M D'Agostino, RB Cantilena, LR Graumlich, JF Maldonado, S Honig, P Anello, C AF D'Agostino, RB Weintraub, M Russell, HK Stepanians, M D'Agostino, RB Cantilena, LR Graumlich, JF Maldonado, S Honig, P Anello, C TI The effectiveness of antihistamines in reducing the severity of runny nose and sneezing: A meta-analysis SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID CLINICAL-TRIALS; METAANALYSIS C1 Boston Univ, Dept Math, Stat & Consulting Univ, Boston, MA 02215 USA. US FDA, Div Pulm Drugs, ODE,Ctr Drug Evaluat & Res, Rockville, MD USA. Muro Pharmaceut, Tewksbury, MA USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Uniformed Serv Univ Hlth Sci, Div Clin Pharmacol, Bethesda, MD USA. Univ Illinois, Dept Biomed & Therapeut Sci, Peoria, IL USA. RP D'Agostino, RB (reprint author), Boston Univ, Dept Math, Stat & Consulting Univ, 111 Cummington St, Boston, MA 02215 USA. RI Dagostino Jr, Ralph/C-4060-2017 OI Dagostino Jr, Ralph/0000-0002-3550-8395 NR 10 TC 10 Z9 10 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD DEC PY 1998 VL 64 IS 6 BP 579 EP 596 DI 10.1016/S0009-9236(98)90049-2 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 150JM UT WOS:000077661800001 PM 9871423 ER PT J AU Trapnell, CB Donahue, SR Collins, JM Flockhart, DA Thacker, D Abernethy, DR AF Trapnell, CB Donahue, SR Collins, JM Flockhart, DA Thacker, D Abernethy, DR TI Thalidomide does not alter the pharmacokinetics of ethinyl estradiol and norethindrone SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; RECURRENT APHTHOUS STOMATITIS; VERSUS-HOST DISEASE; DRUG-INTERACTIONS; ETHINYLESTRADIOL; PLASMA; ETHYNYLESTRADIOL; RADIOIMMUNOASSAY; METABOLISM; AIDS AB Objective: To evaluate the effect of thalidomide on the plasma pharmacokinetics of ethinyl estradiol (INN, ethinylestradiol) and norethindrone (PNN, norethisterone), Methods: Ten women who had undergone surgical sterilization were enrolled in an open-label crossover study conducted in the Georgetown University Clinical Research Center. The pharmacokinetics of single doses of 0.07 mg ethinyl estradiol and 2 mg norethindrone were measured at baseline and after 3 weeks of 200 mg thalidomide. Compliance with the thalidomide regimen was assessed with use of Medication Event Monitoring System (MEMS) caps. Results: No changes were observed in the pharmacokinetics of ethinyl estradiol or norethindrone with thalidomide therapy. The mean +/- SD area under the plasma concentration-time curve (AUC(0-infinity)) for ethinyl estradiol was 6580 +/- 1100 ng.h/L at baseline and 5970 +/- 1560 ng h/L after the thalidomide regimen (paired t test, P > .05), The values for norethindrone were 103 +/- 54 mu g h/L and 107 +/- 58 mu g.h/L (paired t test, P > .05), No changes were observed for other pharmacokinetic parameters assessed for either ethinyl estradiol or norethindrone. No accumulation of thalidomide was seen after 21 days of therapy: day 1 AUC(0-infinity) 41.1 +/- 13.9 mu g.h/mL; day 21 AUC(0-infinity) 59.6 +/- 27.3 mu g.h/mL, (paired t test, P > .05), No changes were observed for other pharmacokinetic parameters assessed for thalidomide between days 1 and 21, Thalidomide was well tolerated but caused variable degrees of sedation. The average thalidomide compliance rate was 97%, Conclusions: The pharmacokinetics of thalidomide do not change with 3 weeks of daily dosing. Thalidomide does not alter the pharmacokinetics of ethinyl estradiol or norethindrone. Therefore there is no drug interaction between thalidomide and these 2 drugs. The efficacy of oral contraceptives containing ethinyl estradiol and norethindrone should not be affected by concomitant thalidomide therapy. C1 US FDA, Rockville, MD 20857 USA. Georgetown Univ, Med Ctr, Div Clin Pharmacol, Washington, DC 20007 USA. RP Trapnell, CB (reprint author), GloboMax LLC, 7250 Pkwy Dr,Suite 430, Hanover, MD 21076 USA. FU NIA NIH HHS [R01 AG08226-07]; NIGMS NIH HHS [T32 GM08386-08]; PHS HHS [223-93-3011] NR 27 TC 20 Z9 20 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD DEC PY 1998 VL 64 IS 6 BP 597 EP 602 DI 10.1016/S0009-9236(98)90050-9 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 150JM UT WOS:000077661800002 PM 9871424 ER PT J AU Ellenberg, SS AF Ellenberg, SS TI Clinical trials and treatment effects monitoring - Comment SO CONTROLLED CLINICAL TRIALS LA English DT Editorial Material C1 US FDA, Div Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Ellenberg, SS (reprint author), US FDA, Div Biostat & Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-210, Rockville, MD 20852 USA. NR 5 TC 1 Z9 1 U1 0 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 DEC PY 1998 VL 19 IS 6 BP 529 EP 531 PG 3 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 149MN UT WOS:000077609400005 ER PT J AU Lachenbruch, PA AF Lachenbruch, PA TI Sensitivity, specificity, and vaccine efficacy SO CONTROLLED CLINICAL TRIALS LA English DT Article DE vaccine efficacy; sensitivity; specificity; variance of estimate AB We study the effects of imperfect sensitivity and specificity on estimation of vaccine efficacy (VE). We show that a specificity of <1.0 (i.e., some noncases are classified as cases) can reduce the value of the estimate of VE. One may attempt to adjust the estimate by accounting for the values of sensitivity and specificity. This increases the variance of the estimate of VE and leads to larger sample size requirements. Alternatively, one may adopt the diagnosis method as the disease definition. Controlled Clin Trials 1998; 19:569-574 (C) Elsevier Science Inc. 1998. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Lachenbruch, PA (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-215, Rockville, MD 20852 USA. NR 2 TC 20 Z9 21 U1 0 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 DEC PY 1998 VL 19 IS 6 BP 569 EP 574 DI 10.1016/S0197-2456(98)00042-7 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 149MN UT WOS:000077609400013 PM 9875836 ER PT J AU Broadbent, TA Broadbent, HS AF Broadbent, TA Broadbent, HS TI 1 similar to the chemistry and pharmacology of indole-3-carbinol (indole-3-methanol) and 3-(methoxymethyl)indole. [Part II] SO CURRENT MEDICINAL CHEMISTRY LA English DT Review ID GLUTATHIONE-S-TRANSFERASE; NATURALLY-OCCURRING INDOLES; DIETHYLNITROSAMINE-INDUCED HEPATOCARCINOGENESIS; PLANT-COMPOUND INDOLE-3-CARBINOL; MULTIORGAN CARCINOGENESIS MODEL; DRUG-METABOLIZING-ENZYMES; BREAST-CANCER PREVENTION; MAMMARY EPITHELIAL-CELLS; FALL ARMYWORM LARVAE; RAINBOW-TROUT AB Indole-3-carbinol (I3C) (2) is produced endogenously from naturally occurring glucosinolates contained in a wide variety of plant food substances including members of the family Cruciferae, and particularly members of the genus Brassica, whenever they are crushed or cooked. The acid environment of the gut very facilely converts it into a range of polyaromatic indolic compounds, e.g. (3,4,5), which appear to be responsible for many of the physiological effects observed following the ingestion of these foods. These so-called chemopreventive compounds are important because of their enzyme induction and suppression, mutagenic, carcinogenic and, particularly, antimutagenic and anticarcinogenic properties against a variety of classes of carcinogens. These properties as well as other miscellaneous properties of these substances are critically reviewed in detail in this paper of >170 references, the second of two parts. At the present time it appears that 13C and its congeners have considerable potential as natural prophylactic anticancer agents against certain common neoplasms, especially inasmuch modern diets are increasingly deficient in these vegetable-derived substances. A short general assessment of the substantial potential of the title compounds concludes the review. C1 US FDA, Ctr Drug Evaluat & Res, ONDC, DNDC1,Div Neuropharmacol Drug Prod HFD120, Rockville, MD 20852 USA. Brigham Young Univ, Dept Chem, Provo, UT 84602 USA. RP Broadbent, TA (reprint author), US FDA, Ctr Drug Evaluat & Res, ONDC, DNDC1,Div Neuropharmacol Drug Prod HFD120, Woodmont 2,1451 Rockville Pike, Rockville, MD 20852 USA. NR 173 TC 39 Z9 40 U1 1 U2 3 PU BENTHAM SCIENCE PUBL BV PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD DEC PY 1998 VL 5 IS 6 BP 469 EP 491 PG 23 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 141WZ UT WOS:000077168400004 PM 9873111 ER PT J AU Varmus, H Henney, JE AF Varmus, H Henney, JE TI Abstracts of the NIH-FDA Conference "Biomarkers and Surrogate Endpoints: Advancing Clinical Research and Applications" - Foreword SO DISEASE MARKERS LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. RP Varmus, H (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA VAN DIEMENSTRAAT 94, 1013 CN AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PD DEC PY 1998 VL 14 IS 4 BP 188 EP 188 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 220PE UT WOS:000081673700001 ER PT J AU Li, XF Liu, CS Roos, P Hansen, EB Cerniglia, CE Dovichi, NJ AF Li, XF Liu, CS Roos, P Hansen, EB Cerniglia, CE Dovichi, NJ TI Nonaqueous capillary electrophoretic separation and thermo-optical absorbance detection of five tricyclic antidepressants and metabolism of amitriptyline by Cunninghamella elegans SO ELECTROPHORESIS LA English DT Article DE antidepressants; nonaqueous capillary electrophoresis; thermo-optical absorbance ID CHROMATOGRAPHY-MASS-SPECTROMETRY; MINIATURIZED PROTEIN MICROSEQUENCER; PERFORMANCE LIQUID-CHROMATOGRAPHY; AMINO-ACID IDENTIFICATION; GAS-CHROMATOGRAPHY; MAMMALIAN METABOLISM; MICROBIAL MODELS; NORTRIPTYLINE; DRUGS; IMIPRAMINE AB We developed a technique based on nonaqueous capillary electrophoresis and laser-based thermo-optical absorbance detection to assay five antidepressants with similar structures and mass-to-charge ratios. A mixture of methanol and acetonitrile with ammonium acetate was essential to achieve baseline resolution of these compounds. We investigated the effects of ammonium acetate concentration, temperature, applied voltage, and capillary length on separation efficiency. The nonaqueous capillary electrophoresis and laser-based thermo-optical absorbance detection technique was used to study the metabolism of amitriptyline by Cunninghamella elegans. Sample preparation procedures were simplified for fast screening of the parent drug and its metabolites. Reproducible electropherograms were obtained from replicate cultures of C. elegans growing in the presence of amitriptyline. C1 Univ Alberta, Dept Chem, Edmonton, AB T6G 2G2, Canada. Sciex, MDS Hlth Grp, Concord, ON, Canada. US FDA, Natl Ctr Toxicol Res, Div Microbiol & Chem, Jefferson, AR 72079 USA. RP Dovichi, NJ (reprint author), Univ Alberta, Dept Chem, Edmonton, AB T6G 2G2, Canada. OI Li, Xing-Fang/0000-0003-1844-7700 NR 40 TC 23 Z9 24 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD DEC PY 1998 VL 19 IS 18 BP 3178 EP 3182 DI 10.1002/elps.1150191821 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 159ZA UT WOS:000078204800020 PM 9932812 ER PT J AU Liu, CS Li, XF Pinto, D Hansen, EB Cerniglia, CE Dovichi, NJ AF Liu, CS Li, XF Pinto, D Hansen, EB Cerniglia, CE Dovichi, NJ TI On-line nonaqueous capillary electrophoresis and electrospray mass spectrometry of tricyclic antidepressants and metabolic profiling of amitriptyline by Cunninghamella elegans SO ELECTROPHORESIS LA English DT Article DE antidepressants; nonaqueous capillary electrophoresis; electrospray mass spectrometry ID SEPARATION; TAMOXIFEN AB An on-line nonaqueous capillary electrophoresis-electrospray mass spectrometry (ESI-MS) technique was developed using a commercial ion spray interface. The nonaqueous capillary electrophoresis ESI-MS system was used to profile tricyclic antidepressants of similar structures and mass-to-charge ratios. We found that pure methanol can be used as a sheath liquid to obtain stable ion spray from nonaqueous capillary electrophoresis. The flow rate of the coaxial nebulizing gas affected baseline signals, separation efficiency, and migration times. Other nonaqueous capillary electrophoresis operating conditions and electrospray parameters were optimized for enhanced baseline separation and high sensitivity detection. The effect of sample stacking on separation and detection was evaluated. The calculated detection limits were approximately 3 pg injected onto the capillary. ESI mass spectra of tricyclic antidepressants from a single quadrupole MS were obtained and elucidated. The information was used to propose fragmentation pathways of the tricyclic antidepressants. The method was also used to analyze the metabolites of amitriptyline produced by the fungus Cunninghamella elegans. Sixteen metabolites were detected and most of them were tentatively identified as demethylated and/or hydroxylated, and/or N-oxidized products. C1 Univ Alberta, Dept Chem, Edmonton, AB, Canada. Sciex, MDS Hlth Grp, Concord, ON, Canada. US FDA, Natl Ctr Toxicol Res, Div Microbiol & Chem, Jefferson, AR 72079 USA. RP Dovichi, NJ (reprint author), Univ Alberta, Dept Chem, Edmonton, AB, Canada. OI Li, Xing-Fang/0000-0003-1844-7700 NR 22 TC 38 Z9 40 U1 0 U2 6 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD DEC PY 1998 VL 19 IS 18 BP 3183 EP 3189 DI 10.1002/elps.1150191822 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 159ZA UT WOS:000078204800021 PM 9932813 ER PT J AU Hooper, K Petreas, MX Chuvakova, T Kazbekova, G Druz, N Seminova, G Sharmanov, T Hayward, D She, JW Visita, P Winkler, J McKinney, M Wade, TJ Grassman, J Stephens, RD AF Hooper, K Petreas, MX Chuvakova, T Kazbekova, G Druz, N Seminova, G Sharmanov, T Hayward, D She, JW Visita, P Winkler, J McKinney, M Wade, TJ Grassman, J Stephens, RD TI Analysis of breast milk to assess exposure to chlorinated contaminants in Kazakstan: High levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in agricultural villages of southern Kazakstan SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE breast milk; co-planar PCBs; dioxins; exposure assessment; furans; Kazakstan; TCDD ID DIOXIN-LIKE COMPOUNDS; POLYCHLORINATED-BIPHENYLS; PERINATAL EXPOSURE; BODY BURDEN; P-DIOXIN; PCBS; WORKSHOP; PCDD AB To assess levels of chlorinated contaminants in breast milk, we measured organochlorine pesticides, polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) in breast milk samples collected in 1994 according to the World Health Organization protocol From 92 donors that were representative of regional populations in southern Kazakstan. High levels (10-120 pg/g fat) of: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic of the PCDD/PCDF congeners, were found in breast milk samples from an agricultural region. TCDD was the major contributor (75%) to the international toxicity equivalents of these samples. The same distinctive PCDD/PCDF congener pattern was found in 15 breast milk samples and 4 serum samples collected in 1996 in a follow-up study, and has now been confirmed by three analytical laboratories. C1 Calif Environm Protect Agcy, Hazardous Mat Lab, Berkeley, CA 94707 USA. Kazakstan Minist Hlth, Phys Inst Postgrad Training, Almaty, Kazakhstan. Kazmekhanobr Res Ind Ecol, Almaty, Kazakhstan. Inst Nutr, Almaty, Kazakhstan. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Hooper, K (reprint author), Calif Environm Protect Agcy, Hazardous Mat Lab, 2151 Berkeley Way, Berkeley, CA 94707 USA. NR 40 TC 40 Z9 41 U1 3 U2 6 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1998 VL 106 IS 12 BP 797 EP 806 DI 10.1289/ehp.98106797 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 155PB UT WOS:000077954600020 PM 9831540 ER PT J AU Goldstein, LS Weyand, EH Safe, S Steinberg, M Culp, SJ Gaylor, DW Beland, FA Rodriguez, LV AF Goldstein, LS Weyand, EH Safe, S Steinberg, M Culp, SJ Gaylor, DW Beland, FA Rodriguez, LV TI Tumors and DNA adducts in mice exposed to benzo[a]pyrene and coal tars: Implications for risk assessment SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Conference on Current Issues of Chemical Mixtures CY AUG 11-13, 1997 CL FT COLLINS, COLORADO SP Colorado State Univ, Natl Inst Environm Hlth Sci Superfund Basic Res Program, Agcy Tox Subst & Dis Registry, US EPA, Off Solid Waste & Emergency Response, US EPA,. Reg VIII Off, USA Ctr Environm Hlth Res, Elect Power Res Inst DE coal tar; benzo[a]pyrene; benzpyrenediolepoxide; DNA adducts; infant mouse; A/J mouse; liver tumors; lung tumors; forestomach tumors; risk assessment ID GAS PLANT RESIDUE; B6C3F1 MICE; AROMATIC-HYDROCARBONS; GENE-EXPRESSION; CARCINOGENICITY; INDUCTION; INGESTION; MIXTURE AB Current methods to estimate the quantitative cancer risk of complex mixtures of polycyclic aromatic hydrocarbons (PAH) such as coal tar assume that overall potency can be derived from knowledge of the concentration of a few carcinogenic components such as benzo[a]pyrene (B[a]P). Genotoxic damage, such as DNA adducts, is thought to be an essential aspect of PAH-induced tumorigenesis and could be a biomarker for exposure useful for estimating risk. However, the role of B[a]P and the relationship of adduct formation in tumorigenesis have not been tested rigorously in models appropriate for human health risk assessment. Therefore, we directly compared tumor induction and adduct formation by B[a]P and coal tars in several experimental protocols, including one broadly accepted and used by regulators. We found that B[a]P content did not account for tumor incidences after exposure to coal tars. DNA adducts were found in both rumors and tumor-free tissue and tumor outcomes were not predicted by either quantitation of total DNA adducts or by the DNA adduct formed by B[a]P. These data suggest that risk assessments based on B[a]P content may not predict accurately risk to human health posed by environmental PAH. C1 Elect Power Res Inst, Palo Alto, CA 94303 USA. Rutgers State Univ, Coll Pharm, Piscataway, NJ USA. Texas A&M Univ, Dept Vet Physiol & Pharmacol, College Stn, TX 77843 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Texas, MD Anderson Cancer Ctr, Dept Mol Pathol, Houston, TX 77030 USA. RP Goldstein, LS (reprint author), Elect Power Res Inst, 3412 Hillview Ave, Palo Alto, CA 94303 USA. NR 22 TC 40 Z9 43 U1 0 U2 6 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1998 VL 106 SU 6 BP 1325 EP 1330 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 156NT UT WOS:000078008100010 PM 9860888 ER PT J AU Snyderwine, EG Sadrieh, N King, RS Schut, HAJ AF Snyderwine, EG Sadrieh, N King, RS Schut, HAJ TI Formation of DNA adducts of the food-derived mutagen 2-amino-9H-pyrido[2,3-b]indole (A(alpha)C) and bioassay of mammary gland carcinogenicity in Sprague-Dawley rats SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE heterocyclic amines; diet; breast cancer; postlabelling assay; cooked meat ID CIGARETTE-SMOKE CONDENSATE; AMINO-ALPHA-CARBOLINES; HETEROCYCLIC AMINES; COOKED FOOD; IN-VIVO; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; P-32-POSTLABELING METHOD; SOYBEAN GLOBULIN; LIVER-MICROSOMES; SALIVARY-GLANDS AB 2-amino-9H-pyrido[2,3-b]indole (A alpha C) is a heterocyclic amine found at relatively high concentrations in barbecued or grilled meats. In the current study, the mammary gland carcinogenicity of A alpha C was examined in female Sprague-Dawley rats given IO doses of A alpha C (75 mg/kg, orally, once per day starting at 43 days of age) and placed on a defined high-fat diet (23.5% corn oil), a strong promotional factor for rat mammary gland carcinogenesis. Within 1 year, one out of 20 rats dosed with A alpha C developed a tubulopapillary carcinoma, indicating that the-bioassay was largely negative. As DNA adduct formation is considered to play a role in carcinogenesis, A alpha C-DNA adduct levels were measured in the mammary gland and other tissues by the P-32-postlabelling method. Under intensification conditions, one major adduct and up to three minor adducts were detected in isolated mammary gland epithelial cells and other tissues (liver, stomach, small intestine, colon and kidney) of A alpha C-treated rats; the adduct patterns were similar in all tissues examined. The major adduct, comprising 60-100% of total DNA adduct levels in tissues, was chromatographically identical to the principal adduct found in 3'-dGp-A alpha C (synthesized by reacting 3'-phospho-2'-deoxyguanosine (3'-dGp) with N-acetoxy-A alpha C). Of the tissues examined, the highest A alpha C-DNA adduct levels were found in the liver. In male rats given a single dose of A alpha C (75 mg/kg, orally, 3 hr prior to necropsy), no A alpha C-DNA adducts were detected in extrahepatic tissues. In female rats given a single dose or 12 daily doses of A alpha C, hepatic DNA adduct levels were at least 12-13-fold higher than those in any other tissue. Mean total A alpha C-DNA adduct levels in mammary gland epithelial cells and liver from female rats given multiple doses of A alpha C were 3.5 and 50.7 (RAL x 10(7)), respectively. Although factors in addition to DNA adduct formation are likely to play a role in mammary gland carcinogenesis, the results suggest that the weak mammary gland carcinogenicity of A alpha C may in part be associated with low A alpha C-DNA adduct levels in the mammary gland epithelium. Published by Elsevier Science Ltd. C1 NCI, Expt Carcinogenesis Lab, Chem Carcinogenesis Sect, NIH, Bethesda, MD 20892 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Med Coll Ohio, Dept Pathol, Toledo, OH 43614 USA. RP Snyderwine, EG (reprint author), NCI, Expt Carcinogenesis Lab, Chem Carcinogenesis Sect, NIH, Bldg 37,Room 3C28, Bethesda, MD 20892 USA. RI King, Roberta/A-1749-2010 OI King, Roberta/0000-0002-3550-4255 NR 49 TC 13 Z9 13 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD DEC PY 1998 VL 36 IS 12 BP 1033 EP + DI 10.1016/S0278-6915(98)00088-X PG 8 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 147QK UT WOS:000077577400001 PM 9862644 ER PT J AU Chung, KT Lu, Z Chou, MW AF Chung, KT Lu, Z Chou, MW TI Mechanism of inhibition of tannic acid and related compounds on the growth of intestinal bacteria SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE growth; intestinal bacteria; inhibition; iron deprivation; tannic acid ID IRON TRANSPORT COMPOUNDS; CONDENSED TANNINS; PLANT POLYPHENOLS; SIDEROPHORES; MICROORGANISMS; CHEMISTRY; DIETARY AB Tannic acid, propyl gallate and methyl gallate, but not gallic acid, were found to be inhibitory to the growth of intestinal bacteria Bacteroides fragilis ATCC 25285, Clostridium clostridiiforme ATCC 25537, C. perfringens ATCC 13124, C. paraputrificum ATCC 25780, Escherichia coli ATCC 25922, Enterobacter cloacae ATCC 13047, Salmonella typhimurium TA98 and S. typhimurium YG1041 at 100-1000 mu g/ml in culture broth. Neither Bifidobacterium infantis ATCC 15697 nor Lactobacillus acidophilus ATCC 4356 was inhibited by any of the above compounds up to 500 mu g/ml. Tannic acid has a much greater relative binding efficiency to iron than propyl gallate, methyl gallate or gallic acid. The inhibitory effect of tannic acid to the growth of intestinal bacteria may be due to the strong iron binding capacity of tannic acid; whereas the effect of propyl gallate and methyl gallate probably occurs by a different mechanism. The growth of E. coli was restored by the addition of iron to the medium after the precipitate caused by tannic acid was removed. Neither B. infantis nor L. acidophilus require iron for growth. This probably contributes to their resistance to tannic acid. Because tannins are abundant in the human diet, tannins may affect the growth of some intestinal bacteria and thus may have an impact on human health. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Univ Memphis, Dept Microbiol & Mol Cell Sci, Memphis, TN 38152 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Chung, KT (reprint author), Univ Memphis, Dept Microbiol & Mol Cell Sci, Memphis, TN 38152 USA. RI Lu, Zhen/E-5221-2015 NR 38 TC 126 Z9 136 U1 0 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 EI 1873-6351 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD DEC PY 1998 VL 36 IS 12 BP 1053 EP 1060 DI 10.1016/S0278-6915(98)00086-6 PG 8 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 147QK UT WOS:000077577400003 PM 9862646 ER PT J AU Sprando, RL Collins, TFX Black, T Olejnik, N Rorie, J AF Sprando, RL Collins, TFX Black, T Olejnik, N Rorie, J TI Testing the potential of sodium fluoride to affect spermatogenesis: a morphometric study SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE morphology; testis; long-term fluoride exposure; male rat; reproductive toxicology ID REPRODUCTIVE-ORGANS; LEYDIG-CELLS; MALE-MICE; RAT; SPERMATOZOA; RABBITS; TUBULES; MOUSE AB This study provides quantitative information on the effect of sodium fluoride (NaF) on the testes of F-1 generation male rats exposed in utero and during lactation to NaF at one of Four concentrations (25, 100, 175, 250 ppm). At weaning, the F-1 generation males were exposed to NaF in their drinking water for 14 weeks, after which time testicular tissues were perfusion-fixed with glutaraldehyde and observed after being embedded in plastic. The seminiferous tubules comprised 89%, 87%, 88%, 88% and 88% of the total testis volume while the interstitial space occupied 9.3%, 11.2%, 10.2%, 9.8% and 9.9% of the total testis volume for the 0, 25, 100, 175 and 250 ppm NaF treatment groups, respectively. Statistically significant differences between control and NaF-treated rats were not observed with respect to absolute volume of the seminiferous tubules, interstitial space, Leydig cells, blood vessels boundary layer, lymphatic space, macrophages, tubular lumen or absolute tubular length and absolute tubular surface area, mean Sertoli cell nucleoli number per tubular cross-section, mean seminiferous tubule diameter and the mean height of the seminiferous epithelium. A statistically significant decrease in the absolute volume and volume percent of the lymphatic;endothelium was observed in the 175 and 250 ppm NaF-treated groups and in the testicular capsule in the 100 ppm NaF-treated groups. The significance of this finding is unknown at the present time. Overall, the quantitative information obtained suggests that exposure to NaF at the doses used in the present study does not adversely affect testis structure or spermatogenesis in the rat. (C) 1998 Elsevier Science Ltd All rights reserved. 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 47 TC 19 Z9 19 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD DEC PY 1998 VL 36 IS 12 BP 1117 EP 1124 DI 10.1016/S0278-6915(98)00085-4 PG 8 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 147QK UT WOS:000077577400011 PM 9862654 ER PT J AU Smith, MA AF Smith, MA TI Minimizing microbial hazards for fresh produce SO FOOD TECHNOLOGY LA English DT Editorial Material C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Smith, MA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 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 DEC PY 1998 VL 52 IS 12 BP 140 EP 140 PG 1 WC Food Science & Technology SC Food Science & Technology GA 149GB UT WOS:000077595800019 ER PT J AU Li, HM Llera, A Tsuchiya, D Leder, L Ysern, X Schlievert, PM Karjalainen, K Mariuzza, RA AF Li, HM Llera, A Tsuchiya, D Leder, L Ysern, X Schlievert, PM Karjalainen, K Mariuzza, RA TI Three-dimensional structure of the complex between a T cell receptor beta chain and the superantigen staphylococcal enterotoxin B SO IMMUNITY LA English DT Article ID REFINED CRYSTAL-STRUCTURE; CLASS-II MOLECULES; BACTERIAL SUPERANTIGEN; ALPHA-CHAIN; YERSINIA-PSEUDOTUBERCULOSIS; 3-DIMENSIONAL STRUCTURE; ANTIGEN RECEPTOR; SPE-C; MHC; RECOGNITION AB Superantigens (SAGs) are a class of immunostimulatory proteins of bacterial or viral origin that activate T cells by binding to the V beta domain of the T cell antigen receptor (TCR). The three-dimensional structure of the complex between a TCR beta chain (mouse V beta 8.2) and the SAG staphylococcal enterotoxin B (SEB) at 2.4 Angstrom resolution reveals why SEE recognizes only certain V beta families, as well as why only certain SAGs bind mouse V beta 8.2. Models of the TCR-SEB-peptide/MHC class II complex indicate that V alpha interacts with the MHC beta chain in the TCR-SAG-MHC complex. The extent of the interaction is variable and is largely determined by the geometry of V alpha/V beta domain association. This variability can account for the preferential expression of certain V alpha regions among T cells reactive with SEE. C1 Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Univ Minnesota, Sch Med, Dept Microbiol, Minneapolis, MN 55455 USA. Basel Inst Immunol, CH-4005 Basel, Switzerland. RP Mariuzza, RA (reprint author), Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, 9600 Gudelsky Dr, Rockville, MD 20850 USA. EM mariuzza@indigo2.carb.nist.gov RI Karjalainen, Klaus/A-2206-2011 FU CSR NIH HHS [RG2747]; NIAID NIH HHS [AI36900, AI42937] NR 66 TC 139 Z9 144 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 1998 VL 9 IS 6 BP 807 EP 816 DI 10.1016/S1074-7613(00)80646-9 PG 10 WC Immunology SC Immunology GA 153MJ UT WOS:000077836600006 PM 9881971 ER PT J AU Marchalonis, JJ Schluter, SF Bernstein, RM Hohman, VS AF Marchalonis, JJ Schluter, SF Bernstein, RM Hohman, VS TI Antibodies of sharks: revolution and evolution SO IMMUNOLOGICAL REVIEWS LA English DT Review ID IMMUNOGLOBULIN LIGHT-CHAIN; T-CELL RECEPTOR; PHYLOGENETICALLY PRIMITIVE VERTEBRATE; OPEN READING FRAME; HEAVY-CHAIN; MOLECULAR EVOLUTION; GENE ORGANIZATION; IMMUNE-SYSTEM; PRIMORDIAL IMMUNOGLOBULIN; V(D)J RECOMBINATION AB The combinatorial immune response is restricted to jawed vertebrates with cartilaginous fishes being the lowest extant species to have the mechanism for diversification and an extensive panoply of immunoglobulins, T-cell receptors and MHC products. Here, we review the molecular events of the "big bang" or rapid evolutionary appearance of the functionally complete combinatorial immune system coincident with the appearance of ancestral jawed vertebrates, suggesting that this event was catalyzed by horizontal transfer of DNA processing systems. We analyze the nature and extent of variable and constant domain diversity among the distinct immunoglobulin sets of carcharhine sharks focusing upon the lambda-like light chains and the mu and omega heavy chains. The detection and isolation of natural antibodies from the blood of unimmunized sharks illustrates a surprising range of recognition specificities and the existence of polyspecificity suggests that the antibody-forming system of sharks offers unique opportunities for studies of immunological regulation. Although the homologies between shark and mammalian immunoglobulins are unequivocal, major differences in segmental gene organization present challenges to our understanding of basic immunological phenomena such as clonal restriction. C1 Univ Arizona, Dept Microbiol & Immunol, Coll Med, Tucson, AZ 85724 USA. US FDA, Bethesda, MD 20014 USA. MIT, Dept Biol, Cambridge, MA USA. RP Marchalonis, JJ (reprint author), Univ Arizona, Dept Microbiol & Immunol, Coll Med, POB 24-5049, Tucson, AZ 85724 USA. EM dianah@u.arizona.edu NR 109 TC 54 Z9 57 U1 1 U2 9 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD DEC PY 1998 VL 166 BP 103 EP 122 DI 10.1111/j.1600-065X.1998.tb01256.x PG 20 WC Immunology SC Immunology GA 153LV UT WOS:000077835300009 PM 9914906 ER PT J AU Bhushan, R Anthony, BF Frasch, CE AF Bhushan, R Anthony, BF Frasch, CE TI Estimation of group B streptococcus type III polysaccharide-specific antibody concentrations in human sera is antigen dependent SO INFECTION AND IMMUNITY LA English DT Article ID PROTEIN CONJUGATE VACCINE; CAPSULAR POLYSACCHARIDE; IMMUNOGENICITY; DISEASE; INFANTS; ADULTS; ELISA AB The presence of immunoglobulin G (IgG) antibodies against group B streptococcus (GBS) type III polysaccharide (PS) has been correlated with protection against GBS disease. The GBS type III PS is structurally similar to the pneumococcal type 14 PS, differing only in the presence of sialic acid residues. Four different preparations of GBS type III PS were evaluated for their specificity in enzyme-linked immunosorbent assay (ELISA): free PS, free PS mixed with methylated human serum albumin (mHSA), PS conjugated to biotin and PS conjugated to human serum albumin. Three groups of human sera were used to evaluate these PS preparations: sera from recipients of a GBS PS vaccine, sera from women receiving a GBS type III PS-tetanus toroid conjugate vaccine, and sera from nonimmunized healthy women of childbearing age. Estimated antibody concentrations were different depending on the PS preparation used. Using any of the four preparations, we were able to measure less than or equal to 0.05 mu g of IgG antibody to the GBS type III PS per ml. The specificity of the assay was determined by competitive inhibition with homologous and heterologous PS. The pneumococcal type 14 PS did not inhibit binding of antibody to the native GBS type III PS in sera from adults receiving the GBS PS vaccine or in sera from nonimmunized adults (except serum G9). The pneumococcal type 14 PS inhibited 50% in sera from recipients of GBS type III conjugate vaccine and in serum G9 when GBS type III PS conjugated to biotin or to HSA was used as antigen in ELISA. These data show that free GBS type III PS or PS mixed with mHSA is a sensitive and specific antigen for ELISA and that conjugation can alter the antigenic specificity of a PS. C1 US FDA, Lab Bacterial Polysaccharides, Div Bacterial Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Bhushan, R (reprint author), US FDA, Lab Bacterial Polysaccharides, Div Bacterial Prod, Ctr Biol Evaluat & Res, 29 Lincoln Dr, Bethesda, MD 20892 USA. NR 33 TC 14 Z9 15 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1998 VL 66 IS 12 BP 5848 EP 5853 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 142BG UT WOS:000077179600034 PM 9826364 ER PT J AU Khachik, F Steck, A Niggli, UA Pfander, H AF Khachik, F Steck, A Niggli, UA Pfander, H TI Partial synthesis and structural elucidation of the oxidative metabolites of lycopene identified in tomato paste, tomato juice, and human serum SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE 1,16-didehydro-2,6-cyclolycopen-5-ol; 2,6-cyclolycopene-1,5-diol; 2,6-cyclolycopenc-1,5-epoxide; lycopene 1,6 ; 2,5-diepoxide; lycopene 5,6-epoxide; lycopene oxidation products; new serum carotenoids; carotenoid metabolites; NMR; HPLC mass spectrometry ID CAROTENOIDS; PRODUCTS; CANCER AB Two oxidative metabolites of lycopene in tomato paste, tomato juice, and human serum have been prepared by partial synthesis from oxidation of lycopene with m-chloroperbenzoic acid (MCPBA) followed by acidic hydrolysis. Extensive H-1 and C-13 NMR spectroscopy studies of the purified products of these reactions have confirmed that the major oxidation products of lycopene (I) are lycopene 1,2-epoxide (II) and lycopene 5,6-epoxide (III) (tentative assignment). Several diepoxides of lycopene, namely, lycopene 1,2;5,6-diepoxide (IV), lycopene 1,2;5',6'-diepoxide (V), lycopene 5,6;5',6'-diepoxide (VI), and lycopene 1,2;1',2'-diepoxide (VII), which were formed as minor products, were tentatively identified. Whereas lycopene 1,2-epoxide was found to be fairly stable, lycopene 5,6-epoxide underwent cyclization to form a mixture of diastereomeric epoxides A (VIII, major) and B (IX, minor). The trivial names of 2,6-cyclolycopene-l,5-epoxides A (VIII) and B (IX) have been assigned to these compounds with a novel five-membered ring end-group. Hydrolysis of VIII and IX in dilute solutions of sulfuric acid gave an epimeric mixture of 2,6-cyclolycopene-1,5-diols A (X, major) and B (XI, minor). During chromatographic purification on n-silica gel, II and III partially cyclized to 1,16-didehydro-2,6-cyclolycopen-5-ol (XII) and epoxides VIII and IX partially converted to their respective diols, X and XI. In the course of isolation and purification, the oxidation products of lycopene with MCPBA were found to be extremely sensitive to chromatography on n-silica gel and underwent rearrangement to a number of cyclic epoxides and diols. Upon acid treatment of the mixture of lycopene epoxides, a bicyclic diepoxide of lycopene was formed, which was identified as lycopene 1,6;2,5-diepoxide (XIII). Diols X and XI have also been detected at low concentrations in tomato paste, tomato juice, and human serum. All synthetic compounds have been fully characterized by NMR, UV-vis, and MS. C1 Univ Maryland, Dept Chem & Biochem, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. Univ Bern, Dept Chem & Biochem, CH-3012 Bern, Switzerland. RP Khachik, F (reprint author), Univ Maryland, Dept Chem & Biochem, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RI Khachik, Frederick/C-5055-2009 NR 25 TC 37 Z9 37 U1 2 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 DEC PY 1998 VL 46 IS 12 BP 4874 EP 4884 DI 10.1021/jf980322a PG 11 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 150ZZ UT WOS:000077697600014 ER PT J AU Khachik, F Pfander, H Traber, B AF Khachik, F Pfander, H Traber, B TI Proposed mechanisms for the formation of synthetic and naturally occurring metabolites of lycopene in tomato products and human serum SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article; Proceedings Paper CT 11th International Symposium on Carotenoids CY AUG 18-23, 1996 CL LEIDEN, NETHERLANDS SP Int Union Pure & Appl Chem, Natl Inst Hlth, Switzerland, Swiss Natl Fdn, F Hoffmann La Roche Ltd, BASF Nederland B V, Betatene Ltd, Austr, Birkhauser Verlag, Switzerland, Bruker Nederland B V, Coca Cola Co, US, Kemin Ind, US, Wyeth Ayerst, US, European Community, Leiden City Council, Leiden Univ, Royal Dutch Acad Sci, Royal Dutch Chem Soc, Royal Gist Brocades N V, Netherlands, Dutch Soc Biochem & Molec Biol DE 1,16-didehydro-2,6-cyclolycopen-5-ol; 2,6-cyclolycopene-1,5-diol; 2,6-cyclolycopene-1,5-epoxide; lycopene 1,6 ; 2,5-diepoxide; lycopene 1,2-epoxide; lycopene 5,6-epoxide; lycopene oxidation products; new serum carotenoids; carotenoid metabolites ID OXIDATION-PRODUCTS; CAROTENOIDS; IDENTIFICATION AB Oxidation of lycopene (I) with m-chloroperbenzoic acid has been previously shown to yield lycopene 1,2-epoxide (II) and lycopene 5,6-epoxide (III) as major products and lycopene 1,2;5,6-diepoxide (IV), lycopene 1,2;5',6'-diepoxide (V), lycopene 5,6;5',6'-diepoxide (VI), and lycopene 1,2;1',2'-diepoxide (VII) as minor products. Similarly, the acid-catalyzed rearrangement products of these epoxides have been identified as 2,6-cyclolycopene-1,5-epoxide A (VIII) and B (IX), 2,6-cyclolycopene-1,5-diol A (X) and B (XI), 1,16-didehydro-2,6-cyclolycopen-5-ol (XII), and lycopene 1,6;2,5-diepoxide (MII). On the basis of the stereochemistry of the observed products (VIII-M), here, it is proposed that the acid-catalyzed rearrangement of lycopene 5,6-epoxide may be proceeded by S(N)1- and/or S(N)2-type mechanisms, whereas an SN2-type mechanism is preferred for the rearrangement of lycopene 1,2-epoxide. Details of the acid-catalyzed rearrangement of lycopene epoxides by S(N)1; and S(N)2-type reactions are presented. Although II and VII-XI are present in tomato products at low concentrations, only X and XI are found in human serum. Possible pathways leading to the formation of the synthetic compounds and the oxidative metabolites of lycopene in tomato products and human serum are discussed. C1 Univ Maryland, Dept Chem & Biochem, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. Univ Bern, Dept Chem & Biochem, CH-3012 Bern, Switzerland. RP Khachik, F (reprint author), Univ Maryland, Dept Chem & Biochem, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RI Khachik, Frederick/C-5055-2009 NR 12 TC 25 Z9 25 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD DEC PY 1998 VL 46 IS 12 BP 4885 EP 4890 DI 10.1021/jf9803233 PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 150ZZ UT WOS:000077697600015 ER PT J AU Slater, JE Paupore, EJ Elwell, MR Truscott, W AF Slater, JE Paupore, EJ Elwell, MR Truscott, W TI Lipopolysaccharide augments IgG and IgE responses of mice to the latex allergen Hev b 5 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE latex; endotoxin; lipopolysaccharide; mouse; IgE; IgG1; T-H1; T-H2 ID INHALED ENDOTOXIN; MACROPHAGES; INDUCTION; ANTIGENS; IL-4 AB Background: LPS is a common contaminant in the health care environment and in latex examination gloves. Objective: We sought to investigate the role of LPS in enhancing the immune responses of mice to inhaled latex allergen. Methods: As our model allergen, we used a fusion protein containing the potent latex allergen Hev b 5. BALB/c mice were lightly anesthetized and given repeated intranasal doses of saline, LPS, and/or Hev b 5. The doses were given in 2 courses separated by a 6-week period, with the first course consisting of 6 doses and the second consisting of 3 doses. Results: After the first set of immunizations, mice given Hev b 5 alone had no detectable IgG1 or IgE responses to Hev b 5, whereas mice given the antigen along with LPS had significant responses (IgG1, 0.73 U +/- 0.05; IgE, 0.88 U +/- 0.2). No enhancement of specific IgG2a was observed. A stimulatory effect of LPS on all 3 immunoglobulin types was apparent after the second course. Lymphocytes from mice immunized with LPS and Hev b 5 had increased proliferation to Hev b 5 and its fusion partner. Conclusions: LPS may be an important immunoadjuvant for the development of allergic reactions to latex protein allergens. C1 Childrens Natl Med Ctr, Childrens Res Inst, Ctr Mol Mech Dis Res, Washington, DC USA. Expt Pathol Labs Inc, Herndon, VA USA. Safeskin Corp, San Diego, CA USA. RP Slater, JE (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Immunobiochem, 1401 Rockville Rd, Rockville, MD 20852 USA. NR 23 TC 31 Z9 32 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 1998 VL 102 IS 6 BP 977 EP 983 DI 10.1016/S0091-6749(98)70336-7 PN 1 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 150XE UT WOS:000077690700016 PM 9847439 ER PT J AU Eskinazi, D Hoffman, FA AF Eskinazi, D Hoffman, FA TI Progress in complementary and alternative medicine: Contribution of the National Institutes of Health and the Food and Drug Administration SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article AB Since the creation of the Office of Alternative Medicine (OAM) at the National Institutes of Health (NIH), progress has been made in the evaluation and, where appropriate, the clinical and scientific acceptance of "complementary and alternative" medicine (CAM). This progress is due in part to initiatives jointly conducted by the NIH and the U.S. Food and Drug Administration (FDA). In particular, advances in the evaluation and acceptance of two CAM practices, acupuncture and botanical medicine, have resulted from ongoing cooperation between the two agencies. The legalization of the use of acupuncture needles in 1996 came as a result of a workshop sponsored by the OAM with the participation of the FDA, which explored key regulatory issues. Prompted by similar regulatory issues, as well as by the initiation of NIH-funded research projects, the OAM sponsored an international symposium to examine the evidence for and the role of botanical medicine in the United States. This conference generated a series of workshops sponsored by the Drug Information Association in conjunction with NIH and FDA, which explored the scientific, regulatory, and policy issues of heterogeneous botanical products. These efforts resulted in the initiation of a large randomized multicenter clinical trial (sponsored by the National Institute of Mental Health) of the botanical, St. John's wort, for the treatment of depression, and the formation of internal working groups within the FDA that are drafting a guidance policy for the development of botanicals as drugs in the United States. This document is expected to be available in the near future. C1 Columbia Univ Coll Phys & Surg, Rosenthal Ctr Complementary & Alternat Med, New York, NY 10032 USA. US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Eskinazi, D (reprint author), Columbia Univ Coll Phys & Surg, Rosenthal Ctr Complementary & Alternat Med, 630 W 168th St,Box 75, New York, NY 10032 USA. NR 28 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 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD WIN PY 1998 VL 4 IS 4 BP 459 EP 467 DI 10.1089/acm.1998.4.459 PG 9 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 153KM UT WOS:000077832300013 PM 9884181 ER PT J AU Song, YS Hargraves, WA AF Song, YS Hargraves, WA TI Postprocess contamination of flexible pouches challenged by in situ immersion biotest SO JOURNAL OF FOOD PROTECTION LA English DT Article ID CANNED FOODS; LEAKAGE AB Packages were evaluated for leaks by determining microbial penetration through microchannels as a function of test organism concentration, location in a retort, and microchannel diameter and length. A flexible pouch was used in an in situ immersion biotest coupled with a state-of-the-art retort. Microchannel diameters of 10 to 661 mu m with 3- and 6-mm lengths were created by placing tungsten wires in vacuum heat-sealed flexible pouches. After removing the wires, these pouches were subsequently heat processed under pressure. They were then biotested in cooling water containing 10(3) and 10(6) CFU of motile Enterobacter aerogenes per mi for 30 min and were dried immediately after manual unloading. After incubation at 37 degrees C for 3 days, they were visually examined for contamination. The high-temperature retorting process was shown to decrease microchannel diameters by an average of 20%. Generally, the smaller the microchannel diameter, the greater the percent shrinkage. Statistical analysis of the biotesting data showed that microchannel diameter and length had strong effects on microbial penetration (P < 0.01). Microbial concentration had a borderline significant effect (P < 0.05), but the effect of package location in the retort was not significant. At conservative conditions, such as a 3-mm microchannel length and a cooling water contamination level of 10(6) CPU/ml, the selected microorganism can penetrate microchannels with diameters as small as 7 mu m. However, the minimum microchannel diameter for penetration could be as large as 46 mu m at practical conditions of 6-mm microchannel length and contamination levels of 10(3) CFU/ml. C1 US FDA, Natl Ctr Food Safety & Technol, Div Food Proc & Packaging, Summit Argo, IL 60501 USA. 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. EM ysong@charlie.cns.iit.edu FU FDA HHS [FD-000431] NR 21 TC 5 Z9 5 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 1998 VL 61 IS 12 BP 1644 EP 1648 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 147YN UT WOS:000077525500008 PM 9874342 ER PT J AU Miller, AJ Smith, JL Buchanan, RL AF Miller, AJ Smith, JL Buchanan, RL TI Factors affecting the emergence of new pathogens and research strategies leading to their control SO JOURNAL OF FOOD SAFETY LA English DT Article ID ESCHERICHIA-COLI O157-H7; HEMOLYTIC-UREMIC SYNDROME; EMERGING FOODBORNE PATHOGENS; CREUTZFELDT-JAKOB-DISEASE; CHOLERAE O139 BENGAL; STABLE ENTERO-TOXIN; FOOD-BORNE DISEASE; SALMONELLA-ENTERITIDIS; ARCOBACTER-BUTZLERI; HEMORRHAGIC COLITIS AB Control of foodborne emerging or reemerging microbial pathogens has proven to be difficult. Even the HazardAnalysis Critical Control Point (HACCP) approach is intended to manage known hazards. We propose that each change occurring in the food chain - encompassing human, technological, and environmental factors - creates a new selection pressure that drives microbial adaptation and emergence potential. Escherichia coli O157:H7 is examined here, as a case study, to illustrate the multidimensional nature of pathogen emergence. While future emergence or reemergence events are expected, the fundamental questions of what, where, who, when, and how such events will unfold are unknown. Contingency planning can provide responses to probable hazard scenarios, with a goal of developing practical controls. Examples of potential microbial hazards and changes in the food chain are presented. Once a hazard, associated food, locale, and at-risk population are identified, critical acute research questions need to be answered. Longer term research will improve our ability to respond to the next inevitable emergence event. Such coordinated endeavors will permit rapid modification and deployment of a science-based hazard management system that will prevent or minimize human risks. C1 ARS, Microbial Food Safety Res Unit, Eastern Reg Res Ctr, USDA, Wyndmoor, PA 19038 USA. RP Miller, AJ (reprint author), US FDA, 200 C St SW, Washington, DC 20204 USA. EM amiller@bangate.fda.gov NR 84 TC 15 Z9 20 U1 1 U2 8 PU FOOD NUTRITION PRESS INC PI TRUMBULL PA 6527 MAIN ST, P O BOX 374, TRUMBULL, CT 06611 USA SN 0149-6085 J9 J FOOD SAFETY JI J. Food Saf. PD DEC PY 1998 VL 18 IS 4 BP 243 EP 263 DI 10.1111/j.1745-4565.1998.tb00219.x PG 21 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 157VE UT WOS:000078081700001 ER PT J AU Ye, XM Scallet, AC Kascsak, RJ Carp, RI AF Ye, XM Scallet, AC Kascsak, RJ Carp, RI TI Astrocytosis and proliferating cell nuclear antigen expression in brains of scrapie-infected hamsters SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE scrapie; astrocyte; proliferating cell nuclear antigen; glial fibrillary acidic protein; prion ID TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES; PRION PROTEIN-FRAGMENT; MONOCLONAL-ANTIBODY; CYCLE; DNA; IMMUNOHISTOCHEMISTRY; HYPERTROPHY; DISEASE; GROWTH; PCNA AB Scrapie is a neurodegenerative disease in sheep and goats. Neuropathological examination shows astrocytosis. One issue is whether the astrocytosis seen in scrapie is a function of an increase in reactivity of individual cells, or whether there is actual replication of astrocytes. We used double-label immunohistochemistry for proliferating cell nuclear antigen (PCNA) and for glial fibrillary acidic protein (GFAP) to determine the mitotic state of cells and to confirm their identity as astrocytes. Brain sections from hamsters (strain LVG/LAK) infected with 139H or 263K scrapie isolates were examined. GFAP immunostaining was increased in astrocytes in most regions of the brains of scrapie-infected hamsters. These qualitative observations were confirmed by computerized image analysis quantification. A proportion of the hypertrophic astrocytes (0.5-10.8%, depending on specific location) were PCNA immunoreactive. The PCNA-immunopositive astrocytes were most frequently found in cerebral cortex, corpus callosum, subependymal areas, fimbria, caudate, thalamus, hypothalamus, hippocampus, and dentate gyrus. Our results suggest that the astrocytosis seen in scrapie-infected animals is, at least in part, owing to actual replication of astrocytes in these animals. We hypothesize that the astrocytes may be an important locus for the disease process. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USA. Washington State Univ, VCAPP, Pullman, WA 99164 USA. RP Ye, XM (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 29 TC 11 Z9 11 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD DEC PY 1998 VL 11 IS 3 BP 253 EP 263 DI 10.1385/JMN:11:3:253 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 197AL UT WOS:000080342400008 PM 10344795 ER PT J AU Meredith, JM Moffatt, CA Auger, AP Snyder, GL Greengard, P Blaustein, JD AF Meredith, JM Moffatt, CA Auger, AP Snyder, GL Greengard, P Blaustein, JD TI Mating-related stimulation induces phosphorylation of dopamine- and cyclic AMP-regulated phosphoprotein-32 in progestin receptor-containing areas in the female rat brain SO JOURNAL OF NEUROSCIENCE LA English DT Article DE vaginal-cervical stimulation; cervical stimulation; dopamine; estradiol; progestin receptors; phosphorylation; DARPP-32 ID HORMONE-RELEASING HORMONE; SEXUAL-BEHAVIOR; FOS-IMMUNOREACTIVITY; VAGINAL STIMULATION; PREOPTIC AREA; MESSENGER-RNA; ESTROUS-CYCLE; C-FOS; IMMUNOCYTOCHEMICAL LOCALIZATION; VAGINOCERVICAL STIMULATION AB Vaginal-cervical stimulation induces a number of physiological and behavioral events, including the facilitation of mating behavior. Although the facilitation of one component of mating behavior, lordosis, by vaginal-cervical stimulation does not require the presence of progesterone, it appears to be mediated by neural progestin receptors. Abundant evidence suggests that dopamine may play a role in the neural circuitry activated by vaginal-cervical stimulation, including the mating-induced release of dopamine in progestin receptor-containing areas of the brain, changes in the activational state of progestin receptors because of dopamine D-1 receptor stimulation, facilitation of lordosis by D-1 receptor stimulation in estradiol-primed rats via progesterone-independent events, and D-1 agonist-induced neuronal responses in progestin receptor-containing areas and cells. We tested the hypothesis that vaginal-cervical stimulation induces phosphorylation of dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32; M-r = 32,000), a protein phosphorylated predominantly in response to the stimulation of D-1 receptors. At 9 d after ovariectomy, female rats were injected subcutaneously with a behaviorally effective dose of estradiol benzoate. At 48 hr later they received vaginal-cervical or control (perineal) stimulation, and they were perfused 1 hr later. Vaginal-cervical stimulation increased the number of cells expressing pDARPP-32 immunoreactivity by 92% in the medial preoptic nucleus, 134% in the caudal ventromedial hypothalamic nucleus, 123% in the posterodorsal medial amygdala, and 103% in the bed nucleus of the stria terminalis. These results suggest that some of the neuronal effects of vaginal-cervical stimulation, and perhaps other social or environmental stimuli, are mediated by phosphorylation of DARPP-32, perhaps via stimulation of D-1 receptors, within progestin receptor-containing areas. C1 Univ Massachusetts, Ctr Neuroendocrine Studies, Amherst, MA 01003 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10021 USA. RP Blaustein, JD (reprint author), Univ Massachusetts, Ctr Neuroendocrine Studies, Tobin Hall,Box 37720, Amherst, MA 01003 USA. FU NICHD NIH HHS [HD08181]; NIMH NIH HHS [MH11392, MH10560] NR 57 TC 41 Z9 41 U1 1 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 1 PY 1998 VL 18 IS 23 BP 10189 EP 10195 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 141XP UT WOS:000077169800055 PM 9822772 ER PT J AU Chaurasia, CS Chen, CE Rubin, J Dewey, SL AF Chaurasia, CS Chen, CE Rubin, J Dewey, SL TI Effects of tamoxifen on striatal dopamine and 5-hydroxytryptamine release in freely moving male rats: An in-vivo microdialysis investigation SO JOURNAL OF PHARMACY AND PHARMACOLOGY LA English DT Article ID FEMALE RATS; BREAST-CANCER; ACETYLCHOLINE-RELEASE; LOCOMOTOR-ACTIVITY; ESTROGEN; BRAIN; ESTRADIOL; ANTIESTROGENS; METABOLISM; HIPPOCAMPUS AB Recent studies indicating interaction of oestrogens with central cholinergic, dopaminergic and 5-HTergic systems have led to the assumption of a protective role of oestrogens in certain neurodegenerative disorders. The non-steroidal drug tamoxifen, a mixed oestrogen agonist-antagonist, has been shown to modulate central nervous system functions in the corpus striatum. In this study we used a microdialysis technique to examine the effects of tamoxifen upon the striatal dopaminergic and 5-HTergic systems in intact freely moving male rats. The extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindoleacetic acid were measured after intraperitoneal administration of either the control or tamoxifen, and were compared with their corresponding baseline levels. Significant 25-35% increases in the baseline levels of dopamine and 3,4-dihydroxyphenylacetic acid were observed after the highest doses of tamoxifen (1.5 mg kg(-1) and 3.0 mg kg(-1) respectively), whereas the lowest dose of tamoxifen (0.3 mg kg(-1)) elevated dopamine and 3,4-dihydroxyphenylacetic acid levels by a detectable 15% of the basal. In addition, the ratio of 3,4-dihydroxyphenylacetic acid-to-dopamine remained unchanged in comparison with that of the pretreatment levels. Whereas no change in the striatal 5-hydroxyindoleacetic acid concentrations was seen with the lowest and highest dose regimen, the intermediate dose elicited a moderate increase (20%) in basal 5-hydroxyindoleacetic acid levels. The pharmacological relevance of the effects of tamoxifen on the dopaminergic and 5-HTergic systems, as a prelude to the development of non-steroidal oestrogenic compounds in reducing the risk of neurodegenerative disorders such as Alzheimer's disease, is discussed. C1 St Johns Univ, Coll Pharm & Allied Hlth Profess, Jamaica, NY 11439 USA. Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. RP Chaurasia, CS (reprint author), US FDA, Div Bioequivalence, Room 123,Metropk N 2,7500 Standish Pl, Rockville, MD 20855 USA. NR 47 TC 10 Z9 10 U1 0 U2 0 PU ROYAL PHARMACEUTICAL SOC GREAT BRITAIN PI LONDON PA 1 LAMBETH HIGH ST, LONDON SE1 7JN, ENGLAND SN 0022-3573 J9 J PHARM PHARMACOL JI J. Pharm. Pharmacol. PD DEC PY 1998 VL 50 IS 12 BP 1377 EP 1385 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 168KG UT WOS:000078690600009 PM 10052853 ER PT J AU Ferreira, JL Crawford, RG AF Ferreira, JL Crawford, RG TI Detection of type a botulinal toxin-producing organisms subcultured from cheese using an amplified ELISA system SO JOURNAL OF RAPID METHODS AND AUTOMATION IN MICROBIOLOGY LA English DT Article AB Mascarpone cheese implicated in a botulism outbreak was examined for preformed and cultural botulinal toxins using the mouse bioassay. The cheese was also assayed for cultural toxins and for the most probable number (MPN) of toxin producing organisms/g using an amplified ELISA. No preformed botulinal toxins were discovered in the cheese samples (pH range 5.54-5.86) using the mouse bioassay. However, after cheese subculture ii? tryptone-peptone-glucose-yeast extract broth, type A botulinal toxin-producing organisms that formed more than 10,000 MLD (mouse lethal dose)/mL in culture were detected. The ELISA results also revealed that type A toxin was present in the culture with a sensitivity of similar to 10 MLD/mL. The MPN of type A toxin-producing organisms/g in 12 cheese samples examined ranged from < 0.3-9.33. No ELISA cross-reactivity was noted between the type A toxic cultures and other types (B, E, or F). The ELISA sensitivity was similar to 5 MLD/mL casein buffer using purified type A neurotoxin. The advantages of the ELISA test are that the toxin type and approximate lethal dose can be determined within one day compared to the mouse bioassay which takes 3-5 days. 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 10 TC 6 Z9 6 U1 0 U2 2 PU FOOD NUTRITION PRESS INC PI TRUMBULL PA 6527 MAIN ST, P O BOX 374, TRUMBULL, CT 06611 USA SN 1060-3999 J9 J RAPID METH AUT MIC JI J. Rapid Methods Autom. Microbiol. PD DEC PY 1998 VL 6 IS 4 BP 289 EP 296 DI 10.1111/j.1745-4581.1998.tb00209.x PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 159FJ UT WOS:000078161000005 ER PT J AU Martinez, MN AF Martinez, MN TI Special series - Use of pharmacokinetics in veterinary medicine - Article V: Clinically important errors in data interpretation SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article ID TIME; BIOEQUIVALENCE; CURVES C1 US FDA, CVM, Rockville, MD 20855 USA. RP Martinez, MN (reprint author), US FDA, CVM, 7500 Standish Pl, Rockville, MD 20855 USA. NR 22 TC 5 Z9 5 U1 0 U2 2 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD DEC 1 PY 1998 VL 213 IS 11 BP 1564 EP 1569 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA 142NJ UT WOS:000077206300010 PM 9838954 ER PT J AU De Veau, EJI Pedersoli, W Cullison, R Baker, J AF De Veau, EJI Pedersoli, W Cullison, R Baker, J TI Pharmacokinetics of phenylbutazone in plasma and milk of lactating dairy cows SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID PROTEIN BINDING; BOVINE-MILK; EXCRETION; OXYPHENBUTAZONE; METABOLISM; DRUGS AB Phenylbutazone was administered intravenously (i.v,) to a group of four lactating cows at a dosage of 6 mg/kg body weight. Whole plasma, protein-free plasma and milli were analysed for phenylbutazone residues, Pharmacokinetic parameters of total and free phenylbutazone in plasma were calculated using a non compartmental method, In regards to whole plasma data, the mean volume of distribution at steady state (V-ss), was 147 mL/kg body weight, with a mean (+/- SEM) terminal elimination half-life (t(1/2)) of 40 +/- 6 h. The mean clearance (CI) was 3 mL/h/kg body weight, The V-ss as determined from the protein-free plasma fraction was 50 021 mL/kg body weight, This larger V-ss of free phenylbutazone compared to total plasma phenylbutazone was attributed to a high degree of plasma protein binding, as well as the greater penetration of free phenylbutazone into tissues. The mean t(1/2) of free phenylbutazone was 39 +/- 5 h. This similarity to the tilt estimated from total plasma phenylbutazone data is attributed to an equilibrium between free and plasma phenylbutazone during the terminal elimination phase. Mean t(1/2) as determined from milk, applying a urinary excretion rate model, was 47 +/- 4 h. Milk clearance of phenylbutazone was 0.009 mL/h/kg body weight, or about 0.34% of total body clearance. Furthermore, evidence suggests that phenylbutazone either binds to milk proteins, or is actively transported into milk, as its concentration in milk was greater than that predicted due to a simple partitioning from plasma into milk. C1 US FDA, Ctr Vet Med, Res Off, Div Residue Chem, Laurel, MD 20708 USA. US FDA, Ctr Vet Med, Res Off, Div Anim Res, Laurel, MD 20708 USA. US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Div Therapeut Drugs Nonfood Anim, Rockville, MD 20855 USA. RP De Veau, EJI (reprint author), US FDA, Ctr Vet Med, Res Off, Div Residue Chem, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 22 TC 15 Z9 16 U1 2 U2 7 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD DEC PY 1998 VL 21 IS 6 BP 437 EP 443 PG 7 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 161ZK UT WOS:000078320300004 PM 9885966 ER PT J AU Ting, YT Wilson, CA Farrell, KB Chaudry, GJ Eiden, MV AF Ting, YT Wilson, CA Farrell, KB Chaudry, GJ Eiden, MV TI Simian sarcoma-associated virus fails to infect Chinese hamster cells despite the presence of functional Gibbon ape leukemia virus receptors SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS; MURINE CELLS; FUSION; GLYCOPROTEINS; REQUIREMENTS; RETROVIRUS; PROTEIN; TYPE-1; SYSTEM; HIV-1 AB We have sequenced the envelope genes from each of the five members of the gibbon ape leukemia virus (GALV) family of type C retroviruses. Four of the GALVs, including GALV strain SEATO (GALV-S), were originally isolated from gibbon apes, whereas the fifth member of this family, simian sarcoma-associated virus (SSAV), was isolated from a woolly monkey and shares 78% amino acid identity with GALV-S, To determine whether these viruses have identical host ranges, we evaluated the susceptibility of several tell lines to either GALV-S or SSAV infection. GALV-S and SSAV have the same host range with the exception of Chinese hamster lung E36 cells, which are susceptible to GALV-S but not SSAV. We used retroviral vectors that differ only in their envelope composition (e.g., they contain either SSAV or GALV-S envelope protein) to show that the envelope of SSAV restricts entry into E36 cells. Although unable to infect E36 cells, SSAV infects GALV-resistant murine cells expressing the E36-derived viral receptor, HaPit2. These results suggest that the receptors present on E36 cells function for SSAV. We have constructed several vectors containing GALV-S/SSAV chimeric envelope proteins to map the region of the SSAV envelope that blocks infection of E36 cells. Vectors bearing chimeric envelopes comprised of the N-terminal region of the GALV-S SU protein and the C-terminal region of SSAV infect E36 cells, whereas vectors containing the N-terminal portion of the SSAV SU protein and C-terminal portion of GALV-S fail to infect E36 cells. This finding indicates that the region of the SSAV envelope protein responsible for restricting SSAV infection of E36 cells lies within its amino-terminal region. C1 NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Cellular Immunol Lab, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Eiden, MV (reprint author), NIMH, Lab Cellular & Mol Regulat, Bldg 36,Room 2A11, Bethesda, MD 20892 USA. EM m_eiden@codon.nih.gov RI Chaudry, Ghulam/F-9761-2011 NR 35 TC 30 Z9 31 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1998 VL 72 IS 12 BP 9453 EP 9458 PG 6 WC Virology SC Virology GA 137AW UT WOS:000076892100005 PM 9811678 ER PT J AU Weng, YK Weiss, CD AF Weng, YK Weiss, CD TI Mutational analysis of residues in the coiled-coil domain of human immunodeficiency virus type 1 transmembrane protein gp41 SO JOURNAL OF VIROLOGY LA English DT Article ID ENVELOPE GLYCOPROTEIN; MEMBRANE-FUSION; LEUCINE-ZIPPER; HIV-1 GP41; INFLUENZA HEMAGGLUTININ; SYNTHETIC PEPTIDE; RECEPTOR-BINDING; ATOMIC-STRUCTURE; SOLUBLE CD4; GP120 AB The envelope glycoprotein (Env) of human immunodeficiency virus mediates virus entry into cells by undergoing conformational changes that lead to fusion between viral and cellular membranes. A six-helix bundle in gp41, consisting of an interior trimeric coiled-coil core with three exterior helices packed in the grooves (core structure), has been proposed to be part of a fusion-active structure of Pm (D. C. Chan, D. Pass, J. M. Berger, and P. S. Rim, Cell 89:263-273, 1997; W. Weissenhorn, A. Dessen, S. C. Harrison, J. J. Skehel, and D. C. Wiley, Nature 387:426-430, 1997; and K. Tan, J. Liu, J. Wang, S. Shen, and M; Lu, Proc. Natl. Acad. Sci. USA 94: 12303, 1997). We analyzed the effects of amino acid substitutions of arginine or glutamic acid in residues in the coiled-coil (heptad repeat) domain that line the interface between the helices in the gp41 core structure. We found that mutations of leucine to arginine or glutamic acid in position 556 and of alanine to arginine in position 558 resulted in undetectable levels of Env expression. Seven other mutations in six positions completely abolished fusion activity despite incorporation of the mutant Env into virions and normal gp160 processing. Single-residue substitutions of glutamic acid at position 570 or 577 resulted in the only viable mutants among the 16 mutants studied, although both viable mutants exhibited impaired fusion activity compared to that of the wild type. The glutamic acid 577 mutant was more sensitive than the wild type to inhibition by a gp41 coiled-coil peptide (DP-107) but not to that by another peptide corresponding to the C helix in the gp41 core structure (DP-178). These results provide insight into the gp41 fusion mechanism and suggest that the DP-107 peptide may inhibit fusion by binding to the homologous region in gp41, probably by forming a peptide-gp41 coiled-coil structure. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Weiss, CD (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-413,Bldg 29,Room 532,29 Lincoln Dr, Bethesda, MD 20892 USA. RI Weiss, Carol/F-6438-2011 OI Weiss, Carol/0000-0002-9965-1289 NR 40 TC 85 Z9 85 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1998 VL 72 IS 12 BP 9676 EP 9682 PG 7 WC Virology SC Virology GA 137AW UT WOS:000076892100028 PM 9811701 ER PT J AU Tabor, E AF Tabor, E TI Animal models of human hepatitides SO LABORATORY ANIMAL SCIENCE LA English DT Article; Proceedings Paper CT Registry of Comparative Pathology Symposium 1997 - Animal Models of Human Disease for the 21st-Century CY DEC 08-10, 1997 CL WASHINGTON, D.C. C1 US FDA, Bethesda, MD 20014 USA. RP Tabor, E (reprint author), US FDA, Bethesda, MD 20014 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD DEC PY 1998 VL 48 IS 6 BP 593 EP 595 PG 3 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 157DC UT WOS:000078043600011 PM 10090082 ER PT J AU Teruya-Feldstein, J Zauber, P Setsuda, JE Berman, EL Sorbara, L Raffeld, M Tosato, G Jaffe, ES AF Teruya-Feldstein, J Zauber, P Setsuda, JE Berman, EL Sorbara, L Raffeld, M Tosato, G Jaffe, ES TI Expression of human herpesvirus-8 oncogene and cytokine homologues in an HIV-seronegative patient with multicentric Castleman's disease and primary effusion lymphoma SO LABORATORY INVESTIGATION LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; PROTEIN-COUPLED RECEPTOR; EPSTEIN-BARR-VIRUS; KAPOSIS-SARCOMA; MULTIPLE-MYELOMA; BCL-2 HOMOLOG; CELLS; KSHV; ENCODES AB Human herpesvirus-8 (HHV-8) has been described in association with two lymphoproliferative disorders: one benign, multicentric Castleman's disease (MCD), and one malignant, primary effusion lymphoma (PEL). The factors that lead to malignant transformation of lymphoid cells are unknown, although most cases of PEL also are positive for EBV, suggesting a role for EBV as a cofactor in malignant transformation. We encountered a rare case of an HHV-8-associated MCD, followed by the development of an HHV-8-positive pleural PEL and a gastric large cell lymphoma in an HIV-seronegative male patient. The lesions were negative for Epstein-Barr virus (EBV). The combination of these diverse HHV-8-associated lymphoproliferative disorders in a single patient afforded us the ability to study potential differences in gene expression in these conditions. HHV-8 DNA was demonstrated by PCR in lymphoid tissues involved by MCD and PEL. By reverse transcriptase-PCR, HHV-8-related transcripts, including vG-coupled protein receptor, vbcl2, vcyclin D, vIL-6, vMIPI, and vMIPII, were detected in the PEL from the pleural cavity and the gastric lymphoma, whereas these transcripts, except for vIL-6, were not detected in a lymph node biopsy with MCD. Expression of hIL-10 was weak in the PEL from the pleural cavity, and expression of hIL-6 was undetectable in all three lesions. These data suggest that vIL-6 may be integral to the pathogenesis of MCD, whereas other viral transcripts that encode oncogene and chemokine homologues are important for HHV-8 tumorigenicity. C1 NCI, Hematol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. St Barnabas Med Ctr, Livingston, NJ USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Jaffe, ES (reprint author), NCI, Hematol Sect, Pathol Lab, NIH, Bldg 10,Room 2N202,10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. NR 30 TC 65 Z9 66 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD DEC PY 1998 VL 78 IS 12 BP 1637 EP 1642 PG 6 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 153YF UT WOS:000077860600022 PM 9881964 ER PT J AU McLeod, HL Collie-Duguid, ESR Vreken, P Johnson, MR Wei, X Sapone, A Diasio, RB Fernandez-Salguero, P van Kuilenberg, ABP van Gennip, AH Gonzalez, FJ AF McLeod, HL Collie-Duguid, ESR Vreken, P Johnson, MR Wei, X Sapone, A Diasio, RB Fernandez-Salguero, P van Kuilenberg, ABP van Gennip, AH Gonzalez, FJ TI Nomenclature for human DPYD alleles SO PHARMACOGENETICS LA English DT Article DE allele nomenclature; DPYD; dihydropyrimidine dehydrogenase; pyrimidine metabolism ID DIHYDROPYRIMIDINE DEHYDROGENASE-DEFICIENCY; 5-FLUOROURACIL TOXICITY; MONONUCLEAR-CELLS; CANCER-PATIENTS; MOLECULAR-BASIS; GENE; IDENTIFICATION; CHEMOTHERAPY; POPULATION; LIVER AB To standardize DPYD allele nomenclature and to conform with international human gene nomenclature guidelines, an alternative to the current arbitrary system is described. Based on recommendations for human genome nomenclature, we propose that each distinct allele be designed by DPYD followed by an asterisk and an Arabic numeral. The number specifies the key mutation and, where appropriate, a letter following the number indicates an additional mutation on the mutant allele, Criteria for classification as a distinct allele are also presented. Pharmacogenetics 8:455-459. (C) 1998 Lippincott Williams & Wilkins. C1 Univ Aberdeen, Inst Med Sci, Dept Med & Therapeut, Aberdeen AB25 2ZD, Scotland. Emma Childrens Hosp, Amsterdam Med Ctr, Dept Clin Chem, Amsterdam, Netherlands. Univ Alabama, Dept Pharmacol & Toxicol, Birmingham, AL USA. US FDA, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. NCI, Lab Metab, NIH, Bethesda, MD USA. Univ Extremadura, Fac Ciencias, Lab Bioquim & Biol Mol, E-06071 Badajoz, Spain. RP McLeod, HL (reprint author), Univ Aberdeen, Inst Med Sci, Dept Med & Therapeut, Aberdeen AB25 2ZD, Scotland. EM h.l.mcleod@abdn.ac.uk RI Sapone, Andrea/E-6704-2013; Collie-Duguid, Elaina/A-4432-2017; OI Sapone, Andrea/0000-0001-8496-6977; Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 34 TC 66 Z9 72 U1 1 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 1998 VL 8 IS 6 BP 455 EP 459 DI 10.1097/00008571-199812000-00001 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 157JY UT WOS:000078058800001 PM 9918128 ER PT J AU Klein, LC Popke, EJ Grunberg, NE AF Klein, LC Popke, EJ Grunberg, NE TI Sex differences in effects of opioid blockade on stress-induced freezing behavior SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE freezing; endogenous opioid peptides; naloxone; sex differences; stress; footshock ID FEMALE RATS; ENHANCEMENT; NALTREXONE; SHOCK; FEAR; NEUROENDOCRINE; CORTICOSTERONE; INHIBITION; AVOIDANCE; PITUITARY AB The present experiment examined the effects of naloxone on freezing behavior in male and female rats following stress and no-stress conditions. Twelve male and 12 female Wistar rats were exposed to 10 min of mild, unpredictable footshock stress and to a comparable no-stress condition. Immediately following stress or no-stress conditions, subjects were injected with naloxone or saline, and two independent observers measured freezing behavior. In male rats, naloxone potentiated freezing following stress but had no effect on freezing following no-stress. In females, naloxone did not affect freezing regardless of stress conditions. These results reveal a sex difference in effects of naloxone on freezing behavior and suggest that sex differences may exist with respect to the role of endogenous opioids under stress. (C) 1998 Elsevier Science Inc. C1 Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA. RP Klein, LC (reprint author), Univ Calif Los Angeles, Dept Psychol, Box 9515663,5586 Franz Hall, Los Angeles, CA 90095 USA. RI Klein, Laura/L-4231-2013 OI Klein, Laura/0000-0002-6215-3155 NR 23 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD DEC PY 1998 VL 61 IS 4 BP 413 EP 417 DI 10.1016/S0091-3057(98)00135-X PG 5 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 130DM UT WOS:000076504500011 PM 9802836 ER PT J AU Bayorh, MA Ogbolu, EC Williams, E Thierry-Palmer, M Sanford, G Emmett, N Harris-Hooker, S Socci, RR Chu, TC Chenault, VM AF Bayorh, MA Ogbolu, EC Williams, E Thierry-Palmer, M Sanford, G Emmett, N Harris-Hooker, S Socci, RR Chu, TC Chenault, VM TI Possible mechanisms of salt-induced hypertension in Dahl salt-sensitive rats SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE Dahl rats; blood flow; blood pressure; cyclic GMP; norepinephrine release ID CENTRAL NERVOUS-SYSTEM; CYCLIC-GMP; BLOOD-PRESSURE; NITRIC-OXIDE; VASOPRESSIN; RESPONSES; HEMODYNAMICS; INHIBITION; ZAPRINAST; STRAIN AB Genetic factors, diet, and salt sensitivity have all been implicated in hypertension. To further understand the mechanisms involved in salt-induced hypertension, cardiovascular, hemodynamics, and biochemical parameters in Dahl salt-sensitive rats were evaluated in animals on high- and low-sodium diets. During a 4-week treatment period, blood pressure was significantly elevated in the high (8.0%) salt group compared to the low (0.3%) salt group (p less than or equal to 0.05 for weeks 2 and 4, respectively). No significant changes were observed in heart rate. The increase in blood pressure was associated with significant increases in lower abdominal aortic and renal vascular resistance, along with a reduction in blood flow. A fourfold increase in arginine vasopressin was observed in animals on the high-salt diet. In contrast, there was no effect on plasma sodium, potassium, or aldosterone levels during the treatment period. As measured in isolated aortic rings, the high-salt diet also caused a significant elevation in stimulated norepinephrine release and a reduction in cyclic GMP levels. These data suggest that salt-induced elevation in blood pressure is due to activation of both the sympathetic and arginine vasopressin systems via mechanisms involving decreased cyclic GMP generation in vascular smooth muscle. (C) 1998 Elsevier Science Inc. C1 Morehouse Sch Med, Dept Pharmacol Toxicol, Atlanta, GA 30310 USA. Morehouse Sch Med, Dept Biochem, Atlanta, GA 30310 USA. Morehouse Sch Med, Dept Physiol, Atlanta, GA 30310 USA. Morehouse Sch Med, Dept Med, Atlanta, GA 30310 USA. US FDA, CDRH, ODE, DCLD, Rockville, MD 20850 USA. RP Bayorh, MA (reprint author), Morehouse Sch Med, Dept Pharmacol Toxicol, 720 Westview Dr SW, Atlanta, GA 30310 USA. FU NCRR NIH HHS [RR03034] NR 36 TC 16 Z9 19 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD DEC 1 PY 1998 VL 65 IS 3 BP 563 EP 568 DI 10.1016/S0031-9384(98)00194-2 PG 6 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 150HW UT WOS:000077659900021 PM 9877424 ER PT J AU Itzhak, Y Ali, SF Martin, JL Black, MD Huang, PL AF Itzhak, Y Ali, SF Martin, JL Black, MD Huang, PL TI Resistance of neuronal nitric oxide synthase-deficient mice to cocaine-induced locomotor sensitization SO PSYCHOPHARMACOLOGY LA English DT Article DE cocaine; locomotor activity; sensitization; nitric oxide; knockout mice ID INDUCED BEHAVIORAL SENSITIZATION; LONG-TERM POTENTIATION; EXCITATORY AMINO-ACIDS; NUCLEUS-ACCUMBENS; REVERSE TOLERANCE; AMPHETAMINE; DOPAMINE; MK-801; BRAIN; GLUTAMATE AB In brain, nitric oxide (NO) is considered as a retrograde messenger involved in synaptic plasticity. The present study was undertaken to investigate whether mice lacking the neuronal nitric oxide synthase (nNOS) gene are protected from cocaine-induced behavioral sensitization. Mice were administered, IP, either saline or cocaine (15 mg/kg) for 5 days. Sensitization was determined as an increase in cocaine-induced locomotor activity on day 5 compared with day 1 and an amplified response of cocaine-experienced mice to a challenge cocaine injection given after a 10-day drug free period (e.g., on day 15). To investigate the development of a context-dependent locomotion (conditioning), the responses of cocaine- and saline-experienced mice to a saline injection were determined on day 17. Male homozygote nNOS(-/-) mice were sensitive to the acute effect of cocaine (15 mg/kg) on day 1; however, they developed neither a sensitized response to cocaine ion day 5 and 15! nor a conditioned locomotion. Female homozygote nNOS(-/-) mice neither were responsive to 15 mg/kg cocaine on day 1, 5 and 15, nor did they develop a conditioned locomotion. In contrast, the same cocaine regimen delivered to male and female heterozygote nNOS(+/-) mice, and wild type mice (B6 J/sv129, C57BL/6 and sv129) resulted in sensitization to cocaine-induced locomotor activity and context-dependent locomotion. Investigation of [H-3]cocaine disposition in the striatum and frontal cortex of the mice revealed neither gender nor strain differences in the drug disposition. Also, no major difference in striatal dopaminergic markers between homozygote nNOS(-/-) and wild type mice was observed. The most significant distinction, however, was the finding that nNOS(-/-) mice are completely deficient in striatal nNOS binding sites. Taken together, our results suggest that the resistance of homozygote nNOS(-/-) mice to cocaine-induced behavioral sensitization is primarily due to the deletion of the nNOS gene. Considering the role of NO in synaptic plasticity, it is conceivable that reduced brain NOS activity blunts the processes that underlie the development of sensitization to cocaine. C1 Univ Miami, Sch Med, Dept Biochem & Mol Biol, Miami, FL 33101 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Itzhak, Y (reprint author), Univ Miami, Sch Med, Dept Biochem & Mol Biol, POB 016129, Miami, FL 33101 USA. FU NIDA NIH HHS [R01DA08584]; NINDS NIH HHS [NS33335] NR 34 TC 44 Z9 45 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 1998 VL 140 IS 3 BP 378 EP 386 DI 10.1007/s002130050779 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 147EP UT WOS:000077475600015 PM 9877018 ER PT J AU Olsen, AR AF Olsen, AR TI Regulatory action criteria for filth and other extraneous materials I. Review of hard or sharp foreign objects as physical hazards in food SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID UPPER GASTROINTESTINAL-TRACT; BODIES; MANAGEMENT; BODY; INJURIES; PERFORATION; ASPIRATION; TOOTHPICK; ESOPHAGUS; CHILDHOOD AB A review of the scientific literature concerning physical hazards in food products is combined with the results of 190 evaluations of foreign objects in food that were conducted by the FDA Health Hazard Evaluation Board over a period of 25 years. Hard or sharp objects 7 mm or longer in size were found to be a potential health hazard from laceration, perforation wound, and possible secondary infection. Objects less than 7 mm in size represent a possible hazard, especially if a special-risk group (e.g., infants, elderly) is among the intended consumers of the product. The results proved consistent with U.S. Department of Agriculture guidance concerning foreign objects in food. Hazard Analysis Critical Control Point applications for physical hazards in food are discussed. C1 US FDA, Microanalyt Branch, Washington, DC 20204 USA. RP Olsen, AR (reprint author), US FDA, Microanalyt Branch, HFS-315,200 C St SW, Washington, DC 20204 USA. NR 55 TC 12 Z9 12 U1 0 U2 9 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 DEC PY 1998 VL 28 IS 3 BP 181 EP 189 DI 10.1006/rtph.1998.1249 PG 9 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 171GA UT WOS:000078853500001 PM 10049789 ER PT J AU Olsen, AR AF Olsen, AR TI Regulatory action criteria for filth and other extraneous materials II. Allergenic mites: An emerging food safety issue SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID HOUSE DUST MITES; STORAGE MITES; DERMATOPHAGOIDES-PTERONYSSINUS; TYROPHAGUS-PUTRESCENTIAE; LEPIDOGLYPHUS-DESTRUCTOR; ANAPHYLAXIS; INGESTION; ASTHMA; CARMINE; CHILDREN AB Four species of food contaminating mites have recently been reported to have caused IgE-mediated allergic reactions, including anaphylaxis, in persons who consumed mite contaminated foods. The mite species are the American house dust mite, Dermatophagoides farinae Hughes (Acarina: Pyroglyphidae); the scaly grain mite, Suidasia sp. prob. pontifica Oudemans (Acarina: Suidasiidae), an acarid mite, Thyreophagus entomophagus Portus & Gomez (Acarina: Acaridae); and the mold mite, Tyrophagus putrescentiae (Schrank) (Acarina: Acaridae). Allergenic mites are an emerging food safety issue as ingested allergens in mite-contaminated food. C1 US FDA, Microanalyt Branch, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Olsen, AR (reprint author), US FDA, Microanalyt Branch, Ctr Food Safety & Appl Nutr, HFS-315,200 C St SW, Washington, DC 20204 USA. NR 83 TC 15 Z9 19 U1 0 U2 8 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 DEC PY 1998 VL 28 IS 3 BP 190 EP 198 DI 10.1006/rtph.1998.1270 PG 9 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 171GA UT WOS:000078853500002 PM 10049790 ER PT J AU Olsen, AR AF Olsen, AR TI Regulatory action criteria for filth and other extraneous materials III. Review of flies and foodborne enteric disease SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Review ID CHRYSOMYA-MEGACEPHALA DIPTERA; HOUSEFLIES MUSCA-DOMESTICA; SALTED-DRIED FISH; SOUTH-EAST ASIA; DIARRHEAL DISEASE; RISK-FACTORS; CALLIPHORIDAE; TRANSMISSION; SHIGELLOSIS; HEALTH AB Forty-seven species of flies have been reliably associated with filthy conditions that might allow the spread of foodborne pathogens. These are categorized as "filth flies." Of that 47, only 21 species represent a potential threat to human health as scientifically proven causative agents of foodborne myiasis or as carriers of enteropathogenic Escherichia coli, Salmonella, Shigella, and other foodborne pathogens. These 21 species are categorized as "disease-causing flies" based on strict scientific criteria. The criteria are association with E. coli, Salmonella, AND Shigella; synanthropy; endophily; communicative behavior; attraction to both excrement and food products; and recognition by authorities as a potential health hazard, Within Hazard Analysis and Critical Control Point and other U.S. Food and Drug Administration regulatory frameworks, disease-causing flies are contributing factors to the spread of foodborne disease that require preventive and corrective actions as appropriate under Sanitation Standard Operating Procedures, Good Manufacturing Practices, or pest control programs. C1 US FDA, Ctr Food Safety & Appl Nutr, Microanalyt Branch, Washington, DC 20204 USA. RP Olsen, AR (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Microanalyt Branch, HFS-315,200 C St SW, Washington, DC 20204 USA. NR 145 TC 43 Z9 47 U1 4 U2 13 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 DEC PY 1998 VL 28 IS 3 BP 199 EP 211 DI 10.1006/rtph.1998.1271 PG 13 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 171GA UT WOS:000078853500003 PM 10049791 ER PT J AU Gaylor, DW Gold, LS AF Gaylor, DW Gold, LS TI Regulatory cancer risk assessment based an a quick estimate of a benchmark dose derived from the maximum tolerated dose SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID CARCINOGENIC POTENCY; ACUTE TOXICITY; UNCERTAINTY; BIOASSAYS; SAFETY AB The proposed U.S. Environmental Protection Agency carcinogen risk assessment guidelines employ a benchmark dose as a point of departure (POD) for low-dose risk assessment. If information on the carcinogenic mode of action for a chemical supports a nonlinear dose-response curve below the POD, a margin-of-exposure ratio between the POD and anticipated human exposure would be considered. The POD would be divided by uncertainty (safety) factors to arrive at a reference dose that is likely to produce no, or at most negligible, cancer risk for humans. If nonlinearity below the POD is not supported by sufficient evidence, then linear extrapolation from the incidence at the POD to zero would be used for low-dose cancer risk estimation. The carcinogen guidelines suggest that the lower 95% confidence limit on the dose estimated to produce an excess of tumors in 10% of the animals (LTD10) be used for the POD. Due to the relatively narrow range of doses in 2-year rodent bioassays and the limited range of statistically significant tumor incidence rates, the estimate of the LTD10 obtained from 2-year bioassays is constrained to a relatively narrow range of values. Because of this constraint, a simple, quick, and relatively precise determination of the LTD10 can be obtained by the maximum tolerated dose (MTD) divided by 7. All that is needed is a 90-day study to establish the MTD. It is shown that the LTD10 determined by this relatively easy procedure is generally within a factor of 10 of the LTD10 that would be estimated using tumor incidence rates from 2-year bioassays. Estimates of cancer potency from replicated 2-year bioassays, and hence estimates of cancer risk, have been show to vary by a factor of 4 around a median value. Thus, there may be little gain in precision of cancer risk estimates derived from a a-year bioassay, compared to the estimate based on the MTD from a 90-day study. If the anticipated human exposure were estimated to be small relative to the MTD/7 = LTD10, there may be little value in conducting a chronic 2-year study in rodents because the estimate of cancer risk would be low regardless of the results of a 2-year bioassay. Linear extrapolation to a risk of less than 1 in 100,000 and use of an uncertainty factor, e.g., of 10,000, would give the same regulatory "safe dose." Linear extrapolation to a virtually safe dose associated with a cancer risk estimate of less than one in a million mould be 10 times lower than the reference dose based on the LTD10/10,000. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Lawrence Berkeley Lab, Berkeley, CA 94720 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. RP Gaylor, DW (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 15 TC 18 Z9 18 U1 0 U2 3 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 DEC PY 1998 VL 28 IS 3 BP 222 EP 225 DI 10.1006/rtph.1998.1258 PG 4 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 171GA UT WOS:000078853500005 PM 10049793 ER PT J AU Matthews, EJ Contrera, JF AF Matthews, EJ Contrera, JF TI A new highly specific method for predicting the carcinogenic potential of pharmaceuticals in rodents using enhanced MCASE QSAR-ES software SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE chemical carcinogenesis; pharmaceutical (or drug); rodent carcinogenicity study; tumor; structure-activity relationship (SAR) software ID AUTOMATED STRUCTURE EVALUATION; NATIONAL-TOXICOLOGY-PROGRAM; CHEMICAL-STRUCTURE; MUTAGENICITY; BIOASSAYS; IDENTIFICATION; SALMONELLA AB This report describes in detail a new quantitative structure-activity relational expert system (QSAR-ES) method for predicting the carcinogenic potential of pharmaceuticals and other organic chemicals in rodents, and a beta-test evaluation of its performance. The method employs an optimized, computer-automated structure evaluation (MCASE) software program and new database modules which were developed under a Cooperative Research and Development Agreement (CRADA) between FDA and Multicase, Inc. The beta-test utilized 126 compounds with carcinogenicity studies not included in control database modules and three sets of modules, including: A07-9 (Multicase, Inc.), AF1-4 (FDA-OTR/Multicase, Inc.), and AF5-8 (FDA-OTR/proprietary). The investigation demonstrated that the standard MCASE(A07-9) system which had a small data-set (n = 319), detected few structure alerts (SA) for carcinogenicity (n = 17), and had poor coverage for beta-test compounds (51%). Conversely, the new, optimized FDA-OTR/MCASE(AF5-8) system had a large data-set (n = 934), detected many SA (n = 58) and had good coverage (94%). In addition, the study showed the standard MCASE(A07-9) software had poor predictive value for carcinogens and specificity for noncarcinogens (50 and 42%), detected many false positives (58%), and exhibited poor concordance (46%). Conversely, the new, FDA-OTR/MCASE(AF5-8) system demonstrated excellent predictive value for carcinogens and specificity for non-carcinogens (97%, 98%), detected only one false positive (2%), and exhibited good concordance (75%). The dramatic improvements in the performance of the MCASE were due to numerous modifications, including: (a) enhancement of the size of the control database modules, (b) optimization of MCASE SAR assay evaluation criteria, (c) incorporation of a carcinogenic potency scale for control compound activity and MCASE bio-phores, (d) construction of individual rodent gender- and species-specific modules, and (e) defining assay acceptance criteria for query and control database compounds. C1 US FDA, Ctr Drug Evaluat & Res HFD901, Rockville, MD 20850 USA. RP Matthews, EJ (reprint author), US FDA, Ctr Drug Evaluat & Res HFD901, 5600 Fishers Lane, Rockville, MD 20850 USA. NR 43 TC 96 Z9 98 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD DEC PY 1998 VL 28 IS 3 BP 242 EP 264 DI 10.1006/rtph.1998.1259 PG 23 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 171GA UT WOS:000078853500008 PM 10049796 ER PT J AU Mahmood, I AF Mahmood, I TI Is 10 milligrams selegiline essential as an adjunct therapy for the symptomatic treatment of Parkinson's disease? SO THERAPEUTIC DRUG MONITORING LA English DT Article DE selegiline; MAO-B inhibition; reduction in dose ID MAO-B-INHIBITOR; OXIDASE TYPE-B; DEPRENYL AB Selegiline is used as an adjunct to levodopa in the symptomatic treatment of Parkinson's disease (PD). The normal daily dose of selegiline is 10 mg administered orally. This study, based on monoamine oxidase-B (MAO-B) inhibition, investigates whether a reduction in selegiline dose can provide the same beneficial effects seen with a 10-mg dose. The inhibition of platelet MAO-B activity against multiple dosing of selegiline (2.5, 5, and 7.5 mg) was predicted from the data obtained from literature (0.5, 1.0, 1.5, and 10 mg). A pharmacokinetic-pharmacodynamic model for selegiline was also developed. The data suggested that by 96 hours (four doses) the inhibition of platelet MAO-B activity is approximately 95% after a daily dose of 2.5 mg selegiline, whereas it takes only 48 hours (two doses) for doses of 5 mg and 7.5 mg to achieve this degree of inhibition. The pharmacokinetic-pharmacodynamic model was best described by a sigmoidal E-max model with an effect compartment. Based on the inhibition of MAO-B activity, a reduction in daily oral dose of selegiline appears possible without compromising the therapeutic effect. Therefore, lower doses of selegiline should be tested in clinical trials. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1 HFD860, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1 HFD860, Woodmont Off Ctr 2,1451 Rockville Pike, Rockville, MD 20852 USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD DEC PY 1998 VL 20 IS 6 BP 717 EP 721 DI 10.1097/00007691-199812000-00024 PG 5 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA 142WJ UT WOS:000077223100024 PM 9853994 ER PT J AU Abbas, HK Shier, WT Seo, JA Lee, YW Musser, SM AF Abbas, HK Shier, WT Seo, JA Lee, YW Musser, SM TI Phytotoxicity and cytotoxicity of the fumonisin C and P series of mycotoxins from Fusarium spp. Fungi SO TOXICON LA English DT Article ID MAMMALIAN-CELL CULTURES; BIOLOGICAL-ACTIVITIES; AAL-TOXIN; MONILIFORME; IDENTIFICATION; JIMSONWEED AB Fumonisin C (FC) and P (FP) are two recently identified series of sphingosine-analog mycotoxins, for which biological activities have not previously been reported. FC1, FC2 and OH-FC1 (1 mu M) exhibited strong phytotoxicity comparable to the standard FBI in duckweed (Lemna pausicotata L.) cultures, whereas FC3 and FC4 were moderately phytotoxic. Conversely, FP1 exhibited weak phytotoxicity only at higher concentrations (greater than or equal to 10 mu M). These mycotoxins exhibited a similar pattern of cytotoxicity with FBI-sensitive cultured mammalian cell lines, H4TG and MDCK. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 ARS, USDA, So Weed Res Unit, Stoneville, MS 38776 USA. Univ Minnesota, Dept Med Chem, Minneapolis, MN 55455 USA. Seoul Natl Univ, Dept Agr Biol, Coll Agr & Life Sci, Suwon 441744, South Korea. Seoul Natl Univ, Res Ctr New Biomat Agr, Coll Agr & Life Sci, Suwon 441744, South Korea. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Abbas, HK (reprint author), ARS, USDA, So Weed Res Unit, Stoneville, MS 38776 USA. NR 24 TC 23 Z9 27 U1 2 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD DEC PY 1998 VL 36 IS 12 BP 2033 EP 2037 DI 10.1016/S0041-0101(98)00115-9 PG 5 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 139BC UT WOS:000077006700025 PM 9839687 ER PT J AU Fernandez, IM Golding, H Benaissa-Trouw, BJ de Vos, NM Harmsen, M Nottet, HSLM Golding, B Puijk, WC Meloen, RH Snippe, H Kraaijeveld, CA AF Fernandez, IM Golding, H Benaissa-Trouw, BJ de Vos, NM Harmsen, M Nottet, HSLM Golding, B Puijk, WC Meloen, RH Snippe, H Kraaijeveld, CA TI Induction of HIV-1 IIIb neutralizing antibodies in BALB/c mice by a chimaeric peptide consisting of a T-helper cell epitope of Semliki Forest virus and a B-cell epitope of HIV SO VACCINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NUCLEOTIDE-SEQUENCE; ADJUVANT ACTIVITY; BRUCELLA-ABORTUS; V3 DOMAIN; HTLV-III; TYPE-1; IMMUNOGENICITY; CHIMPANZEES; DETERMINANT AB A colinearly synthesized peptide consisting of a H-2(d) restricted T-helper cell epitope of Semliki Forest virus (SFV) ann triple repents of sequence GPGRAF, derived from the V3 domain of HN-I strains, was used to immunize BALB/c (H-2(d)) mice. Pepscan analysis of sera from peptide-immunized mice revealed that the chimaeric peptide GREKFTIRPHYGKEIGPGRAFGPGRAFGPGRAF contains three distinct antibody-reactive sequences GREKFTIR, PHYGKEI and GPGRAF. The chimaeric peptide evoked HN-I IIIb neutralizing antibodies in serum as measured in vitro by reduction of syncytia formation and reduction of p24 production as well. So, the T-helper cell epitope of SFV provided help to a small linear neutralization epitope of HIV-1 strains. Interestingly; the T-helper cell epitope alone might induce antibodies cross-reactive with HN-I IIIb specific peptide GPGRAFVTIGK which shows some homology (residues underlined) with the antibody-reactive sequence GREKTIR of SFV. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Univ Utrecht Hosp, Eijkman Winkler Inst Microbiol Infect Dis & Infla, NL-3584 CX Utrecht, Netherlands. US FDA, Lab Plasma Derivat, Div Hematol, Off Blood,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. ID DLO, NL-8200 AB Lelystad, Netherlands. RP Snippe, H (reprint author), Univ Utrecht Hosp, Eijkman Winkler Inst Microbiol Infect Dis & Infla, Room G04-614,Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. EM H.Snippe@lab.azu.nl NR 35 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD DEC PY 1998 VL 16 IS 20 BP 1936 EP 1940 DI 10.1016/S0264-410X(98)00128-5 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 127ER UT WOS:000076338100008 PM 9796047 ER PT J AU Wyatt, LS Carroll, MW Czerny, CP Merchlinsky, M Sisler, JR Moss, B AF Wyatt, LS Carroll, MW Czerny, CP Merchlinsky, M Sisler, JR Moss, B TI Marker rescue of the host range restriction defects of modified vaccinia virus Ankara SO VIROLOGY LA English DT Article ID ATTENUATED MVA STRAIN; HAMSTER OVARY CELLS; RECOMBINANT VECTOR; GENE-EXPRESSION; RNA-POLYMERASE; DELETION; SEQUENCE; MUTANTS; GENOME; TRANSPOSITION AB The severely attenuated and host range (HR) restricted modified vaccinia virus Ankara (MVA) was derived by >500 passages in chick embryo fibroblasts, during which multiple deletions and mutations occurred. To determine the basis of the HR defect, we prepared cosmids from the parental vaccinia virus Ankara genome and transfected them into nonpermissive monkey BS-C-1 cells that had been infected with MVA. Recombinant viruses that formed macroscopic plaques were detected after transfections with DNA segments that mapped near the left end of the viral genome. Plaque-forming viruses, generated by transfections with four individual cosmids and one pair of minimally overlapping cosmids, were purified, and their HRs were evaluated in BS-C-1 cells, rabbit RK-13 cells, and human HeLa, MRC-5, and A549 cells. The acquisition of the K1L and SPI-1 HR genes and the repair of large deletions were determined by polymerase chain reaction or pulse-field gel electrophoresis of Notl restriction enzyme digests of genomic DNA. The following results indicated the presence of previously unrecognized vaccinia virus HR genes: (1) the major mutations that restrict HR are within the left end of the MVA genome because the phenotypes of some recombinants approached that of the parental virus, (2) acquisition of the K1L gene correlated with the ability of recombinant viruses to propagate in RK-13 cells but did not enhance replication in human or monkey cell lines, (3) acquisition of the SPI-1 gene correlated with virus propagation in A549 cells but not with the extent of virus spread in monkey or other human cell lines, (4) there are at least two impaired HR genes because rescue occurred with nonoverlapping or minimally overlapping cosmids and recombinant viruses with intermediate HRs were isolated, and (5) at least one of the new HR genes did not map within any of the major deletions because the size of the left terminal Notl fragment was not appreciably altered in some recombinant viruses. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab DNA Viruses, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM bmoss@nih.gov NR 46 TC 52 Z9 53 U1 0 U2 3 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 NOV 25 PY 1998 VL 251 IS 2 BP 334 EP 342 DI 10.1006/viro.1998.9397 PG 9 WC Virology SC Virology GA 141FB UT WOS:000077131000014 PM 9837798 ER PT J AU Mahmood, I AF Mahmood, I TI Interspecies scaling of renally secreted drugs SO LIFE SCIENCES LA English DT Article DE allometry; renal secretion; drug clearance; volume of distribution; half-life; interspecies scaling ID ANIMAL DATA; PHARMACOKINETICS; CIPROFLOXACIN; CLEARANCE; HUMANS; DISPOSITION; PARAMETERS; RANITIDINE; PREDICTION; EXCRETION AB The objective of this study is to predict pharmacokinetic parameters (clearance, volume of distribution at steady state, and elimination half-life) in humans from animal data for drugs which are renally secreted in humans. Pharmacokinetic parameters of ten drugs were scaled-up from animal data obtained from the literature. Using simple allometry (pharmacokinetic parameter of interest vs body weight), total, renal and nonrenal clearances, volume of distribution and half-life were predicted in humans. The predicted parameters were compared with the observed parameters. The results of the study indicated that it is likely that the predicted total and renal clearances from animal data will be underestimated in humans for renally secreted drugs. The prediction of renal clearance was improved by normalizing the renal clearance by a ' correction factor' for animals who exhibited renal secretion. The predicted volume and half-life were comparable with the observed values in man. Overall, the results of this study indicate that caution should be employed in interpreting the total and renal clearance of renally secreted drugs predicted by the allometric approach. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Woodmont Off Ctr 2, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Woodmont Off Ctr 2, HFD-860,1451 Rockville Pike, Rockville, MD 20852 USA. NR 25 TC 56 Z9 56 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD NOV 20 PY 1998 VL 63 IS 26 BP 2365 EP 2371 DI 10.1016/S0024-3205(98)00525-6 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 142NK UT WOS:000077206400009 PM 9877226 ER PT J AU Shallow, S Daily, P Rothrock, G Reingold, A Vugia, D Waterman, S Fiorentino, T Marcus, R Ryder, R Mshar, P Cartter, M Hadler, J Farley, M Bardsley, M Baughman, W Koehler, J Blake, P Toomey, K Wicklund, J Hedberg, C Osterholm, M Cassidy, M McGivern, T Stanton, R Shiferaw, B Cieslak, P Fleming, D AF Shallow, S Daily, P Rothrock, G Reingold, A Vugia, D Waterman, S Fiorentino, T Marcus, R Ryder, R Mshar, P Cartter, M Hadler, J Farley, M Bardsley, M Baughman, W Koehler, J Blake, P Toomey, K Wicklund, J Hedberg, C Osterholm, M Cassidy, M McGivern, T Stanton, R Shiferaw, B Cieslak, P Fleming, D TI Incidence of foodborne Illnesses - FoodNet, 1997 (Reprinted from MMWR, vol 47, pg 782-786, 1998) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Univ Calif Berkeley, Calif Emerg Infect Program, Berkeley, CA 94720 USA. Calif Dept Hlth Serv, Sacramento, CA USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. Connecticut State Dept Publ Hlth, Hartford, CT USA. Atlanta Metropolitan Act Surveillance Project, Atlanta, GA USA. Georgia Dept Human Resources, Div Publ Hlth, Atlanta, GA USA. Minnesota Dept Publ Hlth, St Paul, MN USA. Oregon Dept Human Resources, State Hlth Div, Salem, OR USA. US Food Safety & Inspect Serv, USDA, Washington, DC 20250 USA. US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. CDC, Foodborne & Diarrheal Dis Branch, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. CDC, Epidemiol Branch, Div Parasit Dis, Atlanta, GA 30333 USA. CDC, Off Director, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. RP Shallow, S (reprint author), Univ Calif Berkeley, Calif Emerg Infect Program, Berkeley, CA 94720 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 18 PY 1998 VL 280 IS 19 BP 1651 EP 1652 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 138PD UT WOS:000076980700010 ER PT J AU Tomasz, M Das, A Tang, KS Ford, MGJ Minnock, A Musser, SM Waring, MJ AF Tomasz, M Das, A Tang, KS Ford, MGJ Minnock, A Musser, SM Waring, MJ TI The purine 2-amino group as the critical recognition element for sequence-specific alkylation and cross-linking of DNA by mitomycin C SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID DUPLEX; BINDING; AGENTS; ADDUCT; MONOADDUCTS; PREFERENCES; MECHANISM; FRAGMENTS; CLEAVAGE; GUANINE AB Mitomycin C (MC) is a G.C-specific antitumor antibiotic that alkylates and cross-links DNA at 2-amino groups of guanine residues. Both reactions are known to be enhanced at guanines in the CpG sequence by independent mechanisms. The mechanisms were probed by substituting 2,6-diaminopurine (D) into oligonucleotides and into a 162-bp tyrT DNA restriction fragment and determining their alkylation and crosslinking by MC. Covalent D-MC adducts were isolated and structurally characterized. The results indicated that 2,6-diaminopurine functioned as a substrate analogue of guanine and displayed enhanced reactivity toward MC in all systems. The observed TpD sequence selectivity of the modifications by MC was analogous to the CPG sequence selectivity of guanine modifications. Selective monoalkylation and cross-linking was observed also at the TpG.CpD sequence, indicating that two purine 2-amino groups are necessary and sufficient for the selectivity regardless of whether they are supplied by G or by D. These findings reinforce the previously proposed mechanism in which the selectivity of monoalkylation by MC is attributed to a specific H-bond between the drug and the 2-amino group of a guanine. The specific sequence required for D-D and D-G cross-link formation was established as TpD TpD and TpG CpD, respectively, determined by the same minor groove structural factors as in the CpG CpG cross-linking process. MC cross-linking was also probed in a 162-bp tyrT DNA fragment in which Gs and As were replaced by inosine and 2,6-diaminopurine, respectively, using PCR. Cross-linked sites were quantitated and mapped on the basis of an empirical correlation between the electrophoretic mobility of cross-linked DNA and the position of the cross-links relative to the center of the sequence. In the natural DNA sequence hotspots for formation of MC-cross-links were identified. The cross-links were shown to be translocated from CpG CpG in the natural DNA to TpD TpD or TpG CpD in the substituted DNAs, demonstrating the dominant role of the purine 2-amino group for cross-link site selection by MC. C1 CUNY Hunter Coll, Dept Chem, New York, NY 10021 USA. US FDA, Washington, DC 20204 USA. Univ Cambridge, Dept Pharmacol, Cambridge CB2 1QJ, England. RP Tomasz, M (reprint author), CUNY Hunter Coll, Dept Chem, New York, NY 10021 USA. NR 35 TC 36 Z9 36 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 18 PY 1998 VL 120 IS 45 BP 11581 EP 11593 DI 10.1021/ja9824019 PG 13 WC Chemistry, Multidisciplinary SC Chemistry GA 141AC UT WOS:000077119600007 ER PT J AU Nordahl, TE Stein, MB Benkelfat, C Semple, WE Andreason, P Zametkin, A Uhde, TW Cohen, RM AF Nordahl, TE Stein, MB Benkelfat, C Semple, WE Andreason, P Zametkin, A Uhde, TW Cohen, RM TI Regional cerebral metabolic asymmetries replicated in an independent group of patients with panic disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE panic disorder; regional cerebral glucose metabolism; hemispheric asymmetries ID OBSESSIVE-COMPULSIVE DISORDER; POSITRON EMISSION TOMOGRAPHY; GLUCOSE-UTILIZATION; PREFRONTAL CORTEX; BLOOD-FLOW; DEPRESSION; ANXIETY; RATES; ADULTS AB Background: Abnormal left/right (L/R) hemispheric ratios of regional cerebral glucose metabolic rates (rCMRglc) (hippocampus and inferior prefrontal cortex) have been noted in unmedicated panic disorder patients, Methods: An independent group of panic disorder patients placed on imipramine was studied with positron-emission tomography, testing for evidence of normalization versus persistence of the abnormal rCMRglc ratios, Differences in orbital frontal rCMRglc values between the imipramine-treated and the previously reported unmedicated panic disorder patients were tested examining for evidence that the differences would resemble those noted in obsessive-compulsive disorder (OCD) patients treated with clomipramine. Results: We found the same abnormally low UR hippocampal and posterior inferior prefrontal rCMRglc ratios in the imipramine-treated panic disorder patients, In addition, we found posterior orbital frontal rCMRglc decreases in the imipramine-treated panic disorder patients compared with the unmedicated panic disorder patients, Conclusions: These abnormal asymmetries found in unmedicated panic disorder patients and now, in imipramine-treated panic disorder patients may reflect a trait abnormality, The orbital frontal rCMRglc differences between the imipramine-treated and unmedicated patients are similar to changes noted in OCD patients treated with clomipramine and may reflect direct or indirect effects of imipramine treatment in panic disorder patients, (C) 1998 Society of Biological Psychiatry. C1 Univ Calif Berkeley, Lawrence Berkeley Lab, Ctr Funct Imaging, Berkeley, CA 94720 USA. Univ Calif Davis, Med Ctr, Dept Psychiat, Sacramento, CA 95817 USA. Napa State Hosp, Napa, CA USA. Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. McGill Univ, Dept Psychiat, Neurobiol Psychiat Unit, Montreal, PQ, Canada. Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. US FDA, Rockville, MD 20857 USA. NIMH, Bethesda, MD 20892 USA. Wayne State Univ, Dept Psychiat, Detroit, MI USA. RP Nordahl, TE (reprint author), Univ Calif Berkeley, Lawrence Berkeley Lab, Ctr Funct Imaging, MS 55-121,1 Cyclotron Rd, Berkeley, CA 94720 USA. RI Nordahl, Thomas/J-7643-2013 OI Nordahl, Thomas/0000-0002-8627-0356 NR 30 TC 50 Z9 53 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 1998 VL 44 IS 10 BP 998 EP 1006 DI 10.1016/S0006-3223(98)00026-2 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 137WA UT WOS:000076938700008 PM 9821564 ER PT J AU Chang, AC Jacobs, H Weinstein, MJ Kessler, CM AF Chang, AC Jacobs, H Weinstein, MJ Kessler, CM TI The correlation of closure the and von Willebrand factor activity of factor VIII concentrates. SO BLOOD LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Off Blood Res & Review,Lab Hemostasis, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Div Hematol & Oncol, Washington, DC 20007 USA. NR 0 TC 1 Z9 1 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 743 BP 184A EP 184A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300739 ER PT J AU Aoki, Y Jaffe, ES Chang, Y Jones, K Teruya-Feldstein, J Moore, PS Tosato, G AF Aoki, Y Jaffe, ES Chang, Y Jones, K Teruya-Feldstein, J Moore, PS Tosato, G TI Angiogenesis and hematopoiesis induced by KSHV-encoded interleukin-6. SO BLOOD LA English DT Meeting Abstract C1 NCI, Hematopathol Sect, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Columbia Univ, Sch Publ Hlth, Dept Pathol, New York, NY 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1238 BP 302A EP 303A PN 1 PG 2 WC Hematology SC Hematology GA 141AW UT WOS:000077121301230 ER PT J AU Gutierrez, MI Hussain, A Zacharchuk, C Cherney, B Magrath, IT Bhatia, K AF Gutierrez, MI Hussain, A Zacharchuk, C Cherney, B Magrath, IT Bhatia, K TI Placement of the proapoptic protein bax in the Fas mediated death pathway in Burkitts lymphomas. SO BLOOD LA English DT Meeting Abstract C1 NCI, Div Clin Sci, NIH, Bethesda, MD 20892 USA. US FDA, Div Hematol Prod, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1994 BP 484A EP 484A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301984 ER PT J AU Lamb, LS Gee, AP Musk, P O'Hanlon, TP Hazlett, LJ Geier, SS Folk, RS Harris, WG McPherson, K Parrish, RS Lee, C Henslee-Downey, P AF Lamb, LS Gee, AP Musk, P O'Hanlon, TP Hazlett, LJ Geier, SS Folk, RS Harris, WG McPherson, K Parrish, RS Lee, C Henslee-Downey, P TI Influence of T cell depletion method on circulating gamma delta T cell reconstitution and potential role in the graft versus leukemia effect. SO BLOOD LA English DT Meeting Abstract C1 Univ S Carolina, Sch Med, Div Transplantat Med, Columbia, SC USA. US FDA, Bethesda, MD 20014 USA. Univ Texas, MD Anderson Cancer Ctr, Dept Blood & Marrow Transplantat, Houston, TX 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2028 BP 492A EP 492A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302018 ER PT J AU Holada, K Theisen, P MacAuley, C Rohwer, RG Vostal, JG AF Holada, K Theisen, P MacAuley, C Rohwer, RG Vostal, JG TI Prion protein is distributed differently on hamster and human blood cells. SO BLOOD LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol Ctr, Bethesda, MD USA. Vet Adm Med Ctr, Baltimore, MD 21218 USA. NR 0 TC 1 Z9 1 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2069 BP 502A EP 503A PN 1 PG 2 WC Hematology SC Hematology GA 141AW UT WOS:000077121302059 ER PT J AU Hrinczenko, BW Brockner-Ryan, B Alayash, AI Pannell, LK Wojtkowski, T Noguchi, CT Rodgers, GP Schechter, AN AF Hrinczenko, BW Brockner-Ryan, B Alayash, AI Pannell, LK Wojtkowski, T Noguchi, CT Rodgers, GP Schechter, AN TI Selective nitrosylation of the beta-chains of hemoglobin by nitric oxide donor compounds. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Plasma Derivat, 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2152 BP 524A EP 524A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302142 ER PT J AU Rivera, CE Mostowski, H Max, EE AF Rivera, CE Mostowski, H Max, EE TI Epstein-Barr virus infection occurs at a high percentage in human IgE producing B lymphocytes. SO BLOOD LA English DT Meeting Abstract C1 NIH, Warren G Magnuson Clin Ctr, Hematol Serv, Bethesda, MD 20892 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2236 BP 544A EP 544A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302225 ER PT J AU Mondoro, TH Vostal, JG AF Mondoro, TH Vostal, JG TI Cold temperatures reduce sensitivity of stored platelets to disaggregating agents. SO BLOOD LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2324 BP 565A EP 565A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302311 ER PT J AU Martinez, MN AF Martinez, MN TI Article IV: Clinical application of pharmacokinetics SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article ID ESCHERICHIA-COLI; CIPROFLOXACIN; ANTIBIOTICS; PRINCIPLES C1 US FDA, CVM, Rockville, MD 20855 USA. RP Martinez, MN (reprint author), US FDA, CVM, 7500 Standish Pl, Rockville, MD 20855 USA. NR 33 TC 1 Z9 1 U1 0 U2 1 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD NOV 15 PY 1998 VL 213 IS 10 BP 1418 EP 1420 PG 3 WC Veterinary Sciences SC Veterinary Sciences GA 139GZ UT WOS:000077021300010 PM 9828932 ER PT J AU Albert, JM Ioannidis, JPA Reichelderfer, P Conway, B Coombs, RW Crane, L Demasi, R Dixon, DO Flandre, P Hughes, MD Kalish, LA Larntz, K Lin, DY Marschner, IC Munoz, A Murray, J Neaton, J Pettinelli, C Rida, W Taylor, JMG Welles, SL AF Albert, JM Ioannidis, JPA Reichelderfer, P Conway, B Coombs, RW Crane, L Demasi, R Dixon, DO Flandre, P Hughes, MD Kalish, LA Larntz, K Lin, DY Marschner, IC Munoz, A Murray, J Neaton, J Pettinelli, C Rida, W Taylor, JMG Welles, SL CA NIAID Workshop TI Statistical issues for HIV surrogate endpoints: Point/counterpoint SO STATISTICS IN MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SYNCYTIUM-INDUCING PHENOTYPE; CLINICAL-TRIALS; LYMPHOCYTE COUNTS; VIRAL LOAD; RNA LEVELS; DISEASE PROGRESSION; ZIDOVUDINE THERAPY; CUBIC MILLIMETER; PROGNOSTIC VALUE AB This paper summarizes the proceedings of an NIAID-sponsored workshop on statistical issues for HIV surrogate endpoints. The workshop brought together statisticians and clinicians in an attempt to shed light on some unresolved issues in the use of HIV laboratory markers (such as HIV RNA and CD4 + cell counts) in the design and analysis of clinical studies and in patient management. Utilizing a debate format, the workshop explored a series of specific questions dealing with the relationship between markers and clinical endpoints, and the choice of endpoints and methods of analysis in clinical studies. This paper provides the position statements from the two debaters on each issue. Consensus conclusions, based on the presentations and discussion, are outlined. While not providing final answers, we hope that these discussions have helped clarify a number of issues, and will stimulate further consideration of some of the highlighted problems. These issues will be critical in the proper assessment and use of future therapies for HIV disease. (C) 1998 John Wiley & Sons, Ltd. C1 NIAID, Div Aids, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Univ Washington, Seattle, WA 98195 USA. Wayne State Univ, Detroit Med Ctr, Detroit, MI 48202 USA. London Sch Hyg & Trop Med, London WC1, England. New England Res Inst, Watertown, MA USA. Univ Minnesota, Minneapolis, MN 55455 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. US FDA, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Albert, JM (reprint author), NIAID, Div Aids, Biostat Res Branch, NIH, 6003 Execut Blvd, Bethesda, MD 20892 USA. EM ja24o@nih.gov RI Ioannidis, John/G-9836-2011 FU NIAID NIH HHS [AI30731, AI27664, AI27757] NR 71 TC 31 Z9 32 U1 0 U2 3 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 NOV 15 PY 1998 VL 17 IS 21 BP 2435 EP 2462 DI 10.1002/(SICI)1097-0258(19981115)17:21<2435::AID-SIM994>3.3.CO;2-7 PG 28 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 132JF UT WOS:000076626000002 PM 9819838 ER PT J AU Nightingale, SL AF Nightingale, SL TI New drug to treat HIV/AIDS approved SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 27 Z9 28 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 4 PY 1998 VL 280 IS 17 BP 1472 EP 1472 DI 10.1001/jama.280.17.1472-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 134RR UT WOS:000076757200004 PM 9809716 ER PT J AU Nightingale, SL AF Nightingale, SL TI Emergency contraception kit approved SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 27 Z9 28 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 4 PY 1998 VL 280 IS 17 BP 1472 EP 1472 DI 10.1001/jama.280.17.1472-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 134RR UT WOS:000076757200003 PM 9809716 ER PT J AU Lobel, HO Coyne, PE Rosenthal, PJ AF Lobel, HO Coyne, PE Rosenthal, PJ TI Drug overdoses with antimalarial agents: Prescribing and dispensing errors SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. US FDA, Rockville, MD 20857 USA. Univ Calif San Francisco, San Francisco Gen Hosp, San Francisco, CA USA. RP Lobel, HO (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. NR 4 TC 8 Z9 8 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 4 PY 1998 VL 280 IS 17 BP 1483 EP 1483 DI 10.1001/jama.280.17.1483 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 134RR UT WOS:000076757200018 PM 9809726 ER PT J AU Weinger, MB Pantiskas, C Wiklund, ME Carstensen, P AF Weinger, MB Pantiskas, C Wiklund, ME Carstensen, P TI Incorporating human factors into the design of medical devices SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 Univ Calif San Diego, La Jolla, CA 92093 USA. Space Labs Med Inc, Redmond, WA USA. Amer Inst Res, Concord, MA USA. US FDA, Rockville, MD 20857 USA. RP Weinger, MB (reprint author), Univ Calif San Diego, La Jolla, CA 92093 USA. NR 5 TC 37 Z9 37 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 NOV 4 PY 1998 VL 280 IS 17 BP 1484 EP 1484 DI 10.1001/jama.280.17.1484-a PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 134RR UT WOS:000076757200019 PM 9809727 ER PT J AU Cook, KA Dobbs, TE Hlady, G Wells, JG Barrett, TJ Puhr, ND Lancette, GA Bodager, DW Toth, BL Genese, CA Highsmith, AK Pilot, KE Finelli, L Swerdlow, DL AF Cook, KA Dobbs, TE Hlady, G Wells, JG Barrett, TJ Puhr, ND Lancette, GA Bodager, DW Toth, BL Genese, CA Highsmith, AK Pilot, KE Finelli, L Swerdlow, DL TI Outbreak of Salmonella serotype hartford infections associated with unpasteurized orange juice SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HEMOLYTIC UREMIC SYNDROME; ESCHERICHIA-COLI O157-H7; PRESSED APPLE CIDER; ODDS RATIO; FRESH AB Context.-Acidic foods such as orange juice have been thought to be unlikely vehicles of foodborne illness. Objective.-To investigate an outbreak of Salmonella enterica serotype Hartford (Salmonella Hartford) infections among persons visiting a theme park in Orlando, Fla, in 1995, Design.-Review of surveillance data, matched case-control study, laboratory investigation, and environmental studies. Setting.-General community, Participants.-The surveillance case definition was Salmonella Harfford or Salmonella serogroup C-1 infection in a resident of or a visitor to Orlando in May or June 1995. In the case-control study, case patients were limited to theme park hotel visitors and controls were matched to case patients by age group and hotel check-in date. Main Outcome Measures.-Risk factors for infection and source of implicated food. Results.-Sixty-two case patients from 21 states were identified, Both Salmonella Harfford and Salmonella enterica serotype Gaminara (Salmonella Gaminara) were isolated from stool samples of 1 ill person. Thirty-two case patients and 83 controls were enrolled in the case-control study, Ninety-seven percent of case patients had drunk orange juice in the theme park vs 54% of controls (matched odds ratio, undefined; 95% confidence interval, 5.2 to undefined). The orange juice was unpasteurized and locally produced. Salmonella Gaminara was isolated from 10 of 12 containers of orange juice produced during May and July, indicating ongoing contamination of juice probably because of inadequately sanitized processing equipment. Conclusions.-Unpasteurized orange juice caused an outbreak of salmonellosis in a large Florida theme park. All orange juice was recalled and the processing plant closed, Pasteurization or other equally effective risk-management strategies should be used in the production of all juices. C1 Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Bacterial & Mycot Dis, Foodborne & Diarrheal Dis Branch, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Epidemiol Program Off, Epidem Intelligence Serv, Atlanta, GA 30333 USA. US FDA, SE Reg Lab, Atlanta, GA USA. Florida Dept Hlth, Tallahassee, FL USA. Orange Cty Publ Hlth Unit, Orlando, FL USA. New Jersey Dept Hlth & Senior Serv, Trenton, NJ USA. RP Cook, KA (reprint author), Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Bacterial & Mycot Dis, Foodborne & Diarrheal Dis Branch, 1600 Clifton Rd NE,MS A38, Atlanta, GA 30333 USA. NR 38 TC 100 Z9 106 U1 2 U2 15 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 4 PY 1998 VL 280 IS 17 BP 1504 EP 1509 DI 10.1001/jama.280.17.1504 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 134RR UT WOS:000076757200024 PM 9809731 ER PT J AU Ye, XM Sallet, AC Kascsak, RJ Carp, RI AF Ye, XM Sallet, AC Kascsak, RJ Carp, RI TI Astrocytosis and amyloid deposition in scrapie-infected hamsters SO BRAIN RESEARCH LA English DT Article DE scrapie; astrocyte; GFAP; PrP; hamster ID PRION PROTEIN-FRAGMENT; AGENT PROTEIN; HISTOPATHOLOGICAL CHANGES; INCREASED EXPRESSION; MOUSE SCRAPIE; 139H STRAIN; MICE; LOCALIZATION; DISEASE; BRAINS AB In scrapie infection, prion protein (PrPSc) is localized in areas where there is neurodegeneration and astrocytosis. It is thought that PrPSc is toxic to neurons and trophic for astrocytes. In our study, paraffin sections from scrapie infected (263K and 139H) and control hamsters were examined with histological and immunocytochemical staining. We found that PrPSc was present in the ependymal cells of both 263K- and 139H-infected hamsters. In 139H-infected hamsters, PrPSc was found in the cytoplasm of neurons in cerebral cortex and in hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. In contrast, neuronal cytoplasm and nuclei, were positive for PrPSc in most areas such as cortex, hippocampus, and thalamus in 263K-infected hamsters. Many aggregations of PrPSc could be seen in the cortex, hippocampus, substantia nigra and around the Pia mater, corpus callosum, fimbria, ventricles, and blood vessels in sections from 139H- and/or 263K-positive animals. Furthermore, PrPSc was also co-localized with glial fibrillary acidic protein (GFAP) in many reactive astrocytes (approximately 90%) in certain areas such as the hippocampus in 263K-infected hamsters, but not 139H-infected hamsters. The patterns of astrocytosis and PrPSc formation were different between 139H- and 263K-infected hamsters, which may be used for a diagnosis purpose. Our results suggest a hypothesis that multiple cell-types are capable of PrPSc production. Our results also confirm that reactive astrocytes can produce and/or accumulate PrPSc during some scrapie strain infections. The findings suggest a 'snowball effect', that is: astrocytosis might play an important role in amyloidosis, while amyloidosis may induce further astrocytosis at least in 263K-infected hamsters. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USA. RP Ye, XM (reprint author), Washington State Univ, VCAPP, 205 Wegner Hall, Pullman, WA 99163 USA. FU NIA NIH HHS [AG09017] NR 46 TC 43 Z9 44 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 NOV 2 PY 1998 VL 809 IS 2 BP 277 EP 287 DI 10.1016/S0006-8993(98)00833-6 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 134BG UT WOS:000076722500017 PM 9853120 ER PT J AU Robbins, PA Roderiquez, GL Peden, KWC Norcross, MA AF Robbins, PA Roderiquez, GL Peden, KWC Norcross, MA TI Human immunodeficiency virus type 1 infection of antigen-specific CD4 cytotoxic T lymphocytes SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; HIV-1 INFECTION; EQUIVALENT RECOGNITION; PERIPHERAL-BLOOD; IMMUNE-RESPONSE; CELL TROPISM; V3 LOOP; CD8+; REPLICATION; RECEPTOR AB The effect of macrophage (M)-tropic and T cell line (T)-tropic human immunodeficiency virus type-1 (HIV-1) infection on antigen-specific CD4 cytotoxic T lymphocytes (CTLs) has been studied using a CD4 CTL line specific for a peptide from influenza B virus hemagglutinin, In the absence of antigen presentation, the production of CC chemokines was low. Both the M-tropic HIV-1 strain (HIV-1(AD)) and the T-tropic HIV-1 strain (HIV-1(LAL)) established productive infections in the CD4 CTLs, decreasing antigen-specific cytotoxicity, Peptide presented to the CD4 CTLs increased their secretion of RANTES and MIP-1 beta, suppressed IM-tropic HIV-1 replication, downmodulated CCR5 expression, and preserved CTL recognition. The suppression of M-tropic HIV-1 replication and downmodulation of the CCR5 receptor likely resulted from CC chemokine secretion since antibodies to CC chemokines restored M-tropic HIV-1 replication, Antigen presentation did not protect CD4 CTLs from T-tropic HIV-1 infection or preserve their CTL recognition. Thus, these CD4 CTLs do not make suppressor factors that inhibit the T-tropic HIV-1(LAI) isolate. The results indicate that these CD4 CTLs can either harbor or suppress M-tropic HIV-1 infection, depending on whether antigen is present. CD4 CTLs might therefore provide some protection in the early stages of HIV-1 infection when M-tropic isolates are present. C1 US FDA, Lab Cell & Viral Regulat, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Lab Retrovirus Res, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Robbins, PA (reprint author), US FDA, Lab Cell & Viral Regulat, Ctr Biol Evaluat & Res, NIH Bldg 29B,Rm 5E14,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 58 TC 7 Z9 7 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV 1 PY 1998 VL 14 IS 16 BP 1397 EP 1406 DI 10.1089/aid.1998.14.1397 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 137VA UT WOS:000076936100001 PM 9824317 ER PT J AU Buchanan, RL Edelson, SG Snipes, K Boyd, G AF Buchanan, RL Edelson, SG Snipes, K Boyd, G TI Inactivation of Escherichia coli O157 : H7 in apple juice by irradiation SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID HEMOLYTIC UREMIC SYNDROME; ACID TOLERANCE; CIDER; OUTBREAK; SURVIVAL AB Three strains (932, Ent-C9490, and SEA13B88) of Escherichia coli O157:H7 were used to determine the effectiveness of low-dose gamma irradiation for eliminating E. coli O157:H7 from apple juice or cider and to characterize the effect of inducing pa-dependent, stationary-phase acid resistance on radiation resistance. The strains were grown in tryptic soy broth with or without 1% dextrose for 18 h to produce cells that were or were not induced to pa-dependent stationary-phase acid resistance. The bacteria were then transferred to clarified apple juice and irradiated at 2 degrees C with a cesium-137 irradiator. Non-acid-adapted cells had radiation D values (radiation doses needed to decrease a microbial population by 90%) ranging from 0.12 to 0.21 kGy, D values increased to 0.22 to 0.31 kGy for acid-adapted cells. When acid-adapted SEA13B88 cells were tested in five apple juice brands having different levels of suspended solids (absorbances ranging from 0.04 to 2.01 at 550 nm), radiation resistance increased with increasing levels of suspended solids, with D values ranging from 0.26 to 0.35 kGy, Based on these results, a dose of 1.8 kGy should be sufficient to achieve the 5D inactivation of E, coli recommended by the National Advisory Committee for Microbiological Criteria for Foods. C1 USDA ARS, Eastern Reg Res Ctr, Food Safety Res Unit, Wyndmoor, PA 19038 USA. RP Buchanan, RL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 15 TC 76 Z9 78 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD NOV PY 1998 VL 64 IS 11 BP 4533 EP 4535 PG 3 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 133PD UT WOS:000076694200065 PM 9797319 ER PT J AU Nawaz, MS Zhang, D Khan, AA Cerniglia, CE AF Nawaz, MS Zhang, D Khan, AA Cerniglia, CE TI Isolation and characterization of Enterobacter cloacae capable of metabolizing asparagine SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID PURIFICATION; ACRYLAMIDE; ENZYMES AB A gram-negative, rod-shaped bacterium capable of utilizing L-asparagine as its sole source of carbon and nitrogen was isolated from soil and identified as Enterobacter cloacae. An intracellularly expressed L-asparaginase was detected and it deaminated L-asparagine to aspartic acid and ammonia. High-pressure liquid chromatography analysis of a cell-free asparaginase reaction mixture indicated that 2.8 mM L-asparagine was hydrolyzed to 2.2 and 2.8 mM aspartic acid and ammonia, respectively, within 20 min of incubation. High asparaginase activity was found in cells cultured on L-fructose, D-galactose, saccharose, or maltose, and in cells cultured on L-asparagine as the sole nitrogen source. The pH and temperature optimum of L-asparaginase was 8.5 and 37-42 degrees C, respectively. The half-life of the enzyme at 30 degrees C and 37 degrees C was 10 and 8 h, respectively. C1 Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Nawaz, MS (reprint author), Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 27 TC 15 Z9 16 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD NOV PY 1998 VL 50 IS 5 BP 568 EP 572 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 146PQ UT WOS:000077439900009 PM 9866175 ER PT J AU Lin, DX Tang, YM Peng, Q Lu, SX Ambrosone, CB Kadlubar, FF AF Lin, DX Tang, YM Peng, Q Lu, SX Ambrosone, CB Kadlubar, FF TI Susceptibility to esophageal cancer and genetic polymorphisms in glutathione S-transferases T1, P1, and M1 and cytochrome P450 2E1 SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SQUAMOUS-CELL CARCINOMA; SURGICAL LIVER SAMPLES; HUMAN CYP2E1 GENE; LUNG-CANCER; HEPATOCELLULAR-CARCINOMA; 5'-FLANKING REGION; EPOXIDE HYDROLASE; RSAI POLYMORPHISM; BLADDER-CANCER; COLON-CANCER AB Genetic polymorphisms in enzymes involved in carcinogen metabolism have been shown to influence susceptibility to canter. Cytochrome P450 2E1 (CYP2E1) is primarily responsible for the bioactivation of many low molecular weight carcinogens, including certain nitrosamines, whereas glutathione S-transferases (GSTs) are involved in detoxifying many other carcinogenic electrophiles, Esophageal cancer, which is prevalent in China, is hypothesized to be related to environmental nitrosamine exposure. Thus, we conducted a pilot case-control study to examine the association between CYP2E1, GSTM1, GSTT1, and GSTP1 genetic polymorphisms and esophageal cancer susceptibility. DNA samples were isolated from surgically removed esophageal tissues or scraped esophageal epithelium from cases with cancer (n = 45), cases with severe epithelial hyperplasia (n = 45), and normal controls (n = 46) from a high-risk area, Linxian County, China. RFLPs in the CYP2E1 and the GSTP1 genes were determined by PCR amplification followed by digestion with RsaI or DraI and Alw26I, respectively, Deletion of the GSTM1 and GSTT1 genes was examined by a multiplex PCR, The CYP2E1 polymorphism detected by RsaI was significantly different between controls (56%) and cases with cancer (20%) or severe epithelial hyperplasia (17%; P < 0.001), Persons without the RsaI variant alleles had more than a 4-6-fold risk of developing severe epithelial hyperplasia (adjusted odds ratio, 6.0; 95% confidence interval, 2.3-16.0) and cancer (adjusted odds ratio, 4.8; 95% confidence interval, 1.8-12.4). Polymorphisms in the GSTs were not associated with increased esophageal cancer risk. These results indicate that CYP2E1 may be a genetic susceptibility factor involved in the early events leading to the development of esophageal cancer. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Chinese Acad Med Sci, Inst Canc, Dept Chem Etiol & Carcinogenesis, Beijing 100021, Peoples R China. Beijing Union Med Coll, Beijing 100021, Peoples R China. RP Kadlubar, FF (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, 3900 NCTR Dr, Jefferson, AR 72079 USA. NR 67 TC 132 Z9 149 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 1998 VL 7 IS 11 BP 1013 EP 1018 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 136UP UT WOS:000076877800008 PM 9829710 ER PT J AU Lewis, AJ Walle, UK King, RS Kadlubar, FF Falany, CN Walle, T AF Lewis, AJ Walle, UK King, RS Kadlubar, FF Falany, CN Walle, T TI Bioactivation of the cooked food mutagen N-hydroxy-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine by estrogen sulfotransferase in cultured human mammary epithelial cells SO CARCINOGENESIS LA English DT Article ID HUMAN-LIVER-MICROSOMES; HUMAN BREAST-CANCER; HETEROCYCLIC AMINES; METABOLIC-ACTIVATION; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; DNA-ADDUCTS; SALMONELLA MUTAGENICITY; N-ACETYLTRANSFERASE; CARCINOGEN; EXPRESSION AB Cooked food mutagens from fried meat and fish have recently been suggested to contribute to the etiology of breast cancer, Thus, the most prevalent of these compounds, i.e. 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, or rather its more mutagenic N-hydroxylated metabolite (N-OH-PhIP), forms DNA adducts in mammary cells, including human mammary epithelial (HME) cells. The objective of this study was to determine the involvement of estrogen sulfotransferase (EST), the only sulfotransferase identified in HME cells, in the further bioactivation of N-OH-PhIP, These studies were done in vitro using human recombinant EST and in intact HME cells. Human recombinant EST increased the covalent binding of [H-3]N-OH-PhIP to calf thymus DNA similar to 3.5-fold in the presence of the sulfotransferase co-substrate 3'-phosphoadenosine-5'-phosphosulfate at each N-OH-PhIP concentration (1, 10 and 100 mu M) (n = 6, P < 0.001), In contrast, EST did not catalyze the DNA binding of two other cooked food mutagens, N-hydroxy-2-amino-3-methylimidazo[4,5-f]quinoline and N-hydroxy-2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline, which are mainly hepatocarcinogens, Cultured HME cells displayed high EST activity, which could be completely inhibited by 1 mu M estrone, When the cells were incubated with [H-3]N-OH-PhIP, binding to native DNA occurred at 60-240 pmol/mg DNA, This binding was inhibited to 55% of control by 1 mu M estrone (P < 0.01, n = 8). suggesting that EST plays a significant role in carcinogen bioactivation in human breast tissue. C1 Med Univ S Carolina, Dept Cell & Mol Pharmacol & Expt Therapeut, Charleston, SC 29425 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Alabama, Dept Pharmacol & Toxicol, Birmingham, AL 35294 USA. RP Walle, T (reprint author), Med Univ S Carolina, Dept Cell & Mol Pharmacol & Expt Therapeut, 171 Ashley Ave, Charleston, SC 29425 USA. EM wallet@musc.edu RI King, Roberta/A-1749-2010 OI King, Roberta/0000-0002-3550-4255 FU NCI NIH HHS [CA3386] NR 40 TC 58 Z9 59 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1998 VL 19 IS 11 BP 2049 EP 2053 DI 10.1093/carcin/19.11.2049 PG 5 WC Oncology SC Oncology GA 140JR UT WOS:000077084600027 PM 9855023 ER PT J AU Sacchi, CT Lemos, APS Brandt, ME Whitney, AM Melles, CEA Solari, CA Frasch, CE Mayer, LW AF Sacchi, CT Lemos, APS Brandt, ME Whitney, AM Melles, CEA Solari, CA Frasch, CE Mayer, LW TI Proposed standardization of Neisseria meningitidis PorA variable-region typing nomenclature SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEIN; AMINO-ACID-SEQUENCES; MONOCLONAL-ANTIBODIES; ANTIGENIC DIVERSITY; VACCINE DESIGN; CLASS-1; STRAINS; NORWAY; GENE; MENINGOCOCCI AB Neisseria meningitidis isolates are conventionally classified by serosubtyping, which characterizes the reactivities of the PorA outer membrane protein variable-region (VR) epitopes with monoclonal antibodies (MAbs). A newer method (PorA VR typing) uses predicted amino acid sequences derived from DNA sequence analysis. The resulting classification schemes are not standardized, offering conflicting and sometimes irreconcilable data from the two methods. In this paper, we propose a standardization of the PorA VR typing nomenclature that incorporates serologic information from traditional PorA serosubtyping with molecular data from predicted VR sequences. We performed a comprehensive literature and database search, generating a collection of strains and DNA sequences that reflects the diversity within PorA that exists to date. We have arranged this information in a comprehensive logical model that includes both serosubtype and PorA VR type assignments. Our data demonstrate that the current panel of serosubtype-defining MAbs underestimates PorA VR variability by at least 50%. Our proposal for VR typing is informative because amino acid sequence and serologic information, when serosubtype-defining MAbs are available, can be deduced simultaneously from the PorA VR designation. This scheme will be useful in future classification and applied epidemiologic studies of N. meningitidis, being a systematic way of selecting PorA vaccine candidates and analyzing vaccine coverage and failure. C1 Adolfo Lutz Inst, Dept Bacteriol, Div Med Biol, Sao Paulo, Brazil. Fdn Oswaldo Cruz, Dept Bacteriol, Rio De Janeiro, Brazil. Univ Fed Rio de Janeiro, Sch Med & Surg, Dept Pathol & Clin Med, Rio De Janeiro, Brazil. Ctr Dis Control & Prevent, Meningitis & Special Pathogens Branch, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Sacchi, CT (reprint author), Ctr Dis Control & Prevent, Meningitis & Special Pathogens Branch, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, Mailstop D-11,1600 Clifton Rd, Atlanta, GA 30333 USA. EM cls9@cdc.gov NR 36 TC 56 Z9 59 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD NOV PY 1998 VL 5 IS 6 BP 845 EP 855 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 136TB UT WOS:000076874300021 PM 9801347 ER PT J AU Mahmood, I Tammara, VK Baweja, RK AF Mahmood, I Tammara, VK Baweja, RK TI Does percent reduction in seizure frequency correlate with plasma concentration of anticonvulsant drugs? Experience with four anticonvulsant drugs SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID INTERICTAL SPIKES; EEG AB Objective: To investigate the relationship between the percentage reduction in seizure frequency in patients with epilepsy and plasma concentrations after oral administration of 4 anticonvulsant drugs, Methods: Patients with a minimum of 25% reduction in their seizure frequency from their baseline value were declared responders. The percentage reduction in seizure frequency was plotted against plasma concentrations with use of pharmacodynamic models (Linear, log-linear, E-max, and sigmoidal E-max models). Zn addition to pharmacodynamic models, a logistic regression model was also fitted to the concentration-response data, with a value of 1 for responders and 0 for nonresponders, Results: The concentration-effect relationship could not be adequately described either by the pharmacodynamic models or by the logistic regression analysis. Conclusions: Based on the results obtained from both pharmacodynamic models and logistic regression analysis the percentage reduction in seizure frequency may not be a true surrogate marker for anticonvulsant drugs to establish a pharmacodynamic relationship with plasma concentrations. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1 HFD860, Woodmont Off Ctr 2, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1 HFD860, Woodmont Off Ctr 2, 1451 Rockville Pike, Rockville, MD 20852 USA. FU DRS NIH HHS [RSR-96-025] NR 14 TC 13 Z9 13 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD NOV PY 1998 VL 64 IS 5 BP 547 EP 552 DI 10.1016/S0009-9236(98)90138-2 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 141WT UT WOS:000077167800010 PM 9834047 ER PT J AU Kapetanovic, IM Torchin, CD Thompson, CD Miller, TA McNeilly, PJ MacDonald, TL Kupferberg, HJ Perhach, JL Sofia, RD Strong, JM AF Kapetanovic, IM Torchin, CD Thompson, CD Miller, TA McNeilly, PJ MacDonald, TL Kupferberg, HJ Perhach, JL Sofia, RD Strong, JM TI Potentially reactive cyclic carbamate metabolite of the antiepileptic drug felbamate produced by human liver tissue in vitro SO DRUG METABOLISM AND DISPOSITION LA English DT Article; Proceedings Paper CT 8th North American International Society-for-the-Study-of-Xenobiotics Meeting CY OCT 26-30, 1997 CL HILTON HEAD ISL, SOUTH CAROLINA SP N Amer Int Soc Study Xenobiot ID IN-VITRO; RAT; IDENTIFICATION; OXIDATION AB Felbamate (FBM) is a novel antiepileptic drug that was approved in 1993 for treatment of several forms of epilepsy. After its introduction, toxic reactions (aplastic anemia and hepatotoxicity) associated with its use were reported. It is unknown whether FBM or one of its metabolites is responsible for these idiosyncratic adverse reactions. Although the metabolism of FBM has not been fully characterized, three primary metabolites of FBM have been identified, i.e. 2-hydroxy, p-hydroxy, and monocarbamate metabolites. In addition, the monocarbamate metabolite leads to a carboxylic acid, which is the major metabolite of FBM in humans. Formation of the hydroxylated products of FBM involves cytochrome P450 enzymes, but the enzymes involved in the formation and further metabolism of the monocarbamate have not yet been elucidated. Recently, mercapturate metabolites of FBM have been identified in human urine, and a metabolic scheme involving reactive aldehyde metabolite formation from the monocarbamate metabolite has been proposed. The present study confirmed the formation of the proposed metabolites using human liver tissue in vitro. The aldehyde intermediates were trapped as oxime derivatives, and the cyclic equilibrium product (proposed as a storage and transport form for the aldehydes) was monitored directly bit HPLC or CC/MS. Formation of putative toxic aldehyde intermediates and the major carboxylic acid metabolite of FBM was differentially effected with the cofactors NADP(+) and NAD(+). It is possible that the cofactors may influence the relative metabolism via activation and inactivation pathways. C1 US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, Laurel, MD 20708 USA. Univ Virginia, Dept Chem, Charlottesville, VA 22903 USA. NINDS, Epilepsy Branch, Bethesda, MD 20892 USA. RP Strong, JM (reprint author), US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, MOD-1 CDER Room 2017,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 17 TC 39 Z9 39 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD NOV PY 1998 VL 26 IS 11 BP 1089 EP 1095 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 136PV UT WOS:000076869100007 PM 9806951 ER PT J AU Luu, HMD AF Luu, HMD TI Lifetime risk from polyurethane covered breast implants - Response SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Luu, HMD (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1998 VL 106 IS 11 BP A527 EP A527 DI 10.2307/3434243 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 144TM UT WOS:000077331200003 ER PT J AU Mendola, P Moysich, KB Freudenheim, JL Shields, PG Schisterman, EF Graham, S Vena, JE Marshall, JR Ambrosone, CB AF Mendola, P Moysich, KB Freudenheim, JL Shields, PG Schisterman, EF Graham, S Vena, JE Marshall, JR Ambrosone, CB TI Risk of recurrent spontaneous abortion, cigarette smoking, and genetic polymorphisms in NAT2 and GSTM1 SO EPIDEMIOLOGY LA English DT Article DE N-acetyltransferase 2; glutathione S-transferase M1; spontaneous abortion; genetic polymorphism; gene-environment interaction; molecular epidemiology ID POSTMENOPAUSAL BREAST-CANCER; N-ACETYLTRANSFERASE; EPIDEMIOLOGY AB Maternal smoking increases the risk of spontaneous abortion. Polymorphic N-acetyltransferase (NAT2) and glutathione S-transferase (GSTM1) affect metabolism of some mutagens found in tobacco smoke. Genotypes and smoking were studied in women with at least two spontaneous abortions (N = 32) and those with at least two livebirths (N = 179). Smoking slightly increased risk (odds ratio = 1.3; 95% confidence interval = 0.6-2.9), but NAT2 and GSTM1 did not. NAT2 or GSTM1 polymorphisms did not appreciably modify smoking-related risk. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY USA. NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Ambrosone, CB (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, HFT-100,3900 NCTR Rd, Jefferson, AR 72079 USA. RI Shields, Peter/I-1644-2012; OI Mendola, Pauline/0000-0001-5330-2844; Schisterman, Enrique/0000-0003-3757-641X FU NCI NIH HHS [CA-01633, CA-11535, CA-62995] NR 17 TC 10 Z9 10 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 1998 VL 9 IS 6 BP 666 EP 668 DI 10.1097/00001648-199811000-00018 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 130BR UT WOS:000076499800018 PM 9799179 ER PT J AU Carlson, M Thompson, RD AF Carlson, M Thompson, RD TI Determination of borates in caviare by ion-exclusion chromatography SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE borates; caviare; adulteration; ion-exclusion ID SPECTROMETRY; BORON; FOODS; ACID AB A specific and rapid analytical procedure for the determination of borates in caviare was developed using ion-exclusion chromatography. Products require minimal pre-treatment, are simply extracted with eluent and filtered prior to chromatography. Isolation of the analyte as a 2:1 sorbitol-borate complex was accomplished using an anion exchange column with an eluent consisting of 2mm sorbitol, and conductivity detection was used. Among five sugar alcohols examined for complexation, sorbitol was found to provide optimum resolution and a 3-4 times enhancement of response over borate anion alone. The response of the complex was linear over at least a 100 fold range in concentration (0.1-10 mu g boron/ml) with a correlation coefficient of 0.9997. Using a boric acid standard solution, the limits of detection and quantitation were 0.065 mu g/ml and 0.216 mu g/ml, respectively, calculated as boron. Replicate analyses (n = 5) for samples having commercially added borate (equivalent to 300-1000 mu g/g boron) gave RSD values of 1.18-2.03%. Recoveries of borate from fortified samples having commercially added borate present varied from 94.5 to 101.1% while untreated samples exhibited recoveries of 78.5-108.0% over a concentration range of 23-1039 mu g/g, calculated as boron. C1 US FDA, Minneapolis, MN 55401 USA. RP Carlson, M (reprint author), US FDA, 240 Hennepin Ave, Minneapolis, MN 55401 USA. NR 24 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD NOV-DEC PY 1998 VL 15 IS 8 BP 898 EP 905 PG 8 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 149FX UT WOS:000077595400005 PM 10366999 ER PT J AU Ikeda, GJ Sapienza, PP Ross, IA AF Ikeda, GJ Sapienza, PP Ross, IA TI Distribution and excretion of radiolabelled tert-butylhydroquinone in Fischer 344 rats SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE tert-butylhydroquinone; C-14-TBHQ; distribution; excretion; Fischer 344; rats ID BUTYLATED HYDROXYANISOLE; MICROSOMAL FRACTIONS; 3-TERT-BUTYL-4-HYDROXYANISOLE; METABOLITES; HEPATOCYTES; DISPOSITION; URINE AB Uniformly C-14-ring-labelled tert-butylhydroquinone (TBHQ) was diluted with non-radioactive TBHQ and administered orally (for excretion studies) to Fischer 344 rats. An average of 72.9% and 10.6% of the administered radioactivity was recovered in the urine and faeces, respectively, of male rats, and 77.3% and 8.2% in the urine and faeces, respectively, of female rats in 4 days. No significant sex-related differences were found-in either excretion, tissue distribution or urinary metabolites of TBHQ-derived radiolabel. For distribution studies, intraperitoneal doses were administered to female rats, and tissue levels of radiolabel were determined at various times after dosing. The parent; compound quickly disappeared from tissue in vivo. The highest concentrations of radiolabel were found,in the liver and kidneys. The urinary metabolites consisted of conjugated TBHQ and unidentified polar substance(s). (C) 1998 Elsevier Science Ltd. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Toxicol, Laurel, MD 20708 USA. RP Ikeda, GJ (reprint author), US FDA, Dept Hlth & Human Serv, 200 C St SW, Washington, DC 20204 USA. NR 11 TC 4 Z9 6 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD NOV PY 1998 VL 36 IS 11 BP 907 EP 914 DI 10.1016/S0278-6915(98)00075-1 PG 8 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 124VU UT WOS:000076204100002 PM 9771551 ER PT J AU Vionnet, JA McGowen, MM Scates, BA Vann, WF AF Vionnet, JA McGowen, MM Scates, BA Vann, WF TI Expression of the Escherichia coli K92 polysialyltransferase 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 PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 1998 VL 8 IS 11 MA 79 BP 1124 EP 1125 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 130CC UT WOS:000076505300086 ER PT J AU Johnson, K AF Johnson, K TI Fundamentals of performance measurement SO HEALTH AFFAIRS LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Johnson, K (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 1998 VL 17 IS 6 BP 253 EP 254 DI 10.1377/hlthaff.17.6.253-a PG 2 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 138RK UT WOS:000076986200031 PM 9916374 ER PT J AU Rubinstein, LJ Garcia-Ojeda, PA Michon, F Jennings, HJ Stein, KE AF Rubinstein, LJ Garcia-Ojeda, PA Michon, F Jennings, HJ Stein, KE TI Murine immune responses to Neisseria meningitidis group C capsular polysaccharide and a thymus-dependent toxoid conjugate vaccine SO INFECTION AND IMMUNITY LA English DT Article ID INFLUENZAE TYPE-B; MEMBRANE PROTEIN COMPLEX; GROUP-A; ANTIBODY-RESPONSE; SEROGROUP-C; IMMUNOLOGICAL MEMORY; CLINICAL-EVALUATION; YOUNG-CHILDREN; IMMUNOGENICITY; IMMUNIZATION AB The polysaccharide (PS) capsules of many pathogenic bacteria are poor immunogens in infants and young children as a result of the delayed response to PS antigens during ontogeny. The development of polysaccharide-protein conjugate vaccines for Haemophilus influenzae type b, which have proven to be efficacious in this age group, has led to active development by a number of investigators of conjugate vaccines for other diseases. We describe here the response of several mouse strains to the capsular PS of Neisseria meningitidis group C (MCPS) conjugated to tetanus toroid (MCPS-TT) and the same response in BALB/c mice as a model of the immune consequences of conjugate vaccine immunization. The use of a conjugate vaccine results in a shift in the isotype elicited in response to the MCPS, from immunoglobulin M (IgM) and IgG3 to primarily IgG1. A response to MCPS-TT is seen even among mouse strains which respond poorly to MCPS itself, emphasizing the importance of a strain survey when choosing a mouse model for a vaccine. The marked increase in IgG1 antibody titer was accompanied by a large increase in bactericidal activity of sera from these animals. Animals primed with the conjugate vaccine demonstrated a booster response after secondary immunization with either the MCPS or the conjugate. The ability to produce a boosted IgG1 anti-MCPS response to the MCPS can be transferred to adoptive recipients by B cells alone from mice primed with MCPS-TT but not mice primed with MCPS alone. These data indicate that in BALB/c mice a single immunization with MCPS-TT is sufficient to induce a shift to IgG1 and generate a memory B-cell population that does not require T cells for boosting. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. Natl Res Council Canada, Div Biol Sci, Ottawa, ON K1A 0R6, Canada. RP Stein, KE (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. NR 69 TC 21 Z9 22 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1998 VL 66 IS 11 BP 5450 EP 5456 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 132HT UT WOS:000076624800054 PM 9784556 ER PT J AU Hurlbut, JA Carr, JR Singleton, ER Faul, KC Madson, MR Storey, JM Thomas, TL AF Hurlbut, JA Carr, JR Singleton, ER Faul, KC Madson, MR Storey, JM Thomas, TL TI Solid-phase extraction cleanup and liquid chromatography with ultraviolet detection of ephedrine alkaloids in herbal products SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID CAPILLARY ELECTROPHORESIS; URINE; PSEUDOEPHEDRINE; IDENTIFICATION; SUPPLEMENTS; AMINES AB A solid-phase extraction (SPE) cleanup and a liquid chromatographic (LC) method with UV detection is presented for analysis of up to 7 ephedrine alkaloids in herbal products. Alkaloids from herbal products are extracted with acidified buffer, isolated on a propylsulfonic acid SPE column, eluted with a high-ionic-strength buffer, and separated by LC with detection at 255 nm. LC separation is performed by isocratic elution on a YMC phenyl column with 0.1M sodium acetate-acetic acid (pH = 4.8) containing triethyl-amine and 2% acetonitrile. Ephedrine alkaloids are completely separated in 15 min. Average recovery of 5 common alkaloids from 3 spiked matrixes is 90%, with an average relative standard deviation (RSD) of 4.4% for alkaloid spikes between 0.5 and 16 mg/g, Average quantitation of ephedrine and pseudoephedrine from 6 herbal products is 97% of declared label claims, and average quantitation of synephrine from an herbal dietary product is 85% of label claim (RSD, 3.2%), Recoveries of synephrine, norephedrine, ephedrine, pseudoephedrine, N-methylephedrine, and N-methylpseudoephedrine spiked in 4 herbal products averaged 95%, Results of ruggedness testing and of a second laboratory validation of the procedure are also presented. C1 Metropolitan State Coll, Dept Chem, Denver, CO 80217 USA. US FDA, Denver Fed Ctr, Chem Sect, Denver, CO 80225 USA. RP Hurlbut, JA (reprint author), Metropolitan State Coll, Dept Chem, POB 173362, Denver, CO 80217 USA. NR 26 TC 28 Z9 31 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 1998 VL 81 IS 6 BP 1121 EP 1127 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 145JX UT WOS:000077368700004 PM 9850573 ER PT J AU Biles, PV Ziobro, GC AF Biles, PV Ziobro, GC TI Identification of the source of reagent variability in the xanthydrol/urea method SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Contamination of food and food packaging material by rodent urine is evidence of insanitary conditions. Urea from rodent urine is used as a chemical indicator of contamination. The limit of detection of the xanthydrol/urea AOAC Method 959.14 by formation of dixanthylurea crystals is 4 mu g urea isolated from urine on packaging material. Six different lots of xanthydrol from 5 different manufacturers were compared. Differences in urea detection sensitivity of the xanthydrol of up to 1000-fold were observed. Melting points showed further evidence of variability and impurities in xanthydrol lots. A liquid chromatographic method was developed to separate and identify the impurities. Confirmation of analytes was performed by gas chromatography/mass spectrometry. C1 US FDA, Div Nat Prod, Microanalyt Branch, Washington, DC 20204 USA. RP Biles, PV (reprint author), US FDA, Div Nat Prod, Microanalyt Branch, 200 C St,SW, Washington, DC 20204 USA. NR 12 TC 1 Z9 1 U1 0 U2 5 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 1998 VL 81 IS 6 BP 1155 EP 1161 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 145JX UT WOS:000077368700009 PM 9850577 ER PT J AU Whitaker, TB Trucksess, MW Johansson, AS Giesbrecht, FG Hagler, WM Bowman, DT AF Whitaker, TB Trucksess, MW Johansson, AS Giesbrecht, FG Hagler, WM Bowman, DT TI Variability associated with testing shelled corn for fumonisin SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID AFLATOXIN AB Variances associated with sampling, sample preparation, and analytical steps of a test procedure that measures fumonisin in shelled corn were estimated, The variance associated with each stop of the test procedure increases with fumonisin concentration. Functional relationships between variance and fumonisin concentration were estimated by regression analysis. For each variance component, functional relationships were independent of fumonisin type (total, B1, B2, and B3 fumonisins). At 2 ppm, coefficients of variation associated with sampling (1.1 kg sample), sample preparation (Romer mill and 25 g subsample), and analysis are 16.6, 9.1, and 9.7%, respectively, The coefficient of variation associated with the total fumonisin test procedure was 45% and is about the same order of magnitude as that for measuring aflatoxin in shelled corn with a similar test procedure. C1 N Carolina State Univ, USDA ARS, Raleigh, NC 27695 USA. US FDA, Washington, DC 20204 USA. N Carolina State Univ, Dept Biol & Agr Engn, Raleigh, NC 27695 USA. N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. N Carolina State Univ, Dept Poultry Sci, Mycotoxin Lab, Raleigh, NC 27695 USA. N Carolina State Univ, Dept Crop Sci, Raleigh, NC 27695 USA. RP Whitaker, TB (reprint author), N Carolina State Univ, USDA ARS, Box 7625, Raleigh, NC 27695 USA. OI Bowman, Daryl T./0000-0001-6623-4035 NR 9 TC 37 Z9 38 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 1998 VL 81 IS 6 BP 1162 EP 1168 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 145JX UT WOS:000077368700010 PM 9850578 ER PT J AU Carlson, M Thompson, RD AF Carlson, M Thompson, RD TI Determination of phosphine residues in whole grains and soybeans by ion chromatography via conversion to phosphate SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB An ion chromatographic (IC) method was developed for determining phosphine (PH3) in whole grains (barley, corn, oats, rice, rye, and wheat) and soybeans. The method converts phosphine to phosphate (i.e., orthophosphate) and isolates the phosphate by IC with eluent-suppressed conductivity detection. Recoveries of unbound phosphine by the method were similar to those obtained by an established colorimetric method for 7 different products fortified at 3 levels. Mean recoveries were low (i.e., 30-60%) and varied with product type and level of fortification. Recoveries of PH3 from previously fumigated products fortified with aluminum phosphide ranged from 19.0% for barley fortified at 0.734 ppm to 88.3% for corn fortified at 1.691 ppm. Precision data from 3 products based on replicate analyses (n = 4 or 5) gave relative standard deviations of 1.78-4.66% for mean laboratory-fumigated PH3 levels of 0.679-1.309 ppm. Estimated limits of detection (LOD) and quantitation (LOQ) for PH3 were 0.010 mu g/g (10 ppb) and 0.0275 mu g/g (27.5 ppb) at signal-to-noise ratios (S/N) of 4:1 and 10:1, respectively. These values were also determined for a nonchemically suppressed IC system with LOD of 0.02 mu g/g (20 ppb) and LOQ of 0.055 mu g/g (55 ppb) at SIN of 4:1 and 10:1, respectively Phosphate response was linear over the concentration range equivalent to 0.30-10.0 mu g P/mL, with a mean correlation coefficient of 0.9988 based on replicate standard curves. The relationship of product composition to recovery from various products was also examined. C1 US FDA, Minneapolis, MN 55401 USA. RP Carlson, M (reprint author), US FDA, 240 Hennepin Ave, Minneapolis, MN 55401 USA. NR 30 TC 6 Z9 6 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 NOV-DEC PY 1998 VL 81 IS 6 BP 1190 EP 1201 PG 12 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 145JX UT WOS:000077368700014 PM 9850582 ER PT J AU Levine, RA Luchtefeld, RG Hopper, RL Salmon, GD AF Levine, RA Luchtefeld, RG Hopper, RL Salmon, GD TI Automated method for cleanup and determination of benomyl and thiabendazole in table-ready foods SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LIQUID-CHROMATOGRAPHIC DETERMINATION; FORMETANATE HYDROCHLORIDE; BENZIMIDAZOLE FUNGICIDES; FLUORESCENCE DETECTION; RESIDUES; EXTRACTION; PRODUCTS; FRUITS; MILK AB An automated solid-phase extraction (SPE) cleanup with on-line liquid chromatographic (LC) analysis was developed to determine residues of benomyl (as carbendazim) and thiabendazole in table-ready food items from the U.S. Food and Drug Administration Total Diet Study (TDS). A strong-cation-exchange cleanup of an acetone extract replaces the methylene chloride solvent partitioning steps in the procedure described in the Pesticide Analytical Manual (PAM). LC analysis is accomplished with a Cs analytical column and tandem fluorescence and UV detection. Recoveries of both analytes from 32 representative IDS foods fortified at 0.05 and 0.5 mu g/g were determined. Method precision was evaluated with triplicate recovery assays on 11 foods fortified at both levels. Accuracy was tested further by assaying 47 foods for incurred residues in parallel with the validated PAM procedure for comparison, and good agreement was found. The automated SPE method reduces solvent consumption, analysis time, and labor. C1 US FDA, Total Diet & Pesticide Res Ctr, Lenexa, KS 66285 USA. RP Levine, RA (reprint author), US FDA, Total Diet & Pesticide Res Ctr, POB 15905, Lenexa, KS 66285 USA. NR 18 TC 5 Z9 9 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 1998 VL 81 IS 6 BP 1217 EP 1223 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 145JX UT WOS:000077368700017 PM 9850584 ER PT J AU Siitonen, PH Thompson, HC AF Siitonen, PH Thompson, HC TI Determination of calcium by inductively coupled plasma-atomic emission spectrometry, and lead by graphite furnace atomic absorption spectrometry, in calcium supplements after microwave dissolution or dry-ash digestion: Method trial SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID EXPOSURE AB A 3-laboratory method trial was conducted to evaluate 2 sample digestion procedures and instrumental determination parameters for analysis of calcium and lead in Ca supplements. Calcium supplements were treated by dry-ash digestion or microwave dissolution prior to spectrometric analysis. In each case, ph was determined by graphite furnace atomic absorption spectrometry and Ca by inductively coupled plasma-atomic emission spectrometry. Blind duplicates of 6 Ca supplement samples were analyzed after each sample treatment procedure. Matrix pairs contained dissimilar Pb levels to cover the analyte range encountered during method development. Calcium content of the Ca supplement samples also reflected the range seen during method development. Stock solutions of Ca and Pb were supplied to collaborators for preparation of quantitation standards to remove a variable external to the method. National Institute of Standards and Technology Standard Reference Material (NIST SRM) 1486, bone meal, was included to assess method accuracy and recovery at NIST certificate Ca and ph levels for this material (26.58 +/- 0.24% Ca and 1.335 +/- 0.014 mu g Pb/g), Analyses of the NIST SRM yielded 25.9 +/- 1.1 and 27.2 +/- 2.3% Ca and 1.53 +/- 0.19 and 1.26 +/- 0.19 mu g Pb/g for dry-ash and microwave procedures, respectively. Statistical analyses of data indicated acceptable repeatability and reproducibility for determination of Pb and Ca in various Ca supplements. With either sample preparation technique, the method is appropriate for determining Pb or Ca in Ca supplements. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Siitonen, PH (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 15 TC 3 Z9 3 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 NOV-DEC PY 1998 VL 81 IS 6 BP 1233 EP 1239 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 145JX UT WOS:000077368700019 PM 9850585 ER PT J AU Horwitz, W Britton, P Chirtel, SJ AF Horwitz, W Britton, P Chirtel, SJ TI A simple method for evaluating data from an interlaboratory study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PROTOCOL; LABORATORIES; CONDUCT; DESIGN AB Large-scale laboratory- and method-performance studies involving more than about 30 laboratories may be evaluated by calculating the HORRAT ratio for each test sample (HORRAT = [experimentally found among-laboratories relative standard deviation] divided by [relative standard deviation calculated from the Horwitz formula]). The chemical analytical method is deemed acceptable per se if HORRAT approximate to 1.0 (+/- 0.5). If HORRAT is greater than or similar to 2.0, the most extreme values are removed successively until an "acceptable" ratio is obtained. The laboratories responsible for the extreme values that are removed should examine their technique and procedures. If greater than or similar to 15% of the values have to be removed, the instructions and the methods should be examined. This suggested computation procedure is simple and does not require statistical outlier tables. Proposed action limits may be adjusted according to experience. Data supporting U.S. Environmental Protection Agency method 245.1 for mercury in waters (manual cold-vapor atomic absorption spectrometry), supplemented by subsequent laboratory-performance data, were reexamined in this manner. Method-performance parameters (means and among-laboratories relative standard deviations) were comparable with results from the original statistical analysis that used a robust biweight procedure for outlier removal. The precision of the current controlled performance is better by a factor of 4 than that of estimates resulting from the original method-performance study, at the expense of rejecting more experimental values as outliers. C1 US FDA, Washington, DC 20204 USA. US EPA, Natl Exposure Res Lab, Cincinnati, OH 45268 USA. RP Horwitz, W (reprint author), US FDA, HFS-500, Washington, DC 20204 USA. NR 14 TC 24 Z9 26 U1 1 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 1998 VL 81 IS 6 BP 1257 EP 1265 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 145JX UT WOS:000077368700023 PM 9850588 ER PT J AU Kraeling, MEK Reddy, G Bronaugh, RL AF Kraeling, MEK Reddy, G Bronaugh, RL TI Percutaneous absorption of trinitrobenzene: Animal models for human skin SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE percutaneous absorption; trinitrobenzene; animal skin models; human skin ID HAIRLESS GUINEA-PIG; METABOLISM; PENETRATION; BENZOCAINE AB The percutaneous absorption of 1,3,5-trinitrobenzene (TNB) was studied in viable skin from hairless guinea pigs (HGP), Fischer 344 rats and humans. Skin was dermatomed and assembled in flow-through diffusion cells followed by TNB application in either an acetone or a water vehicle, Skin absorption was expressed as the percentage of applied dose absorbed into skin and receptor fluid within 24 h, Rapid absorption of TNB by rodent skin was obtained with both vehicles. For HGP skin, TNB absorption was 72.7 +/- 5.5% in the acetone vehicle and 82.3 +/- 4.5% in the water vehicle. For rat skin, TNB absorption was 61.0 +/- 4.1% (acetone) and 66.5 +/- 4.1% (water), Absorption of TNB from acetone was significantly reduced (38.0 +/- 11.0%, P = 0.0118) in human skin, but absorption from water remained high (75.5 +/- 10.8%), Little TNB remained in skin when a thin (200 mu m) dermatome section was used (HGP and human skin). A thicker dermatome section was required (350 mu m) with haired rat skin, and 13-21% of the absorbed radioactivity remained in the skin at 24h, Rodent skin did not simulate satisfactorily the barrier properties of human skin when TNB absorption was reduced by application in a volatile solvent. (C) 1998 John Wiley & Sons, Ltd. C1 US FDA, Cosmet Toxicol Branch, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, Laurel, MD 20708 USA. USA, Ctr Hlth Promot & Prevent Med, Aberdeen Proving Ground, MD 21010 USA. RP Kraeling, MEK (reprint author), US FDA, Cosmet Toxicol Branch, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, HFS-128,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 22 TC 5 Z9 5 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD NOV-DEC PY 1998 VL 18 IS 6 BP 387 EP 392 DI 10.1002/(SICI)1099-1263(199811/12)18:6<387::AID-JAT526>3.0.CO;2-W PG 6 WC Toxicology SC Toxicology GA 140GD UT WOS:000077078500001 PM 9840746 ER PT J AU Echavarria, M Forman, M Ticehurst, J Dumler, JS Charache, P AF Echavarria, M Forman, M Ticehurst, J Dumler, JS Charache, P TI PCR method for detection of adenovirus in urine of healthy and human immunodeficiency virus-infected individuals SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; PATIENT AB Adenoviruses (AdV) cause diseases that range from localized, self-limited illnesses to fatal infections in immunocompromised patients. Culture is assumed to be sensitive but requires viable virus and up to 3 weeks for detection, and it can be inhibited by bacterial contamination, A new PCR method amplifying a region of the hexon gene was developed in order to detect AdV in urine more rapidly and with greater sensitivity than obtainable by culture technology. All 18 serotypes tested were detected, Quantitatively, with optimized urine processing, AdV PCR detected 0.2 PFU/ml (serotype 11) and 10 DNA copies/ml (serotype 2), Serially collected urine samples from human immunodeficiency virus (HN)-infected patients with concurrent cytomegalovirus retinitis were divided into three groups: AdV culture-positive samples, AdV culture-negative or bacterially contaminated samples from patients with a history of AdV culture-positive urines, and AdV culture-negative samples from patients without a history of AdV culture positivity. Urine samples from healthy adults were also tested by culture and PCR to screen for asymptomatic shedding. Amplification was assessed with and without prior DNA purification. AdV was detected by PCR in 90% of culture-positive urines (100% of unclotted samples, e.g,, those culture positive after storage for PCR testing), 71% of culture-negative or bacterially contaminated urines from AdV-infected patients, and 28% from AdV culture-negative patients. Healthy volunteers were culture negative for AdV, and 96% were PCR negative, The new AdV PCR method is rapid and sensitive and can detect viral DNA in samples for which culturing is problematic. The role of AdV replication during HIV infection merits further investigation with sensitive tools such as PCR. C1 Johns Hopkins Med Inst, Dept Pathol, Div Med Microbiol, Baltimore, MD USA. US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Clin Lab Devices,Microbiol Branch, Rockville, MD USA. RP Charache, P (reprint author), Johns Hopkins Hosp, Dept Pathol, Div Med Microbiol, 600 N Wolfe St, Baltimore, MD 21287 USA. EM pcharach@pathlan.path.jhu.edu RI Ticehurst, John/I-7532-2012 FU NEI NIH HHS [EY 10268] NR 15 TC 111 Z9 115 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 1998 VL 36 IS 11 BP 3323 EP 3326 PG 4 WC Microbiology SC Microbiology GA 129YG UT WOS:000076491200038 PM 9774586 ER PT J AU Tortorello, ML Reineke, KF Stewart, DS Raybourne, RB AF Tortorello, ML Reineke, KF Stewart, DS Raybourne, RB TI Comparison of methods for determining the presence of Escherichia coli O157 : H7 in apple juice SO JOURNAL OF FOOD PROTECTION LA English DT Article ID IMMUNOMAGNETIC SEPARATION; 24-H CONFIRMATION; CIDER; BEEF; PHASE AB Six methods were compared for detection of three strains of Escherichia coli O157:H7 in enrichments of inoculated apple juice. Juice was inoculated at levels varying from 0.1 to 100 CFU/ml and centrifuged after overnight storage at 4 degrees C, and pellets were incubated at 37 degrees C in nonselective enrichment broth. At hourly intervals between 5 and 10 h and at 24 h, the enrichments were tested for E. coli O157:H7 by direct fluorescent antibody (DFA), antibody-direct epifluorescent filter technique (Ab-DEFT), direct selective plating on sorbitol MacConkey agar (SMA), immunomagnetic separation coupled to either selective plating (IMS-SMA) or the polymerase chain reaction (IMS-PCR), and flow cytometry (FC). The most consistent detection of 0.1 CFU/ml of the slowest growing strain of the pathogen was provided by the IMS-SMA and IMS-PCR after 8 h of enrichment. The time required for detection at the level of 0.1 CFU/ml for each assay was Ab-DEFT, 11 h; IMS-PCR, 16 h; FC, 24 h; IMS-SMA, 32 h; and SMA, 48 h. Absolute detection limits (without enrichment) were: IMS-PCR, 10(3) CFU/ml; Ab-DEFT and IMS-SMA, 10(4) CFLT/ml; SMA, 10(5) CFU/mL; and DFA, 10(6) CFU/ml. Recovery of the pathogen (10 CFU/ml) in apple juice after 28 days of 4 degrees C storage was possible by means of an 8-h enrichment and Ab-DEFT, IMS-PCR, or IMS-SMA. C1 US FDA, NCFST, Summit Argo, IL 60501 USA. Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Tortorello, ML (reprint author), US FDA, NCFST, 6502 S Archer Rd, Summit Argo, IL 60501 USA. FU FDA HHS [FD-000431] NR 17 TC 23 Z9 23 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 NOV PY 1998 VL 61 IS 11 BP 1425 EP 1430 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 138TG UT WOS:000076988500001 PM 9829180 ER PT J AU Jinneman, KC Wetherington, JH Hill, WE Adams, AM Johnson, JM Tenge, BJ Dang, NL Manger, RL Wekell, MM AF Jinneman, KC Wetherington, JH Hill, WE Adams, AM Johnson, JM Tenge, BJ Dang, NL Manger, RL Wekell, MM TI Template preparation for PCR and RFLP of amplification products for the detection and identification of Cyclospora sp. and Eimeria spp. oocysts directly from raspberries SO JOURNAL OF FOOD PROTECTION LA English DT Article ID POLYMERASE CHAIN-REACTION; OUTBREAK; PATHOGEN; HUMANS; WATER; DNA AB Raspberries were epidemiologically associated with cyclosporiasis outbreaks during 1996 and 1997. The 18S rRNA genes of Cyclospora cayetanensis and several species of a closely related genus, Eimeria, were sequenced and primers for a nested PCR developed in a previous study. The ability to distinguish amplified products of Cyclospora sp. from those of Eimeria spp. is important for testing food and environmental samples. Therefore, an RFLP analysis of amplified products was used to differentiate Cyclospora cayetanensis from Eimeria spp. PCR inhibitors and the low levels of Cyclospora oocysts present in raspberries make template preparation for PCR challenging. Several approaches for PCR template preparation from raspberry samples were evaluated. Template preparation methods using various washing and concentration steps, oocyst disruption protocols, resin matrix treatment, DNA precipitation, and/or the addition of nonfat dried milk solution to a PCR using modified primers were evaluated first with oocysts of Eimeria tenella then refined with oocysts of C. cayetanensis. Approximately 10 E. tenella oocysts per PCR or approximately 19 C. cayetanensis oocysts per PCR were detected with the optimized template preparation method. The addition of 20 mu l of raspberry wash sediment extract and nonfat dried milk solution did not inhibit the amplification of DNA from as few as 10 E. tenella and 25 C. cayetanensis oocysts in a 100-mu l PCR. The nucleotide sequences of C. cayetanensis and the Eimeria spp. are 94 to 96% similar in the amplified region, but the amplification products from the two genera were distinguished using an RFLP analysis with the restriction enzyme MnlI. C1 US FDA, Seafood Prod Res Ctr, Bothell, WA 98041 USA. US FDA, Sci Branch, Seattle Dist, Bothell, WA 98041 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. RP Jinneman, KC (reprint author), US FDA, Seafood Prod Res Ctr, 22201 23rd Dr S E,POB 3012, Bothell, WA 98041 USA. NR 27 TC 33 Z9 38 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 NOV PY 1998 VL 61 IS 11 BP 1497 EP 1503 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 138TG UT WOS:000076988500013 PM 9829192 ER PT J AU Buchanan, RL Whiting, RC AF Buchanan, RL Whiting, RC TI Risk assessment: A means for linking HACCP plans and public health SO JOURNAL OF FOOD PROTECTION LA English DT Article; Proceedings Paper CT Symposium on Science-Based Approaches for Protecting our Global Food Supply at the 84th IAMFES Annual Meeting CY JUL 06-09, 1997 CL ORLANDO, FLORIDA SP IAMFES, ILSI, N Amer Tech Comm Food Microbiol AB HACCP plan adoption has greatly enhanced the food industry's ability to systematically design programs to ensure the microbiological safety of foods. Yet, this widening acceptance of the HACCP system has revealed several areas where its application is limited due to reliance on qualitative consideration of hazards and their control. In particular, HACCP planning is limited both conceptually and practically by its inability to quantify the potential combined influence of multiple control-point deviations and to relate the successful operation of a HACCP system to a measurable public-health impact. Recent advances in quantitative microbiological risk assessment appear to offer a means of overcoming these limitations. The integration of HACCP plans with the development of dynamic risk-assessment models offers a means for considering the entire farm-to-table continuum and for relating food-manufacturing operations to public health goals. Such capabilities may be critical to establishing equivalence among HACCP systems. C1 USDA ARS, Eastern Reg Res Ctr, Wyndmoor, PA 19038 USA. RP Whiting, RC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 8 TC 43 Z9 45 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 NOV PY 1998 VL 61 IS 11 BP 1531 EP 1534 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 138TG UT WOS:000076988500022 PM 9829200 ER PT J AU Mesmer, MZ Satzger, RD AF Mesmer, MZ Satzger, RD TI Determination of gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL) by HPLC/UV-VIS spectrophotometry and HPLC/thermospray mass spectrometry. (vol 43, pg 489, 1998) SO JOURNAL OF FORENSIC SCIENCES LA English DT Correction C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45202 USA. RP Mesmer, MZ (reprint author), US FDA, Forens Chem Ctr, 1141 Cent Pkwy, Cincinnati, OH 45202 USA. NR 1 TC 0 Z9 0 U1 1 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 NOV PY 1998 VL 43 IS 6 BP 1259 EP 1260 PG 2 WC Medicine, Legal SC Legal Medicine GA 143VC UT WOS:000077276900033 ER PT J AU Park, E Condrate, RA Hoelzer, DT Fischman, GS AF Park, E Condrate, RA Hoelzer, DT Fischman, GS TI Interfacial characterization of plasma-spray coated calcium phosphate on Ti-6Al-4V SO JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE LA English DT Article ID TITANIUM; COATINGS AB Microstructural characterization was performed on plasma-spray coated calcium phosphate and its interface with Ti-6Al-4V using scanning and transmission electron microscopy. The amorphous calcium phosphate phase was found near the coating/substrate interface, usually in between the crystalline hydroxyapatite grains and the Ti-6Al-4V substrate. The presence of the amorphous calcium phosphate and the channels extending from the interface to the coating surface was attributed to the low interfacial bond strength in a physiological environment. There was an indication of titanium diffusing into the amorphous regions. However, no reaction phases were found between the coating and the Ti-6Al-4V substrate. In the coating area remote from the interface, no intergranular amorphous calcium phosphate phase was observed. The microstructure of the Ti-6Al-4V substrate near the interface was observed to be affected by heat generated during plasma spraying. (C) 1998 Kluwer Academic Publishers. C1 Alfred Univ, New York State Coll Ceram, Alfred, NY 14802 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Park, E (reprint author), Alfred Univ, New York State Coll Ceram, Alfred, NY 14802 USA. RI Hoelzer, David/L-1558-2016 NR 12 TC 37 Z9 39 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-4530 J9 J MATER SCI-MATER M JI J. Mater. Sci.-Mater. Med. PD NOV PY 1998 VL 9 IS 11 BP 643 EP 649 DI 10.1023/A:1008931508465 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 170YR UT WOS:000078835300005 PM 15348682 ER PT J AU Niu, CH Chiu, YY AF Niu, CH Chiu, YY TI FDA perspective on peptide formulation and stability issues SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article; Proceedings Paper CT 2nd Annual Conference on Formulations and Drug Delivery CY OCT 05-08, 1997 CL LA JOLLA, CALIFORNIA SP Div Biotechnol, Amer Chem Soc, Controlled Release Soc Inc AB Traditionally, peptide drugs are prepared as sterile solutions and administered to patients by daily injection. However, this form of drug delivery causes pain and inconvenience to patients and thus has been poorly accepted. In addition to improving patient compliance, many novel delivery systems have been developed to address the need for prolonged, localized (targeted), or pulsatile drug action. Examples include, but are not limited to oral, nasal, or long-acting controlled release injectable dosage forms; a number of them have been approved by FDA recently. The unique characteristics and the relevant regulatory issues with respect to each type of delivery system are presented. C1 US FDA, Ctr Drug Evaluat & Res, Off New Drug Chem, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Niu, CH (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drug Chem, Off Pharmaceut Sci, Parklawn Bldg,Room 14B-45 5600 Fishers Lane, Rockville, MD 20857 USA. NR 24 TC 19 Z9 21 U1 0 U2 3 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD NOV PY 1998 VL 87 IS 11 BP 1331 EP 1334 DI 10.1021/js9800782 PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 136VB UT WOS:000076878900012 PM 9811485 ER PT J AU Lytle, CD Clavet, CR Chaput, MP Varney, GW To, TM Carey, RF Baker, KH AF Lytle, CD Clavet, CR Chaput, MP Varney, GW To, TM Carey, RF Baker, KH TI Evaluation of three methodologies for testing disposable ENT endoscope sheaths as viral barriers SO JOURNAL OF TESTING AND EVALUATION LA English DT Article DE endoscope sheath; air deflation test; viral barrier tests; air bubble test; quality assurance ID IMMUNODEFICIENCY-VIRUS TYPE-1; SURROGATE VIRUSES; CONDOMS AB Three methods to determine the barrier function of ENT endoscope sheaths were evaluated: (1) the air deflation test, a candidate quality assurance test, compared differences in pressure between a test sheath and an intact one; (2) a virus barrier test challenged with bacteriophage phi X174 outside the sheath, with barrier penetration determined by rinsing inside and assaying for penetrated virus; (3) another virus barrier test challenged from inside, with virus penetration determined by assaying a collection/submersion solution. Sheaths with laser-drilled holes or tears generated by acupuncture needles were tested. Five-mu m holes and larger were detected by air deflation or inside virus challenge. Outside virus challenge could reliably detect only 30-mu m holes. Tears of 35-mu m length were detected by inside virus challenge, while all three tests detected 85-mu m tears. In addition, air bubbles during submersion detected and located 5-mu m holes and larger, suggesting another quality assurance test. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. RP Lytle, CD (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. NR 18 TC 5 Z9 5 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 NOV PY 1998 VL 26 IS 6 BP 587 EP 593 PG 7 WC Materials Science, Characterization & Testing SC Materials Science GA 143VK UT WOS:000077277600009 ER PT J AU Hefflin, BJ AF Hefflin, BJ TI Final-year-of-life pacemaker recipients SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID PERMANENT PACEMAKER; INSTITUTIONALIZATION; IMPLANTATION AB BACKGROUND: Older persons who have initial cardiac pacemakers implanted during their final year of life have not been characterized as a group, which makes it difficult to evaluate the suitability of some of their health services utilizations. OBJECTIVE: To help determine how prudently pacemakers are used in this group, we assessed its pacemaker candidates from the perspective of health and ability to perform physical activities of daily living. DESIGN: A retrospective, population-based, cross-sectional study. SETTING: The 1993 National Mortality Followback Survey. PARTICIPANTS: An estimated 1,647,955 persons aged 65 years or older who died in the US in 1993. MEASUREMENTS: Demographic and cause-of-death frequencies obtained by analyzing age, sex, race, and underlying cause-of-death variables in the survey. For persons who had initial pacemakers implanted during their last year of life, we determined the percent of persons, within 10-year age groups, who had no difficulty at any time during their final year of life performing 11 specific physical activities of daily living (e.g., climbing stairs, preparing meals, bathing). These data were obtained from negative responses to questions that asked if the decedents, at any time during their last year of life, had difficulty performing the specific activities. RESULTS: Of the estimated 78,941 persons aged 65 years or older with a pacemaker who died in the US in 1993, 14,158 (18%) had their first pacemaker implanted during their last year of life. Estimated median survival of the final-year-of-life recipients of pacemakers after pacemaker implantation was 5 months. Compared with the general older population that died in 1993, the final-year-of-life recipients of pacemakers group had higher percentages of persons who died of acute disorders (49% vs 19%) and who lived alone in a private home (47% vs 20%), and a lower percentage of persons with Alzheimer's disease (1% vs 7%). The age-stratified means of the percentages of final-year-of-life recipients of pacemakers who had no difficulty performing each physical activity of daily living were all greater than 50. CONCLUSION: Our results suggest that older persons who had initial pacemakers implanted during their final year of life and who died in 1993 were not terminally ill, inactive pacemaker candidates, in general, but relatively independent, physically functional candidates who frequently died abruptly. The physical, mental, and life expectancy factors recommended for consideration by expert guidelines for the implantation of cardiac pacemakers were generally applied to persons in this subgroup. C1 US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20850 USA. RP Hefflin, BJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, HFZ-541,1350 Piccard Dr, Rockville, MD 20850 USA. NR 12 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 1998 VL 46 IS 11 BP 1396 EP 1400 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 135CZ UT WOS:000076784000009 PM 9809761 ER PT J AU Martinez, MN AF Martinez, MN TI Use of pharmacokinetics in veterinary medicine - Article III: Physicochemical properties of pharmaceuticals SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article ID PROTEIN-BINDING; PARTITION-COEFFICIENT; BASIC DRUGS; SULFADIMETHOXINE; GLYCOPROTEIN; PREDICTION; HEALTH; PIGS C1 US FDA, CVM, Rockville, MD 20855 USA. RP Martinez, MN (reprint author), US FDA, CVM, 7300 Standish Pl, Rockville, MD 20855 USA. NR 33 TC 10 Z9 10 U1 0 U2 2 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD NOV 1 PY 1998 VL 213 IS 9 BP 1274 EP 1277 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 135CD UT WOS:000076781800017 PM 9810382 ER PT J AU Southern, FN Cruz, N Fink, LM Cooney, CA Barone, GW Eidt, JF Moursi, MM AF Southern, FN Cruz, N Fink, LM Cooney, CA Barone, GW Eidt, JF Moursi, MM TI Hyperhomocysteinemia increases intimal hyperplasia in a rat carotid endarterectomy model SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the Southern-Association-for-Vascular-Surgery CY JAN 21-24, 1998 CL RIO GRANDE, PUERTO RICO SP So Assoc Vasc Surg ID RISK FACTOR; PLASMA HOMOCYST(E)INE; NEOINTIMAL FORMATION; HOMOCYSTEINE LEVELS; ARTERIAL INJURY; VASCULAR INJURY; ATHEROSCLEROSIS; DISEASE; ACID; MYOFIBROBLASTS AB Purpose: This preliminary study investigated the ability to elevate the serum homocysteine (H[e]) levels and investigated the increases in postoperative neointimal hyperplasia (IH) in an environment with hyperhomocysteinemia and the resultant restenosis in a rat carotid endarterectomy (CEA) model. Method: The 9 rats for the control group were fed rat chow, and the 8 rats for the H(e) group were fed H(e)-supplemented rat chow for 2 weeks before and after CEA. The animals underwent anesthesia, and a left common CEA was performed. After 14 days, the serum H(e) levels were measured and the left carotid artery was harvested and elastin stained. Morphometric measurements were used to calculate the area of stenosis of the lumen. The mean and the standard deviation of the mean were determined. The 2 groups were compared with the Mann-Whitney test and a linear regression model. Three additional rats per group were studied, with carotid artery sectioning with double immunohistochemical staining for 5-bromodeoxyuridine (BrdU) and alpha-smooth muscle (alpha-SM) actin. Results: The serum H(e) level in the H(e) group was 36.32 mu mol/L +/- 15.28, and in the control group the level was 5.53 mu mol/L +/- 2.06 (P = .0007). IH presented as percent lumen stenosis was 21.89% +/- 4.82% in the H(e) group and 4.82% +/- 1.64% in the control group (P = .0007). The linear regression model of the serum H(e) levels and the percent stenosis showed a linear relationship (r(2) = .72). The alpha-SM actin staining revealed that nearly all of the cells in the IH area were of smooth muscle or myofibroblast origin and that 10.1% +/- 2.6% of the cells were-stained for BrdU in the control group versus 23% +/- 7.1% in the H(e) group. Also, 9.3% +/- 2.6% of the cells in the IH area were stained for BrdU and for alpha-SM actin versus 19.1% +/- 5.6% stained for both BrdU and alpha-SM actin in the H(e) group. Conclusion: This is the first study to examine IH after CEA and hyperhomocysteinemia in rats. The study shows that the elevation of serum H(e) levels can be obtained by feeding rats modified diets with added H(e). The consistent elevation of serum H(e) levels was associated with more than 4 times the amount of IH after a CEA in a rat model. C1 Univ Arkansas Med Sci, Dept Surg, Div Vasc Surg, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. Vet Adm Hosp, Little Rock, AR USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR USA. RP Moursi, MM (reprint author), Vet Adm Med Ctr, Div Vasc Surg, Vasc Lab, 112PV-LR,4300 W 7th St, Little Rock, AR 72205 USA. NR 27 TC 44 Z9 47 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD NOV PY 1998 VL 28 IS 5 BP 909 EP 918 DI 10.1016/S0741-5214(98)70069-2 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 136VA UT WOS:000076878800020 PM 9808861 ER PT J AU Lowery, JC Hiller, LD Davis, JA Shore, CJ AF Lowery, JC Hiller, LD Davis, JA Shore, CJ TI Comparison of professional judgment versus an algorithm for nutrition status classification SO MEDICAL CARE LA English DT Article DE nutrition status; nutrition screening; nutrition evaluation ID GASTROINTESTINAL SURGERY; HOSPITAL STAY; NECK-CANCER; MALNUTRITION; CARE; DIAGNOSIS; RELIABILITY; RECOGNITION; OUTCOMES; LENGTH AB OBJECTIVES. The classification of a patient's nutrition status is important for identifying patients who require nutrition care, for designing effective nutrition interventions, and for measuring severity of illness. The objective of this study was to evaluate the reliability and validity of two variants of the Department of Veterans Affairs' nutrition status classification: professional judgment versus an algorithm. METHODS. The study consisted of two phases, both of which included providing a sample of approximately 60 registered dietitians and 60 clinical dietetic technicians with data on 16 (phase I) and 20 (phase II) patients, to which they assigned nutrition statuses using both professional judgment and the algorithm. Improvements in instructions and training were implemented between the two phases. Interrater reliability of the responses was calculated, and content validity was measured by comparing the staff's responses with those of an expert panel. RESULTS. Reliability improved significantly between phases for both professional judgment and the algorithm. Greater reliability and validity were observed with use of the algorithm, by both dietitians and technicians, during both phases. CONCLUSION. Classification of a patient's nutrition status is important in the delivery of cost-effective health care. The Department of Veterans Affairs' nutrition status classification is a good one for assessing nutrition status quickly and reliably, especially when an algorithm is used. The results underscore the advantages of a classification system based on an algorithm when the system is designed to be used by many different staff across multiple facilities. C1 VA Hlth Serv Res & Dev Field Program, Ann Arbor, MI 48113 USA. James A Haley VA Hosp, Nutr & Food Serv, Tampa, FL USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Lowery, JC (reprint author), VA Hlth Serv Res & Dev Field Program, POB 130170, Ann Arbor, MI 48113 USA. NR 39 TC 5 Z9 5 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 1998 VL 36 IS 11 BP 1578 EP 1588 DI 10.1097/00005650-199811000-00007 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 136VN UT WOS:000076880000007 PM 9821945 ER PT J AU Rao, P Dougherty, SF Pluznik, DH AF Rao, P Dougherty, SF Pluznik, DH TI Microtubule disruption enhances lipopolysaccharide (LPS)- and IL-1 beta-stimulated induction of GM-CSF expression in B cells; Possible involvement of the JNK/SAPK pathway. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1330 BP 230A EP 230A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701332 ER PT J AU Orlandi, PA Fishman, PH AF Orlandi, PA Fishman, PH TI Cholera toxin-mediated ADP-ribosylation of Gs alpha and activation of adenylyl cyclase occurs at the plasma membrane of CaCo-2 cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 CFSAN, Div Virulence Assessment, FDA, Washington, DC 20204 USA. NINDS, LMCN, Membrane Biochem Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2361 BP 407A EP 407A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702363 ER PT J AU Parsons, BL Heflich, RH AF Parsons, BL Heflich, RH TI Detection of a mouse H-ras codon 61 mutation using a modified allele-specific competitive blocker PCR genotypic selection method SO MUTAGENESIS LA English DT Article ID POLYMERASE CHAIN-REACTION; PFU DNA-POLYMERASE; POINT MUTATIONS; GENOMIC DNA; GENE; MUTS; AMPLIFICATION; EXTENSION; PRIMERS AB A modified allele-specific competitive blocker PCR (ACB-PCR) has been developed as an approach for genotypic selection, the detection of a rare mutant allele based solely upon its altered nucleotide sequence. ACB-PCR genotypic selection operates through the preferential PCR amplification of mutant DNA using a primer that has more mismatches to the wild-type allele than the mutant allele, In addition, a blocker-primer with a 3'-terminal dideoxynucleotide and more mismatches to the mutant allele than the wild-type allele is incorporated to reduce the background and increase sensitivity. Using ACB-PCR, the CAA --> AAA base substitution at codon 61 of the mouse H-ras gene was detected regularly at mutant fractions of 10(-5). To accurately quantify the occurrence of this particular mutation, an internal amplification standard (AS) DNA was constructed. The H-ras and AS DNAs were subject to the same genotypic selection but were amplified using different upstream primers to give PCR products that can be distinguished by size. Defined mixtures of mutant and wild-type AS DNAs were used to study the effects of various components of the ACB-PCR. The concentration of dNTPs, blocker primer and Perfect Match(R) Polymerase Enhancer, as well as the choice of thermostable DNA polymerase and annealing temperature were examined. Conditions were identified for the concurrent detection of the CAA --> AAA mutation in the H-ras and AS DNAs. Using the identified conditions, approximately equal signals were obtained from equivalent amounts of the two DNA templates over a wide range of mutant fractions (1 in 10 to 1 in 10(5)). This ACB-PCR method can be used for any application where it is necessary to quantify relatively small mutant fractions. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Parsons, BL (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM bparsons@nctr.fda.gov NR 28 TC 16 Z9 16 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD NOV PY 1998 VL 13 IS 6 BP 581 EP 588 DI 10.1093/mutage/13.6.581 PG 8 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 140HY UT WOS:000077082900005 PM 9862188 ER PT J AU Genter, MB Ali, SF AF Genter, MB Ali, SF TI Age-related susceptibility to 3,3 '-iminodipropionitrile-induced olfactory mucosal damage SO NEUROBIOLOGY OF AGING LA English DT Article DE aging heat shock protein; cytochrome P450; 3,3 '-iminodipropionitrile (IDPN); eosinophilic globules olfactory mucosa; flavin-containing monooxygenases (FMO); susceptibility ID FLAVIN-CONTAINING MONOOXYGENASE; BETA,BETA'-IMINODIPROPIONITRILE IDPN; MOUSE-LIVER; RAT; NEUROTOXICITY; TOXICITY; EXPRESSION; EXPOSURE; MPTP; MICE AB 3,3'-Iminodipropionitrile (IDPN) causes degeneration of the olfactory mucosa (OM) in rodents following systemic exposure. Approximately 30% of the OM degenerates in 21-day- and 10-week-old rats Following a single 200 or 400 mg/kg intraperitoneal (i.p.) dose of IDPN, whereas 100% olfactory mucosal degeneration occurred in 21-month-old rats. Age-related changes in the flavin-containing monooxygenases (FMOs,) or heat shock protein 70 (HSP70) were hypothesized to be responsible for altered olfactory mucosal susceptibility to IDPN. FMO activity in OM was higher than in liver in rats up to 40 weeks of age. Western blots of OM and liver revealed no change in FMO1 protein; however, FMO2, 3, and 5 decreased in olfactory microsomes with age. FMO3 and FMO5 increased in liver microsomes with age. Heat shock protein 70 did not differ between 10-week- and 10-month-old rats in either tissue, The mechanism underlying the increased susceptibility of older rats is likely a complex interaction between the activities of one or more of the enzymes involved in IDPN metabolism in OM and liver. (C) 1999 Elsevier Science Inc. C1 Univ Cincinnati, Dept Mol & Cellular Physiol, Cincinnati, OH 45267 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pharmacol Toxicol, Little Rock, AR 72205 USA. RP Genter, MB (reprint author), Univ Cincinnati, Dept Environm Hlth, Kettering 250, Cincinnati, OH 45267 USA. FU NIA NIH HHS [AG-13837]; NIEHS NIH HHS [ES-00044] NR 44 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV-DEC PY 1998 VL 19 IS 6 BP 569 EP 574 DI 10.1016/S0197-4580(98)00104-3 PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 175RJ UT WOS:000079108500009 PM 10192216 ER PT J AU Ferguson, SA Holson, RR Gazzara, RA Siitonen, PH AF Ferguson, SA Holson, RR Gazzara, RA Siitonen, PH TI Minimal behavioral effects from moderate postnatal lead treatment in rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE lead toxicity; lead acetate; blood lead; bone lead; brain lead; burrowing; play behavior ID LEARNING-DEFICITS; EXPOSURE; BRAIN; PLAY; CHILDREN; SYSTEM; TASKS AB Developmental lead exposure continues to be a worldwide problem. This study investigated the behavioral effects resulting from developmental lead treatment in rats with corresponding physiological measures of lead exposure. Sprague-Dawley rats were treated with 350 ppm lead acetate from birth to weaning via the dam's drinking water. Behavioral measures assessed in the offspring included residential activity tests, complex maze performance, acoustic startle response, emergence behavior (light/dark preference), prepulse inhibition, and ethological assessments of play, dominance, and burrowing. Pb blood levels averaged 53 mu g/dl in the dam at the time of offspring weaning and 46 mu g/dl in weanling female offspring. Pb levels averaged 277 ng/g and 32 mu g/g in the brain and bone, respectively, of female offspring at weaning. No behavioral assessment indicated any lead-related functional alterations nor were there any statistically significant differences when the lead-treated group was restricted to rats in those litters that were above the median Pb blood lead level at weaning. These results indicate that any lead-related functional alterations at this dose may be subtle and require a sufficient demand on the system far detection. (C) 1998 Elsevier Science Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 39 TC 10 Z9 11 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD NOV-DEC PY 1998 VL 20 IS 6 BP 637 EP 643 DI 10.1016/S0892-0362(98)00023-3 PG 7 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 137HF UT WOS:000076908100008 PM 9831125 ER PT J AU Braun, MM Terracciano, G Salive, ME Blumberg, DA Vermeer-de Bondt, PE Heijbel, H Evans, G Patriarca, PA Ellenberg, SS AF Braun, MM Terracciano, G Salive, ME Blumberg, DA Vermeer-de Bondt, PE Heijbel, H Evans, G Patriarca, PA Ellenberg, SS TI Report of a US Public Health Service Workshop on hypotonic-hyporesponsive episode (HHE) after pertussis immunization SO PEDIATRICS LA English DT Article DE vaccine; pertussis vaccine; acellular pertussis vaccine; hypotonic-hyporesponsive episode; collapse; vaccine safety; adverse reaction ID ADVERSE REACTIONS; SYSTEM VAERS; VACCINE; CHILDREN; INFANTS; EVENTS; DTP AB Hypotonic-hyporesponsive episode (HHE) is a term used to describe a somewhat heterogenous group of clinical disorders that have been reported primarily in association with whole-cell pertussis vaccination. A 1991 review by the Institute of Medicine determined that the evidence available was indeed consistent with a causal relation between whole-cell pertussis-diphtheria-tetanus immunization and HHE, but that the evidence was insufficient to indicate a causal relationship between HHE and the subsequent development of permanent neurologic damage. More recent data from clinical trials conducted in Europe suggest that HHE also occurs after vaccination with acellular pertussis vaccines. The US Food and Drug Administration, in collaboration with the US Public Health Service, sponsored a workshop on HHE in Rockville, Maryland, on June 19, 1997. The primary goals of the workshop were to develop a case definition of HHE and to evaluate the general design and feasibility of possible studies of HHE using the federal Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance system. The goals of such studies would be to understand better the acute HHE event and to evaluate the possibility of longterm sequelae. Case Definition. There has been no generally accepted definition of HHE, and a standard definition would be useful for vaccine safety work and would potentially facilitate interstudy comparisons of the growing number of licensed vaccines containing acellular pertussis components. The workshop defined HHE as an event of sudden onset occurring within 48 hours of immunization, with duration of the episode ranging from 1 minute to 48 hours, in children younger than 10 years of age. All of the following must be present: 1) limpness or hypotonia, 2) reduced responsiveness or hyporesponsiveness, and 3) pallor or cyanosis or failure to observe or to recall skin coloration. HHE is not considered to have occurred if there is a known cause for these signs leg, postictal), if urticaria is present during the event, if normal skin coloration is observed throughout the episode, or if the child is simply sleeping. This inclusive (sensitive) case definition will allow investigators, through the technique of stratification according to certain characteristics leg, time from vaccination to onset of HHE), to attempt to hone the definition and make it more specific. Refinement of the definition of HHE has been hindered by the lack of information on its pathophysiology and by the lack of pathognomonic signs, symptoms, and diagnostic tests. Another hindrance is that by the time the child presents for medical evaluation, the signs of HHE often have normalized. Moreover, different mechanisms may be involved in different individuals whose events meet this workshop's HHE definition. Further Study of HHE. Probably the most important question about HHE is whether it has any permanent sequelae. The workshop assessed the possible contribution VAERS-based studies could make to answering this question and found substantial methodologic problems; however, ongoing studies in Sweden and The Netherlands have the potential to provide useful information on this question. The most useful contribution of VAERS data would be in a descriptive study of HHE, with a possible case-control study of factors that may affect the risk of HHE after vaccination, rather than a study of possible permanent sequelae. The workshop participants felt that a detailed descriptive study of similar to 100 HHE events reported during a 1- to 2-year period could provide a more in-depth description of HHE cases in greater numbers than has been published previously, but the study would not address the issue of long-term sequelae of HHE. Better descriptive data may lead to new hypotheses concerning risk factors, etiology, and pathophysiology of HHE that might be evaluated further by studying subsequent cases and controls from VAERS or from other sources, depending on the hypotheses being tested. Workshop participants agreed that the question of possible long-term sequelae of HHE may currently be best answered in studies being conducted outside of the United States. A cohort of 82 892 infants was enrolled in the Stockholm II randomized, double-blind, controlled trial of one whole-cell and three acellular pertussis vaccines in Sweden in 1993-1994. In this trial, 101 infants developed HHE after vaccination. Of these children, 100 (1 had left Sweden) were evaluated subsequently at 18 months of age, using routine screening tests of motor and cognitive development intended to detect moderate to serious developmental problems. All 100 were found to be developing normally. At older ages, when more subtle developmental problems are detectable, comparison of the physical development and neurodevelopment of these children with a sample of trial participants without a history of HHE should be feasible. A protocol for a study to make such a comparison at ages 5 1/2 and 8 1/2 years is being prepared. In The Netherlands, a case-control study of infants who had HHE reported in 1995 is ongoing. The HHE events were detected through national surveillance linked to the health care delivery system. Growth, health, and neurodevelopment are being assessed. Data presented at the workshop concerning children with HHE reported in 1994 indicate that all 101 children followed during the second year of life (mean age, 1.5 years) were in good health and developing normally. An interesting finding of this follow-up study was the low rate of recurrent collapse (subsequent HHE occurrences) after repeat doses of pertussis vaccine. Summary. Despite increasingly widespread use of acellular pertussis vaccine in infants, HHE will continue to occur. The HHE definition proposed by this workshop should facilitate interstudy comparisons of HHE incidence among in the growing number of vaccines containing acellular pertussis components and perhaps of other vaccines as well. This definition also may aid study in VAERS and elsewhere of the etiology, pathophysiology, and descriptive epidemiology of HHE. Ongoing investigations in Sweden and The Netherlands have the potential to expand substantially knowledge of the possibility of long-term sequelae of HHE. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Ctr Dis Control & Prevent, Natl Immunizat Program, Atlanta, GA USA. Univ Calif Davis, Med Ctr, Dept Pediat Infect Dis, Sacramento, CA 95817 USA. Natl Inst Publ Hlth & Environm, Lab Clin Vaccine Res, NL-3720 BA Bilthoven, Netherlands. Swedish Inst Infect Dis Control, Vaccine Safety Project, Stockholm, Sweden. US Hlth Resources & Serv Adm, Div Vaccine Injury Compensat, Rockville, MD 20857 USA. RP Braun, MM (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 20 TC 23 Z9 24 U1 0 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 1998 VL 102 IS 5 AR e52 DI 10.1542/peds.102.5.e52 PG 5 WC Pediatrics SC Pediatrics GA 134ZT UT WOS:000076774600004 PM 9794982 ER PT J AU Meyer, MC Straughn, AB Mhatre, RM Shah, VP Williams, RL Lesko, LJ AF Meyer, MC Straughn, AB Mhatre, RM Shah, VP Williams, RL Lesko, LJ TI The relative bioavailability and in vivo in vitro correlations for four marketed carbamazepine tablets SO PHARMACEUTICAL RESEARCH LA English DT Article DE carbamazepine; human; bioavailability; gender; dissolution AB Purpose. To determine if three marketed generic carbamazepine tablets were bioequivalent to the innovator formulation, as well as to each other. In addition, to examine in vivo-in vitro relationships among the four formulations. Methods. Each formulation was given as a single dose to 18 healthy male and female subjects using a crossover design. Blood samples were collected for 169 hr. Carbamazepine was assayed by HPLC with UV detection. Results. In vivo fraction absorbed plots indicated that the three generic formulations were absorbed more rapidly than the innovator product, and the mean time of maximum plasma concentration was 6-7 hr sooner for the generic formulations. The mean maximum plasma concentration ranged from 17-19 percent higher for the generic products compared to the innovator, and the 90% confidence limits for Cmax data ranged from 111% to 126%. The mean AUC(0-infinity) for the generic products ranged from 101-104% compared to the innovator, and the confidence limits for AUC ranged from 97-108%. Conclusions. The generic products were all more rapidly absorbed than the innovator, but simulations of steady-state concentrations indicated that it would be unlikely that these differences would have any significant clinical effect. An excellent association was seen between the Cmax and the percent of drug dissolved in vitro. The correlation was used to accurately predict the Cmax of four other 200 mg tablets evaluated in an earlier study. C1 Univ Tennessee, Coll Pharm, Dept Pharmaceut Sci, Memphis, TN 38163 USA. US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20855 USA. RP Meyer, MC (reprint author), Univ Tennessee, Coll Pharm, Dept Pharmaceut Sci, Memphis, TN 38163 USA. FU PHS HHS [223-91-1803] NR 11 TC 44 Z9 44 U1 1 U2 6 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD NOV PY 1998 VL 15 IS 11 BP 1787 EP 1791 DI 10.1023/A:1011929300613 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 138VR UT WOS:000076994500024 PM 9834004 ER PT J AU Brown, SL Parmentier, CM Woo, EK Vishnuvajjala, RL Headrick, ML AF Brown, SL Parmentier, CM Woo, EK Vishnuvajjala, RL Headrick, ML TI Silicone gel breast implant adverse event reports to the food and drug administration, 1984-1995 SO PUBLIC HEALTH REPORTS LA English DT Article ID CONNECTIVE-TISSUE DISEASES; CANCER; AUGMENTATION; COMPLICATIONS; ASSOCIATION; PROSTHESES; CARCINOMA; DECISION; SURGERY; RISK AB Objectives. To characterize the adverse event reports on silicone gel breast imp ants (SGBIs), including death reports, submitted to the Food and Drug Administration (FDA) from 1984 through 1995 and to analyze changes in the type and complexity or reports Following extensive media coverage of breast implants. Methods. The authors analyzed mandatory and voluntary reports from the adverse events report;ng system for medical devices at the FDA. Results. In 1988, adverse event reports related to SGBIs accounted for 2.4% of the 14,473 mandatory reports entered into the FDA database on medical devices. In 1992, SGBI-related reports accounted For 30.3% of the total 66,476 mandatory reports of adverse events, The most frequently reported adverse event in 1988, before the widespread publicity on breast mplants, was implant burst or rupture. In contrast, in 1992 the most frequently reported event was reaction, a term used to describe a range of adverse effects. Conclusions. The numbers of mandatory and voluntary reports of SGBI-related adverse events increased exponentially, as did the complexity of the reports, following publicity over the lack of safety data on breast implants and a short voluntary moratorium on their sale. A significant proportion of reports lacked information on on specific medical symptoms or diagnoses. C1 US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20850 USA. RP Brown, SL (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, 1350 Piccard Dr,HFZ-541, Rockville, MD 20850 USA. EM syb@cdrh.fda.gov NR 35 TC 15 Z9 15 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD NOV-DEC PY 1998 VL 113 IS 6 BP 535 EP 543 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 161RW UT WOS:000078303700022 PM 9847926 ER PT J AU Eisch, AJ Schmued, LC Marshall, JF AF Eisch, AJ Schmued, LC Marshall, JF TI Characterizing cortical neuron injury with Fluoro-Jade labeling after a neurotoxic regimen of methamphetamine SO SYNAPSE LA English DT Article DE drugs of abuse; degeneration; dopamine; amphetamine; somatosensory cortex; apoptosis ID RAT SOMATOSENSORY CORTEX; CELL-DEATH; GLUTAMATE; DEGENERATION; APOPTOSIS; ORGANIZATION; NEOSTRIATUM; PROJECTIONS; EXPRESSION; NEOCORTEX AB We used Fluoro-Jade, a recently-developed fluorescent indicator of neuronal damage, to identify neurons injured 1-21 days after repeated injections of methamphetamine (m-AMPH) or saline. The m-AMPH-treated rats showed Fluoro-Jade positive neurons in parietal cortex (layers III and IV) and had less striatal tyrosine hydroxylase immunoreactivity than did saline-injected controls. Fluoro-Jade positive neurons were greatest in number 3 days post-treatment; some fluorescent neurons displayed bud-like surface protrusions. These observations support the hypothesis that certain neocortical neurons degenerate after m-AMPH. Synapse 30:329-333, 1998. (C) 1998 Wiley-Liss, Inc. C1 Univ Calif Irvine, Dept Psychobiol, Irvine, CA 92697 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Marshall, JF (reprint author), Univ Calif Irvine, Dept Psychobiol, Irvine, CA 92697 USA. EM jfmarsha@uci.edu FU NIDA NIH HHS [DA 10249, DA 05647, DA 08052] NR 25 TC 91 Z9 92 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 0887-4476 J9 SYNAPSE JI Synapse PD NOV PY 1998 VL 30 IS 3 BP 329 EP 333 DI 10.1002/(SICI)1098-2396(199811)30:3<329::AID-SYN10>3.0.CO;2-V PG 5 WC Neurosciences SC Neurosciences & Neurology GA 123JM UT WOS:000076122100010 PM 9776136 ER PT J AU Spenser, EL AF Spenser, EL TI United States Food and Drug laws and ratites as emerging food animals SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article ID EMUS DROMAIUS-NOVAEHOLLANDIAE; ERYSIPELOTHRIX-RHUSIOPATHIAE INFECTION; RHEAS RHEA-AMERICANA; DISPOSITION AB Ostriches and emus are emerging as food animals in North America. The absence of approved drugs, and a dearth of knowledge regarding pharmokinetic and tissue residue data represents a challenge to practitioners. The potential for food-borne transmission of pathogens is a significant public health concern. This brief overview of United States Food and Drug laws is intended to remind practitioners of their obligations with respect to ratites intended for human consumption. C1 US FDA, Ctr Vet Med, Div Epidemiol & Surveillance, Rockville, MD 20855 USA. RP Spenser, EL (reprint author), US FDA, Ctr Vet Med, Div Epidemiol & Surveillance, 7500 Standish Pl,HFV-210, Rockville, MD 20855 USA. NR 26 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 0749-0720 J9 VET CLIN N AM-FOOD A JI Vet. Clin. N. Am.-Food Anim. Pract. PD NOV PY 1998 VL 14 IS 3 BP 533 EP + PG 9 WC Veterinary Sciences SC Veterinary Sciences GA 131XT UT WOS:000076601100011 PM 10098241 ER PT J AU Miller, NC Ross, DL Nasr, MM AF Miller, NC Ross, DL Nasr, MM TI Effect of formulation factors on the observed bounce in cascade impactors used to measure the spray particle size of metered dose inhalers SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE aerosol; size; metered dose inhaler; cascade impactor; bounce ID SINGLE; MDIS AB This study was conducted to investigate the extent of particle reentrainment, or bounce, in cascade impactors used to measure the size of the spray from single and multiple doses of metered dose inhalers (MDIs), and to determine the effect of some common formulation properties on the observed bounce. MDIs were formulated as suspensions or solutions, with varying levels of surfactant. These were fired into two impactors (the Andersen Sampler Mark II and the Marple-Miller model 150), the collection surfaces of which were uncoated or coated with silicone oil or glycerin, The amount of drug from a formulation collected on each stage was determined and comparison was made between results with coated and uncoated stages. Efficacy of the coating for eliminating bounce was demonstrated by comparing single shots with multiple shots. Different ways of describing bounce effects offer varying indications of its significance. The suspension formulations (containing surfactant) all showed evidence of bounce, but solution formulations showed little or none. Silicone oil and glycerin were equally effective in eliminating bounce. Results with impactors of two different designs were similar. Particle bounce was shown to occur with a variety of formulations when impactor stages are not coated. (C) 1998 Elsevier Science B.V. All rights reserved. C1 US FDA, CDER, Div Testing & Appl Analyt Dev, St Louis, MO USA. Nephele Enterprises, White Bear Lake, MN 55110 USA. 3M Co, Pharmaceut, Inhalat Drug Delivery Lab, St Paul, MN 55144 USA. RP Nasr, MM (reprint author), US FDA, CDER, Div Testing & Appl Analyt Dev, St Louis, MO USA. NR 9 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARM JI Int. J. Pharm. PD OCT 30 PY 1998 VL 173 IS 1-2 BP 93 EP 102 DI 10.1016/S0378-5173(98)00217-8 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 131RZ UT WOS:000076590200011 ER PT J AU Chen, TT Ng, TH AF Chen, TT Ng, TH TI Optimal flexible designs in phase II clinical trials SO STATISTICS IN MEDICINE LA English DT Article ID MULTIPLE TESTING PROCEDURE; TOXICITY AB In the conduct of a phase II cancer clinical trial, patients usually enter in two stages. If the response rate from the first stage is low, then the study terminates. Within various two-stage designs, Simon proposed the optimal and minimax criteria. In the co-operative group setting, practical considerations make it difficult to arrive at the planned sample size exactly. Green and Dahlberg proposed and compared several flexible designs. In this paper, we explicitly define a flexible design as a collection of two-stage designs where the first stage size is in a set of consecutive values (n(1), ..., n(k)) and the second stage size is also in another set of consecutive values (N-1, ..., N-k), and each of k(2) possible designs has the same probability of occurrence. We apply Simon's optimal and minimax criteria to flexible designs for phase II trials in order to minimize the number of patients tested on an ineffective drug. (C) 1998 John Wiley & Sons, Ltd. This paper was produced under the auspices of the US Government and is therefore not subject to copyright in the US. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. US FDA, Div Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Chen, TT (reprint author), NCI, Biometr Res Branch, EPN-739, Bethesda, MD 20892 USA. EM tchen@helix.nih.gov NR 14 TC 91 Z9 92 U1 0 U2 3 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 OCT 30 PY 1998 VL 17 IS 20 BP 2301 EP 2312 DI 10.1002/(SICI)1097-0258(19981030)17:20<2301::AID-SIM927>3.0.CO;2-X 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 130YK UT WOS:000076548100002 PM 9819829 ER PT J AU Bowyer, JF Peterson, SL Rountree, RL Tor-Agbidye, J Wang, GJ AF Bowyer, JF Peterson, SL Rountree, RL Tor-Agbidye, J Wang, GJ TI Neuronal degeneration in rat forebrain resulting from D-amphetamine-induced convulsions is dependent on seizure severity and age SO BRAIN RESEARCH LA English DT Article DE amphetamine; limbic system; seizure; neurodegeneration; glutamate; catecholamine; basal ganglia ID PIRIFORM CORTEX; METHAMPHETAMINE NEUROTOXICITY; GLUTAMATE RECEPTORS; PERIRHINAL CORTEX; INDUSIUM GRISEUM; PYRAMIDAL CELLS; NERVOUS-SYSTEM; SEROTONIN 5-HT; BRAIN; MOUSE AB Neuronal damage and degeneration in the rat forebrain was characterized by B4 isolectin and Fluoro-Jade labeling techniques after 4 doses of 15 mg/kg amphetamine i.p. in 70- and 180-day-old Sprague-Dawley rats. In amphetamine-dosed rats some seizure activity occurred in all rats exhibiting pronounced hyperthermia but the degree of seizure activity varied greatly between individual rats. Over 90% of the rats in both age groups that showed behavioral signs of limbic seizures had somatic degeneration in the taenia tecta within 3 days of amphetamine exposure. Degenerating small star-shaped cells were seen in the septum and hippocampus in 70-day-old rats having extensive seizure activity. Although somatic degeneration only sporadically occurred in the piriform cortex of the younger rats, extensive B4 isolectin binding to activated microglia was observed in this area. In older rats prominent somatic degeneration was seen in the piriform cortex and orbital and insular areas of the frontal cortex of rats having seizures. Damage to the basal ganglia and related areas, including the thalamus, parietal cortex and dorsal medial striatum, occurred in rats with pronounced hyperthermia but only correlated with seizures in older rats. In the more severe cases of thalamic damage the highest density of neurodegeneration was localized perivascularIy. Thus, amphetamine can produce notable damage to the limbic system when seizures occur and to the basal ganglia and related areas when hyperthermia occurs but the neurotoxicity profiles in these areas are age-dependent and not produced solely by hyperthermia. Further studies to determine whether neuronal damage is the result of or the cause of amphetamine-induced seizures are necessary. (C) 1998 Elsevier Science B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ New Mexico, Coll Pharm, Albuquerque, NM 87131 USA. RP Bowyer, JF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132, Jefferson, AR 72079 USA. EM jbowyer@nctr.fda.gov NR 46 TC 53 Z9 57 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 OCT 26 PY 1998 VL 809 IS 1 BP 77 EP 90 DI 10.1016/S0006-8993(98)00846-4 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 134BJ UT WOS:000076722700010 PM 9795148 ER PT J AU Harindranath, N Mills, FC Mitchell, M Meindl, A Max, EE AF Harindranath, N Mills, FC Mitchell, M Meindl, A Max, EE TI The human elk-1 gene family: the functional gene and two processed pseudogenes embedded in the IgH locus SO GENE LA English DT Article DE immunoglobulin; ERV; ternary complex factor; psi elk-2.1; psi elk-2.2; Ets family ID DNA-BINDING; CHROMOSOME-X; ETS; REGION; PROPERDIN; SEQUENCES; MOUSE AB Elk-1 is a transcription factor whose activation by several mitogen-activated protein kinases (MAPKs) mediates the immediate early responses of the c-fos promoter to growth factors and other stimuli. Here, we report the structure of the human elk-1 gene, which we have localized about 6.5 kb upstream of the properdin gene on the X chromosome. The coding sequence is interrupted by four introns; two additional introns lie within the 5' untranslated region. We have also found two elk-1-related processed pseudogenes in the human immunoglobulin heavy chain (IgH) locus, accounting for 'elk-2' previously visualized by in-situ hybridization at 14q32. A processed pseudogene evidently inserted downstream of a primordial immunoglobulin Cu gene and was duplicated along with part of the IgH locus. Gene/pseudogene sequence comparisons and Southern blots of primate DNAs suggest that both the pseudogene insertion and the locus duplication occurred between about 30 and 60 million years ago. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Munich, Kinderpoliklin, Abt Padiat Genet, D-80336 Munich, Germany. RP Max, EE (reprint author), US FDA, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM max@cber.cber.fda.gov NR 24 TC 11 Z9 12 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD OCT 23 PY 1998 VL 221 IS 2 BP 215 EP 224 DI 10.1016/S0378-1119(98)00448-X PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 139KF UT WOS:000077027300007 PM 9795224 ER PT J AU Carson, MC Heller, DN AF Carson, MC Heller, DN TI Confirmation of spectinomycin in milk using ion-pair solid-phase extraction and liquid chromatography electrospray ion trap mass spectrometry SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE spectinomycin ID AMINOGLYCOSIDE ANTIBIOTICS; CHICKEN PLASMA; SWINE; CALF AB A confirmation procedure is described for residues of spectinomycin in bovine milk. Spectinomycin is extracted from raw milk using ion-pair reversed-phase solid-phase extraction. The extracts are ion-pair chromatographed on a polymeric reversed-phase column and analyzed on a quadrupole ion trap mass spectrometer equipped with an electrospray interface. MS-MS data are acquired in the scan mode of product ions deriving from m/z 333, the protonated molecular ion. The estimated limit of confirmation is between 0.05 and 0.1 mu g/ml. The procedure was validated with control milk, fortified milk (0.1-5.0 mu g/ml), and milk from cows dosed with spectinomycin. 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 12 TC 36 Z9 39 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD OCT 23 PY 1998 VL 718 IS 1 BP 95 EP 102 DI 10.1016/S0378-4347(98)00331-4 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 135CF UT WOS:000076782000012 PM 9832365 ER PT J AU Stewart, CW Scalzo, FM Valentine, J Holson, RR Ali, SF Slikker, W AF Stewart, CW Scalzo, FM Valentine, J Holson, RR Ali, SF Slikker, W TI Gestational exposure to cocaine or pharmacologically related compounds: Effects on behavior and striatal dopamine receptors SO LIFE SCIENCES LA English DT Article DE prenatal cocaine exposure; reuptake blockade; behavior; monoamines; quinpirole ID PRENATAL COCAINE; RAT-BRAIN; TRANSPORTER BINDING; MATERNAL TOXICITY; ADULT-RATS; PREFERENCE; RESPONSES; SYSTEM AB Gestational cocaine (COC) exposure has been reported to alter behavior and possibly dopamine (DA) receptors. In this paper, we further examined the effects of prenatal COC (40 mg/kg, s.c.) on DA receptor binding and the behavioral response to quinpirole, a DA D-2 receptor agonist. In an attempt to elucidate possible mechanisms of such effects, we exposed pregnant dams to specific reuptake blockers; fluoxetine 12.5 mg/kg, a serotonin reuptake blocker; desipramine 10 mg/kg, a norepinephrine reuptake blocker; GBR-12909 10 mg/kg, a DA reuptake blocker; or to a local anesthetic, lidocaine 40 mg/kg. Drugs were administered once daily over gestational days 8-20. Control dams were injected with saline (SAL) or pair-fed to the COC group. Quinpirole challenge was performed in the offspring on post natal day 19. Two pups per litter were injected (s.c.) with 0.03 or 0.09 mg/kg quinpirole-HCl on post-natal day 19. The remaining pups in each litter were sacrificed for analysis of-striatal DA receptors. Results showed that only COC exposure altered the behavioral response to the quinpirole challenge by increasing quinpirole-induced stereotypy and motor activity relative to SAL controls. DA receptor analysis showed no alteration in K-D or B-MAX for striatal D-1 or D-2 sites in any group. These results suggest that prenatal COC exposure produces alterations in function of the D-2 receptor complex which are not reflected in K-D or B-MAX and that these effects are not fully mimicked by exposure to specific monoamine reuptake blockers or a local anesthetic. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. RP Stewart, CW (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 21 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD OCT 23 PY 1998 VL 63 IS 22 BP 2015 EP 2022 DI 10.1016/S0024-3205(98)00479-2 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 135GD UT WOS:000076791800007 PM 9839545 ER PT J AU Hilbert, DM Theisen, PW Rudikoff, EK Bauer, SR AF Hilbert, DM Theisen, PW Rudikoff, EK Bauer, SR TI Interaction of abl and raf with IL-7 signaling pathway and transformation of pre-B cells from resistant mice SO ONCOGENE LA English DT Article DE pre-B lymphomagenesis; JAK-STAT signaling; raf/myc retrovirus; abl/myc retrovirus; IL-7 signal transduction ID T-CELLS; MURINE PLASMACYTOMAGENESIS; LEUKEMIA-VIRUS; MYC ONCOGENES; V-ABL; EXPRESSION; ABROGATION; MOUSE; DEPENDENCE; RETROVIRUS AB After in vivo inoculation with abl/myc- and raf/myc-containing retroviruses, BALB/c mice predominantly develop late stage B cell tumors (plasmacytomas) and less frequently develop earlier B-lineage tumors while DBA/2 mice do not develop B-lineage tumors. We have investigated the in vitro tumorigenic potential of these viruses using cultured normal pre-B cell lymphocytes from both BALB/c and DBA/2 mice. Interestingly, both viruses infect cultured pre-B lymphocytes from both mouse strains. Following infection, IL-7 dependent pre-B cells become independent of normal in vitro growth requirements within 24 h and can rapidly form in vivo pre-B lymphomas in both mouse strains, Mechanisms mediating loss of IL-7 dependence are different depending on whether the I nf or abl gene is present in myc-containing viruses. IL-7 JAK-STAT signaling is constitutively active in abl/myc induced pre-B cell tumors, In contrast, IL-7 JAK-STAT signaling is not constitutive in raf/myc induced pre-B cell tumors, demonstrating that subversion of this component of IL-7 signal transduction is not obligatory for pre-B cell transformation or loss of IL-7 dependence. C1 US FDA, Mol Immunol Lab, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Rockville, MD 20852 USA. NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Bauer, SR (reprint author), US FDA, Mol Immunol Lab, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bldg 29B,2E16 HFM-521,1401 Rockville Pike, Rockville, MD 20852 USA. RI Bauer, Steven/G-5559-2012; OI Bauer, Steven/0000-0003-2831-846X NR 38 TC 5 Z9 5 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 22 PY 1998 VL 17 IS 16 BP 2125 EP 2135 DI 10.1038/sj.onc.1202134 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 130VK UT WOS:000076540900012 PM 9798684 ER PT J AU Spry, L Stivers, A Morin, R Timmons, T Weaver, S Douglas, C Safranek, T Roche, J Groves, C Portesi, D Hawkins, M Dwyer, D AF Spry, L Stivers, A Morin, R Timmons, T Weaver, S Douglas, C Safranek, T Roche, J Groves, C Portesi, D Hawkins, M Dwyer, D TI Multistate outbreak of hemolysis in hemodialysis patients - Nebraska and Maryland, 1998 (Reprinted from Morbidity and Mortality Weekly Report, vol 47, pg 483-484, 1998) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Dialysis Ctr Lincoln, Lincoln, NE USA. Bryan Mem Hosp, Lincoln, NE USA. Lincoln Lancaster Cty Hlth Dept, Lincoln, NE USA. Nebraska Hlth & Human Svcs Syst, Lincoln, NE USA. Maryland Dept Hlth & Mental Hyg, Baltimore, MD 21201 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. US FDA, Off Regulatory Affairs, Rockville, MD 20857 USA. Natl Ctr Chron Dis Prevent & Hlth Promot, Div Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. Natl Ctr Environm Hlth, Int Emergency & Refugee Hlth Program, Atlanta, GA USA. Natl Ctr Infect Dis, Hosp Infect Program, Atlanta, GA USA. CDC, Atlanta, GA 30333 USA. RP Spry, L (reprint author), Dialysis Ctr Lincoln, Lincoln, NE USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 21 PY 1998 VL 280 IS 15 BP 1299 EP 1300 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 129PQ UT WOS:000076472500010 ER PT J AU Holson, RR Gazzara, RA Gough, B AF Holson, RR Gazzara, RA Gough, B TI Declines in stimulated striatal dopamine release over the first 32 h following microdialysis probe insertion: generalization across releasing mechanisms SO BRAIN RESEARCH LA English DT Article DE bupropion; potassium; haloperidol; microdialysis; striatum; dopamine; DOPAC; time course; axotomy; rat ID INTRACEREBRAL MICRODIALYSIS; BRAIN MICRODIALYSIS; INVIVO; RATS; METHAMPHETAMINE; METABOLISM; DIALYSIS; SYSTEM; ACID AB In a recent paper [R.R. Holson, J.F. Bowyer, P. Clausing, B. Gough, Methamphetamine-stimulated striatal dopamine release declines rapidly over time following microdialysis probe insertion, Brain Res. 739 (1996) 301-307] we reported that methamphetamine-stimulated striatal dopamine release declined rapidly over the first eight hours following microdialysis probe insertion. This decline was strictly a function of time post-probe implantation, and not due to tolerance or desensitization. To further examine this phenomenon, we subjected rats to three brief pulses of several DA-releasing compounds at 2, 4 and 6 h post-probe insertion, and compared these results to those caused by a single pulse 6 h post-insertion, or in some cases to pulses given more than 24 h post-insertion. We found that when buproprion, a dopamine reuptake blocker, was infused briefly into the striatum via the microdialysis probe, there was a pronounced drop in the amount of dopamine released at 6 h vs. 2 h post insertion; this drop was not due to repeated exposure, since dopamine release at 6 h post-insertion was the same for a single pulse, or when preceded by two earlier pulses. Twenty-four hours later, buproprion-stimulated dopamine release was still lower, but did not appear to drop further thereafter. Potassium-stimulated dopamine release, on the other hand, dropped rapidly over the first 8 h post-insertion, and this decline continued throughout the 24-32 h interval post-insertion. Similarly, a single i.p. injection of 0.5 mg/kg haloperidol released three times as much dopamine when given two compared to six hours post-implantation. Both bupropion- and potassium-stimulated dopamine release were accompanied by declines in extracellular DOPAC concentrations, and these declines were the same 2 or 26 h post-insertion. In contrast, haloperidol exposure increased extracellular DOPAC, and this haloperidol-stimulated DOPAC increase was also greatly attenuated at 6 compared to 2 h post-insertion. We conclude that there is a general decline over time post-probe implantation in the ability of the striatal dopamine system to release dopamine, and perhaps to increase dopamine synthesis, in response to pharmacological challenges. (C) 1998 Elsevier Science B.V. All rights reserved. C1 New Mexico Tech, Dept Psychol, Socorro, NM 87801 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Holson, RR (reprint author), New Mexico Tech, Dept Psychol, Socorro, NM 87801 USA. NR 24 TC 16 Z9 16 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 OCT 19 PY 1998 VL 808 IS 2 BP 182 EP 189 DI 10.1016/S0006-8993(98)00816-6 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 133NT UT WOS:000076693200007 PM 9767162 ER PT J AU Gilkeson, GS Conover, J Halpern, M Pisetsky, DS Feagin, A Klinman, DM AF Gilkeson, GS Conover, J Halpern, M Pisetsky, DS Feagin, A Klinman, DM TI Effects of bacterial DNA on cytokine production by (NZB/NZW)F-1 mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; NECROSIS-FACTOR-ALPHA; INTERFERON-GAMMA; ANTI-DNA; NZB/W F1-MICE; CPG MOTIFS; IMMUNIZATION; MURINE; ANTIBODIES; CELLS AB Microbial DNA has multiple immune effects including the capacity to induce polyclonal B cell activation and cytokine production in normal mice. We recently described the accelerated induction of anti-DNA Abs in NZB/NZW mice immunized with Escherichia coli (EC) dsDNA; paradoxically; these mice developed less renal disease than unimmunized mice or mice immunized with calf thymus DNA. We postulated that alterations in cytokine production induced by bacterial DNA may play a key role in renal protection. To determine the effect of bacterial DNA on cytokine production in NZB/NZW mice, we measured the serum cytokine levels, cell culture supernatant cytokine levels, and number of cytokine-producing splenocytes in NZB/NZW mice injected with EC DNA, calf thymus DNA, or an immune active oligonucleotide. There was a 10- to 25-fold increase in the number of cells secreting IFN-gamma compared with IL-4 in mice immunized with EC DNA. IL-12-secreting cells were also increased by bacterial DNA immunization, In parallel with the increase in IFN-gamma secreting cells, there was a significant rise in serum IFN-gamma levels in mice receiving EC DNA. These results indicate that EC DNA modulates systemic cytokine levels in NZB/NZW mice, selectively increasing IL-12 and IFN-gamma while decreasing IL-4 production, The cytokine response of NZB/NZW mice to bacterial DNA may be of significance in disease pathogenesis and relevant to the treatment of lupus-like disease. C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. Duke Univ, Med Ctr, Durham, NC 27705 USA. Durham Vet Affairs Med Ctr, Durham, NC 27705 USA. US FDA, Sect Retroviral Res, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Gilkeson, GS (reprint author), Med Univ S Carolina, 912 Clin Sci Bldg,171 Ashley Ave, Charleston, SC 29425 USA. FU NIAMS NIH HHS [AR43891] NR 26 TC 35 Z9 36 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 OCT 15 PY 1998 VL 161 IS 8 BP 3890 EP 3895 PG 6 WC Immunology SC Immunology GA 127GV UT WOS:000076343300014 PM 9780154 ER PT J AU Martinez, MN AF Martinez, MN TI Special series - Use of pharmacokinetics in veterinary medicine - Article II: Volume, clearance, and half-life SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article ID BASIC PRINCIPLES; PROTEIN-BINDING; DRUGS; PREDICTION; CATTLE; CATS C1 FDA CVM, Rockville, MD 20855 USA. RP Martinez, MN (reprint author), FDA CVM, 7500 Standish Pl, Rockville, MD 20855 USA. NR 38 TC 21 Z9 21 U1 1 U2 2 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD OCT 15 PY 1998 VL 213 IS 8 BP 1122 EP 1127 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA 128WX UT WOS:000076432300011 PM 9787378 ER PT J AU Lachenbruch, PA Lynch, CJ AF Lachenbruch, PA Lynch, CJ TI Assessing screening tests: Extensions of McNemar's test SO STATISTICS IN MEDICINE LA English DT Article ID EQUIVALENCE AB We address the problem of comparing a new screening test to a currently available screening test in the absence of a gold standard. When both tests are given to each participant in a clinical trial, the usual analytical approach is to apply McNemar's test for equality of the off-diagonal probabilities, with rejection of the null hypothesis implying that the tests differ. For assessing equivalence, however, we consider a compound null hypothesis that the new test gives either fewer or more positive results than the standard. If bath parts of this hypothesis are rejected, we assert equivalence in the rate of positive responses. We propose an extension of McNemar's test for this situation. A companion step is to construct a confidence interval for the ratio of the marginal probabilities and assert equivalence if the interval is sufficiently small. It is also important that the tests agree a large proportion of the time. This can be verified with a complementary two-tailed binomial test. Another situation arises when there is a gold standard for disease diagnosis, and we wish to compare the sensitivity and specificity of two screening tests. We show that a 2 degrees-of-freedom chi-square test based on two McNemar-like tables is an appropriate test. (C) 1998 John Wiley & Sons, Ltd. C1 US FDA, CBER, HFM 215, Rockville, MD 20852 USA. RP Lynch, CJ (reprint author), US FDA, CBER, HFM 215, 1401 Rockville Pike,Rm 235, Rockville, MD 20852 USA. NR 7 TC 60 Z9 63 U1 2 U2 9 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 OCT 15 PY 1998 VL 17 IS 19 BP 2207 EP 2217 DI 10.1002/(SICI)1097-0258(19981015)17:19<2207::AID-SIM920>3.3.CO;2-P PG 11 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 126ML UT WOS:000076297200004 PM 9802179 ER PT J AU Menozzi, FD Bischoff, R Fort, E Brennan, MJ Locht, C AF Menozzi, FD Bischoff, R Fort, E Brennan, MJ Locht, C TI Molecular characterization of the mycobacterial heparin-binding hemagglutinin, a mycobacterial adhesin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COMPLEMENT COMPONENT-C3; BORDETELLA-PERTUSSIS; EPITHELIAL-CELLS; TUBERCULOSIS; GLYCOSYLATION; RECEPTORS; SULFATE; PROTEOGLYCANS; ANTIGENS; AVIUM AB Although it generally is accepted that the interaction of Mycobacterium tuberculosis with alveolar macrophages is a key step in the pathogenesis of tuberculosis, interactions with other cell types, especially epithelial cells, also may be important. In this study we describe the molecular characterization of a mycobacterial heparin-binding hemagglutinin (HBHA), a protein that functions as an adhesin for epithelial cells. The structural gene was cloned from M. tuberculosis and bacillus Calmette-Guerin, and the sequence was found to be identical between the two species. The calculated M,was smaller than the observed M,when analyzed by SDS/PAGE, This difference can be attributed to the Lys/Pro-rich repeats that occur at the C-terminal end of the protein and to a putative carbohydrate moiety, Glycosylation of HBHA appears to protect the protein from proteolytic degradation, which results in the removal of the C-terminal Lys/Pro-rich region responsible for binding of HBHA to sulfated carbohydrates. Evidence suggests that glycosylation is also important for HBHA-mediated hemagglutination and for certain immunologic properties of the protein. Finally, the absence of a signal peptide in the coding region of HBHA raises the possibility that this protein is not secreted via the general secretion pathway. C1 Inst Pasteur, INSERM U447, Lab Microbiol Genet & Mol, F-59019 Lille, France. Transgene SA, F-67082 Strasbourg, France. US FDA, Ctr Biol Evaluat & Res, Lab Mycobacteria, Rockville, MD 20852 USA. RP Inst Pasteur, INSERM U447, Lab Microbiol Genet & Mol, 1 Rue Calmette, F-59019 Lille, France. EM Camille.Locht@pasteur-lille.fr RI Bischoff, Rainer/H-5404-2011 NR 44 TC 93 Z9 102 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 13 PY 1998 VL 95 IS 21 BP 12625 EP 12630 DI 10.1073/pnas.95.21.12625 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 129DL UT WOS:000076447900098 PM 9770536 ER PT J AU Harris, A Adler, M Brink, J Lin, R Foehr, M Ferrer, M Langton-Webster, BC Harkins, RN Thompson, SA AF Harris, A Adler, M Brink, J Lin, R Foehr, M Ferrer, M Langton-Webster, BC Harkins, RN Thompson, SA TI Homologue scanning mutagenesis of heregulin reveals receptor specific binding epitopes SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID NEU DIFFERENTIATION FACTOR; EPIDERMAL GROWTH-FACTOR; CELLS; GLYCOPROTEIN; EXPRESSION; PROTEIN; LIGAND; ARIA AB The EGF domain of heregulin has all the receptor binding characteristics of full-length heregulin and has strong homology to the ligands for erbB-1. Despite this, it does not bind erbB-1 but instead binds erbB-3 and erbB-4, The sequence similarity between HRG and the erbB-1 ligands suggest that a few residues are responsible for receptor binding specificity. To determine the sequences involved in receptor binding, we performed homologue scanning mutagenesis on the EGF domain of HRG alpha using sequences of TGF alpha or EGF. We found three sets of mutations in the N-terminal subdomain that were responsible for receptor binding specificity, Mutations in the C-terminal subdomain affected the binding affinity, but did appear to confer any specificity. (C) 1998 Aademic Press. C1 Berlex Biosci, Dept Biodiscovery Res, Richmond, CA 94804 USA. Natl Ctr Toxicol Res, Dept Genet Toxicol, Jefferson, AR 72079 USA. LXR Biotechnol Inc, Mfg & Proc Dev, Richmond, CA 94804 USA. RP Thompson, SA (reprint author), Berlex Biosci, Dept Prot Biochem, 15049 San Pablo Ave, Richmond, CA 94804 USA. EM stewartthompson@berlex.com NR 17 TC 9 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 9 PY 1998 VL 251 IS 1 BP 220 EP 224 DI 10.1006/bbrc.1998.9436 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 132PM UT WOS:000076638800038 PM 9790934 ER PT J AU Wilkes, JG Sutherland, JB AF Wilkes, JG Sutherland, JB TI Sample preparation and high-resolution separation of mycotoxins possessing carboxyl groups SO JOURNAL OF CHROMATOGRAPHY B LA English DT Review DE reviews; mycotoxins; fumonisin B-1; ochratoxin A; citrinin ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ELECTROSPRAY MASS-SPECTROMETRY; HYDROLYZED FUMONISIN B-1; FAST-ATOM-BOMBARDMENT; F-SP-LYCOPERSICI; FUSARIUM-MONILIFORME; OCHRATOXIN-A; FLUORESCENCE DETECTION; ALTERNARIA-ALTERNATA; CAPILLARY ELECTROPHORESIS AB The chromatographic analysis of carboxyl-containing mycotoxins, such as fumonisin B-1, ochratoxin A, and citrinin, presents a continual challenge. Toxins must first be extracted from foods or tissues and then cleaned up before chromatographic separation and detection. Liquid-liquid extraction efficiencies for some carboxylic mycotoxins are marginal for spiked samples and uncertain for incurred residues. Immunoaffinity columns may be useful for concentrating mycotoxins from samples before chromatography. In almost every case, more than one analytical method must be used to confirm the identification of the mycotoxin. The fumonisins are especially troublesome to analyze because they are relatively insoluble in organic solvents, they are not separated easily by gas chromatography, and they do not respond to the usual absorbance or fluorescence detectors used in liquid chromatography. Fluorescence derivatization and electrospray liquid chromatography-mass spectrometry have now made it possible to detect trace levels of mycotoxins. The purity of mycotoxin standards for toxicological studies can be determined by liquid chromatography with either an evaporative light scattering detector or electrospray mass spectrometer. New developments in capillary electrophoresis, nonporous microsphere liquid chromatography, and detection methods for low-volatility compounds show promise for improving the analysis of mycotoxins in the future. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Sutherland, JB (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 104 TC 27 Z9 28 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD OCT 9 PY 1998 VL 717 IS 1-2 BP 135 EP 156 DI 10.1016/S0378-4347(97)00664-6 PG 22 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 134BW UT WOS:000076723800009 PM 9832244 ER PT J AU Nightingale, SL AF Nightingale, SL TI Off-label use of Haemophilus vaccine in combination with DTaP vaccine SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 5 Z9 5 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 OCT 7 PY 1998 VL 280 IS 13 BP 1128 EP 1128 DI 10.1001/jama.280.13.1128 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 124YR UT WOS:000076210800007 PM 9777799 ER PT J AU Nightingale, SL AF Nightingale, SL TI Questions raised regarding benefit of albumin or PPF for seriously ill patients SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 5 Z9 5 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 OCT 7 PY 1998 VL 280 IS 13 BP 1128 EP 1128 DI 10.1001/jama.280.13.1128 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 124YR UT WOS:000076210800006 PM 9777799 ER PT J AU Nightingale, SL AF Nightingale, SL TI New safety information added to antiretroviral package inserts SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 5 Z9 5 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 OCT 7 PY 1998 VL 280 IS 13 BP 1128 EP 1128 DI 10.1001/jama.280.13.1128 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 124YR UT WOS:000076210800005 PM 9777799 ER PT J AU Nightingale, SL AF Nightingale, SL TI Crohn's disease treatment approved SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 5 Z9 5 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 OCT 7 PY 1998 VL 280 IS 13 BP 1128 EP 1128 DI 10.1001/jama.280.13.1128 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 124YR UT WOS:000076210800004 PM 9777799 ER PT J AU Hayakawa, T Chang, MCJ Bell, JM Seeman, R Rapoport, SI Appel, NM AF Hayakawa, T Chang, MCJ Bell, JM Seeman, R Rapoport, SI Appel, NM TI Fatty acid incorporation depicts brain activity in a rat model of Parkinson's disease SO BRAIN RESEARCH LA English DT Article DE arachidonic acid; autoradiography; basal ganglia; brain metabolism; fatty acid; functional brain imaging; 6-hydroxydopamine; Parkinson's disease; phospholipase A(2) ID CHOLINERGIC STIMULATION; UNANESTHETIZED RATS; GLUCOSE-UTILIZATION; ARACHIDONIC-ACID; SUBSTANTIA NIGRA; DOPAMINE; 6-HYDROXYDOPAMINE; RELEASE AB Following pulse labeling with [H-3]arachidonic acid ([H-3]AA), its incorporation pattern in brain reflects regional changes in neurotransmitter signal transduction using phospholipase A(2). that is, functional activity. In a rat model of Parkinson's disease, unilateral 6-hydroxydopamine lesion in the substantia nigra, [H-3]AA acid incorporation from blood was increased in cerebral cortex, caudate putamen, globus pallidus, entopeduncular nucleus, subthalamic nucleus and substantia nigra pars reticulata ipsilateral to the lesion. This increased [H-3]AA incorporation likely reflects disinhibition of basal ganglia and cortical circuits secondary to absent inhibitory nigrostriatal dopaminergic input. (C) 1998 Elsevier Science B.V. All rights reserved. C1 US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, Div Appl Pharmacol Res, Laurel, MD 20708 USA. NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. Tokyo Med & Dent Univ, Dept Neurosurg, Bunkyo Ku, Tokyo 113, Japan. RP Appel, NM (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, Div Appl Pharmacol Res, 8301 Muirkirk Rd,Room 2013, Laurel, MD 20708 USA. EM appeln@cder.fda.gov NR 25 TC 18 Z9 18 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 OCT 5 PY 1998 VL 807 IS 1-2 BP 177 EP 181 DI 10.1016/S0006-8993(98)00751-3 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 127TZ UT WOS:000076367800021 PM 9757030 ER PT J AU Goldenthal, KL Vaillancourt, JM Geber, A Lucey, DR AF Goldenthal, KL Vaillancourt, JM Geber, A Lucey, DR TI Preventive HIV type 1 vaccine clinical trials: A regulatory perspective SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACELLULAR PERTUSSIS VACCINES; INFECTION; EFFICACY; ISSUES; VOLUNTEERS; DESIGN AB The clinical development of a human immunodeficiency virus (HIV) vaccine should be planned so that adequate safety and efficacy data can be obtained in an efficient manner to permit a risk/benefit assessment. Phase 1 and 2 studies should support the selection of an appropriate vaccine formulation, dose and schedule for evaluation in efficacy trials, Evaluation of the immune response(s) elicited by an HIV vaccine has an important role, even early in clinical development. Immune assay results and viral detection/quantitation technology may be used to identify and characterize HIV infections occurring during the trials. Thus, information about the performance parameters of these assays is important. Considerable research and development may be needed in this regard, especially when multiple endemic HIV-1 subtypes (clades) are expected, Prior to initiating an efficacy trial, background epidemiological information (e.g., recent seroincidence, endemic clades), as well as safety and immunogenicity data with the candidate vaccine, should be obtained in the intended efficacy trial population. The effects of antiretroviral therapy use and sensitive viral detection assays on the evaluation of the primary efficacy end point (as well as secondary end points) are important considerations. The detailed statistical plan for an efficacy trial should consider the 95% confidence limits on the estimate of vaccine efficacy; this may be of exceptional importance when relatively low point estimates of efficacy are expected. C1 US FDA, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Goldenthal, KL (reprint author), US FDA, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, HFM-475,1401 Rockville Pike, Rockville, MD 20852 USA. NR 58 TC 5 Z9 5 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 1998 VL 14 SU 3 BP S333 EP S340 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 133CV UT WOS:000076669600022 PM 9814962 ER PT J AU Heyward, WL MacQueen, KM Goldenthal, KL AF Heyward, WL MacQueen, KM Goldenthal, KL TI HIV vaccine development and evaluation: Realistic expectations SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID REASSORTANT ROTAVIRUS VACCINE; HEPATITIS-B VACCINE; RHESUS-HUMAN; CONTROLLED TRIAL; RISK BEHAVIOR; EFFICACY; SAFETY; CHILDREN; VIRUS; AIDS AB As of January 1998, more than 85 vaccines for 24 clinical indications are currently licensed in the United States. From the time of discovery of the etiologic agent to the development of a licensed vaccine, many years have usually been required. Although many vaccines have been licensed on the basis of one efficacy trial, multiple vaccine concepts and multiple efficacy trials (both in the United States and internationally) have at times been necessary. Over a relatively short period of time, there has been remarkable progress in human immunodeficiency virus (HIV) vaccine development, with over 34 different HIV candidate vaccines having been tested in phase 1 trials, and three having been tested in phase 2 trials. In spite of our incomplete understanding of HIV pathogenesis and correlates of protection, the first phase 3 efficacy trial has been initiated in the U.S. and tentative plans have been announced for three other phase 3 efficacy trials with the most advanced HIV candidate vaccines to begin in the next 3 years. Like many previous vaccine development efforts, these initial HIV vaccine efficacy trials could be the first of many large-scale efficacy trials in the future, testing various vaccine design concepts among different high-risk populations in both developed and developing countries, The choice of when and how to proceed to phase 3 trials remains a complex decision, but it is likely that only through such trials will further knowledge be gained to advance this important effort and reach our goal of a safe and effective HIV vaccine. C1 Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Off Commun, Natl Ctr HIV STD & TB Prevent, Atlanta, GA 30333 USA. US FDA, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Gaithersburg, MD 20852 USA. RP Heyward, WL (reprint author), Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Off Commun, Natl Ctr HIV STD & TB Prevent, Mailstop E-06,1600 Clifton Rd, Atlanta, GA 30333 USA. NR 42 TC 15 Z9 15 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 1998 VL 14 SU 3 BP S205 EP S210 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 133CV UT WOS:000076669600005 PM 9814945 ER PT J AU Pi-Sunyer, FX Becker, DM Bouchard, C Carleton, RA Colditz, GA Dietz, WH Foreyt, JP Garrison, RJ Grundy, SM Hansen, BC Higgins, M Hill, JO Howard, BV Kuczmarski, RJ Kumanyika, S Legako, RD Prewitt, TE Rocchini, AP Smith, PL Snetselaar, LG Sowers, JR Weintraub, M Williamson, DF Wilson, GT AF Pi-Sunyer, FX Becker, DM Bouchard, C Carleton, RA Colditz, GA Dietz, WH Foreyt, JP Garrison, RJ Grundy, SM Hansen, BC Higgins, M Hill, JO Howard, BV Kuczmarski, RJ Kumanyika, S Legako, RD Prewitt, TE Rocchini, AP Smith, PL Snetselaar, LG Sowers, JR Weintraub, M Williamson, DF Wilson, GT CA Expert Panel Identification, Evaluation, T TI Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: Executive summary SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article C1 Columbia Univ, St Lukes Roosevelt Hosp Ctr, Obes Res Ctr, New York, NY 10025 USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. Univ Laval, Phys Act Sci Lab, St Foy, PQ G1K 7P4, Canada. Brown Univ, Sch Med, Pawtucket, RI USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Nutr & Phys Act, Atlanta, GA USA. Baylor Coll Med, Nutr Res Clin, Houston, TX 77030 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. Univ Texas, SW Med Ctr, Ctr Human Nutr, Dallas, TX 75235 USA. Univ Maryland, Sch Med, Obes & Diabet Res Ctr, Baltimore, MD 21201 USA. Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. Univ Colorado, Hlth Sci Ctr, Ctr Human Nutr, Denver, CO USA. Medlant Res Inst, Washington, DC USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. Univ Illinois, Dept Human Nutr & dietet MC 517, Chicago, IL USA. Prime Care Canyon Pk Family Phys Inc, Edmond, OK USA. Loyola Univ, Med Ctr, Dept Prevent Med & Epidemiol, Maywood, IL 60153 USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Johns Hopkins Asthma & Allergy Ctr, Div Pulm & Crit Care Med, Baltimore, MD USA. Univ Iowa, Dept Prevent Med, Iowa City, IA USA. Wayne State Univ, Sch Med, Div Endocrinol Metab & Hypertens, Univ Hlth Ctr, Detroit, MI USA. US FDA, Div Diabet Tranlat K 10, Rockville, MD 20857 USA. Rutgers Eating Disorders Clin, Piscataway, NJ USA. RP Pi-Sunyer, FX (reprint author), Columbia Univ, St Lukes Roosevelt Hosp Ctr, Obes Res Ctr, New York, NY 10025 USA. RI Hansen, Barbara/J-8723-2012; Bouchard, Claude/A-7637-2009; Colditz, Graham/A-3963-2009 OI Hansen, Barbara/0000-0001-9646-3525; Colditz, Graham/0000-0002-7307-0291 NR 0 TC 486 Z9 506 U1 3 U2 56 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 1998 VL 68 IS 4 BP 899 EP 917 PG 19 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 124QE UT WOS:000076192600021 ER PT J AU Gholami, P Lew, SQ Klontz, KC AF Gholami, P Lew, SQ Klontz, KC TI Raw shellfish consumption among renal disease patients - A risk factor for severe Vibrio vulnificus infection SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE renal disease; shellfish; Vibrio infections AB Background: Raw shellfish-associated Vibrio vulnificus septicemia, with a case-fatality rate of nearly 50%, occurs most commonly in immunocompromised patients or those with liver disease. Methods: Sixty patients with renal disease treated with hemodialysis at The George Washington University and a awaiting renal transplantation completed an initial survey that assessed their ra iv shellfish eating habits and knowledge regarding the pathogen V. vulnificus. Patients were then given educational materials describing the risks of eating raw shellfish and, one month later, completed a second sun ey that assessed their knowledge retention and intent to eat or not eat raw shellfish in the future. Results: Sixty of 68 (88%) eligible patients completed the survey. Forty-eight percent of patients reported having eaten raw shellfish after being diagnosed with kidney disease, with the highest rates reported among subjects less than or equal to 49 years old and subjects with more than a high school education. Prior to receiving the educational materials, no patient had heard of the pathogen I: vulnificus. Three quarters of patients reported never having been advised by a physician to avoid eating raw shellfish. One month after reading the educational materials, 75% of patients said they would refrain from eating raw shellfish in the future. Conclusion: In view of their immunocompromised status, patients with end-stage renal disease should be counseled to abstain from eating raw shellfish. C1 US FDA, Epidemiol Branch, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. George Washington Univ, Dept Med, Masters Publ Hlth Program, Div Renal Dis & Hypertens, Washington, DC USA. RP Klontz, KC (reprint author), US FDA, Epidemiol Branch, Ctr Food Safety & Appl Nutr, HFS-728,200 C St SW, Washington, DC 20204 USA. NR 8 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 1998 VL 15 IS 3 BP 243 EP 245 DI 10.1016/S0749-3797(98)00051-8 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 122ZR UT WOS:000076101800011 PM 9791643 ER PT J AU Meredith, JM Turek, FW Levine, JE AF Meredith, JM Turek, FW Levine, JE TI Effects of gonadotropin-releasing hormone pulse frequency modulation on the reproductive axis of photoinhibited male Siberian hamsters SO BIOLOGY OF REPRODUCTION LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; PHOTOSTIMULATED DJUNGARIAN HAMSTERS; PULSATILE LH-RELEASE; PHODOPUS-SUNGORUS; TESTICULAR GROWTH; PITUITARY-CELLS; GOLDEN-HAMSTERS; RHESUS-MONKEY; SECRETION; RAT AB In Siberian hamsters, photostimulation evokes differential release of the gonadotropins, with FSH rising rapidly and LH levels rising much later. We have tested the hypothesis that differential release of gonadotropins in this species can be mediated by changes in the frequency of pulsatile GnRH stimulation. Photoinhibited Siberian hamsters received GnRH pulses at frequencies of 1 pulse every 45 (fast), 90 (medium), or 180 min (slow). Animals were killed at 0, 3, 5, 10, 20, and 30 days after treatment. There was a clear GnRH pulse frequency effect on LH release, with fast pulses > medium pulses > slow pulses > short-day (SD) controls. In addition, 10 days of fast-frequency GnRH pulses produced LH levels significantly greater than LH levels in animals exposed to in days of medium or slow GnRH pulse frequencies. Pulsatile GnRH produced the following serum FSH relationships: medium pulses > fast pulses > SD. The FSH response to slow GnRH frequency fell between the two faster frequencies. The effect of GnRH pulse frequency an paired testes weight was as follows: fast pulses = medium pulses > slow pulses > SD controls. The differing GnRH pulse frequencies produced the following testosterone relationships; fast pulses > medium pulses = slow pulses = SD controls. These results agree with studies showing that slower GnRH pulse frequencies facilitate FSH release, while faster GnRH pulse frequencies favor LH release. Our observations are also consistent with the idea that the singular release of FSH after transfer of hamsters to a long-day photoperiod is mediated by alterations in the frequency of endogenous pulsatile GnRH release. C1 Northwestern Univ, Dept Neurobiol & Physiol, Evanston, IL 60208 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Levine, JE (reprint author), Northwestern Univ, Dept Neurobiol & Physiol, 2153 Sheridan Rd, Evanston, IL 60208 USA. EM jlevine@nwu.edu FU NICHD NIH HHS [P30-HD28048, P01-HD21921, R01-HD09885] NR 29 TC 21 Z9 21 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD OCT PY 1998 VL 59 IS 4 BP 813 EP 819 DI 10.1095/biolreprod59.4.813 PG 7 WC Reproductive Biology SC Reproductive Biology GA 124NF UT WOS:000076188100013 PM 9746730 ER PT J AU Mahmood, H AF Mahmood, H TI Response to the comments on the commentary 'Prediction of absolute bioavailability for drugs using oral and renal clearance following a single oral dose: A critical view' SO BIOPHARMACEUTICS & DRUG DISPOSITION LA English DT Letter ID PHARMACOKINETICS; CIBENZOLINE; TIOPRONIN C1 US FDA, Div Pharmaceut Evaluat HFD 860 1, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20852 USA. RP Mahmood, H (reprint author), US FDA, Div Pharmaceut Evaluat HFD 860 1, Off Clin Pharmacol & Biopharmaceut, 1451 Rockville Pike, Rockville, MD 20852 USA. NR 10 TC 1 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0142-2782 J9 BIOPHARM DRUG DISPOS JI Biopharm. Drug Dispos. PD OCT PY 1998 VL 19 IS 7 BP 483 EP 484 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 129VW UT WOS:000076485600010 ER PT J AU Holada, K Mondoro, TK Muller, J Vostal, JG AF Holada, K Mondoro, TK Muller, J Vostal, JG TI Increased expression of phosphatidylinositol-specific phospholipase C resistant prion proteins on the surface of activated platelets SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE prion; platelets; platelet activation; flow cytometry; monoclonal antibody 3F4 ID SCRAPIE; DISEASE; SHEETS AB The surface expression of prion protein (PrPC) on human platelets, as detected by now cytometry with the monoclonal antibody 3F4, increased more than two-fold (4300 v 1800 molecules/platelet) after full activation. Maximal surface expression of PrPC occurred within 3 min of platelet activation and declined to approximately half of maximal levels by 2 h at 37 degrees C. In comparison. PrPC on the surface of platelets, activated at 22 degrees C took 10 min to reach maximum but then remained constant for 2 h, In sonicated resting platelets, PrPC and P-selectin remained in intact granules after subcellular fractionation, Both glycoproteins were found in the ruptured membranes of activated platelets, suggesting that the PrPC was translocated from internal granules to the plasma membrane during activation, as is P-selectin, Platelet PrPC was not removed from the surface of platelets by phosphatidylinositol-specific phospholipase C (PIPLC) treatment but was degraded by proteinase K. Platelets may serve as a useful model for following the cellular processing of PrPC. C1 US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Vostal, JG (reprint author), US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bldg 29,Room 323,HFM-335,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 24 TC 44 Z9 44 U1 0 U2 0 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 OCT PY 1998 VL 103 IS 1 BP 276 EP 282 DI 10.1046/j.1365-2141.1998.01032.x PG 7 WC Hematology SC Hematology GA 131KM UT WOS:000076575200042 PM 9792322 ER PT J AU Takahashi, S Tamano, S Hirose, M Kimoto, N Ikeda, Y Sakakibara, M Tada, M Kadlubar, FF Ito, N Shirai, T AF Takahashi, S Tamano, S Hirose, M Kimoto, N Ikeda, Y Sakakibara, M Tada, M Kadlubar, FF Ito, N Shirai, T TI Immunohistochemical demonstration of carcinogen-DNA adducts in tissues of rats given 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP): Detection in paraffin-embedded sections and tissue distribution SO CANCER RESEARCH LA English DT Article ID FOOD MUTAGENS; HETEROCYCLIC AMINES; COOKED-FOOD; IDENTIFICATION; ANTIBODIES; CHROMATOGRAPHY; LYMPHOMA; EXPOSURE; PROSTATE; SMOKERS AB A polyclonal antibody against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA adducts was raised for their immunohistochemical demonstration in paraffin-embedded sections. Specificity of this antibody was confirmed by competitive ELISA, Positive signals were immunohistochemically detected in acetone-fixed but not in formalin- or ethanol-fixed sections from F344 rats treated by gavage with a single dose of PhIP at 37.5-300 mg/kg and killed at 1, 2, and 7 days thereafter. Dose-dependent positive staining was observed in almost all organs of both sexes, including the colon, prostate, and mammary gland but largely independent of the tumor response. Repair activity, judged by disappearance of adducts with time, differed according to the organ or cell type. One exception was hepatocytes, the liver incidentally being a nontarget organ. The results suggest that the generated antibody is applicable for detection of cells targeted by PhIP in paraffin-embedded sections and also for the investigation of the mechanisms of PhIP-carcinogenesis. C1 Nagoya City Univ, Sch Med, Dept Pathol 1, Mizuho Ku, Nagoya, Aichi 4678601, Japan. Daiyukai Inst Med Sci, Ichinomiya 4910113, Japan. Aichi Shukutoku Univ, Aichi 4801100, Japan. Natl Ctr Toxicol Res, Res Off, Jefferson, AR 72079 USA. RP Takahashi, S (reprint author), 1 Kawasumi,Mizuho Cho,Mizuho Ku, Nagoya, Aichi 4678601, Japan. NR 33 TC 40 Z9 40 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 1 PY 1998 VL 58 IS 19 BP 4307 EP 4313 PG 7 WC Oncology SC Oncology GA 125CD UT WOS:000076219100021 PM 9766658 ER PT J AU Lopatina, NG Vanyushin, BF Cronin, GM Poirier, LA AF Lopatina, NG Vanyushin, BF Cronin, GM Poirier, LA TI Elevated expression and altered pattern of activity of DNA methyltransferase in liver tumors of rats fed methyl-deficient diets SO CARCINOGENESIS LA English DT Article ID ACID-DEFINED DIETS; CHOLINE-DEVOID DIET; P53 GENE; HYPOMETHYLATION; CANCER; HEPATOCARCINOGENESIS; HYPERMETHYLATION; APPEARANCE; CELLS AB DNA methyltransferase (MTase) activity in nuclear extracts from neoplastic and preneoplastic livers of rats fed a methyl-deficient diet (MDD) is elevated compared with that seen in the livers of control rats. Nuclear proteins were prepared in the presence of protease inhibitors including trans-epoxy succinyl-L-leucylamido-(4-guanido)butane and were fractionated by isoelectric focusing. In normal, control liver, two distinct MTase fractions were observed. In MDD-induced malignant liver, a third fraction, in addition to the previous two, was also seen. Both the DNA substrate and the cytosine site specificities of the third MTase fraction differ from those of the other two fractions. The distinct MTase activity in liver tumor has significantly more de novo MTase activity than do the MTase fractions of normal, control liver. Thus, normal and neoplastic rat livers differ in DNA MTase fractionation patterns and site specificities, The altered DNA MTase activity observed in rat liver tumors caused by MDDs may be one of the critical factors contributing to cancer formation through abnormal DNA methylation. C1 Natl Ctr Toxicol Res, Div Nutr Toxicol, Jefferson, AR 72079 USA. RP Poirier, LA (reprint author), Natl Ctr Toxicol Res, Div Nutr Toxicol, NCTR Dr, Jefferson, AR 72079 USA. NR 35 TC 30 Z9 34 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 OCT PY 1998 VL 19 IS 10 BP 1777 EP 1781 DI 10.1093/carcin/19.10.1777 PG 5 WC Oncology SC Oncology GA 130GL UT WOS:000076511800010 PM 9806158 ER PT J AU Faisal, M MacIntyre, EA Adham, KG Tall, BD Kothary, MH La Peyre, JF AF Faisal, M MacIntyre, EA Adham, KG Tall, BD Kothary, MH La Peyre, JF TI Evidence for the presence of protease inhibitors in eastern (Crassostrea virginica) and Pacific (Crassostrea gigas) oysters SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE oyster; Perkinsus marinus; protease inhibitors; Vibrio vulnificus ID MARINUS EXTRACELLULAR PRODUCTS; PERKINSUS-MARINUS; VIBRIO-VULNIFICUS; ELASTOLYTIC PROTEASE; ALPHA-MACROGLOBULIN; RAINBOW-TROUT; UNITED-STATES; DISEASE; ALPHA-2-MACROGLOBULIN; EPIZOOTIOLOGY AB The plasma of eastern (Crassostrea virginica) and Pacific (Crassostrea gigas) oysters were compared for levels of inhibitory activities against a variety of proteases. Representatives of the serine, cysteine, metallo and aspartic protease mechanistic classes were analyzed, including extracellular proteases produced by two oyster-associated pathogens; Perkinsus marinus and Vibrio io vulnificus. In comparison to C. virginica, C. gigas plasma exhibited significantly higher specific inhibition levels (ng protease inhibited/mu g plasma protein) for papain (P < 0.001), pepsin (P < 0.001), P. marinus protease (P < 0.001), trypsin (P = 0.015), and V. vulnificus protease (P <0.001). Plasma of C. gigas did not inhibit the metalloprotease thermolysin. Instead, a significant increase in substrate hydrolysis was seen in wells containing plasma and thermolysin in comparison to wells containing thermolysin only. A similar trend was noted for thermolysin with the eastern oyster samples. These studies indicate the presence of protease inhibitors in the plasma of Crassostrea spp., which may have an impact upon host defense mechanisms, in addition to other physiological roles. (C) 1998 Elsevier Science Inc. All rights reserved. C1 Coll William & Mary, Sch Marine Sci, Virginia Inst Marine Sci, Dept Environm Sci, Gloucester Point, VA 23062 USA. US FDA, Microbial Ecol Branch, Washington, DC 20204 USA. RP Faisal, M (reprint author), Coll William & Mary, Sch Marine Sci, Virginia Inst Marine Sci, Dept Environm Sci, Gloucester Point, VA 23062 USA. EM faisal@vims.edu OI Tall, Ben/0000-0003-0399-3629 NR 38 TC 44 Z9 44 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0305-0491 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD OCT PY 1998 VL 121 IS 2 BP 161 EP 168 DI 10.1016/S0305-0491(98)10084-6 PG 8 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA 150WB UT WOS:000077687800006 ER PT J AU Knatterud, GL Rockhold, FW George, SL Barton, FB Davis, CE Fairweather, WR Honohan, T Mowery, R O'Neill, R AF Knatterud, GL Rockhold, FW George, SL Barton, FB Davis, CE Fairweather, WR Honohan, T Mowery, R O'Neill, R TI Guidelines for quality assurance in multicenter trials: A position paper SO CONTROLLED CLINICAL TRIALS LA English DT Article DE quality control; monitoring; data integrity; auditing; errors; scientific misconduct ID BREAST-CANCER TRIALS; CLINICAL-TRIALS; CRITERIA; OUTCOMES; SYSTEMS AB In the wake of reports of falsified data in one of the trials of the National Surgical Adjuvant Project for Breast and Bowel Cancer supported by the National Cancer Institute, clinical trials came under close scrutiny by the public, the press, and Congress. Questions were asked about the quality and integrity of the collected data and the analyses and conclusions of trials. In 1995, the leaders of the Society for Clinical Trials (the Chair of the Policy Committee, Dr. David DeMets, and the President of the Society, Dr. Sylvan Green) asked two members of the Society (Dr. Genell Knatterud and Dr. Frank Rockhold) to act as co-chairs of a newly formed subcommittee to discuss the issues of data integrity and auditing. In consultation with Drs. DeMets and Green, the co-chairs selected other members (Ms. France Barton, Dr. C.E. Davis, Dr. Bill Fairweather, Dr. Stephen George, Mr. Tom Honohan, Dr. Richard Mowery, and Dr. Robert O'Neill) to serve on the subcommittee. The subcommittee considered "how clean clinical trial data should be, to what extent auditing procedures are required, and who should conduct audits and how often." During the initial discussions, the subcommittee concluded that data auditing was insufficient to achieve data integrity. Accordingly, the subcommittee prepared this set of guidelines for standards of quality assurance for multicenter clinical trials. We include recommendations for appropriate action if problems are detected. (C) Elsevier Science Inc. 1998. C1 Maryland Med Res Inst, Baltimore, MD 21210 USA. Merck Res Labs, W Point, PA USA. Univ N Carolina, Chapel Hill, NC USA. US FDA, Rockville, MD 20857 USA. Duke Univ, Med Ctr, Durham, NC USA. Rhone Poulenc Rorer, Collegeville, PA USA. NCI, Bethesda, MD 20892 USA. RP Knatterud, GL (reprint author), Maryland Med Res Inst, 600 Wyndhurst Ave, Baltimore, MD 21210 USA. NR 35 TC 40 Z9 43 U1 0 U2 7 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 1998 VL 19 IS 5 BP 477 EP 493 DI 10.1016/S0197-2456(98)00033-6 PG 17 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 115WC UT WOS:000075688400007 PM 9741868 ER PT J AU Broadbent, TA Broadbent, HS AF Broadbent, TA Broadbent, HS TI 1 similar to 1 The chemistry and pharmacology of indole-3-carbinol (indole-3-methanol) and 3-(methoxymethyl)indole. [Part I] SO CURRENT MEDICINAL CHEMISTRY LA English DT Review ID PERFORMANCE LIQUID-CHROMATOGRAPHY; WHEAT LEAF SEGMENTS; ELECTROKINETIC CAPILLARY CHROMATOGRAPHY; SENSITIZED AQUEOUS PHOTOOXIDATION; HYPERVALENT IODINE; 1-METHYL-3-INDOLEACETIC ACID; HORSERADISH-PEROXIDASE; 3-SUBSTITUTED INDOLES; INDOLYLMETHYL CATIONS; 3-INDOLEACETIC ACID AB Indole-3-carbinol (I3C) (2) is produced endogenously from naturally occurring glucosinolates contained in a wide variety of plant food substances including members of the family Cruciferae, and particularly members of the genus Brassica, whenever they are crushed or cooked. The acid environment of the gut very facilely converts it into a range of polyaromatic indolic compounds, e.g. (3,4,5), which appear to be responsible for many of the physiological effects observed following the ingestion of these foods. 3-(Methoxymethyl)indole (6) is formed with great ease whenever 2 contacts methylating agents, including methanol, and it is often found as a contaminant of 2, This contamination is often not recognized or easily removed because of the great similarities of the two in melting points and solubilities. However, their biological properties are essentially identical. These so-called chemopreventive compounds are important because of their enzyme induction and suppression, mutagenic, carcinogenic and, particularly, antimutagenic and anticarcinogenic properties. The natural occurrence, formation, preparation, identification, separation, quantification, chemical transformations and general toxicological properties of these substances are critically reviewed in detail in this paper of 146 references, the first of two parts. The enzyme induction and suppression, mutagenic, antimutagenic, mutagenic, anticarcinogenic and carcinogenic effects will be published later as Part II. At the present time it appears that these have considerable potential as natural prophylactic anticancer agents against certain common neoplasms, especially inasmuch modern diets are increasingly deficient in these vegetable-derived substances. C1 US FDA, Ctr Drug Evaluat & Res, ONDC, DNDC1,Div Neuropharmacol Drug Prod HFD120, Rockville, MD 20852 USA. RP Broadbent, TA (reprint author), US FDA, Ctr Drug Evaluat & Res, ONDC, DNDC1,Div Neuropharmacol Drug Prod HFD120, Woodmont 2,1451 Rockville Pike, Rockville, MD 20852 USA. NR 152 TC 31 Z9 32 U1 1 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD OCT PY 1998 VL 5 IS 5 BP 337 EP 352 PG 16 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 129QY UT WOS:000076475500001 PM 9756978 ER PT J AU Henderson, LO Marti, GE Gaigalas, A Hannon, WH Vogt, RF AF Henderson, LO Marti, GE Gaigalas, A Hannon, WH Vogt, RF TI Terminology and nomenclature for standardization in quantitative fluorescence cytometry SO CYTOMETRY LA English DT Article; Proceedings Paper CT Conference on Quantitative Immunofluorescence Measurement CY NOV, 1997 CL OTTAWA, CANADA DE flow cytometry; fluorescence intensity; molecules of equivalent soluble fluorochrome; MESF; antibody binding capacity; ABC; cell receptors; quality control; standardization AB Terminology in any field is a complex mix of established conventions, accepted usages, disputed terms, and occasional misnomers. The terminology that has evolved for quantitative fluorescence cytometry (QFCM) is especially multifarious, in part because QFCM encompasses a range from subjective visual assessments to objective photon counts. Thus, while descriptive terms such as "dim" and "bright" are still quite useful, quantitative terms such as "binding capacity" should be used with collective understanding of their exact meanings. This article reviews current usage and proposes definitions that, with refinement from suppliers and users of QFCM technology, can provide the required clarity (C) 1998 Wiley-Liss,Inc.(dagger). C1 Ctr Dis Control & Prevent, Natl Diabet Reference Lab, Atlanta, GA USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NIST, Div Biotechnol, Gaithersburg, MD 20899 USA. RP Vogt, RF (reprint author), Mailstop F19, Atlanta, GA 30341 USA. EM rfv1@cdc.gov NR 11 TC 36 Z9 36 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOMETRY JI Cytometry PD OCT 1 PY 1998 VL 33 IS 2 BP 97 EP 105 DI 10.1002/(SICI)1097-0320(19981001)33:2<97::AID-CYTO3>3.0.CO;2-H PG 9 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 124WL UT WOS:000076205700002 PM 9773869 ER PT J AU Schwartz, A Marti, GE Poon, R Gratama, JW Fernandez-Repollet, E AF Schwartz, A Marti, GE Poon, R Gratama, JW Fernandez-Repollet, E TI Standardizing flow cytometry: A classification system of fluorescence standards used for flow cytometry SO CYTOMETRY LA English DT Article; Proceedings Paper CT Conference on Quantitative Immunofluorescence Measurement CY NOV, 1997 CL OTTAWA, CANADA DE flow cytometry; fluorescence standards; classification; standardization; calibration; instrument setup; fluorescence quantitation ID INTENSITY; CALIBRATION; ANTIGENS; DONORS; BLOOD AB The growing number of standards commercially available in the field of now cytometry makes it difficult to know which standards to use to obtain a desired level of quality assurance. A classification system of fluorescence standards has been developed on the basis of their physical characteristics. In turn, these physical characteristics determine the ability of the specific standards to perform selected functions, such as alignment, target referencing, compensation, and calibration. Knocking the properties and limitations of specific standards will help flow cytometer users to select the appropriate standard for the application that they will be performing, especially in regard to intra- and interlaboratory quality assurance. Common protocols used in conjunction with specific classifications of reference standards can provide unified analysis regions or window of analysis across different instruments and/or laboratories. In addition, specific classifications of calibration standards can help select those standards that will provide independent and direct comparison of instrument performance parameters, especially in studies involving multiple laboratories. Knowledge and understanding of the classification system can guide flow cytometer users in more efficient and accurate instrument setup and quality control when conducting research, as well as clinical applications. (C) 1998 Wiley-Liss, Inc. C1 Flow Cytometry Stand Corp, San Juan, PR USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Sigma Chem Co, St Louis, MO USA. Dept Clin & Tumor Immunol, Rotterdam, Netherlands. Univ Puerto Rico, Sch Med, Dept Pharmacol, San Juan, PR 00936 USA. RP Schwartz, A (reprint author), POB 194344, San Juan, PR 00919 USA. EM fcsc@caribe.net FU NCRR NIH HHS [RR 08224, G12-RR 03051] NR 35 TC 73 Z9 76 U1 1 U2 2 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 1 PY 1998 VL 33 IS 2 BP 106 EP 114 DI 10.1002/(SICI)1097-0320(19981001)33:2<106::AID-CYTO4>3.0.CO;2-H PG 9 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 124WL UT WOS:000076205700003 PM 9773870 ER PT J AU Zenger, VE Vogt, R Mandy, F Schwartz, A Marti, GE AF Zenger, VE Vogt, R Mandy, F Schwartz, A Marti, GE TI Quantitative flow cytometry: Inter-laboratory variation SO CYTOMETRY LA English DT Article; Proceedings Paper CT Conference on Quantitative Immunofluorescence Measurement CY NOV, 1997 CL OTTAWA, CANADA DE quantitative flow cytometry; molecular equivalent of soluble fluorochrome; antibody-binding capacity; microbead standards; calibration curve ID EXPRESSION; ANTIGENS; LYMPHOCYTES; STANDARDS; CELLS AB Quantitative how cytometry (QFCM) offers a means of standardization within and between flow cytometers, QFCM parameters were set by determining the antibody-binding capacity (ABC) of CD4, CD8, and CD3 cells from 10 normal donors with the use of eight FACScan flow cytometers. QC3 beads and a certified blank bead were used to set up the instruments. Fluorescein isothiocyanate (FITC) conjugated to molecular equivalents of soluble fluorochrome (MESF) microbead standards was used before and after the donor samples were run to ensure that the machines were operating consistently. Lyophilized cells (Cytotrol) were used as a target, to control for antigen expression in the cell preparation, Quantitative Simply Cellular (QSC) beads were used to establish a standard calibration curve for each of the FITC and phycoerythrin antibody conjugates on each of the instruments. Single-parameter fluorescent histograms derived from list-mode files were used to calculate the slope (coefficient of response), intercept (zero channel), number of channels per decade, and ABC or MESF threshold (blank bead). The fluorescence intensity (geometric mean) of the positive and negative donor cell populations was compared with the standard curves, and the ABCs were calculated. The results show consistent instrument performance between laboratories. However, after standardization of CD3, CD4, and CD8 ABCs to microbeads, large variations were noted between donors and laboratories. The source of this variation does not appear to be in the instrumentation but may be due to the lack of an unified set-up protocol, introducing issues of antibody saturation, methods for whole blood lysis and fixation, and the behavior of the microbead standards. (C) 1998 Wiley-Liss,Inc.(dagger). C1 NIH, US FDA, Div Cellular & Gene Therapies, Off Therapeut Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Ctr Dis Control, Atlanta, GA 30333 USA. Lab Ctr Dis Control, Ottawa, ON, Canada. Carribean Microparticles, Hato Rey, PR USA. RP Marti, GE (reprint author), NIH, US FDA, Div Cellular & Gene Therapies, Off Therapeut Res & Review,Ctr Biol Evaluat & Res, Bldg 29B,Rm 2NN08,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 21 TC 40 Z9 40 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOMETRY JI Cytometry PD OCT 1 PY 1998 VL 33 IS 2 BP 138 EP 145 DI 10.1002/(SICI)1097-0320(19981001)33:2<138::AID-CYTO8>3.0.CO;2-F PG 8 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 124WL UT WOS:000076205700007 PM 9773874 ER PT J AU Lenkei, R Gratama, JW Rothe, G Schmitz, G D'hautcourt, JL Arekrans, A Mandy, F Marti, G AF Lenkei, R Gratama, JW Rothe, G Schmitz, G D'hautcourt, JL Arekrans, A Mandy, F Marti, G TI Performance of calibration standards for antigen quantitation with flow cytometry SO CYTOMETRY LA English DT Article; Proceedings Paper CT Conference on Quantitative Immunofluorescence Measurement CY NOV, 1997 CL OTTAWA, CANADA DE calibration; standards; quantitative; flow cytometry ID ANTIBODY-BINDING CAPACITY; PERIPHERAL-BLOOD; ACTIVATION MARKERS; IMMUNE ACTIVATION; HIV DISEASE; HLA-DR; EXPRESSION; LYMPHOCYTES; PROGRESSION; MEMBRANE AB In the frame of the activities initiated by the Task Force for Antigen Quantitation of the European Working Group on Clinical Cell Analysis (EWGCCA), an experiment was conducted to evaluate microbead standards used for quantitative flow cytometry (QFCM). An unified window of analysis UWA) was established on three different instruments (EPICS XL [Coulter Corporation, Miami, FL], FACScan and FAGS Calibur [Becton Dickinson, San Jose, CA] with QC3 microbeads (FCSC, PR). By using this defined fluorescence intensity scale, the performance of several monoclonal antibodies directed to CD3, CD4, and CD8 (conjugated and unconjugated), from three manufacturers (BDIS, Coulter [Immunotech], and DAKO) was tested. In addition, the QIFI system (DAKO) and QuantiBRITE (BDIS), and a method of relative fluorescence intensity (RFI, method of Giorgi), were compared. mAbs reacting with three more antigens, CD16, CD19, and CD38 were tested on the FACScan instrument. Quantitation was carried out using a single batch of cryopreserved peripheral blood leukocytes, and all tests mere performed as single color analyses. Significant correlations were observed between the antibody-binding capacity (ABC) values of the same CD antigen measured with various calibrators and with antibodies differing in respect to vendor, labeling and possible epitope recognition. Despite the significant correlations, the ABC values of most monoclonal antibodies differed by 20-40% when determined by the different fluorochrome conjugates and different calibrators. The results of this study indicate that, at the present stage of QFCM consistent ABC values may be attained between laboratories provided that a specific calibration system is used including specific calibrators, reagents, and protocols. (C) 1998 Wiley-Liss,Inc. C1 St Gorans Hosp, Flow Cytometry Lab, CALAB Res, NOVA Med, S-11281 Stockholm, Sweden. Univ Hosp, Dr Daniel Den Hoed Canc Ctr, Dept Clin & Tumor Immunol, Rotterdam, Netherlands. Univ Regensburg, Inst Clin Chem & Lab Med, D-93042 Regensburg, Germany. Warguignies Hosp, Cytometry Lab, Boussu, Belgium. Becton Dickinson, Stockholm, Sweden. Bur Labs & Res Serv, Ottawa, ON, Canada. Fed Ctr AIDS NHW, Ottawa, ON, Canada. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Lenkei, R (reprint author), St Gorans Hosp, Flow Cytometry Lab, CALAB Res, NOVA Med, S-11281 Stockholm, Sweden. OI Schmitz, Gerd/0000-0002-1325-1007 NR 32 TC 64 Z9 65 U1 2 U2 4 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 1 PY 1998 VL 33 IS 2 BP 188 EP 196 DI 10.1002/(SICI)1097-0320(19981001)33:2<188::AID-CYTO13>3.0.CO;2-Q PG 9 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 124WL UT WOS:000076205700012 PM 9773879 ER PT J AU Haffner, ME AF Haffner, ME TI Designing clinical trials to study rare disease treatment SO DRUG INFORMATION JOURNAL LA English DT Article DE orphan drugs; clinical trial design; Orphan Drug Act; Office of Orphan Products Development; rare diseases AB This paper provides an overview of the design of clinical trials for rare diseases and the impact of the Orphan Drug Act on the successful study of diseases found in small, widely dispersed patient populations. Orphan drugs are defined. Randomized, placebo-control trials may not always be an option for studying orphan drugs; designs which may work better include: open protocol, open label, historical control, crossover trials, withdrawal design trials, or trials with surrogate endpoints. Each of these is discussed The benefits of studying orphan drugs and the procedure for approval of trial design by the Food and Drug Administration are outlined. C1 US FDA HF 35, Off Orphan Prod Dev, Rockville, MD 20878 USA. RP Haffner, ME (reprint author), US FDA HF 35, Off Orphan Prod Dev, 5600 Fishers Lane,Rm 8-73, Rockville, MD 20878 USA. NR 0 TC 3 Z9 3 U1 0 U2 4 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 1998 VL 32 IS 4 BP 957 EP 960 PG 4 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA V2589 UT WOS:000165531300013 ER PT J AU Sensabaugh, SM AF Sensabaugh, SM TI A primer on CBER's regulatory review structure and process SO DRUG INFORMATION JOURNAL LA English DT Article DE CBER; regulatory affairs; project management; biological products; review process AB The Center for Biologics Evaluation and Research (CBER) is the Food and Drug Administration (FDA) component responsible for ensuring the safety, potency purity, and efficiency of biological products intended for use in the treatment, prevention, and cure of human diseases. As technology and medical research move forward in the development of novel biological products to aid in this endeavor regulatory affairs and project management professionals are finding that they are interacting with CBER for the first time and that these interactions are increasing in frequency. The purpose of this article is to facilitate these interactions by providing a general understanding of CBER. Areas to be discussed include how CBER is unique as an FDA center; its areas of responsibility, the authority under which CBER operates, its regulatory mechanisms for review and approval, and the center's organizational structure. Also discussed is the manner in which CBER forms teams for review and approval of biological product submissions, responsibility of these team members, and management of CBER's review process. C1 US FDA, Off Ctr Director, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Sensabaugh, SM (reprint author), US FDA, Off Ctr Director, Ctr Biol Evaluat & Res, WOC 1,200N-HFM-90,1401 Rockville Pike, Rockville, MD 20852 USA. NR 13 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 1998 VL 32 IS 4 BP 1011 EP 1030 PG 20 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA V2589 UT WOS:000165531300022 ER PT J AU Sensabaugh, SM AF Sensabaugh, SM TI CBER's new Managed Review Process: A managed and integrated regulatory process which is continuous from discovery to post marketing SO DRUG INFORMATION JOURNAL LA English DT Article DE CBER; Managed Review Process; project management; performance goals; milestones AB One of the goals of the Center for Biologics Evaluation and Research's (CBER's) strategic vision for 2004 is: "a managed and integrated regulatory process which is continuous from discovery through post marketing." A strategy utilized to reach this goal is to apply the principles of managed review to the entire regulatory process. Managed review principles include the design of a review process which is streamlined, consistent, and efficient. Control of this review process is through performance goals in the form of review events which move the process forward. CBER has extended and enhanced its current Managed Review Process, thereby achieving this goal. This new Managed Review Process is presently being implemented in the center It spans from discovery to post marketing, includes all regulatory mechanisms used for submission review and approval, proposes a change in the review team leadership structure, reinforces the importance of project management activities, and enhances performance goals through the addition of new review milestones and target dates. C1 US FDA, Off Ctr Director, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Sensabaugh, SM (reprint author), US FDA, Off Ctr Director, Ctr Biol Evaluat & Res, WOC 1,200N-HFM-90,1401 Rockville Pike, Rockville, MD 20852 USA. NR 2 TC 1 Z9 1 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 1998 VL 32 IS 4 BP 1031 EP 1041 PG 11 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA V2589 UT WOS:000165531300023 ER PT J AU Barton, BL AF Barton, BL TI International conference on harmonization - Good clinical practices update SO DRUG INFORMATION JOURNAL LA English DT Article DE International Conference on Harmonization; Good Clinical Practices; Food and Drug Administration AB This paper presents an introduction to the "International Conference on Harmonization Good Clinical Practices Consolidated Guideline" for professionals who are already familiar with Food and Drug Administration (FDA) clinical trial standards. A brief background on the International Conference on Harmonization (ICH) is provided ICH-GCP is then compared to FDA standards. ICH guidelines are well supported by industry and FDA. As a result of ICH, regulatory requirements are becoming clearer and more harmonized the quality of clinical studies is improving, and the acceptance of foreign data is increasing within the ICH regions. Harmonization of the format and content of marketing applications, which is anticipated to be completed in the next few years, will bring more benefits. C1 US FDA, Ctr Drug Evaluat & Res, OC, DSI,CIB HRD 344, Rockville, MD 20855 USA. RP Barton, BL (reprint author), US FDA, Ctr Drug Evaluat & Res, OC, DSI,CIB HRD 344, 7520 Standish Pl,Room 125, Rockville, MD 20855 USA. NR 1 TC 2 Z9 2 U1 2 U2 5 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 1998 VL 32 IS 4 BP 1143 EP 1147 PG 5 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA V2589 UT WOS:000165531300034 ER PT J AU Chen, ML AF Chen, ML TI Ethnic factors in new drug evaluations: Pharmacokinetic and pharmacodynamic considerations SO DRUG INFORMATION JOURNAL LA English DT Meeting Abstract C1 US FDA HFD 870, Div Pharmaceut Evaluat 2, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DRUG INFORMATION ASSOCIATION PI FORT WASHINGTON PA 501 OFFICE CENTER DR, STE 450, FORT WASHINGTON, PA 19034-3212 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD OCT-DEC PY 1998 VL 32 SU S BP 1299S EP 1299S PG 1 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA V2590 UT WOS:000165531400023 ER PT J AU Chi, GYH AF Chi, GYH TI Multiple testings: Multiple comparisons and multiple endpoints SO DRUG INFORMATION JOURNAL LA English DT Article DE multiple comparisons; closed testing procedure; multiple endpoints; primary, coprimary, secondary endpoints; global test; clinical decision rule; type I error; strong control; power; bootstrap; clinical trials AB This paper gives a brief overview of some issues and some general concepts related to multiple testing problems as they are encountered in clinical drug trials. Some recent methods for handling multiple comparisons ave discussed. Emphasis is given to the p-value-based procedures and the general closed testing procedure of Marcus, Peritz, and Gabriel (1), Examples are given to illustrate these procedures and to highlight some important issues. Regarding multiple endpoints, the discussion focuses on the need to have a better definition of what primary coprimary, and secondary endpoints should mean, and suggests that a clinical decision rule defined in terms of primary, coprimary, and relevant secondary endpoints is a clinically relevant way of reducing the dimensionality problem of multiple endpoints. These clinical decision rules, however often lack a statistical support structure. Further research in this area is needed. C1 US FDA, Div Biometr 1, Rockville, MD 20857 USA. RP Chi, GYH (reprint author), US FDA, Div Biometr 1, HFD-710,WOCII,FM 5050,5600 Fishers Lane, Rockville, MD 20857 USA. NR 26 TC 19 Z9 19 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 1998 VL 32 SU S BP 1347S EP 1362S PG 16 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA V2590 UT WOS:000165531400031 ER PT J AU Alesina, A Ardagna, S AF Alesina, A Ardagna, S TI Tales of fiscal adjustment SO ECONOMIC POLICY LA English DT Article; Proceedings Paper CT Economic-Policy Panel Discussion CY 1998 CL LONDON, ENGLAND SP Econ Policy, HM Treasury, Bank England AB This paper examines the evidence on fiscal adjustments in OECD countries from the early 1960s to today. The results shed light on the recently observed phenomenon of fiscal tightening that produces (non-Keynesian) expansionary effects. One interpretation is that a serious fiscal tightening increases demand Wealth rises when future tax burdens decline, and when interest rates decline credibility is restored and inflation or default risks abate. Both consumption and investment rise. For this effect to produce an expansion, the tightening must be sizeable and occur after a period of stress when the budget is quickly deteriorating and public debt is building up. Another interpretation emphasizes the supply side. Typically, a fiscal consolidation based on tax increases is short-lived. To be long lasting, it must include cuts in public employment, transfers and government wages. lo be politically possible, such a policy must be supported by trade unions. These measures result in more efficient labour markets and boost the supply side. Based both on statistical evidence and on a detailed analysis often cares of major fiscal adjustment, this article provides cautious support to the supply-side view, without denying a more limited role for the demand-side channel. C1 Harvard Univ, CBER, NBER, Cambridge, MA 02138 USA. Boston Coll, Chestnut Hill, MA 02167 USA. RP Alesina, A (reprint author), Harvard Univ, CBER, NBER, Cambridge, MA 02138 USA. NR 31 TC 25 Z9 27 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0266-4658 EI 1468-0327 J9 ECON POLICY JI Econ. Policy PD OCT PY 1998 IS 27 BP 487 EP 545 PG 59 WC Economics SC Business & Economics GA 138TB UT WOS:000076987900004 ER PT J AU Arichi, T Shirai, M Chen, M Nishioka, M Ikeda, K Takahashi, H Enomoto, N Saito, T Major, ME Nakazawa, T Akatsuka, T Feinstone, SM Berzofsky, JA AF Arichi, T Shirai, M Chen, M Nishioka, M Ikeda, K Takahashi, H Enomoto, N Saito, T Major, ME Nakazawa, T Akatsuka, T Feinstone, SM Berzofsky, JA TI T cell recognition of hypervariable region 1 from hepatitis C virus envelope protein with multiple class II MHC molecules in mice and humans: Preferential help for induction of antibodies the hypervariable region. SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. Yamaguchi Univ, Sch Med, Yamaguchi, Japan. Kagawa Med Sch, Dept Internal Med 3, Kagawa 76107, Japan. Kagawa Med Sch, Dept Transfus Med, Kagawa 76107, Japan. Nippon Med Sch, Tokyo 113, Japan. Tokyo Med & Dent Univ, Tokyo 113, Japan. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, 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 1998 VL 28 IS 4 SU S MA 10 BP 165A EP 165A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100012 ER PT J AU Hsia, CC Minemura, M Kashanchi, F Kim, SJ Tabor, E AF Hsia, CC Minemura, M Kashanchi, F Kim, SJ Tabor, E TI Dual effects of hepatitis B virus X gene on the transforming growth factor-beta 1 promoter: Transactivation and suppression. SO HEPATOLOGY LA English DT Meeting Abstract C1 US FDA, Div Transfus Transmitted Dis, Bethesda, MD 20014 USA. NCI, Div Basic Sci, NIH, 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 1998 VL 28 IS 4 SU S MA 1285 BP 484A EP 484A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101284 ER PT J AU Yu, MW Farshid, M Mason, BL Tan, D Koch, WH Yuwen, H Hsia, CC Tabor, E AF Yu, MW Farshid, M Mason, BL Tan, D Koch, WH Yuwen, H Hsia, CC Tabor, E TI Formulation of a hepatitis C virus RNA panel for standardization of nucleic acid testing of blood, plasma, and their derived products. SO HEPATOLOGY LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Transfus Transmitted Dis, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 1998 VL 28 IS 4 SU S MA 1614 BP 566A EP 566A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101614 ER PT J AU Momosaki, S Hsia, CC Nakashima, Y Kojiro, M Tabor, E AF Momosaki, S Hsia, CC Nakashima, Y Kojiro, M Tabor, E TI Use of "genome walking" to determine gene sequences adjacent to integrated hepatitis B virus DNA in hepatocellular carcinomas SO HEPATOLOGY LA English DT Meeting Abstract C1 US FDA, Bethesda, MD 20014 USA. Kurume Univ, Dept Pathol 1, Fukuoka, Japan. 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 1998 VL 28 IS 4 SU S MA 1677 BP 582A EP 582A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101676 ER PT J AU Henry, SH Page, SW Bolger, PM AF Henry, SH Page, SW Bolger, PM TI Hazard assessment of ackee fruit (Blighia sapida) SO HUMAN AND ECOLOGICAL RISK ASSESSMENT LA English DT Article DE toxicity; fruit; risk; hypoglycin; ingestion; susceptible ID ACYL-COA DEHYDROGENASE; JAMAICAN VOMITING SICKNESS; HYPOGLYCIN-A; INACTIVATION; METABOLITE; INVIVO AB Ackee toxicity is associated with consumption of the fruit of the tree Blighia sapida. The problem is endemic in Jamaica, and a number of cases have been reported in the U.S. among Jamaican immigrants. Illness is associated with the method of preparation of the fruit and its ripeness. Malnourished individuals and children appear to be the most susceptible. Levels of the toxic compound, hypoglycin, which are found in the arils and seeds of the fruit, significantly decrease in the arils with ripeness (from 1000 ppm to <0.1 ppm). Symptoms of ackee poisoning in humans occur 6 to 48 hours after ingestion and include vomiting, muscular and mental exhaustion, hypoglycemia, coma and death. Intravenous glucose relieves the hypoglycemia. The most likely mechanism of action occurs through the incorporation of hypoglycin into fatty acid metabolic pathways. Hypoglycin or its primary metabolite methylenecyclopropylacetyl-CoA inhibits the oxidation of fatty acids and leucine and the activity of acyl-CoA dehydrogenases. The dose required to elicit acute responses is not known with any precision, nor is it possible to eliminate the likelihood of adverse effects with long-term ingestion of the toxin. Ingestion of unripe aril or pod and seeds represents a significant health hazard; this hazard diminishes considerably with the consumption of properly processed or prepared ripe fruit. C1 US FDA, Ctr Food Safety & Appl Nutr, Contaminants Stand & Monitoring Branch, Washington, DC 20204 USA. US FDA, Ctr Food Safety & Appl Nutr, Div Nat Prod, Washington, DC 20204 USA. RP Henry, SH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Contaminants Stand & Monitoring Branch, HFS-308,200 C St SW, Washington, DC 20204 USA. EM mzb@vm.cfsan.fda.gov NR 27 TC 11 Z9 11 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1080-7039 J9 HUM ECOL RISK ASSESS JI Hum. Ecol. Risk Assess. PD OCT PY 1998 VL 4 IS 5 BP 1175 EP 1187 DI 10.1080/10807039891285045 PG 13 WC Biodiversity Conservation; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 136MR UT WOS:000076863600010 ER PT J AU Bosio, CM Orme, IM AF Bosio, CM Orme, IM TI Effective, nonsensitizing vaccination with culture filtrate proteins against virulent Mycobacterium bovis infections in mice SO INFECTION AND IMMUNITY LA English DT Article ID DELAYED-TYPE HYPERSENSITIVITY; IMMUNOLOGICAL ADJUVANT; PROTECTIVE IMMUNITY; GUINEA-PIGS; TUBERCULOSIS; QS-21; BCG; RESPONSES; ANTIGENS; IMMUNIZATION AB Vaccination of mice with Mycobacterium bovis culture filtrate proteins (CFP), prepared in a variety of adjuvants (aluminum hydroxide, Quil-A, and dimethyldioctyldecyl ammonium bromide [DDA]), provided significant protection against an aerosol challenge of virulent nl. bovis. Additionally, vaccination with CFP in DDA or Quil-A did not sensitize mice to ill bovis purified protein derivative. C1 Colorado State Univ, Dept Microbiol, Mycobacterial Res Labs, Ft Collins, CO 80523 USA. RP Bosio, CM (reprint author), US FDA, CBER, Lab Mycobacteria, Div Bacterial Prod, 1401 Rockville Pike,HFM 431, Rockville, MD 20852 USA. RI Bosio, Catharine/D-7456-2015 NR 30 TC 34 Z9 36 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 1998 VL 66 IS 10 BP 5048 EP 5051 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 122WU UT WOS:000076095100065 PM 9746617 ER PT J AU Zaitseva, MB Mojcik, CF Salomon, DR Shevach, EM Golding, H AF Zaitseva, MB Mojcik, CF Salomon, DR Shevach, EM Golding, H TI Co-ligation of alpha(4)beta(1) integrin and TCR rescues human thymocytes from steroid-induced apoptosis SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE adhesion molecules; thymus; programmed cell death ID FOCAL ADHESION KINASE; T-CELL DEVELOPMENT; THYMIC STROMAL CELLS; POSITIVE SELECTION; NEGATIVE SELECTION; CD4(+)CD8(+) THYMOCYTES; EXTRACELLULAR-MATRIX; IN-VITRO; RECEPTOR; FIBRONECTIN AB Maturation of thymocytes represents a sequence of events during which thymocytes expressing TCR with moderate avidity for self antigen/MHC are positively selected, whereas those with high or insufficient TCR avidity die.Glucocorticoids are produced intrathymically and can contribute to apoptosis of unselected thymocytes. Thymocytes differentiate in a close contact with epithelial cells, expressing vascular adhesion molecule-1 (VCAM-1) and secreting glucocorticoids, with bone marrow-derived macrophages, and with extracellular matrix containing fibronectin (FN) and collagen, Their contact with FN is mediated by alpha(4)beta(1) and alpha(5)beta(1) integrins, We examined the contribution of TCR and integrin signaling to the survival of thymocytes from dexamethasone (Dex)-induced apoptosis, We demonstrate that FN and VCAM-1 (both of which bind alpha(4)beta(1) integrin), but not collagen, considerably augment TCR-mediated protection of thymocytes from Dex-induced apoptosis, This 'survival' signal is transduced through the alpha(4)beta(1), but not through the alpha(5)beta(1) integrin, The observed protection from Dex-induced apoptosis correlated with an increase in bcl-2 protein levels. FN-alpha(4)beta(1) and VCAM-1-alpha(4)beta(1) engagement induced up-regulation bcl-2 protein, while alpha(5)beta(1) binding to FN induced a negative signal that was blocked by anti-alpha(5)beta(1) antibody, These data suggest that alpha(4)beta(1) integrin may contribute to protection of thymocytes with moderate avidity TCR from glucocorticoid-induced death during intrathymic maturation. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Rockville, MD 20857 USA. NIAID, Immunol Lab, Cellular Immunol Sect, NIH, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. RP Zaitseva, MB (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Rockville, MD 20857 USA. RI Salomon, Daniel/E-9380-2012 NR 45 TC 21 Z9 21 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD OCT PY 1998 VL 10 IS 10 BP 1551 EP 1561 DI 10.1093/intimm/10.10.1551 PG 11 WC Immunology SC Immunology GA 129JL UT WOS:000076460000017 PM 9796922 ER PT J AU Mahmood, I AF Mahmood, I TI Assessment of metabolites in bioequivalence studies: Should bioequivalence criteria be applied on the sum of parent compound and metabolite? SO INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE bioequivalence; parent compound; metabolite; sum of parent and metabolite; confidence interval ID LINEAR PHARMACOKINETICS; BIOAVAILABILITY AB Objectives: The objective of this study was to demonstrate the impact of the sum of parent compound and metabolite in bioequivalence assessment. Methods: Four drugs with active metabolite were selected to assess bioequivalence. Bioequivalence criteria of 80 - 125% were applied to the parent compound, the metabolite, and the sum of parent compound and metabolite. Results: The results indicated that the application of 80 - 125% bioequivalence criteria to the sum of parent compound and metabolite might be misleading. Conclusion: The 90% confidence interval should be applied separately to the parent compound and each metabolite. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1, Woodmont Off Ctr, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1, Woodmont Off Ctr, Hfd-860,Room 4079,1451 Rockville Pike, Rockville, MD 20852 USA. NR 10 TC 8 Z9 8 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI MUNCHEN-DEISENHOFEN PA BAHNHOFSTRABE 9 POSTFACH 49, W-8024 MUNCHEN-DEISENHOFEN, GERMANY SN 0946-1965 J9 INT J CLIN PHARM TH JI Int. J. Clin. Pharmacol. Ther. PD OCT PY 1998 VL 36 IS 10 BP 540 EP 544 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 127WH UT WOS:000076373200006 PM 9799058 ER PT J AU Wang, YM Ray, SC Laeyendecker, O Ticehurst, JR Thomas, DL AF Wang, YM Ray, SC Laeyendecker, O Ticehurst, JR Thomas, DL TI Assessment of hepatitis C virus sequence complexity by electrophoretic mobilities of both single- and double-stranded DNAs SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMORPHISM SSCP ANALYSIS; GEL SHIFT ANALYSIS; CONFORMATION POLYMORPHISM; INTERFERON THERAPY; HYPERVARIABLE REGION; GENETIC DRIFT; HETERODUPLEX; GENOTYPES; PROGRESSION; MUTATIONS AB To assess genetic variation in hepatitis C virus (HCV) sequences accurately, we optimized a method for identifying distinct viral clones without determining the nucleotide sequence of each clone. Twelve serum samples were obtained from seven individuals soon after they acquired HCV during a prospective study, and a 452-bp fragment from the E2 region was amplified by reverse transcriptase PCR and cloned. Thirty-three cloned cDNAs representing each specimen were assessed by a method that combined heteroduplex analysis (HDA) and a single-stranded conformational polymorphism (SSCP) method to determine the number of clonotypes (electrophoretically indistinguishable cloned cDNAs) as a measure of genetic complexity (this combined method is referred to herein as the HDA+SSCP method). We calculated Shannon entropy, incorporating the number and distribution of clonotypes into a single quantifier of complexity. These measures were evaluated for their correlation with nucleotide sequence diversity. Blinded analysis revealed that the sensitivity (ability to detect variants) and specificity (avoidance of false detection) of the HDA+SSCP method were very high. The genetic distance (mean +/- standard deviation) between indistinguishable cloned cDNAs (intraclonotype diversity) was 0.6% +/- 0.9%, and 98.7% of cDNAs differed by < 2%, while the mean distance between cloned cDNAs with different patterns was 4.0% +/- 3.2%. The sensitivity of the HDA+SSCP method compared favorably with either HDA or the SSCP method alone, which resulted in intraclonotype diversities of 1.6% +/- 1.8% and 3.5% +/- 3.4%, respectively. The: number of clonotypes correlated strongly with genetic diversity (R-2, 0.93), but this correlation fell off sharply when fewer clones were assessed. This HDA+SSCP method accurately reflected nucleotide sequence diversity among a large number of viral cDNA clones, which should enhance analyses to determine the effects of viral diversity on HCV-associated disease. If sequence diversity becomes recognized as an important parameter for staging or monitoring of HCV infection, this method should be practical enough for use in laboratories that perform nucleic acid testing. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21218 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Thomas, DL (reprint author), Div Infect Dis, 720 Rutland Ave,Ross 1159, Baltimore, MD 21205 USA. RI Laeyendecker, Oliver/B-9331-2009; Ray, Stuart/B-7527-2008; Ticehurst, John/I-7532-2012; OI Ray, Stuart/0000-0002-1051-7260; Laeyendecker, Oliver/0000-0002-6429-4760 FU Intramural NIH HHS [Z99 AI999999]; NIAID NIH HHS [N01AI40035, AI-40035, U19 AI040035]; NIDA NIH HHS [DA-04334, DA-08004, R01 DA004334, R37 DA004334, R56 DA004334] NR 47 TC 30 Z9 41 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 1998 VL 36 IS 10 BP 2982 EP 2989 PG 8 WC Microbiology SC Microbiology GA 119LD UT WOS:000075896800031 PM 9738054 ER PT J AU Altekruse, SF Timbo, BB Mowbray, JC Bean, NH Potter, ME AF Altekruse, SF Timbo, BB Mowbray, JC Bean, NH Potter, ME TI Cheese-associated outbreaks of human illness in the United States, 1973 to 1992: Sanitary manufacturing practices protect consumers SO JOURNAL OF FOOD PROTECTION LA English DT Review ID ESCHERICHIA-COLI; CHEDDAR CHEESE; SALMONELLA-TYPHIMURIUM; MULTISTATE OUTBREAK; BRUCELLOSIS; FATE AB To identify contributing factors for cheese-associated outbreaks, we reviewed all cheese-associated outbreaks of human illness reported to the Centers for Disease Control and Prevention (CDC) with onsets during 1973 to 1992. The infrequency of large, cheese-associated outbreaks was notable because such outbreaks had been a frequent public health problem before the mid-20th century. Of 32 reported cheese-associated outbreaks, 11 attributed to manufacturing errors caused most of the illnesses and hospitalizations and all 58 deaths. Important factors in these 11 outbreaks were manufacturing cheese with raw or improperly pasteurized milk and postpasteurization contamination. If current Food and Drug Administration sanitary requirements for cheesemaking had been met, these outbreaks would have been preventable. In two outbreaks of Salmonella infections, fewer than 10 Salmonella per 100 g of cheese were detected. In two outbreaks of Brucella infections, efforts to recover the pathogen from the implicated cheese were unsuccessful, emphasizing the inadequacy of end product testing for assuring consumer safety. Curing cheeses kills most bacteria present in cheeses; however, evidence from sources other than the CDC Foodborne Disease Outbreak Surveillance System suggests that curing alone may not be a sufficient pathogen control step to eliminate Salmonella, Listeria, and E. coli O157:H7 from cheese. C1 US Dept HHS, Publ Hlth Serv, Ctr Dis Control & Prevent,Food & Drug Adm Liaison, Natl Ctr Infect Dis,Foodborne & Diarrheal Dis Bra, Atlanta, GA 30333 USA. US Dept HHS, Ctr Food Safety & Appl Nutr, US FDA, Publ Hlth Serv, Washington, DC 20204 USA. US Dept HHS, Publ Hlth Serv, Ctr Dis Control & Prevent, Div Bacterial & Mycot Dis C09,Natl Ctr Infect Dis, Atlanta, GA 30333 USA. RP Altekruse, SF (reprint author), US Dept HHS, Publ Hlth Serv, Ctr Dis Control & Prevent,Food & Drug Adm Liaison, Natl Ctr Infect Dis,Foodborne & Diarrheal Dis Bra, Atlanta, GA 30333 USA. NR 23 TC 78 Z9 84 U1 2 U2 7 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 1998 VL 61 IS 10 BP 1405 EP 1407 PG 3 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 129UD UT WOS:000076481100028 PM 9798166 ER PT J AU Zoeteweij, JP Golding, H Mostowski, H Blauvelt, A AF Zoeteweij, JP Golding, H Mostowski, H Blauvelt, A TI Cutting edge: Cytokines regulate expression and function of the HIV coreceptor CXCR4 on human mature dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LANGERHANS CELLS; T-LYMPHOCYTES; INFECTION; RECEPTOR; AIDS; PROGRESSION; ENTRY; MONOCYTES; DISEASE; VIRUS AB HIV-infected dendritic cells (DC) efficiently transmit infection to CD4(+) T cells during the process of T cell activation. To further understand interactions between DC and HIV, cytokine regulation of HIV coreceptors on cultured Langerhans cells (cLC, as prototypes of mature DC) was studied. Expression of cell surface CXCR4 on cLC was up-regulated by IL-4 and TGF-beta 1 and inhibited by IFN-alpha, IFN-beta, and IFN-gamma, whereas cytokines did not appreciably regulate CCR5. Changes in cell surface CXCR4 expression on cLC correlated with T cell-tropic (X4)-HIV envelope-mediated syncytium formation and XI-HIV infection levels. A relative increase in the ratio of type 2/type 1 cytokine production, which can occur in HIV disease, may up-regulate CXCR4 expression on mature DC and promote infection by X4 viruses. Importantly, these findings suggest that cytokine dysregulation may be linked to the emergence of X4-HIV strains as HIV-infected individuals progress to AIDS. C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Blauvelt, A (reprint author), Bldg 10,Room 12N238,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. EM Andrew_Blauvelt@nih.gov NR 32 TC 52 Z9 53 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 OCT 1 PY 1998 VL 161 IS 7 BP 3219 EP 3223 PG 5 WC Immunology SC Immunology GA 122GY UT WOS:000076064700003 PM 9759835 ER PT J AU Sutherland, JB Freeman, JP Williams, AJ Deck, J AF Sutherland, JB Freeman, JP Williams, AJ Deck, J TI Metabolism of cinnoline to N-oxidation products by Cunninghamella elegans and Aspergillus niger SO JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article DE azaarenes; biotransformation; fungi; heterocyclic compounds; N-oxidation ID FUNGI AB Cultures of the fungi Cunninghamella elegans and Aspergillus niger were grown in fluid Sabouraud medium at 28 degrees C for 3 days and then dosed with cinnoline (1,2-diazanaphthalene). After 3 more days, metabolites were extracted from the cultures with ethyl acetate, separated by high-performance liquid chromatography, and identified by mass spectrometry and proton nuclear magnetic resonance spectroscopy. Both fungi oxidized 2-10% of the added cinnoline to mixtures of cinnoline 2-oxide and cinnoline 1-oxide. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 14 TC 3 Z9 3 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1367-5435 J9 J IND MICROBIOL BIOT JI J. Ind. Microbiol. Biotechnol. PD OCT-NOV PY 1998 VL 21 IS 4-5 BP 225 EP 227 DI 10.1038/sj.jim.2900574 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 158VC UT WOS:000078137200010 ER PT J AU Baratta, EJ AF Baratta, EJ TI Methodology for the US food and drug administration's radionuclides in foods program SO JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY LA English DT Article; Proceedings Paper CT 4th International Conference on Methods and Applications of Radioanalytical Chemistry CY APR 06-11, 1997 CL KAILUA KONA, HAWAII SP Amer Nucl Soc, Isotopes & Radiat Div, Amer Nucl Soc, Biol & Med Div, Canadian Nucl Soc, Amer Chem Soc, Div Nucl Chem & Technol AB The U.S. Food and Drug Administration (FDA) is responsible for the wholesomeness of the nation's food supply. The FDA modified its food monitoring program in January, 1973, to include radioactive isotopes. The methodology used to perform analyses on these food products are taken from the standard setting societies such as the AOAC International, American Society for Testing Materials and American Public Health Association Standard Methods. In addition, methods not tested by these societies are taken from the literature or from Department of Energy manuals such as the Health and Safety Laboratory and also from Environmental Protection Agency, Public Health Service, and Food and Agricultural Organization manuals. These include the methods for long-lived radionuclides such as tritium, strontium-90, cesium-137 and plutonium. Also, the short-lived radionuclides such as iodine-131, radiocesium, radiocerium and radioruthenium. In addition, they include the natural occurring radionuclides such as radium and uranium isotopes. The activity concentrations of gamma-emitters such as radiocesium, iodine-131 and radioruthenium are determined by gamma-ray spectrometry. This is done using intrinsic germanium detectors with the appropriate hardware and software. The alpha and "pure" beta-emitters are determined by various radiochemical methods and techniques. The radiochemical methodology and equipment used in analyzing these radionuclides are described and discussed. Also, the methodology and equipment for the gamma-emitters are described in more detail in this paper. In addition, the limits of detection for the methods used will be discussed. C1 US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. RP Baratta, EJ (reprint author), US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. EM EdmondBaratta@ora.fda.gov NR 27 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0236-5731 J9 J RADIOANAL NUCL CH JI J. Radioanal. Nucl. Chem. PD OCT PY 1998 VL 236 IS 1-2 BP 139 EP 144 DI 10.1007/BF02386331 PG 6 WC Chemistry, Analytical; Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA 131KD UT WOS:000076574100024 ER PT J AU Sehat, N Yurawecz, MP Roach, JAG Mossoba, MM Eulitz, K Mazzola, EP Ku, Y AF Sehat, N Yurawecz, MP Roach, JAG Mossoba, MM Eulitz, K Mazzola, EP Ku, Y TI Autoxidation of the furan fatty acid ester, methyl 9,12-epoxyoctadeca-9,11-dienoate SO JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY LA English DT Article DE autoxidation of furan fatty acids; conjugated linoleic acid (CLA); furan fatty acids ID SOYBEAN LIPOXYGENASE-1; LINOLEIC-ACID; OXIDATION; INHIBITION; PRODUCTS AB The objective of this study was to identify autoxidation products of methyl 9,12-epoxyoctadeca-9,11-dienoate (F-9,F-12) Previous work has shown that F-9,F-12 is a product both of autoxidation and singlet oxygen oxidation of the methyl ester derivative of conjugated linoleic acid (CLA). F-9,F-12, 95% pure, was synthesized from methyl ricinoleate. The synthetic F9,12 was heated at 50 degrees C in sealed tubes containing air. Each tube contained 6 mg F-9,F-12 and 1 mg methyl stearate as an internal standard. Samples were taken at 4.5, 7, 23, 46.5, 69.5, and 93 h. The oxidized F-9,F-12 was dissolved in isooctane and analyzed by gas chromatography (GC), CC-direct deposition-Fourier transform infrared spectroscopy, and CC-electron ionization mass spectrometry. CLA methyl ester was oxidized in a similar manner. Under these conditions, the half-lives of CLA and Fs,12 were 40 and 35 h, respectively. Oxidation products of F9,12 that were identified included: 5-hexyl-2-furaldehyde (1), methyl 8-oxooctanoate (II), methyl 13-oxo-9,12-epoxytrideca-9,11-dienoate (III), methyl 8-oxo-9,12-epoxy-9,11-octadecadienoate (IV), and methyl 13-oxo-9,1 2-epoxy-9,11-octadecadienoate (V). C1 US FDA, Ctr Food Safety & Appl Nutr, Off Food Labeling HFS175, Washington, DC 20204 USA. RP Yurawecz, MP (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Food Labeling HFS175, 200 C St SW, Washington, DC 20204 USA. NR 24 TC 4 Z9 4 U1 0 U2 1 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0003-021X J9 J AM OIL CHEM SOC JI J. Am. Oil Chem. Soc. PD OCT PY 1998 VL 75 IS 10 BP 1313 EP 1319 DI 10.1007/s11746-998-0177-6 PG 7 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 135CL UT WOS:000076782600011 ER PT J AU Martinez, MN AF Martinez, MN TI Special series - Use of pharmacokinetics in veterinary medicine - Article I: Noncompartmental methods of drug characterization: statistical moment theory SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article ID SYSTEMIC AVAILABILITY; ABSORPTION; TIME; SHEEP; BIOAVAILABILITY; DISPOSITION; FOOD; BIOEQUIVALENCE; PRINCIPLES; KINETICS C1 FDA, CVM, Rockville, MD 20855 USA. RP Martinez, MN (reprint author), FDA, CVM, 7500 Standish Pl, Rockville, MD 20855 USA. NR 45 TC 24 Z9 25 U1 1 U2 3 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 OCT 1 PY 1998 VL 213 IS 7 BP 974 EP 980 PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 126DP UT WOS:000076277900032 PM 9776992 ER PT J AU Katz, JB Alstad, D Jenny, AL Carbone, KM Rubin, SA Waltrip, RW AF Katz, JB Alstad, D Jenny, AL Carbone, KM Rubin, SA Waltrip, RW TI Clinical, serologic, and histopathologic characterization of experimental Borna disease in ponies SO JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION LA English DT Article ID INFECTED-RATS; VIRUS; ANTIBODIES; EXPRESSION; PROTEIN; HORSES; CELLS AB Borna disease was originally described as an equine neurologic syndrome over 200 years ago, although the infectious etiology of the disorder was unproven until the early 20th century. Borna disease virus (BDV) was finally isolated from horses dying of the disorder, and that virus has been used to experimentally reproduce Borna disease in several species of laboratory animals. However, BDV has never been inoculated back into horses to experimentally and etiologically confirm the classic clinical, pathologic, and serologic characteristics of the disease in that species. Three ponies were intracerebrally inoculated with different amounts of BDV and were evaluated clinically, serologically, and neurohistopathologically. All 3 animals developed the clinical signs characteristically described for naturally occurring Borna disease, including ataxia, torticollis, postural unawareness, rhythmic repetitive motor activities, muscle fasciculation, and cutaneous hyperesthesia and hypoesthesia over several body surfaces. Two ponies died after rapid onset of these signs 28-30 days postinoculation. The third animal made a nearly complete clinical recovery. Seroconversion occurred only after the onset of signs and to a marked degree only in the convalescent animal. Virus was recovered postmortem from 2 of the 3 ponies, and a BDV-specific nucleic acid sequence was detectable in all 3 animals using a reverse transcription-polymerase chain reaction procedure. Gross neural lesions were absent, but histopathologically there was generalized intense mononuclear perivascular cuffing, glial nodule formation, and astrocytosis in all 3 brains. Confirming a diagnosis of Borna disease is difficult and perhaps best accomplished using a combination of the clinical, serologic, and histopathologic indicators of this unusual disease supported by positive reverse transcription-polymerase chain reaction findings. C1 Anim & Plant Hlth Inspect Serv, Diagnost Virol Lab, Natl Vet Serv Labs, USDA, Ames, IA 50010 USA. US FDA, Lab Pediat Viral Dis & Resp Viruses, US Dept HHS, Bethesda, MD 20892 USA. RP Katz, JB (reprint author), Anim & Plant Hlth Inspect Serv, Diagnost Virol Lab, Natl Vet Serv Labs, USDA, Ames, IA 50010 USA. NR 18 TC 22 Z9 23 U1 0 U2 2 PU AMER ASSOC VETERINARY LABORATORY DIAGNOSTICIANS INC PI TURLOCK PA PO BOX 1522, TURLOCK, CA 95381 USA SN 1040-6387 J9 J VET DIAGN INVEST JI J. Vet. Diagn. Invest. PD OCT PY 1998 VL 10 IS 4 BP 338 EP 343 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA 126QA UT WOS:000076303600005 PM 9786521 ER PT J AU Rubin, SA Pletnikov, M Carbone, KM AF Rubin, SA Pletnikov, M Carbone, KM TI Comparison of the neurovirulence of a vaccine and a wild-type mumps virus strain in the developing rat brain SO JOURNAL OF VIROLOGY LA English DT Article ID GUIDED NEURONAL MIGRATION; MYELITIS FOLLOWING MUMPS; BORNA-DISEASE; SINDBIS VIRUS; AQUEDUCTAL STENOSIS; ASEPTIC-MENINGITIS; NONCODING REGION; RUBELLA VACCINE; E2 GLYCOPROTEIN; RABIES VIRUS AB Prior to the adoption of widespread vaccination programs, mumps virus was the leading cause of virus-induced central nervous system (CNS) disease. Mumps virus-associated CNS complications in vaccinees continue to be reported; outside the United States, some of these complications have been attributed to vaccination with insufficiently attenuated neurovirulent vaccine strains. The development of potentially neurovirulent, live, attenuated mumps virus vaccines stems largely from the lack of an animal model that can reliably predict the neurovirulence of mumps virus vaccine candidates in humans. The lack of an effective safety test with which to measure mumps virus neurovirulence has also hindered analysis of the neuropathogenesis of mumps virus infection and the identification of molecular determinants of neurovirulence. In this report we show, for the first time, that mumps virus infection of the neonatal rat leads to developmental abnormalities in the cerebellum due to cerebellar granule cell migration defects. The incidence of the cerebellar abnormalities and other neuropathological and clinical outcomes of mumps virus infection of the neonatal rat brain demonstrated the ability of this model to distinguish neurovirulent (Kilham) from nonneurovirulent (Jeryl Lynn) mumps virus strains. Thus, this neonatal rat model may prove useful in evaluating the neurovirulence potential of new live, attenuated vaccine strains and may also be of value in elucidating the molecular basis of mumps virus neurovirulence. C1 US FDA, Ctr Biol Evaluat & Res, DVP, OVRR, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Psychiat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD 21205 USA. RP Carbone, KM (reprint author), US FDA, Ctr Biol Evaluat & Res, DVP, OVRR, Bldg 29A,Room 1A-21,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 71 TC 39 Z9 40 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1998 VL 72 IS 10 BP 8037 EP 8042 PG 6 WC Virology SC Virology GA 118WN UT WOS:000075864100038 PM 9733843 ER PT J AU Burris, JA Flynn, BM Dexter, SL AF Burris, JA Flynn, BM Dexter, SL TI A novel parasite in macaques - Pseudoparasite SO LAB ANIMAL LA English DT Article C1 US FDA, Rockville, MD 20852 USA. NCI, Lab Anim Med Sect, Bethesda, MD 20892 USA. AAALAC Int, Rockville, MD USA. RP Burris, JA (reprint author), US FDA, 1451 Rockville Pike, Rockville, MD 20852 USA. NR 3 TC 1 Z9 1 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD OCT PY 1998 VL 27 IS 9 BP 21 EP 22 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA 129LK UT WOS:000076464700003 ER PT J AU Timenetsky, J Barile, MF AF Timenetsky, J Barile, MF TI Immune response of chimpanzees infected with human mycoplasmas SO LABORATORY ANIMAL SCIENCE LA English DT Article ID UREAPLASMA-UREALYTICUM; MONOCLONAL-ANTIBODIES; RESPIRATORY EPITHELIUM; PNEUMONIAE INFECTION; ANTIGENIC VARIATION; PROTEIN ANTIGENS; GENE-PRODUCTS; HOMINIS; ADHERENCE; IDENTIFICATION AB Seven chimpanzees were inoculated intra-articularly with one of three Mycoplasma species. Three chimpanzees were inoculated with clinical synovial isolate 1620, and one was inoculated with type strain PG-21 of M. hominis. The fifth animal was inoculated with clinical synovial isolate 2010B, and the sixth was inoculated with the type strain CO of Ureaplasma urealyticum. The seventh animal was inoculated with clinical isolate PI-1428 of M. pneumoniae. The synovial isolates induced intense antibody responses, antibodies recognized more antigens, and the reactive antigens were distinct from the corresponding type strains. Chimpanzees infected with synovial isolate 1620, but not type strain PG-21, recognized antigens of molecular mass 223, 208, 168, 165, 155, 150, 142, 134, 115, 105, 52, 50, 45, 38, and 36 kDa. The chimpanzee infected with synovial isolate 2010B, but not type strain CO, recognized antigens at about 277, 237, 62, 57, and 43 kDa. The major antibody reactive antigens of M. pneumoniae isolate PI-1428 migrated at about 170, 90, 56, 40, 32, and 30 kDa. The reported biologic activities of antigenic proteins derived from these Mycoplasma species are reviewed. C1 US FDA, Lab Mycoplasma, Ctr Biol Res & Review, Bethesda, MD 20014 USA. Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, Lab Micoplasma, BR-05508 Sao Paulo, Brazil. RP Barile, MF (reprint author), US FDA, Lab Mycoplasma, Ctr Biol Res & Review, Bethesda, MD 20014 USA. NR 44 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 USA SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD OCT PY 1998 VL 48 IS 5 BP 463 EP 468 PG 6 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 139PN UT WOS:000077038100009 PM 10090059 ER PT J AU Sehat, N Kramer, JKG Mossoba, MM Yurawecz, MP Roach, JAG Eulitz, K Morehouse, KM Ku, Y AF Sehat, N Kramer, JKG Mossoba, MM Yurawecz, MP Roach, JAG Eulitz, K Morehouse, KM Ku, Y TI Identification of conjugated linoleic acid isomers in cheese by gas chromatography, silver ion high performance liquid chromatography and mass spectral reconstructed ion profiles. Comparison of chromatographic elution sequences SO LIPIDS LA English DT Article ID FATTY-ACIDS; MILK-FAT; DAIRY-PRODUCTS; METHYL-ESTERS; BOVINE-MILK; DERIVATIVES; BIOHYDROGENATION; ATHEROSCLEROSIS; SPECTROMETRY; LOCATION AB Commercial cheese products were analyzed for their composition and content of conjugated linoleic acid (CLA) isomers. The total lipids were extracted from cheese using petroleum ether/diethyl ether and methylated using NaOCH3. The fatty acid methyl esters (FAME) were separated by gas chromatography (GC), using a 100-m polar capillary column, into nine minor peaks besides that of the major rumenic acid, 9c,11 t-octadecadienoic acid (18:2), and were attributed to 19 CLA isomers. By using silver ion-high performance liquid chromatography (Ag+-HPLC), CLA isomers were resolved into seven trans,trans (5-9%), three cis/trans (10-13%), and five cis,cis (<1%) peaks, totaling 15, in addition to that of the 9c,11 t-18:2 (78-84%). The FAME of total cheese lipids were fractionated by semipreparative Ag+-HPLC and converted to their 4,4-dimethyl-oxazoline derivatives after hydrolysis to free fatty acids. The geometrical configuration of the CLA isomers was confirmed by CC-direct deposition-fourier transform infrared, and their double bond positions were established by CC-electron ionization mass spectrometry. Reconstructed mass spectral ion profiles of the m + 2 allylic ion and the m + 3 ion (where m is the position of the second double bond in the parent conjugated fatty acid) were used to identify the minor CLA isomers in cheese. Cheese contained 7t,9c-18:2 and the previously unreported 11t, 13 c- 18:2 and 12 c, 14t-18:2, and their trans,trans and cis,cis geometric isomers. Minor amounts of 8, 10-, and 10, 12-18:2 were also found. The predicted elution orders of the different CLA isomers on long polar capillary GC and Ag+-HPLC columns are also presented. C1 US FDA, Off Food Labeling HFS175, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Agr & Agri Food Canada, Food Res Ctr, So Crop Protect, Guelph, ON N1G 2W1, Canada. RP Yurawecz, MP (reprint author), US FDA, Off Food Labeling HFS175, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 48 TC 164 Z9 174 U1 2 U2 17 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PD OCT PY 1998 VL 33 IS 10 BP 963 EP 971 DI 10.1007/s11745-998-0293-8 PG 9 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 136AV UT WOS:000076836200002 PM 9832075 ER PT J AU Bright, RA AF Bright, RA TI Dialysis therapy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID CONVERTING ENZYME-INHIBITORS; ANAPHYLACTOID REACTIONS; HEMODIALYSIS C1 US FDA, Rockville, MD 20855 USA. RP Bright, RA (reprint author), US FDA, Rockville, MD 20855 USA. RI Bright, Roselie/D-2240-2016 NR 5 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 1 PY 1998 VL 339 IS 14 BP 1004 EP 1005 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 124MW UT WOS:000076186900025 PM 9766988 ER PT J AU Summers, RM Brune, AM Choyke, PL Chow, CK Patronas, NJ Miller, FW White, PH Malley, JD Rider, LG AF Summers, RM Brune, AM Choyke, PL Chow, CK Patronas, NJ Miller, FW White, PH Malley, JD Rider, LG TI Juvenile idiopathic inflammatory myopathy: Exercise-induced changes in muscle at short inversion time inversion-recovery MR imaging SO RADIOLOGY LA English DT Article DE dermatomyositis; muscles, diseases; muscles, MR; myositis ID MAGNETIC-RESONANCE SPECTROSCOPY; SKELETAL-MUSCLE; TRANSVERSE RELAXATION; LEG MUSCLE; DERMATOMYOSITIS; DISEASE; WORK; T2; CHILDREN; IMAGES AB PURPOSE: To study the effect of exercise on short inversion time inversion-recovery (STIR) magnetic resonance (MR) images of thigh muscles in children with juvenile idiopathic inflammatory myopathy. MATERIALS AND METHODS: Thirty-two MR studies were performed in 19 patients with juvenile idiopathic inflammatory myopathy who performed stair-stepping exercise for up to 10 minutes (mean, 5.7 minutes). Baseline T1-weighted (n = 32) and STIR (n = 32) images and STIR images immediately (n = 32) and at 30 (n = 24) and 60 (n = 29) minutes after exercise were obtained at 0.5 T. Four radiologists graded STIR signal intensity changes, in observer performance experiments in which they were blinded to the order of image acquisition in relation to exercise. RESULTS: Changes in muscle signal intensity were observed on STIR images obtained immediately after exercise in 20 of 32 (63%) studies. The mean signal intensity score immediately after exercise (1.7 +/- 1.0 [SD]) increased compared with the mean baseline score (1.4 +/- 1.1) (P = .0005) and resolved by 30 minutes after exercise. The magnitude of exercise-induced changes correlated with the amount of work performed (r = 0.51, P = .003) but not with disease activity or baseline signal intensity when the changes were corrected for work (r < 0.17, P > .35). Radiologists demonstrated moderate to substantial agreement in the grading of signal intensity changes after exercise (kappa = 0.60-0.84). CONCLUSION: In patients with juvenile idiopathic inflammatory myopathy, stair-stepping exercise induces signal intensity changes on STIR MR studies of muscle for approximately 30 minutes after exercise, in a distribution that may mimic active muscle inflammation. C1 US FDA, Ctr Biol Evaluat & Res, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NIAMSD, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. NIH, Computat Biosci & Engn Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Pediat Rheumatol, Washington, DC 20010 USA. RP Summers, RM (reprint author), US FDA, Ctr Biol Evaluat & Res, Dept Diagnost Radiol, Bldg 10,Rm 1C660,10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA. OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 NR 26 TC 17 Z9 18 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 1998 VL 209 IS 1 BP 191 EP 196 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 121QK UT WOS:000076024700032 PM 9769831 ER PT J AU Gaylor, D Ryan, L Krewski, D Zhu, YL AF Gaylor, D Ryan, L Krewski, D Zhu, YL TI Procedures for calculating benchmark doses for health risk assessment SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE benchmark dose; risk assessment; quantal data; clustered data; continuous data ID DEVELOPMENTAL TOXICITY EXPERIMENTS; LONGITUDINAL DATA-ANALYSIS; RESPONSE MODELS; TOXICOLOGICAL EXPERIMENTS; FETAL WEIGHT; TERATOLOGICAL EXPERIMENTS; TRINOMIAL RESPONSES; CONTINUOUS OUTCOMES; BINARY DATA; MALFORMATION AB Safety assessment for noncancer health effects generally has been based upon dividing a no observed adverse effect (NOAEL) by uncertainty (safety) factors to provide an acceptable daily intake (ADI) or reference dose (RfD). Since the NOAEL does not utilize all of the available dose-response data, allows higher ADI from poorer experiments, and may have an unknown, unacceptable level of risk, the benchmark dose (BD) with a specified, controlled low level of risk has become popular as an adjunct to the NOAEL or the low observed adverse effect level (LOAEL) in the safety assessment process. The purpose of this paper is to summarize statistical procedures available for calculating BDs and their confidence limits for noncancer endpoints. Procedures are presented and illustrated for quantal (binary), quasicontinuous (proportion), and continuous data. Quasicontinuous data arise in developmental studies where the measure of an effect for a fetus is quantal (normal or abnormal) but the experimental unit is the mother (litter) so that results can be expressed as the proportion of abnormal fetuses per litter. However, the correlation of effects among fetuses within a litter poses some additional statistical problems. Also, developmental studies usually include some continuous measures, such as fetal body weight or length. With continuous data there generally is not a clear demarcation between normal and adverse measurements. In such cases, extremely high and/or low measurements at some designated percentile(s) can be considered abnormal. Then the probability (risk) of abnormal individuals can be estimated as a function of dose. The procedure for estimating a ED with continuous data is illustrated using neurotoxicity data. When multiple measures of adverse effects are available, a BD can be estimated based on a selected endpoint or the appearance of any combination of endpoints. Multivariate procedures are illustrated using developmental and reproductive toxicity data. (C) 1998 Academic Press. C1 Univ S Florida, Dept Epidemiol & Biostat, Tampa, FL 33612 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Hlth Canada, Hlth Protect Branch, Ottawa, ON K1A 0L2, Canada. Carleton Univ, Dept Math & Stat, Ottawa, ON K1A 0L2, Canada. RP Zhu, YL (reprint author), Univ S Florida, Dept Epidemiol & Biostat, 13201 Bruce B Downs Blvd, Tampa, FL 33612 USA. EM yzhu@com1.med.usf.edu RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 62 TC 72 Z9 77 U1 0 U2 8 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 OCT PY 1998 VL 28 IS 2 BP 150 EP 164 DI 10.1006/rtph.1998.1247 PG 15 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 167EV UT WOS:000078620300010 PM 9927564 ER PT J AU Gaylor, DW Moolgavkar, S Krewski, D Goldstein, LS AF Gaylor, DW Moolgavkar, S Krewski, D Goldstein, LS TI Recent bioassay results on coal tars and benzo(a)pyrene: Implications for risk assessment SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Editorial Material C1 Elect Power Res Inst, Palo Alto, CA 94304 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Ottawa, Fac Med, Ottawa, ON K1H 8M5, Canada. RP Goldstein, LS (reprint author), Elect Power Res Inst, 3412 Hillview Ave, Palo Alto, CA 94304 USA. NR 0 TC 5 Z9 5 U1 0 U2 1 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 OCT PY 1998 VL 28 IS 2 BP 178 EP 179 DI 10.1006/rtph.1998.1237 PG 2 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 167EV UT WOS:000078620300012 PM 9927566 ER PT J AU Ramaiah, SK Bucci, TJ Warbritton, A Soni, MG Mehendale, HM AF Ramaiah, SK Bucci, TJ Warbritton, A Soni, MG Mehendale, HM TI Temporal changes in tissue repair permit survival of diet-restricted rats from an acute lethal dose of thioacetamide SO TOXICOLOGICAL SCIENCES LA English DT Article ID EPIDERMAL GROWTH-FACTOR; LIVER-REGENERATION; HEPATOCELLULAR REGENERATION; HEPATOTOXICITY; INJURY; TOXICITY; EXPRESSION; METALLOTHIONEIN; AUTOPROTECTION; COLCHICINE AB Although, diet restriction (DR) has been shown to substantially increase longevity while reducing or delaying the onset of age-related diseases, little is known about the mechanisms underlying the beneficial effects of DR on acute toxic outcomes. An earlier study (S. K. Ramaiah ct at, 1998, Toxicol. Appl. Pharmacol. 150, 12-21) revealed that a 35% DR compared to ad libitum (AL) feeding leads to a substantial increase in liver injury of thioacetamide (TA) at a low dose (50 mg/kg, ip). Higher liver injury was accompanied by enhanced survival. A prompt and enhanced tissue repair response in DR rats at the low dose (sixfold higher liver injury) occurred, whereas at equitoxic doses (50 mg/kg in DR and 600 mg/kg in AL rats) tissue repair in AL rats was substantially diminished and delayed. The extent of liver injury did not appear to be closely related to the extent of stimulated tissue repair response, The purpose of the present study was to investigate the time course (0-120 h) of liver injury and liver tissue repair at the high dose (600 mg TA/kg, ip, lethal in AL rats) in AL and DR rats. Male Sprague-Dawley rats (225-275 g) were 35% diet restricted compared to their AL cohorts for 21 days and on day 22 they received a single dose of TA (600 mg/kg, ip). Liver injury was assessed by plasma ALT and by histopathological examination of liver sections. Tissue repair was assessed by [H-3]thymidine incorporation into hepatonuclear DNA and proliferating cell nuclear antigen (PCNA) immunohistochemistry during 0-120 h after TA injection. In AL-fed rats hepatic necrosis was evident at 12 h, peaked at 60 h. and persisted thereafter until mortality (3 to 6 days). Peak liver injury was approximately twofold higher in DR rats compared to that seen in AL rats. Hepatic necrosis was evident at 36 h, peaked at 48 h, persisted until 96 h, and returned to normal by 120 h, Light microscopy of liver sections revealed progression of hepatic injury in AL rats whereas injury regressed completely leading to recovery of DR rats by 120 h. Progression of injury led to 90% mortality in AL rats vs 30% mortality in DR group. In the surviving AL rats, S-phase DNA synthesis was evident at 60 h, peaked at 72 h, and declined to base level by 120 h, whereas in DR rats S-phase DNA synthesis was evident at 36 h and was consistently higher until 96 h reaching control levels by 120 h. PCNA studies showed a corresponding increase in cells in S and M phase in the AL and DR groups. DR resulted in abolition of the delay in tissue repair associated with the lethal dose of TA in ad libitum rats. Temporal changes and higher tissue repair response in DR rats (earlier and prolonged) are the conduits that anew a significant number of diet restricted rats to escape lethal consequence. (C) 1998 Society of Toxicology. C1 NE Louisiana Univ, Coll Pharm & Hlth Sci, Div Toxicol, Monroe, LA 71209 USA. NE Louisiana Univ, Coll Pharm & Hlth Sci, Louisiana Inst Toxicol, Monroe, LA 71209 USA. Natl Ctr Toxicol Res, Pathol Associates Inc, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), NE Louisiana Univ, Coll Pharm & Hlth Sci, Div Toxicol, Monroe, LA 71209 USA. EM pymehendale@alpha.nlu.edu FU NIEHS NIH HHS [ES-08604] NR 50 TC 20 Z9 20 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD OCT PY 1998 VL 45 IS 2 BP 233 EP 241 DI 10.1093/toxsci/45.2.233 PG 9 WC Toxicology SC Toxicology GA 136XA UT WOS:000076883300012 PM 9848130 ER PT J AU Lee, JH AF Lee, JH CA CC Review Grp TI FDA review of computer crossmatch submissions. SO TRANSFUSION LA English DT Meeting Abstract C1 US FDA, CC Review Grp, 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 1998 VL 38 IS 10 SU S MA A73 BP 126S EP 126S PG 1 WC Hematology SC Hematology GA 124FM UT WOS:000076171800492 ER PT J AU McCullough, J Bianco, C Busch, M Dodd, R Hewlett, IK Jackson, JB Katz, LM McFarland, A Mied, P Page, P Preston, MS Simon, T Stramer, S Stroncek, D Young, CT AF McCullough, J Bianco, C Busch, M Dodd, R Hewlett, IK Jackson, JB Katz, LM McFarland, A Mied, P Page, P Preston, MS Simon, T Stramer, S Stroncek, D Young, CT TI Interagency Genome Amplification Testing Task Force: preliminary report SO TRANSFUSION LA English DT Editorial Material C1 Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA. New York Blood Ctr Inc, Med Affairs, New York, NY USA. Pacific Irwin Ctr, Ctr Blood, Res & Sci Serv, San Francisco, CA USA. Amer Red Cross, Blood Serv, Jerome C Holland Lab, Transmissible Dis Dept, Rockville, MD USA. US FDA, Mol Virol Lab, Div Transfus Transmitted Dis, Bethesda, MD 20014 USA. Johns Hopkins Hosp, Dept Pathol, Baltimore, MD 21287 USA. Mississippi Valley Reg Blood Ctr, Davenport, IA USA. Blood Ctr SE Wisconsin Inc, Med Affairs, Milwaukee, WI 53233 USA. Amer Red Cross, Arlington, VA USA. Alpha Therapeut Corp, Qual & Regulatory Affairs, Los Angeles, CA USA. Serol Inc, Med & Sci Affairs, Clarkston, GA USA. Amer Red Cross, Natl Confirmatory Testing Lab, Gaithersburg, MD USA. NIH, Lab Serv Sect, Dept Transfus Med, Bethesda, MD 20892 USA. Rhode Isl Blood Ctr, DNA HLA Reference & Educ Serv, Providence, RI USA. RP McCullough, J (reprint author), Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA. NR 3 TC 6 Z9 6 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 1998 VL 38 IS 10 BP 903 EP 904 DI 10.1046/j.1537-2995.1998.381098440852.x PG 2 WC Hematology SC Hematology GA 124AL UT WOS:000076158100002 PM 9767738 ER PT J AU Woerner, AM Weir, JP AF Woerner, AM Weir, JP TI Characterization of the initiator and downstream promoter elements of herpes simplex virus 1 late genes SO VIROLOGY LA English DT Article ID GLYCOPROTEIN-C GENE; RNA-POLYMERASE-II; TYPE-1 LATE GENE; TRANSCRIPTION FACTOR; MUTATIONAL ANALYSIS; EXPRESSION; BINDING; SITE; SEQUENCES; PROTEIN AB Previously identified cis-acting regulatory elements of herpes simplex virus (HSV) 1 late promoters include a TATA element upstream from the start of transcription, an initiator-like element at the start of transcription, and sequences downstream from the start of transcription. To determine whether these elements are functionally equivalent to similar elements from other eukaryotic genes, model late promoters were constructed using well-characterized regulatory elements from non-HSV genes. These modular promoters were then inserted into the viral genome upstream from a lacZ marker gene. Results showed that a eukaryotic initiator element, along with a TATA element, can function as a late HSV promoter. Several initiator sequences from both viral and nonviral genes were functionally similar to the initiator-like element in HSV-1 late promoters; however, a random sequence of the same size and a similarly located sequence from the HSV-1 early thymidine kinase promoter could not substitute for the initiator element. These results indicate that eukaryotic initiator elements are functionally equivalent to HSV-1 late promoter initiator elements. In addition, the downstream element of the late glycoprotein C promoter was further analyzed by construction of a series of small deletions and insertions. The presence of the downstream glycoprotein C region in a promoter consisting of a strong TATA and initiator element increased mRNA expression by a modest amount; this effect appeared to be sequence specific and dependent on its exact alignment with the upstream elements of the promoter. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Weir, JP (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, 1401 Rockville Pike, Bethesda, MD 20892 USA. NR 35 TC 4 Z9 4 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 30 PY 1998 VL 249 IS 2 BP 219 EP 230 DI 10.1006/viro.1998.9339 PG 12 WC Virology SC Virology GA 128BD UT WOS:000076384600003 PM 9791014 ER PT J AU Donato, KA Pi-Sunyer, FX Becker, DM Bouchard, C Carleton, RA Colditz, GA Dietz, WH Foreyt, JP Garrison, RJ Grundy, SM Hansen, BC Higgins, M Hill, JO Howard, BV Kuczmarski, RJ Kumanyika, S Legako, RD Prewitt, TE Rocchini, AP Snetselaar, LG Weintraub, M Williamson, DF Wilson, GT Brown, CD Ernst, N Hill, DR Horan, MJ Kiley, JP Obarzanck, E Hubbard, VS Schriger, D Chiquette, E AF Donato, KA Pi-Sunyer, FX Becker, DM Bouchard, C Carleton, RA Colditz, GA Dietz, WH Foreyt, JP Garrison, RJ Grundy, SM Hansen, BC Higgins, M Hill, JO Howard, BV Kuczmarski, RJ Kumanyika, S Legako, RD Prewitt, TE Rocchini, AP Snetselaar, LG Weintraub, M Williamson, DF Wilson, GT Brown, CD Ernst, N Hill, DR Horan, MJ Kiley, JP Obarzanck, E Hubbard, VS Schriger, D Chiquette, E CA Expert Panel Identification, Evaluation, T TI Executive summary of the clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article AB An estimated 97 million adults in the United States are overweight or obese, a condition that substantially raises their risk of morbidity from hypertension, dyslipidemia, type 2 diabetes, coronary heart disease, stroke, gallbladder disease, osteoarthritis, sleep apnea and respiratory problems, and endometrial, breast, prostate, and colon cancers.(1) Higher body weights are also associated with increases in all-cause mortality. Obese individuals may also suffer from social stigmatization and discrimination. As a major contributor to preventive death in the United States today, overweight and obesity pose a major public health challenge. C1 Columbia Univ, Coll Phys & Surg, New York, NY 10027 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Laval, St Foy, PQ G1K 7P4, Canada. Brown Univ, Sch Med, Pawtucket, RI USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Tennessee, Memphis, TN USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Medlant Res Inst, Washington, DC USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. Univ Illinois, Chicago, IL 60680 USA. Prime Care Canyon Pk Family Phys Inc, Edmond, OK USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD USA. Univ Iowa, Iowa City, IA 52242 USA. Wayne State Univ, Sch Med, Univ Hlth Ctr, Detroit, MI USA. US FDA, Off Drug Evaluat 5, Rockville, MD 20857 USA. Rutgers State Univ, Eating Disorders Clin, Piscataway, NJ USA. RP Donato, KA (reprint author), Columbia Univ, Coll Phys & Surg, New York, NY 10027 USA. RI Hansen, Barbara/J-8723-2012; Bouchard, Claude/A-7637-2009; Colditz, Graham/A-3963-2009 OI Hansen, Barbara/0000-0001-9646-3525; Colditz, Graham/0000-0002-7307-0291 NR 4 TC 409 Z9 415 U1 1 U2 21 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 SEP 28 PY 1998 VL 158 IS 17 BP 1855 EP 1867 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 124DV UT WOS:000076166800001 ER PT J AU Knudsen, JF Friedman, B Chen, M Goldwasser, JE AF Knudsen, JF Friedman, B Chen, M Goldwasser, JE TI Ischemic colitis and sumatriptan use SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CHEST PAIN AB Sumatriptan succinate, a serotonin-1 (5-hydroxytryptamine-1) receptor agonist, is an antimigraine drug that is reported to act by selectively constricting intracranial arteries. Recently, vasopressor responses that are distinct from the cranial circulation have been demonstrated to occur in the systemic, pulmonary, and coronary circulations. Cases have been published of coronary vasospasm, myocardial ischemia, and myocardial infarction occurring after sumatriptan use. We report on the development of 8 serious cases of ischemic colitis in patients with migraine treated with sumatriptan. C1 US FDA, Ctr Drug Evaluat & Res, Off Epidemiol & Biostat, Div Pharmacovigilance & Epidemiol, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Off Epidemiol & Biostat, Div Neuropharmacol Drug Prod, Rockville, MD 20857 USA. Univ Calif Los Angeles, Sch Med, Cedars Sinai Med Ctr, Dept Internal Med,Div Gastroenterol, Los Angeles, CA USA. RP Friedman, B (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Epidemiol & Biostat, Div Pharmacovigilance & Epidemiol, HFD-735,5600 Fishers Ln, Rockville, MD 20857 USA. NR 15 TC 53 Z9 53 U1 0 U2 1 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 SEP 28 PY 1998 VL 158 IS 17 BP 1946 EP 1948 DI 10.1001/archinte.158.17.1946 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 124DV UT WOS:000076166800013 PM 9759693 ER PT J AU Kessler, L Richter, K AF Kessler, L Richter, K TI Technology assessment of medical devices at the center for devices and radiological health SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID CATHETERIZATION; DEFIBRILLATOR; RISK AB We reviewed the Food and Drug Administration's regulatory process for medical devices and described the issues that arise in assessing device safety and effectiveness during the postmarket period. The Center for Devices and Radiological Health (CDRH), an organization within the Food and Drug Administration, has the legal authority and responsibility for ensuring that medical devices marketed in the United States are both reasonably safe and effective for their intended use. This is an enormous challenge given the diversity of medical devices and the large number of different types of devices on the market. Many scientific and regulatory activities are necessary to ensure device safety and effectiveness, including technology assessment, albeit in a manner quite different from that of conventional technology assessment. The basic approach taken at the CDRH to ensure device safety and effectiveness is to develop an understanding of the way in which a medical device works and how it will perform in clinical situations. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Kessler, L (reprint author), US FDA, Ctr Devices & Radiol Hlth, 1350 Piccard Dr,HFZ 500, Rockville, MD 20850 USA. NR 10 TC 8 Z9 8 U1 0 U2 1 PU AMER MED PUBLISHING, M W C COMPANY PI OLD BRIDGE PA 1816 ENGLISHTOWN RD, STE 101, OLD BRIDGE, NJ 08857 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD SEP 25 PY 1998 VL 4 SI SI BP SP129 EP SP135 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 129AB UT WOS:000076439700003 PM 10185989 ER PT J AU Scott, DE Golding, H Huang, LY Inman, J Golding, B AF Scott, DE Golding, H Huang, LY Inman, J Golding, B TI HIV peptide conjugated to heat-killed bacteria promotes antiviral responses in immunodeficient mice SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID MHC CLASS-II; CYTOKINE GENE-EXPRESSION; T-CELL RESPONSES; BRUCELLA-ABORTUS; IFN-GAMMA; IMMUNE-RESPONSES; INTERLEUKIN-12 PRODUCTION; ANTIBODY-RESPONSE; ISOTYPE SELECTION; DEFICIENT MICE AB Enhancement of immunity in the setting of HIV infection is difficult owing to loss of functional CD4(+) T cells, The MHC class II-deficient mouse (II-/-) environment simulates that of the immunocompromised HIV-infected individual, since these mice have low CD4(+) T cell numbers, defective CD4-dependent responses, and are susceptible to opportunistic infection. This strain was used to test whether heat-killed Brucella abortus (BA), covalently conjugated to the V3 peptide of HIV-1 (MN), could elicit anti-HIV responses, V3-BA, but not the T-dependent antigen V3-KLH, induced high levels of IL-12, IFN-gamma, and IL-10 mRNA in both wild-type (WT) and II-/- mice within 24 hr of injection. V3-BA-treated, but not V3-KLH-treated, II-/- mice developed serum IgG and IgA anti-V3 antibodies, with IgG(2b) and IgG(3) as the predominant isotype. Viral neutralization studies, using a syncytium inhibition assay, demonstrated that the antibodies generated by V3-BA in II-/- mice were capable of neutralizing HN. These experiments demonstrate that a heat-inactivated bacterium such as BA, when used as a carrier, can generate a cytokine environment that results in the production of neutralizing antiviral antibodies in an immunodeficient host. Such strategies could be important in the development of immunotherapies and vaccines for HIV-1 patients. C1 US FDA, Ctr Biol Evaluat & Res, Lab Plasma Derivat, Div Hematol, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Retrovirus Res, Div Viral Prod, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Scott, DE (reprint author), Bldg 29,Room 232,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 51 TC 9 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP 20 PY 1998 VL 14 IS 14 BP 1263 EP 1269 DI 10.1089/aid.1998.14.1263 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 130YB UT WOS:000076547000006 PM 9764910 ER PT J AU Kadlubar, FF Anderson, KE Haussermann, S Lang, NP Barone, GW Thompson, PA MacLeod, SL Chou, MW Mikhailova, M Plastaras, J Marnett, LJ Nair, J Velic, I Bartsch, H AF Kadlubar, FF Anderson, KE Haussermann, S Lang, NP Barone, GW Thompson, PA MacLeod, SL Chou, MW Mikhailova, M Plastaras, J Marnett, LJ Nair, J Velic, I Bartsch, H TI Comparison of DNA adduct levels associated with oxidative stress in human pancreas SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT Satellite Meeting on Cancer and Genetic Risk Assessment - Low Dose-Effect Studies CY SEP 04-06, 1997 CL HEIDELBERG, GERMANY SP Deutsche Forsch Gemeinsch, BASF AG, Bayer AG, Boehringer Mannheim GmbH, GSF, Forsch Zentrum fur Umwelt & Gesundheit, DKFZ, Deutsch Krebsforsch Zentrum, GUM, Gesell Umwelt Mutat Forsch e V, Hoechst Marion Roussel, Merck AG, Hoffmann-La Roche AG, Sandoz Pharma AG, Schering AG DE etheno adduct; malondialdehyde adduct; 8-oxo-2 '-deoxyguanosine; glutathione S-transferase; quinone reductase; DNA adduct; human pancreas ID WHITE BLOOD-CELLS; LIPID-PEROXIDATION; LIVER DNA; 8-HYDROXYDEOXYGUANOSINE; DAMAGE; MALONDIALDEHYDE; INCREASE; EXPOSURE; SMOKING; CANCER AB DNA adducts associated with oxidative stress are believed to involve the formation of endogenous reactive species generated by oxidative damage and lipid peroxidation. Although these adducts have been reported in several human tissues by different laboratories, a comparison of the levels of these adducts in the same tissue samples has not been carried out. In this study, we isolated DNA from the pancreas of 15 smokers and 15 non-smokers, and measured the levels of 1,N-6-etheno(2'-deoxy)guanosine (edA), 3,N-4-etheno(2'-deoxy)cytidine (edC), 8-oxo-2'-deoxyguanosine (8-oxo-dG), and pyrimido[1,2-alpha]purin-10(3H)-one (m(1)G). Using the same DNA, the glutathione S-transferase (GST) MI, GSTT1, and NAD(P)H quinone reductase-l (NQO(1)) genotypes were determined in order to assess the role of their gene products in modulating adduct levels through their involvement in detoxification of lipid peroxidation products and redox cycling, respectively. The highest adduct levels observed were for m(1)G, followed by 8-oxo-dG, edA, and edC, but there were no differences in adduct levels between smokers and non-smokers and no correlation with the age, sex or body mass index of the subject. Moreover, there was no correlation in adduct levels between edA and eC, or between edA or edC and m(1)G or 8-oxo-dG. However, there was a significant correlation (r = 0.76; p < 0.01) between the levels of 8-oxo-dG and m(1)G in human pancreas DNA. Neither GSTM1 nor NQO(1) genotypes were associated with differences in any of the adduct levels. Although the sample set was Limited, the data suggest that endogenous DNA adduct formation in human pancreas is not clearly derived from cigarette smoking or from (NQO(1))-mediated redox cycling. Further, it appears that neither GSTM1 nor GSTT1 appreciably protects against endogenous adduct formation. Together with the lack of correlation between m(1)G and edA or edC, these data indicate that the malondialdehyde derived from lipid peroxidation may not contribute significantly to m(1)G adduct formation. On the other hand, the apparent correlation between m(1)G and 8-oxo-dG and their comparable high levels are consistent with the hypothesis that m(1)G is formed primarily by reaction of DNA with a base propenal, which, like 8-oxo-dG, is thought to be derived from hydroxyl radical attack on the DNA. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Minnesota, Minneapolis, MN 55455 USA. German Canc Res Ctr, D-69120 Heidelberg, Germany. John L McClellan Mem Vet Adm Med Ctr, Little Rock, AR 72205 USA. Arkansas Canc Res Ctr, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Vanderbilt Univ, Nashville, TN 37232 USA. RP Kadlubar, FF (reprint author), Natl Ctr Toxicol Res, HFT-100, Jefferson, AR 72079 USA. NR 27 TC 81 Z9 82 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD SEP 20 PY 1998 VL 405 IS 2 BP 125 EP 133 DI 10.1016/S0027-5107(98)00129-8 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 122WJ UT WOS:000076094200003 PM 9748537 ER PT J AU Slifman, NR Obermeyer, WR Aloi, BK Musser, SM Correll, WA Cichowicz, SM Betz, JM Love, LA AF Slifman, NR Obermeyer, WR Aloi, BK Musser, SM Correll, WA Cichowicz, SM Betz, JM Love, LA TI Contamination of botanical dietary supplements by Digitalis lanata SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID FAB ANTIBODY FRAGMENTS; CARDIAC-GLYCOSIDES; DIGOXIN; AFFINITY; TEA C1 US FDA, Clin Res & Rev Staff, Off Special Nutr, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. US FDA, Div Nat Prod, Off Plant & Dairy Foods & Beverages, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. US FDA, Div Enforcement & Programs, Off Field Programs, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. US FDA, Instrumentat & Biophys Branch, Off Sci Anal & Supp, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Love, LA (reprint author), US FDA, Clin Res & Rev Staff, Off Special Nutr, Ctr Food Safety & Appl Nutr, HFS-452,200 C St SW, Washington, DC 20204 USA. NR 38 TC 151 Z9 152 U1 1 U2 7 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 17 PY 1998 VL 339 IS 12 BP 806 EP 811 DI 10.1056/NEJM199809173391204 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 119QT UT WOS:000075909200004 PM 9738088 ER PT J AU Jerian, S Keegan, P Siegel, J AF Jerian, S Keegan, P Siegel, J TI Cytokine therapy in metastatic renal cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US Food & Drug Adm, Rockville, MD 20852 USA. RP Jerian, S (reprint author), US Food & Drug Adm, Rockville, MD 20852 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 17 PY 1998 VL 339 IS 12 BP 849 EP 850 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 119QT UT WOS:000075909200020 PM 9750083 ER PT J AU Rheinstein, PH Tsai, VW AF Rheinstein, PH Tsai, VW TI Keeping abreast of new drug approvals and labeling changes SO AMERICAN FAMILY PHYSICIAN LA English DT Article C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Rheinstein, PH (reprint author), US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. NR 4 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 SEP 15 PY 1998 VL 58 IS 4 BP 995 EP 998 PG 4 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 123VA UT WOS:000076145000023 PM 9767730 ER PT J AU Ulyanov, NB Ivanov, VI Minyat, EE Khomyakova, EB Petrova, MV Lesiak, K James, TL AF Ulyanov, NB Ivanov, VI Minyat, EE Khomyakova, EB Petrova, MV Lesiak, K James, TL TI A pseudosquare knot structure of DNA in solution SO BIOCHEMISTRY LA English DT Article ID SLIPPED LOOP-DNA; S1 NUCLEASE; HOLLIDAY JUNCTIONS; NMR STRUCTURE; RNA; COMPLEX; MODEL; RESOLUTION; SEQUENCE; REPEAT AB We report a high-resolution NMR structure of a homodimer formed by a synthetic 25 residue DNA oligonucleotide GCTCCCATGGTTTTTGTGCACGAGC. This structure presents a novel structural motif for single-stranded nucleic acids, called a pseudosquare knot (PSQ). The oligonucleotide was originally designed to mimic a slipped-loop structure (SLS), another "unusual" DNA structure postulated as an alternative conformation for short direct repeats in double-stranded DNA. The design of the sequence is compatible with both SLS and PSQ structures, both of which possess identical sets of base-paired and unpaired nucleotides but different tertiary folds. We used deuteration of the H8 positions of purines to ascertain that the PSQ is actually formed under the conditions used. The PSQ structure was solved based on homonuclear proton nuclear Overhauser effect data using complete relaxation matrix methods. The structure essentially consists of two side-by-side helices connected by single-stranded loops. Each of the helices is well-defined; however, the relative orientation of the two remains undetermined by the NMR data. The sequences compatible with the PSQ formation are frequent in single-stranded genomes; this structure may play a role as a dimerization motif. C1 Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow, Russia. US FDA, Ctr Biol Evaluat & Res, Div Allergen Prod & Parasitol, Biophys Lab, Rockville, MD 20852 USA. RP James, TL (reprint author), Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. EM james@picasso.ucsf.edu RI Ulyanov, Nikolai/G-6998-2014 FU FIC NIH HHS [TW 00438]; NCRR NIH HHS [RR 01081]; NIGMS NIH HHS [GM 39247] NR 41 TC 7 Z9 7 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 15 PY 1998 VL 37 IS 37 BP 12715 EP 12726 DI 10.1021/bi981018d PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 125NR UT WOS:000076244100005 PM 9737848 ER PT J AU Sarobe, P Pendleton, CD Akatsuka, T Lau, D Engelhard, VH Feinstone, SM Berzofsky, JA AF Sarobe, P Pendleton, CD Akatsuka, T Lau, D Engelhard, VH Feinstone, SM Berzofsky, JA TI Enhanced in vitro potency and in vivo immunogenicity of a CTL epitope from hepatitis C virus core protein following amino acid replacement at secondary HLA-A2.1 binding positions SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE cytotoxic T lymphocyte; epitope enhancement; major histocompatibility complex class I affinity peptide, synthetic; vaccine ID CYTOTOXIC T-LYMPHOCYTE; CLASS-I MOLECULES; DESIGNING PEPTIDE VACCINES; PAPILLOMAVIRUS TYPE-16 E6; NON-B-HEPATITIS; TRANSGENIC MICE; NUCLEOTIDE-SEQUENCE; NON-A; VIRAL-HEPATITIS; ALPHA-3 DOMAIN AB Since the natural immune response to hepatitis C virus (HCV) is often unable to clear the infection, to enhance immunogenicity we studied substituted peptides from an HCV cytotoxic T lymphocyte (CTL) epitope (C7A2) from a conserved region of the HCV core protein (DLMGYIPLV) recognized by CTL lines from HLA-A2.1(+) HCV-infected patients and HLA-A2.1 transgenic mice. HLA-A2.1 binding, human and murine CTL recognition, and in vivo immunogenicity (using mice transgenic for human HLA-A2 in lieu of immunizing humans) were analyzed to define peptides with enhanced immunogenicity. Peptides substituted at position 1 showed enhanced HLA-A2 binding affinity, but paradoxically poorer immunogenicity. A peptide with Ala substituted at position 8 (8A) showed higher HLA-A2 binding affinity and CTL recognition and was a more potent in vivo immunogen in HLA-A2-transgenic mice, inducing higher CTL responses with higher avidity against native C7A2 than induced by C7A2 itself. These results suggest that peptide 8A is a more potent in vitro antigen and in vivo immunogen than C7A2 and may be useful as a vaccine component. They provide proof of principle that the strategy of epitope enhancement can enhance immunogenicity of a CTL epitope recognized by human CTL. C1 NCI, NIH, Metab Branch, Mol Immunogenet & Vaccine Res Sect, Bethesda, MD 20892 USA. NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA. NIH, Div Viral Prod, Lab Hepatitis Viruses, Ctr Biol Evaluat & Res,Food & Drug Adm, Bethesda, MD 20892 USA. RP Berzofsky, JA (reprint author), NCI, NIH, Metab Branch, Mol Immunogenet & Vaccine Res Sect, Bldg 10,Room 6B12, Bethesda, MD 20892 USA. RI Sarobe, Pablo/D-6976-2017 OI Sarobe, Pablo/0000-0003-0503-7905 FU NIAID NIH HHS [AI-21393] NR 69 TC 82 Z9 84 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP 15 PY 1998 VL 102 IS 6 BP 1239 EP 1248 DI 10.1172/JCI3714 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 122EX UT WOS:000076059900019 PM 9739058 ER PT J AU Zaitseva, MB Lee, S Rabin, RL Tiffany, HL Farber, JM Peden, KWC Murphy, PM Golding, H AF Zaitseva, MB Lee, S Rabin, RL Tiffany, HL Farber, JM Peden, KWC Murphy, PM Golding, H TI CXCR4 and CCR5 on human thymocytes: Biological function and role in HIV-1 infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID VIRUS TYPE-1 INFECTION; ACQUIRED IMMUNODEFICIENCY SYNDROME; LINE-TROPIC HIV-1; SCID-HU MOUSE; T-CELL; IN-VITRO; HUMAN THYMUS; ENVELOPE GLYCOPROTEIN; PROGENITOR CELLS; PERIPHERAL-BLOOD AB Thymocyte infection with HIV-1 is associated with thymic involution and impaired thymopoiesis, particularly in pediatric patients. To define mechanisms of thymocyte infection,,ve examined human thymocytes for expression and function of CXCR4 and CCR5, the major cell entry coreceptors for T cell line-tropic (T-tropic) and macrophage-tropic (M-tropic) strains of HIV-1, respectively, CXCR4 was detected on the surface of all thymocytes, CXCR4 expression on mature, high level TCR thymocytes was similar to that on peripheral blood T cells, but,vas much lower than that on immature thymocytes, including CD34(+) thymic progenitors. Consistent with this, stroma-derived factor-1 (SDF-1) induced calcium flux primarily in immature thymocytes, with CD34(+) progenitors giving the strongest response, In addition, SDF-1 mRNA was detected in thymic-derived stromal cells, and SDF-1 induced chemotaxis of thymocytes, suggesting that CXCR4; may play a role in thymocyte migration. Infection of immature thymocytes by the T-tropic HIV-1 strain LAI was 10-fold more efficient than that in mature thymocytes, consistent with their relative CXCR4 surface expression. Anti-CXCR4 antiserum or SDF-1 blocked fusion of thymocytes with cells expressing the LAI envelope. In contrast to CXCR4, CCR5 was detected at low levels on thymocytes, and CCR5 agonists did not induce calcium flux of chemotaxis in thymocytes, However, CD4(+) mature thymocytes;were productively infected with the CCR5-tropic strain Ba-L, and this infection was specifically inhibited with the CCR5 agonist, macrophage inflammatory protein-1 beta. Our data provide strong evidence that CXCR4 and CCR5 function as coreceptors for HIV-1. infection of human thymocytes. C1 US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Zaitseva, MB (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bldg 29B,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 58 TC 103 Z9 109 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1998 VL 161 IS 6 BP 3103 EP 3113 PG 11 WC Immunology SC Immunology GA 118WU UT WOS:000075864600057 PM 9743377 ER PT J AU Malozowski, S Stadel, BV Pian, LP AF Malozowski, S Stadel, BV Pian, LP TI Comparison of beclomethasone, salmeterol, and placebo in children with asthma 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 1 TC 3 Z9 3 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 3 PY 1998 VL 339 IS 10 BP 704 EP 704 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 115WA UT WOS:000075688100022 PM 9729145 ER PT J AU Laine, L Hopkins, RJ Girardi, LS AF Laine, L Hopkins, RJ Girardi, LS TI Has the impact of Helicobacter pylori therapy on ulcer recurrence in the United States been overstated? A meta-analysis of rigorously designed trials SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID CITRATE PLUS CLARITHROMYCIN; HEALING DUODENAL-ULCERS; RISK-FACTORS; PEPTIC-ULCER; DOUBLE-BLIND; OMEPRAZOLE; AMOXICILLIN; ERADICATION; INFECTION; RANITIDINE AB Objective: The aim of this study was to assess the effect of H. pylori eradication on ulcer recurrence in North American duodenal ulcer patients by examining only treatment studies that met rigorous methodologic criteria, Methods: Data sources were computerized bibliographic searches from 1983, review of reference lists, communication with companies that manufacture medications used for H, pylori therapy in the U.S., and H. pylori investigators, review of open presentations to the Food and Drug Administration, and review of abstracts from annual scientific meetings, Criteria for study inclusion were double blind, randomized North American trials of H, pylori therapy for duodenal ulcer, scheduled endoscopic follow-up exams for greater than or equal to 6 months, and H, pylori cure documented greater than or equal to 4 wk after completion of therapy by at least two endoscopic biopsy tests, Seven relevant trials were identified, Data were abstracted independently and disagreement was resolved by consensus, We obtained missing data and identified erroneous assessments through contact with an author or sponsor of all studies, Results: The common odds ratio for ulcer recurrence was 0.20 (95% CI, 0.13-0.31) and 2.8 patients would need to be successfully treated to prevent one ulcer recurrence at 6 months, The pooled ulcer recurrence rate at 6 months in patients with H, pylori eradication was 20%, Conclusion: Results of North American studies of highest methodological quality confirm that H, pylori eradication markedly decreases ulcer recurrence, Nevertheless, 20% of patients in these studies had ulcer recurrence within 6 months, despite successful cure of infection and no reported use of NSAIDs. Non-H. pylori, non-NSAID ulcers may be more common in the U.S. than previously believed, (Am J Gastroenterol 1998;93: 1409-1415, (C) 1998 by Am, Coil, of Gastroenterology). C1 Univ So Calif, Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA. US FDA, Div Antiinfect Drug Prod, Rockville, MD 20857 USA. RP Laine, L (reprint author), Univ So Calif, Sch Med, Dept Med, GI Div, LAC 12-137,2025 Zonal Ave, Los Angeles, CA 90033 USA. NR 29 TC 119 Z9 134 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 1998 VL 93 IS 9 BP 1409 EP 1415 DI 10.1111/j.1572-0241.1998.452_a.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 116VU UT WOS:000075746400003 PM 9732917 ER PT J AU Goldman, DW Breyer, RJ Yeh, D Brockner-Ryan, BA Alayash, AI AF Goldman, DW Breyer, RJ Yeh, D Brockner-Ryan, BA Alayash, AI TI Acellular hemoglobin-mediated oxidative stress toward endothelium: a role for ferryl iron SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE apoptosis; blood substitutes ID CROSS-LINKED HEMOGLOBIN; BLOOD SUBSTITUTE; NITRIC-OXIDE; HYDROGEN-PEROXIDE; DNA FRAGMENTATION; CELLS; INJURY; FERRYLMYOGLOBIN; OXYHEMOGLOBIN; DERIVATIVES AB We tested the hypothesis that chemical modifications used to produce stable, oxygen-carrying, Hb-based blood substitutes can induce cytotoxicity in endothelial cells in culture because of altered redox activity. We examined the interaction of hydrogen peroxide with nonmodified hemoglobin (HbA(0)) and two chemically modified hemoglobins, alpha-cross-linked hemoglobin (alpha-DBBF) and its polymerized form (poly-alpha-DBBF). Hydrogen peroxide-induced cell death (as assessed by lactate dehydrogenase release) in bovine aortic endothelial cells (BAEC) was completely inhibited by all three hemoglobin preparations, consistent with their known pseudoperoxidase activity [hemoglobin consumes peroxide as it cycles between ferric (Fe3+) and ferryl (Fe4+) hemes]. However, reaction of the modified hemoglobins, but not HbA(0), with hydrogen peroxide induced apoptotic cell death (as assessed by morphological changes and DNA fragmentation) that correlated with the formation of a long-lived ferrylhemoglobin. A preparation of ferryl-alpha-DBBF free of residual peroxide rapidly induced morphological changes and DNA fragmentation in BAEC, indicative of apoptotic cell death. Redox cycling of chemically modified hemoglobins by peroxide yielded a persistent ferryl iron that was cytotoxic to endothelial cells. C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bldg 29,Rm 112,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 56 TC 61 Z9 61 U1 1 U2 6 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 SEP PY 1998 VL 275 IS 3 BP H1046 EP H1053 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 114QR UT WOS:000075620800039 PM 9724312 ER PT J AU Berinstein, NL Grillo-Lopez, AJ White, CA Bence-Bruckler, I Maloney, D Czuczman, M Green, D Rosenberg, J McLaughlin, P Shen, D AF Berinstein, NL Grillo-Lopez, AJ White, CA Bence-Bruckler, I Maloney, D Czuczman, M Green, D Rosenberg, J McLaughlin, P Shen, D TI Association of serum Rituximab (IDEC-C2B8) concentration and anti-tumor response in the treatment of recurrent low-grade or follicular non-Hodgkin's lymphoma SO ANNALS OF ONCOLOGY LA English DT Article DE C2B8; follicular lymphoma; IDEC; immunotherapy; low grade; MABTHERA; monoclonal antibody; Rituxan ID B-CELL LYMPHOMA; CHIMERIC MONOCLONAL-ANTIBODY; CLINICAL-TRIAL; THERAPY; SEROTHERAPY; LEUKEMIA; CD20 AB Background, Monoclonal antibodies are being utilized for treatment of patients with low-grade non-Hodgkin's lymphoma as well as other cancers. Results from phase I and II clinical studies has shown that the chimeric monoclonal antibody Rituximab has minimal toxicity and significant therapeutic activity in low grade non-Hodgkin's lymphoma. Patients and methods: We have recently reported on a multicentre pivotal phase III clinical trial involving 166 patients with recurrent low-grade lymphoma who were treated with four infusions of Rituximab. Eighty patients (48%) achieved objective responses including 10 patients (6%) with complete responses. Overall, 126 patients (76%) had a greater than or equal to 20% reduction in overall tumor size. The median response duration and time to progression are 11.6 and 13.2 months, respectively. The infusional and long term toxicities were limited. Results. In this report we describe the pharmacokinetic data obtained on these patients. Measurable concentrations of Rituximab were detected in all patients after the first infusion and increased throughout the treatment course. The half-life of the monoclonal antibody increased from 76.3 hours after the first infusion to 205.8 hours after the fourth infusion and was concomitant with a four-fold decrease in the antibody clearance. At three months and six months post-treatment, the median Rituximab serum levels were 20.3 mu g/ml (range 0.0 to 96.8 mu g/ml in 104 patients) and 1.3 mu g/ml(range 0.0-28.7 mu g/ml in 13 patients), respectively. A statistically significant correlation was found between the median antibody concentration and response for multiple time points during the treatment and followup. The mean serum antibody concentration was also inversely correlated with measurements of tumor bulk and with the number of circulating B cells at baseline. Conclusions. We conclude that Rituximab is therapeutically effective against B-cell lymphoma. Pharmacokinetic data suggests that certain subsets of patients may possibly benefit from increased dosing and studies to address this are currently underway. C1 Toronto Sunnybrook Reg Canc Ctr, Dept Med, Toronto, ON M4N 3M5, Canada. Toronto Sunnybrook Reg Canc Ctr, Dept Immunol, Toronto, ON M4N 3M5, Canada. Univ Toronto, Toronto, ON, Canada. Idec Pharmaceut Corp, San Diego, CA USA. Ottawa Gen Hosp, Ottawa, ON K1H 8L6, Canada. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Univ Texas, MD Anderson Cancer Ctr, Houston, TX 77030 USA. RP Berinstein, NL (reprint author), Toronto Sunnybrook Reg Canc Ctr, Dept Med, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. NR 27 TC 341 Z9 358 U1 1 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 1998 VL 9 IS 9 BP 995 EP 1001 DI 10.1023/A:1008416911099 PG 7 WC Oncology SC Oncology GA 136BP UT WOS:000076838200018 PM 9818074 ER PT J AU Bala, S Hastings, KL Kazempour, K Inglis, S Dempsey, WL AF Bala, S Hastings, KL Kazempour, K Inglis, S Dempsey, WL TI Inhibition of tumor necrosis factor alpha alters resistance to Mycobacterium avium complex infection in mice SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; BEIGE MICE; HUMAN MONOCYTES; CELL DEFECT; IFN-GAMMA; TNF-ALPHA; T-CELLS; MACROPHAGES; INTRACELLULARE; REPLICATION AB Increased production of tumor necrosis factor alpha (TNF-alpha) appears to play an important role in the progression of human immunodeficiency virus disease. One treatment strategy being explored is the use of TNF-alpha inhibitors. TNF-alpha also appears to be important in conferring resistance to infections, and the inhibition of this cytokine may exacerbate the emergence of opportunistic pathogens, such as Mycobacterium avium complex (MAC). The present study examines the possibility that inhibition of TNF-alpha will increase the progression of disease in mice infected with MAC, C57BL/6 beige (bg/bg) mice have been shown to be highly susceptible to infection with MAC and are routinely used for testing of antimycobacterial drugs. However, bg/bg mice are known to exhibit impaired phagocyte and natural killer cell function, Since these cell types are important sources of TNF-alpha, the susceptibility of the bg/bg strain to infection with MAC was compared with those of the heterozygous (bg/+) and wild-type (+/+) strains of C57BL/6 mice. The susceptibilities of the bg/bg and bg/+ strains of mice infected with MAC were found to be comparable. The +/+ strain was the least susceptible, Mycobacterial burden and serum TNF-alpha levels increased over time in all the strains of mice tested. The bg/+ strain of C57BL/6 mice was then chosen to measure the activity of TNF-alpha antagonists. Treatment with dexamethasone decreased serum TNF-alpha levels and increased mycobacterial burden. Treatment with anti-TNF-alpha antibody or pentoxifylline did not significantly alter serum TNF-alpha levels but increased mycobacterial burden. Treatment with thalidomide neither consistently altered mycobacterial burden in the spleens or livers of infected mice nor affected serum TNF-alpha levels. C1 US FDA, Div Special Pathogen & Immunol Drug Prod HFD590, Rockville, MD 20857 USA. US FDA, Div Antiviral Drug Prod HFD530, Rockville, MD 20857 USA. RP Bala, S (reprint author), US FDA, Div Special Pathogen & Immunol Drug Prod HFD590, 5600 Fishers Ln, Rockville, MD 20857 USA. NR 36 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 1998 VL 42 IS 9 BP 2336 EP 2341 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 116RB UT WOS:000075737400033 PM 9736559 ER PT J AU Crofford, LJ Tan, B Donnelly, R AF Crofford, LJ Tan, B Donnelly, R TI STATs induced by IFN-gamma and IL-4 in primary rheumatoid synoviocytes bind to the cyclooxygenase-2 promoter. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. US FDA, Bethesda, MD 20892 USA. RI Crofford, Leslie/J-8010-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 620 BP S136 EP S136 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600621 ER PT J AU Kuipers, JG Bialowons, A Dollmann, P Yu, DTY Raybourne, RB Kohler, L Wollenhaupt, J Zeidler, H AF Kuipers, JG Bialowons, A Dollmann, P Yu, DTY Raybourne, RB Kohler, L Wollenhaupt, J Zeidler, H TI The effect of HLA-B27 on Chlamydial invasion and replication in the host cell. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Hannover Med Sch, Div Rheumatol, D-3000 Hannover, Germany. Univ Calif Los Angeles, Div Rheumatol, Los Angeles, CA USA. US FDA, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 699 BP S149 EP S149 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600700 ER PT J AU Shamin, E Rider, L Perez, M Cawkwell, G Wise, R Miller, F AF Shamin, E Rider, L Perez, M Cawkwell, G Wise, R Miller, F TI Demographic and clinical features of patients who develop myositis following immunization. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ S Florida, St Petersburg, FL 33701 USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1030 BP S204 EP S204 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601031 ER PT J AU Malinauskas, RA Sarraf, P Barber, KM Truskey, GA AF Malinauskas, RA Sarraf, P Barber, KM Truskey, GA TI Association between secondary flow in models of the aorto-celiac junction and subendothelial macrophages in the normal rabbit SO ATHEROSCLEROSIS LA English DT Article DE flow visualization; hemodynamics; arteries; atherosclerosis; macrophages ID WALL SHEAR-STRESS; HUMAN CAROTID BIFURCATION; HUMAN ABDOMINAL-AORTA; ATHEROSCLEROTIC LESIONS; PULSATILE FLOW; BLOOD-FLOW; ARTERIAL; LOCALIZATION; BRANCHES; PATTERNS AB In order to examine the association between arterial fluid dynamics and the distribution of subendothelial macrophages in the normal rabbit aorta, steady and pulsatile particle flow visualization was performed in a geometrically realistic model of the rabbit aorto-celiac junction region. Over a range of aorto-celiac steady flow ratios, particle pathlines along the upstream lateral aortic walls curved to enter the celiac orifice, while two asymmetric regions of reversing spiral secondary flow originated along the downstream lateral portions of the orifice flow divider. These regions increased in size as either the Reynolds number or flow into the celiac artery increased. In pulsatile flow studies, particles along the lateral aortic walls near the celiac orifice began to spiral into the branch during peak systole. During systolic deceleration, the size of this spiral flow region increased as particles reversed direction to enter the celiac orifice. This contrasted with flow patterns directly upstream and downstream of the orifice, which remained unidirectional throughout this period even along the distal lip of the orifice. The highest frequency of subendothelial white blood cells in the normal rabbit aorta was associated with regions where secondary flow patterns occurred, and where the orientation of endothelial cell nuclei deviated from the major direction of aortic flow. Secondary flow patterns may aid the accumulation of monocytes and macrophages about the lateral regions of the celiac artery flow divider by transporting monocytes to the walls, allowing them time to attach to the endothelial cells, or by stimulating the endothelial cells to express leukocyte adhesion molecules. These same regions are associated with increased endothelial permeability to low density lipoprotein and, under hypercholesterolemic conditions, lesion origination. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. RP Malinauskas, RA (reprint author), US Food & Drug Adm, Ctr Devices & Radiol Hlth, Off Sci & Technol, 9200 Corp Blvd HFZ-132, Rockville, MD 20850 USA. RI Truskey, George/B-2215-2012 FU NHLBI NIH HHS [HL41372] NR 46 TC 17 Z9 17 U1 0 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD SEP PY 1998 VL 140 IS 1 BP 121 EP 134 DI 10.1016/S0021-9150(98)00129-4 PG 14 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 112LD UT WOS:000075495400014 PM 9733223 ER PT J AU Demian, HW McDermott, K AF Demian, HW McDermott, K TI Regulatory perspective on characterization and testing of orthopedic bone cements SO BIOMATERIALS LA English DT Article DE PMMA; bone cement; pre-clinical test methods; US regulatory perspective ID FAILURE MECHANISMS; IMPLANT INTERFACE; HIP-ARTHROPLASTY; FATIGUE; METHACRYLATE; MACROPHAGES; INCLUSIONS; POROSITY; FRACTURE; INVITRO AB This paper provides a general regulatory background of acrylic bone cements, chemical composition information on several commercially available bone cements, physical and chemical methods of analyses, mechanical test methods, and risks and failure mechanisms of acrylic bone cements. Suggestions and recommendations presented in Tables 2 and 3 are not mandatory requirements but reflect data and methodologies which the FDA's Orthopedic Devices Branch (ORDB) believes to be acceptable to evaluate most pre-clinical data. FDA may require information in addition to that contained in this paper. In some instances, a sponsor may be able to sufficiently justify the omission of some tests. Although this paper describes certain administrative requirements, it does not take the place of the requirements contained in Title 21 of the Code of Federal Regulations (21 CFR) Parts 801, 807, 812, and 814 or those found in the statute. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Rockville, MD 20850 USA. RP Demian, HW (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, 9200 Corp Blvd HFZ-410, Rockville, MD 20850 USA. EM hwd@fdadr.cdrh.fda.gov NR 92 TC 26 Z9 26 U1 0 U2 7 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 SEP PY 1998 VL 19 IS 17 BP 1607 EP 1618 DI 10.1016/S0142-9612(97)00122-1 PG 12 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 132YQ UT WOS:000076659900009 PM 9830987 ER PT J AU Liao, W Chiu, K Mabuni, C Soliman, M AF Liao, W Chiu, K Mabuni, C Soliman, M TI Analysis of sennosides A and B from dieter's tea by HPLC-diode array spectrophotometry and negative ion electrospray mass spectrometry SO BULLETIN OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY C1 Calif Dept Hlth Serv, Div Food Drug & Radiat Safety, Food & Drug Lab Branch, Los Angeles, CA 90015 USA. US FDA, Los Angeles Dist Lab, Los Angeles, CA 90015 USA. RP Liao, W (reprint author), Calif Dept Hlth Serv, Div Food Drug & Radiat Safety, Food & Drug Lab Branch, 1521 W Pico Blvd, Los Angeles, CA 90015 USA. NR 7 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0007-4861 J9 B ENVIRON CONTAM TOX JI Bull. Environ. Contam. Toxicol. PD SEP PY 1998 VL 61 IS 3 BP 317 EP 324 PG 8 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 114TX UT WOS:000075626200006 PM 9724354 ER PT J AU Yi, P Sun, X Doerge, DR Fu, PP AF Yi, P Sun, X Doerge, DR Fu, PP TI An improved P-32-postlabeling/high-performance liquid chromatography method for the analysis of the malondialdehye-derived 1,N-2-Propanodeoxyguanosine DNA adduct in animal and human tissues SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID LIPID-PEROXIDATION PRODUCTS; WHITE BLOOD-CELLS; DEOXYGUANOSINE ADDUCT; CARBONYL-COMPOUNDS; ESCHERICHIA-COLI; NUCLEIC-ACID; LIVER DNA; MALONALDEHYDE; ALDEHYDES; ACROLEIN AB Malondialdehyde (MDA) is a major lipid peroxidation product that is mutagenic and tumorigenic. The MDA-modified DNA adduct, 3-(2-deoxy-beta-D-erythro-pentofuranosyl)pyr [1,2-alpha]purin-10(3H)-one (M(1)G), has been detected in human tissues and may be a marker of human cancer risk. In this paper, we describe an improved P-32-postlabeling/HPLC method for sensitive detection and quantitation of this MDA-modified 2'-deoxyribonucleotide adduct. Specific improvements include (i) unequivocal structural identification of the postlabeling products, both the 3',5'-bisphosphate of M(1)G (MDA-3',5'-dGDP) and the 5'-monophosphate of M1G (MDA-5'-dGMP); (ii) efficient separation of the P-32-postlabeling products by HPLC; and (iii) the incorporation of a synthetically prepared MDA-modified DNA (or the 3'-monophosphate of M(1)G) with a known modification level as an internal standard. This improved quantitative methodology provides high intra- and inter-assay reproducibility and has been applied to the analysis of this adduct in rodent and human samples. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM pfu@nctr.fda.gov NR 59 TC 29 Z9 29 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD SEP PY 1998 VL 11 IS 9 BP 1032 EP 1041 DI 10.1021/tx9800497 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 123AE UT WOS:000076103000007 PM 9760277 ER PT J AU Doerge, DR Chang, HC Divi, RL Churchwell, MI AF Doerge, DR Chang, HC Divi, RL Churchwell, MI TI Mechanism for inhibition of thyroid peroxidase by leucomalachite green SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID FREE-RADICAL FORMATION; MALACHITE GREEN; GENTIAN-VIOLET; CHRONIC TOXICITY; CRYSTAL VIOLET; CARCINOGENICITY; IODINATION; METABOLISM; REDUCTION; RATS AB The triphenylmethane dye, malachite green (MG), is used to treat and prevent; fungal and parasitic infections in the aquaculture industry. It has been reported that the reduced metabolite of MG, leucomalachite green (LMG), accumulates in the tissues of fish treated with MG. MG is structurally related to other triphenylmethane dyes (e.g., gentian violet and pararosaniline) that are carcinogenic in the liver, thyroid, and other organs of experimental animals. The ability of LMG to inhibit thyroid peroxidase (TPO), the enzyme that catalyzes the iodination and coupling reactions required for thyroid hormone synthesis, was determined in this study. LMG inhibited TPO-catalyzed tyrosine iodination (half-maximal inhibition at ca. 10 mu M). LMG also inhibited the TPO-catalyzed formation of thyroxine in low-iodine human goiter thyroglobulin (half-maximal inhibition at ca. 10 mu M) using a model system that measures simultaneous iodination and coupling. Direct inhibition of the coupling reaction by LMG was shown using a coupling-only system containing chemically preiodinated thyroglobulin as the substrate. Incubation of LMG with TPO, iodide, and tyrosine in the presence of a H2O2-generating system yielded oxidation products that were identified by using on-line LC/APCI-MS as desmethyl LMG, 2desmethyl LMG, 3desmethyl LMG, MG, and MG N-oxide. Similar products from LMG were observed in incubations with TPO and H2O2 alone. These findings suggest that the anti-thyroid effects (increased serum thyroid-stimulating hormone and decreased serum thyroxine) observed in rats treated with LMG result from blockade of hormone synthesis through alternate substrate inhibition and that chronic exposure could cause thyroid follicular cell tumors through a hormonal mechanism. The observed TPO-catalyzed oxidative demethylation of LMG to a primary arylamine also suggests a genotoxic mechanism for tumor formation is possible. C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. EM ddoerge@nctr.fda.gov FU PHS HHS [224-93-0001] NR 30 TC 37 Z9 47 U1 1 U2 6 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 SEP PY 1998 VL 11 IS 9 BP 1098 EP 1104 DI 10.1021/tx970226o PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 123AE UT WOS:000076103000015 PM 9760285 ER PT J AU Honig, PK Gillespie, BK AF Honig, PK Gillespie, BK TI Clinical significance of pharmacokinetic drug interactions with over-the-counter (OTC) drugs SO CLINICAL PHARMACOKINETICS LA English DT Review ID SELF-MEDICATION; GASTRIC-ACIDITY; RANITIDINE; ABSORPTION; ANTACIDS; BIOAVAILABILITY; CIPROFLOXACIN; THEOPHYLLINE; POLYPHARMACY; KETOCONAZOLE C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. Georgetown Univ, Dept Med, Washington, DC USA. RP Gillespie, BK (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, 5600 Fishers Lane, Rockville, MD 20857 USA. EM Gillespieb@CDER.FDA.GOV NR 42 TC 12 Z9 13 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PD SEP PY 1998 VL 35 IS 3 BP 167 EP 171 DI 10.2165/00003088-199835030-00001 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 122ZL UT WOS:000076101300001 PM 9784931 ER PT J AU Vanyushin, BF Lopatina, NG Wise, CK Fullerton, FR Poirier, LA AF Vanyushin, BF Lopatina, NG Wise, CK Fullerton, FR Poirier, LA TI Butylated hydroxytoluene modulates DNA methylation in rats SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE butylated hydroxytoluene; cancer; DNA methylation DNA methyl transferase; 5-methyldeoxycytidine ID CYTOSINE METHYLTRANSFERASE; S-ADENOSYLHOMOCYSTEINE; LIVER CARCINOGENESIS; MESSENGER-RNA; IN-VITRO; EXPRESSION; GENE; ANTIOXIDANTS; DIETHYLNITROSAMINE; ADENOSYLMETHIONINE AB The major observation of this investigation is that a single intraperitoneal injection of butylated hydroxytoluene (BHT 60 mg/kg body mass) results within a few hours in a strong increase in nuclear DNA(cytosine-5)-methyl transferase (methyl transferase) activity in the liver, kidneys, heart, spleen, brain and lungs of male rats In most organs, the rise in methyl transferase activity is observed as early as 4 h after BHT injection, it reaches a maximum at 8 h and then, except for lungs and brain, gradually decreases to its initial level at 16 h. At the maximum induction times, the methyl transferase activity in liver, kidney and spleen increases by about 16-, 3- and 5-fold, respectively. A second BHT injection at 96 h results in a secondary rise in hepatic methyl transferase activity. Isoelectric focusing electrophoresis of control rat liver nuclear extracts showed methyl transferase activity in the pi 4.7 and 7.4 protein fractions. Both fractions methylate calf thymus DNA better than they do Drosophila melanogaster DNA. In similar extracts from BHT-treated rats, the methyl transferase activity is found in three protein fractions with pi values equal to 4.0, 6.2 and 9.5, respectively. Most of the methyl transferase fractions from the livers of BHT-treated rats methylate the completely unmethylated D. melanogaster DNA better than they do calf thymus DNA. Thus, BHT induces methyl transferase activity that preferably provides de novo DNA methylation. BHT injection had no significant effect on the hepatic contents of S-adenosylmethionine (AdoMet), S-adenosylhomocysteine (AdoHcy) and AdoMet/AdoHcy ratios. While BHT injection did not alter the 5-methyldeoxycytidine content in liver DNA, it did appear to alter such content in other organs. BHT appears to cause the reversible changes in the methylation status of an internal cytosine residue in some CCGG sites of the rat liver cytosine DNA-methyl transferase gene. BHT induces also hypomethylation of the renal methyl transferase gene and the hepatic c-Ha-ms gene. While BHT also increases the hepatic mRNA transcripts for the S-adenosylmethionine synthetase and the p53 genes, it had no detectable effects on the corresponding mRNA transcripts for methyl transferase homologous to murine methyl transferase. Thus, BHT induces tissue-specific reversible changes in methyl transferase activity and methylation of total DNA and various genes in rats. A strong increase in methyl transferase activity in rat liver is accompanied with BHT-induced change in the methyl transferase set observed in this organ. C1 Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Div Mol Basis Ontogenesis, Moscow 119899, Russia. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Vanyushin, BF (reprint author), Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Div Mol Basis Ontogenesis, Moscow 119899, Russia. NR 66 TC 12 Z9 13 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD SEP PY 1998 VL 256 IS 3 BP 518 EP 527 DI 10.1046/j.1432-1327.1998.2560518.x PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 120NW UT WOS:000075963300003 PM 9780227 ER PT J AU Krauthamer, V Jones, JL AF Krauthamer, V Jones, JL TI Effects of biphasic electric shocks on calcium changes in cultured cardiac myocytes SO IN VITRO & MOLECULAR TOXICOLOGY-A JOURNAL OF BASIC AND APPLIED RESEARCH LA English DT Article ID FIELD STIMULATION; MYOCARDIAL-CELLS; DEFIBRILLATION; COUNTERSHOCK; WAVEFORMS AB We hypothesize that different electric shock waveforms will have different effects on the intracellular calcium response of heart cells. Spatial and temporal changes in intracellular calcium ion concentration were recorded optically from isolated heart cells exposed to two different electric shock waveforms. Isolated chick-embryo cardiac myocytes were cultured and loaded with fura-2 AM, a calcium-specific dye. Calcium-related fluorescence changes were measured during the application of either asymmetric or symmetric biphasic electric shocks. Both shock waveforms produced an initial calcium peak followed by a prolonged calcium elevation, which made cells refractory to pacing. The prolonged elevation lasted longer with symmetric biphasic shocks. For asymmetric shocks, calcium elevations were earlier and higher at cell regions near the anode. The result that symmetric biphasic shocks produce a more prolonged cytosolic calcium elevation is consistent with previous findings that electric shocks induce transmembrane potential changes, which cause post-shock dysfunction. C1 US FDA, Div Phys Sci, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20852 USA. Vet Affairs Med Ctr, Cardiac Res Lab, Washington, DC 20422 USA. RP Krauthamer, V (reprint author), US FDA, Div Phys Sci, Ctr Devices & Radiol Hlth, Off Sci & Technol, HFZ 133,12725 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 25 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1097-9336 J9 IN VITRO MOL TOXICOL JI In Vitro Mol. Toxicol.-J. Basic Appl. Res. PD FAL PY 1998 VL 11 IS 3 BP 221 EP 228 PG 8 WC Toxicology SC Toxicology GA 138TZ UT WOS:000076990300002 ER PT J AU Wang, RB Doolan, DL Charoenvit, Y Hedstrom, RC Gardner, MJ Hobart, P Tine, J Sedegah, M Fallarme, V Sacci, JB Kaur, M Klinman, DM Hoffman, SL Weiss, WR AF Wang, RB Doolan, DL Charoenvit, Y Hedstrom, RC Gardner, MJ Hobart, P Tine, J Sedegah, M Fallarme, V Sacci, JB Kaur, M Klinman, DM Hoffman, SL Weiss, WR TI Simultaneous induction of multiple antigen-specific cytotoxic T lymphocytes in nonhuman primates by immunization with a mixture of four Plasmodium falciparum DNA plasmids SO INFECTION AND IMMUNITY LA English DT Article ID SPOROZOITE SURFACE PROTEIN-2; INTRADERMAL GENE IMMUNIZATION; HUMAN MALARIA PARASITE; CIRCUMSPOROZOITE PROTEIN; RHESUS-MONKEYS; INFECTED HEPATOCYTES; VACCINE CANDIDATE; SYNTHETIC PEPTIDE; INTERFERON-GAMMA; CELL EPITOPES AB CD8(+) T cells have been implicated as critical effector cells in protective immunity against malaria parasites developing within hepatocytes, A vaccine that protects against malaria by inducing CD8(+) T cells will probably have to include multiple epitopes on the same protein or different proteins, because of parasite polymorphism and genetic restriction of T-cell responses. To determine if CD8(+) T-cell responses against multiple P. falciparum proteins can be induced in primates by immunization with plasmid DNA, rhesus monkeys were immunized intramuscularly with a mixture of DNA plasmids encoding four P. falciparum proteins or with individual plasmids. All six monkeys immunized with PfCSP DNA, seven of nine immunized with PfSSP2 DNA, and five of six immunized with PfExp-1 or PfLSA-1 DNA had detectable antigen-specific cytotoxic T lymphocytes (CTL) after in vitro restimulation of peripheral blood mononuclear cells. CTL activity was genetically restricted and dependent on CD8(+) T cells. By providing the first evidence for primates that immunization with a mixture of DNA plasmids induces CD8(+) T-cell responses against all the components of the mixture, these studies provide the foundation for multigene immunization of humans. C1 USN, Med Res Inst, Malaria Program, Rockville, MD 20889 USA. Henry M Jackson Fdn, Rockville, MD 20852 USA. Vical Inc, San Diego, CA 92121 USA. Virogenet Corp, Troy, NY 12180 USA. Univ Maryland, Dept Immunol & Microbiol, Baltimore, MD 21201 USA. US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. RP Weiss, WR (reprint author), USN, Med Res Inst, Malaria Program, 12300 Washington Ave, Rockville, MD 20852 USA. RI Doolan, Denise/F-1969-2015 NR 60 TC 54 Z9 59 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1998 VL 66 IS 9 BP 4193 EP 4202 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 113RF UT WOS:000075564500028 PM 9712767 ER PT J AU Merkel, TJ Stibitz, S Keith, JM Leef, M Shahin, R AF Merkel, TJ Stibitz, S Keith, JM Leef, M Shahin, R TI Contribution of regulation by the bvg locus to respiratory infection of mice by Bordetella pertussis SO INFECTION AND IMMUNITY LA English DT Article ID SIGNAL-TRANSDUCTION; VIRULENCE FACTORS; ELECTROPHORETIC TRANSFER; POLYACRYLAMIDE GELS; REPRESSED GENES; RNA-POLYMERASE; BRONCHISEPTICA; VIR; EXPRESSION; MUTATIONS AB Whooping cough is an acute respiratory disease caused by the small, gram-negative bacterium Bordetella pertussis. B. pertussis expresses several factors that contribute to its ability to cause disease. These factors include surface-associated molecules, which are involved in the adherence of the organism to respiratory epithelial cells, as well as several extracellular toxins that inhibit host defenses and induce damage to host tissues, The expression of virulence factors in B, pertussis is dependent upon the bvg locus, which consists of three genes: bvgA, bvgS, and bvgR, The bvgAS genes encode a two-component regulatory system consisting of a sensor protein, BvgS, and a transcriptional activator, BvgA. Upon modification by BvgS, BvgA binds to the promoter regions of the bvg-activated genes and activates transcription. One of the bvg-activated genes, bvgR, is responsible for the regulation of the bvg-repressed genes, the functions of which are unknown, The fact that these genes are regulated by the bvg locus suggests that they play a role in the pathogenesis of the bacterium. In order to evaluate the contribution of bvg-mediated regulation to the virulence of B. pertussis and determine if expression of the bvg-repressed genes is required for the virulence of B. pertussis, we examined the ability of B. pertussis mutants, defective in their ability to regulate the expression of the bvg-activated and/or the bvg-repressed genes, to cause disease in the mouse aerosol challenge model. Our results indicate that the bvgR-mediated regulation of gene expression contributes to respiratory infection of mice. C1 NIDR, OIIB, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Merkel, TJ (reprint author), NIDR, OIIB, NIH, Bldg 30,Rm 303,30 Convent Dr,MSC 4350, Bethesda, MD 20892 USA. NR 48 TC 52 Z9 53 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1998 VL 66 IS 9 BP 4367 EP 4373 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 113RF UT WOS:000075564500050 PM 9712789 ER PT J AU Furuke, K Bloom, ET AF Furuke, K Bloom, ET TI Redox-sensitive events in Fas-induced apoptosis in human NK cells include ceramide generation and protein tyrosine dephosphorylation SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE CPP32; IL-2; NK cells; oxidation-reduction; phosphorylation ID NATURAL-KILLER-CELLS; PERIPHERAL T-CELLS; MEDIATED APOPTOSIS; DEATH FACTOR; EXPRESSION; INVOLVEMENT; LIGAND; CYTOTOXICITY; REQUIREMENT; ACTIVATION AB We previously reported that intracellular oxidation-reduction (redox) regulates NK cell functions and that IL-2-activated NK cells undergo apoptosis upon contact with NK-sensitive target cells. We now report that apoptosis in activated human NK cells is also regulated by redox, Thiol deprivation increased apoptosis in NK cells induced by anti-fas mAb or Fas ligand-transfected cells, and pretreatment of cells with N-acetyl cysteine, which increased intracellular glutathione, partially inhibited the apoptosis and reversed the effect of thiol-deficient medium, suggesting that Fas-induced apoptosis in NK cells is also redox sensitive. Thiol deprivation did not alter cell surface Fas expression, but did increase ceramide generation following Fas engagement. Although exogenous ceramides induced apoptosis of NK cells, thiol depletion had no effect on this apoptosis. Thiol deprivation increased CPP32 activation induced by Fas engagement, but not by ceramides, These findings suggest that, if ceramide is required for Fas-induced apoptosis, thiol deprivation affects the Fas-mediated signaling pathway at the generation of ceramide and/or upstream thereof. Though tyrosine phosphorylation following Fas engagement was not significantly affected by thiol deprivation, tyrosine dephosphorylation was delayed, suggesting that tyrosine phosphatases may also be redox sensitive. The notion that dephosphorylation is important in the Fas signaling pathway is supported by the finding that tyrosine phosphatase inhibitors significantly enhanced both CPP32 activity and apoptosis following Fas ligation, We conclude that events downstream of tyrosine phosphorylation and upstream of CPP32 activation, including tyrosine dephosphorylation and possibly ceramide generation, are sensitive to regulation by redox in human NK cells, requiring a reducing environment for optimal protection from apoptosis induced by Fas ligation. C1 US FDA, Ctr Biol Evaluat & Res, Cellular Immunol Lab, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Bloom, ET (reprint author), US FDA, Ctr Biol Evaluat & Res, Cellular Immunol Lab, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. NR 63 TC 17 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD SEP PY 1998 VL 10 IS 9 BP 1261 EP 1272 DI 10.1093/intimm/10.9.1261 PG 12 WC Immunology SC Immunology GA 120DT UT WOS:000075940100002 PM 9786425 ER PT J AU Rorke, EA Sizemore, N Mukhtar, H Couch, LH Howard, PC AF Rorke, EA Sizemore, N Mukhtar, H Couch, LH Howard, PC TI Polycyclic aromatic hydrocarbons enhance terminal cell death of human ectocervical cells SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE ectocervical cells; p53; 3-methylcholanthrene; immortalization; human papilloma virus; P-32-postlabeling ID HUMAN PAPILLOMAVIRUS TYPE-16; CERVICAL-CANCER; DNA-ADDUCTS; EPITHELIAL-CELLS; P-32-POSTLABELING ANALYSIS; TRANSGLUTAMINASE ACTIVITY; RECEPTOR EXPRESSION; RETINOID REGULATION; SMOKE CONSTITUENTS; ENVELOPE FORMATION AB Polycyclic aromatic hydrocarbons (PAH) are a class of chemical carcinogens whose active metabolites form DNA adducts, resulting in specific mutational events. The tumor suppressor protein p53 is believed to play a pivotal role in the ability of cells to response to DNA damage, resulting in either cell cycle arrest in G(1) or apoptosis under conditions Of excessive damage This growth inhibition it is associated with the concomitant induction of p53 and enhanced terminal cell differentiation. In this study we evaluated the effects of PAH on cell growth, cell differentiation, xenobiotic metabolism, and DNA adduct levels in normal ectocervical epithelial cells (ECE) and compared them to cervical cells whose p53 have been inactivated either by binding to viral HPV E6 oncogene (ECE16-1) or by mutation (C33A). The PAH 3-methylcholanthrene (3MC) inhibited normal ECE and to a lesser extent ECE16-1 cell proliferation. Not only did the growth inhibition occur at lower concentrations in the normal cells but the extent of inhibition was also greater in normal as compared to immortalized cells. Benzanthracene (BA) had a minor effect on normal ECE cells with no effect on immortalized ECE16-1 cells. C33A cell growth was unaffected by 3MC and BA. Terminal cell death was enhanced only in normal ECE cells as evidenced by increased envelope formation and was paralleled by an increase in the level of p53 following 3MC treatment. The differentiation status of the 3MC-treated cells was similar to untreated cells as indicated by three independent markers of cell differentiation; transglutaminase, involucrin, keratin expression. There was no difference in the pattern or level of DNA adducts formed in normal and immortalized cells following 3MC treatment. In addition the basal level of metabolism of C-14-BaP to phenols, diols and quinnones was unaltered by pretreatment with either 3MC or BA. These results demonstrate that immortalized cervical cells are less sensitive to toxicant damage [i.e. cell proliferation and terminal differentiation], and as a result, immortalized cells proliferate in the presence of genotoxic damage and are at increased risk for mutations and cancer. C1 Case Western Reserve Univ, Dept Environm Hlth Sci, Sch Med, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Reprod Biol, Sch Med, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Dermatol, Sch Med, Cleveland, OH 44106 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Rorke, EA (reprint author), Case Western Reserve Univ, Dept Environm Hlth Sci, Sch Med, Cleveland, OH 44106 USA. FU NIEHS NIH HHS [ES03648, ES05227] NR 60 TC 20 Z9 20 U1 0 U2 2 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD SEP PY 1998 VL 13 IS 3 BP 557 EP 563 PG 7 WC Oncology SC Oncology GA 110GL UT WOS:000075371900021 PM 9683793 ER PT J AU Osterberg, RE AF Osterberg, RE TI Symposium XII: Current and future directions of phototoxicity - Presentations from the 17th Annual Meeting of the American College of Toxicology, November 10-13, 1996 - Introductory remarks SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Editorial Material C1 US FDA, CDER, Rockville, MD USA. RP Osterberg, RE (reprint author), US FDA, CDER, HFD-520, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD SEP-OCT PY 1998 VL 17 IS 5 BP 533 EP 536 DI 10.1080/109158198226026 PG 4 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 116FZ UT WOS:000075714800001 ER PT J AU Kornhauser, A Wei, RR Wamer, WG AF Kornhauser, A Wei, RR Wamer, WG TI In vitro assays for phototoxicity SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE biomarkers; in vitro; photosensitizers; phototoxicity ID INVITRO AB This paper summarizes a few in vitro methods to assess photodamage in cells irradiated with UV of various wavelengths in the presence of a number of photosensitizers. A single in vitro assay for phototoxicity (photoirritation) is not likely to be predictive because of different mechanisms of phototoxicity and diverse cellular targets for injury. A number of methods have to be combined to provide a better prediction of these phenomena. Measurement of mechanistically relevant biomarkers also represents a promising area of in vitro testing for phototoxicity, and it is also briefly reviewed in this paper: Photodynamic sensitizers, representing a large class of phototoxic agents, can now be identified by sensitive measurement of photooxidative damage to cellular RNA and DNA. Currently, US government agencies have not identified a single in vitro assay for phototoxicity which would be acceptable for replacing an in vivo assay for regulatory purposes. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Kornhauser, A (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HSF-128, Washington, DC 20204 USA. NR 13 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD SEP-OCT PY 1998 VL 17 IS 5 BP 567 EP 570 PG 4 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 116FZ UT WOS:000075714800006 ER PT J AU Ellis, AL AF Ellis, AL TI Regulatory perspective on in vitro assays as predictors of phototoxicity and photo co-carcinogenicity SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE drugs; FDA; photo co-carcinogenicity; photogenotoxicity; photosensitization; phototoxicity ID SKIN-CANCER; RISK AB Drugs from a variety of chemical classes used for a wide range of therapeutic indications can be photosensitizers in humans Several drags are phototoxic in animal models as well; there are no nonclinical data for many. In vitro tests have been developed as predictors of phototoxicity and although they have been used as screens, none have replaced the in vivo tests done in rodents (usually mice or guinea pigs) since these have been good predictors of clinical phototoxicity. Some phototoxic drug classes are co-carcinogens with ultraviolet radiation (UVA and/or UVB) in hairless mice, specifically psoralens, retinoids, and fluoroquinolones. Treatment with 8-methoxypsoralen and ultraviolet A radiation for psoriasis is also carcinogenic in humans. It has been suggested that in, vitro photogenotoxicity assays using microorganisms or mammalian. cells may be predictive of photo co-carcinogenicity. Some attractions of these in vitro assays, compared to the hairless mouse photo co-carcinogenicity assay, are their generally shorter duration and lower cost as well as reducing the number of animals used in research. Currently, personnel at the Food and Drug Administration (FDA) are examining the available data on phototoxicity, photogenotoxicity, and photo co-carcinogenicity to determine how this information can best be used to regulate and label drug products, and considering which assays should be recommended under specific circumstances. C1 US FDA, Ctr Drug Evaluat & Res, Div Antiinfect Drug Prod, Rockville, MD 20850 USA. RP Ellis, AL (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Antiinfect Drug Prod, 9201 Corp Blvd,HFD-520, Rockville, MD 20850 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD SEP-OCT PY 1998 VL 17 IS 5 BP 571 EP 575 DI 10.1080/109158198226080 PG 5 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 116FZ UT WOS:000075714800007 ER PT J AU Howard, PC Churchwell, MI Couch, LH Marques, MM Doerge, DR AF Howard, PC Churchwell, MI Couch, LH Marques, MM Doerge, DR TI Formation of N-(carboxymethyl)fumonisin B(1), following the reaction of fumonisin B(1) with reducing sugars SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE fumonisin B(1); fumonisins; N-(carboxymethyl)fumonisin B(1); detoxification; Amadori rearrangement; Maillard reaction; reducing sugars; mycotoxin ID FUSARIUM-MONILIFORME STRAINS; SPHINGOLIPID BIOSYNTHESIS; F-MONILIFORME; RAT-LIVER; CORN; MYCOTOXINS; TOXICITY; LEUKOENCEPHALOMALACIA; CANCER; SWINE AB The fumonisins are mycotoxins produced by fungi that contaminate primarily corn and are toxic through interruption of intracellular sphingolipid synthesis. Several reports have indicated that fumonisin B(1) concentrations decreased when heated in aqueous solutions of reducing sugars. The incubation of fumonisin B1 with D-glucose resulted in the formation of N-(carboxymethyl)fumonisin BL, which was characterized by NMR and electrospray mass spectroscopy. We determined the methylene carbon of the carboxymethyl group is derived from C1 on glucose, while the carbonyl carbon is derived from the C2 of glucose, using (13)C glucose. Apparently N-(carboxymethyl)fumonisin B1 arises from Schiffs base formation, Amadori rearrangement to a B-ketoamine, and oxidation with molecular oxygen. N-(Carboxymethyl)fumonisin B1 formation is favored by alkaline conditions (pH > 7), requires molecular oxygen, and is catalyzed by several reducing sugars. N-(carboxymethyl)fumonisin B(1) was detected in raw corn samples that contained fumonisin B(1) (0.5-1.4 ppm) at an average of 4% of the fumonisin B(1) levels. C1 US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Microbiol & Chem, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Howard, PC (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM phoward@nctr.fda.gov RI Marques, M. Matilde/E-2535-2012 OI Marques, M. Matilde/0000-0002-7526-4962 NR 53 TC 52 Z9 52 U1 0 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 SEP PY 1998 VL 46 IS 9 BP 3546 EP 3557 DI 10.1021/jf980194q PG 12 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 122QG UT WOS:000076082500025 ER PT J AU Slater, JE Paupore, E Zhang, YT Colberg-Poley, AM AF Slater, JE Paupore, E Zhang, YT Colberg-Poley, AM TI The latex allergen Hev b 5 transcript is widely distributed after subcutaneous injection in BALB/c mice of its DNA vaccine SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE rodent; allergy; vaccination; immunotherapy; latex ID DIRECT GENE-TRANSFER; IMMUNE-RESPONSE; PLASMID DNA; IN-VIVO; DENDRITIC CELLS; SURFACE-ANTIGEN; MOUSE MUSCLE; IMMUNIZATION; VIRUS; PROTECTION AB Background: DNA vaccines reduce IgE responses to selected allergens, but severe reactions to the expressed antigen may limit the usefulness of the technique in allergen immunotherapy. Objective: We sought to determine the extent of spread of an injected DNA vaccine in mice. Methods: We placed the gene encoding the potent Hevea latex allergen Hev b 5 in a mammalian expression vector and injected this DNA vaccine subcutaneously into BALB/c mice. At several times after injection, the presence of Hev b 5 transcript was determined in multiple tissues by RT-PCR, The identity of the amplification product was confirmed by Southern hybridization and restriction analyses. Results: Hev b 5 RNA appeared at the injection site and in the lymph nodes, spleen, and lungs within 1 day after injection and persisted for at least 14 days. Hev b 5 RNA was also identified in the blood and tongue 14 days after injection. Antibody and cell-mediated responses to Hev b 5 were also noted in the immunized animals at later time points. As expected, animals injected with the identical plasmid containing the Hev b 5 DNA in the antisense orientation mounted no immune response to Hev b 5. Conclusions: The rapid and widespread appearance of the Hev b 5 transcript in the injected mice confirms that DNA is translocated from the injection site, transcribed, and expressed in immune and nonimmune tissues after injection. Controlling the extent and degree of expression in specific target tissues may allow therapeutic DNA vaccination with plasmids that encode potentially toxic allergens. C1 Childrens Natl Med Ctr, Dept Allergy Immunol & Pulm Med, Childrens Res Inst, Ctr Mol Mechanisms Dis Res, Washington, DC 20010 USA. George Washington Univ, Sch Med, Washington, DC USA. Childrens Natl Med Ctr, Childrens Res Inst, Ctr Virol Immunol & Infect Dis Res, Washington, DC 20010 USA. RP Slater, JE (reprint author), US FDA, Lab Immunobiochem, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 29 TC 45 Z9 46 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 1998 VL 102 IS 3 BP 469 EP 475 DI 10.1016/S0091-6749(98)70137-X PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 124ZN UT WOS:000076212800023 PM 9768590 ER PT J AU Chou, HJ AF Chou, HJ TI Determination of diethanolamine and N-nitrosodiethanolamine in fatty acid diethanolamides SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID CHROMATOGRAPHY AB Diethanolamine (DEA) is a precursor of N-nitrosodiethanolamine (NDELA), an animal carcinogen. A gas chromatographic (GC) method was developed for determining DEA in fatty acid diethanolamides that are commonly used in cosmetic products. Methanolic solutions of the amides were analyzed by GC with flame ionization detection on either a wide-bore methyl silicone (Rt(x)-1) or 95% dimethyl-5% diphenyl polysiloxane (SPB-5) capillary column. Recovery of DEA from fatty acid dialkanolamides at fortification levels of 0.50, 1.00, and 5.00% ranged from 94 to 100%, In a survey of commercial fatty acid diethanolamides, DEA was found at levels ranging from 1.1 to 14.0%, and most were in good agreement with manufacturer's DEA specifications. Fatty acid diethanolamides also were analyzed for NDELA by liquid chromatography interfaced to a thermal energy analyzer. Recovery of NDELA from fatty acid diethanolamides at fortification levels of 50, 100, and 200 ppb averaged 95%, No NDELA was found in any of the fatty acid diethanolamide samples analyzed. C1 US FDA, Washington, DC 20204 USA. RP Chou, HJ (reprint author), US FDA, 200 C St SW, Washington, DC 20204 USA. NR 15 TC 12 Z9 12 U1 1 U2 2 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 1998 VL 81 IS 5 BP 943 EP 947 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 123GL UT WOS:000076117400005 PM 9772735 ER PT J AU Schermerhorn, PG Chu, PS Ngoh, MA AF Schermerhorn, PG Chu, PS Ngoh, MA TI Determination of cephapirin and ceftiofur residues in bovine milk by liquid chromatography with ultraviolet detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A method capable of quantitating cephapirin at a level of 20 ng/mL and ceftiofur at a level of 50 ng/mL was developed for raw bovine milk. Raw bovine milk is deproteinated with acetonitrile. The supernatant is collected and then acetonitrile is removed under reduced pressure while warming in a water bath at 40 degrees-50 degrees C. The extract is mixed with water and loaded onto a conditioned C-18 solid-phase extraction column. Analytes are eluted with acetonitrile, which is removed completely under a stream of nitrogen gas. Analytes are separated from coextractives by gradient elution with an ion-pair mobile phase on a reversed-phase column and are detected by ultraviolet absorbance at 290 nm. Mean recoveries from fortified milk samples ranged from 79 to 87% for cephapirin and from 76 to 86% for ceftiofur, with intralaboratory coefficients of variation ranging of 6-10% and 7-14%, respectively. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Schermerhorn, PG (reprint author), US EPA, BARC E, Bldg 306, Beltsville, MD 20705 USA. NR 8 TC 9 Z9 10 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 1998 VL 81 IS 5 BP 973 EP 977 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 123GL UT WOS:000076117400009 PM 9772739 ER PT J AU Stibitz, S AF Stibitz, S TI IS481 and IS1002 of Bordetella pertussis create a 6-base-pair duplication upon insertion at a consensus target site SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SEQUENCE AB The insertion sequence IS481 and its isoform IS1002 have been observed to transpose into the bvgAS locus of Bordetella pertussis, for which the DNA sequence has previously been determined. Upon insertion of IS481 at three different sites and IS1002 at one site, a 6-bp sequence originally present was found at the junction of bvg and insertion sequence DNA. This indicates that, contrary to prior reports, IS481 and IS1002 do create a duplication upon insertion. In this light, examination of these and other examples of IS481 and IS1002 reported in the literature leads to the observation that the 6-bp recognition sequence usually fits the consensus NCTAGN. The near-palindromic nature of this sequence, when directly repeated at the ends of IS481 or IS1002, apparently led to the interpretation that 5 of these base pairs were part of the terminal inverted repeats flanking these elements. C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, Bethesda, MD 20892 USA. RP Stibitz, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 8 TC 19 Z9 22 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 1998 VL 180 IS 18 BP 4963 EP 4966 PG 4 WC Microbiology SC Microbiology GA 120WG UT WOS:000075979900029 PM 9733704 ER PT J AU Shi, YF Chang, AC Jiang, H Wu, TC AF Shi, YF Chang, AC Jiang, H Wu, TC TI Advances in biomedical research - The Fifth Annual Joint Scientific Symposium of NIH/FDA CAA and Washington DC Chapter of SCBA, Bethesda, Md., August 29, 1998 SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article C1 Amer Red Cross, Holland Lab, Washington, DC 20006 USA. US FDA, Rockville, MD 20857 USA. NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. RP Shi, YF (reprint author), Amer Red Cross, Holland Lab, Washington, DC 20006 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD SEP-OCT PY 1998 VL 5 IS 5 BP 395 EP 399 DI 10.1007/BF02253449 PG 5 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 127WP UT WOS:000076373800009 ER PT J AU Skinner, GE Larkin, JW AF Skinner, GE Larkin, JW TI Conservative prediction of time to Clostridium botulinum toxin formation for use with time-temperature indicators to ensure the safety of foods SO JOURNAL OF FOOD PROTECTION LA English DT Article ID MODIFIED ATMOSPHERES; EXTENDED DURABILITY; REFRIGERATED FOODS; PROCESSED FOODS; LAG PHASE; GROWTH; PRODUCTS; STORAGE; MICROBIOLOGY; INTEGRATORS AB Integrating-type time-temperature indicators (TTIs) may be utilized to warn food processors and consumers about storage conditions that may have rendered a food potentially hazardous. As an example of how integrated TTIs could be manufactured to emulate an infinite set of time-temperature situations, a set of conditions which have supported C. botulinum growth and toxin production was compiled. The time-temperature curve representing conservative times required for toxin formation was constructed with data from literature relating to toxin formation as a function of temperature in any media or food product. This set of critical time-temperature data is fit by a conservative empirical relationship that can be used to predict combinations of incubation times and storage temperatures that represent a potential health risk from C. botulinum in foods. A TTI could be constructed to indicate deviation from such a given set of conditions to bring attention to foods that may have been exposed to potentially hazardous temperatures with respect to C. botulinum toxin formation. C1 US FDA, Natl Ctr Food Safety & Technol, Div Food Proc & Packaging, Food Proc Hazard Anal Branch, Summit Argo, IL 60501 USA. RP Skinner, GE (reprint author), US FDA, Natl Ctr Food Safety & Technol, Div Food Proc & Packaging, Food Proc Hazard Anal Branch, Summit Argo, IL 60501 USA. EM ges@vm.cfsan.fda.gov NR 46 TC 23 Z9 23 U1 0 U2 8 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 SEP PY 1998 VL 61 IS 9 BP 1154 EP 1160 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 118ZQ UT WOS:000075871200011 PM 9766067 ER PT J AU Sado, PN Jinneman, KC Husby, GJ Sorg, SM Omiecinski, CJ AF Sado, PN Jinneman, KC Husby, GJ Sorg, SM Omiecinski, CJ TI Identification of Listeria monocytogenes from unpasteurized apple juice using rapid test kits SO JOURNAL OF FOOD PROTECTION LA English DT Article ID EPIDEMIC LISTERIOSIS; ESCHERICHIA-COLI; SODIUM-CHLORIDE; PH; TEMPERATURE; GROWTH; OUTBREAK; PRODUCTS; SURVIVAL; MILK AB A microbiological survey of 50 retail juices was conducted in the fall of 1996. These juices were analyzed for Listeria monocytogenes, Escherichia coli O157:H7, Salmonella, coliforms, fecal coliforms, and pH. Two unpasteurized juices were positive for L. monocytogenes: an apple juice and an apple raspberry blend with a pH of 3.78 and 3.75, respectively. Three L. monocytogenes isolates were characterized. The colonies were typical for Listeria sp. on Oxford and Lithium chloride-phenylethanol-moxalactam agars and were beta-hemolytic on sheep blood agar. The isolates required 5 days of incubation at 35 degrees C to produce a positive rhamnose reaction in a phenol red carbohydrate broth. This slow rhamnose utilization resulted in these isolates not being identified using the Micro-ID test strip (Organon Technika). However, the isolates were positive for L. monocytogenes using the API Listeria strip (BioMerieux) and a multiplex polymerase chain reaction for detection of the hemolysis (hyla) and invasion-associated protein (iap) genes. C1 US FDA, Bothell, WA 98041 USA. Washington State Dept Agr, Olympia, WA 98501 USA. Univ Washington, Dept Environm Hlth, Seattle, WA 98195 USA. RP Sado, PN (reprint author), US FDA, Bothell, WA 98041 USA. EM psado@ora.fda.gov FU NIEHS NIH HHS [P42 ES004696] NR 19 TC 50 Z9 52 U1 0 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 SEP PY 1998 VL 61 IS 9 BP 1199 EP 1202 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 118ZQ UT WOS:000075871200021 PM 9766077 ER PT J AU Dollins, AB Cestaro, VL Pettit, DJ AF Dollins, AB Cestaro, VL Pettit, DJ TI Efficacy of repeated psychophysiological detection of deception testing SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; psychophysiological detection of deception; peak of tension; habituation; repeated measures; respiration; galvanic skin resistance; heart rate; statistical analysis ID GUILTY KNOWLEDGE; MOTIVATION; POWER AB Physiological measures were recorded during repeated psychophysiological detection of deception (PDD) tests to determine if reaction levels change with test repetition. Two groups of 22 healthy male subjects completed six peak of tension PDD tests on each of two test days. A minimum between test day interval of six days was maintained. The treatment group was programmed to respond deceptively to one of seven test questions while the control group was programmed to respond truthfully to all questions. The respiration and galvanic skin resistance (GSR) line lengths, GSR peak response amplitude and latency, and cardiovascular inter-beat-interval (LEI) were calculated for each response. Analyses indicated that, except for GSR peak response latency, differential physiological reactivity during a PDD test did not change significantly over repeated tests or days; there was a decrease in average respiration line lengths at the initial test(s) of each day; and differential changes in average respiration line length, GSR peak latency. and cardiovascular IBI responses corresponded to deception. Power analyses were calculated to assist in result interpretation. It is suggested that PDD decision accuracy, concerning:: subject veracity, should not decrease during repeated testing. C1 Dept Def Polygraph Inst, Ft McClellan, AL USA. US FDA, Off Criminal Invest, Rockville, MD 20857 USA. RP Dollins, AB (reprint author), Bldg 3195, Ft McClellan, AL 36205 USA. NR 44 TC 3 Z9 3 U1 1 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 SEP PY 1998 VL 43 IS 5 BP 1016 EP 1023 PG 8 WC Medicine, Legal SC Legal Medicine GA 113UW UT WOS:000075572900014 PM 9729818 ER PT J AU Fitzsimmons, SP Rotz, BT Shapiro, MA AF Fitzsimmons, SP Rotz, BT Shapiro, MA TI Asymmetric contribution to ig repertoire diversity by V kappa exons: Differences in the utilization of v kappa 10 exons SO JOURNAL OF IMMUNOLOGY LA English DT Article ID B-CELL LINES; REPETITIVE DNA-SEQUENCES; GENE FAMILY EXPRESSION; VARIABLE REGION GENES; MONOCLONAL-ANTIBODIES; V(D)J RECOMBINATION; TRANSCRIPTION EFFICIENCY; IMMUNOGLOBULIN GENES; CONSERVED SEQUENCE; METHYLATION STATUS AB The mouse has approximately 140 germline V kappa genes, and functional V kappa exons are expressed at roughly equivalent levels in the preimmune repertoire. We have examined the expression of individual members of the V kappa 10 family. V kappa 10A and V kappa 10B genes have been utilized in numerous hybridomas and myelomas, while V kappa 10C has not, In this study, we have cloned the V kappa 10C gene and shown that it is structurally functional, has the expected promoter elements and recombination signal sequences, and that it is capable of recombination, V kappa 10C mRNA, however, is present at levels at least 1000-fold lower than V kappa 10A end V kappa 10B in adult spleens. While there are no sequence differences in the octamer or TATA box between V kappa 10C and V kappa 10A, there are three nucleotide changes in the promoter region. These promoters equally drive the expression of a reporter gene in B cells or plasma cells, but the V kappa 10A promoter is able to drive expression in pre-B cell lines significantly better than the V kappa 10C promoter (p < 0.05). V kappa 10C rearrangements can be detected in bone marrow and splenic DNA, Therefore, the lack of V kappa 10C expression may reflect the inability of V kappa 10C-rearranged cells to undergo positive or negative selection. Our results suggest that the available Ab repertoire is shaped not only by the number of structurally functional genes, but also by the ability of assembled genes to be expressed at critical points during B cell maturation. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20892 USA. RP Shapiro, MA (reprint author), US FDA, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, 1401 Rockville Pike,Bldg 29B,Room 5E12, Rockville, MD 20852 USA. EM Fitzsimmons@cber.fda.gov; Shapirom@cber.fda.gov NR 73 TC 6 Z9 6 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 1 PY 1998 VL 161 IS 5 BP 2290 EP 2300 PG 11 WC Immunology SC Immunology GA 112UB UT WOS:000075511600028 PM 9725223 ER PT J AU Weiss, WR Ishii, KJ Hedstrom, RC Sedegah, M Ichino, M Barnhart, K Klinman, DM Hoffman, SL AF Weiss, WR Ishii, KJ Hedstrom, RC Sedegah, M Ichino, M Barnhart, K Klinman, DM Hoffman, SL TI A plasmid encoding murine granulocyte-macrophage colony-stimulating factor increases protection conferred by a malaria DNA vaccine SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD8+ T-CELLS; PLASMODIUM-YOELII SPOROZOITES; MARROW-DERIVED CELLS; INTERFERON-GAMMA; CIRCUMSPOROZOITE PROTEIN; CPG MOTIFS; INFECTED HEPATOCYTES; BACTERIAL-DNA; EXPRESSION VECTOR; ANTIBODY-RESPONSE AB Using the murine parasite Plasmodium yoelii (Py) as a model for malaria vaccine development, we have previously shown that a DNA plasmid encoding the Py circumsporozoite protein (PyCSP) can protect mice against sporozoite infection. We now report that mixing a new plasmid PyCSP1012 with a plasmid encoding murine granulocyte-macrophage colony-stimulating factor (GM-CSF) increases protection against malaria, and we have characterized in detail the increased immune responses due to GM-CSF, PyCSP1012 plasmid alone protected 28% of mice, and protection increased to 58% when GM-CSF was added (p < 0.0001). GM-CSF plasmid alone did not protect, and control plasmid expressing inactive GM-CSP did not enhance protection. GM-CSF plasmid increased Abs to PyCSP of IgG1, IgG2a, and IgG2b isotypes, but not IgG3 or IgM. IFN-gamma responses of CD8(+) T cells to the PyCSP 280-288 amino acid epitope increased but CTL activity did not change. The most dramatic changes after adding GM-CSF plasmid were increases in Ag-specific IL-2 production and CD4(+) T cell proliferation. We hypothesize that GM-CSF may act on dendritic cells to enhance presentation of the PyCSP Ag, with enhanced IL-2 production and CD4(+) T cell activation driving the increases in Abs and CD8(+) T cell function. Recombinant GM-CSP is already used in humans for medical purposes, and GM-CSF protein or plasmids may be useful as enhancers of DNA vaccines. C1 USN, Med Res Inst, Malaria Program, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Sect Retroviral Immunol, Bethesda, MD 20892 USA. Univ Maryland, Baltimore, MD 21201 USA. Vical Inc, San Diego, CA 92121 USA. RP Weiss, WR (reprint author), USN, Med Res Inst, Malaria Program, 12300 Washington Ave, Rockville, MD 20852 USA. RI Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 49 TC 130 Z9 143 U1 1 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1998 VL 161 IS 5 BP 2325 EP 2332 PG 8 WC Immunology SC Immunology GA 112UB UT WOS:000075511600032 PM 9725227 ER PT J AU Nass, PH Elkins, KL Weir, JP AF Nass, PH Elkins, KL Weir, JP TI Antibody response and protective capacity of plasmid vaccines expressing three different herpes simplex virus glycoproteins SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 22nd International Herpesvirus Workshop CY AUG 02-08, 1997 CL SAN DIEGO, CALIFORNIA ID INTRADERMAL GENE IMMUNIZATION; GENITAL HERPES; DNA VACCINES; IMMUNE-RESPONSES; TYPE-1; VACCINATION; MICE; INFECTION; CHALLENGE; INDUCTION AB Plasmid expression vectors were constructed that contained the genes encoding herpes simplex virus 1 (HSV-1) glycoproteins C (gC), D (gD), and E (gE), Mice receiving two intramuscular injections of expression plasmid (50 mu g) produced a specific HSV-1 antibody response. Mice receiving the go plasmid were protected against a lethal intraperitoneal challenge of HSV-1 (5 x 10(4) pfu) but not against more demanding challenge doses. Protection with gC or gE plasmid vaccination could be demonstrated only if the inoculating dose of DNA was increased to 250 mu g. In contrast, all mice immunized with vaccinia recombinants expressing either gC or gE survived HSV-1 challenge. Analysis of the HSV-1 antibody isotype produced by plasmid immunization revealed a response dominated by IgG2a, Combination delivery of all three glycoprotein expression plasmids provided better protection against lethal challenge, but mice receiving the combination were still not able to withstand increased challenge doses of virus. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab DNA Viruses, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Mycobacteria, Rockville, MD 20852 USA. RP Weir, JP (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab DNA Viruses, HFM-457,1401 Rockville Pike, Rockville, MD 20852 USA. NR 28 TC 27 Z9 27 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1998 VL 178 IS 3 BP 611 EP 617 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 112UL UT WOS:000075512700002 PM 9728527 ER PT J AU Shapiro, RL Altekruse, S Hutwagner, L Bishop, R Hammond, R Wilson, S Ray, B Thompson, S Tauxe, RV Griffin, PM AF Shapiro, RL Altekruse, S Hutwagner, L Bishop, R Hammond, R Wilson, S Ray, B Thompson, S Tauxe, RV Griffin, PM CA Vibrio Working Grp TI The role of Gulf Coast oysters harvested in warmer months in Vibrio vulnificus infections in the United States, 1988-1996 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Infectious-Diseases-Society-of-America CY SEP 07-16, 1997 CL SAN FRANCISCO, CALIFORNIA SP Infect Dis Soc Amer ID IRON; EPIDEMIOLOGY; ASSOCIATION; SATURATION; SHELLSTOCK; DISEASE; FLORIDA; CHOLERA; SERUM AB Vibrio vulnificus infections are highly lethal and associated with consumption of raw shellfish and exposure of wounds to seawater. V. vulnificus infections were reported to the Centers for Disease Control and Prevention from 23 states. For primary septicemia infections, oyster trace-backs were performed and water temperature data obtained at harvesting sites. Between 1988 and 1996, 422 infections were reported; 45% were wound infections, 43% primary septicemia, 5% gastroenteritis, and 7% from undetermined exposure. Eighty-six percent of patients were male, and 96% with primary septicemia consumed raw oysters. Sixty-one percent with primary septicemia died; underlying liver disease was associated with fatal outcome, All trace-backs with complete information implicated oysters harvested in the Gulf of Mexico; 89% were harvested in water >22 degrees C, the mean annual temperature at the harvesting sites (P <.0001), Control measures should focus on the increased risk from oysters harvested from the Gulf of Mexico during warm months as well as education about host susceptibility factors. C1 Ctr Dis Control & Prevent, Foodborne & Diarrheal Dis Branch, Epidem Intelligence Serv, Epidemiol Program Off, Atlanta, GA USA. Ctr Dis Control & Prevent, Biostat & Informat Management Branch, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, Atlanta, GA USA. US FDA, Epidemiol Branch, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Bur Environ Epidemiol, State Florida Dept Hlth, Tallahassee, FL USA. State Louisiana Dept Hlth & Hosp, Epidemiol Sect, New Orleans, LA USA. Texas Dept Hlth, Infect Dis Epidemiol & Surveillance Div, Austin, TX 78756 USA. Alabama Dept Publ Hlth, Div Epidemiol, Montgomery, AL 36102 USA. RP Shapiro, RL (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Fruit St, Boston, MA 02114 USA. NR 25 TC 126 Z9 147 U1 0 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1998 VL 178 IS 3 BP 752 EP 759 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 112UL UT WOS:000075512700019 PM 9728544 ER PT J AU Kanegane, C Sgadari, C Kanegane, H Teruya-Feldstein, J Yao, L Gupta, G Farber, JM Liao, F Liu, L Tosato, G AF Kanegane, C Sgadari, C Kanegane, H Teruya-Feldstein, J Yao, L Gupta, G Farber, JM Liao, F Liu, L Tosato, G TI Contribution of the CXC chemokines IF-10 and Mig to the antitumor effects of IL-12 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE Burkitt lymphoma; athymic mice, angiogenesis; cancer treatment ID CELL STIMULATORY FACTOR; NATURAL-KILLER-CELLS; INTERFERON-INDUCIBLE PROTEIN-10; LYMPHOCYTE MATURATION FACTOR; ANGIOGENESIS IN-VIVO; X-C CHEMOKINE; IFN-GAMMA; HETERODIMERIC CYTOKINE; FACTOR INTERLEUKIN-12; RECOMBINANT IL-12 AB The mechanisms by which interleukin-12 (IL-12) exerts antitumor effects have been difficult to dissect. In this study, we examined the potential contribution of the chemokines interferon-gamma-inducible protein-10 (IP-10) and Mig to the antitumor effects of IL-12. Using an athymic mouse model, local inoculations with IL-12 consistently produced tumor size reductions associated with characteristic tumor necrosis and vascular damage. These effects were indistinguishable from those produced by IF-10 or Mg injected locally in the same tumor model. Local and systemic treatment with IL-12 was associated with expression of the interferon-gamma (IFN-gamma), IP-10, and Mig genes and proteins in the tumor. Levels of IF-10 and Mig expression in the tumor; the liver, and the kidney were inversely correlated with tumor size. Administration in vivo of neutralizing antibodies to IF-10 and Mig reduced substantially the antitumor effects of IL-12 inoculated locally into the tumors. These results support the notion that IF-10 and Mig contribute to the antitumor effects of IL-12 through their inhibitory effects on tumor vasculature. C1 Food & Drug Adm, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NCI, Pathol Lab, Hematopathol Sect, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. PharMingen, San Diego, CA USA. RP Tosato, G (reprint author), Food & Drug Adm, Ctr Biol Evaluat & Res, Bldg 29A,Rm 2D16,1401 Rockville Pike HFM-538, Rockville, MD 20852 USA. RI Sgadari, Cecilia/H-4302-2016 OI Sgadari, Cecilia/0000-0003-0364-4912 NR 42 TC 131 Z9 136 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. PD SEP PY 1998 VL 64 IS 3 BP 384 EP 392 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 116VE UT WOS:000075745100014 PM 9738666 ER PT J AU Berlin, E Bhathena, SJ McClure, D Peters, RC AF Berlin, E Bhathena, SJ McClure, D Peters, RC TI Dietary menhaden and corn oils and the red blood cell membrane lipid composition and fluidity in hyper- and normocholesterolemic miniature swine SO JOURNAL OF NUTRITION LA English DT Article DE cholesterol; (n-3) fatty acids; (n-6) fatty acids; membrane fluidity; miniature swine ID FATTY-ACID COMPOSITION; ERYTHROCYTE-MEMBRANE; FLUORESCENCE POLARIZATION; FISH-OIL; PLASMA-MEMBRANE; INSULIN BINDING; LINOLENIC ACID; CHOLESTEROL; HEART; LIVER AB Fatty acids in the diet are readily incorporated into lipids in various tissues. However, it is not clear whether all tissues have the same level of incorporation. Second, (n-6) unsaturated fatty acids increase the fluidity of membranes, but this has not been shown for (n-3) fatty acids. in this study, we measured the incorporation of (n-6) and (n-3) fatty acids into erythrocyte membrane lipids and studied their effects on the fluidity of erythrocyte membranes. One group of female miniature swine was made hypercholesterolemic by feeding the swine cholesterol and lard for 2 mo; the other group served as controls and was fed a stock diet. Both groups were then fed either corn oil or menhaden oil or a mixture of the two for 23 additional weeks. Blood was collected at 0, 2, 4, 12 and 23 wk after initialization of the experimental diets, and fatty acid composition of phospholipids was assessed. Membrane phospholipids of pigs fed menhaden oil had elevated (n-3) fatty acids (20:5 and 22:6), and lower 18:2 than those fed corn oil. There was no difference in 20:4 content. The fatty acid changes occurred as early as 2 wk after consumption of the corn oil or menhaden oil in pigs previously fed a stock diet, but it took longer in pigs previously fed lard + cholesterol, indicating residual effects of pretreatment. Menhaden oil increased anisotropy (indicating decreased fluidity) more than corn oil for the nonpolar probe diphenylhexatriene (DPH) at earlier time points, but not at 23 wk. Erythrocyte membrane fluidity was significantly related to membrane polyunsaturate content, with (n-6) fatty acids having a greater influence than (n-3) fatty acids. A comparison of the present red blood cell fatty acid compositions with brain synaptosome fatty acid compositions for the same animals showed poor correlations for some of the fatty acids. There was no significant direct relationship between docosahexaenoate (DHA) concentrations in erythrocyte membranes with DHA concentrations in brain synaptosomes from cerebellum, forebrain and caudate nucleus. C1 ARS, Phytonutrients Lab, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD 20705 USA. ARS, Metab & Nutrient Interact Lab, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD 20705 USA. US FDA, Ctr Food Safety & Appl Nutr, Div Toxicol Studies, Beltsville Res Facil,US Dept Hlth & Human Serv, Laurel, MD 20708 USA. RP Bhathena, SJ (reprint author), ARS, Phytonutrients Lab, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD 20705 USA. NR 47 TC 34 Z9 37 U1 0 U2 2 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD SEP PY 1998 VL 128 IS 9 BP 1421 EP 1428 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 117ML UT WOS:000075785200003 PM 9732300 ER PT J AU Daveby, YD Aman, P Betz, JM Musser, SM AF Daveby, YD Aman, P Betz, JM Musser, SM TI Effect of storage and extraction on ratio of soyasaponin I to 2,3-dihydro-2,5-dihydroxy-6-methyl-4-pyrone-conjugated soyasaponin I in dehulled peas (Pisum sativum L) SO JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE LA English DT Article DE Pisum sativum; dehulled seeds; hulls; soyasaponins; DDMP-conjugate; storage; extraction ID STRUCTURAL ELUCIDATION; SAPONIN CONTENT; SEED AB The effects of solvent and time on extraction of 2,3-dihydro-2,5-dihydroxy-6-methyl-4-pyrone (DDMP)-conjugated soyasaponin I in dehulled peas (Pisum sativum L) were studied. Extraction in 80% ethanol gave a higher and more stable yield than 100% methanol over the time studied. Acetonitrile did not extract any detectable saponins. Both soyasaponin I and the DDMP-conjugated form were present in the extracts of dehulled, dried peas. The proportion of soyasaponin I to the DDMP-conjugate, calculated as the ratio of the molecular ions, increased with increasing extraction time, from an initial 0.24 after 0.5 h to 0.55 after 24 h of extraction in 80% ethanol, showing that the DDMP-conjugate was hydrolysed during the extraction. Storage of dried dehulled peas also increased the proportion of soyasaponin I, from 0.063 in newly harvested peas to 0.34 after 9 months of storage. Peas harvested in 1988 and stored for 7 years had a ratio of 0.78. These results clearly show that the DDMP-conjugate was converted to soyasaponin I both during storage and extraction of the peas. (C) 1998 Society of Chemical Industry. C1 Swedish Univ Agr Sci, Dept Food Sci, S-75007 Uppsala, Sweden. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Daveby, YD (reprint author), Swedish Univ Agr Sci, Dept Food Sci, S-75007 Uppsala, Sweden. NR 17 TC 26 Z9 26 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-5142 J9 J SCI FOOD AGR JI J. Sci. Food Agric. PD SEP PY 1998 VL 78 IS 1 BP 141 EP 146 PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 118XR UT WOS:000075866700019 ER PT J AU Park, EJ Vujcic, LK Anand, R Theodore, TS Quinnan, GV AF Park, EJ Vujcic, LK Anand, R Theodore, TS Quinnan, GV TI Mutations in both gp120 and gp41 are responsible for the broad neutralization resistance of variant human immunodeficiency virus type 1 MN to antibodies directed at V3 and non-V3 epitopes SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODIES; ENVELOPE GLYCOPROTEIN; TRANSMEMBRANE PROTEIN; ANTIGENIC VARIATION; POINT MUTATION; IN-VIVO; HIV-1; INFECTION; GENERATION; REGION AB The escape of human immunodeficiency virus type 1 from effects of neutralizing antibodies was studied by using neutralization-resistant (NR) variants generated by growing the neutralization-sensitive (NS) wild-type MN virus in the presence of human serum with neutralizing antibodies, more than 99% of which were directed at the V3 region of gp120. The variants obtained had broad neutralization resistance to human sera, without limitation with respect to the V3 specificity of the sera. The molecular basis for the resistance was evaluated with molecularly cloned viruses, as well as with pseudoviruses expressing envelope glycoproteins of the NS and NR phenotypes. Nucleotide sequence analyses comparing NS and NR clones revealed a number of polymorphisms, including six in the V1/V2 region, two in C4/V5 of gp120, three in the leucine zipper (LZ) domain of gp41, and two id the second external putative alpha-helix region of gp41. A series of chimeras from NS and NR env genes was constructed, and each was presented on pseudoviruses to locate the domain(s) which conferred the phenotypic changes. The neutralization phenotypes of the chimeric clones were found to be dependent on mutations in both the C4/V5 region of gp120 and the LZ region of gp41. Additionally, interaction between mutations in gp120 and gp41 was demonstrated in that a chimeric env gene consisting of a gp120 coding sequence from an NS clone and a gp41 sequence from an NR clone yielded a pseudovirus with minimal infectivity. The possible significance of predicted amino acid changes in these domains is discussed. The results indicate that polyvalent antibodies predominantly directed against V3 can induce NR through selection for mutations that alter interactions of other domains in the envelope complex. C1 Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. US Food & Drug Adm, Ctr Biol Evaluat & Res, Rockville, MD 20850 USA. NIAID, Mol Biol Lab, Bethesda, MD 20892 USA. RP Quinnan, GV (reprint author), Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM Quinnan@USUHSB.USUHS.mil FU NIAID NIH HHS [R21 AI037438, AI37438, R01 AI037438] NR 79 TC 49 Z9 51 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1998 VL 72 IS 9 BP 7099 EP 7107 PG 9 WC Virology SC Virology GA 109NK UT WOS:000075328600016 PM 9696803 ER PT J AU Zeng, LL Falgout, B Markoff, L AF Zeng, LL Falgout, B Markoff, L TI Identification of specific nucleotide sequences within the conserved 3 '-SL in the dengue type 2 virus genome required for replication SO JOURNAL OF VIROLOGY LA English DT Article ID YELLOW-FEVER VIRUS; PSEUDOKNOT STRUCTURE; SECONDARY STRUCTURE; CELL-PROTEINS; 3' TERMINUS; RNA GENOME; EXPRESSION; STRAIN; BIND AB The flavivirus genome is a positive-stranded similar to 11-kb RNA including 5' and 3' noncoding regions (NCR) of approximately 100 and 400 to 600 nucleotides (nt), respectively. The 3' NCR contains adjacent, thermodynamically stable, conserved short and long stem-and-loop structures (the 3' SL), formed by the 3' terminal similar to 100 nt. The nucleotide sequences within the 3'-SL are not well conserved among species. We examined the requirement for the 3'-SL in the context of dengue virus type 2 (DEN2) replication by mutagenesis of an infectious cDNA copy of a DEN2 genome. Genomic full-length RNA was transcribed in vitro and used to transfect monkey kidney cells. A substitution mutation, in which the 3'-terminal 93 nt constituting the wild-type (wt) DEN2 3'-SL sequence were replaced by the 96-nt sequence of the West Nile virus Wn) 3'-SL, was sublethal for virus replication. An analysis of the growth phenotypes of additional mutant viruses derived from RNAs containing DEN2-WN chimeric 3'-SL structures suggested that the wt DEN2 nucleotide sequence forming the bottom half of the long stem and loop in the 3'-SL was required for viability. One 7-bp substitution mutation in this domain resulted in a mutant virus that grew well in monkey kidney cells but was severely restricted in cultured mosquito cells. In contrast, transpositions of and/or substitutions In the wt DEN2 nucleo tide sequence in the top half of the long stem and in the short stem and loop were relatively well tolerated, provided the stem-loop secondary structure was conserved. C1 US FDA, Ctr Biol Evaluat & Res, Lab Vector Borne Virus Dis, Div Viral Prod, Bethesda, MD 20892 USA. RP US FDA, Ctr Biol Evaluat & Res, Lab Vector Borne Virus Dis, Div Viral Prod, Bldg 29A,Rm 1B17,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 34 TC 126 Z9 137 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD SEP PY 1998 VL 72 IS 9 BP 7510 EP 7522 PG 13 WC Virology SC Virology GA 109NK UT WOS:000075328600061 PM 9696848 ER PT J AU Wang, JH Roderiquez, G Oravecz, T Norcross, MA AF Wang, JH Roderiquez, G Oravecz, T Norcross, MA TI Cytokine regulation of human immunodeficiency virus type 1 entry and replication in human monocytes/macrophages through modulation of CCR5 expression SO JOURNAL OF VIROLOGY LA English DT Article ID MONOCYTE-DERIVED MACROPHAGES; GM-CSF PRODUCTION; MONONUCLEAR PHAGOCYTES; MOLECULAR-CLONING; HIV-1 INFECTION; T-LYMPHOCYTES; CDNA CLONING; CELL-LINES; IN-VITRO; RECEPTOR AB Human macrophages express chemokine receptors that act as coreceptors for human immunodeficiency virus type 1 (HIV-1) and are major targets for HIV-1 infection in vivo. The effects of cytokines on HIV-1 infection of macrophages and on the expression of CCR5, the principal coreceptor for macrophage-tropic viruses, have now been investigated. Expression of CCR5 on the surface of freshly isolated human monocytes was virtually undetectable by flow cytometry with the monoclonal antibody 5C7. However, after culture of monocytes for 48 h in serum-free medium, approximately 30% of the resulting macrophages expressed CCR5 and the cells were susceptible to infection by macrophage-tropic HIV-1. Addition of either macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) to the cultures markedly increased both the extent of HIV-1 entry and replication as well as surface expression of CCR5. In contrast, addition of the T-helper 2 (Th2) cell-derived cytokine interleukin-il (IL-4) or IL-13 prevented the expression of CCR5 induced by culture in medium alone, and IL-il inhibited virus entry, replication, and cytopathicity under these conditions. IL-4 or IL-13 also prevented the stimulatory effects of M-CSF or GM-CSF on CCR5 expression as well as HIV-1 entry and replication. In addition, IL-10 reversed the increase in CCR5 expression induced by pretreatment of cells with M-CSF. Although IL-10 also inhibits HIV-1 replication in macrophages, it did not suppress surface CCR5 expression induced by colony-stimulating factors. These results indicate that the cytokine environment determines the susceptibility of macrophages to HIV-1 infection by various mechanisms, one of which is the regulation of HIV-1 coreceptor expression. C1 NIH, US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. RP Norcross, MA (reprint author), NIH, US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bldg 29B,Room 4E12, Bethesda, MD 20892 USA. NR 65 TC 112 Z9 114 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1998 VL 72 IS 9 BP 7642 EP 7647 PG 6 WC Virology SC Virology GA 109NK UT WOS:000075328600081 PM 9696868 ER PT J AU Mikovits, JA Young, HA Vertino, P Issa, JPJ Pitha, PM Turcoski-Corrales, S Taub, DD Petrow, CL Baylin, SB Ruscetti, FW AF Mikovits, JA Young, HA Vertino, P Issa, JPJ Pitha, PM Turcoski-Corrales, S Taub, DD Petrow, CL Baylin, SB Ruscetti, FW TI Infection with human immunodeficiency virus type 1 upregulates DNA methyltransferase, resulting in de novo methylation of the gamma interferon (IFN-gamma) promoter and subsequent downregulation of IFN-gamma production SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; T-CELLS; HIV-INFECTION; COLON-CANCER; HUMAN FIBROBLASTS; CPG METHYLATION; HUMAN NEOPLASIA; LYMPH-NODES; EXPRESSION; PROGRESSION AB The immune response to pathogens is regulated by a delicate balance of cytokines. The dysregulation of cytokine gene expression, including interleukin-12 tumor necrosis factor alpha, and gamma interferon (IFN-gamma), following human retrovirus infection is well documented. One process by which such gene expression may be modulated is altered DNA methylation. In subsets of T-helper cells, the expression of IFN-gamma, a cytokine important to the immune response to viral infection, is regulated in part by DNA methylation such that mRNA expression inversely correlates with the methylation status of the promoter. Of the many possible genes whose methylation status could be affected by viral infection, we examined the IFN-gamma gene as a candidate. We show here that acute infection of cells with human immunodeficiency virus type 1 (HIV 1) results in (i) increased DNA methyltransferase expression and activity, (ii) an overall increase in methylation of DNA in infected cells, and (iii) the de novo methylation of a CpG dinucleotide in the IFN-gamma gene promoter, resulting in the subsequent downregulation of expression of this cytokine. The introduction of an antisense methyltransferase construct into lymphoid cells resulted in markedly decreased methyltransferase expression, hypomethylation throughout the IFN-gamma gene, and increased IFN-gamma production, demonstrating a direct link between methyltransferase and IFN-gamma gene expression. The ability of increased DNA methyltransferase activity to downregulate the expression of genes like the IFN-gamma gene may be one of the mechanisms for dysfunction of T cells in HIV-1-infected individuals. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Leukocyte Biol, Div Basic Sci, Frederick, MD 21702 USA. Johns Hopkins Med Inst, Ctr Oncol, Baltimore, MD 21231 USA. CBER, Rockville, MD 20892 USA. NIA, Immunol Lab, Baltimore, MD 21224 USA. RP Mikovits, JA (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, POB B,Bldg 567,Rm 253, Frederick, MD 21702 USA. FU NCI NIH HHS [CA43318, N0I-CO-56000, R01 CA043318] NR 87 TC 109 Z9 112 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1998 VL 18 IS 9 BP 5166 EP 5177 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 112FW UT WOS:000075484300024 PM 9710601 ER PT J AU Bauer, SR Ruiz-Hidalgo, MJ Rudikoff, EK Goldstein, J Laborda, J AF Bauer, SR Ruiz-Hidalgo, MJ Rudikoff, EK Goldstein, J Laborda, J TI Modulated expression of the epidermal growth factor-like homeotic protein dlk influences stromal-cell-pre-B-cell interactions, stromal cell adipogenesis, and pre-B-cell interleukin-7 requirements SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BONE-MARROW CULTURES; LONG-TERM CULTURE; ADIPOCYTE DIFFERENTIATION; LYMPHOCYTES-B; GENE; LYMPHOPOIESIS; INSULIN; MOUSE; HEMATOPOIESIS; INVITRO AB A close relationship exists between adipocyte differentiation of stromal cells and their capacity to support hematopoiesis. The molecular basis for this is unknown. We have studied whether dlk, an epidermal growth factor-like molecule that intervenes in adipogenesis and fetal liver hematopoiesis, affects both stromal cell adipogenesis and B-cell lymphopoiesis in an established pre-B-cell culture system. Pre B cell cultures require both soluble interleukin-7 (IL-7) and interactions with stromal cells to promote cell growth and prevent B-cell maturation or apoptosis. We found that BALB/c 3T3 fibroblasts express dlk and function as stromal cells. Transfection of these cells with antisense dlk decreased dlk expression and increased insulin-induced adipocytic differentiation. When antisense transfectants were used as stroma, IL-7 was no longer required to support the growth of pre-B cells and prevent maturation or apoptosis. Antisense dlk transfectants of S10 stromal cells also promoted pre-B-cell growth in the absence of IL-7. These results show that modulation of dlk on stromal cells can influence their adipogenesis and the IL-7 requirements of the pre-B cells growing in contact with them. These results indicate that dlk influences differentiation signals directed both to the stromal cells and to the lymphocyte precursors, suggesting that dlk may play an important role in the bone marrow hematopoietic environment. C1 Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Div Monoclonal Antibodies, Rockville, MD 20852 USA. Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Div Cellular & Gene Therapy, Rockville, MD 20852 USA. RP Laborda, J (reprint author), Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Div Monoclonal Antibodies, 1401 Rockville Pike, Rockville, MD 20852 USA. EM laborda@helix.nih.gov RI Bauer, Steven/G-5559-2012; Laborda, Jorge/L-5726-2014; Ruiz-Hidalgo, Maria/L-1956-2014; OI Laborda, Jorge/0000-0002-9210-838X; Bauer, Steven/0000-0003-2831-846X NR 51 TC 55 Z9 56 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1998 VL 18 IS 9 BP 5247 EP 5255 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 112FW UT WOS:000075484300032 PM 9710609 ER PT J AU Khromykh, LM Sklyarov, LY Sbitneva, IN Kopina, NA Zaitseva, MB Kazanskii, DB AF Khromykh, LM Sklyarov, LY Sbitneva, IN Kopina, NA Zaitseva, MB Kazanskii, DB TI Interaction of peptides of HIV proteins with continuous cell lines of different origin SO MOLECULAR BIOLOGY LA English DT Article DE HIV-1; gp120 and gp41 peptides; multiplet RGDS and RFDS forms; ForMLP; cell lines AB One of the most important peculiarities of viruses is their ability to mimic the natural biologically active ligands influencing proliferation of target cells. Three groups of peptides from separate regions of HIV proteins gp120 and gp41 were studied, including peptides homologous to HLA class II, linear peptides modified by multiplet fragments of proteins responsible for contact interaction, and multiplet forms of these fragments. The following fragments were used: RGDS, the adhesive part of extracellular matrix protein; RFDS, a peptide of HLA DR domain beta 1, and ForMLP peptide of chemotaxis. Human cell lines of different origin (T and B lymphocytes, as well as erythroblastoma K-562 cells) were used as test systems. The above-mentioned peptides are able to influence the proliferative activity of the cells. The presence of unmodified peptides homologous to those of class II HLA and of linear modified peptides able to contact with the CD4 coreceptor results in an enhanced proliferative response of the T cell line MOLT-4. Unmodified peptides homologous to class II HLA are able to interact with B cells IM-9 and CESS, as well as with nonlymphoid cells K-562 and stimulate their growth. Multiplet forms of RGDS and RFDS exhibit a specific effect on migration of different cell types. Cell activation by these peptides is mediated by their interaction with the integrin-type membrane structures which are specific for each cell subpopulation. C1 Russian Acad Med Sci, Blokhin Res Ctr Oncol, Moscow 115478, Russia. Russian Minist Hlth, Inst Immunol, Moscow 115478, Russia. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Khromykh, LM (reprint author), Russian Acad Med Sci, Blokhin Res Ctr Oncol, Moscow 115478, Russia. NR 19 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA CONSULTANTS BUREAU, 233 SPRING ST, NEW YORK, NY 10013 USA SN 0026-8933 J9 MOL BIOL+ JI Mol. Biol. PD SEP-OCT PY 1998 VL 32 IS 5 BP 725 EP 729 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 133HA UT WOS:000076680100015 ER PT J AU Lazarovici, P Jiang, H Fink, D AF Lazarovici, P Jiang, H Fink, D TI The 38-amino-acid form of pituitary adenylate cyclase-activating polypeptide induces neurite outgrowth in PC12 cells that is dependent on protein kinase C and extracellular signal-regulated kinase but not on protein kinase A, nerve growth factor receptor tyrosine kinase, p21(ras) G protein, and pp60(c-src) cytoplasmic tyrosine kinase SO MOLECULAR PHARMACOLOGY LA English DT Article ID MAP KINASE; NEURONAL DIFFERENTIATION; PHEOCHROMOCYTOMA CELLS; NEUROTROPHIN RECEPTORS; SELECTIVE INHIBITOR; DOWN-REGULATION; PC-12 CELLS; CYCLIC-AMP; ACID FORM; CAMP AB The 38-amino-acid isoform of pituitary adenylate cyclase-activating polypeptide (PACAP38) elicits a robust outgrowth of neurites in cultured PC12 cells. Initiation of neurite outgrowth occurs within 4-8 hr after the addition of PACAP38. Treatment with PACAP38 does not elicit collateral activation of p140(trk) nerve growth factor receptor tyrosine kinase activity, nor is it associated with tyrosine phosphorylation of suc1-associated neurotrophic factor target, a selective target of neurotrophin tyrosine kinase receptors. Coadministration of epidermal growth factor with PACAP38 elicits an enhanced response. Induction of neurites is also observed on the addition of PACAP38 to dominant negative Src and Ras PC12 cell variants. PACAP38 stimulates extracellular signal-regulated kinase (Erk) activity >10-fold within 5 min, and the effect is augmented by cotreatment with epidermal growth factor. Pretreatment with the cAMP-dependent protein kinase-selective inhibitor, H-89, is ineffective as an antagonist of PACAP38-induced neurite outgrowth, whereas down-regulation of protein kinase C (PKC) by phorbol ester or incubation with PKC-selective inhibitors GF109203X and calphostin C effectively blocks PACAP38-stimulated neurite formation. Stimulation of Erk activity is inhibited by incubation with PD90859, a pharmacological antagonist of the threonine/tyrosine dual-specificity Erk. inhibition of ligand-stimulated Erk activation prevents PACAP38-induced neurite outgrowth. Collectively, these findings indicate that PACAP38-stimulated neuritogenesis requires PKC and Erk activation but is independent of cAMP-dependent protein kinase, nerve growth factor receptor tyrosine kinase, p21(ras) G protein, and pp60(c-src) cytoplasmic tyrosine kinase. C1 Hebrew Univ Jerusalem, Fac Med, Sch Pharm, Dept Pharmacol, IL-91010 Jerusalem, Israel. NICHHD, Growth Factors Sect, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. RP Fink, D (reprint author), US FDA, CBER, Div Cytokine Biol, 1401 Rockville Pike,Suite 200 N-HFM-505, Rockville, MD 20852 USA. NR 38 TC 75 Z9 75 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 1998 VL 54 IS 3 BP 547 EP 558 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 120BH UT WOS:000075934300012 PM 9730914 ER PT J AU Garnick, MB Fair, WR Goldenberg, SL Gleave, M Fourcroy, J Grignon, D Srougi, M Porterfield, H Hart, C AF Garnick, MB Fair, WR Goldenberg, SL Gleave, M Fourcroy, J Grignon, D Srougi, M Porterfield, H Hart, C TI Third International Conference on Neoadjuvant Hormonal Therapy of Prostate Cancer: Overview consensus statement SO MOLECULAR UROLOGY LA English DT Editorial Material C1 Harvard Med Sch, Beth Israel Hosp, Boston, MA 02215 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. US FDA, Rockville, MD 20857 USA. Wayne State Univ, Harper Hosp, Detroit, MI 48202 USA. Univ Fed Sao Paulo, Sao Paulo, Brazil. UsTOO, Oakbrook, IL USA. RP Garnick, MB (reprint author), Harvard Med Sch, Beth Israel Hosp, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 1998 VL 2 IS 3 BP 87 EP 89 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 154NV UT WOS:000077895900001 ER PT J AU Rabbani, F Garnick, MB Goldenberg, SL Gleave, M Fourcroy, J AF Rabbani, F Garnick, MB Goldenberg, SL Gleave, M Fourcroy, J TI Randomized trial of neoadjuvant androgen ablation prior to radical prostatectomy: 24-month post-treatment PSA results - Discussion SO MOLECULAR UROLOGY LA English DT Editorial Material C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. US FDA, Rockville, MD 20857 USA. RP Rabbani, F (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 1998 VL 2 IS 3 BP 169 EP 169 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 154NV UT WOS:000077895900020 ER PT J AU Fourcroy, J AF Fourcroy, J TI Regulatory history of hormone therapy for prostate cancer SO MOLECULAR UROLOGY LA English DT Article ID WITHDRAWAL SYNDROME; RANDOMIZED TRIAL; FLUTAMIDE; CARCINOMA; ANALOG; NILUTAMIDE; ZOLADEX; DEPOT AB The Food and Drug Administration is charged with ensuring that the drugs sold in the United States are both safe and effective and that they are advertised honestly. This article reviews the application of these responsibilities during the clinical development of the hormonal products used in the treatment of prostate cancer. C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Fourcroy, J (reprint author), US FDA, Off Hlth Affairs, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 34 TC 3 Z9 3 U1 0 U2 0 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 1998 VL 2 IS 3 BP 215 EP 220 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 154NV UT WOS:000077895900031 ER PT J AU Valentine, CR AF Valentine, CR TI The association of nonsense codons with exon skipping SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Review DE RT-PCR artifact; premature termination codon; stop codon; reinitiation; mRNA abundance ID SPLICE-SITE SELECTION; DUCHENNE MUSCULAR-DYSTROPHY; HUMAN LYMPHOBLASTOID-CELLS; DIPLOID HUMAN FIBROBLASTS; NASAL EPITHELIAL-CELLS; NUCLEAR MESSENGER-RNA; HAMSTER OVARY CELLS; GUANINE PHOSPHORIBOSYLTRANSFERASE GENE; X-LINKED AGAMMAGLOBULINEMIA; ACID DEHYDROGENASE COMPLEX AB Some genes that contain premature nonsense codons express alternatively-spliced mRNA that has skipped the exon containing the nonsense codon. This paradoxical association of translation signals (nonsense codons) and RNA splicing has inspired numerous explanations. The first is based on the fact that premature nonsense codons often reduce mRNA abundance, The reduction in abundance of full-length mRNA then allows more efficient amplification during PCR of normal, minor, exon-deleted products. This mechanism has been demonstrated to explain an extensive correlation between nonsense codons and exon-skipping for the hamster Hprt gene. The second explanation is that the mutation producing an in-frame nonsense codon has an effect on exon definition. This has been demonstrated for the Mup and hamster Hprt gene by virtue of the fact that missense mutations at the same sites also are associated with the same exon-deleted mRNA, The third general explanation is that a hypothetical process takes place in the nucleus that recognizes nonsense codons, termed 'nuclear scanning', which then has an effect on mRNA splicing, Definitive evidence for nuclear scanning is lacking. My analysis of both nonsense and missense mutations associated with exon skipping in a large number of genes revealed that both types of mutations frequently introduce a T into a purine-rich DNA sequence and are often within 30 base pairs of the nearest exon boundary. This is intriguing given that purine-rich splicing enhancers are known to be inhibited by the introduction of a T. Almost all mutations associated with exon skipping occur in purine-rich or A/C-rich sequences, also characteristics of splicing enhancers. I conclude that most cases of exon skipping associated with premature termination codons may be adequately explained either by a structural effect on exon definition or by nonquantitative methods to measure mRNA, rather than an effect on a putative nuclear scanning mechanism. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Valentine, CR (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM cvalentine@nctr.fda.gov NR 133 TC 110 Z9 112 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD SEP PY 1998 VL 411 IS 2 BP 87 EP 117 DI 10.1016/S1383-5742(98)00010-6 PG 31 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 122JZ UT WOS:000076069600001 PM 9806422 ER PT J AU Ryder, M Scott, W Helm, A AF Ryder, M Scott, W Helm, A TI Is downsizing and disbanding specialty care teams a counterproductive strategy for cost reduction in health care? SO NUTRITION LA English DT Article ID TOTAL PARENTERAL-NUTRITION; BLOOD-STREAM INFECTIONS; NOSOCOMIAL INFECTIONS; CATHETER SEPSIS; COMPLICATIONS; PREVENTION; MORTALITY; IMPACT; RATES C1 Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94143 USA. US PHS, US FDA, Ctr Devices & Radiol Hlth, Rockville, MD USA. Oregon Hlth Sci Univ, Sch Med, Dept Community Hlth, Portland, OR 97201 USA. RP Ryder, M (reprint author), 1504 Forge Rd, San Mateo, CA 94402 USA. NR 36 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 0899-9007 J9 NUTRITION JI Nutrition PD SEP PY 1998 VL 14 IS 9 BP 725 EP 728 DI 10.1016/S0899-9007(98)00071-9 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 117PR UT WOS:000075791400020 PM 9760601 ER PT J AU Bassen, HI Moore, HJ Ruggera, PS AF Bassen, HI Moore, HJ Ruggera, PS TI Cellular phone interference testing of implantable cardiac defibrillators in vitro SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE cellular phone; EMC; electromagnetic; interference; compatibility; pacemaker ID PACEMAKER AB An in vitro study was undertaken to investigate the potential for cellular telephones to interfere with representative models of presently used ICDs. Digital cellular phones (DCPs) generate strong, amplitude modulated fields with pulse repetition rates near the physiological range sensed by the ICD as an arrhythmia. DCPs with Time Division Multiple Access (TDMA) pulsed amplitude modulation caused the most pronounced effect-high voltage firing or inhibition of pacing output of the ICDs. This electromagnetic interference (EMI) occurred only when the phones were within 2.3-5.8 cm of the ICD pulse generator that was submerged 0.5 cm in 0.18% saline. ICD performance always reverted to baseline when the cellular phones were removed from the immediate proximity of the ICD. Three models of ICDs were subjected to EMI susceptibility testing using two types of digital phones and one analog cellular phone, each operating at their respective maximum output power. EMI was observed in varying degrees from all DCPs. Inhibition of pacer output occurred in one ICD, and high voltage firing occurred in the two other ICDs, when a TDMA-11 Hz DCP was placed within 2.3 cm of the ICD. For the ICD that was most sensitive to delivering unintended therapy, inhibition followed by firing occurred at distances up to 5.8 cm. When a TDMA-50 Hz phone was placed at the minimum test distance of 2.3 cm, inhibition followed by firing was observed in one of the ICDs, EMI occurred most frequently when the lower portion of the monopole antenna of the cellular phone was placed over the ICD header. C1 Ctr Devices & Radiol Hlth, FDA, Rockville, MD 20852 USA. RP Bassen, HI (reprint author), Ctr Devices & Radiol Hlth, FDA, HFZ-133,12725 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 20 TC 26 Z9 27 U1 0 U2 1 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD SEP PY 1998 VL 21 IS 9 BP 1709 EP 1715 DI 10.1111/j.1540-8159.1998.tb00268.x PG 7 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 116LH UT WOS:000075725800005 PM 9744432 ER PT J AU Betz, JM Andrzejewski, D Troy, A Casey, RE Obermeyer, WR Page, SW Woldemariam, TZ AF Betz, JM Andrzejewski, D Troy, A Casey, RE Obermeyer, WR Page, SW Woldemariam, TZ TI Gas chromatographic determination of toxic quinolizidine alkaloids in blue cohosh Caulophyllum thalictroides (L,) Michx SO PHYTOCHEMICAL ANALYSIS LA English DT Article DE gas chromatography; blue cohosh; dietary supplements; quinolizidine alkaloids ID THERMOPSIS-MONTANA; LUPINUS; CATTLE AB Blue cohosh (Caulophyllum thalictroides (L.) Michx., Berberidaceae) is a North American perennial herb which is found as an ingredient in dietary supplement products in the United States. The plant contains the alkaloids N-methylcytisine, baptifoline, anagyrine and magnoflorine. Some of the alkaloids, including the quinolizidine alkaloid anagyrine, are toxic to range animals and have been implicated as teratogens in higher animals. Since the traditional use of the herb involves administration to women of reproductive age to treat menstrual cramps, and to pregnant women in the last 3-4 weeks of pregnancy to ease parturition, therefore the safety of these products to the fetus is of concern. Three of these alkaloids have been determined in authentic bible cohosh and several dietary supplements. Levels found were: 5-850 ppm for N-methylcytisine, 2-390 ppm for anagyrine, and 9-900 ppm for baptifoline. The lower alkaloid concentrations were found in products containing liquid extracts. Alkaloid identities were confirmed by mass spectrometry. (C) 1998 John Wiley & Sons, Ltd. C1 US FDA, Div Nat Prod HFS347, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Univ London Kings Coll, Dept Pharm, London SW3 6LX, England. RP Betz, JM (reprint author), US FDA, Div Nat Prod HFS347, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. EM jbetz@bangate.fda.gov OI Casey, Ryan/0000-0001-9894-914X NR 34 TC 16 Z9 18 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0958-0344 J9 PHYTOCHEM ANALYSIS JI Phytochem. Anal. PD SEP-OCT PY 1998 VL 9 IS 5 BP 232 EP 236 DI 10.1002/(SICI)1099-1565(199809/10)9:5<232::AID-PCA412>3.0.CO;2-5 PG 5 WC Biochemical Research Methods; Plant Sciences; Chemistry, Analytical SC Biochemistry & Molecular Biology; Plant Sciences; Chemistry GA 123PN UT WOS:000076133700004 ER PT J AU Calvey, EM White, KD Matusik, JE Sha, DY Block, E AF Calvey, EM White, KD Matusik, JE Sha, DY Block, E TI Allium chemistry: Identification of organosulfur compounds in ramp (Allium tricoccum) homogenates SO PHYTOCHEMISTRY LA English DT Article DE Allium tricoccum Ait.; Alliaceae (Liliaceae); ramp; supercritical fluid extraction; liquid chromatography mass spectrometry; thiosulfinates; cepaenes ID SUPERCRITICAL-FLUID EXTRACTION; PLATELET-AGGREGATION; HPLC ANALYSIS; ONION; VINYLDITHIINS; VICTORIALIS; DISULFIDES; INHIBITORS; CEPAENES; SHALLOT AB Supercritical fluid (SF) extracts of homogenized ramp (Allium tricoccum Ait.) were separated and characterized with liquid chromatography coupled with atmospheric pressure chemical ionization mass spectrometric identification. The profiles of SF extracts of aqueous homogenates of ramp bulbs from three different seasons and growing regions revealed that the thiosulfinates were major components. In addition, some of the cepaenes (alpha-sulfinyldisulfides) found in extracts of onion juice, as well as allyl containing cepaenes (2-propenyl 1-(2-propenylsulfinyl)propyl disulfide), are present in the ramp extracts. The amount of allicin in ramp bulb homogenates ranged from approximately 10% to 50% of that found in extracts of aqueous garlic homogenates. The greater amount of the methyl l-propenyl thiosulfinates in the ramp extracts relative to that found in the garlic extracts correlates with the flavor characteristics of ramp bulbs. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. SUNY Albany, Dept Chem, Albany, NY 12222 USA. RP Calvey, EM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RI Block, Eric/D-3989-2014 FU NCI NIH HHS [CA45164] NR 25 TC 22 Z9 23 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9422 J9 PHYTOCHEMISTRY JI Phytochemistry PD SEP PY 1998 VL 49 IS 2 BP 359 EP 364 DI 10.1016/S0031-9422(98)00191-5 PG 6 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA 118HN UT WOS:000075832600011 PM 9747536 ER PT J AU Fischer, R Houn, F Van De Griek, A Tucker, SA Meyers, D Murphy, M Unis, G AF Fischer, R Houn, F Van De Griek, A Tucker, SA Meyers, D Murphy, M Unis, G TI The impact of the mammography quality standards act on the availability of mammography facilities SO PREVENTIVE MEDICINE LA English DT Article DE mammography; regulations; access; breast cancer; early detection ID CARE; RACE AB Background. The Mammography Quality Standards Act (MQSA) became effective October 1, 1994, and requires all mammography facilities to meet quality standards as promulgated by the Food and Drug Administration (FDA). The FDA undertook an assessment of the MQSA federal certification requirements on the availability of mammography facilities. Methods. A survey of states on mammography facility closures between October 1, 1993, and October 1, 1994, was conducted. MapInfo software was used to link zip codes to demographic databases, The characteristics of closed facilities were compared to certified facilities as of December 15, 1994. Results. A total of 369 facilities (3.5%) had closed. This closure rate was comparable to previous years' rates (2.5-10%). As of December 15, 1994, 10,142 certified facilities were operating. Relative to their distribution in the United States, closures in rural areas were proportional, but there were more facility closures in the minority areas and in poverty areas, However, the relative distributions of facilities to these areas' populations were unchanged. Conclusions. Impact on facility availability has been minimal. (C) 1998 American Health Foundation and Academic Press. C1 US FDA, Div Mammog Qual & Radiat Programs, Off Hlth & Ind Programs, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. US FDA, Off Planning & Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Eastern Res Grp, Lexington, MA 02173 USA. RP Fischer, R (reprint author), US FDA, Div Mammog Qual & Radiat Programs, Off Hlth & Ind Programs, Ctr Devices & Radiol Hlth, 1350 Piccard Dr,HFZ-240, Rockville, MD 20857 USA. NR 20 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP-OCT PY 1998 VL 27 IS 5 BP 697 EP 701 DI 10.1006/pmed.1998.0347 PN 1 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 127UM UT WOS:000076369000008 PM 9808801 ER PT J AU Finder, CA Kisielewski, RW Kedas, AM AF Finder, CA Kisielewski, RW Kedas, AM TI Residual metal shavings and fragments associated with large-core biopsy needles: A follow-up SO RADIOLOGY LA English DT Letter ID BREAST-LESIONS C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Finder, CA (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-240,1350 Piccard Dr, Rockville, MD 20850 USA. NR 4 TC 3 Z9 3 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 1998 VL 208 IS 3 BP 833 EP 834 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 112HN UT WOS:000075488200050 PM 9722871 ER PT J AU Bailey, B Morris, P McMartin, KI Klein, J Duhart, HM Gillam, MP Binienda, Z Slikker, W Paule, MG Koren, G AF Bailey, B Morris, P McMartin, KI Klein, J Duhart, HM Gillam, MP Binienda, Z Slikker, W Paule, MG Koren, G TI Transplacental pharmacokinetics of cocaine and benzoylecgonine in plasma and hair of rhesus monkeys SO REPRODUCTIVE TOXICOLOGY LA English DT Article; Proceedings Paper CT 98th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 05-08, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Soc Clin Pharm & Therapeut DE cocaine; benzoylecgonine; hair; transplacental pharmacokinetics; monkeys ID FETAL EXPOSURE; INFANT OUTCOMES; DRUGS; METABOLITES; PREGNANCY; HUMANS; ABUSE; FETUS; TORONTO; SMOKING AB There is large variability in the rate and extent of fetal damage from cocaine in humans; however, the sources of such variability are not presently known. In order to study the relationship between maternal cocaine pharmacokinetics at the end of pregnancy and maternal or infant cocaine and benzoylecgonine hair concentrations at birth, ten rhesus monkeys were administered cocaine intramuscularly throughout pregnancy, Cocaine and benzoylecgonine hair concentrations were determined at birth and correlated with maternal pharmacokinetics during pregnancy. There were no correlations between either maternal cocaine C-max or AUC(0-infinity) and maternal and infant hair cocaine or benzoylecgonine concentrations. There were no significant correlations between maternal hair benzoylecgonine concentrations and either maternal benzoylecgonine AUC(0-120) (r = 0.60; P = 0.07) or benzoylecgonine C-max (r = 0.60; P = 0.07). No correlations existed between infant hair benzoylecgonine concentrations and either maternal benzoylecgonine AUC(0-120) (r = 0.30; P = 0.40) or benzoylecgonine C-max (r = 0.30; P = 0.40), Also, no correlation was found between maternal cocaine dose and maternal or infant cocaine and benzoylecgonine hair concentrations. In comparison to toxicants such as nicotine and carbon monoxide for which there is a good correlation between maternal systemic exposure and neonatal concentrations, the lack of a similar relationship for cocaine is consistent with the role of the placenta in contributing to the variability in the amounts of cocaine reaching the fetus and hence, potentially to the risk of adverse fetal outcome. (C) 1998 Elsevier Science Inc. C1 Hosp Sick Children, Div Clin Pharmacol & Toxicol, Toronto, ON M5G 1X8, Canada. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Pediat, Toronto, ON, Canada. Univ Toronto, Dept Med, Toronto, ON, Canada. Univ Toronto, Dept Pharmacol, Toronto, ON, Canada. RP Koren, G (reprint author), Hosp Sick Children, Div Clin Pharmacol & Toxicol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. FU PHS HHS [224-89-003] NR 30 TC 2 Z9 2 U1 1 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 SEP-OCT PY 1998 VL 12 IS 5 BP 517 EP 523 DI 10.1016/S0890-6238(98)00031-8 PG 7 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 118TJ UT WOS:000075855800003 PM 9763243 ER PT J AU Morris, SM Chen, JJ Domon, OE McGarrity, LJ Bishop, ME Manjanatha, MG Casciano, DA AF Morris, SM Chen, JJ Domon, OE McGarrity, LJ Bishop, ME Manjanatha, MG Casciano, DA TI p53, mutations, and apoptosis in genistein-exposed human lymphoblastoid cells SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE genistein; human lymphoblastoid cells; thymidine kinase mutations; hypoxanthine phophoribosyl transferase mutations; apoptosis; p53 functional status ID KINASE INHIBITOR GENISTEIN; SUPPRESSES MAMMARY-CANCER; MOUSE LYMPHOMA-CELLS; DNA TOPOISOMERASE-II; TYROSINE KINASE; MUTAGENIC RESPONSES; HUMAN-LYMPHOCYTES; LEUKEMIA-CELLS; SINGLE-DONOR; BONE-MARROW AB The phytoestrogen, genistein, is a naturally occurring isoflavone found in soy products. On a biochemical basis, genistein is a competitive inhibitor of tyrosine kinases and the DNA synthesis-related enzyme, topoisomerase-II (topo-II). Exposure of mammalian cells to genistein results in DNA damage that is similar to that induced by the topo-II inhibitor and chromosomal mutagen, m-amsa. In order to determine the potential genotoxicity of genistein, human lymphoblastoid cells which differ in the functional status of the tumor suppressor gene, p53, were exposed to genistein and the induction of micronuclei quantified by microscopic analysis. In addition, the mutant fraction at the thymidine kinase (tk) locus (both the normal-growth and slow-growth phenotypes) was determined by resistance to trifluorothymidine (TFT) and at the hypoxanthine phosphoribosyl transferase (hprt) locus by resistance to 6-thioguanine (6-TG). Flow cytometric analysis of the percentage of viable, apoptotic and degenerating cells was utilized to determine the rate and kinetics of cell death after genistein exposure. The detection of micronuclei in both cell lines indicated that genistein-induced damage had occurred in both AHH-1 tk(+/-) and L3. Linear regression analysis detected a significant increase in the number of 6-TG-resistant clones in both AHH-1 tk+/- (p53(+/-)) and L3 (p53(+/+)). A comparison of slopes revealed no difference between the lines. In contrast, a significant, concentration-dependent increase in the number of TFT-resistant clones with the slow-growth phenotype was detected in AHH-1 tk(+/-) (mutant p53), but not in L3 (wild-type p53), Cell death occurred primarily by apoptosis in both cell lines; however, a concentration-dependent decrease in the percentage of viable cells was detected immediately after exposure in L3, but not until 32 h after exposure in AHH-1 tk(+/-). A comparison of the slopes of the concentration-response curves for the percentage of viable cells revealed no difference between the cell lines in the effect of genistein on cell viability. Our results may be interpreted that genistein is a chromosomal mutagen and that p53 functional status affects the recovery of chromosomal mutants, possibly by signalling cells into the apoptosis pathways. (C) 1998 Elsevier Science B.V. All rights reserved. C1 US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Dept Hlth & Human Serv,DGRT, Jefferson, AR 72079 USA. US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Dept Hlth & Human Serv, Jefferson, AR 72079 USA. RP Morris, SM (reprint author), US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Dept Hlth & Human Serv,DGRT, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM smorris@nctr.fda.gov NR 79 TC 42 Z9 44 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 AUG 31 PY 1998 VL 405 IS 1 BP 41 EP 56 DI 10.1016/S0027-5107(98)00126-2 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 113WP UT WOS:000075577100005 PM 9729267 ER PT J AU Kadlubar, FF Huber, WW AF Kadlubar, FF Huber, WW TI Cancer chemoprevention from the food-borne carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine: reconsideration of the evidence SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Letter C1 Natl Ctr Toxicol Res, Div Mol Engn, Jefferson, AR 72079 USA. Inst Tumor Biol & Canc Res, A-1090 Vienna, Austria. RP Kadlubar, FF (reprint author), Natl Ctr Toxicol Res, Div Mol Engn, Jefferson, AR 72079 USA. NR 5 TC 2 Z9 2 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 AUG 31 PY 1998 VL 405 IS 1 BP 111 EP 112 DI 10.1016/S0027-5107(98)00120-1 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 113WP UT WOS:000075577100011 PM 9729316 ER PT J AU O'Neill, RT AF O'Neill, RT TI Biostatistical considerations in pharmacovigilance and pharmacoepidemiology: Linking quantitative risk assessment in pre-market licensure application safety data, post-market alert reports and formal epidemiological studies SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Conference on Statistical Issues in Pharmaceutical Development, Collaboration between Europe and the USA and the Regulation of Medicines from Research to Marketing CY JUL 16-18, 1996 CL DE MONTFORT UNIV, DEPT MED STAT, LEICESTER, ENGLAND HO DE MONTFORT UNIV, DEPT MED STAT AB This paper deals with a conceptual discussion of a variety of statistical concepts, methods and strategies that are relevant to the quantitative assessment of risk derived from safety data collected during the pre- and post-marketing phase of a new drug's life cycle. A call is made for the use of more standard approaches to the analysis of safety data that are statistically and epidemiologically rigorous and for attempts to link the strategies for pre-market safety assessment with strategies for post-market safety evaluation. This link may be facilitated by recognizing the limitations and complementary roles played by pre- and post-market safety data collection schemes and by linking the quantitative analyses utilized for either exploratory or confirmatory purposes of risk assessment in each phase of safety data collection. Examples are provided of studies specifically designed to evaluate risk in a post approval setting and several available guidelines intended to improve the quality of these studies are discussed. (C) 1998 John Wiley & Sons, Ltd. C1 US FDA, Div Biometr, Rockville, MD 20857 USA. RP O'Neill, RT (reprint author), US FDA, Div Biometr, 5600 Fishers Lane,HFD 710,Room 18845, Rockville, MD 20857 USA. NR 6 TC 8 Z9 8 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 1998 VL 17 IS 15-16 BP 1851 EP 1858 DI 10.1002/(SICI)1097-0258(19980815/30)17:15/16<1851::AID-SIM987>3.0.CO;2-Z PG 8 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 110ZH UT WOS:000075411900020 PM 9749452 ER PT J AU Alexandrov, I Romanova, L Mushinski, F Nordan, R AF Alexandrov, I Romanova, L Mushinski, F Nordan, R TI Sodium butyrate suppresses apoptosis in human Burkitt lymphomas and murine plasmacytomas bearing c-myc translocations SO FEBS LETTERS LA English DT Article DE plasmacytoma; butyrate; apoptosis; c-myc ID CELL-CYCLE; REGULATORY ELEMENTS; CARCINOMA CELLS; WILD-TYPE; EXPRESSION; GENE; FIBROBLASTS; INTERLEUKIN-3; ACTIVATION; MODULATION AB We report that sodium butyrate, a natural product of fiber degradation by colonic bacteria, markedly suppresses c-Myc-mediated apoptosis induced in murine plasmacytomas and human Burkitt lymphomas by growth factor deprivation, but not in cell lines devoid of c-myc translocations. Attenuation of cell death is associated with downregulation of the rearranged c-myc and activation of pRb via its dephosphorylation, We suggest that in vivo sodium butyrate may play an important role in plasmacytomagenesis by supporting the survival of cells,vith c-myc translocations, which otherwise mould be eliminated by the lack of growth factors. (C) 1998 Federation of European Biochemical Societies. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Alexandrov, I (reprint author), Russian Acad Med Sci, Mental Hlth Res Ctr, Lab Cytogenet, Zagorodne Sh 2, Moscow 113152, Russia. NR 29 TC 3 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD AUG 28 PY 1998 VL 434 IS 1-2 BP 209 EP 214 DI 10.1016/S0014-5793(98)00926-0 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 117RG UT WOS:000075795100041 PM 9738480 ER PT J AU Pierce, LR Finlayson, JS Epstein, JS AF Pierce, LR Finlayson, JS Epstein, JS TI More on dangerous dilution of 25 percent albumin - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20852 USA. RP Pierce, LR (reprint author), US FDA, Rockville, MD 20852 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 27 PY 1998 VL 339 IS 9 BP 635 EP 635 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 113LR UT WOS:000075552900021 ER PT J AU Fu, TJ Abbott, UR AF Fu, TJ Abbott, UR TI Effects of cell culture processes on natural toxin formation in tomato cell cultures. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Summit Agro, IL 60501 USA. IIT, Natl Ctr Food Safety & Technol, 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 23 PY 1998 VL 216 MA 152-BIOT BP U293 EP U293 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234900802 ER PT J AU Fu, TJ Abbott, UR AF Fu, TJ Abbott, UR TI Stability of food allergens to digestion and acid hydrolysis in comparison to proteins with unproven allergenicity. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Illinois Institute Technology, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. US Food & Drug Adm, 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 23 PY 1998 VL 216 MA 081-AGFD BP U48 EP U48 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234900081 ER PT J AU Gendel, SM AF Gendel, SM TI Sequence analysis for allergen risk assessment. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, 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 23 PY 1998 VL 216 MA 026-AGFD BP U32 EP U32 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234900026 ER PT J AU Jackson, LS Fingerhut, DD Bullerman, LB AF Jackson, LS Fingerhut, DD Bullerman, LB TI Effect of added sugars on fumonisin levels in corn muffins and tortilla chips. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US Food & Drug Adm, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. Univ Nebraska, Dept Food Sci & Technol, Lincoln, NE 68583 USA. Illinois Institute Technology, 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 23 PY 1998 VL 216 MA 066-AGFD BP U44 EP U44 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234900066 ER PT J AU Jackson, LS AF Jackson, LS TI Effect of processing on mycotoxins in food SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US Food & Drug Adm, Natl Ctr Food Safety & Technol, 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 23 PY 1998 VL 216 MA 028-AGFD BP U33 EP U33 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234900028 ER PT J AU Kim, Y Conte, E Miller, DW AF Kim, Y Conte, E Miller, DW TI The improvement of dimethylamine (DMA) and trimethylamine (TMA) determination in seafood. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson Labs, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 062-AGFD BP U43 EP U43 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234900062 ER PT J AU Lai, CC Chen, HJ Fu, PP AF Lai, CC Chen, HJ Fu, PP TI Synthesis of isomeric 1-,2-,3-,4-,5-, and 6-Ethylchrysenes and vinylchrysenes. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Providence Univ, Inst Appl Chem, Taichung 43301, Taiwan. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 036-TOXI BP U556 EP U556 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234901606 ER PT J AU Layloff, TP AF Layloff, TP TI Analytical chemistry practices in an FDA regulated laboratory. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, DTAAD, St Louis, MO 63101 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 23 PY 1998 VL 216 MA 034-CHED BP U385 EP U385 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234901078 ER PT J AU Luu, HMD Hutter, JC AF Luu, HMD Hutter, JC TI A physiologically-based pharmacokinetic model of 4,4 '-methylenedianiline released from polyurethane medical devices. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Chem Grp, Div Mech & Mat Sci, Off Sci & Technol, Rockville, MD 20850 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 23 PY 1998 VL 216 MA 086-COMP BP U708 EP U709 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234902108 ER PT J AU McNeal, TP Biles, JE Begley, TH AF McNeal, TP Biles, JE Begley, TH TI Determination of suspected endocrine disruptors in foods and food packaging. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 2 U2 4 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 23 PY 1998 VL 216 MA 169-ENVR BP U811 EP U811 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234902389 ER PT J AU Miller, DW Kim, Y Lansden, J AF Miller, DW Kim, Y Lansden, J TI Analysis of biogenic amines in seafood product tissue as the benzoylate derivative. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson Labs, Jefferson, AR 72079 USA. US FDA, SE Reg Lab, ORA, Atlanta, GA 30301 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 23 PY 1998 VL 216 MA 063-AGFD BP U43 EP U43 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234900063 ER PT J AU Raybourne, RB AF Raybourne, RB TI T and B lymphocyte epitopes of food allergens. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US Food & Drug Adm, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 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 23 PY 1998 VL 216 MA 025-AGFD BP U32 EP U32 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234900025 ER PT J AU Samokyszyn, VM Doerge, D Freyaldenhoven, MA AF Samokyszyn, VM Doerge, D Freyaldenhoven, MA TI (E)-retinoic acid-dependent inhibition of 2,2 '-azobis(2amidinopropane)-initiated autoxidation of dilinoleoylphosphatidylcholine liposomes. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Jefferson, AR 72072 USA. Univ Arkansas Med Sci, Div Toxicol, Little Rock, AR 72205 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 23 PY 1998 VL 216 MA 040-TOXI BP U557 EP U557 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234901610 ER PT J AU Schroeder, LW AF Schroeder, LW TI Biostable polymers? Measuring and predicting stability? SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Devices & Radiol Hlth, Div Mech & Mat 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 23 PY 1998 VL 216 MA 224-PMSE BP U882 EP U882 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235002650 ER PT J AU Song, YS Park, HJ Komolprasert, V AF Song, YS Park, HJ Komolprasert, V TI Analytical methods for quantifying anthracene, benzophenone, dimethyl phthalate, methyl stearate, and pentachlorophenol in recycled paper/paperboard. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US Food & Drug Adm, Natl Ctr Food Safety & Technol, Summit, IL 60501 USA. Rural Living Sci Inst, Suwon, South Korea. 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 23 PY 1998 VL 216 MA 061-AGFD BP U43 EP U43 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234900061 ER PT J AU Wright, PR Richfield-Fratz, N Weisz, A AF Wright, PR Richfield-Fratz, N Weisz, A TI Quantitative analysis of components of the color additive D & C yellow NO. 10 (Quinoline Yellow) by thin-layer chromatography and video densitometry SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Off Cosmet & Colors, 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 23 PY 1998 VL 216 MA 088-ANYL BP U166 EP U166 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234900430 ER PT J AU Kumar, A Dhawan, S Aggarwal, BB AF Kumar, A Dhawan, S Aggarwal, BB TI Emodin (3-methyl-1,6,8-trihydroxyanthraquinone) inhibits TNF-induced NF-kappa B activation, I kappa B degradation, and expression of cell surface adhesion proteins in human vascular endothelial cells SO ONCOGENE LA English DT Article DE emodin; TNF; NF-kappa B; adhesion; I kappa-B alpha; endothelial cells ID TYROSINE KINASE INHIBITOR; CANCER CELLS; MOLECULE-1; PHOSPHORYLATION; GENE AB Most inflammatory agents activate nuclear transcription factor-kappa B (NF-kappa B) which results in expression of genes for cytokines, adhesion molecules, and enzymes involved in amplification and perpetuation of inflammation. Emodin (3-methyl-1,6,8-trihydroxyanthraquinone) is an active component from the roots of Polygonum cuspidatum that has been reported to exhibit antiinflammatory properties but the mechanism is not known. In the present study we investigated the effects of emodin on the activation of NF-kappa B in human umbelical vein endothelial cells (EC), Treatment of EC with TNF activated NF-kappa B; preincubation with emodin inhibited this activation in a dose- and time-dependent manner. Emodin did not chemically modify NF-kappa B subunits but rather inhibited degradation of I kappa B, an inhibitory subunit of NF-kappa B. Since the promoter regions of ICAM-1, VCAM-1, and ELAM-1 contain NF-kappa B binding sites and these adhesion molecules are involved in the attachment of leukocytes to EC, the effect of emodin on the adhesion of monocytes to EC and the expression of these adhesion molecules was also studied. Treatment of EC with TNF for 6 h increased the adhesion of monocytes to EC, which correlated with increases in cell surface expression of ICAM-1, VCAM-1 and ELAM-1. Pretreatment of EC for Ih with emodin inhibited both monocyte-EC attachment and expression of ICAM-1, ELAM-1 and VCAM-1, These results indicate that emodin is a potent inhibitor of NF-kappa B activation and expression of adhesion molecules and thus could be useful in treating various inflammatory diseases. C1 Univ Texas, MD Anderson Cancer Ctr, Dept Med Oncol, Cytokine Res Sect, Houston, TX 77030 USA. US FDA, Lab Immunochem, Div Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Aggarwal, BB (reprint author), Univ Texas, MD Anderson Cancer Ctr, Dept Med Oncol, Cytokine Res Sect, Houston, TX 77030 USA. RI Aggarwal, Bharat/G-3388-2013 NR 26 TC 120 Z9 145 U1 0 U2 7 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 20 PY 1998 VL 17 IS 7 BP 913 EP 918 DI 10.1038/sj.onc.1201998 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 111QH UT WOS:000075448800013 PM 9780008 ER PT J AU Graham, LJ Stoica, BA Shapiro, M DeBell, KE Rellahan, B Laborda, J Bonvini, E AF Graham, LJ Stoica, BA Shapiro, M DeBell, KE Rellahan, B Laborda, J Bonvini, E TI Sequences surrounding the Src-homology 3 domain of phospholipase C gamma-1 increase the domain's association with Cbl SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID C-CBL; SH3 DOMAIN; PROTEIN PRODUCT; TYROSINE KINASE; JURKAT CELLS; V-CBL; GRB2; BINDING; PROTOONCOGENE; TRUNCATION AB SH3 domains are protein modules that interact with proline-rich polypeptide fragments. Cbl is an adapter-like protein known to interact with several SH3 domains, including the PLC gamma 1 SH3 domain and the Grb2 amino terminal SH3 domain. Here we explore whether sequences surrounding the PLC gamma 1 SH3 domain core sequence (aa.796-851) can affect the binding to Cbl, a target used as a prototypical ligand. Consistent with previous reports, our results demonstrated a weak binding of Cbl to GST fusion proteins that strictly encompass the structural core of the PLC gamma 1 SH3 domain but a high-avidity binding to the Grb2 amino-terminal SH3 domain. Inclusion of amino acids immediately flanking the PLC gamma 1 SH3 core domain, however, substantially increased binding of Cbl to a level comparable to that of the Grb2 amino-terminal SH3 domain. The interaction of this extended PLC gamma 1 SH3 domain fusion protein with Cbl was shown to depend entirely upon the interaction of the domain with a proline-rich motif in Cbl, ruling out the possibility that amino acids adjacent to the core SH3 domain of PLC gamma 1 provide independent Cbl binding. These data suggest that sequences surrounding the SH3 domain of PLC gamma 1 may contribute to or stabilize the association of the domain with the target protein, thus increasing its binding efficiency. (C) 1998 Academic Press. C1 US FDA, Immunobiol Lab, Div Monoclonal Antibodies, Off Therapeut Res & Review,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Off Therapeut Res & Review,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Bonvini, E (reprint author), US FDA, Immunobiol Lab, Div Monoclonal Antibodies, Off Therapeut Res & Review,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RI STOICA, BOGDAN/H-9782-2013; Laborda, Jorge/L-5726-2014 OI STOICA, BOGDAN/0000-0002-2501-6434; Laborda, Jorge/0000-0002-9210-838X NR 23 TC 19 Z9 19 U1 0 U2 0 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 AUG 19 PY 1998 VL 249 IS 2 BP 537 EP 541 DI 10.1006/bbrc.1998.9177 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 112VT UT WOS:000075515900043 PM 9712732 ER PT J AU Goodwin, TE Holland, RD Lay, JO Raney, KD AF Goodwin, TE Holland, RD Lay, JO Raney, KD TI A simple procedure for solid-phase synthesis of peptide nucleic acids with N-terminal cysteine SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID PNA; DNA; CHIMERA AB Problems were encountered during attempts to prepare N-terminal cysteine-substituted peptide nucleic acids (PNAs) from commercially available, Fmoc-protected monomers. These problems have been surmounted by the use of an S-t-butylmercapto protecting group on the cysteine moiety. The solid-phase syntheses are carried out via a simplified procedure which should be generally useful for manual PNA synthesis. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. Hendrix Coll, Dept Chem, Conway, AR 72032 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Raney, KD (reprint author), Univ Arkansas Med Sci, Dept Biochem & Mol Biol, 4301 W Markham, Little Rock, AR 72205 USA. RI Lay, Jackson/G-1007-2011 OI Lay, Jackson/0000-0003-3789-2527 NR 15 TC 15 Z9 15 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD AUG 18 PY 1998 VL 8 IS 16 BP 2231 EP 2234 DI 10.1016/S0960-894X(98)00400-4 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 115XT UT WOS:000075692200034 PM 9873519 ER PT J AU Husain, SR Behari, N Kreitman, RJ Pastan, I Puri, RK AF Husain, SR Behari, N Kreitman, RJ Pastan, I Puri, RK TI Complete regression of established human glioblastoma tumor xenograft by interleukin-4 toxin therapy SO CANCER RESEARCH LA English DT Article ID CIRCULARLY PERMUTED INTERLEUKIN-4; KAPOSIS-SARCOMA CELLS; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; FUSION PROTEIN; RECEPTOR; MULTIFORME; CARCINOMA; EFFICACY; GLIOMAS AB No curative therapy is available for malignant gliomas, We have discovered that human glioblastoma cells express high affinity interleukin-4 receptor (IL-4R), which is an attractive target for receptor-directed IL-4 toxin therapy. The IL-4 toxin, IL-4(38-37)-PE38KDEL, is a fusion protein containing translocation and enzymatic domains of Pseudomonas exotoxin and a circularly permuted human IL-4. The IL-4 toxin binds specifically to the IL-4R and is highly cytotoxic to glioblastoma cells, as determined by clonogenic and protein synthesis inhibition assays. Intratumoral administration of the IL-4 toxin given on alternate days for 3-4 doses into U251 glioblastoma flank tumors in nude mice, showed a complete remission of small (similar to 13 mm(3)) and large (similar to 60 mm(3)) tumors in all animals, without any evidence of toxicity. A significant antitumor activity was also observed when the IL-4 toxin was administered via i.p. and i.v. routes. These results demonstrate that the IL-4 toxin may be a new therapeutic drug for the treatment of human glioblastoma, Therefore, we have begun a Phase I clinical trial with IL-4(38-37)-PE38KDEL for treatment of human glioblastoma. C1 NIH, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,Food & Drug Adm, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), NIH, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,Food & Drug Adm, Bldg 29B,Room 2NN10,29 Lincoln Dr MSC 4555, Bethesda, MD 20892 USA. EM Puri@A1.CBER.FDA.GOV NR 22 TC 63 Z9 65 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 1998 VL 58 IS 16 BP 3649 EP 3653 PG 5 WC Oncology SC Oncology GA 112EU UT WOS:000075481800030 PM 9721874 ER PT J AU Vallejo, A Heredia, A Mas, A Lee, SF Epstein, JS Soriano, V Hewlett, IK AF Vallejo, A Heredia, A Mas, A Lee, SF Epstein, JS Soriano, V Hewlett, IK TI Tropism, coreceptor use, and phylogenetic analysis of both the V3 loop and the protease gene of three novel HIV-1 group O isolates SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV-1; group O tropism; coreceptor; monocyte-derived macrophages; isolation; sequencing ID HUMAN-IMMUNODEFICIENCY-VIRUS; BIOLOGICAL PHENOTYPE; UNITED-STATES; TYPE-1; INFECTION; SEQUENCE; ENVELOPE; RECEPTOR; ENTRY; CCR5 AB HIV-1 has been subdivided into two groups, M and O, based on phylogenetic analysis. To better understand the pathogenesis of group O viruses, we studied biologic and genetic characteristics of two primary isolates from Spain, ES1158.1 and ES1159.1, and one from the United States, MD.1. After viral isolation, we studied the replication kinetics in peripheral blood mononuclear cells (PBMCs) and macrophages, as well as in different cell lines. All three isolates could replicate in both PBMCs and macrophages. Because no syncytium formation was detected in the MT-2 cell line, viruses were classified as non-syncytium inducing (NSI). Ail three isolates used the CCR5 coreceptor for entry into the human osteosarcoma (HOS) CD4 cells. Phylogenetic analysis of V3 loop sequences showed that ES1158.1 and ES1159.1 isolates were closely related to the ANT70 strain, whereas MD.1 isolate clustered with the MVP-5180 strain in the same branch. Interestingly, all viruses appeared to be more closely related to the MVP-5180 strain when the protease gene was analyzed, although accessible sequences of this region are very limited. C1 US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Bethesda, MD USA. Inst Salud Carlos III, Infect Dis Serv, Madrid, Spain. RP Hewlett, IK (reprint author), US FDA, CBER, HFM 315,1401 Rockville Pike, Rockville, MD 20852 USA. RI Vallejo, Alejandro/I-5881-2015; Mas, Antonio/F-2505-2011 OI Vallejo, Alejandro/0000-0001-5360-878X; Mas, Antonio/0000-0003-2563-570X NR 45 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD AUG 15 PY 1998 VL 18 IS 5 BP 417 EP 425 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 113VX UT WOS:000075575500002 PM 9715837 ER PT J AU Calabresi, PA Tranquill, LR McFarland, HF Cowan, EP AF Calabresi, PA Tranquill, LR McFarland, HF Cowan, EP TI Cytokine gene expression in cells derived from CSF of multiple sclerosis patients SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE PCR; tumor necrosis factor; interferon; interleukin; MRI ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; RESONANCE-IMAGING LESIONS; MESSENGER-RNA EXPRESSION; FLUID MONONUCLEAR-CELLS; CENTRAL-NERVOUS-SYSTEM; NECROSIS-FACTOR-ALPHA; CEREBROSPINAL-FLUID; DISEASE-ACTIVITY; INTERFERON-BETA; T-LYMPHOCYTES AB Cytokines are produced by numerous cell types in the peripheral blood and central nervous system (CNS), and have been implicated in the immunopathogenesis of multiple sclerosis (MS). We examined the relationship between cytokine gene expression of cerebrospinal fluid (CSF) derived cells from MS patients and disease activity as measured by contrast enhanced MRI. There was a significant correlation between the number of CSF cells and the number of contrast enhancing MRI lesions. Cytokine gene expression of TNF-alpha, IFN-gamma, and IL-10 was routinely seen, but IL-4 expression was absent except in two clinically quiescent patients. Trends were observed toward decreased TNF-alpha expression, but increased IL-10 expression, after treatment with IFN-beta 1b. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Brown Univ, Rhode Isl Hosp, Dept Neurol, Providence, RI 02903 USA. NINDS, Neuroimmunol Branch, Bethesda, MD 20892 USA. US FDA, Div Transfus Transmitted Dis, CBER, OBRR, Rockville, MD 20852 USA. RP Calabresi, PA (reprint author), Brown Univ, Rhode Isl Hosp, Dept Neurol, 110 Lockwood St,Suite 342, Providence, RI 02903 USA. NR 27 TC 45 Z9 45 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD AUG 14 PY 1998 VL 89 IS 1-2 BP 198 EP 205 DI 10.1016/S0165-5728(98)00139-8 PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 113UH UT WOS:000075571000025 PM 9726843 ER PT J AU Carson, MC Ngoh, MA Hadley, SW AF Carson, MC Ngoh, MA Hadley, SW TI Confirmation of multiple tetracycline residues in milk and oxytetracycline in shrimp by liquid chromatography particle beam mass spectrometry SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE tetracyclines ID CHELATE AFFINITY-CHROMATOGRAPHY; CHEMICAL-ANALYSIS; IMPROVEMENT; ANTIBIOTICS; TISSUES; HPLC AB A confirmation procedure is described for detection of residues of six tetracyclines in bovine milk, and oxytetracycline in shrimp. Residues are extracted from milk or shrimp tissue using metal chelate affinity chromatography. The extracts are desalted, further concentrated using polymeric solid-phase extraction, and chromatographed on a polymeric reversed-phase column. Analysis is by methane negative ion chemical ionization on a quadrupole mass spectrometer using a particle beam interface. Data are acquired in partial scan mode, monitoring from m/z 378 to m/z 480. The procedure was validated with control milk and shrimp, fortified milk (30 ng/ml) and shrimp (100 ng/g), and milk and tissue from animals treated with the drugs. Published by Elsevier Science B.V. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. US FDA, Off Regulatory Affairs, Seafood Prod Res Ctr, Seattle, WA 98021 USA. RP Carson, MC (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 20 TC 50 Z9 51 U1 4 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD AUG 7 PY 1998 VL 712 IS 1-2 BP 113 EP 128 DI 10.1016/S0378-4347(98)00171-6 PG 16 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 100RW UT WOS:000074830000012 PM 9698234 ER PT J AU Daley, WR AF Daley, WR TI Factors associated with implantation of single- versus dual-chamber pacemakers in 1992 SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID SICK SINUS SYNDROME; SURVIVAL; COMPLICATIONS; SELECTION; BLOCK AB Characteristics of hospitalized patients receiving initial pacemaker implantation were determined using a multistate inpatient discharge database. Analysis revealed a significant association of pacemaker type with patient age and income level, even after controlling for diagnostic factors. C1 US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20857 USA. RP Daley, WR (reprint author), CDC, NCEH, EHHE, HSB, Mailstop F-46,4770 Buford Hwy NE, Chamblee, GA 30341 USA. NR 11 TC 3 Z9 3 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 1998 VL 82 IS 3 BP 392 EP + DI 10.1016/S0002-9149(98)00327-0 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 107EK UT WOS:000075193900027 PM 9708676 ER PT J AU Whittaker, P AF Whittaker, P TI Iron and zinc interactions in humans SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Zinc for Child Health Symposium CY NOV 17-19, 1996 CL BALTIMORE, MARYLAND SP Johns Hopkins Family Health & Child Survival, Harvard Univ Appl Res Child Health Project, WHO Div Child Health & Dev, ICCDE,B Ctr Health & Populat Res, Jhons Hopkins Vitamin A for Health, UNICEF, Johns Hopkins Ctr Human Nutrit, Opportunities for Micronutrient Intervent Project DE iron; zinc; interactions; absorption; fortification; human; supplements ID ORAL IRON; ABSORPTION; BIOAVAILABILITY; FORTIFICATION; HEME AB Iron deficiency is the most common nutritional deficiency in the world; zinc deficiency is associated with poor growth and development and impaired immune response. Several Third World countries are taking measures to increase the dietary intake of iron and zinc with fortification of foods or dietary supplements. Several studies showed that high iron concentrations can negatively affect zinc absorption in adults when these trace minerals are given in solution. However, when iron and zinc are given in a meal, this effect is not observed. Solomons (J Nutr 1986;116:927-35) postulated that the total amount of ionic species affects the absorption of zinc and that a total dose of >25 mg Fe may produce a measurable effect on zinc absorption. This could occur if iron supplements are taken with a meal, and iron experts recommend that iron supplements be taken between meals. Recent studies using stable isotopes showed that fortifying foods with iron at current fortification amounts has no adverse effect on zinc absorption. There are 5 zinc salts listed as generally recommended as safe (GRAS) by the US Food and Drug Administration for food fortification. From 1970 to 1987, the total amount of zinc salts used in food continually increased, with zinc oxide and zinc sulfate showing the largest increases. Twelve iron sources are listed as GRAS; elemental iron has become the source of choice because it is less expensive to produce and has fewer organoleptic problems. Use of ferrous fumarate is also increasing. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Whittaker, P (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 16 TC 67 Z9 77 U1 0 U2 7 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 1998 VL 68 IS 2 SU S BP 442S EP 446S PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 107LD UT WOS:000075208600008 PM 9701159 ER PT J AU Headrick, ML Korangy, S Bean, NH Angulo, FJ Altekruse, SF Potter, ME Klontz, KC AF Headrick, ML Korangy, S Bean, NH Angulo, FJ Altekruse, SF Potter, ME Klontz, KC TI The epidemiology of raw milk-associated foodborne disease outbreaks reported in the United States, 1973 through 1992 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article AB Objectives. This study describes the epidemiology of raw milk-associated outbreaks reported to the Centers for Disease Control and Prevention from 1973 through 1992. Methods. Surveillance data for each reported raw milk-associated outbreak were reviewed. A national survey was conducted to determine the legal status of intrastate raw milk sales for the period 1973 through 1995. Results. Forty-six raw milk-associated outbreaks were reported during the study period; 40 outbreaks (87%) occurred in states where the intrastate sale of raw milk was legal. Conclusions. Consumption of raw milk remains a preventable cause of foodborne disease outbreaks. C1 US FDA, Ctr Food Safety & Appl Nutr, Epidemiol Branch, Washington, DC 20204 USA. Ctr Dis Control, Natl Ctr Infect Dis, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. RP Klontz, KC (reprint author), HFS-728,200 C St SW, Washington, DC 20204 USA. NR 14 TC 70 Z9 74 U1 0 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD AUG PY 1998 VL 88 IS 8 BP 1219 EP 1221 DI 10.2105/AJPH.88.8.1219 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 106XJ UT WOS:000075176300015 PM 9702153 ER PT J AU Pothuluri, JV Sutherland, JB Freeman, JP Cerniglia, CE AF Pothuluri, JV Sutherland, JB Freeman, JP Cerniglia, CE TI Fungal biotransformation of 6-nitrochrysene SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; DNA ADDUCT FORMATION; NITROAROMATIC COMPOUNDS; CUNNINGHAMELLA-ELEGANS; INTESTINAL MICROFLORA; METABOLISM; MICE; DERIVATIVES; 3-NITROFLUORANTHENE; DETOXIFICATION AB The fungus Cunninghamella elegans was used to biotransform 6-nitrochrysene,a mutagen that is a widespread environmental contaminant. After 6 days, 74% of the (3)H-labeled 6-nitrochrysene added had been metabolized to two isomeric sulfate conjugates. These conjugates were separated by high-performance liquid chromatography and identified by UV-visible,(1)H nuclear magnetic resonance, and mass spectral techniques as 6-nitrochrysene 1-sulfate and 6-nitrochrysene 2-sulfate. C1 US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Pothuluri, JV (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, HFT-250, Jefferson, AR 72079 USA. EM Jpothuluri@nctr.fda.gov NR 37 TC 16 Z9 17 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 AUG PY 1998 VL 64 IS 8 BP 3106 EP 3109 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 106JY UT WOS:000075127200058 PM 9687485 ER PT J AU Zmudzka, BZ Beer, JZ AF Zmudzka, BZ Beer, JZ TI Ultraviolet therapy and patients with HIV infection SO ARCHIVES OF DERMATOLOGY LA English DT Editorial Material ID HUMAN IMMUNODEFICIENCY VIRUS; UVB PHOTOTHERAPY; ACTIVATION; CELLS C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Zmudzka, BZ (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-114,9200 Corp Blvd, Rockville, MD 20850 USA. NR 16 TC 2 Z9 2 U1 0 U2 1 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 AUG PY 1998 VL 134 IS 8 BP 1025 EP 1026 DI 10.1001/archderm.134.8.1025 PG 2 WC Dermatology SC Dermatology GA 110ZY UT WOS:000075413900019 PM 9722738 ER PT J AU Brorson, K AF Brorson, K TI Electronic companion to molecular cell biology SO ASM NEWS LA English DT Software Review C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0044-7897 J9 ASM NEWS JI ASM News PD AUG PY 1998 VL 64 IS 8 BP 467 EP 467 PG 1 WC Microbiology SC Microbiology GA 109WK UT WOS:000075347200017 ER PT J AU Johnson, RN AF Johnson, RN TI Ensuring laboratory compliance SO BIOPHARM-THE APPLIED TECHNOLOGIES OF BIOPHARMACEUTICAL DEVELOPMENT LA English DT Article AB Based on her own years of experience in the field, an FDA inspector offers practical advice for complying with good manufacturing practices in biopharmaceutical laboratories. C1 US FDA, NW Reg Lab, Bothell, WA 98041 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 1040-8304 J9 BIOPHARM-APPL T BIO JI Biopharm-Appl Technol. Biopharm. Dev. PD AUG PY 1998 VL 11 IS 8 BP 28 EP 30 PG 3 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 109GF UT WOS:000075312700003 ER PT J AU Harris, AJ Shaddock, JG Manjanatha, MG Lisenbey, JA Casciano, DA AF Harris, AJ Shaddock, JG Manjanatha, MG Lisenbey, JA Casciano, DA TI Identification of differentially expressed genes in aflatoxin B-1-treated cultured primary rat hepatocytes and Fischer 344 rats SO CARCINOGENESIS LA English DT Article ID CORTICOSTEROID-BINDING GLOBULIN; GLUTATHIONE S-TRANSFERASES; HUMAN-LIVER; HEPATOCELLULAR-CARCINOMA; MOLECULAR-CLONING; MESSENGER-RNA; P53 GENE; DNA; B-1; ACTIVATION AB Aflatoxin B-1 (AFB(1)), a mutagen and hepatocarcinogen in rats and humans, is a contaminant of the human food supply, particularly in parts of Africa and Asia. AFB(1-)induced changes in gene expression may play a part in the development of the toxic, immunosuppressive and carcinogenic properties of this fungal metabolite. An understanding of the role of AFB1 in modulating gene regulation should provide insight regarding mechanisms of AFB(1-)induced carcinogenesis. We used three PCR-based subtractive techniques to identify AFB(1)-responsive genes in cultured primary rat hepatocyte RNA: differential display PCR (DD-PCR), representational difference analysis (RDA) and suppression subtractive hybridization (SSH), Each of the three techniques identified AFB1-responsive genes, although no individual cDNA was isolated by more than one technique. Nine cDNAs isolated using DD-PCR, RDA or SSH were found to represent eight genes that are differentially expressed as a result of AFB1 exposure. Genes whose mRNA levels were increased in cultured primary rat hepatocytes after AFB1 treatment were corticosteroid binding globulin (CBG), cytochrome P450 4F1 (CYP4F1), alpha-2 microglobulin, C4b-binding protein (C4BP), serum amyloid A-2 and glutathione S-transferase Yb2 (GST). Transferrin and a small CYP3A-like cDNA had reduced mRNA levels after AFB1 exposure. Full-length CYP3A mRNA levels were increased. When liver RNA from AFB(1)-treated male F344 rats was evaluated for transferrin, CBC, GST, CYP3A and CYP4F1 expression, a decrease in transferrin mRNA and an increase in CBG, GST, CYP3A and CYP4F1 mRNA levels was also seen. Analysis of the potential function of these genes in maintaining cellular homeostasis suggests that their differential expression could contribute to the toxicity associated with AFB1 exposure. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Harris, AJ (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. EM ajharris@nctr.fda.gov NR 69 TC 23 Z9 24 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 1998 VL 19 IS 8 BP 1451 EP 1458 DI 10.1093/carcin/19.8.1451 PG 8 WC Oncology SC Oncology GA 111TW UT WOS:000075454900019 PM 9744542 ER PT J AU Steinmetz, KL Pogribny, IP James, SJ Pitot, HC AF Steinmetz, KL Pogribny, IP James, SJ Pitot, HC TI Hypomethylation of the rat glutathione S-transferase pi(GSTP) promoter region isolated from methyl-deficient livers and GSTP-positive liver neoplasms SO CARCINOGENESIS LA English DT Article ID ALTERED HEPATIC FOCI; RECEPTOR CPG ISLAND; DNA METHYLATION; P-GENE; HUMAN CANCERS; EXPRESSION; SP1; HEPATOCARCINOGENESIS; TUMORS; DIETHYLNITROSAMINE AB DNA methylation at the 5-position on the cytosine ring in CpG dinucleotides (CpG sites) appears to play an important role in regulating gene expression. In general, there is an inverse relationship between promoter CpG site methylation and the potential for transcription. Thus, changes in DNA methylation density may lead to altered levels of proteins such as glutathione S-transferase pi (GSTP), which is frequently used as a marker to detect hepatocellular foci and neoplasms in the rat, In the present study, the level of CPG methylation in the rat GSTP promoter region was determined in bisulfite-treated DNA isolated from control (untreated) rat livers, chemically induced, GSTP-positive rat liver neoplasms, and methyl-deficient rat livers that contained numerous GSTP-positive foci after administration of a defined diet deficient in folate and choline and low in methionine (0.18%), Eight cytosines between -235 and +140 in the GSTP promoter region were methylated in a site-specific manner in GSTP-negative control liver, whereas these same sites were hypomethylated in all four chemically-induced, GSTP-positive neoplasms. Similarly, all CpG sites were unmethylated in methyl-deficient liver DNA within 3 weeks of the rats receiving the methyl-deficient diet, and they remained unmethylated throughout the 36-week treatment period. Five of the eight CpG sites are located within consensus sequences for the DNA binding proteins Spl and E2F. This indicates at least one possible mechanism that could potentially lead to transcriptional activation of GSTP in hepatocellular foci and neoplasms during rat hepatocarcinogenesis, These findings suggest that methylation of critical cytosines within the promoter region rather than all CpG-associated cytosines may be a determining factor in regulation of GSTP expression. C1 Univ Wisconsin, Mcardle Lab Canc Res, Madison, WI 53706 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Pitot, HC (reprint author), Univ Wisconsin, Mcardle Lab Canc Res, 1400 Univ Ave, Madison, WI 53706 USA. NR 72 TC 27 Z9 28 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 AUG PY 1998 VL 19 IS 8 BP 1487 EP 1494 DI 10.1093/carcin/19.8.1487 PG 8 WC Oncology SC Oncology GA 111TW UT WOS:000075454900024 PM 9744547 ER PT J AU Fu, PP Von Tungeln, LS Chiu, LH Zhan, DJ Deck, J Bucci, T Wang, JC AF Fu, PP Von Tungeln, LS Chiu, LH Zhan, DJ Deck, J Bucci, T Wang, JC TI Structure, tumorigenicity, microsomal metabolism, and DNA binding of 7-nitrodibenz[a,h]anthracene SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; DIRECT-ACTING MUTAGENICITY; NITRO-GROUP ORIENTATION; RAT-LIVER MICROSOMES; STEREOSELECTIVE METABOLISM; BACTERIAL MUTAGENICITY; SALMONELLA-TYPHIMURIUM; MOUSE ASSAY; DERIVATIVES; SUBSTITUENT AB It has been previously proposed that a nitropolycyclic aromatic hydrocarbon (nitro-PAH) with its nitro functional group perpendicular or nearly perpendicular to the aromatic moiety exhibits lower tumorigenicity than the corresponding parent aromatic hydrocarbon. We also hypothesized that reduction of the nitro group is not involved, or contributed less significantly in the metabolic activation of this class of nitro-PAHs. To verify this hypothesis, we selected 7-nitrodibenz[a,h]anthracene (7-NDB[a,h]A) for study. The X-ray crystallographic structure of 7-NDB[a,h]A was determined and indicated that the dihedral angle between the nitro functional group and the aromatic dibenz[a,h]anthracenyl moiety was 80.6 degrees, indicating the nitro group preferentially adopts a nearly perpendicular orientation. The tumorigenicity of 7-NDB[a,h]A and dibenz[a,h]anthracene (DB[a,h]A) was determined in the male B6C3F(1) neonatal mouse. Mice were administered ip injections of 1/7, 2/7, and 4/7 of the total dose of 7-NDB[a,h]A (400 nmol in 35 mu L of DMSO per mouse) within 24 h of birth and at 8 and 15 days of age, respectively, and sacrificed at 12 months of age. DB[a,h]A induced 78 and 96% hepatocellular adenomas and carcinomas, respectively. However, 7-NDB[a,h]A induced only 50 and 8% hepatocellular adenomas and carcinomas compared with the 8 and 4% hepatocellular adenomas and carcinomas induced by the solvent vehicle, DMSO. Aerobic metabolism of 7-NDB[a,h]A by liver microsomes of 15-day old male B6C3F(1) neonatal mice resulted in trans-3,4-dihydroxy-3,4-dihydro-7-nitrodibenz[a,h]anthracene (7-NDB[a,h]A trans-3,4-dihydrodiol) and trans-10,11-dihydroxy-10,11-dihydro-7-nitrodibenz[a,h]anthracene (7-NDB[a,h]A trans-10,11-dihydrodiol) as predominant metabolites. Under anaerobic conditions, 7-NDB[a,h]A was not metabolized (nitroreduced). The DNA adduct levels in liver and lung tissues of male B6C3F1 mice treated with 7-NDB[a,h]A and sacrificed 24 h and 6 days after final dosing were determined by P-32-postlabeling/TLC. In all cases, the DNA adducts derived from 7-NDB[a,h]A trans-3,4-dihydrodiol and 7-NDB[a,h]A trans-10,11-dihydrodiol were formed. These results suggest that both of the metabolites, 7-NDB[a, h]A trans-3,4-dihydrodiol and 7-NDB[a,h]A trans-10,11-dihydrodiol, are involved in the metabolic activation of 7-NDB[a,h]A, leading to tumor induction in the neonatal mouse. Thus, our results described in this paper support our hypotheses that a nitro-PAH with a perpendicular nitro orientation exhibits lower tumorigenicity than the corresponding parent PAH and that nitroreduction contributes less significantly in the metabolic activation. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Soochow Univ, Dept Chem, Taipei, Taiwan. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 38 TC 17 Z9 17 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD AUG PY 1998 VL 11 IS 8 BP 937 EP 945 DI 10.1021/tx980079+ PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 112EW UT WOS:000075482000012 PM 9705756 ER PT J AU Brasher, CW DePaola, A Jones, DD Bej, AK AF Brasher, CW DePaola, A Jones, DD Bej, AK TI Detection of microbial pathogens in shellfish with multiplex PCR SO CURRENT MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; THERMOSTABLE DIRECT HEMOLYSIN; VIBRIO-PARAHAEMOLYTICUS; ESCHERICHIA-COLI; GENE PROBES; SALMONELLA; VULNIFICUS; AMPLIFICATION; SEQUENCES; CHOLERAE AB Multiplex PCR amplification of uidA, cth, invA, ctx, and tl genes was developed enabling simultaneous detection in shellfish of Escherichia coli, an indicator of fecal contamination and microbial pathogens, Salmonella typhimurium, Vibrio vulnificus, V. cholerae, and V. parahaemolyticus, respectively. Each of the five pairs of oligonucleotide primers was found to support PCR amplifications of only its targeted gene. The optimized multiplex, PCR reaction utilized a PCR reaction buffer containing 2.5 mM MgCl2 and primer annealing temperature of 55 degrees C. Oyster tissue homogenate seeded with these microbial pathogens was subjected to DNA purification by the Chelex(TM) 100 (BioRad) method. The sensitivity of detection for each of the microbial pathogens was less than or equal to 10(1)-10(2) cells following a "double" multiplex PCR amplification approach. Amplified target genes in a multiplex PCR reaction were subjected to a colorimetric GeneComb(TM) (BioRad) DNA-DNA hybridization assay. This assay was rapid and showed sensitivity of detection comparable to the agarose gel electrophoresis method. The colorimetric GeneComb(TM) assay avoids use of hazardous materials inherent in conventional gel electrophoresis and radioactive-based hybridization methods. Multiplex PCR amplification, followed by colorimetric GeneComb(TM) DNA-DNA hybridization, has been shown to be an effective, sensitive, and rapid method to detect microbial pathogens in shellfish. C1 Univ Alabama, Dept Biol, Birmingham, AL 35294 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. RP Bej, AK (reprint author), Univ Alabama, Dept Biol, 1300 Univ Blvd, Birmingham, AL 35294 USA. NR 41 TC 113 Z9 118 U1 0 U2 6 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0343-8651 J9 CURR MICROBIOL JI Curr. Microbiol. PD AUG PY 1998 VL 37 IS 2 BP 101 EP 107 DI 10.1007/s002849900346 PG 7 WC Microbiology SC Microbiology GA 100VQ UT WOS:000074836400005 PM 9662609 ER PT J AU Muller, FMC Schnitzler, N Cloot, O Kockelkorn, P Haase, G Li, ZM AF Muller, FMC Schnitzler, N Cloot, O Kockelkorn, P Haase, G Li, ZM TI The rationale and method for constructing internal control DNA used in pertussis polymerase chain reaction SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article ID BORDETELLA-PERTUSSIS; NASOPHARYNGEAL SWABS; MYCOBACTERIUM-TUBERCULOSIS; PCR AMPLIFICATION; OVERLAP EXTENSION; REACTION ASSAY; IDENTIFICATION; DIAGNOSIS; GENE; PARAPERTUSSIS AB The inclusion of an appropriate internal control DNA in polymerase chain reaction (PCR) is a rapid and simple method for the detection of PCR failure. Two PCR coamplification internal control DNAs (ICD I and ICD II) with the same primer-binding sequences as the target DNA for the detection of Bordetella pertussis and Bordetella parapertussis were produced using an overlap extension technique and a PCR MIMIC(TM) construction kit, respectively. The ICD II was further evaluated in a prospective clinical study in 360 patients with a clinical diagnosis of pertussis. From 360 nasopharyngeal swabs the internal control was positive in 318 (88%) samples, but was negative in 42 (12%). After phenol-chloroform extraction an additional 10 internal controls became positive. For the detection of PCR failure, the use of internal control DNA is highly recommended for PCR-based identification of B. pertussis and B. parapertussis organisms from nasopharyngeal swabs and aspirates. (C) 1998 Elsevier Science Inc. C1 Childrens Hosp, Aachen, Germany. Univ Aachen, Inst Med Microbiol, D-5100 Aachen, Germany. US FDA, Div Bacterial Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Muller, FMC (reprint author), Univ Wurzburg, Inst Mol Infekt Biol, Rontgenring 11, D-97070 Wurzburg, Germany. RI Haase, Gerhard/C-6492-2009 OI Haase, Gerhard/0000-0001-7771-3189 NR 47 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 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD AUG PY 1998 VL 31 IS 4 BP 517 EP 523 DI 10.1016/S0732-8893(98)00043-1 PG 7 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 115EJ UT WOS:000075650300003 PM 9764389 ER PT J AU Kim, CS Ross, IA Sandberg, JA Preston, E AF Kim, CS Ross, IA Sandberg, JA Preston, E TI Quantitative low-dose assessment of seafood toxin, domoic acid, in the rat brain: application of physiologically-based pharmacokinetic (PBPK) modeling SO ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE pharmacokinetic modeling; domoic acid; neurotoxicity risk assessment ID RABBIT BRAIN; TRANSFER CONSTANTS; TRANSPORT; BARRIER; DOSIMETRY; CLEARANCE; MICE AB The purpose of this study was to construct a physiologically based pharmacokinetic model and demonstrate its ability to predict low-dose uptake of domoic acid, a seafood contaminant, in discrete areas of the rat brain. The model we used was derived from the generic PBPK model of our previous studies with 2,4-dichlorophenoxyacetic acid (Kim et al., 1994. Pharmacokinetic modeling of 2,4-dichlorophenoxyacetic acid (2,4-D) in rats and in rabbits brain following single dose administration. Toxicol. Lett. 74, 189; Kim et al., 1995. Development of a physiologically based pharmacokinetic model for 2,4-dichlorophenoxyacetic acid dosimetry in discrete areas of the rabbit brain. Neurotoxicol. Teratol. 17, 111), to which physiological- and chemical-specific parameters for domoic acid were applied. It incorporates two body compartments along with compartments for venous and arterial blood, cerebrospinal fluid, brain plasma and seven brain regions. Uptake of the blood-borne toxin is membrane-limited by the blood-brain barrier with clearance from the brain provided by cerebrospinal fluid 'sink' mechanisms. This model generated predicted profiles of toxin level in brain and blood over a l-h period that compared reasonably well with concentrations calculated from in vivo data of rats that had been given [H-3]domoic acid intravenously (Preston and Hynie, 1991. Transfer constants for blood-brain barrier permeation of the neuroexcitatory shellfish toxin, domoic acid. Can. J. Neurol. Sci. 18, 39). This PBPK model should be an effective tool for evaluating the target doses that produce the potential neurotoxicity of domoic acid found in foods. (C) 1998 Elsevier Science B.V. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Toxicol Res HFS506, Washington, DC 20204 USA. Chem Ind Inst Toxicol, Res Triangle Pk, NC 27709 USA. Natl Ctr Toxicol Res, Div Neurotoxicol HFT132, Jefferson, AR 72079 USA. Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A OR6, Canada. RP Kim, CS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Toxicol Res HFS506, Washington, DC 20204 USA. NR 23 TC 7 Z9 9 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1382-6689 J9 ENVIRON TOXICOL PHAR JI Environ. Toxicol. Pharmacol. PD AUG PY 1998 VL 6 IS 1 BP 49 EP 58 DI 10.1016/S1382-6689(98)00019-2 PG 10 WC Environmental Sciences; Pharmacology & Pharmacy; Toxicology SC Environmental Sciences & Ecology; Pharmacology & Pharmacy; Toxicology GA 108XH UT WOS:000075290700006 PM 21781881 ER PT J AU Rao, P Dougherty, SF Pluznik, DH AF Rao, P Dougherty, SF Pluznik, DH TI Induction of granulocyte-macrophage colony stimulating factor (GM-CSF) expression by lipopolysaccharide (LPS), taxol, and interleukin-1 beta (IL-1 beta) in B cells is enhanced by microtubule depolymerization. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 US FDA, Div Hematol Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1998 VL 26 IS 8 MA 144 BP 721 EP 721 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 118GT UT WOS:000075830600146 ER PT J AU Wolff, GL Kodell, RL Moore, SR Cooney, CA AF Wolff, GL Kodell, RL Moore, SR Cooney, CA TI Maternal epigenetics and methyl supplements affect agouti gene expression in A(vy)/a mice SO FASEB JOURNAL LA English DT Article DE maternal diet; methyl supplementation; DNA methylation; epigenetic regulation of gene expression; yellow mice ID X-CHROMOSOME INACTIVATION; NEURAL-TUBE DEFECTS; DNA METHYLTRANSFERASE; MOUSE; PARTICLE; MUTATION; CHOLINE; INHERITANCE; METABOLISM; METHIONINE AB 'Viable yellow' (A(vy)/alpha) mice are larger, obese, hyperinsulinemic, more susceptible to cancer, and, on average, shorter lived than their non-yellow siblings. They are epigenetic mosaics ranging from a yellow phenotype with maximum ectopic agouti overexpression, through a continuum of mottled agouti/yellow phenotypes with partial agouti overexpression, to a pseudoagouti phenotype with minimal ectopic expression. Pseudoagouti A(vy)/a mice are lean, healthy, and longer lived than their yellow siblings. Here we report that feeding pregnant black a/a dams methyl-supplemented diets alters epigenetic regulation of agouti expression in their offspring, as indicated by increased agouti/black mottling in the direction of the pseudoagouti phenotype, We also present confirmatory evidence that epigenetic phenotypes are maternally heritable. Thus A(vy) expression, already known to be modulated by imprinting, strain-specific modification, and maternal epigenetic inheritance, is also modulated by maternal diet. These observations suggest, at least in this special case, that maternal dietary supplementation may positively affect health and longevity of the offspring, Therefore, this experimental system should be useful for identifying maternal factors that modulate epigenetic mechanisms, especially DNA methylation, in developing embryos. C1 US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Biochem Mol Biol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pharmacol Interdisciplinary Toxicol, Little Rock, AR 72205 USA. Bionet Corp, Jefferson, AR 72079 USA. RP Wolff, GL (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. OI Cooney, Craig/0000-0003-4279-557X NR 53 TC 595 Z9 614 U1 7 U2 68 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD AUG PY 1998 VL 12 IS 11 BP 949 EP 957 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 110GR UT WOS:000075372600005 PM 9707167 ER PT J AU Collins, TFX Sprando, RL Black, TN Shackelford, ME Laborde, JB Hansen, DK Eppley, RM Trucksess, MW Howard, PC Bryant, MA Ruggles, DI Olejnik, N Rorie, JI AF Collins, TFX Sprando, RL Black, TN Shackelford, ME Laborde, JB Hansen, DK Eppley, RM Trucksess, MW Howard, PC Bryant, MA Ruggles, DI Olejnik, N Rorie, JI TI Effects of fumonisin B(1) in pregnant rats. Part 2 SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE fumonisin; mycotoxin; developmental toxicity; sphinganine; sphingosine; rat ID ESOPHAGEAL CANCER AREAS; FUSARIUM-MONILIFORME; DEVELOPMENTAL TOXICITY; SPHINGOLIPID BIOSYNTHESIS; CORN SCREENINGS; MYCOTOXINS; CONTAMINATION; SWINE; INHIBITION; TRANSKEI AB The developmental toxicity of purified fumonisin B(1) (FB1), a mycotoxin from the common corn fungus Fusarium moniliforme, was examined in Charles River rats: Pregnant rats were dosed orally on gestation days 3-16 at 0, 6.25, 12.5, 25 or 50 mg FB1/kg body weight/day. FB1 was not teratogenic at the doses tested. At 50 mg/kg, maternal toxicity (inappetence, emaciation, lethargy, death, resorption of entire litters) and foetal toxicity (increased number of late deaths, decreased foetal body weight, decreased crown-rump length, increased incidence of hydrocephalus, increased incidence of skeletal anomalies) were seen. The foetal toxicity observed at 50 mg/kg may be related to maternal toxicity. Histopathological evaluation of tissues from dams of control and all treated groups revealed dose-related toxic changes in kidney and liver tissues. Acute toxic tubular nephrosis was seen in kidneys from all treated groups. Hepatocellular cytoplasmic alteration and individual cellular necrosis of the liver was seen in the two high-dose groups. Sphinganine (Sa) and sphingosine (So) were measured in day-17 adult and foetal tissues. Dose related increases in Sa/So ratios were seen in maternal liver, kidney, serum and brain, but there was no effect on foetal liver, kidney and brain. These data suggest that FBI does not cross the placenta and further suggest that the observed foetal toxicity is a secondary response to maternal toxicity. (C) 1998 Elsevier Science Ltd. All rights reserved C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Collins, TFX (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. NR 76 TC 17 Z9 17 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD AUG PY 1998 VL 36 IS 8 BP 673 EP 685 DI 10.1016/S0278-6915(98)00036-2 PG 13 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 110QE UT WOS:000075391200008 PM 9734718 ER PT J AU Rader, JI Weaver, CM Angyal, G AF Rader, JI Weaver, CM Angyal, G TI Use of a microbiological assay with tri-enzyme extraction for measurement of pre-fortification levels of folates in enriched cereal-grain products SO FOOD CHEMISTRY LA English DT Article ID LIQUID-CHROMATOGRAPHIC DETERMINATION; LACTOBACILLUS-CASEI; FOLIC-ACID; FOOD FORTIFICATION; INFANT FORMULA; MONOGLUTAMATES; DERIVATIVES; RADIOASSAY; VITAMIN AB January 1, 1998 was the effective date for FDA regulations that mandated the fortification in the USA of a wide range of enriched cereal-grain products with folic acid at levels specified in federal regulations. Because data on prefortification levels of folate in such products are limited, we measured folate in 56 enriched foods, including enriched breads and rolls, flours, corn grits and meals, rices, and macaroni and noodle products. Folate was measured by a modification of the Association of Official Analytical Chemists' microbiological method 992.05 using Lactobacillus casei. Foods were composited, suspended in 0.1 M phosphate buffer containing 1% ascorbic acid (pH 7.8), autoclaved and cooled. Chicken pancreas conjugase was added and the suspensions were incubated for 16 h at 37 degrees C. Values for folate in enriched products were (mu g/100 g): bread and rolls, 24-40; flours, 19-24; corn grits and meals, 22-32; macaroni and noodle products, 27-42; rice, 19-32. Because the single-enzyme method is usually insufficient to liberate food-bound folates, suspensions of foods were also incubated with alpha-amylase and conjugase followed by treatment with protease to determine the effects of the tri-enzyme digestion on release of folates. For many foods, total folate was 20-30% higher after the tri-enzyme digestion than after incubation with conjugase alone. The modifications of AOAC method 992.05 described here provide a microbiological assay method for the determination of folates in cereal-grain products that may be appropriate for collaborative testing. (C) 1998 Elsevier Science Ltd. All rights reserved C1 US FDA, Off Food Labeling, Washington, DC 20204 USA. RP Rader, JI (reprint author), US FDA, Off Food Labeling, Washington, DC 20204 USA. NR 43 TC 65 Z9 68 U1 1 U2 13 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 PY 1998 VL 62 IS 4 BP 451 EP 465 DI 10.1016/S0308-8146(98)00089-2 PG 15 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA 110XF UT WOS:000075406300008 ER PT J AU Turturro, A Hass, B Hart, RW AF Turturro, A Hass, B Hart, RW TI Hormesis - Implications for risk assessment caloric intake (body weight) as an exemplar SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Article DE hormesis; bioassay; dietary control; body weight; nonmonotonic; caloric intake ID RATS; RESTRICTION; TOXICITY; CANCER; DIET AB Hormesis can he considered as a parameter which has a non-monotonic relationship with some endpoint. Since caloric intake is such a parameter, and the impact of this parameter on risk assessment has been fairly well characterized, it can provide clues as to how to integrate the information from a hermetic parameter into risk assessments for toxicants. Based on the work with caloric intake, one could: (a) define a biomarker for hermetic effect; (b) integrate specific information on when in the animals lifespan the parameter is active to influence parameters such as survival; (c) evaluate component effects of the overall hermetic response; and (d) address the consequences of a non-monotonic relationship between the hermetic parameter and end-points critical for risk assessment. These impacts on risk assessments have been characterized for chronic tests, but are also true for short-term tests. A priority is the characterization of the dose-response curves for hermetic parameters. This quantification will be critical in utilizing them in risk assessment. With this information, one could better quantitatively address the changes one expects to result from the hermetic parameter, and limit the uncertainty and variability which occurs in toxicity testing. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Off Director, Jefferson, AR 72079 USA. RP Turturro, A (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 31 TC 15 Z9 17 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0144-5952 J9 HUM EXP TOXICOL JI Hum. Exp. Toxicol. PD AUG PY 1998 VL 17 IS 8 BP 454 EP 459 DI 10.1191/096032798678909089 PG 6 WC Toxicology SC Toxicology GA 116DQ UT WOS:000075708700009 PM 9756140 ER PT J AU Fernandez-Prada, C Tall, BD Elliott, SE Hoover, DL Nataro, JP Venkatesan, MM AF Fernandez-Prada, C Tall, BD Elliott, SE Hoover, DL Nataro, JP Venkatesan, MM TI Hemolysin-positive enteroaggregative and cell-detaching Escherichia coli strains cause oncosis of human monocyte-derived macrophages and apoptosis of murine J774 cells SO INFECTION AND IMMUNITY LA English DT Article ID LISTERIA-MONOCYTOGENES; INTESTINAL-MUCOSA; T-LYMPHOCYTES; ADHERENCE; PATTERNS; TOXIN; DEATH; BORDETELLA; DIARRHEA; CHILDREN AB Infection of human monocyte-derived macrophages (HMDM) and J774 cells (murine macrophage cell line) with several enteroaggregative and cytodetaching Escherichia coli (EAggEC and CDEC, respectively) strains demonstrated that some strains could induce macrophage cell death accompanied by release of lactate dehydrogenase activity and interleukin 1 beta (IL-1 beta) into culture supernatants. The mode of cell death differed in the two types of macrophages. Damage to macrophage plasma membrane integrity without changes in nuclear morphology resulted in cytolysis of HMDM. This mechanism of cell death has been previously described for virulent Shigella infection of HMDM and is termed oncosis. In contrast, infection of J774 tells by EAggEC and CDEC strains resulted in apoptosis. The presence of alpha-hemolysin (Hly) in EAggEC and CDEC strains appears to be critical for both oncosis in HMDM and apoptosis in J774 cells. Bacteria lacking Hly, including Hly(-) EAggEC strains as well as enterotoxigenic, enteropathogenic, and enterohemorrhagic E. coli strains, behaved like avirulent Shigella flexneri in that the macrophage monolayers were intact, with no release of lactate dehydrogenase activity or IL-1 beta into the culture supernatants. C1 Walter Reed Army Inst Res, Dept Enter Infect, Div Communicable Dis & Immunol, Washington, DC 20307 USA. US FDA, Ctr Food Safety & Appl Nutr, Microbial Ecol Branch, Washington, DC 20204 USA. Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. RP Venkatesan, MM (reprint author), Walter Reed Army Inst Res, Dept Enter Infect, Div Communicable Dis & Immunol, Bldg 40,Room B020, Washington, DC 20307 USA. EM dr._malabi_venkatesan@wrsmtp-ccmail.army.mil OI Tall, Ben/0000-0003-0399-3629 NR 45 TC 47 Z9 47 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1998 VL 66 IS 8 BP 3918 EP 3924 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 103TJ UT WOS:000074973700057 PM 9673280 ER PT J AU Finn, TM Amsbaugh, DF AF Finn, TM Amsbaugh, DF TI Vag8, a Bordetella pertussis bvg-regulated protein SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEINS; ENVELOPE PROTEINS; FILAMENTOUS HEMAGGLUTININ; COLONIZATION FACTOR; VIRULENCE FACTORS; CLONING; VIR; CONSTRUCTION; MUTATIONS; VECTORS AB Bordetella pertussis expresses a bvg-regulated 95-kDa protein, Vag8, encoded by vag-8. Southern blot analysis indicates that strains of Bordetella bronchiseptica and Bordetella parapertussis have DNA homologous to vag-8. Antiserum raised to a fusion of maltose binding protein to an N-terminal 60-kDa fragment of Vag8 recognizes the native 95-kDa protein in immunoblots of B. pertussis and B. bronchiseptica but not B. parapertussis. A 95-kDa protein-negative derivative of B. pertussis 18323 containing a deletion of vag-8 colonized mice as efficiently as the parent B. pertussis strain in a mouse aerosol model of pertussis. C1 US FDA, Ctr Biol Evaluat & Res, Lab Pertussis, Bethesda, MD 20892 USA. RP Finn, TM (reprint author), US FDA, CBER, HFM434,1401 Rockville Pike, Rockville, MD 20852 USA. EM finn@cber.cber.fda.gov NR 29 TC 35 Z9 36 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1998 VL 66 IS 8 BP 3985 EP 3989 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 103TJ UT WOS:000074973700070 PM 9673293 ER PT J AU Murata, T Husain, SR Mohri, H Puri, RK AF Murata, T Husain, SR Mohri, H Puri, RK TI Two different IL-13 receptor chains are expressed in normal human skin fibroblasts, and IL-4 and IL-13 mediate signal transduction through a common pathway SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE activation; IL-13 receptor structure; insulin response substrate (IRS); Janus (JAK) kinase; phosphorylation; signal transduction and activator of transcription (STAT) ID HUMAN INTERLEUKIN-4 RECEPTOR; CARCINOMA CELL-LINES; GAMMA-CHAIN; JANUS KINASE; ALPHA CHAIN; B-CELLS; GROWTH; PHOSPHORYLATION; PROLIFERATION; SIMILARITIES AB IL-13 and IL-4, pleiotropic immune regulatory cytokines, have been shown to mediate similar prominent effects in human fibroblast cell lines, However, molecular mechanisms for their redundant effects are not known. Here, we have investigated the structure of IL-13 receptors (IL-13R) and molecular mechanisms of signal transduction through IL-13 and IL-4 receptors in non-transformed normal skin fibroblast cell lines. We demonstrate that high-affinity IL-13R is expressed in normal skin fibroblast cell lines. Upon [I-125]IL-13 cross-linking, a similar to 60-70 kDa band was observed in sk559 and sk574 fibroblast cell lines. By RT-PCR analysis, mRNA for IL-13R alpha, IL-13R alpha' and IL-4R beta chains were expressed; however, the lL-2R gamma chain, shown to participate and modulate IL-4 and IL-13 binding, was not expressed in any of the cell lines examined, The Janus kinase (JAK)2 and Tyk2 were phosphorylated in response to IL-4 or IL-13 in sk559 and sk574 cell lines, JAK1 was also phosphorylated in one of two cell lines while JAK3 was present but not phosphorylated in any of the cell lines studied, A signal transduction and activator of transcription (STAT)6 was also activated in response to both IL. An insulin receptor substrate (IRS)-1 was constitutively phosphorylated and its phosphorylation level was augmented in response to both IL, These results suggest that the mechanism of signal transduction through IL-13 and IL-4 receptors in human fibroblast cell lines is similar, and this may, at least in part, be responsible for the redundant effects of these two cytokines, In addition, JAK2 tyrosine kinase instead of JAK3 appears to play a major role in IL-4- and IL-13-induced signal transduction in human fibroblasts. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapy, Bethesda, MD 20892 USA. Yokohama City Univ, Sch Med, Dept Internal Med 1, Yokohama, Kanagawa 236, Japan. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapy, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr MSC 4555, Bethesda, MD 20892 USA. NR 32 TC 72 Z9 75 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD AUG PY 1998 VL 10 IS 8 BP 1103 EP 1110 DI 10.1093/intimm/10.8.1103 PG 8 WC Immunology SC Immunology GA 111GY UT WOS:000075430000010 PM 9723696 ER PT J AU Pawlowski, TM Poole, CF AF Pawlowski, TM Poole, CF TI Extraction of thiabendazole and carbendazim from foods using pressurized hot (subcritical) water for extraction a feasibility study SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE thiabendazole; carbendazim; benomyl; subcritical; water; extraction; ion-pairing HPLC ID SUPERCRITICAL-FLUID EXTRACTION; BENZIMIDAZOLE FUNGICIDES; ENVIRONMENTAL SOLIDS; PESTICIDE-RESIDUES; CHROMATOGRAPHY; FRUITS AB Pressurized hot water was used to extract two fungicides, thiabendazole (TBZ) and carbendazim (MBC), from agricultural commodities including banana pulp, whole lemons, orange pulp, mushrooms, and rice at extraction temperatures below 100 degrees C and an extraction pressure of 50 atm. The extraction parameters that were studied include temperature, equilibration time, flow rate, pH, and collection volume. Liquid-liquid partitioning using ethyl acetate was then used to partition MBC and TBZ from the aqueous extractant and concentrate the analytes for final analysis and the determination of recovery. Residues of TBZ were also determined in incurred matrixes which had already been analyzed by another laboratory using validated methodology. Reversed-phase ion-pairing HPLC with UV absorbance and fluorescence detection was used to determine the recoveries of TBZ and MBC from fortified homogenates. Using an extraction temperature of 75 OC, the average recoveries of MBC and TBZ ranged 80.9-100.5% at fortification levels ranging from 0.14 ppm in fresh mushrooms to 10 ppm in whole lemon homogenates. The relative standard deviations were 10% or less. C1 Wayne State Univ, Dept Chem, Detroit, MI 48202 USA. US FDA, Total Diet Pesticide Res Ctr, Detroit, MI 48207 USA. RP Poole, CF (reprint author), Wayne State Univ, Dept Chem, 5101 Cass Ave, Detroit, MI 48202 USA. EM CFP@chem.wayne.edu NR 25 TC 37 Z9 38 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 AUG PY 1998 VL 46 IS 8 BP 3124 EP 3132 DI 10.1021/jf980016x PG 9 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 112DD UT WOS:000075478100036 ER PT J AU Allen, LB Siitonen, PH Thompson, HC AF Allen, LB Siitonen, PH Thompson, HC TI Impact of membrane desolvation on the effects of sodium on response in inductively coupled plasma atomic emission spectrometry with ultrasonic sample introduction SO JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY LA English DT Article DE inductively coupled plasma atomic emission spectrometry; ultrasonic sample introduction; microporous membrane desolvation; easily ionizable elements ID NEBULIZER; SPECTROSCOPY; EXCITATION; WATER AB This report compares the influence of sodium on response with ICP-AES for copper, cadmium, lead and cobalt with ultrasonic sample introduction in the presence and absence of a microporous membrane desolvation (MMD). Comparisons are reported at viewing positions of 8, 14, and 20 mm above the load coil, for injector gas flow rates of 0, 70, 0.85 and 1.00 l min(-1), and at sodium concentrations ranging from 0.00 to 0.08 M Na. Blank emission intensities were depressed in the presence of sodium regardless of the operating condition(s), Depressions in the blank emission intensities were greater without the MMD, but were less than 20%, The magnitude of depression in the blank emission intensities did not vary significantly among the analyte lines or with the viewing position, The impact of sodium on signal intensities with and without the MMD was greater than the impact on the blank emission intensities, with changes approaching 150%, At the lower viewing positions, signal enhancement in the presence of sodium was common and the degree of enhancement was greater with the MMD, Response changes with respect to sodium concentration were also different with and without the MMD low in the plasma. Higher in the plasma, element-to-element variation occurred in the nature of the impact of sodium, For signals that were enhanced, the degree of enhancement was generally greater with the MMD, but when signals were depressed, there was no correlation to the presence or absence of the MMD. In contrast to the lower viewing position, higher in the plasma response changes with respect to the sodium concentration were similar. These results suggest that although the plasma is physically different with and without the MMD, the MMD does not alter the mechanism(s) by which sodium impacts response. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Allen, LB (reprint author), Univ Wisconsin Parkside, 900 Wood Rd, Kenosha, WI 53141 USA. NR 18 TC 9 Z9 9 U1 0 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON ROAD, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 0267-9477 J9 J ANAL ATOM SPECTROM JI J. Anal. At. Spectrom. PD AUG PY 1998 VL 13 IS 8 BP 735 EP 741 DI 10.1039/a800837j PG 7 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 110MV UT WOS:000075385700008 ER PT J AU Feng, P Sandlin, RC Park, CH Wilson, RA Nishibuchi, M AF Feng, P Sandlin, RC Park, CH Wilson, RA Nishibuchi, M TI Identification of a rough strain of Escherichia coli O157 : H7 that produces no detectable O157 antigen SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SEROTYPE O157-H7; MULTIPLEX PCR; VARIANTS AB MA6, an O157:H7-like strain, did not react with most anti-O157 kits examined; however, it had the rfbE gene that is essential for O157 expression and carried O157:H7 virulence factors. Lipopolysaccharide analysis showed that MA6 is a rough strain that does not produce the O157 antigen, but genetically, it belongs in the O157:H7 clonal group. C1 US FDA, Div Microbiol Studies, Washington, DC 20204 USA. Uniformed Serv Univ Hlth Sci, Dept Immunol & Microbiol, Bethesda, MD 20814 USA. Fairfax Hosp, INOVA, Falls Church, VA 22042 USA. Penn State Univ, Escherichia Coli Reference Ctr, University Pk, PA 16802 USA. Kyoto Univ, Ctr SE Asian Studies, Kyoto 60601, Japan. RP Feng, P (reprint author), US FDA, Div Microbiol Studies, HFS-516,200 C St SW, Washington, DC 20204 USA. NR 17 TC 20 Z9 22 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD AUG PY 1998 VL 36 IS 8 BP 2339 EP 2341 PG 3 WC Microbiology SC Microbiology GA ZZ359 UT WOS:000074721500035 PM 9666018 ER PT J AU Chakrabarti, K Bandyopadhyay, PK Barkyoumb, JH AF Chakrabarti, K Bandyopadhyay, PK Barkyoumb, JH TI Copper doped alkali halides for computed radiography and digital imaging SO JOURNAL OF DIGITAL IMAGING LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Computer-Applications-in-Radiology CY JUN 04-07, 1998 CL BALTIMORE, MD SP Soc Comp Applicat Radiol (SCAR), Amer Coll Radiol (ACR) ID THERMALLY STIMULATED LUMINESCENCE AB We report here the results of our x-ray fluorescence, photostimulated luminescence, and time resolved laser spectroscopy studies in KCl:Cu. This material seems to possess some desirable properties for being used as an imaging plate in computed radiography. This is a US government work. There are no restrictions on its use. C1 US FDA, Div Mammog Qual & Radiat Programs, Rockville, MD 20902 USA. Hendrix Coll, Conway, AR USA. USN, Ctr Surface Warfare, Carderock Div, Bethesda, MD USA. RP Chakrabarti, K (reprint author), US FDA, Div Mammog Qual & Radiat Programs, 1350 Piccard Dr, Rockville, MD 20902 USA. NR 17 TC 2 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0897-1889 EI 1618-727X J9 J DIGIT IMAGING JI J. Digit. Imaging PD AUG PY 1998 VL 11 IS 3 SU 1 BP 174 EP 177 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 111NH UT WOS:000075443600052 PM 9735463 ER PT J AU Waynant, RW Chakrabarti, K Kaczmerak, R Suleiman, O Rowberg, A AF Waynant, RW Chakrabarti, K Kaczmerak, R Suleiman, O Rowberg, A TI Improved sensitivity and specificity of mammograms by producing uniform luminance from viewboxes SO JOURNAL OF DIGITAL IMAGING LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Computer-Applications-in-Radiology CY JUN 04-07, 1998 CL BALTIMORE, MARYLAND SP Soc Comp Applicat Radiol (SCAR), Amer Coll Radiol (ACR) C1 US FDA, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. RP Waynant, RW (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-134,12725 Twinbrook Pkwy, Rockville, MD 20857 USA. NR 9 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD AUG PY 1998 VL 11 IS 3 SU 1 BP 189 EP 191 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 111NH UT WOS:000075443600057 PM 9735466 ER PT J AU Buchanan, R AF Buchanan, R CA Natl Advisory Comm Microbiological Criteria Foo TI Principles of risk assessment for illness caused by foodborne biological agents SO JOURNAL OF FOOD PROTECTION LA English DT Article AB The Risk Assessment Subcommittee of the National Advisory Committee on Microbiological Criteria in Foods has prepared a generic document on the principles of risk assessment as applied to biological agents that can cause human foodborne disease. Typical biological agents include bacteria, viruses, fungi, helminths, protozoa, algae, parasites, and the toxic products that these agents may produce. Basic principles elaborated to characterize food pathogen risks include the four broadly accepted components of risk assessment. The role of surveillance and investigational activities to link biological agents and their food sources to consumer illness is described as is the role of predictive modeling for food pathogens. C1 US FDA, Ctr Food Safety & Appl Nutr, DHHS, Washington, DC 20204 USA. RP Buchanan, R (reprint author), US FDA, Ctr Food Safety & Appl Nutr, DHHS, 200 C St SW,HFS-500, Washington, DC 20204 USA. NR 2 TC 15 Z9 16 U1 1 U2 3 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD AUG PY 1998 VL 61 IS 8 BP 1071 EP 1074 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 108KX UT WOS:000075266500027 PM 9713775 ER PT J AU Hansal, SA Morris, DI Sechler, JMG Love, PE Rosenberg, AS AF Hansal, SA Morris, DI Sechler, JMG Love, PE Rosenberg, AS TI Cutting edge: Induction of antigen-specific hyporesponsiveness by transplantation of hemopoietic cells containing an MHC class I transgene regulated by a lymphocyte-specific promoter SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GRAFT-REJECTION; VETO CELLS; T-CELLS; TOLERANCE; EXPRESSION; CHIMERISM; MARROW; MICE; SKIN; CD2 AB We explored a novel approach to tolerance induction by the transplantation of bone marrow (BM) cells (BMCs) that themselves do not express a foreign histocompatibility Ag, but which give rise to mature lymphocytes that do so. Lines of transgenic (FVB) mice were generated that contained an MHC class I D-d cDNA regulated by a CD2 promoter. Because the CD2 promoter is lymphocyte-specific and activated relatively late in lymphocyte ontogeny, D-d is expressed on most mature lymphocytes in the periphery but only on developing B cells in the BM of transgenic mice. Transgenic BMCs are tolerogenic and reproducibly engraft in nontransgenic mice using a conditioning regimen that is nonpermissive for the engraftment of conventional (MHC promoter) D-d-transgenic BMCs, Engrafted BMCs generate transgene-expressing lymphocytes and confer a state of Ag-specific hyporesponsiveness on the host that is primarily attributable to a peripheral mechanism. The strategies by which tolerance can be optimized in this system are discussed. C1 US FDA, Ctr Biol Evaluat & Res, Immunol Lab, Div Hematol Prod, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Rosenberg, AS (reprint author), US FDA, Ctr Biol Evaluat & Res, Immunol Lab, Div Hematol Prod, 29A,2B-12,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 25 TC 6 Z9 6 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 AUG 1 PY 1998 VL 161 IS 3 BP 1063 EP 1068 PG 6 WC Immunology SC Immunology GA 102VA UT WOS:000074944900001 PM 9686561 ER PT J AU Alexander, D DePaola, A Chirtel, S Young, RB AF Alexander, D DePaola, A Chirtel, S Young, RB TI Detection of Vibrio cholerae in oyster (Crassostrea virginica) homogenate based on centrifugal removal of antimicrobial agents SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE V cholerae; detection method; oyster; antimicrobial agent ID STATES GULF-COAST; UNITED-STATES; GIGAS; TEMPERATURE; VULNIFICUS; HEMOLYMPH; BAY AB Detection of Vibrio cholerae in oysters requires homogenization, enrichment in alkaline peptone water (APW) and isolation on selective medium. An antimicrobial substance(s) indigenous to oysters apparently inhibits V. cholerae recovery, thus, requiring extensive dilution of the oyster homogenate in APW (1:100, v/v) during enrichment. Centrifugation of oyster homogenates partitions antimicrobial agent(s) into the supernatant fraction. The antimicrobial agent(s) was not removed by filtration (0.2 mu m) of the supernatant, thus eliminating bacterial competition as the source of inhibition. Growth curves conducted in filtered sterilized oyster supernatant-APW (1:10) at 42 degrees C demonstrated logarithmic V. cholerae growth until cell density reached 10(8) ml(-1) (6-12 h) followed by logarithmic death. Antimicrobial agents were inactivated by pretreatment of the supernatant at 80 degrees C, or with pronase, but were stable at 75 degrees C and with trypsin or lipase treatment. While a rapid pH drop was noted prior to cell death, low pH alone was not sufficient for V. cholerae lethality. Vibrio vulnificus was also susceptible to inhibitory agent(s) in oysters, but no inhibition was observed with other Vibrio and non-vibrio species tested. Removal of the supernatant followed by enrichment of the pellet formed the basis of a novel procedure, which was as sensitive as the dilution procedure for V. cholerae detection (<1 cfu g(-1)). Published by Elsevier Science B.V. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Univ Alabama, Dept Biol Sci, Huntsville, AL 35899 USA. US FDA, Div Math, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP DePaola, A (reprint author), US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. NR 27 TC 1 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD AUG PY 1998 VL 33 IS 3 BP 237 EP 244 DI 10.1016/S0167-7012(98)00064-5 PG 8 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 131JX UT WOS:000076573400007 ER PT J AU Carlin, A Gregory, N Simmons, J AF Carlin, A Gregory, N Simmons, J TI Stability of isoniazid in isoniazid syrup: formation of hydrazine SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE isoniazid; hydrazine; capillary gas chromatography; electron capture detection; carcinogens; tuberculosis C1 US FDA, Prod Qual Assurance Lab, Div Prod Qual Res, Ctr Drug Evaluat & Res, Rockville, MD 20850 USA. US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20855 USA. US FDA, Off New Drug Chem, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. RP Carlin, A (reprint author), US FDA, Prod Qual Assurance Lab, Div Prod Qual Res, Ctr Drug Evaluat & Res, 4 Res Court, Rockville, MD 20850 USA. NR 9 TC 21 Z9 21 U1 1 U2 2 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 AUG PY 1998 VL 17 IS 4-5 BP 885 EP 890 DI 10.1016/S0731-7085(98)00002-8 PG 6 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 102LQ UT WOS:000074926200032 PM 9682174 ER PT J AU Bowyer, JF Frame, LT Clausing, P Nagamoto-Combs, K Osterhout, CA Sterling, CR Tank, AW AF Bowyer, JF Frame, LT Clausing, P Nagamoto-Combs, K Osterhout, CA Sterling, CR Tank, AW TI Long-term effects of amphetamine neurotoxicity on tyrosine hydroxylase mRNA and protein in aged rats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID METHAMPHETAMINE NEUROTOXICITY; DOPAMINERGIC-NEURONS; STRIATAL DOPAMINE; SUBSTANTIA-NIGRA; GENE-EXPRESSION; CELL LOSS; BRAIN; DEGENERATION; 6-HYDROXYDOPAMINE; PARKINSONISM AB Four injections (intraperitoneal) of 3 mg/kg amphetamine (2 hr apart) produced pronounced hyperthermia and sustained decreases in dopamine levels and tyrosine hydroxylase (TH) protein levels in the striatum of 15-month-old male rats. A partial recovery of striatal dopamine levels was observed at 4 months after amphetamine. in contrast, TH mRNA and TH protein levels in the midbrain were unaffected at all time points tested up to 4 months after amphetamine treatment. The number of TH-immunopositive cells in the midbrain was also unchanged at 4 months after amphetamine, even though the number of TH-positive axons in the striatum remained dramatically decreased at this time point. Interestingly, TH-immunopositive cell bodies were observed 4 months after amphetamine in the lateral caudate/putamen, defined anteriorly by the genu of the corpus collosum and posteriorly by the junction of the anterior commissures; these striatal TH-positive cells were not observed in saline- or amphetamine-treated rats that did not become hyperthermic. In addition, low levels (orders of magnitude lower than that present in the midbrain) of TH mRNA were detected using reverse transcription-polymerase chain reaction in the striatum of these amphetamine-treated rats. Our results suggest that even though there is a partial recovery of striatal dopamine levels, which occurs within 4 months after amphetamine treatment, this recovery is not associated with increased TH gene expression in the midbrain. Furthermore, new TH-positive cells are generated in the striatum at this 4-month time point. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Arkansas, Med Ctr, Dept Surg, Little Rock, AR 72204 USA. Univ Rochester, Med Ctr, Dept Physiol & Pharmacol, Rochester, NY 14642 USA. Univ Rochester, Med Ctr, Neurosci Program, Rochester, NY 14642 USA. RP Bowyer, JF (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132, Jefferson, AR 72079 USA. FU NIGMS NIH HHS [GM08427]; PHS HHS [5014] NR 37 TC 46 Z9 46 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 AUG PY 1998 VL 286 IS 2 BP 1074 EP 1085 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 110BP UT WOS:000075359600065 PM 9694971 ER PT J AU Daley, WR Kaczmarek, RG AF Daley, WR Kaczmarek, RG TI The epidemiology of cardiac pacemakers in the older US population SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID UNITED-STATES AB OBJECTIVES: This study estimates the age distribution of older patients (>64 years) receiving implantable cardiac pacemakers in non-federal US hospitals and determines major characteristics of this group using a massive, nationally representative sample of inpatient discharge records. DESIGN: Discharge records were obtained from the 1992 Nationwide Inpatient Sample. Correlation with census data from 1992 was used to determine age and gender specific rates. SETTING: The Nationwide Inpatient Sample is a 20% stratified probability sample of non-federal US hospitals. PATIENTS: Records of all recipients (26,425) of an initial or replacement pacemaker were selected. RESULTS: Individuals 65 years of age and older received an estimated 131,361 initial and replacement pacemaker pulse generators (87% of the total) in non-federal US hospitals in 1992. Pacemaker implantation was performed in urban teaching hospitals (28.9%), non-teaching urban hospitals (57.8%), and rural hospitals (13.3%). The age specific implantation rates per 100,000 population were 226.5 (age 65-74 years), 585.9 (age 75-84 years), 874.9 (age 85-94 years), and 540.4 (more than 94 years). The age-adjusted rate for men was 70% greater than the corresponding rate for women. Major diagnoses of implant recipients included atrioventricular block (37.8%) and atrial fibrillation (28.5%). Two percent of pacemaker recipients died before discharge. CONCLUSIONS: The rate of pacemaker implantation increases sharply up to age 95. As the number of older people in the US population grows, particularly those in the age ranges greater than 75 and 85 years, a sharply increased number of pacemakers will be implanted unless other factors decrease the need for these devices. The data also demonstrate diffusion of this technology from academic centers. C1 US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20857 USA. RP Daley, WR (reprint author), Ctr Dis Control & Prevent, CDC, Natl Ctr Environm Hlth, EHHE,HSB, Mailstop F-46,4770 Buford Highway NE, Atlanta, GA 30341 USA. NR 15 TC 16 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 1998 VL 46 IS 8 BP 1016 EP 1019 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 107WB UT WOS:000075233000015 PM 9706894 ER PT J AU Chamberlain, PL Brynes, SD AF Chamberlain, PL Brynes, SD TI The regulatory status of xylazine for use in food-producing animals in the United States SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID CHEMICALS; 2,6-XYLIDINE; TOXICITY; INVIVO; CELLS; TESTS; ASSAY; RAT AB Xylazine is commonly used in veterinary medicine as a tranquillizer or adjunct to surgical anaesthesia. Although its use is approved in companion animals and certain species of deer, xylazine remains unapproved for use in food-producing animals in the United States. This paper reviews existing toxicological and residue chemistry information on xylazine in food animals, particularly cattle, and discusses the regulatory status of the drug in the US, as well as the conclusions reached by the Joint FAO/WHO Expert Committee on Food Additives in its recent evaluation of xylazine. C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Chamberlain, PL (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl, Rockville, MD 20855 USA. NR 38 TC 9 Z9 9 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD AUG PY 1998 VL 21 IS 4 BP 322 EP 329 PG 8 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 108PA UT WOS:000075273600011 PM 9731956 ER PT J AU Feigelstock, D Thompson, P Mattoo, P Zhang, YA Kaplan, GG AF Feigelstock, D Thompson, P Mattoo, P Zhang, YA Kaplan, GG TI The human homolog of HAVcr-1 codes for a hepatitis A virus cellular receptor SO JOURNAL OF VIROLOGY LA English DT Article ID A VIRUS; PATHOGENESIS; POLIOVIRUS; INFECTION; CELLS AB The hepatitis A virus cellular receptor 1 (HAVcr-1) cDNA was isolated from a cDNA expression library of African green monkey kidney (AGMK) cells by using protective monoclonal antibody (MAb) 190/4, which blocks the binding of hepatitis A virus (HAV) to AGMK cells. The HAVcr-1 cDNA codes for havcr-1, a 451-amino-acid class I integral-membrane mucin-like glycoprotein of unknown natural function. To determine the existence of a human homolog(s) of HAVcr-1 (huHAVcr-1), we used HAVcr-1-specific primers to amplify cDNAs from human liver and kidney mRNA by reverse transcription-PCR Nucleotide sequence analysis revealed that the amplified liver and kidney huHAVcr-1 cDNAs were identical and that they coded for a 359-amino-acid glycoprotein, termed huhavcr-1, which was approximately 79% identical to havcr-1. The six Cys residues of the extracellular domain of havcr-1 and its first N-glycosylation site were conserved in huhavcr-1. However, the number of hexameric repeats of the mucin-like region was reduced from 27 in havcr-1 to 13 in huhavcr-1. In addition, 12 C-terminaI amino acids in the cytoplasmic domain of huhavcr-1 were deleted. Northern blot analysis of poIy(A) RNA showed that huhavcr-1 is expressed in every organ analyzed, including the liver, small intestine, colon, and spleen, and that it is expressed at higher levels in the kidney and testis. Although dog cells transfected with the huHAVcr-1 cDNA did not express the protective 190/4 epitope, they bound hepatitis A virus (HAV) and gained limited susceptibility to HAV infection. Treatment with MAb 190/4 did not protect AGMK cell transfectants expressing huhavcr-1 against HAV, suggesting that HAV infected these cells via the huhavcr-l receptor and not the endogenously expressed havcr-1, which was blocked by MAI, 190/4. Our data demonstrate that huhavcr-l is a binding receptor for HAV and suggest that it is also a functional receptor for HAV. C1 NIH, Div Viral Prod, CBER, US FDA,Lab Hepatitis Virus, Bethesda, MD 20892 USA. RP Kaplan, GG (reprint author), NIH, Div Viral Prod, CBER, US FDA,Lab Hepatitis Virus, 880 Rockville Pike,Bldg 29A,Rm 1D10,HFM-448, Bethesda, MD 20892 USA. NR 20 TC 138 Z9 154 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1998 VL 72 IS 8 BP 6621 EP 6628 PG 8 WC Virology SC Virology GA ZZ446 UT WOS:000074730200044 PM 9658108 ER PT J AU Yurawecz, MP Roach, JAG Sehat, N Mossoba, MM Kramer, JKG Fritsche, J Steinhart, H Ku, Y AF Yurawecz, MP Roach, JAG Sehat, N Mossoba, MM Kramer, JKG Fritsche, J Steinhart, H Ku, Y TI A new conjugated linoleic acid isomer, 7 trans, 9 cis-octadecadienoic acid, in cow milk, cheese, beef and human milk and adipose tissue SO LIPIDS LA English DT Article ID FATTY-ACIDS; DAIRY-PRODUCTS; BOVINE-MILK; IDENTIFICATION; DERIVATIVES; METHYLATION AB The identity of a previously unrecognized conjugated linoleic acid (CLA) isomer, 7 trans, 9 cis-octadecadienoic acid (18:2) was confirmed in milk, cheese, beef, human milk, and human adipose tissue. The 7 trans, 9 cis-18:2 isomer was resolved chromatographically as the methyl ester by silver ion-high-performance liquid chromatography (Ag+-HPLC); it eluted after the major 9 cis, ii trans-1 8:2 isomer (rumenic acid) in the natural products analyzed. In the biological matrices investigated by Ag+-HPLC, the 7 trans, 9 cis-18:2 peak was generally clue to the most abundant minor CLA isomer, ranging in concentration from 3 to 16% of total CLA. By gas chromatography (GC) with long polar capillary columns, the methyl ester of 7 trans, 9 cis-18:2 was shown to elute near the leading edge of the major 9 cis, ii trans-18:2 peak, while the 4,4-dimethyloxazo line (DMOX) derivative permitted partial resolution of these two CLA isomers. The DMOX derivative of this new CLA isomer was analyzed by gas chromatography-electron ionization mass spectrometry (GC-EIMS). The double bond positions were at Delta 7 and Delta 9 as indicated by the characteristic mass spectral fragment ions at m/z 168, 180, 194, and 206, and their allylic cleavages at m/z 154 and 234. The cis/trans double-bond configuration was established by CC-direct deposition-fourier transform infrared as evidenced from the doublet at 988 and 949 cm(-1) and absorptions at 3020 and 3002 cm(-1). The 7 trans, 9 cis-18:2 configuration was established by GC-EIMS for the DMOX derivative of the natural products examined, and by comparison to a similar product obtained from treatment of a mixture of methyl 8-hydroxy- and 11-hydroxyoctadec-9 cis enoates with BF3 in methanol. C1 US FDA, Off Food Labeling, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Agr & Agri Food Canada, Food Res Ctr, So Crop Protect, Guelph, ON N1G 2W1, Canada. Univ Hamburg, Inst Food Chem, Hamburg, Germany. RP Yurawecz, MP (reprint author), US FDA, Off Food Labeling, Ctr Food Safety & Appl Nutr, HFS-175,200 C St SW, Washington, DC 20204 USA. EM mpy@cfsan.fda.gov NR 34 TC 109 Z9 112 U1 0 U2 8 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PD AUG PY 1998 VL 33 IS 8 BP 803 EP 809 DI 10.1007/s11745-998-0273-z PG 7 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 110VC UT WOS:000075400900009 PM 9727611 ER PT J AU Zheng, Q AF Zheng, Q TI Computer algebra is indispensable in some problems of mathematical biology SO MATHEMATICAL BIOSCIENCES LA English DT Letter ID IDENTIFIABILITY C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Zheng, Q (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, HFT-20,3900 NCTR Dr, Jefferson, AR 72079 USA. EM qzheng@nctr.fda.gov NR 7 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0025-5564 J9 MATH BIOSCI JI Math. Biosci. PD AUG 1 PY 1998 VL 151 IS 2 BP 219 EP 225 DI 10.1016/S0025-5564(98)10015-9 PG 7 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 107MZ UT WOS:000075214200007 PM 9711051 ER PT J AU Wojnowski, L Stancato, LF Zimmer, AM Hahn, H Beck, TW Larner, AC Rapp, UR Zimmer, A AF Wojnowski, L Stancato, LF Zimmer, AM Hahn, H Beck, TW Larner, AC Rapp, UR Zimmer, A TI Craf-1 protein kinase is essential for mouse development SO MECHANISMS OF DEVELOPMENT LA English DT Article DE Craf-1 protein kinase; development; cell mutation; mouse embryo ID B-RAF; EGF RECEPTOR; A-RAF; DIFFERENTIAL REGULATION; TARGETED DISRUPTION; MICE LACKING; DEFECTS; CELLS; GENE; PATHWAY AB The three mammalian Raf serine/threonine protein kinases mediate the transduction of proliferative and differentiative signals from a variety of cell surface receptors to the nucleus. We report here that Craf-1 is essential for mouse development, as its mutation results in embryonic lethality. Developmental defects are: found in mutant placentas as well as in the skin and in the lungs of mutant embryos. Craf-1 mutants also display a generalized growth retardation which is consistent with the ubiquitous expression of Craf-1 and which could be due to the reduced proliferation of mutant cells. Interestingly, the time-point of embryonal death varies depending on the genetic background. This suggests that Craf-1-mediated signaling is affected by genetic background-specific alleles of other genes. (C) 1998 Elsevier Science Inland Ltd. All rights reserved. C1 NIMH, Genet Sect, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD USA. Univ Wurzburg, Inst Med Strahlenkunde & Zellforsch, Wurzburg, Germany. RP Zimmer, A (reprint author), NIMH, Genet Sect, 36 Convent Dr 3D06, Bethesda, MD 20892 USA. RI Zimmer, Andreas/B-8357-2009 NR 30 TC 84 Z9 84 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD AUG PY 1998 VL 76 IS 1-2 BP 141 EP 149 DI 10.1016/S0925-4773(98)00111-7 PG 9 WC Developmental Biology SC Developmental Biology GA 129FW UT WOS:000076454000012 PM 9767153 ER PT J AU Wang, RF Pothuluri, JV Steele, RS Paine, DD Assaf, NA Cerniglia, CE AF Wang, RF Pothuluri, JV Steele, RS Paine, DD Assaf, NA Cerniglia, CE TI Molecular identification of a Stenotrophomonas species used in the bioassay for erythromycin in aquaculture samples SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE erythromycin detection; Xanthomonas; Stenotrophomonas; 16S rRNA gene sequencing ID MALTOPHILIA; SEQUENCE; GENE AB A bacterial strain isolated from aquaculture pond slurry, which was extremely sensitive to erythromycin, was used to detect erythromycin at levels as low as 0.05 mu g ml(-1) in aquaculture water, sediments and soil samples. Identification of the indicator organism was attempted by 16S rRNA sequencing, biochemical profile, fatty-acid analysis and polymerase chain reaction (PCR). GenBank comparison showed that the 16S rRNA sequence of the strain was similar to those of more than 20 species of Xanthomonas and Stenotrophomonas. The position of the strain in a phylogenetic tree based on the 16S rRNA gene sequence comparison is in a cluster of Stenotrophomonas. The fatty-acid analysis also showed that the strain is similar to Stenotrophomonas maltophilia. However, the biochemical profile of the strain is most similar to Xanthomonas campestris, except that it can utilize maltose, which is similar to S. maltophilia. Polymerase chain reaction results showed that the strain is different from X. campestris, S. maltophilia and other Xanthomonas species tested. Based on these results, the authors named this strain as Stenotrophomonas sp, strain NCTR. (C) 1998 Academic Press. C1 US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Wang, RF (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 9 TC 4 Z9 4 U1 0 U2 1 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 AUG PY 1998 VL 12 IS 4 BP 249 EP 254 DI 10.1006/mcpr.1998.0178 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 111EX UT WOS:000075425300011 PM 9727203 ER PT J AU Pan, Q Huang, P Mills, FC Hammarstrom, L AF Pan, Q Huang, P Mills, FC Hammarstrom, L TI Role of the 3' immunoglobulin gene enhancer in immunodeficiency patients SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract C1 Huddinge Hosp, Karolinska Inst, IMPI, Div Clin Immunol, S-14186 Huddinge, Sweden. US FDA, Div Hematol Prod, Bethesda, MD 20892 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 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD AUG PY 1998 VL 35 IS 11-12 BP 722 EP 722 DI 10.1016/S0161-5890(98)90386-8 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 131BA UT WOS:000076554800054 ER PT J AU Hunyady, L Ji, H Jagadeesh, G Zhang, M Gaborik, Z Mihalik, B Catt, KJ AF Hunyady, L Ji, H Jagadeesh, G Zhang, M Gaborik, Z Mihalik, B Catt, KJ TI Dependence of AT(1) angiotensin receptor function on adjacent asparagine residues in the seventh transmembrane helix SO MOLECULAR PHARMACOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; ADRENAL GLOMERULOSA CELLS; II RECEPTOR; SIGNAL-TRANSDUCTION; PROJECTION STRUCTURE; BINDING-SITE; NONPEPTIDE; AGONIST; ANTAGONISTS; ACTIVATION AB For several G protein-coupled receptors, amino acids in the seventh transmembrane helix have been implicated in ligand binding and receptor activation. The function of this region in the AT(1) angiotensin receptor was further investigated by mutation of two conserved polar residues (Asn294 and Asn295) and the adjacent Phe293 residue. Analysis of the properties of the mutant receptors expressed in COS-7 cells revealed that alanine replacement of Phe293 had no major effect on AT(1) receptor function. Substitution of the adjacent Asn294 residue with alanine (N294A) reduced receptor binding affinities for angiotensin II, two nonpeptide agonists (L-162,313 and L-163,491), and the AT(1)-selective nonpeptide antagonist losartan but not that for the peptide antagonist [Sar(1),Ile(8)]angiotensin II. The N294A receptor also showed impaired G protein coupling and severely attenuated inositol phosphate generation. In contrast, alanine replacement of Asn295 decreased receptor binding affinities for all angiotensin II ligands but did not impair signal transduction. Additional substitutions of Asn295 with a variety of amino acids did not identify specific structural elements for ligand binding. These findings indicate that Asn295 is required for the integrity of the intramembrane binding pocket of the AT(1a) receptor but is not essential for signal generation. They also demonstrate the importance of transmembrane helices in the formation of the binding site for nonpeptide AT(1) receptor agonists. We conclude that the Asn294 residue of the AT(1) receptor is an essential determinant of receptor activation and that the adjacent Asn295 residue is required for normal ligand binding. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Semmelweis Univ Med, Dept Physiol, H-1088 Budapest, Hungary. US FDA, Div Cardiorenal Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Catt, KJ (reprint author), NICHHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Room 6A-36, Bethesda, MD 20892 USA. EM catt@helix.nih.gov RI Jagadeesh, Gowraganahalli/G-6408-2010 NR 41 TC 44 Z9 44 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD AUG PY 1998 VL 54 IS 2 BP 427 EP 434 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 108CW UT WOS:000075249300023 PM 9687585 ER PT J AU Berlin, CM McCarver, DG Notterman, DA Ward, RM Weismann, DN Wilson, GS Wilson, JT AF Berlin, CM McCarver, DG Notterman, DA Ward, RM Weismann, DN Wilson, GS Wilson, JT CA Comm Drugs TI Prevention of medication errors in the pediatric inpatient setting SO PEDIATRICS LA English DT Article ID ADVERSE DRUG EVENTS AB Medication errors that occur on a pediatric medical/surgical inpatient care unit are usually avoidable. Several steps are recommended to reduce these errors, beginning with the physician and including every member of the health care team. Pediatricians should help hospitals develop effective programs for safely providing treatment with medications to hospitalized children. C1 Amer Coll Obstetricians & Gynecologists, Washington, DC USA. Pharmaceut Res & Manufacturers Assoc Amer, Washington, DC USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Canadian Paediat Soc, Ottawa, ON, Canada. US FDA, Rockville, MD 20857 USA. Amer Acad Child & Adolescent Psychiat, Washington, DC USA. NIH, Bethesda, MD USA. Amer Acad Family Phys, Kansas City, MO USA. Natl Assoc Childrens Hosp & Related Inst, Alexandria, VA USA. Joint Commis Accreditat Healthcare Org, Chicago, IL USA. NR 11 TC 31 Z9 34 U1 1 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD AUG PY 1998 VL 102 IS 2 BP 428 EP 430 PG 3 WC Pediatrics SC Pediatrics GA 106JH UT WOS:000075125800026 ER PT J AU Endrenyi, L Csizmadia, F Tothfalusi, L Chen, ML AF Endrenyi, L Csizmadia, F Tothfalusi, L Chen, ML TI Metrics comparing simulated early concentration profiles for the determination of bioequivalence SO PHARMACEUTICAL RESEARCH LA English DT Article DE bioequivalence; intercept metric; early exposure; absorption rate; partial AUC; experimental design ID ABSORPTION RATE; EQUIVALENCE AB Purpose. To compare the effectiveness of various metrics which evaluate bioequivalence in the early phase of concentration-time profiles. Methods. Two-period crossover trials were simulated with increasing assumed ratios of the true absorption rate constants of the two formulations, and with various kinetic models. Kinetic sensitivities (KS) and standard errors (SE) of the various metrics were recorded and the percentage of trials accepting bioequivalence (the statistical power) was evaluated. The principal metrics included the partial AUC (AUC(p)), the intercept obtained by linear extrapolation of the ratios of the lower over higher concentrations (C) measured for the two formulations (I-L/H), and the ratios of intercepts extrapolated from logarithmic CI time values of the two products (M-log). For comparison, also properties of C-max and an ideally evaluated measure (Id) were determined. Results. M-log, showed generally the highest statistical power and KS, and also the largest SE, closely followed by I-L/H Partial AUC exhibited lower power and KS, but also smaller SE than the intercept procedures. The three methods had much higher power, KS and SE than C-max. These comparisons were maintained over various kinetic conditions and experimental designs. The effective evaluation of bioequivalence in the early phase of studies is assured with 3 (or more) measurements until the population average peak of the reference formulation. Conclusions. The three principal methods assess bioequivalence very effectively in the early phase of a concentration-time profile. M-log had the highest statistical power, closely followed by I-L/H and then by partial AUC. C1 Univ Toronto, Dept Pharmacol, Toronto, ON M5S 1A8, Canada. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Endrenyi, L (reprint author), Univ Toronto, Dept Pharmacol, Med Sci Bldg, Toronto, ON M5S 1A8, Canada. RI Tothfalusi, Laszlo/J-9301-2012 NR 13 TC 18 Z9 18 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD AUG PY 1998 VL 15 IS 8 BP 1292 EP 1299 DI 10.1023/A:1011912512966 PG 8 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 106KW UT WOS:000075129300024 PM 9706064 ER PT J AU Berglund, BA Boring, DL Wilken, GH Makriyannis, A Howlett, AC AF Berglund, BA Boring, DL Wilken, GH Makriyannis, A Howlett, AC TI Structural requirements for arachidonylethanolamide interaction with CB1 and CB2 cannabinoid receptors: pharmacology of the carbonyl and ethanolamide groups SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID ANANDAMIDE ANALOGS; PHENOLIC HYDROXYL; BINDING; MEMBRANES AB Analogs of arachidonylethanolamide (anandamide) were prepared to investigate the structural requirements for ligand binding to and activation of the CB1 and CB2 cannabinoid receptors. The importance of the presence and the placement of the carbonyl was examined with analogs lacking the carbonyl or with the carbonyl amide order reversed. The presence and location of the carbonyl is essential for high-affinity binding to both cannabinoid receptor subtypes, and for determination of signal transduction via G-proteins. Methyl groups were substituted on the 1'- and 2'-positions of arachidonylethanolamide and the significance of chirality was examined. Stereochemical differences in the ethanolamide group influence the affinity for both cannabinoid receptor subtypes and the signal transduction capabilities of the methanandamide derivatives. C1 St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63104 USA. US FDA, Ctr Drug Evaluat & Res, Div New Drug Synth, Rockville, MD 20857 USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20962 USA. Univ Connecticut, Sch Pharm, Storrs, CT 06269 USA. Univ Connecticut, Inst Sci Mat, Storrs, CT 06269 USA. RP Howlett, AC (reprint author), St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, 1402 S Grand, St Louis, MO 63104 USA. OI Howlett, Allyn/0000-0002-2810-0164 FU NIDA NIH HHS [R01-DA06312, R01-DA07215]; PHS HHS [K05-00182] NR 19 TC 19 Z9 19 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD AUG PY 1998 VL 59 IS 2 BP 111 EP 118 DI 10.1016/S0952-3278(98)90089-8 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 120YL UT WOS:000075985400005 PM 9774174 ER PT J AU Herman, EH Ferrans, V AF Herman, EH Ferrans, V TI Preclinical animal models of cardiac protection from anthracycline-induced cardiotoxicity SO SEMINARS IN ONCOLOGY LA English DT Review ID CHRONIC DOXORUBICIN CARDIOTOXICITY; SPONTANEOUSLY HYPERTENSIVE RATS; AGENT ICRF-187 (+)-1,2-BIS(3,5-DIOXOPIPERAZINYL-1-YL)PROPANE; CHRONIC DAUNORUBICIN CARDIOTOXICITY; CONGESTIVE HEART-FAILURE; VITAMIN-E; INDUCED CARDIOMYOPATHY; (+/-)-1,2-BIS(3,5-DIOXOPIPERAZINYL-1-YL)PROPANE ICRF-187; ADRIAMYCIN CARDIOTOXICITY; RENAL TOXICITY C1 US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res HFD 910, Laurel, MD 20708 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Herman, EH (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res HFD 910, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 49 TC 62 Z9 62 U1 0 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 1998 VL 25 IS 4 SU 10 BP 15 EP 21 PG 7 WC Oncology SC Oncology GA 124WT UT WOS:000076206300004 PM 9768819 ER PT J AU Cowan, EP Tabor, E Nemo, G Williams, A Lal, RB Busch, MP AF Cowan, EP Tabor, E Nemo, G Williams, A Lal, RB Busch, MP TI Studies to address reports of human T-lymphotropic virus type I tax sequences in US blood donors SO TRANSFUSION LA English DT Letter C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NHLBI, Transfus Med Branch, Bethesda, MD 20892 USA. Amer Red Cross, Holland Lab, REDS Study Chesapeake Reg, Rockville, MD USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Irwin Mem Blood Ctr, REDS, San Francisco, CA USA. RP Cowan, EP (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 5 TC 1 Z9 1 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 AUG PY 1998 VL 38 IS 8 BP 800 EP 801 DI 10.1046/j.1537-2995.1998.38898375523.x PG 2 WC Hematology SC Hematology GA 109GE UT WOS:000075312600018 PM 9709792 ER PT J AU Binienda, Z Simmons, C Hussain, S Slikker, W Ali, SF AF Binienda, Z Simmons, C Hussain, S Slikker, W Ali, SF TI Effect of acute exposure to 3-nitropropionic acid on activities of endogenous antioxidants in the rat brain SO NEUROSCIENCE LETTERS LA English DT Article DE 3-nitropropionic acid; superoxide dismutase; glutathione peroxidase; catalase; reduced glutathione; oxidative stress ID DISMUTASE TRANSGENIC MICE; SUPEROXIDE-DISMUTASE; SUCCINATE-DEHYDROGENASE; INHIBITION; LESIONS; NEUROTOXICITY; DAMAGE AB The response of endogenous antioxidants to acute exposure of the mitochondrial inhibitor, 3-nitropropionic acid (3-NPA), was investigated in selected rat brain regions. Rats treated with 3-NPA (30 mg/kg, s.c.) were sacrificed at 30, 60, 90 and 120 min after injection to examine the alterations in reduced glutathione levels (GSH), and activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in the hippocampus (HIP), frontal cortex (FC), and caudate nucleus (CN). CAT activity increased in the HIP 90 min after 3-NPA treatment. While cytosolic copper/zinc SOD (CuZn-SOD) and mitochondrial manganese SOD (Mn-SOD) levels increased in the FC at 120 min, only the Mn-SOD increased in the CN 90 min after treatment. The activity of GPx decreased in the HIP 120 min after 3-NPA injection. When compared with the control, administration of 3-NPA led to GSH depletion in HIP within 120 min. The depletion of GSH and induction of antioxidant enzyme activities after the 3-NPA exposure suggest conditions favorable for oxidative stress. 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. EM zbinienda@nctr.fda.gov NR 22 TC 58 Z9 59 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUL 31 PY 1998 VL 251 IS 3 BP 173 EP 176 DI 10.1016/S0304-3940(98)00539-4 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 111QB UT WOS:000075448200008 PM 9726371 ER PT J AU Stancato, LF Yu, CR Petricoin, EF Larner, AC AF Stancato, LF Yu, CR Petricoin, EF Larner, AC TI Activation of Raf-1 by interferon gamma and oncostatin M requires expression of the Stat1 transcription factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE PHOSPHORYLATION; ALPHA-INTERFERON; GENE-EXPRESSION; ACTIVE STAT1; RECEPTOR; PROTEIN; PATHWAY AB A primary signaling cascade responsible for the ex pression of cytokine-stimulated immediate early genes involves the activation of the Jak/Stat pathway. In addition to being tyrosine-phosphorylated, several signal transducers and activators of transcription (Stats), including Stat1 alpha, Stat3, and Stat4, are phosphorylated on a conserved serine residue, which is a consensus phosphorylation site for mitogen-activated protein kinases (MAPKs), Serine phosphorylation of Stat1 alpha is required for maximal transcriptional activation of early response genes by interferon gamma (IFN gamma) as well as the antiviral and antigrowth actions of this cytokine. Incubation of cells with either IFN gamma or oncostatin M (OSM) activates Raf-1, a serine/threonine kinase responsible for the ultimate activation of p42 MAPK. To examine whether any of the signaling components that are required for activation of the Jak/Stat pathway are also necessary for activation of Raf-1 by IFNs and OSM, we examined activation of Raf-1 in cell lines that are deficient in either Stat1 alpha or Stat2. Unexpectedly, incubation of Stat1-deficient, but not Stat2-deficient cells with IFN gamma or OSM for 5 min displayed no increase in Raf-1 activity. In peripheral blood lymphocytes Raf-1 was associated with Stat1, and this interaction was disrupted after incubation of cells with IFN gamma, Stat1-negative cells reconstituted with either Stat1 alpha or Stat1 alpha with a point mutation in the site where it is serine-phosphorylated displayed normal activation of Raf-1 by IFN gamma and OSM, However, activation of Raf-1 was not observed in lines that expressed Stat1 alpha containing a mutation in its tyrosine phosphorylation site or in its SH2 domain. These results provide the first example of a novel role of Stat1 alpha not as a transcription factor, but as a protein which may function to scaffold signaling components required for activation of the distinct Raf/MEK/MAPK signaling cascade. C1 NCI, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Lab, NIH, Frederick, MD 21701 USA. Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. RP Larner, AC (reprint author), Cleveland Clin Fdn, Dept Immunol, 9500 Euclid Ave, Cleveland, OH 44195 USA. FU NCI NIH HHS [CA77366] NR 20 TC 31 Z9 32 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 24 PY 1998 VL 273 IS 30 BP 18701 EP 18704 DI 10.1074/jbc.273.30.18701 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 103TV UT WOS:000074974700007 PM 9668040 ER PT J AU Khan, AS Maudru, T Thompson, A Muller, J Sears, JF Peden, KWC AF Khan, AS Maudru, T Thompson, A Muller, J Sears, JF Peden, KWC TI The reverse transcriptase activity in cell-free medium of chicken embryo fibroblast cultures is not associated with a replication-competent retrovirus SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article DE live, attenuated virus vaccines; chicken embryo cell cultures; specific-pathogen-free eggs; replication-competent retroviruses; reverse transcriptase activity ID DEPENDENT DNA POLYMERASE; VIRUS TYPE-1; ASSAY; VIRIONS; RNA; VACCINES; RECEPTOR; SIGNALS; PRIMATE; EAV-0 AB Background: Reverse transcriptase (RT) activity has previously been reported in concentrated medium of primary chicken embryo cell cultures using the traditional RT assay. Recently, using the newly-developed and highly-sensitive product-enhanced reverse transcriptase (PERT) assay, RT activity has been detected in live, attenuated vaccines grown in chicken cell substrates. Furthermore, this activity has been associated with particles that contain RNA related to an ancient, endogenous avian retrovirus family designated as EAV-0. Objective: To investigate whether the RT activity present in vaccines produced in specific pathogen-free chicken cell substrates is associated with an infectious retrovirus that can replicate in human cells. Study design: The kinetics of RT activity produced by 10-day-old chicken embyro fibroblast (CEF) cultures was determined by analyzing cell-free medium in a PCR-based RT (PBRT) assay. Material containing the peak PERT activity was used as the inoculum to infect various human cell lines and peripheral blood mononuclear cells. Filtered supernatants from control and test cultures were analyzed for the presence of replication-competent retroviruses by the PERT assay. The cells were monitored for other adventitious agents by routine observation for cytopathic effect (CPE) and by transmission electron microscopy (TEM) at culture termination. Results: The PERT activity did not increase above the background level in the human target cells through at least five cell passages, thus indicating the absence of a replicating retrovirus. No other adventitious agents were detected based upon TEM analysis and the absence of CPE. Conclusion: The RT activity produced by chicken primary cell cultures is not associated with a retrovirus that can replicate in human cells. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 US FDA, Lab Retrovirus Res, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Lab Vector Borne Viral Dis, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Amer Type Culture Collect, Rockville, MD 20852 USA. RP Khan, AS (reprint author), US FDA, Lab Retrovirus Res, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM khan@al.cber.fda.gov NR 40 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD JUL 24 PY 1998 VL 11 IS 1 BP 7 EP 18 DI 10.1016/S0928-0197(98)00042-7 PG 12 WC Virology SC Virology GA 142AD UT WOS:000077177000002 PM 9784139 ER PT J AU Maudru, T Peden, KWC AF Maudru, T Peden, KWC CA Cooperating Units TI Analysis of a coded panel of licensed vaccines by polymerase chain reaction-based reverse transcriptase assays: A collaborative study SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article DE coded panel; licensed vaccines; polymerase chain reaction-based reverse transcriptase assays; reverse transcriptase ID HUMAN-IMMUNODEFICIENCY-VIRUS; SIGNALS; RNA AB Background: A recent publication reporting the presence of low levels of reverse transcriptase (RT) activity in certain vaccines for human use necessitated that regulatory agencies address the issue of whether this RT activity presented a risk to humans. Detection of low levels of RT activity corresponding to fewer than ten virions became possible with the development of highly-sensitive polymerase chain reaction (PCR)-based RT (PBRT) assays. Variations of the PERT assay were developed in three laboratories. These assays were reported as being at least one million-fold more sensitive than conventional RT assays. Objective: To ascertain the sensitivity and reliability of PERT assays in different laboratories and to determine which vaccine samples possessed RT activity. Study design: Coded panels of licensed vaccines together with positive and negative controls was assembled at the Center for Biologics Evaluation and Research (CBER) of the Food and Drug Administration (FDA) and distributed to five cooperating laboratories as well as to our laboratory at CBER. Each laboratory carried out their version of the PERT assay and submitted the results to the coordinator at CBER. Results: Results of the PERT analyses carried out in the six laboratories are presented. Five of the six laboratories reported results that were highly consistent. RT activity was detected in live attenuated vaccines that were prepared in chick embryo cells (mumps, measles and yellow fever), but very low or undetectable RT activity was found in vaccines produced in mammalian cells (rabies and rubella). Influenza vaccines from several manufacturers included in the panel displayed the most variability, with different products of this inactivated vaccine having differing amounts of RT activity. Conclusions: Only vaccines produced in chick embryo cells had significant RT activity. Because RT activity was present in the allantoic fluid of uninfected chick embryos and culture medium from chick embryo fibroblasts, the RT activity arises from the cell substrate used for vaccine production. The PERT assays were reliably able to detect the low levels of RT activity in chicken-derived vaccines. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 US FDA, Lab Retrovirus Res, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Peden, KWC (reprint author), US FDA, Lab Retrovirus Res, Ctr Biol Evaluat & Res, Bldg 29A,Room 3D08,29 Lincoln Dr, Bethesda, MD 20892 USA. EM peden@cber.cber.fda.gov NR 21 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD JUL 24 PY 1998 VL 11 IS 1 BP 19 EP 28 DI 10.1016/S0928-0197(98)00044-0 PG 10 WC Virology SC Virology GA 142AD UT WOS:000077177000003 PM 9784140 ER PT J AU Chen, T Aidoo, A Manjanatha, MG Mittelstaedt, RA Shelton, SD Lyn-Cook, LE Casciano, DA Heflich, RH AF Chen, T Aidoo, A Manjanatha, MG Mittelstaedt, RA Shelton, SD Lyn-Cook, LE Casciano, DA Heflich, RH TI Comparison of mutant frequencies and types of mutations induced by thiotepa in the endogenous Hprt gene and transgenic lad gene of Big Blue (R) rats SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE multiplex polymerase chain reaction; reverse transcriptase-polymerase chain reaction; CpG site; transcription-coupled DNA repair; transgene; lymphocyte ID MOUSE MUTAGENESIS ASSAY; IN-VIVO MUTAGENICITY; ETHYL-N-NITROSOUREA; LACI GENE; CHEMOTHERAPEUTIC-AGENTS; INHALATION EXPOSURE; FISCHER-344 RATS; B6C3F1 MICE; DNA; LYMPHOCYTES AB The utility of the lad transgene of Big Blue(R) rats as a reporter of in vivo mutation was evaluated by comparing the frequency and types of mutations induced by thiotepa in the transgene and the endogenous Hprt gene. Transgenic rats were given i.p. injections of 1.4 mg/kg of thiotepa three times per week over a period of 4 weeks (a total dose of 16.8 mg/kg); 1 week after the last injection, mutation assays were performed on spleen lymphocytes isolated from the animals. Thiotepa treatment increased the lad mutant frequency from 34.8 +/- 4.1 x 10(-6) in control animals to 140.9 +/- 64.8 x 10-6 (p = 0.0020) and the Hprt mutant frequency from 3.5 +/- 1.5 x 10-6 to 41.1 +/- 23.2 x 10-6 (p = 0.0028). Sequence analysis of lad mutant DNA and Hprt mutant cDNA produced similar overall mutation patterns: G:C --> T:A transversion was the most common base pair substitution (32% of independent mutations in the lad gene and 28% of Hprt mutations), and deletions and insertions accounted for 34% of mutations in the lacI gene and 28% in the Hprt gene. The majority of thiotepa-induced base pair substitutions in the Hprt gene occurred with the mutated purine on the non-transcribed DNA strand, while no strand-related bias was found for mutations in the lad gene. Substitutions at G:C base pairs in the lad gene, but not in the Hprt gene, were found disproportionately in CpG sites. In addition, multiplex polymerase chain reaction analysis of genomic DNA from the Hprt mutants indicated that 34% had relatively large deletions; none of these deletions was detected by the cDNA analysis. The results indicate that the frequency of thiotepa-induced mutants in Big Blue(R) rats was 2.8-fold greater in the lad gene than in the Hprt gene. Although the Hprt gene recovered a fraction of large deletions not found among the lad mutants, the effects of transcription-coupled DNA repair in the Hprt gene and the targeting of base pair substitutions to G:C base pairs in CpG sites may have contributed to the higher mutant frequencies induced by thiotepa in the lad transgene compared with the Hprt gene. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Chen, T (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 50 TC 23 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD JUL 17 PY 1998 VL 403 IS 1-2 BP 199 EP 214 DI 10.1016/S0027-5107(98)00080-3 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 110TE UT WOS:000075395800021 PM 9726020 ER PT J AU Kumar, A Manna, SK Dhawan, S Aggarwal, BB AF Kumar, A Manna, SK Dhawan, S Aggarwal, BB TI HIV-tat protein activates c-Jun N-terminal kinase and activator protein-1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; FACTOR KAPPA-B; SIGNAL-TRANSDUCTION; GAMMA-RADIATION; GROWTH-FACTOR; CELL-LINE; TYPE-1; TRANSCRIPTION; GENE; EXPRESSION AB Human immunodeficiency virus-P tat (HIV-tat) protein, like other proinflammatory cytokines (such as TNF), activates a wide variety of cellular responses, some of which play a critical role in progression of HIV infection. Whether HIV-tat, like TNF, also activates c-Jun N-terminal kinase (JNK) and the transcription factor activator protein (AP)-1 is not known. We show that treatment of human histiocytic lymphoma U937 cells with the HIV-tat protein causes activation of JNK and AP-1 in a time- and dose-dependent manner, Transfection of a T cell line, H9 cells with the HIV-tat gene also resulted in an activation of JNK that was not further increased by treatment of cells with exogenous HIV-tat protein, Neutralizing Ab against HN-tat inhibited the HIV-tat-mediated JNK activation. The activation of JNK by HIV-tat appears to be mediated through generation of free radical species, since pretreatment of cells with N-acetylcysteine (NAC) abolished the effect. Overall our results demonstrate that HIV-tat activates JNK and AP-P, which may contribute to the pathogenesis of AIDS. C1 Univ Texas, MD Anderson Cancer Ctr, Dept Med Oncol, Cytokine Res Sect, Houston, TX 77030 USA. US FDA, Ctr Biol Evaluat & Res, Lab Immunochem, Div Transfus Transmitted Dis, Bethesda, MD 20892 USA. RP Aggarwal, BB (reprint author), Univ Texas, MD Anderson Cancer Ctr, Dept Med Oncol, Cytokine Res Sect, Houston, TX 77030 USA. RI Aggarwal, Bharat/G-3388-2013 NR 42 TC 100 Z9 102 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 JUL 15 PY 1998 VL 161 IS 2 BP 776 EP 781 PG 6 WC Immunology SC Immunology GA ZZ428 UT WOS:000074728400031 PM 9670954 ER PT J AU Rashid, MM AF Rashid, MM TI Multiple comparisons with a control in repeated measures incomplete block designs using R-estimators SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE control treatment; dispersion function; multiple comparisons; R-estimators AB New multiple comparison with a control (MCC) procedures are developed in repeated measures incomplete block design settings based on R-estimates. It is assumed that the errors within each subject are exchangeable random variables. The R-estimators of the treatment effects are obtained by minimizing a sum of Jaeckel (1972)-type dispersion functions. Based on the R-estimators, Dunnett-type multiple comparison procedures are developed for comparing test-treatments with a control-treatment. Under exchangeable errors, it is demonstrated that for Cox-type designs, the new procedures are more efficient than the existing nonparametric procedures. The new MCC procedures are applied to a data set in a clinical trial which consists of patients with reversible obstructive pulmonary disease. (C) 1998 Elsevier Science B.V. All rights reserved. C1 US FDA, Ctr Drug Evaluat & Res, Div Biometr 3, Rockville, MD 20857 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD JUL 15 PY 1998 VL 70 IS 2 BP 361 EP 380 DI 10.1016/S0378-3758(97)00191-2 PG 20 WC Statistics & Probability SC Mathematics GA 100RD UT WOS:000074828400014 ER PT J AU Keller, WC Bataller, N Oeller, DS AF Keller, WC Bataller, N Oeller, DS TI Processing and evaluation of adverse drug experience reports at the Food and Drug Administration Center for Veterinary Medicine SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article C1 US FDA, Ctr Vet Med, Rockville, MD 20857 USA. RP Keller, WC (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl,HFV-210, Rockville, MD 20857 USA. NR 1 TC 7 Z9 7 U1 0 U2 0 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 JUL 15 PY 1998 VL 213 IS 2 BP 208 EP 211 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA ZZ416 UT WOS:000074727200021 PM 9676589 ER PT J AU Fyfe, M Kelly, MT Yeung, ST Daly, P Schallie, K Buchanan, S Waller, P Kobayashi, J Therien, N Guichard, M Lankford, S Stehr-Green, P Harsch, R DeBess, E Cassidy, M McGivern, T Mauvais, S Fleming, D Lippmann, M Pong, L McKay, RW Cannon, DE Werner, SB Abbott, S Hernandez, M Wojee, C Waddell, J Waterman, S Middaugh, J Sasaki, D Effler, P Groves, C Curtis, N Dwyer, D Dowdle, G Nichols, C AF Fyfe, M Kelly, MT Yeung, ST Daly, P Schallie, K Buchanan, S Waller, P Kobayashi, J Therien, N Guichard, M Lankford, S Stehr-Green, P Harsch, R DeBess, E Cassidy, M McGivern, T Mauvais, S Fleming, D Lippmann, M Pong, L McKay, RW Cannon, DE Werner, SB Abbott, S Hernandez, M Wojee, C Waddell, J Waterman, S Middaugh, J Sasaki, D Effler, P Groves, C Curtis, N Dwyer, D Dowdle, G Nichols, C TI Outbreak of Vibrio parahaemolyticus infections associated with eating raw oysters - Pacific Northwest, 1997 (Reprinted from MMWR, vol 47, pg 457, 1998) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 British Columbia Ctr Dis Control, Prov Lab, Vancouver, BC, Canada. Hlth Canada, Field Epidemiol Training Program, Ottawa, ON, Canada. Vancouver Richmond Hlth Board, Vancouver, BC, Canada. Canadian Food Inspect Agcy, Vancouver, BC, Canada. Washington Dept Hlth, Seattle, WA USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Oregon Dept Human Resources, State Hlth Div, Portland, OR USA. City & Cty San Francisco Dept Publ Hlth, Communicable Dis Control Unit, San Francisco, CA USA. City & Cty San Francisco Dept Publ Hlth, Environm Hlth Management Sect, San Francisco, CA USA. Calif State Dept Hlth Serv, Div Communicable Dis Control, Sacramento, CA 95814 USA. Calif State Dept Hlth Serv, Div Food Drug & Radiat Safety, Sacramento, CA 95814 USA. State Alaska Dept Hlth & Social Serv, Juneau, AK USA. Hawaii Dept Hlth, Honolulu, HI USA. Maryland State Epidemiol & Dis Control, Baltimore, MD USA. Maryland State Dept Hlth & Mental Hyg, Baltimore, MD USA. Utah Dept Hlth, Salt Lake City, UT USA. CDC, Natl Ctr Infect Dis, Foodborne & Diarrheal Dis Branch, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. RP Fyfe, M (reprint author), British Columbia Ctr Dis Control, Prov Lab, Vancouver, BC, Canada. NR 1 TC 5 Z9 5 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 8 PY 1998 VL 280 IS 2 BP 126 EP 127 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA ZY321 UT WOS:000074608400011 ER PT J AU Gutman, S Richter, K Alpert, S AF Gutman, S Richter, K Alpert, S TI Update on FDA regulation of in vitro diagnostic devices SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article C1 US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Gutman, S (reprint author), US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, 2098 Gaither Rd, Rockville, MD 20850 USA. NR 4 TC 4 Z9 4 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 8 PY 1998 VL 280 IS 2 BP 190 EP 192 DI 10.1001/jama.280.2.190 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA ZY321 UT WOS:000074608400039 PM 9669798 ER PT J AU Deb, TB Wong, L Salomon, DS Zhou, GC Dixon, JE Gutkind, JS Thompson, SA Johnson, GR AF Deb, TB Wong, L Salomon, DS Zhou, GC Dixon, JE Gutkind, JS Thompson, SA Johnson, GR TI A common requirement for the catalytic activity and both SH2 domains of SHP-2 in mitogen-activated protein (MAP) kinase activation by the ErbB family of receptors - A specific role for SHP-2 in MAP, but not c-jun amino-terminal kinase activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE-PHOSPHATASE; SIGNAL-TRANSDUCTION; INSULIN; SEVENLESS; SHPTP2; CELLS; PHOSPHORYLATION; STIMULATION; EXPRESSION; HEREGULIN AB The ErbB family of receptors, which include the epidermal growth factor receptor (EGFR), ErbB2, ErbB3, and ErbB4 mediate the actions of a family of bioactive polypeptides. EGF signals through EGFR, whereas heregulin (HRG) signaling is initiated through binding to either ErbB3 or ErbB4. In this report we studied the role of protein-tyrosine phosphatase SHP-2 in ErbB-mediated activation of mitogen-activated protein kinase (MAPK) by overexpressing SHP-2 mutants in COS-7 cells. We demonstrate that enzymatic activity and both NH2- and COOH-terminal SH2 domains of SHP-2 are required for EGF-induced MAPK activation, but not for c-Jun amino-terminal kinase stimulation or MAPK activation which occurred in response to myristoylated son of sevenless, activated Ras, or phorbol ester. Dominant-negative forms of SHP-2 had no effect on EGF-stimulated interaction of GRB2 with EGFR or SHC, nor did they influence phosphorylation of SHC and SHC/EGFR association. The same mutant SHP-2 structures that inhibited EGF-mediated stimulation of MAPK also blocked HRG alpha/beta-induced MAPK activation. EGF or HRG beta caused SHP-2 SH2 domains to engage multiple phosphotyrosine proteins, and mutation of either domain disrupted these associations. These results demonstrate that SHP-2 performs a common and essential function(s) in ligand-stimulated MAPK activation by the ErbB family of receptors. C1 US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. NCI, NIH, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48109 USA. NIDR, NIH, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. Berlex Biosci, Dept Prot Chem & Biophys, Richmond, CA 94804 USA. RP Johnson, GR (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bldg 29A,Rm 3B-16,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009 NR 25 TC 72 Z9 72 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 3 PY 1998 VL 273 IS 27 BP 16643 EP 16646 DI 10.1074/jbc.273.27.16643 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZX700 UT WOS:000074545200004 PM 9642214 ER PT J AU Schenck, FJ Callery, PS AF Schenck, FJ Callery, PS TI Chromatographic methods of analysis of antibiotics in milk SO JOURNAL OF CHROMATOGRAPHY A LA English DT Review DE reviews; milk; food analysis; antibiotics; aminoglycosides; lactams; tetracyclines; macrolides; aminocyclitols; fluoroquinolones ID PERFORMANCE LIQUID-CHROMATOGRAPHY; CHELATE AFFINITY-CHROMATOGRAPHY; BETA-LACTAM ANTIBIOTICS; ELECTROSPRAY MASS-SPECTROMETRY; MULTIPLE TETRACYCLINE RESIDUES; BOVINE-MILK; ELECTROCHEMICAL DETECTION; ULTRAVIOLET DETECTION; PIRLIMYCIN RESIDUE; ANIMAL-TISSUES AB The widespread use of antibiotics in dairy cattle management may result in the presence of antibiotic residues in milk. While rapid screening tests are commonly used to detect the presence of antibiotics in milk, more accurate chromatographic methods are required by government regulatory agencies to identify and confirm the identity and quantity of antibiotic present. This paper reviews recent developments in the chromatographic determination of antibiotic residues in milk. (C) 1998 Elsevier Science B.V. All rights reserved. C1 US FDA, Baltimore Dist Lab, Baltimore, MD 21201 USA. W Virginia Univ, Sch Pharm, Morgantown, WV 26506 USA. RP Schenck, FJ (reprint author), US FDA, Baltimore Dist Lab, 900 Madison Ave, Baltimore, MD 21201 USA. NR 86 TC 104 Z9 108 U1 3 U2 24 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 3 PY 1998 VL 812 IS 1-2 BP 99 EP 109 DI 10.1016/S0021-9673(97)01291-0 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA ZX854 UT WOS:000074562100007 PM 9691311 ER PT J AU Dunten, P Jaffe, H Aksamit, RR AF Dunten, P Jaffe, H Aksamit, RR TI Crystallization of 5-keto-4-deoxyuronate isomerase from Escherichia coli SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID ERWINIA-CHRYSANTHEMI; S-ADENOSYLHOMOCYSTEINASE; PECTIN DEGRADATION; SEQUENCE ANALYSIS; HYDROLASE; GENE; KDGR AB 5-keto-4-deoxyuronate isomerase from Escherichia coli has been crystallized after partial purification. The isomerase was found to be enriched in preparations of an unrelated recombinant protein. Crystals of the isomerase were obtained from two different precipitants despite the fact that the recombinant protein represented roughly 90% of the total protein present. The crystals diffract to 2.7 Angstrom resolution and are suitable for a structure determination. The role of the isomerase in E. coli is uncertain, as E. coli is not known to degrade the polysaccharides which are potential sources of 5-keto-4-deoxyuronate. C1 Swedish Univ Agr Sci, Dept Biol Mol, BMC Box 590, S-75124 Uppsala, Sweden. NINDS, LNC, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NIMH, Lab Comparat & Gen Biochem, NIH, Bethesda, MD 20892 USA. US FDA, Lab Cellular Hematol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Dunten, P (reprint author), Hoffmann La Roche Inc, 340 Kingsland St, Nutley, NJ 07110 USA. EM dunten@xray.bmc.uu.se NR 14 TC 4 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0907-4449 EI 1399-0047 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD JUL 1 PY 1998 VL 54 BP 678 EP 680 DI 10.1107/S090744499701785X PN 4 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 103BZ UT WOS:000074962500031 PM 9761873 ER PT J AU Berkower, I Bridgewater, J AF Berkower, I Bridgewater, J TI Genetic control of the immune response to HIV type 1 envelope glycoprotein 120 in mice: Effects of MHC and transgenic human CD4 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; RECOMBINANT GP160; T-CELLS; NEUTRALIZING ANTIBODIES; CANDIDATE VACCINE; MURINE LEUKEMIA; GP120; INFECTION; IDENTIFICATION AB HIV infection elicits a strong immune response to viral proteins, including broadly cross-reactive antibodies to envelope glycoprotein 120 (gp120), However, vaccination with recombinant gp120 generally produces lower titered antibodies with narrow specificity. We have examined host genes that may control the strength and breadth of the response to gp120 vaccines. Because of the complexity of the human MHC, we have focused on the response of MHC congenic mice, which share an identical genetic background, differing only in H-2 type. The antibody response to gp120 varied markedly with H-2 type. H-2(a) and H-2(k) mice gave consistently high antibody titers, while H-2(s) mice gave 100-fold lower titers, and H-2(b) mice gave low to intermediate responses, Nearly the same genetic control applied for antibodies to both unique and shared determinants and on a variety of different genetic backgrounds, Transgenic mice expressing human CD4 gave the same titers as normal H-2-matched controls, MHC-linked genetic control of the quantity and quality of antibodies indicate a requirement for T cell help in producing antibodies to unique and shared determinants of gp120. C1 US FDA, Immunoregulat Lab, DAPP, Off Vaccine Res,Ctr Biol, Bethesda, MD 20892 USA. RP Berkower, I (reprint author), US FDA, Immunoregulat Lab, DAPP, Off Vaccine Res,Ctr Biol, Bldg 29,Room 523,NIH Campus, Bethesda, MD 20892 USA. NR 54 TC 4 Z9 4 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUL 1 PY 1998 VL 14 IS 10 BP 893 EP 900 DI 10.1089/aid.1998.14.893 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ZW769 UT WOS:000074446500009 PM 9671218 ER PT J AU Fein, SB Roe, B AF Fein, SB Roe, B TI The effect of work status on initiation and duration of breast-feeding SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID MATERNAL EMPLOYMENT; WOMENS EXPERIENCES; POPULATION; DECISIONS AB Objectives. In this study, longitudinal data are used to examine the effect of work status on breast-feeding initiation and duration. Methods. Mothers from a mail panel completed questionnaires during late pregnancy and 10 times in the infant's first year. Mother's work status was categorized for initiation by hours she expected, before delivery to work and for duration by hours she worked at month 3. Covariates were demographics; parity; medical, delivery, and hospital experiences; social support; embarrassment; and health promotion. Results. Expecting to work part-time neither decreased nor increased the probability of breast-feeding relative to expecting not to work (odds ratios [ORs] = .83 and .89, p greater-than .50), but expecting to work full-time decreased the probability of breast-feeding (OR = .47, P less-than .01). Working full-time at 3 months postpartum decreased breast-feeding duration by an average of 8.6 weeks (P less-than .001) relative to not working, but part-time work of 4 or fewer hours per day did not affect duration and part-time work of more than 4 hours per day decreased duration less than full-time work. Conclusion. Part-time work is an effective strategy to help mothers combine breast-feeding and employment. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Fein, SB (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-727,200 C St SW, Washington, DC 20204 USA. EM sbf@cfsan.fda.gov RI Roe, Brian/A-7386-2009 OI Roe, Brian/0000-0003-4228-2889 NR 29 TC 141 Z9 145 U1 1 U2 7 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 1998 VL 88 IS 7 BP 1042 EP 1046 DI 10.2105/AJPH.88.7.1042 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZY340 UT WOS:000074610600011 PM 9663151 ER PT J AU Ette, EI AF Ette, EI TI Statistical graphics in pharmacokinetics and pharmacodynamics: A tutorial SO ANNALS OF PHARMACOTHERAPY LA English DT Review DE pharmacokinetics; pharmacodynamics; statistical graphics AB OBJECTIVE: To discuss the use of statistical graphics in the analysis of pharmacokinetics and pharmacodynamics data. METHODS: Information on graphic techniques and their application was retrieved from a MEDLINE search(January 1980-March 1997) of the English-language literature and bibliographic reviews of review articles and books. Data used to generate plots were extracted from some new drug applications submitted to the Food and Drug Administration and by simulation. DATA SYNTHESIS: In carrying out data analysis, we should look at data in several ways, construct a number of plots, and do several analyses, letting the results of each step suggest the next. The information from a plot should be relevant to the goals of the analysis. Thus, in choosing a graphic method it is necessary to match the capabilities of the method to the need in the context of the application. For example, if linear relationships among variables in a set of multidimensional data are relevant, scatter plots such as the pairs plot with smoothing is likely to be more informative than other graphic methods. It is necessary to recognize what kinds of perceived structure are attributable to the data, and what kinds are artifacts of the display technique itself when using graphs for data analysis. CONCLUSIONS: Graphic techniques enable the data analyst to explore data thoroughly, look for patterns and relationships, confirm or disprove the expected, and discover new phenomena. An important element of statistical graphic techniques is flexibility, both in tailoring the analysis to the structure of the data and in responding to patterns that successive steps of analysis uncover. Statistical graphics can and should be used to enhance numeric statistical analyses. C1 US FDA, Div Biopharmaceut, Rockville, MD 20857 USA. RP Ette, EI (reprint author), Vertex Pharmaceut, Dept Drug Metab Pharmacokinet, Clin Pharmacol, 130 Waverly St, Cambridge, MA 02139 USA. NR 23 TC 19 Z9 20 U1 0 U2 5 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JUL-AUG PY 1998 VL 32 IS 7-8 BP 818 EP 828 DI 10.1345/aph.17304 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 102HT UT WOS:000074918900012 PM 9681098 ER PT J AU Aszalos, A Ross, DD AF Aszalos, A Ross, DD TI Biochemical and clinical aspects of efflux pump related resistance to anti-cancer drugs SO ANTICANCER RESEARCH LA English DT Review DE multidrug resistance; P-glycoprotein; MRP; cancer; resistance modulators ID ACUTE MYELOID-LEUKEMIA; HUMAN MDR1 GENE; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; FLOW-CYTOMETRY; MESSENGER-RNA; BLAST CELLS; PROTEIN; MRP; EXPRESSION AB This review paper will focus on the molecular biological, biochemical and biophysical aspects of the following three efflux pumps. P-glycoprotein (Pgp), Multidrug Resistance Protein (MRP) and Lung cancer Resistance-related Protein. Since suppression of the function of these pumps has clinical implications, novel approaches developed in our laboratory for blocking the function of Pgp and MRP are also discussed. The second part of this review will summarize the clinical significance and the results of clinical trials designed to suppress the effects of these efflux pumps. C1 US FDA, Laurel, MD 20708 USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21045 USA. Univ Maryland, Sch Med, Dept Med, Div Hematol Oncol, Baltimore, MD 21045 USA. Vet Adm Med Ctr, Baltimore, MD 21045 USA. RP Aszalos, A (reprint author), US FDA, HFD-910, Rockville, MD 20857 USA. NR 48 TC 51 Z9 53 U1 2 U2 2 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JUL-AUG PY 1998 VL 18 IS 4C BP 2937 EP 2944 PG 8 WC Oncology SC Oncology GA 106XC UT WOS:000075175700004 PM 9713488 ER PT J AU Trapnell, CB Klecker, RW Jamis-Dow, C Collins, JM AF Trapnell, CB Klecker, RW Jamis-Dow, C Collins, JM TI Glucuronidation of 3 '-azido-3 '-deoxythymidine (zidovudine) by human liver microsomes: Relevance to clinical pharmacokinetic interactions with atovaquone, fluconazole, methadone, and valproic acid SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; IN-VITRO; DRUG-INTERACTIONS; PLASMA-CONCENTRATIONS; METABOLISM; EFFICACY; XENOBIOTICS; INFECTIONS; INHIBITION; CLEARANCE AB Zidovudine (3'-azido-3'-deoxythymidine [AZT]), an antiviral nucleoside analog effective in the treatment of human immunodeficiency virus infection, is primarily metabolized to an inactive glucuronide form, GAZT, via uridine-5'-diphospho-glucuronosyltransferase (UGT) enzymes. UGT enzymes exist as different isoforms, each exhibiting substrate specificity. Published clinical studies have shown that atovaquone, fluconazole, methadone, and valproic acid decreased GAZT formation, presumably due to UGT inhibition. The effect of these drugs on AZT glucuronidation was assessed in vitro by using human hepatic microsomes to begin understanding ire vitro-in vivo correlations for UGT metabolism. The concentrations of each drug studied were equal to those reported with the usual clinical doses and at concentrations at least 10 times higher than would be expected with these doses. High-performance liquid chromatography was used to assess the respective metabolism and formation of AZT and GAZT. All four drugs exhibited concentration-dependent inhibition of AZT glucuronidation. The respective concentrations of atovaquone and methadone which caused 50% inhibition of GAZT were >100 and 8 mu g/ml, well above their usual clinical concentrations. Fluconazole and valproic acid exhibited 50% inhibition of GAZT at 50 and 100 mu g/ml, which are within the clinical ranges of 10 to 100 and 50 to 100 mu g/ml, respectively. These data suggest that inhibition of AZT glucuronidation may be more clinically significant with concomitant fluconazole and valproic acid. Factors such as inter and intraindividual pharmacokinetic variability and changes in AZT intracellular concentrations should be considered as other mechanisms responsible for changes in AZT pharmacokinetics with concomitant therapies. C1 US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Div Clin Trial Design & Anal, Rockville, MD 20852 USA. RP Trapnell, CB (reprint author), GloboMax LLC, 7250 Pkwy Dr,Suite 430, Hanover, MD 21076 USA. EM trapnelc@globomax.com NR 37 TC 58 Z9 58 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 1998 VL 42 IS 7 BP 1592 EP 1596 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA ZX610 UT WOS:000074535500012 PM 9660989 ER PT J AU Miyazaki, H Miyazaki, Y Geber, A Parkinson, T Hitchcock, C Falconer, DJ Ward, DJ Marsden, K Bennett, JE AF Miyazaki, H Miyazaki, Y Geber, A Parkinson, T Hitchcock, C Falconer, DJ Ward, DJ Marsden, K Bennett, JE TI Fluconazole resistance associated with drug efflux and increased transcription of a drug transporter gene, PDH1, in Candida glabrata SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID BINDING CASSETTE TRANSPORTER; AZOLE-RESISTANT; ANTIFUNGAL AGENTS; ORAL CANDIDOSIS; ENCODING GENE; ALBICANS; YEAST; IDENTIFICATION; SEQUENCE; SACCHAROMYCES AB Sequential Candida glabrata isolates were obtained from the mouth of a patient infected with human immunodeficiency virus type 1 who was receiving high doses of fluconazole for oropharyngeal thrush. Fluconazole-susceptible colonies were replaced by resistant colonies that exhibited both increased fluconazole efflux and increased transcripts of a gene which codes for a protein with 72.5% identity to Pdr5p, an ABC multidrug transporter in Saccharomyces cerevisiae. The deduced protein had a molecular mass of 175 kDa and was composed of two homologous halves, each,vith six putative transmembrane domains and highly conserved sequences of ATP-binding domains. When the earliest and most azole-susceptible isolate of C. glabrata from this patient was exposed to fluconazole, increased transcripts of the PDR5 homolog appeared, linking azole exposure to regulation of this gene. C1 NIAID, Ctr Clin, Clin Mycol Sect, Lab Clin Invest,NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Pfizer Ltd, Cent Res, Dept Discovery Biol, Sandwich CT13 9NJ, Kent, England. Dupont Circle Phys Grp, Washington, DC USA. RP Bennett, JE (reprint author), NIAID, Ctr Clin, Clin Mycol Sect, Lab Clin Invest,NIH, Rm 11C304, Bethesda, MD 20892 USA. NR 42 TC 92 Z9 96 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 1998 VL 42 IS 7 BP 1695 EP 1701 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA ZX610 UT WOS:000074535500029 PM 9661006 ER PT J AU Khan, AA Kim, E Cerniglia, CE AF Khan, AA Kim, E Cerniglia, CE TI Molecular cloning, nucleotide sequence, and expression in Escherichia coli of a hemolytic toxin (aerolysin) gene from Aeromonas trota SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ENTERO-TOXIN; HYDROPHILA; SOBRIA; DETERMINANT; DNA; K-12; PURIFICATION; MUTAGENESIS; MEMBRANE AB Aeromonas trota AK2, which was derived from ATCC 49659 and produces the extracellular pore-forming hemolytic toxin aerolysin, was mutagenized with the transposon mini-Tn5Km1 to generate a hemolysin-deficient mutant, designated strain AK253, Southern blotting data indicated that an 8.7-kb NotI fragment of the genomic DNA of strain AK253 contained the kanamycin resistance gene of mini-Tn5Km1, The 8.7-kb NotI DNA fragment was cloned into the vector pGEM5Zf(-) by selecting for kanamycin resistance, and the resultant clone, pAK71, shelved aerolysin activity in Escherichia coli JM109. The nucleotide sequence of the aerA gene, located on the 1.8-kb ApaI-EcoRI fragment, was determined to consist of 1,479 bp and to have an ATG initiation codon and a TAA termination codon. An in vitro coupled transcription-translation analysis of the 1.8-kb region suggested that the aerA gene codes for a 54-kDa protein, in agreement with nucleotide sequence data. The deduced amino acid sequence of the aerA gene product of A. trota exhibited 99% homology with the amino acid sequence of the aerA product of Aeromonas sobria AB3 and 57% homology with the amino acid sequences of the products of the aerA genes of Aeromonas salmonicida 17-2 and A. sobria 33. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Khan, AA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 38 TC 18 Z9 19 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUL PY 1998 VL 64 IS 7 BP 2473 EP 2478 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA ZY646 UT WOS:000074644700023 PM 9647817 ER PT J AU Yang, WC Kwok, SCM Leshin, S Bollo, E Li, WI AF Yang, WC Kwok, SCM Leshin, S Bollo, E Li, WI TI Purified porcine seminal plasma protein enhances in vitro immune activities of porcine peripheral lymphocytes SO BIOLOGY OF REPRODUCTION LA English DT Article ID IMMUNOGLOBULIN BINDING-FACTOR; BLOOD MONONUCLEAR-CELLS; ANTI-MICROBIAL PROTEIN; AMINO-ACID-SEQUENCE; MALE GENITAL-TRACT; IMMUNOSUPPRESSIVE ACTIVITY; REPRODUCTIVE IMMUNOLOGY; PSP-I; SECRETORY PROTEIN; VESICLE FLUID AB The porcine seminal plasma protein (PSP) accounts for much more than 50% of the total proteins in seminal plasma. PSP has been previously purified and its biochemical properties characterized. However, the biological functions of PSP remain to be elucidated. We hypothesize that PSP is involved in the regulatory of uterine immune activity. in the current study effects of PSP on in vitro lymphocyte activities and the presence of PSP binding sites on lymphocytes were examined. In mitogen-induced proliferation assay, lymphocytes from peripheral blood of gifts were cultured with pokeweed mitogen (PWM), phytohemagglutinin (PHA), or concanavalin A (Con A) in the presence or absence of PSP. PSP at 50, 125, and 250 ng/well augmented PWM-induced [H-3]thymidine uptake in a dose-responsive manner by 152.8 +/- 8.1%, 225.9 +/- 35.2%, and 274.8 +/- 53.6%, respectively, compared with that of control. PSP did not alter lymphocyte proliferation in the absence of PWM. Similarly, PSP had little or no effect on PHA- or Can A-induced lymphocyte proliferation. in one-way mixed lymphocyte reactions, PSP at 50, 125, and 250 ng/well enhanced [H-3]thymidine uptake in a dose-responsive manner by 181.5 +/- 16.5%, 339.9 +/- 48.2%, and 600.1 +/- 84.8% of control, respectively. Using biotinylated PSP-I, PSP binding sites were localized on approximately 3-5% of the lymphocyte population. In summary, we have demonstrated that PSP itself is not a mitogen/antigen to porcine lymphocytes but that it has a stimulatory effect on lymphocyte activities initiated by PWM or surface antigens of lymphocytes. PSP may exert its functions by interacting with PSP binding sites on a subpopulation of porcine lymphocytes. The high potency of PSP on lymphocyte activities and the abundance of PSP in seminal plasma have suggested that PSP may play an important role in regulating immune responses in the porcine uterine environment. C1 US FDA, Dept Hlth & Human Serv, Rockville, MD 20857 USA. Univ Georgia, Coll Vet Med, Dept Physiol & Pharmacol, Athens, GA 30602 USA. Albert Einstein Med Ctr, Dept Pathol & Lab Med, Philadelphia, PA 19141 USA. RP Li, WI (reprint author), US FDA, Dept Hlth & Human Serv, Rockville, MD 20857 USA. OI Kwok, Simon/0000-0001-6003-5350 NR 53 TC 26 Z9 27 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 1998 VL 59 IS 1 BP 202 EP 207 DI 10.1095/biolreprod59.1.202 PG 6 WC Reproductive Biology SC Reproductive Biology GA ZX070 UT WOS:000074476400030 PM 9675013 ER PT J AU Eddington, ND Adekoya, F Kharidia, J AF Eddington, ND Adekoya, F Kharidia, J TI The influence of moderate and chronic exercise training on the pharmacokinetics of procainamide and N-acetylprocainamide SO BIOPHARMACEUTICS & DRUG DISPOSITION LA English DT Article DE procainamide; N-acetylprocainamide; exercise; pharmacokinetics ID HEPATIC DRUG-METABOLISM; PHYSICAL-ACTIVITY; RAT-LIVER; FITNESS; HEALTH AB The effect of moderate and prolonged exercise on the disposition and metabolism of drugs has not been extensively examined. The present study examined the effect of exercise training on the pharmacokinetics of procainamide and its active metabolite, N-acetylprocainamide. Male Sprague Dawley rats were randomly assigned to three testing groups: (1) sedentary, (2) 4 weeks of exercise training and (3) 8 weeks of exercise training. Treadmill speed and exercise duration were gradually increased, reaching a final rate of 24 m min(-1) for an hour by the end of the 4-week or 8-week period. Sedentary and exercise trained rats received a single i.p. dose of procainamide (100 mg kg(-1)). Serial blood samples were collected over a 10 h period and plasma samples were analysed by an UV-HPLC method. Noncompartmental analysis was performed to estimate the pharmacokinetic parameters. The i,,, of procainamide was significantly (p < 0.05) higher in the 8 week exercise group (331 min) as compared to the sedentary group (77 min). In addition, there was a significant reduction in the amount of N-acetylprocainamide formed after 8 weeks of exercise (AUC(NAPA) = 739 ng mL(-1) min(-1)). Results of this study suggest that prolonged exercise (8 weeks of training) alters the pharmacokinetics of procainamide by modifying the amount of active metabolite formed. (C) 1998 John Wiley & Sons, Ltd. C1 Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Pharmacokinet & Biopharmaceut Lab, Baltimore, MD 21201 USA. US FDA, CDER, Div Bioequivalence, Rockville, MD 20857 USA. RP Eddington, ND (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Pharmacokinet & Biopharmaceut Lab, Baltimore, MD 21201 USA. NR 23 TC 5 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0142-2782 J9 BIOPHARM DRUG DISPOS JI Biopharm. Drug Dispos. PD JUL PY 1998 VL 19 IS 5 BP 291 EP 296 DI 10.1002/(SICI)1099-081X(199807)19:5<291::AID-BDD106>3.0.CO;2-X PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZY581 UT WOS:000074638000003 PM 9673780 ER PT J AU Wagner, RD Balish, E AF Wagner, RD Balish, E TI Potential hazards of probiotic bacteria for immunodeficient patients SO BULLETIN DE L INSTITUT PASTEUR LA English DT Review ID LACTIC-ACID BACTERIA; ENTEROCOCCUS-FAECALIS; GNOTOBIOTIC MOUSE; CELL-WALL; LACTOBACILLUS; MICE; RESISTANCE; COLONIZATION; CANDIDIASIS; MECHANISMS AB Probiotic bacteria provide a variety of health benefits to immunocompetent hosts; however, their use in immunodeficient patients may pose problems. Some probiotics are closely related to bacteria that are opportunistic pathogens and can transfer antibiotic resistance genes. Intestinal bacteria have recently been associated with inflammatory and autoimmune diseases in immunodeficient hosts; similar problems may arise if probiotics are fed to immunodeficient patients. The safety, efficacy, benefits and costs of feeding probiotic bacteria to immunodeficient patients needs to be carefully considered and fully researched to assure they will not cause infectious, inflammatory or autoimmune diseases in these susceptible hosts. C1 Natl Ctr Toxicol Res, Microbiol Div HFT250, Jefferson, AR 72079 USA. Univ Wisconsin, Sch Med, Dept Surg, Madison, WI USA. Univ Wisconsin, Sch Med, Dept Med Microbiol, Madison, WI USA. RP Wagner, RD (reprint author), Natl Ctr Toxicol Res, Microbiol Div HFT250, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 27 TC 13 Z9 13 U1 2 U2 5 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0020-2452 J9 B I PASTEUR JI Bull. Inst. Pasteur PD JUL-SEP PY 1998 VL 96 IS 3 BP 165 EP 170 DI 10.1016/S0020-2452(98)80011-0 PG 6 WC Immunology; Microbiology; Virology SC Immunology; Microbiology; Virology GA 113VB UT WOS:000075573500003 ER PT J AU Booth, BP Fung, HL AF Booth, BP Fung, HL TI Regulation of in vivo whole blood aggregation in rats by calcitonin gene related peptide SO CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Article DE hemostasis; calcitonin gene related peptide (CGRP); CGRP(8-37); blood pressure; platelet aggregation ID NITRIC-OXIDE; CELLS AB The purpose of these experiments was to determine whether calcitonin gene related peptide (CGRP) mediates physiological control of platelet function in vivo. Rat blood pressure was continuously monitored via a femoral arterial cannula, and whole blood aggregation was assessed periodically ex vivo with an impedance aggregometer before and following a 1.4 nmol/kg bolus dose of CGRP(8-37), a specific receptor antagonist of CGRP. Mean arterial blood pressure was not significantly affected by CGRP(8-37) over a 30-min period (p > 0.05). However, whole blood aggregation increased by 38.4 +/- 18.0% (p < 0.01) and 32.0 +/- 11.2% (p < 0.05), at 5 and 15 min post CGRP(8-37), respectively, when compared with control. Whole blood aggregation was not significantly different from control at 30 min (p > 0.05), suggesting a relatively short duration of action for in vivo CGRP(8-37). These data suggest that CGRP contributes to the maintenance of hemostasis, and that this function may be more important than the better known vasodilatatory effects of this neuropeptide. C1 SUNY Buffalo, Dept Pharmaceut, Buffalo, NY 14260 USA. RP Fung, HL (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, 5600 Fishers Lane,HFD-860,WOC II,Room 2077, Rockville, MD 20857 USA. EM hlfung@acsu.buffalo.edu FU PHS HHS [22273] NR 18 TC 5 Z9 7 U1 0 U2 0 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA, ONTARIO K1A 0R6, CANADA SN 0008-4212 J9 CAN J PHYSIOL PHARM JI Can. J. Physiol. Pharmacol. PD JUL-AUG PY 1998 VL 76 IS 7-8 BP 811 EP 813 DI 10.1139/cjpp-76-7-8-811 PG 3 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA 162AY UT WOS:000078323900017 PM 10030464 ER PT J AU Jansen, DL Meade, BD Lynn, F Gray, GC Putnam, SD AF Jansen, DL Meade, BD Lynn, F Gray, GC Putnam, SD TI Evaluation of pertussis in US Marine Corps trainees - Reply SO CLINICAL INFECTIOUS DISEASES LA English DT Letter ID OPERATION-DESERT-SHIELD; RESPIRATORY-DISEASE; IMMUNE-RESPONSE; PENICILLIN-G; PROPHYLAXIS; INFECTIONS; BENZATHINE; MILITARY; VACCINE C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. USN, Hlth Res Ctr, Emerging Illness Div, San Diego, CA 92152 USA. Univ Iowa, Coll Med, Dept Prevent Med & Environm Hlth, Iowa City, IA 52242 USA. RP Jansen, DL (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-490, Rockville, MD 20852 USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL PY 1998 VL 27 IS 1 BP 231 EP 232 DI 10.1086/517693 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZZ690 UT WOS:000074756900057 ER PT J AU Young, JF AF Young, JF TI Physiologically-based pharmacokinetic model for pregnancy as a tool for investigation of developmental mechanisms SO COMPUTERS IN BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT 9th International Conference on Mechanics in Medicine and Biology CY JUN 30-JUL 04, 1996 CL LJUBLJANA, SLOVENIA SP Slovenian Soc Med & Biol Engn, Jozef Stefan Inst, Ljubljana, Univ Ljubljana, Fac Elect Engn, Univ Med Ctr, Ljubljana, Republic Slovenia, Inst Rehab, Univ Ljubljana, Med Fac, Int Federat Med & Biol Engn, Int Funct Elect Stimulat Soc, European Soc Engn & Med, Soc Exptl Mech, Federat European Simulat Soc, Slovenian Acad Sci & Arts, Minist Sci & Technol Republic Slovenia DE PBPK models; human; pregnancy; gompertz equation; malformations; developmental mechanisms; differential equations ID GROWTH; EMBRYO; MOUSE AB There is no known mechanism of teratogenesis! Although receptor occupancy has been implicated, associated and/or deemed necessary for some malformations in newborns (e.g. estrogen receptors, retinoic acid receptors), the upstream and downstream events from receptor occupancy that definitively tie a xenobiotic exposure with a resultant malformation are essentially unknown. One part of the puzzle that can be delineated is the xenobiotic target-tissue exposure curve. Physiologically-based pharmacokinetic (PBPK) models are designed to provide time-course exposure curves for organs, tissues and fluids of human or animal systems. In this context pregnancy requires special considerations in that the PBPK model must represent the dynamic growth of both the maternal and embryo/fetal systems. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, Jefferson, AR 72079 USA. RP Young, JF (reprint author), Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, 3900 NCTR Dr, Jefferson, AR 72079 USA. NR 11 TC 4 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0010-4825 J9 COMPUT BIOL MED JI Comput. Biol. Med. PD JUL PY 1998 VL 28 IS 4 BP 359 EP 364 DI 10.1016/S0010-4825(98)00024-9 PG 6 WC Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Computer Science; Engineering; Mathematical & Computational Biology GA 131PN UT WOS:000076584600003 PM 9805196 ER PT J AU Fu, PP Von Tungeln, LS Yi, P Xia, QS Casciano, DA Flammang, TJ Kadlubar, FF AF Fu, PP Von Tungeln, LS Yi, P Xia, QS Casciano, DA Flammang, TJ Kadlubar, FF TI Neonatal mouse tumorigenicity bioassay SO DRUG INFORMATION JOURNAL LA English DT Article DE neonatal mouse tumorigenicity bioassay; direct-acting genotoxic chemical carcinogen; DNA adduct; secondary mechanism ID RAT-LIVER MICROSOMES; POLYCYCLIC AROMATIC-HYDROCARBONS; CHEMICALLY-INDUCED HEPATOMAS; ETHYL CARBAMATE URETHANE; DNA ADDUCT FORMATION; TESTER STRAIN TA102; X C3H-HEJ F1-MICE; MALE B6C3F1 MOUSE; H-RAS; CARCINOGENIC METABOLITE AB The International Conference on Harmonisation (ICH) has suggested the use of the newborn mouse bioassay as an alternative tumorigenicity assay. There are sufficient data to conclude that this animal model is highly sensitive to chemical carcinogens that exert their action through mechanisms involving the formation of covalently bound DNA adducts (exogenous adducts) of the administered compound and the processing of these adducts to mutations. Mechanistic studies, including metabolism, DNA adduct formation, and ras-oncogene activation, presented in this paper aid in the interpretation of tumor experiments. By comparison, the data thus far obtained suggest that this bioassay is very likely insensitive to some indirect-acting chemical carcinogens. Ongoing studies are focused on the sensitivity of this bioassay to indirect-acting carcinogens that are believed to exert their tumorigenicity through secondary mechanisms, including: 1. induction of lipid peroxidation and increases in endogenous DNA adducts, 2. endocrine disruption, and 3. induction of peroxisome proliferation. A systematic approach to validate the neonatal mouse tumorigenicity bioassay as a parr of a risk identification procedure is proposed This approach combines the tumorigenicity bioassay with several simple and convenient supportive mechanistic experiments of study so that direct-acting chemical carcinogens, indirect-acting carcinogens, and noncarcinogens can be distinguished. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Off Director, Jefferson, AR 72079 USA. RP Fu, PP (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd,HFT-110, Jefferson, AR 72079 USA. NR 91 TC 11 Z9 11 U1 0 U2 0 PU DRUG INFORMATION ASSOCIATION PI AMBLER PA 321 NORRISTOWN RD, STE 225, AMBLER, PA 19002-2755 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD JUL-SEP PY 1998 VL 32 IS 3 BP 711 EP 728 PG 18 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 128GK UT WOS:000076397200011 ER PT J AU Chamberland, ME Epstein, J Dodd, RY Persing, D Will, RG DeMaria, A Emmanuel, JC Pierce, B Khabbaz, R AF Chamberland, ME Epstein, J Dodd, RY Persing, D Will, RG DeMaria, A Emmanuel, JC Pierce, B Khabbaz, R TI Blood safety SO EMERGING INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT International Conference on Emerging Infectious Diseases CY MAR 08-11, 1998 CL ATLANTA, GEORGIA SP Ctr Dis Control & Prevent, Council State & Terr Epidemiologists, Amer Soc Microbiol, Natl Fdn CDC, Alliance Prudent Use Antibiot, Amer Acad Pediat, Amer Assoc Blood Banks, Amer Assoc Hlth Plans, Amer Canc Soc, Amer Coll Prevent Med, Amer Hosp Assoc, Amer Med Assoc, Amer Mosquito Control Assoc, Amer Publ Hlth Assoc, Amer Sexually Transmitted Dis Assoc, Amer Soc Clin Pathologists, Amer Soc Trop Med & Hyg, Amer Vet Med Assoc, Assoc Amer Vet Med Coll, Assoc Sch Publ Hlth, Assoc State & Terr Directors Hlth Promot & Publ Hlth Educ, Assoc State & Terr Hlth Officials, Assoc State & Terr Publ Hlth Lab Directors, Assoc Teachers Prevent Med, Burroughs Wellcome Fund, Emory Univ, Sch Med, Fogarty Int Ctr, US FDA, Indian Hlth Serv, Infect Dis Soc Amer, Int Life Sci Inst, Int Soc Infect Dis, Int Soc Travel Med, Int Union Hlth Promot & Educ, Int Union Microbiol Soc, Minor Hlth Profess Fdn, Morehouse Sch Med, NASA, Natl Assoc City & County Hlth Officials, Natl Assoc State Publ Hlth Vetinarians, Natl Council Int Hlth, Natl Fdn Infect Dis, Natl Hispan Med Assoc, NIAID, Natl Med Assoc, NOAA, Off Sci & Technol Policy, Pan Amer Hlth Org, Emory Univ, Rollins Sch Publ Hlth, Soc Healthcare Epidemiol Amer, Soc Occupat & Environm Hlth, Soc Publ Hlth Educ, Carter Ctr, Henry J Kaiser Family Fdn, HMO Grp, Robert Wood Johnson Fdn, Rockefeller Fdn, World Bank, Us Agcy Int Dev, USDA, US Dept Def, US Dept State, US Dept Justice, US Dept Vet Affairs, US EPA, WHO C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. US FDA, Washington, DC 20204 USA. Amer Red Cross, Washington, DC 20006 USA. Western Gen Hosp, Edinburgh EH4 2XU, Midlothian, Scotland. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Massachusetts Dept Publ Hlth, Boston, MA 02130 USA. WHO, CH-1211 Geneva, Switzerland. Natl Hemophilia Fdn, New York, NY 10012 USA. RP Chamberland, ME (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JUL-SEP PY 1998 VL 4 IS 3 BP 410 EP 411 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 111JP UT WOS:000075433800017 PM 9716958 ER PT J AU Do Luu, HM Hutter, JC Bushar, HF AF Do Luu, HM Hutter, JC Bushar, HF TI A physiologically based pharmacokinetic model for 2,4-toluenediamine leached from polyurethane foam-covered breast implants SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE implant; PBPK; physiologically based pharmacokinetic model; polyester urethane; risk assessment; 2,4-toluenediamine ID DEGRADATION PRODUCTS; TOLUENEDIAMINES; PATIENT; RATS AB Physiologically based pharmacokinetic (PBPK) modeling was used to assess the low-dose exposure of patients to the carcinogen 2,4-toluenediamine (2,4-TDA) released from the degradation of the polyester urethane foam (PU) used in Meme silicone breast implants. The tissues are represented as five compartments: liver, kidney, gastrointestinal tract, slowly perfused tissues (e.g.; fat), and richly perfused tissues (e.g., muscle). The PBPK model was fitted to the plasma and urine concentrations of 2,4-TDA and its metabolite 4-AAT (4-N-acetyl-2-amino toluene) in mts given low doses of 2,4-TDA intravenously and subcutaneously. The rat model was extrapolated to simulate oral and implant routes in rats. After adjusting for human physiological parameters, the model was then used to predict the bioavailability of 2,4-TDA released from a typical 4.87-g polyester methane foam implant found in a patient who weighed 58 kg with the Meme and had the breast implant for 10 years. A quantitative risk assessment for 2,4-TDA was performed and the polyester urethane foam did present an unreasonable risk to health for the patient. C1 US FDA, Off Sci & Technol, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Do Luu, HM (reprint author), US FDA, Off Sci & Technol, Ctr Devices & Radiol Hlth, HFZ-150,12725 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 30 TC 0 Z9 0 U1 1 U2 3 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 1998 VL 106 IS 7 BP 393 EP 400 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110KW UT WOS:000075380700019 ER PT J AU Schoenwald, RD Tandon, V Wurster, DE Barfknecht, CF AF Schoenwald, RD Tandon, V Wurster, DE Barfknecht, CF TI Significance of melanin binding and metabolism in the activity of 5-acetoxyacetylimino-4-methyl-Delta(2)-1,3,4,-thiadiazoline-2-sulfonamid e SO EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS LA English DT Article DE melanin binding; metabolism; intraocular pressure; carbonic anhydrase inhibitors; rabbits; antiglaucoma agents ID CARBONIC-ANHYDRASE INHIBITOR; RABBIT EYE; AMINOZOLAMIDE; DISPOSITION; TIMOLOL; ALBINO; MODEL; DRUGS AB 5-Acetoxyacetylimino-4-methyl-Delta(2)-1,3,4,-thiadiazoline-2-sulfonamide (compound (1)) is an ester prodrug that lowered intraocular pressure (IOP) in albino New Zealand rabbits, but was found to be inactive in pigmented Dutch Belt rabbits, In order to explain the differences in pharmacological activity for the two rabbit species, metabolism and melanin binding were studied. Depending on the initial concentration, the binding of compound (1) to natural melanin (Sepia officinalis) was 20-60%. The binding constant, K, at 37 degrees C was 4.32 x 10(5) M-1 and the maximum moles bound to melanin, r(max), was 4.5 x 10(-7) mol/mg of melanin. From a determination of binding at temperatures between 25 degrees C and 47 degrees C, a van't Hoff plot was constructed to determine enthalpy and entropy changes accompanying the binding process, Delta H and Delta S, respectively. Values calculated from the plot were -12.7 and -15.4 kcal/(mol deg), respectively. Negative Values for these parameters are consistent with charge transfer interactions and therefore suggest that this may be an operative mechanism between compound (I) and melanin. The in vitro incubation of compound (1) was also studied with various ocular tissues from both albino and pigmented rabbits which were iris-ciliary body, intact cornea, stroma/endothelium and aqueous humor. A major metabolite, MET I, was identified and also observed from in vivo analyses of the same tissues following topical application. The metabolite was isolated and subjected to mass spectroscopy and proton nuclear magnetic resonance spectroscopy analysis. From these analyses, it was hypothesized that the formation of MET 1 involved a GSH conjugation mechanism which displaced the sufonamide (-SO2NH2) group. The metabolism was found to be less extensive in the pigmented rabbit than in the albino rabbit and suggested that the binding affinity of compound (1) for melanin was a better explanation for the lack of IOP activity in the pigmented rabbit than differences in metabolism. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Univ Iowa, Coll Pharm, Div Pharmaceut, Iowa City, IA 52242 USA. US FDA, Rockville, MD 20857 USA. Univ Iowa, Div Med & Nat Prod Chem, Iowa City, IA USA. NR 34 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0939-6411 J9 EUR J PHARM BIOPHARM JI Eur. J. Pharm. Biopharm. PD JUL PY 1998 VL 46 IS 1 BP 39 EP 50 DI 10.1016/S0939-6411(97)00166-5 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 133KU UT WOS:000076686400004 PM 9700021 ER PT J AU Elkins, KL MacIntyre, AT Rhinehart-Jones, TR AF Elkins, KL MacIntyre, AT Rhinehart-Jones, TR TI Nonspecific early protective immunity in Francisella and Listeria infections can be dependent on lymphocytes SO INFECTION AND IMMUNITY LA English DT Article ID SALMONELLA-TYPHIMURIUM; TULARENSIS; MICE; VACCINE; STRAIN; LVS; LIPOPOLYSACCHARIDE; MONOCYTOGENES; GENERATION; RESISTANCE AB Normal mice, but not lymphocyte-deficient or B-cell-deficient mice, given a sublethal infection of Francisella tularensis LVS survive a secondary lethal challenge of more than 10,000 50% lethal doses given 3 days later. In this work, we show that similar early protection that is also strongly lymphocyte dependent operates in Listeria monocytogenes infection. Since sublethal infection with either LVS or L. monocytogenes protects against heterologous lethal challenge, this early protection is nonspecific. C1 US Food & Drug Adm, Ctr Biol Evaluat & Res, Div Bacterial Prod, Lab Mycobacteria, Rockville, MD 20852 USA. RP Elkins, KL (reprint author), US Food & Drug Adm, Ctr Biol Evaluat & Res, Div Bacterial Prod, Lab Mycobacteria, 1401 Rockville Pike,HFM 431, Rockville, MD 20852 USA. NR 15 TC 18 Z9 19 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 1998 VL 66 IS 7 BP 3467 EP 3469 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZW149 UT WOS:000074379900065 PM 9632626 ER PT J AU Nightingale, SL AF Nightingale, SL TI Advisory on need for caution with use of vacuum-assisted delivery devices SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 1 PY 1998 VL 280 IS 1 BP 12 EP 12 DI 10.1001/jama.280.1.12 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ZW145 UT WOS:000074379400006 PM 9660348 ER PT J AU Nightingale, SL AF Nightingale, SL TI Video program on guidelines for the use of antiretroviral agents in pediatric HIV infection SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 1 PY 1998 VL 280 IS 1 BP 12 EP 12 DI 10.1001/jama.280.1.12 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ZW145 UT WOS:000074379400007 PM 9660348 ER PT J AU Nightingale, SL AF Nightingale, SL TI Proposal published on dissemination of information on unapproved uses SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 1 PY 1998 VL 280 IS 1 BP 12 EP 12 DI 10.1001/jama.280.1.12 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ZW145 UT WOS:000074379400005 PM 9660348 ER PT J AU Keller, SE Sullivan, TM AF Keller, SE Sullivan, TM TI Identification of a variant of Fusarium proliferatum that hydrolyzes fumonisin B-1 SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Fusarium proliferatum; fumonisin, esterase ID EQUINE LEUKOENCEPHALOMALACIA; SECTION LISEOLA; MONILIFORME; MYCOTOXINS; STRAINS; TEMPERATURE; CULTURE; AREAS; CORN AB Fumonisins are mycotoxins produced primarily by Fusarium moniliforme and Fusarium proliferatum in corn. Normally, the fumonisins display considerable chemical stability at temperatures up to 100 degrees C at neutral pH and are stable in a pH range of 4-10 at ambient temperature. Fumonisin B-1 (FB1) can be produced in bioreactors using F. proliferatum (M5991). Recently, some bioreactor-grown cultures of F. proliferatum were found to rapidly hydrolyze FB1. Subcultures from stock frozen from these FB1-degrading variants continued to degrade FB1 when grown under the same bioreactor conditions. The initial hydrolysis was catalyzed by an esterase and resulted in the appearance of the aminopentol backbone (AP(1)) of FB1. A cell-free extract retaining the FB1 hydrolytic activity could be obtained by extraction of cell paste with 10% Triton X-100. Activity could be destroyed by heating to 60 degrees C for 5 min or by the addition of acetonitrile. C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Keller, SE (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Ave, Summit Argo, IL 60501 USA. NR 23 TC 2 Z9 2 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUL PY 1998 VL 46 IS 7 BP 2823 EP 2826 DI 10.1021/jf9800312 PG 4 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 104BV UT WOS:000074993100066 ER PT J AU Carlson, M Thompson, RD AF Carlson, M Thompson, RD TI Liquid chromatographic determination of methylxanthines and catechins in herbal preparations containing guarana SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID SEEDS; HPLC AB Herbal preparations derived from the dried seeds of guarana (Paullinia cupana) have become a popular nutritional supplement used for stimulatory purposes. Once considered a drug substance in the United States, guarana currently is classified as a food additive and dietary supplement. The pharmacological activity of guarana-containing products is primarily due to methylxanthine alkaloids, For guarana preparations, methylxanthine levels and, more significantly, the presence of several polyphenol compounds (i.e., catechins) provide phyto-chemical markers of authenticity. Methylxanthines and polyphenols are extracted from sample matrix with a heated phosphate buffer-methanol solution, the cooled extract is filtered, and the extract is injected into the liquid chromatographic (LC) system. A Nova-Pak Cls column eluted with phosphate buffer-methanol mobile phase (pH = 3.50) and monitored at 272 nm gave satisfactory resolution for the methylxanthines theobromine, theophylline, caffeine and the polyphenols (+)-catechin and (-)-epicatechin. Twenty-four products including dried seeds, dried paste, seed powders, tablets, and capsule formulations were assayed and conclusions were drawn about their authenticity, The LC system responded linearly to methylxanthines over the 100-fold range in concentration from 0.043 to 4.30 mu g/mL for theobromine and caffeine and from 0.041 to 4.10 mu g/mL for theophylline. Precision data for the 3 methylxanthines obtained from 10 different products (n = 5) gave relative standard deviation (RSD) values of 1.18-15.52% within a concentration range of 0.01-52.28 mg/g, Recoveries of methylxanthines from fortified products varied from 87.5 to 120.0%, The response for catechins was linear over a 200-fold range in concentration of 0.05-10.0 mu g/mL, Precision data from 5 products (n = 5) gave RSD values of 1.08-5.54% within a concentration range of 0.34-32.65 mg/g, Recoveries from these products ranged from 87.7 to 109.7%, Results and chromatographic profiles for 14 commercial products in solid dosage form indicate that a number of these products may not contain authentic guarana as an active ingredient or contain less than the declared quantity of guarana. The proposed procedure also was applied to 2 carbonated soft drinks and a sample of mate. C1 US FDA, Minneapolis, MN 55401 USA. RP Carlson, M (reprint author), US FDA, 200 Hennepin Ave, Minneapolis, MN 55401 USA. NR 19 TC 36 Z9 38 U1 0 U2 13 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1998 VL 81 IS 4 BP 691 EP 701 PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 101EL UT WOS:000074856600002 PM 9680692 ER PT J AU Pfenning, AP Madson, MR Roybal, JE Turnipseed, SB Gonzales, SA Hurlbut, JA Salmon, GD AF Pfenning, AP Madson, MR Roybal, JE Turnipseed, SB Gonzales, SA Hurlbut, JA Salmon, GD TI Simultaneous determination of chloramphenicol, florfenicol and thiamphenicol residues in milk by gas chromatography with electron capture detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MASS-SPECTROMETRY; ANIMALS; MUSCLES; FISH AB A gas chromatographic (GC) method is described for determining residues of chloramphenicol (CAP), florfenicol (FF), and thiamphenicol (TAP) in raw milk, with meta-nitrochloramphenicol (mCAP) as internal standard. Milk is extracted with acetonitrile, centrifuged, evaporated, reconstituted in water, and passed through a C-18 solid-phase extraction (SPE) column. The SPE column is eluted with 60% methanol, and then the eluate is evaporated and derivatized with Sylon BFT {N,O-bis(trimethylsilyl)trifluoroacetamide [BSTFA]-trimethylchlorosilane [TMCS], 99 + 1}. After derivatization, toluene is added directly to the sample, followed by water, to quench the derivatization process. After centrifugation, the organic layer is carefully removed. Analytes are determined by GC with electron capture detection (ECD). Milk was fortified with fenicols (the collective name for CAP, FF, and TAP) at 5, 10, 20, 40 and 80 ng/mL (target level = 10 ng/ml). Overall recoveries were 92, 100, and 104% for CAP, FF, and TAP, respectively. Overall interassay (between-day) variabilities were 6.1, 6.7, and 6.0% for CAP, FF, and IAP, respectively. Raw milk samples containing incurred residues of FF were also analyzed. C1 US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Denver, CO 80225 USA. RP Pfenning, AP (reprint author), US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Denver, CO 80225 USA. NR 12 TC 43 Z9 50 U1 1 U2 5 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1998 VL 81 IS 4 BP 714 EP 720 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 101EL UT WOS:000074856600005 PM 9680695 ER PT J AU Amaguana, RM Hammack, TS Andrews, WH AF Amaguana, RM Hammack, TS Andrews, WH TI Methods for the recovery of Salmonella spp. from carboxymethylcellulose gum, gum ghatti, and gelatin SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID FOODS AB Foods analyzed for Salmonella spp, by the procedure in the U.S. Food and Drug Administration's Bacteriological Analytical Manual are preenriched at a 1:9 test portion/broth ratio. Various thickening agents preenriched at this ratio become Viscous and nonpipettable after 24 h incubation at 35 degrees C. The effects of 3 factors (presence of inorganic salts, adjustment of pH, and presence of enzymes) on the viscosity of the test portion/preenrichment mixtures of various thickening agents during incubation were determined. Reduction of the viscosities of these thickening agents was accomplished as follows: carboxymethylcellulose gum, addition of cellulase to a final concentration of 0.10% in lactose broth preenrichment and incubation with no pH adjustment; gum ghatti, addition of NaCl to a final concentration of 0.10% in lactose broth preerichment and adjustment of the pH to 6.5; and gelatin, addition of papain to a final concentration of 0.10% in lactose broth preenrichment and adjustment of the pH to 6.8, With these modified preenrichments, one Salmonella spp. cell/25 g (representing an approximate most probable number value of 0.04 cell/g) was generally recovered from the thickening agents. C1 US FDA, Div Microbiol Studies, Washington, DC 20204 USA. RP Amaguana, RM (reprint author), US FDA, Div Microbiol Studies, Washington, DC 20204 USA. NR 13 TC 2 Z9 2 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 1998 VL 81 IS 4 BP 721 EP 726 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 101EL UT WOS:000074856600006 PM 9680696 ER PT J AU Stack, ME AF Stack, ME TI Analysis of fumonisin B-1 and its hydrolysis product in tortillas SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LIQUID-CHROMATOGRAPHIC DETERMINATION; FUSARIUM-PROLIFERATUM; CORN; MONILIFORME; FOODS AB Fumonisins are toxic metabolites of Fusarium moniliforme, a fungus that occurs widely in corn, Fumonisins cause leukoencephalomalacia in horses and pulmonary edema in swine and have been suggested as a possible cause of an increased incidence of neural tube defects among people living along the Texas-Mexico border. As part of an effort to determine levels of fumonisins in human food, a liquid chromatographic (LC) method was devised for determining fumonisin B-1 (FBI) and the total hydrolysis product of FB1 (HB1) in tortillas. The method uses acetonitrile-0.1M phosphate buffer (pH 3; 1 + 1)extraction, solid-phase C-18 cleanup, o-phthalaldehyde and 2-mercaptoethanol derivatization, and reversed-phase LC. Average recoveries from tortillas spiked with FB1 and HB1 at 250, 500, and 1000 ng/g were 86.5% for FB 1 and 82.6% for HB1. Tortillas (54) and masa (8) from the Texas-Mexico border were analyzed for FB1 and HB1. Average amounts of FB1 and HB1 in tortillas were 187 and 82 ng/g, respectively. Average amounts of FB1 and HB1 in masas were 262 and 64 ng/g, respectively. The results show that fumonisin B-1 and its hydrolysis product are present in tortillas consumed by a population experiencing an increased incidence of neural tube defects. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Nat Prod, Washington, DC 20204 USA. RP Stack, ME (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Nat Prod, 200 C St SW, Washington, DC 20204 USA. NR 14 TC 59 Z9 61 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 1998 VL 81 IS 4 BP 737 EP 740 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 101EL UT WOS:000074856600008 PM 9680698 ER PT J AU Luo, WH Ang, CYW Schmitt, TC Betz, JM AF Luo, WH Ang, CYW Schmitt, TC Betz, JM TI Determination of salicin and related compounds in botanical dietary supplements by liquid chromatography with fluorescence detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID FOODS; SALICYLATES AB A sensitive and reliable method is described for quantitative determination of salicin (including salicyl alcohol) and salicylic acid in botanical dietary supplements by reversed-phase liquid chromatography (LC) with wavelength-programmed fluorescence detection. One gram sample material was extracted with 20 mt aqueous phosphate buffer (pH 5.0), which was heated in an 80 degrees C water bath for 30 min. After centrifugation and cooling of the extract to room temperature, the supernatant was diluted with additional buffer. A 1 mt portion of diluted extract was mixed with 1 mt beta-glucosidase solution (2 mg/mL) and incubated for 40 min in a 37 degrees C water bath. The extract was passed through a 0.45 mu m syringe filter and analyzed by LC. Limits of quantitation for salicin and salicylic acid were 20 and 1 mu g/g, respectively. Recoveries from samples fortified with salicin at 20, 100, and 1000 mu g/g and with salicylic acid at 5, 20, and 50 mu g/g ranged from 85 to 110%, with standard deviations less than 7%. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol & Chem, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Appl Nutr, Div Nat Prod, Washington, DC 20204 USA. RP Ang, CYW (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol & Chem, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 9 TC 5 Z9 5 U1 2 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 1998 VL 81 IS 4 BP 757 EP 762 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 101EL UT WOS:000074856600011 PM 9680701 ER PT J AU Horwitz, W AF Horwitz, W TI Uncertainty - A chemist's view SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT Royal-Society-of-Chemistry Meeting on Uncertainty CY DEC 08, 1997 CL ROYAL SOC CHEM, LONDON, ENGLAND HO ROYAL SOC CHEM ID RELIABILITY AB Complete characterization of the performance of analytical methods requires an evaluation of the halo of uncertainty bracketing the reported result. Achieving a satisfactory estimate of this uncertainty is more important than how this estimate is produced. Enumeration of all conceivable error components-the so-called error budget approach-is one way to estimate the uncertainty, but it is not the only way. In fact, when applied to analytical chemistry this approach is likely to (1) overlook important variables and double count others, (2) avoid considering unknown and unknowable interactions and interferences, and (3) adjust for missing variables with an uncontrollable "Type B" component. The problem is one of experimental design, Alternative and more efficient ways of estimating uncertainty in analytical chemistry include the Youden ruggedness procedure, accompanied by a bonus of optimization, and the all-encompassing interlaboratory method-performance trial. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Horwitz, W (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 17 TC 28 Z9 28 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 JUL-AUG PY 1998 VL 81 IS 4 BP 785 EP 794 PG 10 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 101EL UT WOS:000074856600014 PM 9680703 ER PT J AU McClure, FD AF McClure, FD TI Repeatability and reproducibility estimates from collaborative studies based on total concentration of trace analytes SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB In the process of validating a given analytical method for the total concentration of a trace analyte, the precision indicators, repeatability and reproducibility, are obtained from a collaborative study of the method based on a standard one-way completely randomized model. This report discusses the shortcomings of the statistical models used in such studies, defines the component makeup for estimates of the repeatability and reproducibility variances based on these models, and considers suggestions offered as new policy regarding method performance based on total concentration. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Div Math, Washington, DC 20204 USA. RP McClure, FD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Div Math, 200 C St SW, Washington, DC 20204 USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1998 VL 81 IS 4 BP 795 EP 801 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 101EL UT WOS:000074856600015 PM 9680704 ER PT J AU Madson, MR Thompson, RD AF Madson, MR Thompson, RD TI Determination of methylmercury in food commodities by gas-liquid chromatography with atomic emission detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID FDA TOTAL DIET; METHYL MERCURY; FISH; PESTICIDES; CHEMICALS; SHELLFISH; ELEMENTS AB A method was developed for determining methylmercury in various food commodities. The organomercurial species was converted to methyl-mercuric chloride by treatment of a sample homogenized with 1.8M HCl. The resulting chlorinated species was eluted from a Celite 545-sample homogenate column with methylene chloride. The eluate was treated with stannic chloride, and the analyte was isolated from coextractives by using a wide-bore capillary column with microwave-induced plasma atomic emission detection. The method was applied to both high- and low-moisture commodities during analysis of 32 samples of grains, cereal products, fruits, and vegetables. Methylmercury was found at trace levels (i.e., between a signal-to-noise ratio of 3:1 and 10:1) and up to 0.85 ppb. Recoveries of added methylmercury ranged from 70.0 to 114.0%. Limits of quantitation and detection were 0.63 and 0.24 pg an column, respectively, corresponding to 0.30 and 0.11 ng Hg/g sample for a 40 g sample treated according to the method. C1 US FDA, Minneapolis, MN 55401 USA. RP Madson, MR (reprint author), US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Denver, CO 80225 USA. NR 22 TC 11 Z9 11 U1 0 U2 4 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1998 VL 81 IS 4 BP 808 EP 816 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 101EL UT WOS:000074856600017 PM 9680706 ER PT J AU Stewart, D Gendel, SM AF Stewart, D Gendel, SM TI Specificity of the BAX polymerase chain reaction system for detection of the foodborne pathogen Listeria monocytogenes SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB The polymerase chain reaction (PCR) can be used for rapid and specific detection of foodborne pathogens. One commercial kit, the Qualicon BAX system uses PCR to detect Listeria monocytogenes in enrichment cultures derived from food and environmental samples. The specificity and sensitivity of the BAX system for detecting L. monocytogenes were characterized by using both pure and mixed cell cultures, and optimal conditions for production of cell lysates were determined. The BAX system was highly specific for L. monocytogenes, and no interference was seen in the presence of either other Listeria species or microbes from other genera. The assay detected L. monocytogenes at 10(5)-10(6) colony-forming units/mL. This sensitivity is adequate for detecting viable cells after enrichment but prevents false-positive signals from nonviable cells. C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Gendel, SM (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer, Summit Argo, IL 60501 USA. FU FDA HHS [FD000431] NR 8 TC 24 Z9 25 U1 2 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 1998 VL 81 IS 4 BP 817 EP 822 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 101EL UT WOS:000074856600018 PM 9680707 ER PT J AU Munns, RK Turnipseed, SB Pfenning, AP Roybal, JE Holland, DC Long, AR Plakas, SM AF Munns, RK Turnipseed, SB Pfenning, AP Roybal, JE Holland, DC Long, AR Plakas, SM TI Liquid chromatographic determination of flumequine, nalidixic acid, oxolinic acid, and piromidic acid residues in catfish (Ictalurus punctatus) SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID CULTURED FISH; ANTIBACTERIALS; FLUORESCENCE; EXTRACTION; METABOLITE; TISSUES AB A peer-verified, liquid chromatographic (LC) method for simultaneous determination of residues of flumequine (FLU), nalidixic acid (NAL), oxolinic acid (OXO), and piromidic acid (PIR) in catfish muscle is presented. Sample workup involves homogenizing tissue with acetone, defatting with hexane, and extracting quinolones into chloroform. Sample is purified further by partitioning into base and then subsequently back-extracting into chloroform after acidifying the aqueous phase. After solvent is evaporated, the residue is diluted with mobile phase, and analytes are introduced into an LC system where separations are made with a 5 mu m, reversed-phase polymer column and an isocratic, buffered acetonitrile-tetrahydrofuran mobile phase. Determinations are made by UV detection at 280 nm for PIR and by fluorescence detection (excitation at 325 excitation and emission at 365 nm) for the other 3 analytes. Each quinolone was used to fortify catfish muscle at 5, 10, 20, 40, and 80 ng/g. The following recoveries and relative standard deviation (RSD) values represent an average of the 5 levels for each analyte: FLU, 79.7% (RSD = 5.7%); OXO, 80.8% (RSD = 6.3%); PIR, 75.0% (RSD = 5.9%); and NAL, 87.1% (RSD = 10%). Assay of 5 levels (base incurred catfish, plus 4 dilutions with control catfish) of catfish muscle incurred with the 4 quinolones gave the following averages: FLU: base, 198 ng/g (RSD = 2.3%); dilutions, 98.0 ng/g (RSD = 4.2%), 61.6 ng/g (RSD = 4.4%), 21.6 ng/g (RSD = 2.8%), 9.24 ng/g (RSD = 8.7%); OXO, base, 257 ng/g (RSD=6.9%); dilutions, 146 ng/g (RSD = 5.5%), 95.0 ng/g (RSD = 4.1%), 30.7 ng/g (RSD = 3.8%), 13.7 ng/g (RSD = 4.6%); PIR, base, 22.1 ng/g (RSD = 4.2%); dilutions, 13.7 ng/g (RSD = 6.7%), 6.49 ng/g (RSD = 15%), 2.65 ng/g (RSD = 15%); and NAL, base, 75.1 ng/g (RSD = 3.8%); dilutions, 42.3 ng/g (RSD = 5.1%), 24.1 ng/g (RSD = 6.3%), 8.59 ng/g (RSD = 4.8%). A second multiresidue analysis of the 4 quinolones was performed by an outside analyst. Average recoveries from catfish fortified at 5, 10, 20, and 40 ng/g were FLU, 75.9% (RSD = 4.0%); OXO, 84.0% (RSD = 5.5%); NAL, 85.6% (RSD = 8.9%); and PIR, 66.2% (RSD = 8.7%). C1 US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Denver, CO 80225 USA. RP Munns, RK (reprint author), US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, POB 25087,Denver Dist, Denver, CO 80225 USA. NR 15 TC 16 Z9 16 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 JUL-AUG PY 1998 VL 81 IS 4 BP 825 EP 838 PG 14 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 101EL UT WOS:000074856600020 PM 9680708 ER PT J AU Trucksess, MW Page, SW Wood, GE Cho, TH AF Trucksess, MW Page, SW Wood, GE Cho, TH TI Determination of deoxynivalenol in white flour, whole wheat flour, and bran by solid-phase extraction liquid chromatography: Interlaboratory study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID TRICHOTHECENE AB A liquid chromatographic (LC) method for determining deoxynivalenol (DON) in white flour whole wheat flour, and bran at or above the U.S. Food and Drug Administration advisory level of 1 mu g/g was evaluated by an interlaboratory study. Test samples of processed wheat (flour and bran) were extracted by blending with acetonitrile-water (84 + 16). Extracts were filtered and passed through a solid-phase extraction (SPE) column. The eluate was then chromatographed on a reversed-phase LC column with a water-methanol gradient. DON was measured at 220 nm. Naturally contaminated white flour, whole wheat flour, and bran samples and spiking solutions of DON to be added to the 3 commodities at 0.5, 1.0, and 2.0 mu g/g were sent to 4 collaborators in Kansas, Louisiana, Missouri, and Washington states. Three collaborators completed the study. Average recoveries of DON from the 3 commodities spiked at 0.5, 1.0, and 2.0 mu g/g were 94, 87, and 97%, respectively. Within-laboratory relative standard deviations for repeatability (RSDr) ranged from 3.1 to 21.7% and between-laboratory relative standard deviations for reproducibility (RSDR) ranged from 10.8 to 38.7%. On the basis of the results of this study, the SPE/LC method for DON in white flour, whole wheat flour, and bran was adopted as a peer-verified method by AOAC INTERNATIONAL. C1 US FDA, Div Nat Prod, Washington, DC 20204 USA. US FDA, Div Programs & Enforcement Policy, Washington, DC 20204 USA. Seoul Publ Hlth & Environm Inst, Seoul, South Korea. RP Trucksess, MW (reprint author), US FDA, Div Nat Prod, Washington, DC 20204 USA. NR 14 TC 38 Z9 41 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 1998 VL 81 IS 4 BP 880 EP 886 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 101EL UT WOS:000074856600026 PM 9680714 ER PT J AU Tetko, IV Villa, AEP Aksenova, TI Zielinski, WL Brower, J Collantes, ER Welsh, WJ AF Tetko, IV Villa, AEP Aksenova, TI Zielinski, WL Brower, J Collantes, ER Welsh, WJ TI Application of a pruning algorithm to optimize artificial neural networks for pharmaceutical fingerprinting SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article AB The present study investigates an application of artificial neural networks (ANNs) for use in pharmaceutical fingerprinting. Several pruning algorithms were applied to decrease the dimension of the input parameter data set. A localized fingerprint region was identified within the original input parameter space from which a subset of input parameters was extracted leading to enhanced ANN performance. The present results confirm that ANNs can provide a fast, accurate, and consistent methodology applicable to pharmaceutical fingerprinting. C1 Univ Lausanne, Inst Physiol, Lab Neuroheurist, CH-1005 Lausanne, Switzerland. Inst Bioorgan & Petr Chem, Dept Biomed Applicat, UA-253660 Kiev 660, Ukraine. Inst Appl Syst Anal, UA-252056 Kiev, Ukraine. US FDA, Div Drug Anal, St Louis, MO 63101 USA. Univ Missouri, Dept Chem, St Louis, MO 63121 USA. Univ Missouri, Ctr Mol Elect, St Louis, MO 63121 USA. RP Welsh, WJ (reprint author), Univ Lausanne, Inst Physiol, Lab Neuroheurist, Rue Bugnon 7, CH-1005 Lausanne, Switzerland. RI Villa, Alessandro/G-6220-2011; Tetko, Igor/B-1540-2010 OI Villa, Alessandro/0000-0002-4684-0027; Tetko, Igor/0000-0002-6855-0012 NR 26 TC 15 Z9 16 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD JUL-AUG PY 1998 VL 38 IS 4 BP 660 EP 668 DI 10.1021/ci970439j PG 9 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 103UN UT WOS:000074976400016 PM 9691475 ER PT J AU Tong, W Lowis, DR Perkins, R Chen, Y Welsh, WJ Goddette, DW Heritage, TW Sheehan, DM AF Tong, W Lowis, DR Perkins, R Chen, Y Welsh, WJ Goddette, DW Heritage, TW Sheehan, DM TI Evaluation of quantitative structure-activity relationship methods for large-scale prediction of chemicals binding to the estrogen receptor SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article ID MOLECULAR-FIELD ANALYSIS; IDENTIFICATION; REGRESSION; AFFINITIES; SELECTION AB Three different QSAR methods, Comparative Molecular Field Analysis (CoMFA), classical QSAR (utilizing the CODESSA program), and Hologram QSAR (HQSAR), are compared in.terms of their potential for screening large data sets of chemicals as endocrine disrupting compounds (EDCs). While CoMFA and CODESSA (Comprehensive Descriptors for Structural and Statistical Analysis) have been commercially available for some time, HQSAR is a novel QSAR technique. HQSAR attempts to correlate molecular structure with biological activity for a series of compounds using molecular holograms constructed from counts of sub-structural molecular fragments. In addition to using r(2) and q(2) (cross-validated r(2)) in assessing the statistical quality of QSAR models, another statistical parameter was defined to be the ratio of the standard error to the activity range. The statistical quality of the QSAR models constructed using CoMFA and HQSAR techniques were comparable and were generally better than those produced with CODESSA. It is notable that only 2D-connectivity, bond and elemental atom-type information were considered in building HQSAR models. Since HQSAR requires no conformational analysis or structural alignment, it is straightforward to use and lends itself readily to the rapid screening of large numbers of compounds. Among the QSAR methods considered, HQSAR appears to offer many attractive features, such as speed, reproducibility and ease of use, which portend its utility for prioritizing large numbers of potential EDCs for subsequent toxicological testing and risk assessment. C1 ROW Sci Inc, Jefferson, AR 72079 USA. Univ Missouri, Dept Chem, St Louis, MO 63121 USA. Univ Missouri, Ctr Mol Elect, St Louis, MO 63121 USA. Tripos Inc, St Louis, MO 63144 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Tong, W (reprint author), ROW Sci Inc, Jefferson, AR 72079 USA. NR 34 TC 173 Z9 176 U1 0 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD JUL-AUG PY 1998 VL 38 IS 4 BP 669 EP 677 DI 10.1021/ci980008g PG 9 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 103UN UT WOS:000074976400017 PM 9722424 ER PT J AU Koller, EA Green, L Gertner, JM Bost, M Malozowski, SN AF Koller, EA Green, L Gertner, JM Bost, M Malozowski, SN TI Retinal changes mimicking diabetic retinopathy in two nondiabetic, growth hormone-treated patients SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 79th Annual Meeting of the Endocrine-Society CY JUN 10-14, 1997 CL MINNEAPOLIS, MN SP Endocrine Soc ID FACTOR-I; ENDOTHELIAL-CELLS; INSULIN; NEOVASCULARIZATION; PROLIFERATION AB A role for GH in the pathogenesis of diabetic retinopathy has long been postulated. Previous clinical studies, however, have been confounded by hyperglycemia. We have identified 2 cases of retinopathy associated with exogenous GH therapy in nondiabetic patients. Cases were identified through the MedWatch drug surveillance system of the U.S. Food and Drug Administration. Causality by concomitant medications was excluded by a search of the literature and the FDA data base. The first patient, an obese, 31-yr-old male with traumatic hypothalamic injury, presented with nonproliferative retinopathy and macular edema, resulting in decreased visual acuity (OD 20/40 -1; OS count fingers), which required laser surgery. Human GH had been initiated at 0.009 mg/kg day, 14 months earlier, and titrated to 0.017 mg/kg day. The second patient, a nonobese, Il-yr-old girl receiving GH for the management of short stature in Turner's Syndrome, presented with neovascularization. GH doses were 0.033 mg/kg day for the first 17 months and 0.043 mg/kg.day for the following 5 months. Cumulative laboratory and clinical observations suggest that GH and related peptides have a role in retinal pathology independent of the degree of glucose tolerance. C1 US FDA, CDER, Rockville, MD 20857 USA. New York Hosp, Cornell Med Ctr, New York, NY 10021 USA. Cent Univ Hosp, Dept Pediat, Grenoble 09, France. RP Koller, EA (reprint author), US FDA, CDER, Parklawn Bldg,HFD 510,Room 14B04,5600 Fishers Lan, Rockville, MD 20857 USA. EM kollere@cder.fda.gov NR 26 TC 28 Z9 28 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 1998 VL 83 IS 7 BP 2380 EP 2383 DI 10.1210/jc.83.7.2380 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZX855 UT WOS:000074562200027 PM 9661613 ER PT J AU Niu, MT Bethel, J Holodniy, M Standiford, HC Schnittman, SM AF Niu, MT Bethel, J Holodniy, M Standiford, HC Schnittman, SM CA DATRI 002 Study Grp TI Zidovudine treatment in patients with primary (Acute) human immunodeficiency virus type 1 infection: A randomized, double-blind, placebo-controlled trial SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT XIth International Conference on AIDS CY JUL 07-13, 1996 CL VANCOUVER, CANADA ID PRIMARY HIV-1 INFECTION; T-LYMPHOCYTE ACTIVITY; NEUTRALIZING ANTIBODIES; IMMUNE-RESPONSE; ANTIRETROVIRAL THERAPY; CUBIC MILLIMETER; VIRAL DYNAMICS; CELL COUNTS; VIREMIA; PLASMA AB A multicenter, double-blind, placebo-controlled trial randomized 28 patients with primary (acute) human immunodeficiency virus (HIV)-1 infection (PHI) to receive zidovudine, 1000 mg daily, or placebo for 24 weeks. At week 48, compared with placebo patients, zidovudine-treated patients had significantly higher CD4 cell counts (zidovudine, 666 cells/mm(3); placebo, 362; P =.004) and lower peripheral blood mononuclear cell (PBMC) culture titers (zidovudine, 0.58 log infectious units per million cells; placebo, 1.68; P =.02) but no difference in plasma RNA (zidovudine, 3.93 log copies/mL; placebo, 4.00; P =.83). Serious adverse events and minor clinical events were infrequent and comparable in both arms. There were two deaths: 1 patient died of sepsis and renal disease (zidovudine arm), and 1 patient died of sepsis and tension pneumothorax (placebo arm). Six months of high-dose zidovudine initiated during PHI results in higher CD4 cell counts and lower PBMC culture titers but no difference in plasma HIV-1 RNA. Further studies with more potent antiretroviral combination therapies ape warranted. C1 NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. WESTAT Corp, Rockville, MD 20850 USA. Vet Adm Med Ctr, Inst Human Virol, Baltimore, MD 21218 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. VA Palo Alto Hlth Care Syst, AIDS Res Ctr, Palo Alto, CA USA. RP Niu, MT (reprint author), US FDA, Div Biostat & Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-210, Rockville, MD 20852 USA. EM niu@a1.cber.fda.gov FU NIAID NIH HHS [AI-15123] NR 77 TC 29 Z9 29 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL PY 1998 VL 178 IS 1 BP 80 EP 91 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZV943 UT WOS:000074357900011 PM 9652426 ER PT J AU Angulo, FJ Getz, J Taylor, JP Hendricks, KA Hatheway, CL Barth, SS Solomon, HM Larson, AE Johnson, EA Nickey, LN Ries, AA AF Angulo, FJ Getz, J Taylor, JP Hendricks, KA Hatheway, CL Barth, SS Solomon, HM Larson, AE Johnson, EA Nickey, LN Ries, AA TI Large outbreak of botulism: The hazardous baked potato SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 35th Interscience Conference on Antimicrobial Agents and Chemotherapy CY SEP 17-22, 1995 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Microbiol ID UNITED-STATES; A BOTULISM AB In April 1994, the largest outbreak of botulism in the United States since 1978 occurred in El Paso, Texas. Thirty persons were affected; 4 required mechanical ventilation. All ate food from a Greek restaurant. The attack rate among persons who ate a potato-based dip was 86% (19/22) compared with 6% (11/176) among persons who did not eat the dip (relative risk [RR] = 13.8; 95% confidence interval [CI], 7.6-25.1). The attack rate among persons who ate an eggplant-based dip was 67% (6/9) compared with 132 (24/189) among persons who did not (RR = 5.2; 95% CI, 2.9-9.5), Botulism toxin type A was detected from patients and in both dips. Toxin formation resulted from holding aluminum foil-wrapped baked potatoes at room temperature, apparently for several days, before they were used in the dips. Consumers should be informed of the potential hazards caused by holding foil-wrapped potatoes at ambient temperatures after cooking. C1 Ctr Dis Control & Prevent, Foodborne & Diarrheal Dis Branch, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Texas Dept Hlth, Bur Communicable Dis Control, Austin, TX 78756 USA. Texas Dept Hlth, Bur Labs, Austin, TX 78756 USA. El Paso City Cty Hlth & Environm Dist, El Paso, TX USA. US FDA, Div Microbiol Studies, Washington, DC 20204 USA. Univ Wisconsin, Food Res Inst, Madison, WI 53706 USA. RP Angulo, FJ (reprint author), Ctr Dis Control & Prevent, Foodborne & Diarrheal Dis Branch, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, Mailstop A-38,1600 Clifton Rd, Atlanta, GA 30333 USA. NR 17 TC 47 Z9 47 U1 0 U2 9 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL PY 1998 VL 178 IS 1 BP 172 EP 177 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZV943 UT WOS:000074357900022 PM 9652437 ER PT J AU Vickery, MCL Smith, AL DePaola, A Jones, DD Steffan, RJ Bej, AK AF Vickery, MCL Smith, AL DePaola, A Jones, DD Steffan, RJ Bej, AK TI Optimization of the arbitrarily-primed polymerase chain reaction (AP-PCR) for intra-species differentiation of Vibrio vulnificus SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE vibrio vulnificus; polymerase chain reaction; DNA fingerprint; AP-PCR; shellfish ID FIELD GEL-ELECTROPHORESIS; GULF-COAST; OYSTERS; IDENTIFICATION; SALMONELLA; VIRULENCE AB Optimal parameters were established for obtaining unique and reproducible DNA fingerprints of selected clinical and environmental isolates of Vibrio vulnificus by the arbitrarily primed polymerase chain reaction (AP-PCR). Genomic DNA from selected strains was subjected to AP-PCR amplification using a single, arbitrarily selected oligonucleotide primer, R-PSE420. Amplified DNA was analyzed by agarose gel electrophoresis and ProRFLP(R) computer software. Reproducibility of the fingerprint was dependent upon the concentrations of the purified genomic DNA, MgCl2 and oligonucleotide primer, and on PCR cycling parameters. Using 1 mu g of purified genomic DNA, 2.5 mM MgCl2, 1.04 mu M of R-PSE420 oligonucleotide primer and thermal cycling protocols with stepwise increases in the annealing temperatures, DNA fingerprints which were reproducible and free of primer artifacts were generated. By following the optimized AP-PCR amplification protocol, unique DNA fingerprint profiles for each V. vulnificus strain tested were produced. These AP-PCR generated unique DNA fingerprint profiles can be used in the identification, and investigation of the distribution and diversity of various strains of V. vulnificus in bivalve shellfish and their surrounding waters. (C) 1998 Elsevier Science B.V. C1 Univ Alabama, Dept Biol, Birmingham, AL 35294 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. Envirogen Inc, Lawrenceville, NJ 08648 USA. RP Bej, AK (reprint author), Univ Alabama, Dept Biol, 1300 Univ Blvd, Birmingham, AL 35294 USA. NR 41 TC 13 Z9 13 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD JUL PY 1998 VL 33 IS 2 BP 181 EP 189 DI 10.1016/S0167-7012(98)00056-6 PG 9 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 112LU UT WOS:000075496800010 ER PT J AU Jacob, RA Gretz, DM Taylor, PC James, SJ Pogribny, IP Miller, BJ Henning, SM Swendseid, ME AF Jacob, RA Gretz, DM Taylor, PC James, SJ Pogribny, IP Miller, BJ Henning, SM Swendseid, ME TI Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Experimental Biology 97 Conference CY APR 06-10, 1997 CL NEW ORLEANS, LOUISIANA DE folic acid; homocysteine; methylation; DNA; humans ID TERM DIETARY-FOLATE; FOLIC-ACID; NONPREGNANT WOMEN; GROUP RESTRICTION; DEFICIENT RATS; HEALTHY-MEN; POOLS; HYPOMETHYLATION; METHIONINE; METABOLISM AB To determine the human folate requirement on the basis of changes in biochemical pathways, we studied the effect of controlled folate intakes on plasma homocysteine and lymphocyte DNA methylation and deoxynucleotide content in healthy postmenopausal women. Eight women (49-63 y of age) were housed in a metabolic unit and fed a low folate diet containing 56 mu g/d of folate for 91 d. Folate intake was varied by supplementing 55-460 mu g/d of folic acid (pteroylglutamic acid) to the diet to provide total folate intake periods of 5 wk at 56 mu g/d, 4 wk at 111 mu g/d and 3 wk at 286-516 mu g/d. A subclinical folate deficiency with decreased plasma folate was created during the first two periods. This resulted in significantly elevated plasma homocysteine and urinary malondialdehyde, and lymphocyte DNA hypomethylation. The folate depletion also resulted in an increased ratio of dUTP/dTTP in mitogen-stimulated lymphocyte DNA and decreased lymphocyte NAD, changes suggesting misincorporation of uracil into DNA and increased DNA repair activity. The DNA hypomethylation was reversed with 286-516 mu g/d of folate repletion, whereas the elevated homocysteine decreased with 516 but not 286 mu g/d of folate. The results indicate that marginal folate deficiency may alter DNA composition and that the current RDA of 180 mu g/d may not be sufficient to maintain low plasma homocysteine concentrations of some postmenopausal women. C1 USDA ARS, Western Human Nutr Res Ctr, San Francisco, CA 94129 USA. US FDA, Natl Ctr Toxicol Res, Div Nutr Toxicol, Jefferson, AR 72079 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Jacob, RA (reprint author), USDA ARS, Western Human Nutr Res Ctr, POB 29997, San Francisco, CA 94129 USA. NR 48 TC 325 Z9 338 U1 0 U2 8 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JUL PY 1998 VL 128 IS 7 BP 1204 EP 1212 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZY293 UT WOS:000074605600022 PM 9649607 ER PT J AU Levy, AS Fein, SB AF Levy, AS Fein, SB TI Consumers' ability to perform tasks using nutrition labels SO JOURNAL OF NUTRITION EDUCATION LA English DT Article ID INFORMATION; EDUCATION; FORMATS AB Consumers' ability to perform common nutrition label use tasks and specific task components, which revealed the effect of prior knowledge, were analyzed for relationships with demographic characteristics, label reading, and health status. Data were from a mall intercept experimental study. Most consumers (78%) accurately compared two products, 58% accurately evaluated nutrient level claims, 45% comprehensively balanced nutrients over a daily diet, and 20% accurately calculated the contribution of a single food to a daily diet, a task that required complex math. The subjects wine performed significantly poorer were over 55 years of age, nonwhite, and less educated than those who performed best. Not reading food labels and having a diet-related health condition were also related to poorer performance. Task component analysis showed that all types of subjects shared the same response tendencies when making nutrition judgments. The findings suggest that dietary guidance for consumers will be more effective if it does not require quantitative tasks but relies instead on tasks that are easier for consumers. C1 US FDA, Consumer Studies Branch, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Fein, SB (reprint author), US FDA, Consumer Studies Branch, Ctr Food Safety & Appl Nutr, HFS 727,200 C St SW, Washington, DC 20204 USA. NR 56 TC 47 Z9 48 U1 1 U2 11 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0022-3182 J9 J NUTR EDUC JI J. Nutr. Educ. PD JUL-AUG PY 1998 VL 30 IS 4 BP 210 EP 217 DI 10.1016/S0022-3182(98)70321-8 PG 8 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 109VU UT WOS:000075345300006 ER PT J AU Stern, RS Mills, DK Krell, K Zmudzka, BZ Beer, JZ AF Stern, RS Mills, DK Krell, K Zmudzka, BZ Beer, JZ TI HIV-positive patients differ from HIV-negative patients in indications for and type of UV therapy used SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ULTRAVIOLET-B PHOTOTHERAPY; PUVA; INFECTION; ACTIVATION; PSORIASIS; RADIATION; PSORALEN; PREVALENCE; PROMOTER AB Background: Treatments using UV, UVB, or oral psoralen and UVA (PUVA) have been advocated for the care of HIV-infected persons with skin diseases. Concerns about the safety of these treatments exist. Objective: We attempted to determine the characteristics of HIV infected persons receiving UV therapy and establish the reasons for and type of treatment administered. Methods: During two 2-week periods, we prospectively ascertained basic information on all patients treated at 40 phototherapy clinics and detailed clinical information on patients known to be infected with HIV. Results: We identified 3716 persons receiving UV therapy, including 311 known to be infected with HIV. When compared with patients not known to be infected with HIV, HIV-positive patients were significantly more likely to be treated with UVB rather than PUVA and were more likely to be treated for pruritic conditions rather than psoriasis. Conclusion: There were great variations in the relative reliance on WE and PUVA among centers. There appears to be no agreement as to which type of UV therapy is optimal for patients infected with HIV. Most patients known to the treating clinician to be HIV positive are in the advanced stages of HIV disease. The number of persons with less advanced HIV disease receiving treatment remains unquantified but may be even more clinically important. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. US FDA, Rockville, MD 20857 USA. RP Stern, RS (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA. RI Mills, DeEtta/G-8532-2015 OI Mills, DeEtta/0000-0002-9977-7834 NR 32 TC 9 Z9 10 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUL PY 1998 VL 39 IS 1 BP 48 EP 55 DI 10.1016/S0190-9622(98)70401-3 PG 8 WC Dermatology SC Dermatology GA ZY387 UT WOS:000074616200005 PM 9674397 ER PT J AU Cassetti, MC Merchlinsky, M Wolffe, EJ Weisberg, AS Moss, B AF Cassetti, MC Merchlinsky, M Wolffe, EJ Weisberg, AS Moss, B TI DNA packaging mutant: Repression of the vaccinia virus A32 gene results in noninfectious, DNA-deficient, spherical, enveloped particles SO JOURNAL OF VIROLOGY LA English DT Article ID TEMPERATURE-SENSITIVE MUTANTS; ESCHERICHIA-COLI; PSEUDORABIES VIRUS; TERMINAL REPEATS; RNA-POLYMERASE; LAC REPRESSOR; MORPHOGENESIS; PROTEIN; GENOME; TRANSCRIPTION AB The vaccinia virus A32 open reading frame was predicted to encode a protein with a nucleoside triphosphate-binding motif and a mass of 34 kDa, To investigate the role of this protein, we constructed a mutant in which the original A32 gene was replaced by an inducible copy. The recombinant virus, vA32i, has a conditional lethal phenotype: infectious virus formation was dependent on isopropyl-beta-D-thiogalactopyranoside (IPTG), Under nonpermissive conditions, the mutant synthesized early-and late-stage viral proteins, as well as viral DNA that was processed into unit-length genomes, Electron microscopy of cells infected in the absence of IPTG revealed normal-appearing crescents and immature virus particles but very few with nucleoids, Instead of brick-shaped mature particles with defined core structures, there were numerous electron-dense, spherical particles. Some of these spherical particles were wrapped with cisternal membranes, analogous to intracellular and extracellular enveloped virions. Mutant viral particles, purified by sucrose density gradient centrifugation, had low infectivity and transcriptional activity, and the majority were spherical and lacked DNA, Nevertheless, the particle preparation contained representative membrane proteins, cleaved and uncleaved core proteins, the viral RNA polymerase, the early transcription factor and several enzymes, suggesting that incorporation of these components is not strictly coupled to DNA packaging. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. US Food & Drug Adm, Ctr Biol Evaluat & Res, Lab DNA Viruses, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr MSC 0445, Bethesda, MD 20892 USA. EM bmoss@nih.gov NR 53 TC 63 Z9 67 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1998 VL 72 IS 7 BP 5769 EP 5780 PG 12 WC Virology SC Virology GA ZU089 UT WOS:000074160500052 PM 9621036 ER PT J AU Feigelstock, D Thompson, P Mattoo, P Kaplan, GG AF Feigelstock, D Thompson, P Mattoo, P Kaplan, GG TI Polymorphisms of the hepatitis A virus cellular receptor 1 in African green monkey kidney cells result in antigenic variants that do not react with protective monoclonal antibody 190/4 SO JOURNAL OF VIROLOGY LA English DT Article ID POLIOVIRUS AB Monoclonal antibody (MAb) 190/4 blocks binding of hepatitis A virus (HAV) to the HAV cellular receptor 1 (havcr-1) and protects African green monkey kidney (AGMK) clone GL37 cells (GL37 cells) against HAV infection. BS-C-1 and CV-1 cells, two widely used AGMK cell lines, did not react with MAb 190/4 but expressed havcr-1, as judged by Western blot analysis, The cDNA coding for havcr-1 was amplified from BS-C-1 and CV-1 total cellular RNA by reverse transcription-PCR. Alignment of the amino acid sequences inferred from the cDNA nucleotide sequences showed that BS-C-1 and CV-1 havcr-1 differed from GL37 havcr-1 by having two substitutions in the Cys-rich region, N48H and K108Q, and 10 to 11 additional substitutions plus the insertion of 18 to 22 amino acids in the mucin-like region. Studies with chimeras of GL37 havcr-1 and BS-C-1 havcr-1 showed that the K108Q substitution was responsible for the lack of reaction of MAb 190/4 with BS-C-1 and CV-1 cells. Binding studies indicated that HAV bound to dog cell transfectants expressing the BS-C-1 havcr-1 as well as the GL37/BS-C-1 havcr-1 chimeras. These results indicate that antigenic variants of havcr-1 are expressed in AGMK cells and that binding of HAV to these havcr-1 variants tolerates changes in protective epitope 190/4. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Hepatitis Viruses, Bethesda, MD 20892 USA. RP Kaplan, GG (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Hepatitis Viruses, 8800 Rockville Pike,Bldg 29 A-NIH,Room 1D10,HFM-4, Bethesda, MD 20892 USA. NR 10 TC 22 Z9 23 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1998 VL 72 IS 7 BP 6218 EP 6222 PG 5 WC Virology SC Virology GA ZU089 UT WOS:000074160500109 PM 9621093 ER PT J AU Klinman, DM Conover, J Bloom, ET Weiss, W AF Klinman, DM Conover, J Bloom, ET Weiss, W TI Immunogenicity and efficacy of a DNA vaccine in aged mice SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID CD4+ T-CELLS; CIRCUMSPOROZOITE PROTEIN; PLASMID DNA; OLD MICE; INTERFERON-GAMMA; GENE-EXPRESSION; VIRUS; YOUNG; INFLUENZA; CYTOKINE AB The immunogenicity and protective efficacy of a DNA vaccine encoding the circumsporozoite protein of the Plasmodium yoelii malaria parasite was evaluated in young (2 months) versus aged (>26 months) BALB/c mice. The primary and secondary humoral immune response of aged mice was 19- and 7-fold lower, respectively than that of similarly treated young animals (p <.01). Cytotoxic T lymphocyte activity in aged mice, was also lower than ill younger animals. The vaccine response of aged animals was characterized by a 6-fold increase in interleukin-4 and a 3-fold increase ill interferon-gamma (IFN-gamma) secreting cells, whereas in :young animals immunization only stimulated the production of the type I cytokine IFN-gamma. Overall, 80% of young vaccinated mice were protected from subsequent challenge with live malaria sporozoites whereas only 40% of aged mice were protected. These results are the first to demonstrate that DNA vaccination induces less effective immunity in aged than young animals. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Div Viral Prod, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Cellular Immunol Lab, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. USN, Med Res Inst, Malaria Program, Bethesda, MD USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Div Viral Prod, Bldg 29A,Room 3 D 10 HFM 454, Bethesda, MD 20892 USA. NR 38 TC 11 Z9 11 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 1998 VL 53 IS 4 BP B281 EP B286 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 101QR UT WOS:000074880100008 PM 18314558 ER PT J AU Deatly, AM Taffs, RE McAuliffe, JM Nawoschik, SP Coleman, JW McMullen, G Weeks-Levy, C Johnson, AJ Racaniello, VR AF Deatly, AM Taffs, RE McAuliffe, JM Nawoschik, SP Coleman, JW McMullen, G Weeks-Levy, C Johnson, AJ Racaniello, VR TI Characterization of mouse lines transgenic with the human poliovirus receptor gene SO MICROBIAL PATHOGENESIS LA English DT Article DE human poliovirus receptor; transgenic mouse lines; TGM-PRG-1 and TGM-PRG-3; poliovirus neurovirulence; poliovirus susceptibility; receptor dosage ID AMINO-ACID-RESIDUES; CELLULAR RECEPTOR; IMMUNOGLOBULIN SUPERFAMILY; NEUROVIRULENCE TEST; MOLECULAR-CLONING; ANTIGENIC SITE; TISSUE TROPISM; EXPRESSION; MICE; VIRUS AB Two mouse lines transgenic with the human poliovirus receptor gene (PVR), TGM-PRG-1 and TGM-PRG-3, were characterized to determine whether transgene copy number and PVR expression levels influence susceptibility to poliovirus. The mouse lines have been bred for more than 10 generations and the transgene was stably transmitted to progeny as determined by Southern blot hybridization and restriction fragment length polymorphism. The transgene copy number is 10 in the TGM-PRG-3 mouse line and one in the TGM-PRG-1 mouse line. Abundance of PVR RNA is on average three-fold higher in TGM-PRG-3 relative to TGM-PRG-1 tissues, and the abundance of the receptor molecule is three-fold higher in TGM-PRG-3 central nervous system tissues compared to TGM-PRG-1 tissues as determined by Western blot analysis. When TGM-PRG-1 and TGM-PRG-3 mice were inoculated intracranially with a neurovirulent type II[ poliovirus strain, they developed clinical symptoms and CNS lesions characteristic of human poliomyelitis. These results indicate that the PVR gene is expressed as a functional receptor in the CNS of both mouse lines rendering the mice susceptible to poliovirus infection. Even though the two mouse lines have different copy numbers of the transgene and different levels of PVR RNA and protein, they are similar in their susceptibility to poliovirus. (C) 1998 Academic Press. C1 Wyeth Lederle Vaccines & Pediat, Viral Vaccine Res, Pearl River, NY 10965 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Dutchess Community Coll, Poughkeepsie, NY 12601 USA. Wyeth Ayerst Res, CNS Disorders, Princeton, NJ 08543 USA. Biostar, Saskatoon, SK 57N 3R2, Canada. Louisiana State Univ, Sch Vet Med, Dept Vet Pathol, Baton Rouge, LA 70803 USA. Columbia Univ Coll Phys & Surg, Dept Microbiol, New York, NY 10032 USA. RP Deatly, AM (reprint author), Wyeth Lederle Vaccines & Pediat, Viral Vaccine Res, 401 N Middletown Rd, Pearl River, NY 10965 USA. NR 46 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD JUL PY 1998 VL 25 IS 1 BP 43 EP 54 DI 10.1006/mpat.1998.0212 PG 12 WC Immunology; Microbiology SC Immunology; Microbiology GA 108AZ UT WOS:000075245000005 PM 9705248 ER PT J AU D'Agnillo, F Chang, TMS AF D'Agnillo, F Chang, TMS TI Polyhemoglobin superoxide dismutase catalase as a blood substitute with antioxidant properties SO NATURE BIOTECHNOLOGY LA English DT Article DE protein engineering; tissue engineering; hemoglobin ID FREE-RADICALS; REPERFUSION ARRHYTHMIAS; METHEMOGLOBIN FORMATION; HEMOGLOBIN; OXYGEN AB Polyhemoglobin-superoxide dismutase-catalase is designed to function as an oxygen carrier with antioxidant properties. This is based on cross-linking hemoglobin with superoxide dismutase and catalase (PolyHb-SOD-CAT). This study describes the structural and antioxidant properties of this solution. Our studies show that superoxide dismutase and catalase retain their enzymatic activity following glutaraldehyde polymerization with 8:1 and 16:1 glutaraldehyde:hemoglobin ratio. We have analyzed the optimal SOD/CAT ratios to prevent oxidation of hemoglobin in the presence of oxygen free radicals. The circulation half-life of crosslinked hemoglobin, SOD, and catalase in Sprague-Dawley rats correlates with the degree of polymerization as determined by high-performance molecular weight gel filtration. PolyHb-SOD-CAT decreases the formation of oxygen radicals compared with PolyHb in a rat intestinal ischemia-reperfusion model. C1 McGill Univ, Fac Med, Artificial Cells & Organs Res Ctr, Montreal, PQ, Canada. RP Chang, TMS (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD 20892 USA. EM artcell@physio.mcgill.ca NR 36 TC 128 Z9 129 U1 2 U2 13 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUL PY 1998 VL 16 IS 7 BP 667 EP 671 DI 10.1038/nbt0798-667 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA ZX494 UT WOS:000074521800032 PM 9661202 ER PT J AU Jackson, AJ AF Jackson, AJ TI Evaluation of a Cmin and a normalized Cmin method for the confirmation of steady-state in bioequivalence studies SO PHARMACEUTICAL RESEARCH LA English DT Article DE bioequivalence; steady-state; area below the Cmin curve ID SINGLE AB Purpose. Two methods to confirm attainment of steady-state conditions in multiple-dose bioequivalence studies are described and evaluated: (I)the Cmin method and (2) the Area Below the Cmin plasma-concentration-versus-time-curve method (ABCM method). Methods. Cmin Method-After repetitive drug administration to presumed steady-state, successive trough, or Cmin, values are evaluated to determine if they are equal. ABCM Method-The ABCM of successive doses from dose two to presumed steady-state [ABCM(ss)] are divided by the ABCM for the first dose, ABCM(t), to give ABCM(ss)/ABCM(t)=R, which describes the increase in ABCM(n) with successive doses. The quantity, R, is then divided by an accumulation ratio to render the value independent of intra-subject clearance differences. Monte Carlo simulations were done to test the effects of data error and slow-clearing subpopulations on the method's performance. Data from multiple-dose bioequivalence studies were evaluated using confidence intervals for both methods to determine how well each predicted steady-state for immediate-release and controlled-release drug products. Results/Conclusions. The Cmin method more accurately predicted the attainment of steady-state conditions for immediate-release formulations compared to the ABCM method. Conversely, the ABCM procedure more accurately predicted the attainment of steady-state conditions for controlled-release formulations compared to the Cmin method. The simulation results were further supported by the experimental data. 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, HFD-652, Rockville, MD 20857 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD JUL PY 1998 VL 15 IS 7 BP 1077 EP 1084 DI 10.1023/A:1011990413450 PG 8 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 101YX UT WOS:000074897300020 PM 9688063 ER PT J AU Meyer, MC Straughn, AB Mhatre, RM Shah, VP Williams, RL Lesko, LJ AF Meyer, MC Straughn, AB Mhatre, RM Shah, VP Williams, RL Lesko, LJ TI Lack of in vivo in vitro correlations for 50 mg and 250 mg primidone tablets SO PHARMACEUTICAL RESEARCH LA English DT Article DE primidone; bioavailability; human; pharmacokinetics; in vitro dissolution AB Purpose. To determine if large differences in the in vitro dissolution profiles for primidone tablets would result in significant bioavailability differences. Methods. Two separate bioavailability studies were conducted. The first study used 18 healthy subjects and compared the bioavailability of an old 50 mg tablet formulation, a new 50 mg tablet formulation, and a suspension containing 50 mg/ml of primidone. The second study enrolled 24 subjects who were to receive a new 250 mg tablet formulation, two lots of an old 250 mg tablet formulation and a 250 mg tablet from a second manufacturer. In vitro dissolution was conducted over 90 minutes, using USP 23 Apparatus 2 at 50 rpm, with 900 mi of water. Results. Dissolution at 90 minutes for the old and new 50 mg tablets was approximately 20% and 100%, respectively. The dissolution of the four 250 mg tablets ranged from approximately 30% to 100%. The 50 mg tablet that dissolved slower had a longer Tmax and a 14% lower Cmax than the more rapidly dissolving tablet, but the AUC(0-infinity) values differed by only 3%. Only nine subjects completed the 250 mg study because of side effects. The differences in Cmax and AUC(0-infinity) among the four 250 mg tablets were less than 7%. Conclusions. Even though there were large differences in the in vitro dissolution of the 50 mg and the 250 mg primidone tablets, the two 50 mg tablets were shown to be bioequivalent, as were the four 250 mg tablets. C1 Univ Tennessee, Coll Pharm, Dept Pharmaceut Sci, Memphis, TN 38163 USA. US Food & Drug Adm, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, MD 20855 USA. RP Meyer, MC (reprint author), Univ Tennessee, Coll Pharm, Dept Pharmaceut Sci, Memphis, TN 38163 USA. NR 7 TC 10 Z9 10 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD JUL PY 1998 VL 15 IS 7 BP 1085 EP 1089 DI 10.1023/A:1011942530288 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 101YX UT WOS:000074897300021 PM 9688064 ER PT J AU Miller, SA Hamilton, SL Wester, UG Cyr, WH AF Miller, SA Hamilton, SL Wester, UG Cyr, WH TI An analysis of UVA emissions from sunlamps and the potential importance for melanoma SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; EXPOSURE; SUNBEDS; RISK; OUTDOOR AB Exposure to solar UV radiation is a risk factor for cutaneous malignant melanoma (CMM), Epidemiologic studies have also considered the use of sunlamps as a possible contributor to CMM. We measured and analyzed the emission spectra of six different currently marketed sunlamps and a historical sunlamp, the UVB-emitting FS lamp, and compared the results to solar exposure. For a typical tanner (20 sessions @ 2 minimal erythema doses (MED)/session), the annual WA doses from commonly used fluorescent sunlamps were 0.3-1.2 times that received from the sun. For a frequent tanner (100 sessions @ 4 MED/session), the annual UVA doses from fluorescent sunlamps were 1.2-4.7 times that received from the sun and 12 times for recently available, high-pressure sunlamps. To determine biologically effective doses, action spectra for squamous cell carcinoma (SCC) in humans and for melanoma in the Xiphophorus fish (XFM) were applied to the sunlamps' emission spectra, The results for the effective doses using the SCC action spectrum tracked the UVB doses, while the results using the XFM action spectrum tracked the WA doses. When combined with UV exposure received from the sun, typical sunlamp use results in an approximate doubling of annual effective dose, if the XFM action spectrum is applied. Frequent use, however, can increase the annual effective XFM dose by as much as 6 times what would be received from the sun alone for fluorescent sunlamps and as much as 12 times for newer, high-pressure sunlamps. C1 US FDA, Ctr Devices & Radiol Hlth, Electroopt Branch HFZ134, Rockville, MD 20850 USA. US FDA, Winchester Engn Analyt Ctr, Winchester, PA USA. Swedish Radiat Protect Inst, Stockholm, Sweden. RP Miller, SA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Electroopt Branch HFZ134, 9200 Corp Blvd, Rockville, MD 20850 USA. EM SYM@CDRH.FDA.GOV NR 30 TC 61 Z9 63 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUL PY 1998 VL 68 IS 1 BP 63 EP 70 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 102PE UT WOS:000074932400010 PM 9679452 ER PT J AU Owen, RD AF Owen, RD TI MYC mRNA abundance is unchanged in subcultures of HL60 cells exposed to power-line frequency magnetic fields SO RADIATION RESEARCH LA English DT Article ID HUMAN LEUKEMIA-CELLS; ELECTROMAGNETIC-FIELDS; TRANSCRIPT LEVELS; EXPRESSION; DIFFERENTIATION AB Epidemiological data have not demonstrated conclusively that there exists an association between exposure to power-line frequency electric and magnetic fields (EMFs) and cancer. Some laboratory studies performed to investigate possible mechanisms for such an association reported biological effects of EMF exposure, but attempts to confirm some such reports have had mixed success. The most publicized experiments in this regard were studies on the purported EMF-induced increase in MYC expression in. HL60 cells. To address the accuracy and reproducibility of this effect, HL60 cells were exposed to 6-mu T 60 Hz magnetic fields, and MYC expression was measured. Assay methods and exposure conditions were as close as practical to those of the investigators that originally reported a positive effect. A chemical agent was used to demonstrate that the cells were responsive to a known stimulus and that the experimental system was sufficiently sensitive to detect such a stimulus. The experimental system had sufficiently low basal variability to allow the detection of effects of the magnitude that had been reported previously. Using either cells from a commercial source or cells supplied by the original investigators, no evidence was obtained to support the hypothesis that EMF exposure could induce MYC expression. (C) 1998 by Radiation Research Society. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Owen, RD (reprint author), US FDA, Ctr Devices & Radiol Hlth, 9200 Corp Blvd, Rockville, MD 20850 USA. FU NIEHS NIH HHS [Y1-ES-0006, YOI-ES-40272] NR 15 TC 17 Z9 17 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 1998 VL 150 IS 1 BP 23 EP 30 DI 10.2307/3579641 PG 8 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA ZV652 UT WOS:000074327300005 PM 9650598 ER PT J AU Weaver, JL Contrera, JF Rosenzweig, BA Thompson, KL Faustino, PJ Strong, JM Ellison, CD Anderson, LW Prasanna, HR Long-Bradley, PE Lin, KK Zhang, J Sistare, FD AF Weaver, JL Contrera, JF Rosenzweig, BA Thompson, KL Faustino, PJ Strong, JM Ellison, CD Anderson, LW Prasanna, HR Long-Bradley, PE Lin, KK Zhang, J Sistare, FD TI An evaluation of the hemizygous transgenic Tg.AC mouse for carcinogenicity testing of pharmaceuticals. I. Evidence for a confounding nonresponder phenotype SO TOXICOLOGIC PATHOLOGY LA English DT Article DE papillomagenesis; cyclophosphamide; chlorpheniramine; phenolphthalein; skin; tamoxifen; 12-o-tetradecanoylphorbol 13-acetate; zeta-globin AB We have completed 2 26-wk studies to evaluate the hemizygous transgenic Tg.AC mouse, which has been proposed as an alternative short term model for testing carcinogenicity. We attempted to evaluate the response to the known rodent carcinogens cyclophosphamide, phenolphthalein, and tamoxifen and to the noncarcinogen chlorpheniramine following topical application. In the first study, a weak response (2/17 animals) was observed to the positive control 12-O-tetradecanoylphorbol 13-acetate (TPA in ethanol, 1.25 mug), and no response was observed to cyclophosphamide, phenolphthalein, or chlorpheniramine, despite evidence for skin penetration. The second study compared 1.25 mug and 6.25 mug of TPA in ethanol and acetone solutions. Tamoxifen was also evaluated in both solvents and orally. No significant response was observed to tamoxifen by skin paint or oral routes. Over 60% of the high dose TPA-treated animals showed no (0 or 1) papilloma response, and 30% of the animals each developed more than 32 papillomas. The heterogenous response to high dose TPA may be related to variability in the responsiveness of hemizygous animals. In light of these findings, further Tg.AC studies should employ homozygous animals, and the underlying cause for heterogeneity in the tumorigenic response of Tg.AC mice should be identified and eliminated. C1 US FDA, Div Appl Pharmacol Res, Off Testing & Res, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. RP Sistare, FD (reprint author), US FDA, Div Appl Pharmacol Res, Off Testing & Res, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 34 TC 25 Z9 26 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI MT ROYAL PA 19 MANTUA RD, MT ROYAL, NJ 08061 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JUL-AUG PY 1998 VL 26 IS 4 BP 532 EP 540 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA V2647 UT WOS:000165536900009 PM 9715512 ER PT J AU Thompson, KL Rosenzweig, BA Sistare, FD AF Thompson, KL Rosenzweig, BA Sistare, FD TI An evaluation of the hemizygous transgenic Tg.AC mouse for carcinogenicity testing of pharmaceuticals. II. A genotypic marker that predicts tumorigenic responsiveness SO TOXICOLOGIC PATHOLOGY LA English DT Article DE gene amplification; genetic instability; inverted repeat; palindrome; 12-O-tetradecanoylphorbol 13-acetate; Southern blot hybridization; zeta-globin AB The Tg.AC transgenic mouse skin paint assay is one of the short-term carcinogenesis models that has been proposed as a replacement for 1 species in the conventional 2-yr bioassay required for safety testing of pharmaceuticals. In our initial efforts to evaluate the sensitivity and specificity of this model for human pharmaceuticals, 61% of the hemizygous Tg.AC mice in the positive control groups were refractory to treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA). Tg.AC mice are reported to carry less than or equal to 10 copies of a transgene consisting of a zeta -globin promoter fused to the v-Ha-ras structural gene with a terminal simian virus 40 (SV40) polyadenylation signal. Southern blot hybridization of genomic DNA from 66 tail biopsies using a zeta -globin probe revealed that all of the hemizygous Tg.AC mice screened contained approximately 40 copies of the transgene and that mice unresponsive to TPA had lost a 2-kb BamHI fragment containing zeta -globin promoter sequence. By systematic screening of Tg.AC breeder mice for this diagnostic marker of phenotypic responsiveness, it should be possible to selectively enrich the Tg.AC mouse colony to consist exclusively of responders and to guard against further genetic instability. C1 US FDA, Div Appl Pharmacol Res, Off Testing & Res, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. RP Sistare, FD (reprint author), US FDA, Div Appl Pharmacol Res, Off Testing & Res, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 11 TC 40 Z9 41 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI MT ROYAL PA 19 MANTUA RD, MT ROYAL, NJ 08061 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JUL-AUG PY 1998 VL 26 IS 4 BP 548 EP 555 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA V2647 UT WOS:000165536900011 PM 9715514 ER PT J AU Stewart, SFC AF Stewart, SFC TI Aliasing-tolerant color Doppler quantification of regurgitant jets SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE heart valve regurgitation; color Doppler ultrasound; aliasing; finite element analysis ID MITRAL REGURGITATION; NONINVASIVE QUANTIFICATION; FLOW-RATE; INVITRO; ECHOCARDIOGRAPHY; ORIFICE; ULTRASOUND; DIAGNOSIS; MOMENTUM; MODEL AB Conservation of momentum transfer in regurgitant cardiac jets can be used to calculate the how rate from color Doppler velocities. In this study, turbulent jets were simulated by finite elements; pseudocolor Doppler images were interpolated from the computations, with aliasing introduced artificially, Jets were also imaged by color Doppler in an in vitro flow system. To suppress aliasing errors, jet velocities were fitted iteratively to a fluid mechanical model constrained to match the orifice velocity (measured without aliasing by continuous-wave Doppler), At each iteration, the model was used to detect aliased velocities, which were excluded during the next iteration. Iteration continued until the flow rate calculated by the model and number of calculated nonaliased pixels were unchanged. The good correlations between measured and calculated flow rates in the experimental (R-2 = 0.933) and computational studies (R-2 = 0.990) suggest that this may be a clinically useful approach even in aliased images. Published by Elsevier Science Inc. C1 US FDA, Hydrodynam & Acoust Branch, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Stewart, SFC (reprint author), US FDA, Hydrodynam & Acoust Branch, Ctr Devices & Radiol Hlth, 9200 Corp Blvd,HFZ-132, Rockville, MD 20850 USA. NR 36 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD JUL PY 1998 VL 24 IS 6 BP 881 EP 898 DI 10.1016/S0301-5629(98)00051-9 PG 18 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 104QV UT WOS:000075026000010 PM 9740389 ER PT J AU Sundlof, SF AF Sundlof, SF TI Legal and responsible drug use in the cattle industry: Extra-label use SO VETERINARY MEDICINE LA English DT Article C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Sundlof, SF (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl, Rockville, MD 20855 USA. NR 5 TC 2 Z9 2 U1 0 U2 3 PU VETERINARY MEDICINE PUBL CO PI LENEXA PA 15333 W 95TH STREET, LENEXA, KS 66219 USA SN 8750-7943 J9 VET MED-US JI Vet. Med. PD JUL PY 1998 VL 93 IS 7 BP 673 EP + PG 6 WC Veterinary Sciences SC Veterinary Sciences GA 104GU UT WOS:000075007000019 ER PT J AU Sundlof, SF AF Sundlof, SF TI Legal and responsible drug use in the carve industry: The animal drug availability act SO VETERINARY MEDICINE LA English DT Article C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Sundlof, SF (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl, Rockville, MD 20855 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU VETERINARY MEDICINE PUBL CO PI LENEXA PA 15333 W 95TH STREET, LENEXA, KS 66219 USA SN 8750-7943 J9 VET MED-US JI Vet. Med. PD JUL PY 1998 VL 93 IS 7 BP 681 EP 684 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 104GU UT WOS:000075007000020 ER PT J AU Herman, EH Zhang, J Hasinoff, BB Tran, KT Chadwick, DP Clark, JR Ferrans, VJ AF Herman, EH Zhang, J Hasinoff, BB Tran, KT Chadwick, DP Clark, JR Ferrans, VJ TI Comparison of the chronic toxicity of piroxantrone, losoxantrone and doxorubicin in spontaneously hypertensive rats SO TOXICOLOGY LA English DT Article DE piroxantrone; losoxantrone; doxorubicin; cardiotoxicity; nephrotoxicity; reactive oxygen species; electronmicroscopy; iron complexes ID SOUTHWEST-ONCOLOGY-GROUP; METASTATIC BREAST-CANCER; PHASE-II TRIAL; ANTHRAPYRAZOLE; ICRF-187; AGENTS; CARDIOTOXICITY; ANTHRACYCLINE; INHIBITION; COMPLEXES AB Comparisons were made of the toxic effects produced in the heart, kidney and small intestine of spontaneously hypertensive rats (SHR) by the administration of 12 consecutive weekly doses of doxorubicin (I mg/kg), and high, intermediate and low doses of piroxantrone (3, 1.5 and 0.75 mg/kg) and losoxantrone (1, 0.5 and 0.25 mg/kg). Animals receiving saline were used as controls. The toxicities of the three drugs were evaluated by clinical chemistry and hematological determinations, light microscopy and transmission electron microscopy. The severity of the histologic alterations in heart, kidney and small intestine was assessed semiquantitatively. Biochemical and molecular modeling studies were made to evaluate the formation of complexes of Fe(III) with piroxantrone and losoxantrone. The cardiac (myofibrillar loss and dilatation of the sarcoplasmic reticulum) and renal (glomerular vacuolization, tubular damage and laboratory evidence of a nephrotic syndrome) lesions induced by all three agents had similar features. However, the cardiac lesions induced by losoxantrone and doxorubicin were significantly more severe (Billingham scores) than those produced by piroxantrone. The renal lesions induced by piroxantrone and losoxantrone were less severe than those produced by doxorubicin. Similarly losoxantrone and piroxantrone-induced intestinal alterations (denudation of epithelial layer and inflammatory cellular infiltration) were less severe than those occurring after treatment with doxorubicin. Both losoxantrone and piroxantrone were shown to form Fe(III): drug complexes that may cause oxidative damage to various tissues. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 US FDA, Div Appl Pharmacol Res, Laurel, MD 20708 USA. Univ Manitoba, Fac Pharm, Winnipeg, MB R3T 2N2, Canada. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Herman, EH (reprint author), US FDA, Div Appl Pharmacol Res, HFD-910,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 36 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JUN 26 PY 1998 VL 128 IS 1 BP 35 EP 52 DI 10.1016/S0300-483X(98)00049-3 PG 18 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 106RP UT WOS:000075164500005 PM 9704904 ER PT J AU Boone, CW Steele, VE Gaylor, D Kelloff, GJ AF Boone, CW Steele, VE Gaylor, D Kelloff, GJ TI Use of Druckrey analysis to quantitatively evaluate the chemopreventive efficacy of N-difluoromethylornithine (DFMO), a prototype proliferation inhibitor SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 5th International Conference on Mechanisms of Antimutagenesis and Anticarcinogenesis (5th ICMAA) CY DEC 02-06, 1996 CL OKAYAMA, JAPAN DE cancer chemoprevention; TG.AC transgenic mouse; skin paint carcinogenesis; N-difluormethylornithine ID CARCINOGENESIS AB Druckrey analysis of the results of skin painting TG.AC transgenic mice with three different doses of benzo[a]pyrene was used to obtain quantitative estimates of the in vivo cancer chemopreventive efficacy of N-difluoromethylornithine. The percent decrease in mean rate of subvisible tumor development during the tumor latent period produced by 2000 ppm and 4000 ppm DFMO in the diet was 39% and 50%, respectively. Druckrey analysis was also successfully applied to transformations of published data on human cigarette smokers. The time before onset of lung cancer in 2% of smokers was prolonged 17 weeks for every cigarette per day not smoked. The Druckrey model, of substantiated validity because of the results in human smokers, provides a rapid quantitative screening method applicable to large numbers of candidate chemopreventive agents. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NCI, DCPC, Chemoprevent Branch, Bethesda, MD 20894 USA. Natl Ctr Toxicol Res, Little Rock, AR 72202 USA. RP Boone, CW (reprint author), NCI, DCPC, Chemoprevent Branch, Bethesda, MD 20894 USA. NR 6 TC 0 Z9 0 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 JUN 18 PY 1998 VL 402 IS 1-2 BP 173 EP 177 DI 10.1016/S0027-5107(97)00295-9 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 106TJ UT WOS:000075166300021 PM 9675271 ER PT J AU Labarca, J Peterson, C Bendaqa, N Mascola, L Kilman, L Harvey, S Ross, L Meylan, M Teitelbaum, P Waterman, S AF Labarca, J Peterson, C Bendaqa, N Mascola, L Kilman, L Harvey, S Ross, L Meylan, M Teitelbaum, P Waterman, S TI Nosocomial Ralstonia pickettii colonization associated with intrinsically contaminated saline solution - Los Angeles, California, 1998 (Reprinted from MMWR, vol 47, pg 285-286, 1998) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Los Angeles Cty Dept Hlth Svcs, Publ Hlth Microbiol Lab, Los Angeles, CA USA. Acute Communicable Dis Control, Los Angeles, CA 90012 USA. Childrens Hosp Los Angeles, Los Angeles, CA USA. Calif Dept Hlth Serv, Sacramento, CA USA. US FDA, Off Regulatory Affairs, Rockville, MD 20857 USA. CDC, Natl Ctr Infect Dis, Hosp Infect Program, Atlanta, GA 30333 USA. RP Labarca, J (reprint author), Acute Communicable Dis Control, Los Angeles, CA 90012 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 17 PY 1998 VL 279 IS 23 BP 1859 EP 1859 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ZT653 UT WOS:000074109700011 ER PT J AU Rasooly, A Rasooly, RS AF Rasooly, A Rasooly, RS TI Detection and analysis of staphylococcal enterotoxin A in food by Western immunoblotting SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Western blotting; SEA; Staphylococcus aureus; foodborne toxins; enterotoxins ID ASSAY KIT TECRA; PROCESSED FOODS; INACTIVATION; HEAT; SYSTEM AB Western blotting has the potential to overcome some of the major problems associated with enzyme-linked immunosorbent assay (ELISA) detection of toxins in food, such as cross-reactivity with unrelated antigens and insensitivity with heat-treated foods, because the Western procedure solubilizes denatured protein and allows characterization of the antigen that reacts with the antibody. A simple Western immunoblotting protocol was developed to identify and measure the level of Staphylococcus aureus enterotoxin A (SEA) in food. Test samples are merely homogenized with no additional solubilization or pretreatment steps. The immunoblots detect SEA at levels as low as 100 pg/ml. Using the simplified sample preparation, both native and heat-denatured SEA were identified in a variety of foods including mushrooms, milk, potato salad and meat products. Our data suggest that SEA is being secreted at mid-log growth in BHI media as well as in mushrooms. These results suggest that Western blotting is a useful tool for determining the presence of SEA in foods because it allows characterization of the antigen reacting with the antibody and can be used for heat-treated foods, thus overcoming some of the limitations of the ELISA test. (C) 1998 Elsevier Science B.V. C1 US FDA, Div Microbiol Studies, Washington, DC 20204 USA. St Johns Univ, Dept Biol Sci, Jamaica, NY 11439 USA. RP Rasooly, A (reprint author), US FDA, Div Microbiol Studies, Washington, DC 20204 USA. OI Rasooly, Rebekah/0000-0002-6357-5528 NR 22 TC 32 Z9 33 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD JUN 16 PY 1998 VL 41 IS 3 BP 205 EP 212 DI 10.1016/S0168-1605(98)00050-6 PG 8 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 104HB UT WOS:000075007700005 PM 9706788 ER PT J AU Hayes, MP Murphy, FJ Burd, PR AF Hayes, MP Murphy, FJ Burd, PR TI Interferon-gamma-dependent inducible expression of the human interleukin-12 p35 gene in monocytes initiates from a TATA-containing promoter distinct from the CpG-rich promoter active in Epstein-Barr virus-transformed lymphoblastoid cells SO BLOOD LA English DT Article ID BLOOD MONONUCLEAR-CELLS; STIMULATORY FACTOR; DENDRITIC CELLS; IFN-GAMMA; T-CELLS; IL-12; CYTOKINE; PURIFICATION; MODULATION; RESPONSES AB Interleukin-12 (IL-12) production by human monocytes is stringently regulated through the inducibility of both subunits, p35 and p40, and expression of p35 mRNA is the limiting factor for the secretion of the bioactive IL-12 p70 heterodimer, Optimal induction of p35 mRNA requires prim priming of the monocytes by interferon-gamma (IFN-gamma), followed by brief exposure to lipopolysaccharide or other bacterial products, To investigate control of p35 gene expression, we isolated genomic clones containing the human p35 gene and determined the 5' end of the mRNA expressed in monocytes. We discovered that a unique p35 transcript is induced in monocytes that begins downstream of a consensus TATA box that lies within the 5' end of the cDNA originally cloned from Epstein-Barr virus (EBV)-transformed B cells, Analysis of p35 mRNA by Northern blotting showed that the message from monocytes is approximately 200 bases shorter than message derived from the EBV-transformed B-cell line VDS. The initiation sites downstream from the TATA box were confirmed by RNase protection and 5' RACE, The data indicate that p35 transcription can initiate from different sites depending on the cell type and that the shorter inducible transcript in monocytes is the one that accumulates after stimulation. Protein translation of these two forms may result in proteins of different sizes with potential implications for the regulation of IL-12 secretion and function. C1 US FDA, Div Cytokine Biol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Rockville, MD 20857 USA. RP Hayes, MP (reprint author), US FDA, Div Cytokine Biol, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-508, Rockville, MD 20852 USA. NR 35 TC 51 Z9 51 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1998 VL 91 IS 12 BP 4645 EP 4651 PG 7 WC Hematology SC Hematology GA ZT469 UT WOS:000074091000029 PM 9616161 ER PT J AU Gratama, JW Orfao, A Barnett, D Brando, B Huber, A Janossy, G Johnsen, HE Keeney, M Marti, GE Preijers, F Rothe, G Serke, S Sutherland, DR Van der Schoot, CE Schmitz, G Papa, S AF Gratama, JW Orfao, A Barnett, D Brando, B Huber, A Janossy, G Johnsen, HE Keeney, M Marti, GE Preijers, F Rothe, G Serke, S Sutherland, DR Van der Schoot, CE Schmitz, G Papa, S CA European Working Grp Clinical Cell Anal TI Flow cytometric enumeration of CD34(+) hematopoietic stem and progenitor cells SO CYTOMETRY LA English DT Review DE CD34; hematopoietic stem cells; enumeration; flow cytometry; standardization ID UMBILICAL-CORD BLOOD; MOBILIZED PERIPHERAL-BLOOD; COLONY-STIMULATING FACTOR; BONE-MARROW; G-CSF; LEUKAPHERESIS PRODUCTS; MALIGNANT-LYMPHOMA; QUALITY ASSURANCE; NORMAL DONORS; IN-VITRO AB The need for a rapid and reliable marker for the engraftment potential of hematopoietic stem and progenitor cell (HPC) transplants has led to the development of flow cytometric assays to quantitate such cells on the basis of their expression of CD34, The variability associated with enumeration of low-frequency cells (i.e., as low as 0.1% or 5 cells/mu l) is exceedingly large, but recent developments have improved the accuracy and precision of the assay. Here, we review and compare the major techniques. Based on the current state of the art, we recommend i) bright fluorochrome conjugates of class II or III monoclonal antibodies (mAbs) that detect all glycoforms of CD34, 2) use of a vital nucleic acid dye to exclude platelets, unlysed red cells, and debris or use of 7-amino actinomycin D to exclude dead cells during data acquisition, 3) counterstaining with CD45 mAb to be included in the definition of HPC, 4) during list mode data analysis, Boolean gating to resolve the CD34(+) HPCs from irrelevant cell populations on the basis of the low levels of CD45 expression and low sideward light-scatter signals of HPCs, 5) inclusion of CD34(dim) and CD34(bright) populations in the CD34(+) cell count, 6) omission of the negative control staining, and 7) for apheresis products, enumeration of at least 100 CD34+ cells to ensure a 10% precision. Unresolved technical questions are 1) the replacement of conventional dual-platform by single-platform assay formats, i,e,, derivation of absolute CD34+ cell counts from a single flow cytometric assessment instead of from combined flow cytometer (percent CD34(+)) and hematology analyzer (absolute leukocyte count) data, 2) the cross-calibration of the available single-platform assays, and 3) the optimal method for sample preparation. An important clinical question to be addressed is the definition of the precise phenotypes and required numbers of HPCs responsible for short- and long-term recovery to optimize HPC transplant strategies. 1998. (C) 1998 Wiley-Liss, Inc. C1 Dr Daniel Den Hoed Canc Ctr, Dept Clin & Tumor Immunol, NL-3008 AE Rotterdam, Netherlands. Hosp Univ Salamanca, Serv Citometria, Hematol Lab, Salamanca, Spain. Royal Hallamshire Hosp, Dept Haematol, Sheffield S10 2JF, S Yorkshire, England. Osped Niguarda Ca Granda, Lab Unita Trapianto Renale, Milan, Italy. Kantonsspital, Zent Lab, Aarau, Switzerland. Royal Free Hosp, Sch Med, Dept Clin Immunol, London, England. Amtssygehus Herlev, Dept Hematol, Herlev, Denmark. London Hlth Sci Ctr, Dept Hematol, London, ON, Canada. NIH, Mol & Cellular Biol Lab, Ctr Biol Evaluat & Res, Food & Drug Adm, Bethesda, MD USA. Univ Nijmegen Hosp, Dept Hematol, NL-6500 HB Nijmegen, Netherlands. Univ Regensburg, Klinikum, Inst Klin Chem & Lab Med, D-8400 Regensburg, Germany. Humboldt Univ, Abt Hematol Onkol, Virchow Klinikum, Berlin, Germany. Toronto Hosp, Toronto, ON M5T 2S8, Canada. Dutch Res Cross Blood Transfus Serv, Dept Immunohematol, Cent Lab, Amsterdam, Netherlands. Univ Urbino, Ist Sci Morfol, I-61029 Urbino, Italy. RP Gratama, JW (reprint author), Dr Daniel Den Hoed Canc Ctr, Dept Clin & Tumor Immunol, POB 5201, NL-3008 AE Rotterdam, Netherlands. EM gratama@immh.azr.nl RI Preijers, F.W.M.B./L-4586-2015; OI Schmitz, Gerd/0000-0002-1325-1007 NR 109 TC 150 Z9 156 U1 2 U2 12 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 JUN 15 PY 1998 VL 34 IS 3 BP 128 EP 142 DI 10.1002/(SICI)1097-0320(19980615)34:3<128::AID-CYTO3>3.0.CO;2-D PG 15 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 102JN UT WOS:000074921200003 PM 9696157 ER PT J AU Song, XY Gu, ML Jin, WW Klinman, DM Wahl, SM AF Song, XY Gu, ML Jin, WW Klinman, DM Wahl, SM TI Plasmid DNA encoding transforming growth factor-beta 1 suppresses chronic disease in a streptococcal cell wall-induced arthritis model SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE cytokine; inflammation; immunosuppression; gene therapy; arthritis ID FACTOR-BETA; SYNOVIAL INFLAMMATION; GENE-THERAPY; INTRAMUSCULAR INJECTION; SYSTEMIC DELIVERY; IN-VIVO; MICE; EXPRESSION; MUSCLE; HYPERPLASIA AB Transforming growth factor beta is a potent immunomodulator with both pro-and antiinflammatory activities. Based on its immunosuppressive actions, exogenous TGF-beta has been shown to inhibit autoimmune and chronic inflammatory diseases. To further explore the potential therapeutic role of TGF-beta, we administered a plasmid DNA encoding human TGF-beta 1 intramuscularly to rats with streptococcal cell wall-induced arthritis. A single dose of 300 mu g plasmid DNA encoding TGF-beta 1, but not vector DNA, administered at the peak of the acute phase profoundly suppressed the subsequent evolution of chronic erosive disease typified by disabling joint swelling and deformity (articular index = 8.17+/-0.17 vs. 1.25+/-0.76, n = 6, day 26, P < 0.01), Moreover, delivery of the TGF-beta 1 DNA even as the chronic phase commenced virtually eliminated subsequent inflammation and arthritis. Both radiologic and histopathologic as well as molecular evidence supported the marked inhibitory effect of TGF-beta 1 DNA on synovial pathology, with decreases in the inflammatory cell infiltration, pannus formation, cartilage and bone destruction, and the expression of proinflammatory cytokines that characterize this model. Increases in TGF-beta 1 protein were detected in the circulation of TGF-beta 1 DNA-treated animals, consistent with the observed therapeutic effects being TGF-beta 1 dependent. These observations provide the first evidence that gene transfer of plasmid DNA encoding TGF-beta 1 provides a mechanism to deliver this potent cytokine that effectively suppresses ongoing inflammatory pathology in arthritis. C1 NIDR, Oral Infect & Immunity Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Retrovirus Lab, Bethesda, MD 20892 USA. RP Wahl, SM (reprint author), Bldg 30,Room 332,30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA. NR 32 TC 93 Z9 95 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN 15 PY 1998 VL 101 IS 12 BP 2615 EP 2621 DI 10.1172/JCI2480 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZY285 UT WOS:000074604800002 PM 9637694 ER PT J AU Beland, FA Schmitt, TC Fullerton, NF Young, JF AF Beland, FA Schmitt, TC Fullerton, NF Young, JF TI Metabolism of chloral hydrate in mice and rats after single and multiple doses SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A LA English DT Article ID MALE B6C3F1 MOUSE; TRICHLOROACETIC-ACID; ASPERGILLUS-NIDULANS; DICHLOROACETIC ACID; SACCHAROMYCES-CEREVISIAE; LIPID-PEROXIDATION; TRICHLOROETHYLENE; INDUCTION; LIVER; ANEUPLOIDY AB Chloral hydrate is a hepatocarcinogen in mice but not rats. To examine this species related difference, male and female B6C3F1 mice and Fischer (F344) rats were treated by gavage with 1 or 12 doses of chloral hydrate, and concentrations of the drug and its metabolites were determined in plasma at 0.25, 1, 3, 6, and 24 h and 2, 4, 8, and 16 d after the last treatment. Maximum levels of chloral hydrate were observed at the initial sampling time of 0.25 h. By 1 h, levels dropped substantially, and by 3 h, chloral hydrate could not be detected. Trichloroacetic acid was the major metabolite found in the plasma, with peak levels being observed 1-6 h after dosing. The concentrations then slowly decreased such that by 2 d this metabolite could no longer be detected. Trichloroethanol was assayed as both the free alcohol and its glucuronide. Maximum levels of trichoroethanol occurred at 0.25 h, and by 1-3 h approached the limits of detection. A pharmacokinetic model was constructed to describe the metabolic data. The plasma half-life values of chloral hydrate were similar in bath species. In mice, the rate of elimination of trichloroacetic acid was significantly increased after multiple doses; this difference was not observed with rats. The half-life of trichloroethanol and its glucuronide war; significantly greater in rats as compared to mice. None of the metabolic parameters appears to account for the hepatocarcinogenicity of chloral hydrate seen in mice but not rats. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Beland, FA (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT-110, Jefferson, AR 72079 USA. FU NIA NIH HHS [IAG 224-93-0001] NR 39 TC 13 Z9 13 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0098-4108 J9 J TOXICOL ENV HEAL A JI J. TOXICOL. ENV. HEALTH PT A PD JUN 12 PY 1998 VL 54 IS 3 BP 209 EP 226 PG 18 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA ZU582 UT WOS:000074212500004 PM 9643873 ER PT J AU Wysowski, DK Talarico, L Bacsanyi, J Botstein, P AF Wysowski, DK Talarico, L Bacsanyi, J Botstein, P TI Spinal and epidural hematoma and low-molecular-weight heparin SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Wysowski, DK (reprint author), US FDA, Rockville, MD 20857 USA. NR 5 TC 80 Z9 81 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 11 PY 1998 VL 338 IS 24 BP 1774 EP 1774 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ZT654 UT WOS:000074109800023 PM 9625640 ER PT J AU Manjanatha, MG Shelton, SD Aidoo, A Lyn-Cook, LE Casciano, DA AF Manjanatha, MG Shelton, SD Aidoo, A Lyn-Cook, LE Casciano, DA TI Comparison of in vivo mutagenesis in the endogenous Hprt gene and the lacI transgene of Big Blue (R) rats treated with 7,12-dimethylbenz[a]anthracene SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE Hprt; lacI; 6-thioguanine-resistant; Big Blue rat ID MOUSE MUTATION ASSAY; ETHYL-N-NITROSOUREA; MUTANT FREQUENCY; IN-VIVO; 6-THIOGUANINE-RESISTANT LYMPHOCYTES; MAMMARY CARCINOGENESIS; FISCHER-344 RATS; SHUTTLE VECTORS; MICE; CELLS AB The lacI transgene of Big Blue(R) (BB) rats was evaluated as a reporter of in vivo mutation by comparing mutant frequencies (MFs) in it and in the endogenous Hprt gene. Seven-week old female BE rats were given single doses of 0, 20, 75 and 130 mg/kg of 7,12-dimethylbenz(a)anthracene (DMBA) by gavage, and Hprt and lacI MFs in splenic lymphocytes were measured over a period of 18 weeks. The Hprt MFs in treated rats increased for 10 weeks and then declined; 130 mg/kg of DMBA produced a maximum Hprt MF of 168 +/- 11.4 x 10(-6) clonable lymphocytes, while the MF in control rats was 7.4 +/- 1.5 x 10(-6). DMBA exposure of generic F344 rats resulted in a similar time-course of mutant induction but produced about 50% higher Hprt MFs with the 75 and 130 mg/kg doses. In contrast, the lacI MFs increased for 6 weeks and then remained relatively constant; 130 mg/kg of DMBA produced a maximum increase in lacI MF of 341 +/- 83 x 10(-6) PFU compared with 25 +/- 5 x 10(-6) PFU in control rats. The Hprt mutant frequencies in DMBA-treated BB and F344 rats were significantly increased over control values for every dose-time combination examined, while only the 130 mg/kg dose consistently produced lacI MFs that were significantly above the controls. In addition, the fold-increase in MF for treated vs. control rats was two times higher for the Hprt gene than the lacI gene due to the higher MFs in the lacI gene of control rats. Differences between the lacI and Hprt genes in the kinetics of mutant induction, in the frequency of induced mutants, and in the sensitivity of mutant detection could be explained at least partially by the properties of these two genes. (C) 1998 Elsevier Science B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, DGT, US Dept HHS, Jefferson, AR 72079 USA. RP Manjanatha, MG (reprint author), US FDA, Natl Ctr Toxicol Res, DGT, US Dept HHS, HFT-120, Jefferson, AR 72079 USA. EM mmanjanatha@nctr.fda.gov NR 42 TC 36 Z9 36 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD JUN 5 PY 1998 VL 401 IS 1-2 BP 165 EP 178 DI 10.1016/S0027-5107(98)00006-2 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA ZY520 UT WOS:000074630000016 PM 9639698 ER PT J AU Rezapkin, GV Alexander, W Dragunsky, E Parker, M Pomeroy, K Asher, DM Chumakov, KM AF Rezapkin, GV Alexander, W Dragunsky, E Parker, M Pomeroy, K Asher, DM Chumakov, KM TI Genetic stability of Sabin 1 strain of poliovirus: Implications for quality control of oral poliovirus vaccine SO VIROLOGY LA English DT Article ID ATTENUATION PHENOTYPE; TYPE-1 POLIOVIRUS; RNA; VIRUS; DETERMINANTS; EPIDEMIOLOGY; TEMPERATURE; POPULATIONS; MONKEYS; DISEASE AB The Sabin Vaccine strains of poliovirus, like all RNA viruses, exist as a quasispecies of genomic sequences whose composition can be altered during Virus propagation. Since changes in vaccine virus during manufacture can enhance the neurovirulent potential of the vaccine, each monovalent lot of oral poliovirus vaccine (OPV) undergoes several tests to ensure consistency of manufacture, including the monkey neurovirulence test (MNVT). Recently, we proposed a new molecular approach for direct quantification of vaccine Variants with neurovirulent potential as an alternative way to monitor consistency of OPV production. Analysis of the Sabin 1 genome allowed us to identify a limited number of specific loci that exhibit significant change during viral propagation in vitro and in vivo. Here we explore the possible roles of these changes and show that 7427-U-->C and 7441-G-->A alterations in the 3'-UTR or the Sabin 1 virus do not increase monkey neurovirulence. These, as well as our previous results, suggest that only mutations in the 5'-UTR play a significant role in the limited increase in Sabin 1 monkey neurovirulence observed after extended propagation of the virus beyond the passage level used in vaccine production. Our studies with high-passage batches of the Sabin 1 strain confirmed the stability of this strain, which retains acceptable levels of monkey neurovirulence even after serial passages at elevated temperature. Compared to the MNVT, molecular analysis of the genetic composition of Sabin 1 poliovirus provides a more sensitive analytical approach to monitor consistency of vaccine production. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Chumakov, KM (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM 255,1401 Rockville Pike, Rockville, MD 20852 USA. NR 23 TC 8 Z9 11 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 JUN 5 PY 1998 VL 245 IS 2 BP 183 EP 187 DI 10.1006/viro.1998.9191 PG 5 WC Virology SC Virology GA ZU337 UT WOS:000074186800001 PM 9636357 ER PT J AU Nightingale, SL AF Nightingale, SL TI Hypersensitivity to chlorhexidine-impregnated medical devices SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 6 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 3 PY 1998 VL 279 IS 21 BP 1684 EP 1684 DI 10.1001/jama.279.21.1684 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ZQ544 UT WOS:000073878700005 PM 9624011 ER PT J AU Nightingale, SL AF Nightingale, SL TI Viagra approval information on the Internet SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 6 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 3 PY 1998 VL 279 IS 21 BP 1684 EP 1684 DI 10.1001/jama.279.21.1684 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ZQ544 UT WOS:000073878700004 PM 9624011 ER PT J AU Nightingale, SL AF Nightingale, SL TI Web site for "year 2000" information on biomedical equipment SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 6 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 3 PY 1998 VL 279 IS 21 BP 1684 EP 1684 DI 10.1001/jama.279.21.1684 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ZQ544 UT WOS:000073878700006 PM 9624011 ER PT J AU Dall'Acqua, W Goldman, ER Lin, WH Teng, C Tsuchiya, D Li, HM Ysern, X Braden, BC Li, YL Smith-Gill, SJ Mariuzza, RA AF Dall'Acqua, W Goldman, ER Lin, WH Teng, C Tsuchiya, D Li, HM Ysern, X Braden, BC Li, YL Smith-Gill, SJ Mariuzza, RA TI A mutational analysis of binding interactions in an antigen-antibody protein-protein complex SO BIOCHEMISTRY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; DOUBLE-MUTANT CYCLES; EGG-WHITE LYSOZYME; FUNCTIONAL EPITOPE; CRYSTAL-STRUCTURES; FREE-ENERGY; INTERFACE; NEURAMINIDASE; FV; RENATURATION AB Alanine scanning mutagenesis, double mutant cycles, and X-ray crystallography were used to characterize the interface between the anti-hen egg white lysozyme (HEL) antibody D1.3 and HEL. Twelve out of the 13 nonglycine contact residues on HEL, as determined by the high-resolution crystal structure of the D1.3-HEL complex, were individually truncated to alanine. Only four positions showed a Delta Delta G (Delta G(mutant) - Delta G(wild-type)) of greater than 1.0 kcal/mol, with HEL residue Gln121 proving the most critical for binding (Delta Delta G = 2.9 kcal/mol). These residues form a contiguous patch at the periphery of the epitope recognized by D1.3. To understand how potentially disruptive mutations in the antigen are accommodated in the D1.3-HEL interface, we determined the crystal structure to 1.5 Angstrom resolution of the complex between D1.3 and HEL mutant Asp18 --> Ala. This mutation results in a Delta Delta G of only 0.3 kcal/mol, despite the loss of a hydrogen bond and seven van der Waals contacts to the Asp18 side chain. The crystal structure reveals that three additional water molecules ape stably incorporated in the antigen-antibody interface at the site of the mutation. These waters help fill the cavity created by the mutation and form part of a rearranged solvent network linking the two proteins. To further dissect the energetics of specific interactions in the D1.3-HEL interface, double mutant cycles were carried out to measure the coupling of 14 amino acid pairs, 10 of which are in direct contact in the crystal structure. The highest coupling energies, 2.7 and 2.0 kcal/mol, were measured between HEL residue Gln121 and D1.3 residues V(L)Trp92 and V(L)Tyr32, respectively. The interaction between Gln121 and V(L)Trp92 consists of three van der Waals contacts, while the interaction of Gln121 with V(L)Tyr32 is mediated by a hydrogen bond. Surprisingly, however, most cycles between interface residues in direct contact in the crystal structure showed no significant coupling. In particular, a number of hydrogen-bonded residue pairs were found to make no net contribution to complex stabilization. We attribute these results to accessibility of the mutation sites to water, such that the mutated residues exchange their interaction with each other to interact with water. This implies that the strength of the protein-protein hydrogen bonds in these particular cases is comparable to that of the protein-water hydrogen bonds they replace. Thus, the simple fact that two residues are in direct contact in a protein-protein interface cannot be taken as evidence that there necessarily exists a productive interaction between them. Rather, the majority of such contacts may be energetically neutral, as in the D1.3-HEL complex. C1 Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Bowie State Univ, Bowie, MD 20715 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Mariuzza, RA (reprint author), Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, 9600 Gudelsky Dr, Rockville, MD 20850 USA. OI Li, Hongmin/0000-0002-8684-5308 FU NIGMS NIH HHS [GM5280] NR 53 TC 122 Z9 122 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 2 PY 1998 VL 37 IS 22 BP 7981 EP 7991 DI 10.1021/bi980148j PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZT215 UT WOS:000074061600008 PM 9609690 ER PT J AU Rheinstein, PH Akbari, B AF Rheinstein, PH Akbari, B TI Significant FDA approvals in 1997 SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Rheinstein, PH (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 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 JUN PY 1998 VL 57 IS 11 BP 2865 EP 2868 PG 4 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA ZU468 UT WOS:000074200400024 PM 9636343 ER PT J AU Ambrosone, CB Thompson, PA Shields, PG Freudenheim, JL Stone, A Marshall, JR Graham, S Vena, JE Laughlin, R Nemoto, T Kadlubar, FF AF Ambrosone, CB Thompson, PA Shields, PG Freudenheim, JL Stone, A Marshall, JR Graham, S Vena, JE Laughlin, R Nemoto, T Kadlubar, FF TI Catechol-O-methyltransferase (COMT) genetic polymorphisms, smoking and breast cancer risk. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1998 VL 147 IS 11 SU S MA 259 BP S65 EP S65 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZR584 UT WOS:000073992800258 ER PT J AU Shatin, D Gardner, JS Blough, D Fowler, L Alderfer, R Graham, D AF Shatin, D Gardner, JS Blough, D Fowler, L Alderfer, R Graham, D TI Risk of seizures associated with tramadol: A cohort study in an ambulatory setting. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 United HealthCare, Minneapolis, MN 55343 USA. Univ Washington, Seattle, WA 98195 USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1998 VL 147 IS 11 SU S MA 54 BP S14 EP S14 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZR584 UT WOS:000073992800056 ER PT J AU Sinha, R Kulldorff, M Chow, WH Denobile, J Lang, NP Kadlubar, FF Hoover, RN Rothman, N AF Sinha, R Kulldorff, M Chow, WH Denobile, J Lang, NP Kadlubar, FF Hoover, RN Rothman, N TI Heterocyclic amines (HCAs), metabolic variation and risk of colorectal adenomas. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Natl Naval Med Ctr, Bethesda, MD 20892 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RI Kulldorff, Martin/H-4282-2011; Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1998 VL 147 IS 11 SU S MA 258 BP S65 EP S65 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZR584 UT WOS:000073992800259 ER PT J AU Hollingdale, MR McCormick, CJ Heal, KG Taylor-Robinson, AW Reeve, P Boykins, R Kazura, JW AF Hollingdale, MR McCormick, CJ Heal, KG Taylor-Robinson, AW Reeve, P Boykins, R Kazura, JW TI Biology of malaria liver stages: implications for vaccine design SO ANNALS OF TROPICAL MEDICINE AND PARASITOLOGY LA English DT Article; Proceedings Paper CT 9th Malaria Meeting of the British-Society-for-Parasitology CY SEP 15-17, 1997 CL UNIV LIVERPOOL, LIVERPOOL, ENGLAND SP British Soc Parasitol HO UNIV LIVERPOOL ID PLASMODIUM-FALCIPARUM; PROTECTIVE ANTIBODIES; SPOROZOITES; HEPATOCYTES; ANTIGENS; INVITRO; CELLS; LOCALIZATION; BERGHEI; THROMBOSPONDIN AB The molecular events controlling sporozoite invasion and eso-erythrocytic (EE) development within hepatocytes are largely not understood, and EE parasites are probably better defined immunologically than biologically. The observation that the Plasmodium falciparum sporozoite antigen TRAP (thrombospondin-related anonymous protein) contains multiple adhesive domains that recognize endothelial and hepatocyte receptors indicates that, like leucocyte passage across capillaries, sporozoite invasion probably involves a co-ordinated interaction between sporozoite and hepatic molecules. The parallel with leucocyte extravasation is strengthened by the finding that TRIP contains a functional, integrin-like, I domain. EE parasites are an important target of immunity elicited by irradiated sporozoites, and much current effort is focused on developing malaria vaccines targeting EE parasites. Only one EE-specific antigen, liver-stage antigen 1 (LSA-1), is known to be expressed during EE development and may contribute to protective immunity elicited by irradiated P. falciparum sporozoites. In a study in Papua New Guinea, resistance to P. falciparum infection correlated with CD8(+) T-cell interferon-gamma responses to an LSA-1 epitope that contains an HLA All-restricted sequence. Since All is > 40% frequent in this population it is reasonable to suggest that, as with B53 responses to LSA-1 in The Gambia, P. falciparum has driven genetic selection of certain HLA haplotypes, as proposed by Haldane nearly 50 years ago. LSA-1 is thus an important vaccine candidate, and is being expressed in bacterial and phage vectors. C1 Univ Leeds, Sch Biol, Leeds LS2 9JT, W Yorkshire, England. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20853 USA. Case Western Reserve Univ, Div Geog Med, Cleveland, OH 44106 USA. RP Hollingdale, MR (reprint author), Univ Leeds, Sch Biol, Leeds LS2 9JT, W Yorkshire, England. NR 33 TC 19 Z9 19 U1 1 U2 1 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0003-4983 J9 ANN TROP MED PARASIT JI Ann. Trop. Med. Parasitol. PD JUN PY 1998 VL 92 IS 4 BP 411 EP 417 PG 7 WC Public, Environmental & Occupational Health; Parasitology; Tropical Medicine SC Public, Environmental & Occupational Health; Parasitology; Tropical Medicine GA ZW059 UT WOS:000074369800005 PM 9683893 ER PT J AU Chen, RM Chou, MW Ueng, TH AF Chen, RM Chou, MW Ueng, TH TI Induction of cytochrome P450 1A in hamster liver and lung by 6-nitrochrysene SO ARCHIVES OF TOXICOLOGY LA English DT Article DE 6-nitrochrysene; cytochrome P450; mutagenicity; nitroreductase ID DNA ADDUCT FORMATION; AROMATIC-HYDROCARBONS; NEWBORN MICE; METABOLISM; RAT; ENZYMES; MOUSE; METHOXYRESORUFIN; 1-NITROPYRENE; TRANSCRIPTION AB The present study has determined the effect of 6-nitrochrysene (6-NC) on hepatic and pulmonary cytochrome P450 (P450)-dependent monooxygenases using hamsters pretreated with the nitrated polycyclic aromatic hydrocarbon (nitro-PAH) at 5 mg/kg per day for 3 days. Pretreatment with 6-NC elevated serum gamma-glutamyltranspeptidase, lactate dehydrogenase, and bilirubin levels. Liver S9 fractions prepared from controls and hamsters pretreated with 6-NC markedly increased mutagenicity of the nitro-PAH in Salmonella typhimurium tester strains TA98, TA100, and TA102. The pretreatment selectively increased l-nitropyrene reductase activities of lung cytosol and liver and lung microsomes. Pretreatment with 6-NC resulted in increases of microsomal 7-ethoxyresorufin and methoxyresorufin O-dealkylases activities in liver and lung without affecting the monooxygenase activities in kidney. Immunoblot analysis of microsomal proteins using mouse monoclonal antibody 1-12-3 to rat P450 1A1 revealed that 6-NC induced P450 1A-immunorelated proteins in liver and lung. RNA blot analysis using mouse P450 1A1 cDNA showed that 6-NC increased liver and lung P450 1A mRNA. 6-NC had no effect on the kidney P450 protein and mRNA. The present study demonstrates that the hamster enzymes can support 6-NC metabolic activation and the nitro-PAH induces liver and lung P4501A via a pretranslational mechanism. C1 Natl Taiwan Univ, Coll Med, Inst Toxicol, Taipei 10018, Taiwan. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Ueng, TH (reprint author), Natl Taiwan Univ, Coll Med, Inst Toxicol, 1 Jen Ai Rd,Sect 1, Taipei 10018, Taiwan. NR 38 TC 22 Z9 23 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-5761 J9 ARCH TOXICOL JI Arch. Toxicol. PD JUN PY 1998 VL 72 IS 7 BP 395 EP 401 DI 10.1007/s002040050519 PG 7 WC Toxicology SC Toxicology GA 129RB UT WOS:000076475800002 PM 9708878 ER PT J AU Egorin, MJ Rosen, DM Wolff, JH Callery, PS Musser, SM Eiseman, JL AF Egorin, MJ Rosen, DM Wolff, JH Callery, PS Musser, SM Eiseman, JL TI Metabolism of 17-(allylamino)-17-demethoxygeldanamycin (NSC 330507) by murine and human hepatic preparations SO CANCER RESEARCH LA English DT Article ID GENE-PRODUCT P185; BENZOQUINOID ANSAMYCINS; EPOXIDE HYDROLASE; IN-VITRO; GELDANAMYCIN; INHIBITION; BINDING; DERIVATIVES; MECHANISM; DEPLETION AB 17-(Allylamino)-17-demethoxygeldanamycin (17AAG), a compound that is proposed for clinical development, shares the ability of geldanamycin to bind to heat shock protein 90 and GRP94, thereby depleting cells of p185(erbB2), mutant p53, and Raf-1, Urine and plasma from mice treated i.v. with 17AAG contained six materials with absorption spectra similar to that of 17AAG. Therefore, in vitro metabolism of 17AAG by mouse and human hepatic preparations was studied to characterize: (a) the enzymes responsible for 17AAG metabolism; and (b) the structures of the metabolites produced. These materials had retention times on high-performance liquid chromatography of approximately 2, 4, 5, 6, 7, and 9 min, When incubated in an aerobic environment with 17AAG, murine hepatic supernatant (9000 x g) produced each of these compounds; the 4-min metabolite was the major product. This metabolism required an electron donor, and NADPH was favored over NADH, Metabolic activity resided predominantly in the microsomal fraction. Metabolism was decreased by similar to 80% in anaerobic conditions and was essentially ablated by CO. Microsomes prepared from human livers produced essentially the same metabolites as produced by murine hepatic microsomes, but the 2-min metabolite was the major product, and the 4-min metabolite was next largest. There was no metabolism of 17AAG by human liver cytosol, Metabolism of 17AAG by human liver microsomes also required an electron donor, with NADPH being preferred over NADH, was inhibited by similar to 80% under anaerobic conditions, and was essentially ablated by CO. Liquid chromatography/mass spectrometry analysis of human and mouse in vitro reaction mixtures indicated the presence of materials with molecular weights of 545, 601, and 619, compatible with 17-(amino)-17-demethoxygeldanamycin (17AG), an epoxide, and a diol, respectively. The metabolite with retention time of 4 min was identified as 17AG by cochromatography and mass spectral concordance with authentic standard. Human microsomal metabolism of 17AAG was inhibited by ketoconazole, implying 3A4 as the responsible cytochrome P450 isoform, Incubation of 17AAG with cloned CYP3A4 produced metabolites 4 and 6, Incubation of 17AAG with cloned CYP3A4 and cloned microsomal epoxide hydrolase produced metabolites 2 and 4, with greatly decreased amounts of metabolite 6, Incubation of 17AAG with human hepatic microsomes and cyclohexene oxide, a known inhibitor of microsomal epoxide hydrolase, did not affect the production of metabolite 4 but decreased the production of metabolite 2 while increasing the production of metabolite 6. These data imply that metabolite 2 is a diol and metabolite 6 is an epoxide, Mass spectral fragmentation patterns and the fact that 17AG is not metabolized argue for the epoxide and diol being formed on the 17-allylamino portion of 17AAG and not on its ansamycin ring. These data have implications with regard to preclinical toxicology and activity testing of 17AAG as well as its proposed clinical development because: (a) production of 17AG requires concomitant production of acrolein from the cleaved allyl moiety; and (b) 17AG, which was not metabolized by microsomes, has been described as being as active as 17AAG in decreasing cellular p185(erbB2). C1 Univ Maryland, Sch Med, Greenebaum Canc Ctr, Div Dev Therapeut,Bressler Res Labs 9024, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Med, Div Hematol Oncol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. US FDA, Ctr Food Safety & Appl Nutr, Instrumentat & Biophys Branch, Washington, DC 20204 USA. Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. RP Egorin, MJ (reprint author), Univ Maryland, Sch Med, Greenebaum Canc Ctr, Div Dev Therapeut,Bressler Res Labs 9024, 655 W Baltimore St, Baltimore, MD 21201 USA. EM megorin@umabnrt.ab.umd.edu FU NCI NIH HHS [N01-CM57199] NR 32 TC 111 Z9 117 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1998 VL 58 IS 11 BP 2385 EP 2396 PG 12 WC Oncology SC Oncology GA ZR703 UT WOS:000074005300024 PM 9622079 ER PT J AU Chou, HC Ozawa, S Fu, PP Lang, NP Kadlubar, FF AF Chou, HC Ozawa, S Fu, PP Lang, NP Kadlubar, FF TI Metabolic activation of methyl-hydroxylated derivatives of 7,12-dimethylbenz[a]anthracene by human liver dehydroepiandrosterone-steroid sulfotransferase SO CARCINOGENESIS LA English DT Article ID BENZYLIC DNA ADDUCTS; SULFURIC-ACID ESTER; PHENOL SULFOTRANSFERASE; MOLECULAR-CLONING; SULFATE ESTER; IMMUNOCHEMICAL CHARACTERIZATION; IMMUNOLOGICAL CHARACTERIZATION; ESTROGEN SULFOTRANSFERASE; ACTIVE METABOLITE; RAT AB Methyl-hydroxylated metabolites of the potent carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA), namely, 7-hydroxymethyl- 12-methylbenz[a] anthracene (7-OH-DMBA), 7-methyl-12-hydroxymethylbenz[a]anthracene (12-OH-DMBA) and 7,12-dihydroxymethylbenz[a]anthracene (7,12-diOH-DMBA), were examined as substrates for sulfotransferase bioactivation in different human tissue cytosols, Hepatic cytosols, which were able to catalyze the 3'-phosphoadenosine 5'-phosphosulfate (PAPS)-dependent DNA binding of 7-OH-DMBA, 12-OH-DMBA and 7,12-diOH-DMBA, were highly sensitive to inhibition by dehydroepiandrosterone (DHEA), a specific substrate for human DHEA-steroid sulfotransferase (IC50 = 5 mu M), By comparison, 2,6-dichloro-4-nitrophenol, a potent inhibitor of the thermostable (TS)-phenol and estrogen sulfotransferases, did not have an appreciable inhibitory effect. Neither p-nitrophenol, a high affinity substrate for human TS-phenol and estrogen sulfotransferases, nor dopamine, a specific substrate for the thermolabile (TL)-phenol sulfotransferase, significantly inhibited the DNA binding of 12-OH-DMBA catalyzed by hepatic cytosols, Inter-subject variation (n = 12) of the PAPS-dependent DNA binding of 12-OH- and 7,12-diOH-DMBAs also correlated well with DHEA-sulfotransferase activity (r = 0.90; P < 0.00001 and r = 0.92; P < 0,00001, respectively). This sulfation-dependent metabolic activation was not detected in cytosols from human colon, pancreas, larynx or mammary gland. Both TS- and TL-phenol sulfotransferases were active in human liver and colon but only liver contained DHEA-sulfotransferase activity, These results indicate that the sulfotransferase-mediated activation of the methylhydroxylated DMBAs is predominantly catalyzed by DHEA-steroid sulfotransferase in human liver and that TS- and TL-phenol sulfotransferases and estrogen sulfotransferase are not involved in the catalysis. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. John L McClellan Mem Vet Adm Med Ctr, Surg Serv, Little Rock, AR 72205 USA. Arkansas Canc Res Ctr, Div Surg, Little Rock, AR 72205 USA. RP Kadlubar, FF (reprint author), Natl Ctr Toxicol Res, HFT-100, Jefferson, AR 72079 USA. NR 60 TC 20 Z9 21 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 JUN PY 1998 VL 19 IS 6 BP 1071 EP 1076 DI 10.1093/carcin/19.6.1071 PG 6 WC Oncology SC Oncology GA ZV977 UT WOS:000074361300016 PM 9667746 ER PT J AU Ziobro, G AF Ziobro, G TI Filth and food safety SO CHEMISTRY & INDUSTRY LA English DT Article ID FARM-STORED WHEAT; ACOUSTICAL DETECTION; GRAIN; COLEOPTERA; CURCULIONIDAE; BOSTRICHIDAE; INSECTS C1 US FDA, Ctr Food Safety & Appl Nutr, Div Nat Prod, Microanalyt Branch HFS315, Washington, DC 20204 USA. RP Ziobro, G (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Nat Prod, Microanalyt Branch HFS315, 200 C St SW, Washington, DC 20204 USA. NR 14 TC 0 Z9 0 U1 0 U2 1 PU SOC CHEMICAL INDUSTRY PI LONDON PA 14 BELGRAVE SQUARE, LONDON SW1X 8PS, ENGLAND SN 0009-3068 J9 CHEM IND-LONDON JI Chem. Ind. PD JUN 1 PY 1998 IS 11 BP 428 EP 431 PG 4 WC Chemistry, Applied SC Chemistry GA ZT209 UT WOS:000074060600017 ER PT J AU Chen, ET Schroeder, LW Luu, HD AF Chen, ET Schroeder, LW Luu, HD TI Error analysis for three commonly used clinical methods for blood glucose monitoring at two accredited clinical hospital laboratories. SO CLINICAL CHEMISTRY 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 ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1998 VL 44 SU 6 MA 608 BP A139 EP A140 PN 2 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA ZT249 UT WOS:000074065700611 ER PT J AU Niu, MT Salive, M Krueger, C Ellenberg, SS AF Niu, MT Salive, M Krueger, C Ellenberg, SS TI Two-year review of hepatitis A vaccine safety: Data from the Vaccine Adverse Event Reporting System (VAERS) SO CLINICAL INFECTIOUS DISEASES LA English DT Article C1 US FDA, CBER, OELPS, DBE, Rockville, MD 20852 USA. RP Niu, MT (reprint author), US FDA, CBER, OELPS, DBE, 1401 Rockville Pike,HFM-210, Rockville, MD 20852 USA. NR 5 TC 25 Z9 27 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN PY 1998 VL 26 IS 6 BP 1475 EP 1476 DI 10.1086/517673 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZU252 UT WOS:000074177900057 PM 9636890 ER PT J AU Hartman, NR Leo, KU Brewer, TG Strong, JM AF Hartman, NR Leo, KU Brewer, TG Strong, JM TI The in vitro metabolism of penclomedine in mouse, rat, and human systems SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID PRECLINICAL ANTITUMOR-ACTIVITY; IN-VIVO; NSC-338720; MURINE; LIVER; TISSUE AB Penclomedine is a multi-chlorinated alpha-picoline derivative that has demonstrated activity in several murine breast cancer models and is currently in clinical testing for use against solid tumors. This study evaluates the metabolism of penclomedine in several in vitro hepatic models, including microsomes, fresh liver slices, and the isolated perfused rat liver (IPRL), Both human and mouse liver slices as well as human and mouse liver microsomes under aerobic conditions resulted in limited metabolism of penclomedine to several oxidized metabolites, including penclomic acid, 4-demethylpenclomic acid, and 4-demethylpenclomedine. Microsomes under anaerobic conditions vigorously produced mainly reduced metabolites, primarily penclomedine dimers, This is in contrast to in vivo data, which showed rapid metabolism of penclomedine to primarily 4-demethylpenclomedine. The IPRL preparation, however, metabolized 50 mu M penclomedine 90% within 90 min, producing primarily 4-demethylpenclomedine and penclomic acid, These were formed in roughly equimolar amounts and did not undergo significant further metabolism over 4 hr. Numerous highly polar biliary metabolites were also found. The IPRL preparation thus seems to most accurately reflect the in vivo situation. C1 US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol Res, Off Testing & Res,Off Pharmaceut Sci, Laurel, MD 20708 USA. Walter Reed Army Inst Res, Washington, DC 20307 USA. Armed Forces Res Inst Med Sci, Washington, DC USA. RP Hartman, NR (reprint author), US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol Res, Off Testing & Res,Off Pharmaceut Sci, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 21 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JUN PY 1998 VL 26 IS 6 BP 513 EP 519 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZU557 UT WOS:000074210000002 PM 9616185 ER PT J AU Huggett, A Petersen, BJ Walker, R Fisher, CE Notermans, SHW Rombouts, FM Abbott, P Debackere, M Hathaway, SC Hecker, EFF Knaap, AGA Kuznesof, PM Meyland, I Moy, G Narbonne, JF Paakkanen, J Smith, MR Tennant, D Wagstaffe, P Wargo, J Wurtzen, G AF Huggett, A Petersen, BJ Walker, R Fisher, CE Notermans, SHW Rombouts, FM Abbott, P Debackere, M Hathaway, SC Hecker, EFF Knaap, AGA Kuznesof, PM Meyland, I Moy, G Narbonne, JF Paakkanen, J Smith, MR Tennant, D Wagstaffe, P Wargo, J Wurtzen, G TI Towards internationally acceptable standards for food additives and contaminants based on the use of risk analysis SO ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT Conference on Towards Internationally Acceptable Standards for Food Additives and Contaminants Based on the Use of Risk Analysis CY NOV 26-28, 1997 CL EDE, NETHERLANDS SP European Training & Assessment Fdn, Wageningen DE international standards; food additives; contaminants; risk assessment; risk management; dietary intake estimates; interaction of risk assessors and managers; aflatoxins; aspartame AB Internationally acceptable noons need to incorporate sound science and consistent risk management principles in an open and transparent manner, as set out in the Agreement on the Application of Sanitary and Phytosanitary measures (the SPS Agreement). The process of risk analysis provides a procedure to reach these goals. The interaction between risk assessors and risk managers is considered vital to this procedure. This paper reports the outcome of a meeting of risk assessors and risk managers on specific aspects of risk analysis and its application to international standard setting for food additives and contaminants. Case studies on aflatoxins and aspartame were used to identify the key steps of the interaction process which ensure scientific justification for risk management decisions. A series of recommendations were proposed in order to enhance the scientific transparency in these critical phases of the standard setting procedure. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Nestec Ltd, Nestle Res Ctr, CH-1000 Lausanne, Switzerland. Novigen Sci Inc, Washington, DC USA. Univ Surrey, Div Toxicol, Food Safety Grp, Surrey, England. Minist Agr Fisheries & Food, Nutr & Policy Div, London, England. TNO, Div Ind Microbiol, Nutr & Food Res Inst, NL-3700 AJ Zeist, Netherlands. Agr Univ Wageningen, Dept Food Chem & Microbiol, Wageningen, Netherlands. Australia New Zealand Food Author, Canberra, ACT, Australia. MAF Regulatory Author Meat & Seafood, Gisborne, New Zealand. Minist Agr Nat Management & Fisheries, Dept Environm Qual & Hlth, Den Haag, Netherlands. RIVM, Natl Inst Publ Hlth & Environm, Ctr Subst & Risk Assessment, Bilthoven, Netherlands. US FDA, Off Pre Market Approval, Washington, DC 20204 USA. Danish Vet & Food Adm, Soborg, Denmark. WHO, Food Safety Unit, Div Food & Nutr, CH-1211 Geneva, Switzerland. Univ Bordeaux, Lab Toxicol Alimentaire, Bordeaux, France. Food & Agr Org United Nat, Food & Nutr Div, Rome, Italy. Unilever Res, Environm Safety Lab, Bedford, England. TAS Environ, European Sci Regulatory Affairs, London, England. European Commiss, DG Consumer Policy & Consumer Hlth Protect 24, Brussels, Belgium. Yale Univ, Ctr Childrens Environm Hlth, New Haven, CT USA. Coca Cola Nord & No Eurasia Div, Glostrup, Denmark. RP Huggett, A (reprint author), ETAF, POB 182, NL-6700 AD Wageningen, Netherlands. RI Rombouts, Frans/F-9882-2011 NR 13 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1382-6689 J9 ENVIRON TOXICOL PHAR JI Environ. Toxicol. Pharmacol. PD JUN PY 1998 VL 5 IS 4 BP 227 EP 236 DI 10.1016/S1382-6689(98)00017-9 PG 10 WC Environmental Sciences; Pharmacology & Pharmacy; Toxicology SC Environmental Sciences & Ecology; Pharmacology & Pharmacy; Toxicology GA ZY907 UT WOS:000074674500001 PM 21781869 ER PT J AU Woods, TO Berghaus, DG Peacock, HB AF Woods, TO Berghaus, DG Peacock, HB TI Interparticle movement and the mechanical behavior of extruded powder aluminum at elevated temperature SO EXPERIMENTAL MECHANICS LA English DT Article AB This paper proposes a model and a mechanism for explaining the mechanical behavior of extruded powder aluminum at elevated temperature. This behavior is significantly different from that of ingot-cast and drawn aluminum which is subjected to the same tests. Powder aluminum exhibits a strain-softening effect which is evident in a decrease of stress with increasing strain in uniaxial test specimens when the experiment proceeds into the postyield region. Similar behavior is observed in the shear response during biaxial tension-torsion loading. For these tests, the shear stress is additionally reduced with increased axial extension. A model and mechanism are proposed, based on the relative motion of the extruded aluminum particles, to explain this effect. Equations are derived which relate the axial and shear stresses and strains. These equations are fitted to data obtained in a matrix of experiments, which include combined loadings from uniaxial tension to simple shear. Results are presented graphically and are in good agreement with the proposed models. C1 US FDA, Rockville, MD 20850 USA. Georgia Inst Technol, Atlanta, GA 30332 USA. RP Woods, TO (reprint author), US FDA, Rockville, MD 20850 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0014-4851 J9 EXP MECH JI Exp. Mech. PD JUN PY 1998 VL 38 IS 2 BP 110 EP 115 DI 10.1007/BF02321653 PG 6 WC Materials Science, Multidisciplinary; Mechanics; Materials Science, Characterization & Testing SC Materials Science; Mechanics GA ZT336 UT WOS:000074074800007 ER PT J AU Huang, XZ Tall, B Schwan, WR Kopecko, DJ AF Huang, XZ Tall, B Schwan, WR Kopecko, DJ TI Physical limitations on Salmonella typhi entry into cultured human intestinal epithelial cells SO INFECTION AND IMMUNITY LA English DT Article ID TYPHIMURIUM INVASION; ESCHERICHIA-COLI; MAMMALIAN-CELLS; IPA PROTEINS; GROWTH-PHASE; HELA-CELLS; GIFU 10007; BACTERIA; PENETRATION; MACROPINOCYTOSIS AB Kinetic studies of Salmonella typhi invasion of LNT407 cells at different multiplicities of infection (MOIs) have revealed a strict physical limitation on S. typhi entry at MOIs of greater than or equal to 40. Staining of infected monolayers to distinguish intracellular from extracellular bacteria revealed that all monolayer cells are susceptible to infection and that internalized bacteria are typically contained in one to three separate clusters per cell during the first 60 min. Scanning and transmission electron microscopic analyses of time course-infected monolayers showed that at early times postinfection, bacteria bind to shortened, coalesced microvilli in one to three focal aggregate structures per host cell surface. As reported previously for S. typhimurium, focal aggregates progress to conical membrane ruffles that appear to engulf one or a few centrally contained S. typhi cells by a macro-pinocytic process, which enhanced the entry of simultaneously added Escherichia coli HB101 about 30-fold. Additionally, kinetic studies showed that at an MOI of similar or equal to 400, maximal S. typhi entry is virtually completed within 30 to 35 min. Monolayers pretreated with S. typhi for 30 min to saturate the entry process were severely reduced in the ability to internalize subsequently added kanamycin-resistant strains of S. typhi or S. typhimurium, but E. coli HB101(pRI203) expressing the cloned Yersinia inv gene was not reduced in entry. In invasion inhibition assays, anti-beta 1 integrin antibodies markedly reduced E. coli HB101(pRI203) invasion efficiency but did not reduce S. typhi entry. Collectively, these data provide direct physical and visual evidence which indicates that S. typhi organisms are internalized at a limited number (i.e., two to four) of sites on host cells. S. typhi and S. typhimurium likely share INT407 cell entry receptors which do not appear to be members of the beta 1 integrin superfamily. C1 US FDA, Ctr Biol Evaluat & Res, Lab Enter & STDs, HFM 440, Bethesda, MD 20892 USA. US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol Studies, Washington, DC 20204 USA. RP Kopecko, DJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Enter & STDs, HFM 440, Bldg 29,NIH Campus, Bethesda, MD 20892 USA. OI Tall, Ben/0000-0003-0399-3629 NR 46 TC 24 Z9 24 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 1998 VL 66 IS 6 BP 2928 EP 2937 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZP714 UT WOS:000073781100075 PM 9596769 ER PT J AU Umehara, H Huang, JY Kono, T Tabassam, FH Okazaki, T Gouda, S Nagano, Y Bloom, ET Domae, N AF Umehara, H Huang, JY Kono, T Tabassam, FH Okazaki, T Gouda, S Nagano, Y Bloom, ET Domae, N TI Co-stimulation of T cells with CD2 augments TCR-CD3-mediated activation of protein tyrosine kinase p72(syk), resulting in increased tyrosine phosphorylation of adapter proteins, Shc and Cbl SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE adapter protein; CD2; cellular activation; co-stimulatory molecules; protein kinase; signal transduction; T lymphocytes; TCR ID FUNCTION-ASSOCIATED ANTIGEN-1; SHEEP ERYTHROCYTE RECEPTOR; NATURAL-KILLER-CELLS; SIGNAL-TRANSDUCTION; PROTOONCOGENE PRODUCT; IN-VIVO; PHOSPHATIDYLINOSITOL 3-KINASE; ALTERNATIVE PATHWAY; CYTOPLASMIC DOMAIN; LYMPHOCYTES-T AB Complete T cell activation requires not only the first signal via TCR-CD3 engagement, but also a co-stimulatory signal through accessory receptors such as CD2, LFA-1 and CD28, However, the pathway of co-stimulatory signaling through accessory receptors is incompletely understood. We report here that CD2 provides a co-stimulus for activation of CD3-mediated syk/ZAP-70 family kinase, p72(syk) (Syk), in Jurkat T cells, Although cross-linking of CD2 alone or any combination of CD2 with LFA-1 alpha, LFA-1 beta or CD28 did not induce tyrosine phosphorylation of Syk, co-cross-linking of CD2 with CD3 enhanced CD3-mediated tyrosine phosphorylation of Syk, Enhancement of tyrosine phosphorylation of Syk by CD2 co-stimulation was CD2 antibody concentration-dependent, and time course studies showed that CD2 co-stimulation enhanced Syk tyrosine phosphorylation by 30 s and through 5 min stimulation compared with the control. In vitro kinase assay revealed that co-cross-linking of CD2 with CD3 augmented Syk kinase activity using myelin basic protein as a substrate. Furthermore, CD2 co-stimulation with CD3 resulted in enhanced tyrosine phosphorylation of adapter proteins, such as Shc and Cbl, in an antibody concentration-dependent manner. Finally, CD2 provided a co-stimulatory signals for synthesis of IL-2 in Jurkat cells and phytohemagglutinin (PHA)-activated T cells and for proliferation of PHA-activated T cells. Taken together, these results indicate that CD2 is an important co-stimulatory receptor for CD3-mediated T cell activation and functions in concert with CD3. C1 Osaka Dent Univ, Dept Med, Hirakata, Osaka 573, Japan. Nippon Boehringer Ingelheim, Kawanishi Pharma Inst, Dept Mol & Cellular Biol, Topeka, KS 66601 USA. Kyoto Univ, Grad Sch Med, Dept Hematol & Oncol, Sakyo Ku, Kyoto 606, Japan. US FDA, Ctr Biol Evaluat Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Umehara, H (reprint author), Osaka Dent Univ, Dept Med, 8-1 Kuzuha Hanazono Cho, Hirakata, Osaka 573, Japan. NR 68 TC 23 Z9 24 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUN PY 1998 VL 10 IS 6 BP 833 EP 845 DI 10.1093/intimm/10.6.833 PG 13 WC Immunology SC Immunology GA ZW523 UT WOS:000074419500015 PM 9678765 ER PT J AU Niu, MT Rhodes, P Salive, M Lively, T Davis, DM Black, S Shinefield, H Chen, RT Ellenberg, SS AF Niu, MT Rhodes, P Salive, M Lively, T Davis, DM Black, S Shinefield, H Chen, RT Ellenberg, SS CA VAERS Working Grp VSD Working Grp TI Comparative safety of two recombinant hepatitis B vaccines in children: Data from the Vaccine Adverse Event Reporting System (VAERS) and Vaccine Safety Datalink (VSD) SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE hepatitis B vaccine; vaccine safety; children; adverse events; VAERS; VSD ID CLINICAL-EXPERIENCE; PROTECTIVE EFFICACY; POSITIVE MOTHERS; IMMUNOGENICITY; INFANTS; DNA; SURVEILLANCE AB Background: Preliminary review of data from the Vaccine Adverse Event Reporting System (VAERS), 1991-1994, revealed that more serious adverse events were reported in children who received a specific brand of recombinant hepatitis B (HepB) vaccine. Objective: To compare the post-marketing safety experience of the two recombinant HepB vaccines licensed for use in infants and children in the United States. Design: Review of a case series derived from passive surveillance data in the national VAERS. A retrospective cohort study using data from one health maintenance organization participating in Vaccine Safety Datalink (VSD), a computerized record linkage system. Populations Studied: U.S. Children, ages birth-10 year for whom adverse events after HepB vaccine were reported to VAERS, 1991-1994. Children, ages birth-6 years, who received HepB vaccine at Kaiser Permanente Medical Care Program, Northern California, 1991-1994. Main Outcome Measures: VAERS reporting rates for each vaccine by manufacturer were calculated from the numbers of reported events occurring within 30 days of HeB vaccination and the number of doses distributed by the manufacturers. VSD event rates for each vaccine were calculated from the numbers of hospitalization or emergency room visits within 30 days of HepB vaccination and the number of vaccine doses administered to the cohort. Results: In VAERS, higher rates of serious events (i.e., life threatening or resulting in hospitalization or permanent disability) were reported in children who received Vaccine A vs. Vaccine B (relative risk [RR]: 3.13-8.18, P < 0.01), particularly by those vaccinated in the private (RR: 7.62-28.58, P < 0.01), but not public sector (RR: 2.12, P = 0.19). Similar types of events were reported in recipients of both vaccines. In contrast, analysis of VSD data showed no significant difference in rates of hospitalization or ER visits in children who received either HepB vaccine (RR: 0.96-1.25, P > 0.05). Conclusions: Our investigation reveals that it is unlikely there is a true difference between rates of serious events temporally associated with the two HepB vaccines in children. This study demonstrates the dual roles played by VAERS and VSD in providing a more complete picture of the post-marketing safety profile of childhood vaccines, and underscores the importance of using other analytic studies to evaluate findings from passive surveillance systems of adverse events. (C) 1998 Elsevier Science Inc. C1 US FDA, CBER, OELPS, DBE, Rockville, MD 20857 USA. Ctr Dis Control & Prevent, Natl Immunizat Program, Vaccine Safety & Dev Act, Atlanta, GA 30333 USA. No Calif Kaiser Permanente Hlth Syst, Oakland, CA USA. RP Niu, MT (reprint author), US FDA, CBER, OELPS, DBE, 1401 Rockville Pike,HFM-210, Rockville, MD 20857 USA. FU PHS HHS [20094-0820] NR 45 TC 33 Z9 33 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JUN PY 1998 VL 51 IS 6 BP 503 EP 510 DI 10.1016/S0895-4356(98)00014-6 PG 8 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA ZU152 UT WOS:000074167500008 PM 9635999 ER PT J AU Feng, P Lampel, KA Karch, H Whittam, TS AF Feng, P Lampel, KA Karch, H Whittam, TS TI Genotypic and phenotypic changes in the emergence of Escherichia coli O157 : H7 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 3rd International Symposium and Workshop on Shiga Toxin (Verocytotoxin)-Producing Escherichia coli Infections CY JUN, 1997 CL BALTIMORE, MARYLAND ID HEMOLYTIC-UREMIC SYNDROME; CAUSE HEMORRHAGIC COLITIS; SEROTYPE O157-H7; DNA PROBE; IDENTIFICATION; INFECTIONS; ADHERENCE; STRAINS; LOCUS AB Escherichia toil O157:H7 is a foodborne pathogen distinguished from typical E. coli by the production of Shiga toxins (Stx) and the inability to ferment sorbitol (SOR) and to express beta-glucuronidase (GUD) activity. An allele-specific probe for the GUD gene (uidA) and multilocus enzyme electrophoresis were used to elucidate stages in the evolutionary emergence off. coli O157:H7. A point mutation at +92 in uidA was found only in O157:H7 and its nonmotile relatives, including a SOR+ O157:H- clone implicated in outbreaks of hemolytic-uremic syndrome in Germany. The results support a model in which O157:H7 evolved sequentially from an O55:H7 ancestor, first by acquiring the Stx2 gene and then by diverging into two branches; one became GUD(-) SOR-, resulting in the O157:H7 clone that spread worldwide, and the other lost motility, leading to the O157:H- clone that is an increasing public health problem in Europe. C1 Penn State Univ, Dept Biol, Inst Mol Evolut Genet, Mueller Lab 208, University Pk, PA 16802 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Univ Wurzburg, Inst Hyg & Mikrobiol, Wurzburg, Germany. RP Whittam, TS (reprint author), Penn State Univ, Dept Biol, Inst Mol Evolut Genet, Mueller Lab 208, University Pk, PA 16802 USA. EM tsw1@psu.edu NR 15 TC 197 Z9 203 U1 0 U2 10 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1998 VL 177 IS 6 BP 1750 EP 1753 DI 10.1086/517438 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZP618 UT WOS:000073771500047 PM 9607864 ER PT J AU Buyon, JP Hiebert, R Copel, J Craft, J Friedman, D Katholi, M Lee, LA Provost, TT Reichlin, M Rider, L Rupel, A Saleeb, S Weston, WL Skovron, ML AF Buyon, JP Hiebert, R Copel, J Craft, J Friedman, D Katholi, M Lee, LA Provost, TT Reichlin, M Rider, L Rupel, A Saleeb, S Weston, WL Skovron, ML TI Autoimmune-associated congenital heart block: Demographics, mortality, morbidity and recurrence rates obtained from a national neonatal lupus registry SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID COMPLETE ATRIOVENTRICULAR-BLOCK; B LA ANTIBODIES; SS-A/RO; INTRAUTERINE THERAPY; HUMAN KERATINOCYTES; FETAL MYOCARDITIS; ERYTHEMATOSUS; MOTHERS; CHILDREN; RISK AB Objectives. The present study describes the demographics, mortality, morbidity and recurrence rates of autoimmune-associated congenital heart block (CHB) using information from the Research Registry for Neonatal Lupus. Background. Isolated CHB detected at or before birth is strongly associated with maternal autoantibodies to 48-kD SSB/La, 52-kD SSA/Ro and 60-kD SSA/Ro ribonucleoproteins and is a permanent manifestation of the neonatal lupus syndromes (NLS). Available data are limited by the rarity of the disease. Results. The cohort includes 105 mothers whose sera contain anti-SSA/Ro or anti-SSB/La antibodies, or both, and their 113 infants diagnosed with CHB between 1970 and 1997 (56 boys, 57 girls). Of 57 pregnancies in which sufficient medical records were available, bradyarrhythmia confirmed to be CHB was initially detected before 30 weeks of gestation in 71 (82%) (median time 23 weeks). There were no cases in which major congenital cardiac anatomic defects were considered causal for the development of CHB; in 14 there were minor abnormalities. Twenty-two (19%) of the 113 children died, 16 (73%) within 3 months after birth. Cumulative probability of 3-year survival was 79%. Sixty-seven (63%) of 107 live-born children required pacemakers: 35 within 9 days of life, 15 within 1 year, and 17 after 1 year. Forty-nine of the mothers had subsequent pregnancies: 8 (16%) had another infant with CHB and 3 (6%) had a child with an isolated rash consistent with NLS. Conclusions. Data from this large series substantiate that autoantibody-associated CHB is not coincident with major structural abnormalities, is most often identified in the late second trimester, carries a substantial mortality in the neonatal period and frequently requires pacing. The recurrence rate of CHB is at least two- to three-fold higher than the rate for a mother with anti-SSA/Ro-SSB/La antibodies who never had an affected child, supporting close echocardiographic monitoring in all subsequent pregnancies, with heightened surveillance between 18 rand 24 weeks of gestation. (C) 1998 by the American College of Cardiology. C1 NYU, Hosp Joint Dis, Sch Med, Dept rheumatol & Med, New York, NY 10003 USA. Yale Univ, Sch Med, Dept Obstet & Gynecol, New Haven, CT USA. Yale Univ, Sch Med, Rheumatol Sect, New Haven, CT USA. Cornell Univ, Med Ctr, New York Hosp, Div Pediat Cardiol, New York, NY 10021 USA. Univ Colorado, Hlth Sci Ctr, Dept Dermatol, Denver, CO USA. Denver Hlth Med Ctr, Serv Dermatol, Denver, CO USA. Johns Hopkins Univ, Sch Med, Dept Dermatol, Baltimore, MD 21205 USA. Oklahoma Med Res Fdn, Arthritis & Immunol Program, Oklahoma City, OK 73104 USA. US FDA, Ctr Biol Evaluat & Res, Lab Mol Dev Immunol, Bethesda, MD USA. RP Buyon, JP (reprint author), Hosp Joint Dis, Dept Rheumatol, Room 1608,301 E 17th St, New York, NY 10003 USA. EM didonf01@mcrcr6.mcd.nyu.edu OI Rider, Lisa/0000-0002-6912-2458 FU NIAMS NIH HHS [N01-AR-4-2220] NR 38 TC 362 Z9 378 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN PY 1998 VL 31 IS 7 BP 1658 EP 1666 DI 10.1016/S0735-1097(98)00161-2 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZR486 UT WOS:000073982100030 PM 9626848 ER PT J AU Leverett, BD Farrell, KB Eiden, MV Wilson, CA AF Leverett, BD Farrell, KB Eiden, MV Wilson, CA TI Entry of amphotropic murine leukemia virus is influenced by residues in the putative second extracellular domain of its receptor, Pit2 SO JOURNAL OF VIROLOGY LA English DT Article ID A AVIAN-LEUKOSIS; RETROVIRUS RECEPTOR; CELLULAR RECEPTOR; SARCOMA-VIRUSES; INFECTION; PROTEIN; CELLS; TRANSPORTER; BINDING; FAMILY AB Human cells express distinct but related receptors for the gibbon ape leukemia virus (GALV) and the amphotropic murine leukemia virus (A-MuLV), termed Pit1 and Pit2, respectively. Pit1 is not able to function as a receptor for A-MuLV infection, while Pit2 does not confer susceptibility to GALV. Previous studies of chimeric receptors constructed by interchanging regions of Pit1 and Pit2 failed to clarify the determinants unique to Pit2 which correlate with A-MuLV: receptor function. In order to identify which regions of Pit2 are involved in A-MuLV receptor function, we exchanged the putative second and third extracellular domains of Pit1, either individually or together,,vith the corresponding regions of Pit2, Our functional characterization of these receptors indicates a role for the putative second extracellular domain (domain II) in A-MuLV infection. We further investigated the influence of domain LT with respect to A-MuLV: receptor function by performing site-specific mutagenesis within this region of Pit2, Many of the mutations had little or no effect on receptor function. However, the substitution of serine for methionine at position 138 (S138M) in a Pit1 chimera containing domain II of Pit2 resulted in a 1,000-fold reduction in A-MuLV receptor function, Additional mutations made within domain II of the nonfunctional S138M mutant restored receptor function to nearly wild-type efficiency: The high degree of tolerance for mutations as well as the compensatory effect of particular substitutions observed within domain II suggests that an element of secondary structure within this region plays a critical role in the interaction of the receptor with A-MuLV. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD USA. RP Wilson, CA (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, HFM-530,8800 Rockville Pike, Bethesda, MD 20892 USA. EM wilsonc@A1.cber.fda.gov NR 26 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1998 VL 72 IS 6 BP 4956 EP 4961 PG 6 WC Virology SC Virology GA ZM029 UT WOS:000073497600048 PM 9573264 ER PT J AU Kramer, JKG Sehat, N Dugan, MER Mossoba, MM Yurawecz, MP Roach, JAG Eulitz, K Aalhus, JL Schaefer, AL Ku, Y AF Kramer, JKG Sehat, N Dugan, MER Mossoba, MM Yurawecz, MP Roach, JAG Eulitz, K Aalhus, JL Schaefer, AL Ku, Y TI Distributions of conjugated linoleic acid (CLA) isomers in tissue lipid classes of pigs fed a commercial CLA mixture determined by gas chromatography and silver ion high-performance liquid chromatography SO LIPIDS LA English DT Article ID MAMMARY-CANCER PREVENTION; DAIRY-PRODUCTS; BREAST-CANCER; FATTY-ACIDS; MILK; DIET; RAT; CARCINOGENESIS; DERIVATIVES; BEEF AB Pigs were fed a commercial conjugated linoleic acid (CLA) mixture, prepared by alkali isomerization of sunflower oil, at 2% of the basal diet, from 61.5 to 106 kg live weight, and were compared to pigs fed the same basal diet with 2% added sunflower ail. The total lipids from liver, heart, inner back fat, and omental fat of pigs fed the CLA diet were analyzed for the incorporation of CLA isomers into all the tissue lipid classes. A total of 10 lipid classes were isolated by three-directional thin-layer chromatography and analyzed by gas chromatography (GC) on long capillary columns and by silver-ion highperformance liquid chromatography (Ag+-HPLC); cholesterol was determined spectrophotometrically. Only trace amounts (<0.1%; by CC) of the 9,11-18:2 cis/trans and trans,trans isomers were observed in pigs fed the control diet. Ten and twelve CLA isomers in the diet and in pig tissue lipids were separated by GC and Ag+-HPLC, respectively. The relative concentration of all the CLA isomers in the different lipid classes ranged from 1 to 6% of the total fatty acids. The four major cis/trans isomers (18.9% 11 cis,13 trans-18:2; 26.3% 10 trans,12 cis-18:2; 20.4% 9 cis,ll trans-18:2; and 16.1% 8 trans,10 cis-18:2) constituted 82% of the total CIA.isomers in the dietary CLA mixture, and smaller amounts of the corresponding cis,cis (7.4%) and trans, trans (10.1%) isomers were present. The distribution of CLA isomers in inner back fat and in omental fat of the pigs was similar to that found in the diet. The liver triacylglycerols (TAG), free fatty acids (FFA), and cholesteryl esters showed a similar pattern to that found in the diet. The major liver phospholipids showed a marked increase of 9 cis, 11 trans-18:2, ranging from 36 to 54%, compared to that present in the diet. However, liver diphosphatidylglycerol (DPC) showed a high incorporation of the 11 cis,13 trans-18:2 isomer (43%). All heart lipid classes, except TAG, showed a high content of 11 cis,13 trans-18:2, which was in marked contrast to results in the liver. The relative proportion of 11 cis,13 trans-18:2 ranged from 30% in the FFA to 77% in DPC. The second major isomer in all heart lipids was 9 cis,ll trans-18:2. In both liver and heart lipids the relative proportions of both 10 trans,12 cis-18:2 and 8 Irans,10 cis18:2 were significantly lower compared to that found in the diet. The FFA in liver and heart showed the highest content of trans,trans isomers (31 to 36%) among all the lipid classes. The preferential accumulation of the 11 cis,13 trans-18:2 into cardiac lipids, and in particular the major phospholipid in the inner mitochondrial membrane, DPG, in both heart and liver, appears unique and may be of concern. The levels of 11 cis,13 trans-18:2 naturally found in foods have not been established. C1 US FDA, Washington, DC 20204 USA. Agr & Agri Food Canada, Food Res Ctr, Guelph, ON N1G 2W1, Canada. Agr & Agri Food Canada, Lacombe Res Ctr, Lacombe, AB T4L 1W1, Canada. RP Kramer, JKG (reprint author), US FDA, Washington, DC 20204 USA. NR 47 TC 184 Z9 188 U1 2 U2 13 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PD JUN PY 1998 VL 33 IS 6 BP 549 EP 558 DI 10.1007/s11745-998-0239-1 PG 10 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA ZU610 UT WOS:000074215300001 PM 9655369 ER PT J AU Kazachkov, Y Yoffe, B Khaoustov, VI Solomon, H Klintmalm, GBG Tabor, E AF Kazachkov, Y Yoffe, B Khaoustov, VI Solomon, H Klintmalm, GBG Tabor, E TI Microsatellite instability in human hepatocellular carcinoma: relationship to p53 abnormalities SO LIVER LA English DT Article DE hepatocellular carcinoma; microsatellite; p53; tumor suppressor gene ID MISMATCH REPAIR; GENOMIC INSTABILITY; SPLICING MUTATIONS; CANCER; GENE; COLON; SUSCEPTIBILITY; LEUKEMIA; INTRON; TUMOR AB Aims/Background. Microsatellite instability was sought in 10 human hepatocellular carcinomas (HCCs) to determine whether defective DNA mismatch repair might be implicated in the multiple genetic alterations observed in the p53 tumor suppressor gene in some of these patients' tumors. Methods. Genomic DNA from HCCs and adjacent nontumorous livers was subjected to PCR with primers for nine microsatellites, and PCR products were resolved in a denaturing gel. Microsatellite instability was defined as the presence of band shifts or additional bands for at least two microsatellite sequences in an HCC compared to the nontumorous liver tissue from the same patient. Results: Microsatellite instability was detected in four of ten HCCs. Three of these four HCCs did not have p53 exon mutations. However, one HCC had microsatellite instability as well as multiple p53 exon mutations and multiple intron alterations. Four other patients with multiple p53 intron alterations in HCC (compared to their own nontumorous liver), three of whom also had a mutation in the exons, had no microsatellite instability. Conclusions: Defective DNA mismatch repair, as indicated by microsatellite instability, might have played a role in hepatocarcinogenesis in four of the ten patients, but in general it was not associated with p53 alterations. In one of the ten patients, defective DNA mismatch repair might have been the cause of multiple mutations in both the coding and intron sequences of the p53 gene. C1 US FDA, CBER, HFM 310, Rockville, MD 20852 USA. Baylor Coll Med, VAMC, Houston, TX 77030 USA. Baylor Univ, Med Ctr, Dallas, TX USA. RP Tabor, E (reprint author), US FDA, CBER, HFM 310, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 24 TC 21 Z9 23 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0106-9543 J9 LIVER JI Liver PD JUN PY 1998 VL 18 IS 3 BP 156 EP 161 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 102ZT UT WOS:000074956700002 PM 9716224 ER PT J AU Bain, AD Mazzola, EP Page, SW AF Bain, AD Mazzola, EP Page, SW TI A proposed standard sample for nuclear overhauser effect measurements SO MAGNETIC RESONANCE IN CHEMISTRY LA English DT Article DE nuclear Overhauser measurements; standard sample; 1,5-dichloro-2,4-dimethoxybenzene ID SLOW CHEMICAL-EXCHANGE; RELAXATION-TIMES; RESONANCE; SPECTROSCOPY; SPECTRA; COMPLEX AB A standard sample for the measurement of proton-proton nuclear Overhauser effects (NOE) is proposed. 1,5-Dichloro-2,4-dimethoxybenzene (DCDMB) shows an essentially full (50%) enhancement of the proton H-3 when the protons of the flanking methoxyl groups are saturated. The molecule is appropriate as a standard for the following reasons. The molecule is stable and easily synthesized. All the lines in the spectrum appear as singlets, so selective population transfer effects cannot obscure the NOE. The proton at position 6 provides a monitor of other relaxation mechanisms that would reduce the NOE. The NOE was verified by two complementary experiments. One is the standard technique of measuring the intensity with and without irradiation. A second method, based on spin-lattice relaxation rate experiments, provides unbiased data and gives an statistical estimate of the errors. Within experimental error, the NOE for DCDMB is 50%. (C) 1998 John Wiley & Sons, Ltd. C1 McMaster Univ, Dept Chem, Hamilton, ON L8S 4M1, Canada. US FDA, Joint Inst Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Bain, AD (reprint author), McMaster Univ, Dept Chem, 1280 Main St W, Hamilton, ON L8S 4M1, Canada. NR 22 TC 2 Z9 2 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0749-1581 J9 MAGN RESON CHEM JI Magn. Reson. Chem. PD JUN PY 1998 VL 36 IS 6 BP 403 EP 406 DI 10.1002/(SICI)1097-458X(199806)36:6<403::AID-OMR285>3.0.CO;2-A PG 4 WC Chemistry, Multidisciplinary; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA ZU236 UT WOS:000074176000003 ER PT J AU McCrohan, J AF McCrohan, J TI For the proposition SO MEDICAL PHYSICS LA English DT Editorial Material ID MAMMOGRAPHY C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP McCrohan, J (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 1998 VL 25 IS 6 BP 812 EP 812 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZV222 UT WOS:000074282600002 ER PT J AU Bondy, SC Ali, SF Guo-Ross, S AF Bondy, SC Ali, SF Guo-Ross, S TI Aluminum but not iron treatment induces pro-oxidant events in the rat brain SO MOLECULAR AND CHEMICAL NEUROPATHOLOGY LA English DT Article DE aluminum; iron; reactive oxygen species; neurotoxicity; oxidative stress ID GLUTAMINE-SYNTHETASE ACTIVITY; AMYLOID PRECURSOR PROTEIN; FREE-RADICAL FORMATION; ALZHEIMERS-DISEASE; LIPID-PEROXIDATION; OXIDATIVE STRESS; MECHANISM; CULTURES; CELLS; NEUROTOXICITY AB In an attempt to delineate the capacity of aluminum (Al) to promote pro-oxidant events, several indices of oxidative stress have been determined in brains and livers of rats exposed to an Al salt, either alone or in combination with an iron (Fe) compound. Treatment with Al over a 3-wk period increased both cortical levels of glutathione (GSH) and the rates of generation of reactive oxygen species (ROS). Dosing with an Fe compound resulted in no parallel changes, and concurrent exposure to Fe together with Al prevented these elevations. Both Fe and Al dosing elevated glutamine synthetase activity in the cortex. Levels of creatine kinase, another enzyme susceptible to oxidative stress, were also elevated in cortices of Al-treated rats. These data are in contrast to the changes found in liver fractions where exposure to Fe greatly enhanced hepatic pro-oxidant events as judged by changes in all three of the test indices used. Concurrent treatment with Al did not potentiate the pro-oxidant effects of Fe in liver. Al treatment had very minor effects on hepatic parameters of oxidative events. The results suggest that the presence of Al may exert deleterious pro-oxidant changes within the brain, which may be related to induction of oxidant species. These changes are tissue-specific and appear to be independent of any promotion of prooxidant status induced by exogenous Fe. 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 [ES 7992] NR 48 TC 44 Z9 44 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1044-7393 J9 MOL CHEM NEUROPATHOL JI Mol. Chem. Neuropathol. PD JUN-AUG PY 1998 VL 34 IS 2-3 BP 219 EP 232 DI 10.1007/BF02815081 PG 14 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 184VK UT WOS:000079634300009 PM 10327419 ER PT J AU Brown, JL Mucci, D Whiteley, M Dirksen, ML Kassis, JA AF Brown, JL Mucci, D Whiteley, M Dirksen, ML Kassis, JA TI The Drosophila polycomb group gene pleiohomeotic encodes a DNA binding protein with homology to the transcription factor YY1 SO MOLECULAR CELL LA English DT Article ID SEGMENTATION GENE; BITHORAX COMPLEX; REGULATORY SEQUENCES; NEGATIVE REGULATOR; RESPONSE ELEMENT; WHITE GENE; MELANOGASTER; EXPRESSION; SITES; REPRESSION AB Genes of the Polycomb group (PcG) of Drosophila encode proteins necessary for the maintenance of transcriptional repression of homeotic genes. PcG proteins are thought to act by binding as multiprotein complexes to DNA through Polycomb group response elements (PREs); however, specific DNA binding has not been demonstrated for any of the PcG proteins. We have identified a sequence-specific DNA binding protein that interacts with a PRE from the Drosophila engrailed gene. This protein (PHO) is a homolog of the ubiquitous mammalian transcription factor Yin Yang-1 and is encoded by pleiohomeotic, a known member of the PcG. We propose that PHO acts to anchor PcG protein complexes to DNA. C1 US FDA, Dev Biol Lab, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Kassis, JA (reprint author), US FDA, Dev Biol Lab, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM kassis@helix.nih.gov OI Kassis, Judith/0000-0001-9268-3213 NR 72 TC 237 Z9 244 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD JUN PY 1998 VL 1 IS 7 BP 1057 EP 1064 DI 10.1016/S1097-2765(00)80106-9 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZW235 UT WOS:000074389200013 PM 9651589 ER PT J AU Ysern, X Li, HM Mariuzza, RA AF Ysern, X Li, HM Mariuzza, RA TI Imperfect interfaces SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID T-CELL-RECEPTOR; ANTIBODY-ANTIGEN COMPLEX; CRYSTAL-STRUCTURE; POSITIVE SELECTION; FAB COMPLEX; PEPTIDE; AFFINITY; KINETICS; DOMAIN AB The crystal structure of a T cell receptor bound to a self peptide-major histocompatibility complex antigen reveals poor shape complementarity in the interface between the two proteins, as well as large conformational changes in the T cell receptor combining site upon ligand binding. C1 Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Mariuzza, RA (reprint author), Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, 9600 Gudelsky Dr, Rockville, MD 20850 USA. OI Li, Hongmin/0000-0002-8684-5308 NR 25 TC 27 Z9 27 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD JUN PY 1998 VL 5 IS 6 BP 412 EP 414 DI 10.1038/nsb0698-412 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA ZQ612 UT WOS:000073885500003 PM 9628472 ER PT J AU Itzhak, Y Martin, JL Black, MD Ali, SF AF Itzhak, Y Martin, JL Black, MD Ali, SF TI Effect of melatonin on methamphetamine- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity and methamphetamine-induced behavioral sensitization SO NEUROPHARMACOLOGY LA English DT Article DE methamphetamine; MPTP; melatonin; dopaminergic neurotoxicity; free radicals; locomotor activity; sensitization ID NITRIC-OXIDE SYNTHASE; STRIATAL DOPAMINE; TRANSGENIC MICE; CAUDATE-NUCLEUS; FREE-RADICALS; RAT-BRAIN; 7-NITROINDAZOLE; INHIBITION; MOUSE; 1-METHYL-4-PHENYL-1,2,5,6-TETRAHYDROPYRIDINE AB Methamphetamine (METH)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity is thought to be associated with the formation of free radicals. Since evidence suggests that melatonin may act as a free radical scavenger and antioxidant, the present study was undertaken to investigate the effect of melatonin on METH- and MPTP-induced neurotoxicity. In addition, the effect of melatonin on METH-induced locomotor sensitization was investigated. The administration of METH (5 mg kg(-1) x 3) or MPTP (20 mg kg(-1) x 3) to Swiss Webster mice resulted in 45-57% depletion in the content of striatal dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, and 57-59% depletion in dopamine transporter binding sites. The administration of melatonin (10 mg kg(-1)) before each of the three injections of the neurotoxic agents (on day 1), and thereafter for two additional days, afforded a full protection against METH-ieduced depletion of dopamine and its metabolites and dopamine transporter binding sites. In addition, melatonin significantly diminished METH-induced hyperthermia. However, the treatment with melatonin had no significant effect on MPTP-induced depletion of the dopaminergic markers tested. In the set of behavioral experiments, we found that the administration of 1 mg kg(-1) METH to Swiss Webster mice for 5 days resulted in marked locomotor sensitization to a subsequent challenge injection of METH, as well as context-dependent sensitization (conditioning). The pretreatment with melatonin (10 mg kg(-1)) prevented neither the sensitized response to METH nor the development of conditioned locomotion. Results of the present study indicate that melatonin has a differential effect on the dopaminergic neurotoxicity produced by METH and MPTP. Since it is postulated that METH-induced hyperthermia is related to its neurotoxic effect, while regulation of body temperature is unrelated to MPTP-induced neurotoxicity or METH-induced locomotor sensitization, the protective effect of melatonin observed in the present study may be due primarily to diminishing METH-induced hyperthermia. (C) 1998 Published by Elsevier Science Ltd. All rights reserved. C1 Univ Miami, Sch Med, Dept Biochem & Mol Biol R62A, Miami, FL 33101 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR USA. RP Itzhak, Y (reprint author), Univ Miami, Sch Med, Dept Biochem & Mol Biol R62A, POB 016129, Miami, FL 33101 USA. EM YITZHAK@MEDNET.MED.MIAMI.EDU FU NIDA NIH HHS [DA08584] NR 48 TC 46 Z9 46 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JUN PY 1998 VL 37 IS 6 BP 781 EP 791 DI 10.1016/S0028-3908(98)00067-7 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 100MQ UT WOS:000074820200010 PM 9707292 ER PT J AU Slikker, W Keenan, F AF Slikker, W Keenan, F TI Toxicokinetics and bioavailability of manganese: Session II summary and research needs SO NEUROTOXICOLOGY LA English DT Article C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Chemet Inc, Baltimore, MD 21108 USA. RP Slikker, W (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 0 TC 4 Z9 4 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 JUN PY 1998 VL 19 IS 3 BP 475 EP 478 PG 4 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA ZQ617 UT WOS:000073886000012 ER PT J AU Shah, VP Tsong, Y Sathe, P Liu, JP AF Shah, VP Tsong, Y Sathe, P Liu, JP TI In vitro dissolution profile comparison - Statistics and analysis of the similarity factor, f(2) SO PHARMACEUTICAL RESEARCH LA English DT Article DE dissolution; similarity factor; estimation bias; bootstrap confidence interval AB Purpose. To describe the properties of the similarity factor (f(2)) as a measure for assessing the similarity of two dissolution profiles. Discuss the statistical properties of the estimate based on sample means. Methods. The f(2) metrics and the decision rule is evaluated using examples of dissolution profiles. The confidence interval is calculated using bootstrapping method. The bias of the estimate using sample mean dissolution is evaluated. Results. 1. f(2) values were found to be sensitive to number of sample points, after the dissolution plateau has been reached. 2. The statistical evaluation of f(2) could be made using 90% confidence interval approach. 3. The statistical distribution of f(2) metrics could be simulated using 'Bootstrap' method. A relatively robust distribution could be obtained after more than 500 'Bootstraps'. 4. A statistical 'bias correction' was found to reduce the bias. Conclusions. The similarity factor f(2) is a simple measure for the comparison of two dissolution profiles. But the commonly used similarity factor estimate (f) over cap(2) is a biased and conservative estimate of f(2). The bootstrap approach is a useful tool to simulate the confidence interval. C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20852 USA. US FDA, CDER, Div Biometr 3, Off Epidemiol & Biometr, Rockville, MD 20857 USA. Natl Cheng Kung Univ, Dept Stat, Tainan 70101, Taiwan. RP Shah, VP (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, HFD-350,1451 Rockville Pike,WOC 2, Rockville, MD 20852 USA. OI Liu, Jen-pei/0000-0002-9565-1812 NR 16 TC 308 Z9 340 U1 3 U2 37 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD JUN PY 1998 VL 15 IS 6 BP 889 EP 896 DI 10.1023/A:1011976615750 PG 8 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA ZT832 UT WOS:000074132200013 PM 9647355 ER PT J AU Qureshi, MA Brake, J Hamilton, PB Hagler, WM Nesheim, S AF Qureshi, MA Brake, J Hamilton, PB Hagler, WM Nesheim, S TI Dietary exposure of broiler breeders to aflatoxin results in immune dysfunction in progeny chicks SO POULTRY SCIENCE LA English DT Article DE aflatoxin feeding; broiler breeder; residues testing procedure; progeny immune functions; hatchability ID PERITONEAL-MACROPHAGES; EMBRYONIC EXPOSURE; MEDIATED-IMMUNITY; FEED; EGGS; METABOLISM; INDUCTION; POULTRY; INVIVO; HENS AB Broiler breeder hens were fed diets amended with 0 and 10 mg/kg (Trial 1) or 0, 0.2, 1, or 5 mg/kg (Trial 2) of aflatoxin (AF). Fertile eggs collected during 14 d of AF feeding were examined for AF residues. Various immunological endpoints were examined in chicks hatched from these eggs. Eggs collected at 7 d of Al; feeding (Trial 1) had 0.15 to 0.48 ng/g of AFB(1) and 0.22 to 0.51 ng/g of aflatoxicol, whereas eggs collected at 14 d of AF feeding had 0.05 to 0.60 ng of AFB(1)/g and 0.19 to 1.20 ng of aflatoxicol/g. In both trials, AF dietary exposure resulted in embryonic mortality and reduction in hatchability compared to controls. The AF progeny chicks in Trial 2 had total anti-SRBC antibodies similar to the controls during the primary antibody response. However, at 5 and 7 d after secondary SRBC injection, the antibody levels in the 1 and 5 mg/kg AF groups were lower than those of controls. Depression in anti-Brucella abortus antibodies occurred only in chicks from the 5 mg/kg AF group. Furthermore, phagocytosis of SRBC and reactive oxygen intermediate production by macrophages from AF progeny chicks were reduced as compared with the control chicks. The findings of this study imply that the progeny chicks from hens consuming a AF-amended diet may be increasingly susceptible to disease owing to suppression of humoral and cellular immunity. C1 N Carolina State Univ, Dept Poultry Sci, Raleigh, NC 27695 USA. US FDA, Off Plant & Dairy Food & Beverages, Washington, DC 20204 USA. RP Qureshi, MA (reprint author), N Carolina State Univ, Dept Poultry Sci, Box 7608, Raleigh, NC 27695 USA. EM m_qureshi@ncsu.edu NR 40 TC 79 Z9 82 U1 1 U2 7 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874 USA SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PD JUN PY 1998 VL 77 IS 6 BP 812 EP 819 PG 8 WC Agriculture, Dairy & Animal Science SC Agriculture GA ZQ043 UT WOS:000073815700006 PM 9628528 ER PT J AU Zhao, ZL Khachik, F Richie, JP Cohen, LA AF Zhao, ZL Khachik, F Richie, JP Cohen, LA TI Lycopene uptake and tissue disposition in male and female rats SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT International Symposium on Lycopene and Tomato Products in Disease Prevention CY MAR 03, 1997 CL NEW YORK, NEW YORK SP Amer Hlth Fdn, Tomato Res Council ID ALPHA-CAROTENE; BETA-CAROTENE; LIQUID-CHROMATOGRAPHY; SERUM MICRONUTRIENTS; CERVICAL-CANCER; SUBSEQUENT RISK; RETINOL; PROSTATE; MICE AB Epidemiologic and clinical studies suggest that tomato consumption may reduce the risk of cancer, Lycopene, a hydrocarbon carotenoid, is the major carotenoid in tomatoes and, as a potent singlet oxygen quencher, has been considered by some to be the biologically active agent responsible for the reduction of cancer risk associated with tomato consumption. However, little is known concerning lycopene absorption or biological activity in rodent models of cancer, Therefore, the present study was designed to provide information regarding the uptake and tissue disposition of lycopene and related carotenoid after feeding a diet containing a carotenoid mixture extracted from tomatoes (Betatene), Betatene was added to the diet at 2.3, 0.9, 0.45, 0.23, 0.09 and 0 (mM/kg diet) and fed to male and female Fischer-344 rats for a period of 10 weeks. Using reverse phase HPLC methods, it was found that approximately 55% of administered lycopene was excreted in the feces, In both males and females, lycopene concentrations were highest in the fiver (120-42 mu g/g wet wt.); physiologically significant revels were detected in prostate (97-47 ng/g), lung (227-134 ng/g), mammary gland (309-174 ng/g) and serum (285-160 ng/ml). Tissue concentrations were related to dose with the exception of serum, and differences between males and females were minimal. Other carotenoids present in Betatene (i.e., phytoene, phytofluene, z-carotene and beta-carotene) were also absorbed and stored in the river. These results indicate that lycopene, when incorporated into the semipurified AIN-76A diet, is absorbed in both male and female rats in a dose-related manner and can be detected at nanogram levels in a variety of target organs. C1 Amer Hlth Fdn, Sect Nutr & Endocrinol, Div Nutr & Endocrinol, Valhalla, NY 10595 USA. Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. RP Cohen, LA (reprint author), Amer Hlth Fdn, Sect Nutr & Endocrinol, Div Nutr & Endocrinol, 1 Dana Rd, Valhalla, NY 10595 USA. RI Khachik, Frederick/C-5055-2009 NR 22 TC 27 Z9 27 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD JUN PY 1998 VL 218 IS 2 BP 109 EP 114 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZP086 UT WOS:000073729900006 PM 9605207 ER PT J AU Hendrick, RE Chrvala, CA Plott, CM Cutter, GR Jessop, NW Wilcox-Buchalla, P AF Hendrick, RE Chrvala, CA Plott, CM Cutter, GR Jessop, NW Wilcox-Buchalla, P TI Improvement in mammography quality control: 1987-1995 SO RADIOLOGY LA English DT Article DE breast radiography; breast radiography, quality assurance AB PURPOSE: To assess possible changes in quality control (QC) practices at mammography sites in the United States. MATERIALS AND METHODS: Mammography site surveys were conducted in 1990, 1992, and 1995 through the Colorado Mammography Advocacy Project (CMAP). Data from mammography sites applying for American College of Radiology (ACR) accreditation were collected between August 1987 and August 1993 through the ACR Mammography Accreditation Program. Data from both of these surveys were analyzed to assess temporal changes in mammography QC practices in the United States between 1987 and 1995. RESULTS: CMAP results indicated statistically significant improvement in medical physicist QC practices between 1990 and 1992 and in technologist QC practices between 1990 and 1995. Improvements in radiologic technologist QC practices coincided with increases in radiologic technologist continuing education in mammography. ACR results indicated statistically significant improvement in technologist QC practices between 1988 and 1992. CONCLUSION: There have been substantial improvements in QC practices at mammography sites in the United States during the past decade. C1 Univ Colorado, Hlth Sci Ctr, Dept Radiol, Denver, CO 80262 USA. US FDA, Div Mammog Qual, Bethesda, MD 20014 USA. US FDA, Radiat Program, Bethesda, MD 20014 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Radiol, Winston Salem, NC USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Environm Hlth & Safety, Winston Salem, NC USA. Amer Med Ctr Canc Res Ctr, Ctr Res Methodol & Biometr, Denver, CO USA. Amer Coll Radiol, Reston, VA USA. RP Hendrick, RE (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Radiol, 4200 E 9th Ave,C278, Denver, CO 80262 USA. NR 13 TC 12 Z9 12 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 1998 VL 207 IS 3 BP 663 EP 668 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZN534 UT WOS:000073655500017 PM 9609888 ER PT J AU Tabor, E AF Tabor, E TI Human T-lymphotropic virus types I and II in Africa in 1969 SO TRANSFUSION LA English DT Letter ID HTLV-I; OKINAWA; JAPAN C1 US FDA, Ctr Biol Evaluat & Res, Div Transfus & Transmitted Dis, Bethesda, MD 20014 USA. RP Tabor, E (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Transfus & Transmitted Dis, Bethesda, MD 20014 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 1998 VL 38 IS 6 BP 612 EP 613 DI 10.1046/j.1537-2995.1998.38698326343.x PG 2 WC Hematology SC Hematology GA ZX852 UT WOS:000074561900014 PM 9661697 ER PT J AU Wear, KA Garra, BS AF Wear, KA Garra, BS TI Assessment of bone density using ultrasonic backscatter SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE ultrasound; backscatter; bone ID HIP FRACTURE; SPECTRUM ANALYSIS; FREQUENCY; OSTEOPOROSIS; COEFFICIENTS; STATISTICS; TISSUES; SPECKLE; ATTENUATION; PREDICTION AB The goal of this project was to investigate the utility of ultrasonic backscatter for the assessment of bone status. Ultrasound offers a low-cost, portable, nonionizing alternative or complement to common X-ray- or radioisotope (gamma ray)-based methods of bone densitometry, Ultrasonic backscatter may provide useful information not revealed by ultrasonic attenuation and sound-speed densitometers, Backscatter is sensitive to microstructural variations in acoustic impedance and should therefore provide information regarding architecture (which is related to fracture risk), as well as density. Ultrasonic backscatter at 2.25 MHz and CT bone densitometric data have been acquired from 10 healthy human volunteers, The degree of correlation between CT and ultrasonic backscatter is high (r = 0.87, p < 0.001). The envelope signal-to-noise ratio was 1.81 +/- 0.08 (mean a standard deviation). This suggests that the number of scatterers per resolution cell is large, the radiofrequency signal approximately obeys circular Gaussian statistics, and the envelope obeys Rayleigh statistics. These results indicate promise for ultrasonic backscatter as a substitute for or an adjunct to other ultrasonic measurements (attenuation and sound speed) and X-ray measurements for the assessment of bone status. (C) 1998 World Federation for Ultrasound in Medicine gr Biology. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. Georgetown Univ, Med Ctr, Dept Radiol, Washington, DC 20007 USA. RP US FDA, Ctr Devices & Radiol Hlth, HfZ-142,12720 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 41 TC 73 Z9 75 U1 2 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 JUN PY 1998 VL 24 IS 5 BP 689 EP 695 DI 10.1016/S0301-5629(98)00040-4 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA ZV855 UT WOS:000074348400009 PM 9695272 ER PT J AU Plakas, SM El Said, KR Bencsath, FA Musser, SM Hayton, WL AF Plakas, SM El Said, KR Bencsath, FA Musser, SM Hayton, WL TI Pharmacokinetics, tissue distribution and metabolism of acriflavine and proflavine in the channel catfish (Ictalurus punctatus) SO XENOBIOTICA LA English DT Article ID AGENTS; FISH AB 1. The disposition of proflavine (PRO) and acriflavine (ACR) were examined in channel catfish after intravascular (i.v.) dosing (1 mg/kg) or waterborne exposure(10 mg/l for 4 h). 2. After i.v. dosing, plasma concentration-time profiles of parent PRO and ACR were best described by two- and three-compartment pharmacokinetic models respectively. Terminal elimination half-lives of PRO and ACR in plasma were 8.7 and 11.4h respectively. 3. In animals dosed with C-14-PRO or C-14-ACR, total drug equivalent concentrations were highest in the excretory organs and lowest in muscle, fat and plasma. In PRO-dosed animals, residues in the liver and trunk kidney were composed primarily of glucuronosyl and acetyl conjugates of PRO; residues in muscle were composed mostly (> 95 %) of the parent drug. In ACR-dosed animals, the parent compound comprised > 90 % of the total residues in all tissues examined. 4. PRO and ACR were poorly absorbed in catfish during waterborne exposure. At the end of a 4-h exposure, parent PRO and ACR concentrations in muscle were 0.064 and 0.020 mu g/g respectively. Levels in muscle declined below the limit of determination (0.005 mu g/g) within 1-2 weeks. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. US FDA, Instrumentat & Biophys Branch, Washington, DC 20204 USA. Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA. RP Plakas, SM (reprint author), US FDA, Gulf Coast Seafood Lab, POB 158, Dauphin Island, AL 36528 USA. NR 21 TC 9 Z9 10 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD JUN PY 1998 VL 28 IS 6 BP 605 EP 616 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA ZY298 UT WOS:000074606100007 PM 9667083 ER PT J AU Gaborik, Z Mihalik, B Jayadev, S Jagadeesh, G Catt, KJ Hunyady, L AF Gaborik, Z Mihalik, B Jayadev, S Jagadeesh, G Catt, KJ Hunyady, L TI Requirement of membrane-proximal amino acids in the carboxyl-terminal tail for expression of the rat AT(1a) angiotensin receptor SO FEBS LETTERS LA English DT Article DE AT(1) angiotensin receptor; carboxyl-terminal tail; inositol phosphate; receptor expression; Ca2+ mobilizing hormone ID AGONIST-INDUCED INTERNALIZATION; PROTEIN-COUPLED RECEPTORS; SIGNAL-TRANSDUCTION; II RECEPTOR; HORMONE RECEPTOR; C-TERMINUS; DESENSITIZATION; BINDING; REGIONS; MUTAGENESIS AB A series of deletion mutants was created to analyze the function of the membrane-proximal region of the cytoplasmic tail of the rat type 1a (AT(1a)) angiotensin receptor, In transiently transfected COS-7 cells, the truncated mutant receptors showed a progressive decrease in surface expression, with no major change in binding affinity for the peptide antagonist, [Sar(1),Ile(8)]angiotensin II, In parallel with the decrease in receptor expression, a progressive decrease in angiotensin II-induced inositol phosphate responses was observed, Alanine substitutions in the region 307-311 identified the highly conserved phenylalanine(309) and adjacent lysine residues as significant determinants of AT(1a) receptor expression. (C) 1998 Federation of European Biochemical Societies. C1 Semmelweis Univ Med, Dept Physiol, H-1444 Budapest, Hungary. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Div Cardiorenal Prod, Rockville, MD 20857 USA. RP Hunyady, L (reprint author), Semmelweis Univ Med, Dept Physiol, 8,POB 259, H-1444 Budapest, Hungary. NR 38 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAY 29 PY 1998 VL 428 IS 3 BP 147 EP 151 DI 10.1016/S0014-5793(98)00511-0 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA ZT975 UT WOS:000074148000005 PM 9654124 ER PT J AU LeClerc, JE Payne, WL Kupchella, E Cebula, TA AF LeClerc, JE Payne, WL Kupchella, E Cebula, TA TI Detection of mutator subpopulations in Salmonella typhimurium LT2 by reversion of his alleles SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE Salmonella typhimurium; evolution; mutator; mismatch correction; spontaneous mutation; mutS; mutL; mutH; uvrD; horizontal transfer ID ESCHERICHIA-COLI; FRAMESHIFT MUTATIONS; HISTIDINE OPERON; RECOMBINATION; EVOLUTION; BARRIER AB Defects in the methyl-directed mismatch repair lead to both the hypermutability phenotype and removal of a barrier to genetic exchange between species. Mutator bacteria carrying such defects occur frequently among bacterial pathogens, suggesting that subpopulations of mutators are contained within pathogen clones and give rise to the genetic variants that are acted upon by selective forces to allow survival or successful infection. We report here on the detection of the mutator subpopulation in Salmonella typhimurium and determination of its frequency in laboratory cultures. The analysis involved screening for mutators among revertants of S. typhimurium histidine auxotrophs selected for the His(+) phenotype, since the frequency of mutators is expected to be increased in the selected mutant population they helped to spawn. The increases in spontaneous reversion of histidine mutations were first measured in isogenic strains carrying mismatch repair-defective mutH, mutL, mutS, or uvrD alleles, relative to their mismatch repair-proficient counterparts. Screening for the mutator phenotype in nearly 12,000 revertants of repair-proficient strains carrying his mutations highly stimulated for reversion in mutator backgrounds, the base substitution in hisG428 and frameshift in hisC3076, yielded five mutator strains (0.04%). The his(+) reversion mutations contained within the newly-arisen mutator strains were characteristic of the predominant nucleotide changes expected in such mutators, as assessed by comparison with the spectra for reversion events in wild-type and mismatch correction-defective backgrounds. The results show that subpopulations of mutators, residing in normal populations at a finite frequency, can be culled from the culture by strong selection for a required phenotype. We calculate that the frequency of mutators in the unselected population of S. typhimurium is 1-4 x 10(-6), an incidence 10-fold lower than that expected based on studies of laboratory cultures of Escherichia coli. (C) 1998 Elsevier Science B.V. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, Mol Biol Branch HFS 237, Washington, DC 20204 USA. RP Cebula, TA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Mol Biol Branch HFS 237, 200 C St SW, Washington, DC 20204 USA. NR 25 TC 29 Z9 29 U1 1 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 MAY 25 PY 1998 VL 400 IS 1-2 SI SI BP 89 EP 97 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 113JW UT WOS:000075548700010 PM 9685594 ER PT J AU Nightingale, SL AF Nightingale, SL TI Advertising prescription-only drugs SO LANCET LA English DT Letter C1 US FDA, Dept Hlth & Human Serv, Publ Hlth Serv, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Dept Hlth & Human Serv, Publ Hlth Serv, Rockville, MD 20857 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAY 23 PY 1998 VL 351 IS 9115 BP 1582 EP 1582 DI 10.1016/S0140-6736(98)26021-1 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ZQ497 UT WOS:000073868000051 PM 10326559 ER PT J AU Hay, A Schild, G Wood, J Gust, I Hampson, A Nerome, K Canas, L Guo, Y AF Hay, A Schild, G Wood, J Gust, I Hampson, A Nerome, K Canas, L Guo, Y TI Update: Influenza activity - United States and worldwide, 1997-98 season, and composition of the 1998-99 influenza vaccine (Reprinted from MMWR, vol 47, pg 280-284, 1998) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Natl Inst Med Res, London, England. Natl Inst Biol Stand & Controls, S Mimms, Herts, England. Commonwealth Serum Labs, Parkville, Vic 3052, Australia. Natl Inst Infect Dis, Tokyo, Japan. Armstrong Lab, Brooks Air Force Base, San Antonio, TX USA. WHO, Natl Influenza Ctr, Div Emerg & Other Communic Dis Surveill & Contr, Geneva, Switzerland. Natl Ctr Prevent Med, Beijing, Peoples R China. US FDA, Div Virol, Ctr Biol Evaluat & Res,Influenza Branch, Rockville, MD 20857 USA. Ctr Dis Control, Div Viral & Rickettsial Dis, Influenza Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. RP Hay, A (reprint author), Natl Inst Med Res, London, England. NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 20 PY 1998 VL 279 IS 19 BP 1516 EP 1517 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA ZN087 UT WOS:000073608100010 ER PT J AU Debinski, W Gibo, DM Puri, RK AF Debinski, W Gibo, DM Puri, RK TI Novel way to increase targeting specificity to a human glioblastoma-associated receptor for interleukin 13 SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID PSEUDOMONAS EXOTOXIN-A; CELL CARCINOMA-CELLS; COMMON GAMMA-CHAIN; HUMAN GLIOMA-CELLS; COMPLEX; IMMUNOTOXINS; MALIGNANCY; COMPONENT; THERAPY; MUTANT AB Human brain cancers (gliomas) overexpress large numbers of a receptor for interleukin 13 (IL13), making this receptor an attractive target for anti-glioma therapies. We have recently proposed that the glioma-associated IL13 receptor is different from the one expressed on some hemopoietic and somatic cells. In an attempt to identify an even more glioma-specific target, we have used an antagonist of a related cytokine, IL4, which neutralizes the physiological effects of both IL13 and IL4 on normal cells. Here we demonstrate that the IL4 antagonist also counteracts the action of cytotoxins targeted to the IL13 receptor on normal human cells. Importantly, the IL4 antagonist does not inhibit IL13-based cytotoxins on glioma cells at all. Thus, the IL13 receptor on glioma cells can be categorized as tumor-specific in the presence of an IL4 antagonist. We conclude that IL13 receptor-directed cytotoxins can be delivered to glioma cells without being cytotoxic to normal cells. (C) 1998 Wiley-Liss, Inc. C1 Penn State Univ, Milton S Hershey Med Ctr, Dept Surg, Coll Med,Sect Neurosurg, Hershey, PA 17033 USA. US FDA, Lab Mol Tumor Biol, Bethesda, MD 20014 USA. RP Debinski, W (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Dept Surg, Coll Med,Sect Neurosurg, 500 Univ Dr,Biomed Res Bldg C3848A, Hershey, PA 17033 USA. NR 25 TC 27 Z9 29 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 18 PY 1998 VL 76 IS 4 BP 547 EP 551 DI 10.1002/(SICI)1097-0215(19980518)76:4<547::AID-IJC17>3.0.CO;2-4 PG 5 WC Oncology SC Oncology GA ZM006 UT WOS:000073495300017 PM 9590132 ER PT J AU Orlandi, PA Fishman, PH AF Orlandi, PA Fishman, PH TI Filipin-dependent inhibition of cholera toxin: Evidence for toxin internalization and activation through caveolae-like domains SO JOURNAL OF CELL BIOLOGY LA English DT Article ID GPI-ANCHORED PROTEINS; COATED PIT FORMATION; CULTURED-CELLS; ADENYLATE-CYCLASE; EPITHELIAL-CELLS; INTRACELLULAR TRAFFICKING; ENDOPLASMIC-RETICULUM; MEDIATED TRANSPORT; DIPHTHERIA-TOXIN; GOLGI-APPARATUS AB The mechanism by which cholera toxin (CT) is internalized from the plasma membrane before its intracellular reduction and subsequent activation of adenylyl cyclase is not well understood. Ganglioside G(M1), the receptor for CT, is predominantly clustered in detergent-insoluble glycolipid rafts and in caveolae, noncoated, cholesterol-rich invaginations on the plasma membrane. In this study, we used filipin, a sterol-binding agent that disrupts caveolae and caveolae-like structures, to explore their role in the internalization and activation of CT in CaCo-2 human intestinal epithelial cells. When toxin internalization was quantified, only 33% of surface-bound toxin was internalized by filipin-treated cells within 1 h compared with 79% in untreated cells. However, CT activation as determined by its reduction to form the Al peptide and CT activity as measured by cyclic AMP accumulation were inhibited in filipin-treated cells. Another sterol-binding agent, 2-hydroxy-beta-cyclodextrin, gave comparable results. The cationic amphiphilic drug chlorpromazine, an inhibitor of clathrin-dependent, receptor-mediated endocytosis, however, affected neither CT internalization, activation, nor activity in contrast to its inhibitory effects on diphtheria toxin cytotoxicity. As filipin did not inhibit the latter, the two drugs appeared to distinguish between caveolae- and coated pit-mediated processes. In addition to its effects in CaCo-2 cells that express low levels of caveolin, filipin also inhibited CT activity in human epidermoid carcinoma A431 and Jurkat T lymphoma cells that are, respectively, rich in or lack caveolin. Thus, filipin inhibition correlated more closely with alterations in the biochemical characteristics of CT-bound membranes due to the interactions of filipin with cholesterol rather than with the expressed levels of caveolin and caveolar structure. Our results indicated that the internalization and activation of CT was dependent on and mediated through cholesterol-and glycolipid-rich microdomains at the plasma membrane rather than through a specific morphological structure and that these glycolipid microdomains have the necessary components required to mediate endocytosis. C1 NINDS, Membrane Biochem Sect, Cellular & Mol Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Orlandi, PA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, OPDFB, DVA,VMB, HFS-327,200 C St, Washington, DC 20204 USA. NR 47 TC 537 Z9 547 U1 5 U2 31 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAY 18 PY 1998 VL 141 IS 4 BP 905 EP 915 DI 10.1083/jcb.141.4.905 PG 11 WC Cell Biology SC Cell Biology GA ZP540 UT WOS:000073763700006 PM 9585410 ER PT J AU Pierce, LR Gaines, A Varricchio, F Epstein, J AF Pierce, LR Gaines, A Varricchio, F Epstein, J TI Hemolysis and renal failure associated with use of sterile water for injection to dilute 25% human albumin solution SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Letter C1 US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Div Biostat & Epidemiol, Adverse Events Sect, Rockville, MD 20852 USA. RP Pierce, LR (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 6 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD MAY 15 PY 1998 VL 55 IS 10 BP 1057 EP + PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZP313 UT WOS:000073739800020 PM 9606459 ER PT J AU Murata, T Taguchi, J Puri, RK AF Murata, T Taguchi, J Puri, RK TI Interleukin-13 receptor alpha ' but not a chain: A functional component of interleukin-4 receptors SO BLOOD LA English DT Article ID COMMON GAMMA-CHAIN; CARCINOMA-CELLS; SIGNAL-TRANSDUCTION; STAT PROTEINS; EXPRESSION; IL-4; CLONING; MITOGENESIS; INHIBITION; SUBUNIT AB In hematopoietic cells, interleukin-2 receptor (IL-2R) gamma chain (termed gamma(c)) is shown to be a component of the IL-4R system, whereas in nonhematopoietic cells, gamma(c) is absent and it is not a component of the IL-4R system. Here, we show that the IL-13R alpha' chain (termed IL-13R alpha') but not the IL-13R alpha chain (termed IL-13R alpha) can substitute for gamma(c) and, thus, IL-13R alpha' forms a novel component of the IL-4R system, This conclusion was drawn on the basis of chemical cross-linking, immunoprecipitation, the ability of IL-10R alpha' but not IL-13R alpha to augment IL-4 binding affinity, and the requirement of IL-13R alpha' for IL-4-induced STAT6 activation in Chinese hamster ovary (CHO) cells transfected with various receptor subunits. Cotransfection of IL-4 receptor p140 (termed IL-4R beta) with gamma(c) or IL-13R alpha' increased IL-4 binding affinity and allowed for STAT6 activation in response to IL-4, However, cotransfection of all three chains did not further increase IL-4 binding or alter the extent of STAT6 activation suggesting that all three chains together do not seem to participate in IL-4 function. Instead, IL-4R beta heterodimerizes with gamma(c) or IL-13R alpha' and mediates STAT6 activation. Cotransfection of IL-4R beta with IL-13R alpha neither increased IL-4 binding affinity nor allowed for STAT6 activation in response to IL-4 indicating that IL-13R alpha does not convert binding affinity nor transmit signals for IL-4, Because IL-4 phosphorylates JAK1 and JAK2 tyrosine kinases in nonhematopoietic cells, we investigated whether JAK1 and JAK2 are required for IL-4-induced STAT6 activation in various transfectants. Cotransfection experiments with different chains of IL-4R and kinase-deficient JAK1 and JAK2 mutants in CHO cells showed that JAK1 and JAK2 are required for optimal activation of STAT6 in the alpha'beta transfectant but only partially in the beta gamma(c) transfectant, Taken together, our results show that IL-13R alpha' is a novel functional component of the IL-4R system and that JAK1 and JAK2 mediate IL-4-induced optimal activation of STAT6 in nonhematopoietic cells. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. NR 30 TC 103 Z9 103 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 1998 VL 91 IS 10 BP 3884 EP 3891 PG 8 WC Hematology SC Hematology GA ZM210 UT WOS:000073515700039 PM 9573026 ER PT J AU Thompson, PA Shields, PG Freudenheim, JL Stone, A Vena, JE Marshall, JR Graham, S Laughlin, R Nemoto, T Kadlubar, FF Ambrosone, CB AF Thompson, PA Shields, PG Freudenheim, JL Stone, A Vena, JE Marshall, JR Graham, S Laughlin, R Nemoto, T Kadlubar, FF Ambrosone, CB TI Genetic polymorphisms in catechol-O-methyltransferase, menopausal status, and breast cancer risk SO CANCER RESEARCH LA English DT Article ID ESTROGEN METABOLISM AB Polymorphic catechol-O-methyltransferase (COMT) catalyzes the O-methylation of estrogen catechols, In a case-control study, we evaluated the association of the low-activity allele (COMTMet) viith breast cancer risk. Compared to women with COMTVal/Val, COMTMet/Met was associated with an increased risk among premenopausal women [odds ratio (OR), 2.1; confidence interval (CI), 1.4-4.3] but was inversely associated with postmenopausal risk (OR, 0.4; CI, 0.2-0.7). The association of risk with at least one low-activity COMTMet allele was strongest among the heaviest premenopausal a omen (OR, 5.7; CI, 1.1-30.1) and among the leanest postmenopausal women (OR, 0.3; CI, 0.1-0.7), suggesting that COMT, mediated by body mass index, may be playing differential roles in human breast carcinogenesis, dependent upon menopausal status. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA. Arizona Canc Ctr, Tucson, AZ 85724 USA. RP Ambrosone, CB (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. RI Shields, Peter/I-1644-2012 FU NCI NIH HHS [CA/ES62995, CA01633, CA11535] NR 32 TC 166 Z9 169 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 1998 VL 58 IS 10 BP 2107 EP 2110 PG 4 WC Oncology SC Oncology GA ZP382 UT WOS:000073746700015 PM 9605753 ER PT J AU Gadina, M Stancato, LM Bacon, CM Larner, AC O'Shea, JJ AF Gadina, M Stancato, LM Bacon, CM Larner, AC O'Shea, JJ TI Cutting edge: Involvement of SHP-2 in multiple aspects of IL-2 signaling: Evidence for a positive regulatory role SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR-BETA-CHAIN; PROTEIN-TYROSINE-PHOSPHATASE; JANUS KINASES; ACTIVATION; PHOSPHORYLATION; INTERLEUKIN-2; TRANSDUCTION; RECRUITMENT; ASSOCIATION; INHIBITION AB Binding of IL-2 to its receptor activates several biochemical pathways, but precisely how these pathways are linked is incompletely understood. Here, we report that SHP-2, an SH2-domain containing tyrosine phosphatase, associates with different molecules of the IL-2 signaling cascade, Upon IL-2 stimulation, SHP-2 was coimmunoprecipitated with Grb2 and the p85 subunit of phosphatidylinositol 3-kinase. In contrast, SHP-2 was constitutively associated with JAK1 and JAK3, Finally, SHP-2 expression amplified STAT-dependent transcriptional activation whereas a dominant negative allele inhibited transactivation and the IL-2-induced activation of MAPK (mitogen-activated protein kinase), These results demonstrate the involvement of SHP-2 in multiple pathways of the IL-2 signaling cascade and provide evidence for its positive regulatory role. C1 NIAMSD, Lymphocyte Cell Biol Sect, Arthritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20814 USA. RP Gadina, M (reprint author), Bldg 10,Room 9N228,10 Ctr Dr MSC 1820, Bethesda, MD 20892 USA. NR 32 TC 56 Z9 57 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1998 VL 160 IS 10 BP 4657 EP 4661 PG 5 WC Immunology SC Immunology GA ZM053 UT WOS:000073500000001 PM 9590209 ER PT J AU Shaikh, B Rummel, N AF Shaikh, B Rummel, N TI Determination of trichlormethiazide in bovine milk by high-performance liquid chromatography SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE bovine milk; trichlormethiazide; thiazides; diuretics ID DIURETIC DRUGS; THIAZIDE; URINE AB A liquid chromatographic procedure was developed and validated for the quantitative determination of trichlormethiazide (TCMTZ) in bovine milk. Whole milk was defatted by initial centrifugation at 4 degrees C. The resulting skim milk was treated with lead acetate and acetonitrile, vortex mixed, and centrifuged. The acetonitrile from the supernatant was back extracted in ethyl acetate. The organic solvent mixture which contained TCMTZ was further treated with sodium tungstate, vortex mixed, and centrifuged. The top organic layer was removed and evaporated to dryness; the resulting residue was reconstituted in the mobile phase, and the final extract was analyzed by high-performance liquid chromatography (HPLC). The HPLC conditions employed included a polymer column, a mobile phase consisting of 30% acetonitrile or 30% acetonitrile-tetrahydrofuran (2:1, v/v) in a phosphate buffer (pH 3), and a UV detection at 225 nm. The average recoveries of TCMTZ from milk fortified at 7, 14, 35, 70, and 140 ppb were 88, 93, 117, 110, and 99%, respectively, with corresponding C.V. values of 7, 18, 11, 9, and 21%. The method was validated by assaying milk obtained from a cow dosed with Naquasone. TCMTZ concentration was detected only in the 8 h post dose milk samples and was determined to be 6 ppb. (C) 1998 Elsevier Science B.V. C1 US Food & Drug Adm, Ctr Vet Med, Laurel, MD 20708 USA. RP Shaikh, B (reprint author), US Food & Drug Adm, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 11 TC 2 Z9 2 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD MAY 8 PY 1998 VL 709 IS 1 BP 137 EP 143 DI 10.1016/S0378-4347(98)00035-8 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA ZR379 UT WOS:000073968800016 PM 9653935 ER PT J AU Glynn, MK Bopp, C Dewitt, W Dabney, P Mokhtar, M Angulo, FJ AF Glynn, MK Bopp, C Dewitt, W Dabney, P Mokhtar, M Angulo, FJ TI Emergence of multidrug-resistant Salmonella enterica serotype typhimurium DT104 infections in the United States SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ENTERITIDIS; ANIMALS; HUMANS AB Background Strains of salmonella that are resistant to antimicrobial agents have become a worldwide health problem. A distinct strain of Salmonella enterica serotype typhimurium, known as definitive type 104 (DT104), is resistant to ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline and has become a major cause of illness in humans and animals in Europe, especially the United Kingdom. Methods To characterize typhimurium DT104 infections in the United States, we analyzed data collected by local and state health departments and public health laboratories between 1979 and 1996 in national surveys of the antimicrobial-drug resistance of salmonella. Selected typhimurium isolates with the five-drug pattern of resistance were phage typed. Results The prevalence of typhimurium isolates with the five-drug pattern of resistance increased from 0.6 percent in 1979-1980 to 34 percent in 1996. In 1994-1995, such isolates were identified in samples from 36 of the 46 surveillance sites (78 percent). Thirty-nine of 43 typhimurium isolates with the five-drug pattern of resistance identified in 1994-1995 and 1996 were phage type DT104 or a closely related phage type. Conclusions Multidrug-resistant typhimurium DT104 has become a widespread pathogen in the United States. More prudent use of antimicrobial agents in farm animals and more effective disease prevention on farms are necessary to reduce the dissemination of multidrug-resistant typhimurium DT104 and to slow the emergence of resistance to additional agents in this and other strains of salmonella. (C)1998, Massachusetts Medical Society. C1 Ctr Dis Control & Prevent, Foodborne & Diarrheal Dis Branch, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. US FDA, Rockville, MD 20857 USA. RP Glynn, MK (reprint author), Ctr Dis Control & Prevent, Foodborne & Diarrheal Dis Branch, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, 1600 Clifton Rd,MS A-38, Atlanta, GA 30333 USA. NR 32 TC 411 Z9 422 U1 1 U2 16 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 7 PY 1998 VL 338 IS 19 BP 1333 EP 1338 DI 10.1056/NEJM199805073381901 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA ZL720 UT WOS:000073463700001 PM 9571252 ER PT J AU Nightingale, SL AF Nightingale, SL TI New rule proposed for home drug abuse test kits SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 6 PY 1998 VL 279 IS 17 BP 1339 EP 1339 DI 10.1001/jama.279.17.1339 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ZK758 UT WOS:000073359800005 PM 9582030 ER PT J AU Nightingale, SL AF Nightingale, SL TI Advisory on medical telemetry system interference problem SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 6 PY 1998 VL 279 IS 17 BP 1339 EP 1339 DI 10.1001/jama.279.17.1339 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ZK758 UT WOS:000073359800007 PM 9582030 ER PT J AU Nightingale, SL AF Nightingale, SL TI Ultrasound device for evaluating bone strength approved SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 6 PY 1998 VL 279 IS 17 BP 1339 EP 1339 DI 10.1001/jama.279.17.1339 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ZK758 UT WOS:000073359800006 PM 9582030 ER PT J AU Li, M Xu, F Muller, J Hearing, VJ Gorelik, E AF Li, M Xu, F Muller, J Hearing, VJ Gorelik, E TI Ecotropic C-type retrovirus of B16 melanoma and malignant transformation of normal melanocytes SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID MURINE MELANOCYTES; MOUSE; ANTIGEN; CELLS; MICE; EXPRESSION; ONCOGENE; PROTEIN; GENE; DNA AB We reported previously that B16, JB/RH and JB/MS melanomas of C57BL/6 mice express the common melanoma-associated antigen (MAA) recognized by MM2-9B6 monoclonal antibody (MAb). This MAA is encoded by the env gene of an ecotropic MuLV-type retrovirus that somatically emerged in melanomas of C57BL/6 mite. The potential role of this melanoma-associated retrovirus (MelARV) in melanoma formation remains unknown and has not been previously investigated. To test this, normal melanocyte lines (melan-a and C57M) of C57BL/6 mice were infected with the MelARV produced by B16BL6 melanoma. Infection of these melanocytes with the MelARV was associated with the appearance of the MAA recognized by MM2-9B6 MAb. Most of the infected melanocyte sublines were able to grow only in the presence of 12-O-retradecanoylphorbol-13-acetate (TPA). Two infected melanocyte sublines showed morphological changes, were able to grow in the absence of TPA and, after inoculation into C57BL/6 mice, produced rapidly growing, highly pigmented tumors. These new melanomas, derived from the MelARV-infected melan-a and C57M melanocytes, were termed Meli-AI and Meli-BL, respectively. Southern blot analysis of EcoRI- and HindIII-digested DNAs from these melanomas showed several retroviral insertion sites. One copy of MelARV was found to be inserted at the end of the 6th leucine domain of the c-maf proto-oncogene, which encodes a basic region/leucine zipper transcription factor related to the AP-I family that is able to form homodimers or heterodimers with Fos and Jun transcription factors. Our data indicate that c-map is a common insertion sire of MelARV in BL6, Meli-AI and Meli-BL melanomas, whereas pro such insertion site was found in the melanocytes infected with MelARV but not malignantly transformed. Thus, our data imply that the ecotropic MelARV that somatically emerged in B16 and other melanomas of C57BL/6 mice may play a role in malignant transformation. (C) 1998 Wiley-Liss, Inc. C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gorelik, E (reprint author), Univ Pittsburgh, Inst Canc, Biomed Sci Tower,Room W954, Pittsburgh, PA 15213 USA. FU NCI NIH HHS [CA59903] NR 29 TC 15 Z9 15 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 4 PY 1998 VL 76 IS 3 BP 430 EP 436 PG 7 WC Oncology SC Oncology GA ZK245 UT WOS:000073299900023 PM 9579583 ER PT J AU Cavacini, LA Samore, MH Gambertoglio, J Jackson, B Duval, M Wisnewski, A Hammer, S Koziel, C Trapnell, C Posner, MR AF Cavacini, LA Samore, MH Gambertoglio, J Jackson, B Duval, M Wisnewski, A Hammer, S Koziel, C Trapnell, C Posner, MR TI Phase I study of a human monoclonal antibody directed against the CD4-binding site of HIV type 1 glycoprotein 120 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4 BINDING-SITE; PASSIVE IMMUNOTHERAPY; DISEASE PROGRESSION; IMMUNE-RESPONSE; EFFECTS MODELS; V3 LOOP; NEUTRALIZATION; GP120; TRIAL AB A phase I dose escalation study was conducted with the human monoclonal anti-gp120 antibody F105, to evaluate the safety, pharmacokinetics, and functional activity of F105 in HIV-l-infected individuals. F105 is an IgG(1)(kappa) antibody reactive with a discontinuous epitope that overlaps the CD4-binding site of gp120. F105 neutralizes laboratory strains of HIV-1 and some primary isolates, and synergizes with other antibodies in neutralizing an expanded spectrum of isolates. Four patients each with CD4 counts between 200 and 500/mm(3) received a single dose of F105 at 100 or 500 mg/m(2), intravenously, Sustained levels of F105 were obtained in plasma, and there was no evidence of an immune response to F105 as determined by a double-antigen immunoassay, No patient experienced any toxicity. Infused antibody retained full functional activity as detected by the ability of sera to block the binding of labeled F105 to HIV-l-infected cells. Of note, all patients had preexisting antibody to the gp120 CD4-binding site. The ability to culture virus by quantitative microculture remained unchanged by this single dose of antibody. Thus, it can be concluded that F105 is safe and nontoxic as a single injection at the doses tested. Furthermore, the antibody retains full gp120-binding activity. In these patients, with preexisting CD4-binding site antibody, there is no evidence of anti-HIV-l activity following a single antibody infusion. C1 Beth Israel Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Univ Calif San Francisco, Div Clin Pharm, San Francisco, CA 94143 USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA. US FDA, Rockville, MD 20857 USA. RP Cavacini, LA (reprint author), Beth Israel Med Ctr, Dept Med, 21-27 Burlington Ave,POB 15709, Boston, MA 02215 USA. FU NIAID NIH HHS [AI26926] NR 38 TC 42 Z9 44 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY 1 PY 1998 VL 14 IS 7 BP 545 EP 550 DI 10.1089/aid.1998.14.545 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ZL326 UT WOS:000073421600003 PM 9591708 ER PT J AU Sheets, RL Goldenthal, KL AF Sheets, RL Goldenthal, KL TI Traditional approach preventive HIV vaccines: What are the cell substrate and inactivation issues? SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID CULTURE; VIRUSES; SAFETY; CANCER AB A workshop was convened to discuss safety issues for traditional-approach HIV vaccines, especially inactivated vaccines. The topics included issues pertaining to (1) cell substrates used for production and (2) vaccine virus inactivation. The use of cell substrates such as tumor-derived continuous cell lines (TCLs) or virus-transformed CLs may be the most feasible approach to provide commercial-scale virus yields. However, especially because of concerns about tumorigenicity, TCLs have not been used to produce preventive vaccines for human trials with healthy subjects in the United States, Residual TCL material (e.g., DNA, cellular proteins, viruses) may not be removed during purification of intact HIV virions to the same extent achievable for a recombinant protein. Manufacturing processes, e.g., physicochemical methods of destroying DNA, could decrease tumorigenicity risk. Methods to assess potential for tumorigenicity may need further development. Another potential substrate for viral production that merits further study is human peripheral blood mononuclear cells (PBMCs), Regardless of the cell substrate used, extensive testing for adventitious agents (including non-HIV retroviruses) is needed, Vaccine virus inactivation can be considered in statistical terms, i.e., the probability of a surviving infectious particle. One formula to determine a "safety margin" (SM) is reduction of titer in log(10) for all inactivation steps minus initial viral infectivity in log(10), Calculations for appropriate SMs should include all sources of variability (e.g., lot-to-lot differences). Ensuring a specified SM, as the lower bound of the 95% confidence interval, for production lots was discussed. Sensitivity and specificity of infectivity assays may present limitations. C1 US Food & Drug Adm, CBER, Rockville, MD 20852 USA. RP Sheets, RL (reprint author), US Food & Drug Adm, CBER, HFM-475,1401 Rockville Pike, Rockville, MD 20852 USA. NR 37 TC 4 Z9 4 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY 1 PY 1998 VL 14 IS 7 BP 627 EP 633 DI 10.1089/aid.1998.14.627 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ZL326 UT WOS:000073421600012 PM 9591717 ER PT J AU Tolleson, WH AF Tolleson, WH TI Creationism continued SO AMERICAN SCIENTIST LA English DT Letter C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Tolleson, WH (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SIGMA XI-SCI RES SOC PI RES TRIANGLE PK PA PO BOX 13975, RES TRIANGLE PK, NC 27709 USA SN 0003-0996 J9 AM SCI JI Am. Scientist PD MAY-JUN PY 1998 VL 86 IS 3 BP 212 EP 212 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZJ372 UT WOS:000073208000003 ER PT J AU Rafii, F Hansen, EB AF Rafii, F Hansen, EB TI Isolation of nitrofurantoin-resistant mutants of nitroreductase-producing Clostridium sp. strains from the human intestinal tract SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ESCHERICHIA-COLI; AROMATIC NITRO; DNA DAMAGE; REDUCTION; TOXICITY; EFFICACY; FLORA; RAT AB Five spontaneous nitrofurantoin-resistant mutants tone each of Clostridium leptum, Clostridium paraputrificum, two other Clostridium spp, strains from the human intestinal microflora, and Clostridium perfringens ATCC 3626) were selected by growth on a nitrofurantoin-containing medium. All of the Clostridium wild-type and mutant strains produced nitroreductase, as was shown by the conversion of il-nitrobenzoic acid to 4-aminobenzoic acid. High-performance liquid chromatography (HPLC) analysis of the mutants during incubation with 50 mu g of nitrofurantoin per mi showed the gradual disappearance of the nitrofurantoin peak. The nitrofurantoin peak also disappeared when cell-free supernatants instead of cultures of each of the resistant and wild-type bacteria were used, but it persisted if the cell-free supernatants had been inactivated by heat. At least two of the mutants converted nitrofurantoin to metabolites without antibacterial activity, as was shown by a bioassay with a nitrofurantoin-susceptible Bacillus sp. strain. Nitrofurantoin at a high concentration (50 mu g/ml) continued to exert some toxicity, even on the resistant strains, as was evident from the longer lag phases. This study indicates that Clostridium strains can develop resistance to nitrofurantoin while retaining the ability to produce nitroreductase; the mutants metabolized nitrofurantoin to compounds without antibacterial activity. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol & Chem, Jefferson, AR 72079 USA. RP Rafii, F (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol & Chem, Jefferson, AR 72079 USA. NR 30 TC 19 Z9 20 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 1998 VL 42 IS 5 BP 1121 EP 1126 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA ZL001 UT WOS:000073388900023 PM 9593138 ER PT J AU Sacchi, CT Lemos, APS Whitney, AM Solari, CA Brandt, ME Melles, CEA Frasch, CE Mayer, LW AF Sacchi, CT Lemos, APS Whitney, AM Solari, CA Brandt, ME Melles, CEA Frasch, CE Mayer, LW TI Correlation between serological and sequencing analyses of the PorB outer membrane protein in the Neisseria meningitidis serotyping system SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID MENINGOCOCCAL DISEASE; ANTIGENIC DIVERSITY; ANTIBODY-BINDING; VACCINE DESIGN; CLASS-1; GENE; IDENTIFICATION; RESTORATION; SUBTYPES; STRAINS AB The current serological typing scheme for Neisseria meningitidis is not comprehensive; a proportion of isolates are not serotypeable. DNA sequence analysis and predicted amino acid sequences were used to characterize the structures of variable-region (VR) epitopes on N. meningitidis PorB proteins (PorB VR typing). Twenty-six porB gene sequences mere obtained from GenBank and aligned with 41 new sequences. Primary amino acid structures predicted from those genes were grouped into 30 VR families of related variants that displayed at least 60% similarity. We correlated VR families with monoclonal antibody (MAb) reactivities, establishing a relationship between VR families and epitope locations for 15 serotype-defining MAbs. The current panel of serotype-defining MAbs underestimates by at least 50% the PorB VR variability because reagents for several major VR families are lacking or because a number of VR variants within some families are not recognized by serotype-defining MAbs. These difficulties, also reported for serosubtyping based on the PorA protein, are shown as inconsistent results between serological and sequence analyses, leading to inaccurate strain identification and incomplete epidemiological data. The information from this study enabled the expansion of the panel of MAbs currently available for serotyping, by including MAbs of previously undetermined specificities. Use of the expanded serotype panel enabled us to improve the sensitivity of serotyping by resolving a number of formerly nonserotypeable strains. In most cases, this information can be used to predict the VR family placement of unknown PorB proteins without sequencing the entire porB gene. PorB VR typing complements serotyping, and a combination of both techniques may be used for full characterization of meningococcal strains. The present work represents the most complete and integrated data set of PorB VR sequences and MAb reactivities of serogroup B and C meningococci produced to date. C1 Ctr Dis Control & Prevent, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Fundacao Oswaldo Cruz, Dept Bacteriol, Rio De Janeiro, Brazil. Adolfo Lutz Inst, Bacteriol Div, Sao Paulo, Brazil. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Sacchi, CT (reprint author), Ctr Dis Control & Prevent, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, 1600 Clifton Rd, Atlanta, GA 30333 USA. NR 33 TC 52 Z9 53 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD MAY PY 1998 VL 5 IS 3 BP 348 EP 354 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZL785 UT WOS:000073471300016 PM 9605990 ER PT J AU Weiss, SR McFarland, BH Burkhart, GA Ho, PTC AF Weiss, SR McFarland, BH Burkhart, GA Ho, PTC TI Cancer recurrences and second primary cancers after use of antihistamines or antidepressants SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PROMOTE; GROWTH AB Objective: Reports in the scientific literature have described accelerated tumor growth in association with antidepressant and antihistamine exposure in experimental rodent cancer models, This study was designed to determine whether exposure to prescription antidepressants or antihistamines is associated with tumor growth in humans. Methods: Two nested case-control studies were conducted with a cohort of 1467 patients with breast cancer, colon cancer, or melanoma diagnosed between 1988 and 1994. Eligible patients included 95 with a cancer recurrence and 78 with a second primary Lesion diagnosed during the follow-up period. Five control subjects were matched to each case patient according to cancer site, stage, and follow-up time, Conditional logistic regression was used to compare risk for tumor recurrence or occurrence of a second primary tumor among patients using antidepressants or antihistamines with risk among unexposed patients. Results: For a cohort of patients who were predominantly female (78%), with breast cancer (57%) and with a tumor in situ or with localized disease (79%), the average age was 62 years at cancer diagnosis and average duration of follow-up period was 2.2 years, Use of antidepressants or antihistamines was unrelated to risk for tumor recurrence (odds ratio, 0.97; 95% confidence interval, 0.52 to 1.78) or second primary tumors (odds ratio, 0.94; 95% confidence interval, 0.50 to 1.77). Conclusion: Typical use of antidepressant or antihistamine drugs did not increase risk for recurrent or second primary tumors among patients with cancer. C1 Kaiser Permanente Ctr Hlth Res, Portland, OR 97227 USA. Univ Maryland, Sch Pharm, Dept Pharm Practice & Sci, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. RP McFarland, BH (reprint author), Kaiser Permanente Ctr Hlth Res, 3800 N Kaiser Ctr Dr, Portland, OR 97227 USA. NR 14 TC 15 Z9 16 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAY PY 1998 VL 63 IS 5 BP 594 EP 599 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZT386 UT WOS:000074080100011 PM 9630832 ER PT J AU Majahalme, S Turjanmaa, V Weder, AB Lu, H Tuomisto, M Uusitalo, A AF Majahalme, S Turjanmaa, V Weder, AB Lu, H Tuomisto, M Uusitalo, A TI Office and laboratory blood pressures as predictors of daily blood pressure level in normotensive subjects and borderline and mild hypertensive subjects SO CLINICAL PHYSIOLOGY LA English DT Article DE ambulatory BP; exercise BP; intra-arterial BP; postural BP ID LEFT-VENTRICULAR HYPERTROPHY; PROGNOSTIC VALUE; HEART-RATE; VARIABILITY; RISK; TERM; REACTIVITY; EXERCISE; DAYTIME; SLEEP AB A series of standardized laboratory tests [10 min sitting and supine, 9 min standing, dynamic; cycle ergometer (ERG) and isometric exercise; handgrip (HG)] were performed during intra-arterial blood pressure (BP) recording in 97 healthy unmedicated men, initially classified as normotensive (NT, n = 34), borderline hypertensive (BHT, n = 29) or mildly hypertensive (HT, n = 34) by repeated office blood pressure (OBP) measurements. After testing, a 24-h intra-arterial ambulatory BP (IABP) recording was obtained while subjects performed their normal activities. Day and night periods were analysed as well as 24-h averages for systolic BP (SBP) and diastolic BP (DBP) using Pearson correlations and multiple linear regressions. In normotensive subjects, the supine SEP predicted IABP measurements best (r range 0.39-0.69, P<0.05-0.001). In multiple regression, supine SEP explained 49% of 24-h SEP variance (F = 12.4, P = 0.001). For BHT, supine SEP was also the best predictor (r range 0.09-0.64, P NS to P<0.001), and it explained 37% of 24-h SEP variance (F = 15.6, P = 0.0005). In HT, ERG DBP correlated best with IABP (r range 0.52-0.75, P<0.01-0.001). ERG SEP explained 49% of 24-h SEP (F = 31.0, P = 0.0000) and ERG DBP explained 56% of 24-h DBP (F = 35.4, P = 0.0000) variance. Laboratory BP correlations were generally better with day than with night measurements. OSBP correlated moderately well with IABP in NT, and weakly in BHT and HT; ODBP instead correlated with IABP in NT and HT but not significantly in BHT. In conclusion, OBP is less closely related to IABP than laboratory BP, but even laboratory BP generally explains less than 50% of IABP variance. Stressors such as exercise are useful only in HT. For BHT, the prediction of IABP with laboratory measures was even weaker than in other groups, and thus ambulatory measurements cannot be replaced by short-duration laboratory measurements and stress tests. C1 Univ Tampere, Sch Med, Dept Med, FIN-33101 Tampere, Finland. Univ Tampere, Sch Med, Dept Clin Physiol, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland. Univ Michigan, Dept Internal Med, Div Hypertens, Ann Arbor, MI 48109 USA. US FDA, CDER, Off Biometr & Epidemiol, Rockville, MD 20857 USA. RP Majahalme, S (reprint author), Tampere Univ Hosp, Dept Internal Med Cardiol, POB 2000, Tampere 33521, Finland. NR 39 TC 2 Z9 2 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0144-5979 J9 CLIN PHYSIOL JI Clin. Physiol. PD MAY PY 1998 VL 18 IS 3 BP 215 EP 223 PG 9 WC Physiology SC Physiology GA ZU847 UT WOS:000074241600006 PM 9649909 ER PT J AU Leinung, M Koller, EA Fossler, MJ AF Leinung, M Koller, EA Fossler, MJ TI Corticosteroid effects of megestrol acetate SO ENDOCRINOLOGIST LA English DT Review ID ADVANCED BREAST-CANCER; MEDROXYPROGESTERONE ACETATE; DIABETES-MELLITUS; GLUCOCORTICOID RECEPTOR; CUSHINGS-SYNDROME; THERAPY; HORMONE; CATS; PROGESTOGENS; SUPPRESSION AB Megestrol acetate (MA) is a progestational agent that has been used in the management of AIDS cachexia and several types of hormone dependent cancers. An increasing number of reports have suggested that the drug also has corticosteroid effects. Specifically, adrenal suppression, impair ment of glucose tolerance, and Cushing's syn drome have been observed. The severity of symptoms appears to correlate with integrated drug exposure (dose x duration). These findings are supported by in vitro binding studies and prolonged dosing studies in cats as well as by similar clinical findings with the related com pound, medroxyprogesterone acetate. Because the clinical presentation may be insidious, and because patients receiving MA often are those with advanced disease, the iatrogenic association may not be recognized. Clinicians need to be aware of the potential for adrenal insufficiency in patients receiving or withdrawing from megestrol because these complications may be life-threatening. C1 Albany Med Coll, Div Endocrinol & Metab, Albany, NY 12208 USA. US FDA, Ctr Drug Evaluat, Div Endocrine & Metab Drug Prod, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. RP Leinung, M (reprint author), Albany Med Coll, Div Endocrinol & Metab, A-44, Albany, NY 12208 USA. NR 57 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD MAY PY 1998 VL 8 IS 3 BP 153 EP 159 DI 10.1097/00019616-199805000-00006 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZR514 UT WOS:000073985200005 ER PT J AU Henderson, AL Cao, WW Wang, RF Lu, MH Cerniglia, CE AF Henderson, AL Cao, WW Wang, RF Lu, MH Cerniglia, CE TI The effect of food restriction on the composition of intestinal microflora in rats SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE food restriction; intestinal microflora; rats; polymerase chain reaction; cellular fatty acids ID HUMAN FECAL MICROFLORA; COLON-CANCER; FATTY-ACIDS; DIET; METABOLISM; BACTERIA; FLORA AB The effect of a food-restricted diet on the fecal microflora of rats was studied by determining total anaerobic bacteria, bacterial cellular fatty acids, and the predominant intestinal bacteria shown by polymerase chain reaction (PCR) primers specific for the 16S rRNA gene sequences of 12 bacterial species. Twenty-four female Fischer 344 rats, 57 days old were divided into two groups and maintained on an NIH-31 diet. One group was fed ad libitum while the other group received 60% of ad libitium food intake (40% food restriction supplemented with vitamins and minerals equal to the ad libitium animals). After 2, 10, and 20 weeks on this dietary regimen, groups of four animals were sacrificed and the intestinal contents analyzed for changes in the bacterial flora. The anaerobic population for two-week (short-term) food-restricted rats was 3.2 x 10(8) per gram. slightly less than the 9.1 x 10(8) per gram found in the ad libitum-fed rats. The anaerobic populations in 20-week food restricted and ad libitum fed rats were 1.9 x 10(9) and 2.7 x 10-per gram, respectively. The total anaerobic population did not change significantly in either group during the 20-week study. No statistically significant differences were observed in the bacterial cellular fatty acid profiles between the two groups as determined by gas-liquid chromatography. PCR analysis of the intestinal contents indicated no significant shifts in the predominant flora due to dietary changes. The results, using three different methods to detect changes in the rat intestinal microflora, suggest that long-term dietary restriction had little effect on the microflora of female Fischer 344 rats. (C) 1998 Elsevier Science Inc. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM ccerniglia@nctr.fda.gov NR 24 TC 9 Z9 10 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD MAY PY 1998 VL 33 IS 3 BP 239 EP 247 DI 10.1016/S0531-5565(97)00091-0 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA ZJ863 UT WOS:000073261300005 PM 9615922 ER PT J AU Schenck, FJ Podhorniak, LV Wagner, R AF Schenck, FJ Podhorniak, LV Wagner, R TI A highly sensitive gas chromatographic determination of levamisole in milk SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE levamisole; anthelminthic; veterinary drug residue; milk ID PERFORMANCE LIQUID-CHROMATOGRAPHY AB Art efficient extraction and sensitive gas chromatographic method is described for the determination of the anthelminthic drug levamisole in milk. Levamisole was extracted from alkaline milk with ethyl acetate. Clean-up of the extract was by a series of liquid-liquid extraction steps. Levamisole residues in the extract were determined by gas chromatography with a nitrogen-phosphorus detector. This method was satisfactory for determining levamisole residues in milk as low as 0.5 ng/g. Mean recoveries of 0.5-10.0 ng/g fortified milk samples ranged from 84.5 to 95.2%. Five replicate analyses performed on a milk containing incurred levamisole residues yielded a mean of 3.34 ng/g levamisole with a CV of 3.0%. C1 US Food & Drug Adm, Baltimore, MD 21201 USA. RP Schenck, FJ (reprint author), US Food & Drug Adm, Baltimore Dist,900 Madison Ave, Baltimore, MD 21201 USA. NR 9 TC 3 Z9 4 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD MAY-JUN PY 1998 VL 15 IS 4 BP 411 EP 414 PG 4 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA ZN794 UT WOS:000073683300006 PM 9764210 ER PT J AU Collins, TFX Shackelford, ME Sprando, RL Black, TN Laborde, JB Hansen, DK Eppley, RM Trucksess, MW Howard, PC Bryant, MA Ruggles, DI Olejnik, N Rorie, JI AF Collins, TFX Shackelford, ME Sprando, RL Black, TN Laborde, JB Hansen, DK Eppley, RM Trucksess, MW Howard, PC Bryant, MA Ruggles, DI Olejnik, N Rorie, JI TI Effects of fumonisin B(1) in pregnant rats SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID ESOPHAGEAL CANCER AREAS; FUSARIUM-MONILIFORME; DEVELOPMENTAL TOXICITY; SPHINGOLIPID BIOSYNTHESIS; CORN SCREENINGS; CD1 MICE; MYCOTOXINS; SWINE; SPHINGOSINE; INHIBITION AB Fumonisin B(1) (FB1), the major mycotoxin from Fusarium moniliforme, has been implicated as a causative agent in several animal and human diseases. Despite animal toxicity studies and human epidemiological studies of FB1, knowledge of its reproductive effects is scarce. In this study, one of a series of proposed studies that will allow extrapolation to humans, pregnant rats were given oral doses of 0, 1.875, 3.75, 7.5 or 15 mg FB1/kg on gestation days 3-16. Caesarean sections were performed on day 17 or 20, and maternal condition, implantation efficiency, foeta1 viability and foetal development were measured. Dose-related decreases in overall feed consumption and body weight gain were seen, but only the feed consumption decrease at 15 mg/kg, and the decreased body weight gain at 15 mg/kg on days 0-17 were statistically significant. Foetal body weights at day 17 were similar in control and treated groups; but in day-20 foetuses, female weight and crown-rump length were significantly decreased at 15 mg/kg. FBI was not teratogenic at the doses tested, and no dose-related effects were seen in either skeletal or soft-tissue development. In day-I7 animals, maternal and foetal brain, liver and kidney tissues, and maternal serum were preserved to study the levels of sphinganine (Sa), sphingosine (So), and the Sa/So ratios. Dose-related increases were seen in Sa/So ratios in maternal livers, kidneys and serum. Sa/So ratios of maternal brains were not affected, nor were those of foetal kidneys, livers or brains. Published by Elsevier Science Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Collins, TFX (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. FU PHS HHS [224-93-001] NR 63 TC 10 Z9 10 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD MAY PY 1998 VL 36 IS 5 BP 397 EP 408 DI 10.1016/S0278-6915(97)00170-1 PG 12 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA ZU842 UT WOS:000074241100005 PM 9662415 ER PT J AU Gaylor, D AF Gaylor, D TI Safety assessment with hermetic effects SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Article C1 US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. RP Gaylor, D (reprint author), US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. NR 1 TC 3 Z9 3 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0144-5952 J9 HUM EXP TOXICOL JI Hum. Exp. Toxicol. PD MAY PY 1998 VL 17 IS 5 BP 251 EP 253 DI 10.1191/096032798678908693 PG 3 WC Toxicology SC Toxicology GA ZW595 UT WOS:000074427600005 PM 9663931 ER PT J AU Bassen, HI AF Bassen, HI TI Radiofrequency interference with medical devices - A technical information statement SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article ID ELECTROMAGNETIC-INTERFERENCE; PACEMAKERS; PHONES AB The past few years have seen increased reports that medical devices, such as pacemakers, apnea monitors, electrically powered wheelchairs, etc., have failed to operate correctly because of interference from various emitters of radiofrequency energy. This condition is called radiofrequency interference (RFI). The consequences of these failures range from inconvenience to serious injuries and death. Reasons for this problem are twofold: 1) in creasing numbers of electronically controlled medical devices with inadequate electronic protection against RFI, and 2) a significant increase in the number of RF sources in the environment. Medical devices are widely used outside the hospital and may be attached to, or implanted in, patients. Portable wireless communications equipment, including cellular phones, handheld transceivers, and vehicle-mounted transceivers, comprise one of the largest sources of RFI. Some medical devices are especially sensitive to the type of digital modulation that some of the wireless communications devices utilize. The prevailing international standard for the RF immunity of medical devices is the 1993 revision of the International Electrotechnical Commission (IEC) Standard IEC 60601-1-2. This standard sets a minimum immunity level of 3 volts per meter (V/m) in the 26-1000 MHz frequency range. For non-life supporting devices, testing is required only at the specific frequencies of 27.12, 40.68, and 915 MHz. Technology exists to protect, or "harden," most medical devices from RF fields that are much more intense than the 3 V/m level specified in present RFI standards. Most of these techniques, including shielding, grounding, and filtering, are not costly if they are incorporated into the initial design of the electronics system. COMAR recommends that the various parties involved in the manufacture and use of RFI-prone medical devices take steps to avoid serious RFI problems that may lead to safety hazards. Medical device manufacturers should design and test their products to ensure conformance with current RFI standards and educate the users of their devices about the possible symptoms of potential RFI. If there exists the possibility of RFI problems to medical devices, steps should be taken to ensure that all sources of RF energy be kept at a sufficient distance. C1 US FDA, Rockville, MD 20852 USA. RP Bassen, HI (reprint author), US FDA, HFZ-133,12725 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 28 TC 21 Z9 21 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 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD MAY-JUN PY 1998 VL 17 IS 3 BP 111 EP 114 PG 4 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA ZN671 UT WOS:000073670000023 ER PT J AU Gu, XX Chen, J Barenkamp, SJ Robbins, JB Tsai, CM Lim, DJ Battey, J AF Gu, XX Chen, J Barenkamp, SJ Robbins, JB Tsai, CM Lim, DJ Battey, J TI Synthesis and characterization of lipooligosaccharide-based conjugates as vaccine candidates for Moraxella (Branhamella) catarrhalis SO INFECTION AND IMMUNITY LA English DT Article ID NONTYPABLE HAEMOPHILUS-INFLUENZAE; OUTER-MEMBRANE PROTEIN; OTITIS-MEDIA; SEROTYPE-A; LIPOPOLYSACCHARIDE ANTIGENS; IMMUNOLOGICAL PROPERTIES; PROTECTIVE ANTIBODIES; OLIGOSACCHARIDE; INFECTION; CHILDREN AB Moraxella (Branhamella) catarrhalis is an important cause of otitis media and sinusitis in children and of lower respiratory tract infections in adults, Lipooligosaccharide (LOS) is a major surface antigen of the bacterium and elicits bactericidal antibodies. Treatment of the nos from strain ATCC 25238 with anhydrous hydrazine reduced its toxicity 20,000-fold. as assayed in the Limulus amebocyte lysate (LAL) test. The detoxified LOS (dLOS) was coupled to tetanus toroid (TT) or high-molecular-weight proteins (HMP) from nontypeable Haemophilus influenzae through a linker of adipic acid dihydrazide to form dLOS-TT or dLOS-HMP. The molar ratios of dLOS to TT and HMP conjugates were 19:1 and 31:1, respectively. The antigenicity of the two conjugates was similar to that of the nos, as determined by double immunodiffusion. Subcutaneous or intramuscular injection of both conjugates elicited a 50- to 100-fold rite in the geometric mean of immunoglobulin G (IgG) to the homologous LOS in mice after three injections and a 350- to 700-fold rise of anti-nos IgG in rabbits after two injections. The immunogenicity of the conjugate was enhanced by formulation with monophosphoryl lipid A plus trehalose dimycolate. In rabbits, conjugate-induced antisera had complement-mediated bactericidal activity against the homologous strain and heterologous strains of M. catarrhalis. These results indicate that a detoxified LOS-protein conjugate is a candidate for immunization against M. catarrhalis diseases. C1 NIDCD, NIH, Immunol Lab, Rockville, MD 20850 USA. St Louis Univ, Sch Med, Dept Pediat, St Louis, MO 63104 USA. House Ear Inst, Los Angeles, CA 90057 USA. NICHD, Bethesda, MD 20892 USA. US Food & Drug Adm, Bethesda, MD 20892 USA. RP Gu, XX (reprint author), NIDCD, NIH, Immunol Lab, 5 Res Court,2A31, Rockville, MD 20850 USA. EM xgu@pop.nidcd.nih.gov OI Barenkamp, Stephen/0000-0002-3054-8910 NR 61 TC 59 Z9 62 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1998 VL 66 IS 5 BP 1891 EP 1897 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZL243 UT WOS:000073413100012 PM 9573066 ER PT J AU Robie-Suh, KM AF Robie-Suh, KM TI Current status of the FDA approval process: Comparison of requirements for pediatric and adult patients SO INFLAMMATORY BOWEL DISEASES LA English DT Article; Proceedings Paper CT Consensus Conference on the Evaluation of Drugs to Treat Children with Inflammatory Bowel Disease CY OCT 18-19, 1997 CL PHILADELPHIA, PENNSYLVANIA SP Crohns & Colitis Fdn Amer Inc, Schering Plough Res Inst, Hoechst Marion Roussel Inc, Procter & Gamble Pharm Inc, Solvay Pharm Inc DE drug product labeling; pediatric dosing; pediatric drug use C1 US FDA, Div Gastrointestinal & Coagulat Drug Prod, Rockville, MD 20857 USA. RP Robie-Suh, KM (reprint author), US FDA, Div Gastrointestinal & Coagulat Drug Prod, HFD-180,5600 Fishers Lane, Rockville, MD 20857 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 1998 VL 4 IS 2 BP 103 EP 104 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZL117 UT WOS:000073400500007 PM 9687212 ER PT J AU Dean, JH Hincks, J Luster, MI Gerberick, GF Neumann, DA Hastings, KL AF Dean, JH Hincks, J Luster, MI Gerberick, GF Neumann, DA Hastings, KL TI Safety evaluation and risk assessment using immunotoxicology methods SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article ID LYMPH-NODE ASSAY; CONTACT ALLERGENS; IMMUNE; CHEMICALS; MICE; EXPOSURE; INVITRO; IDENTIFICATION; SENSITIZATION; MAXIMIZATION C1 Sanofi Res, Sanofi Pharmaceut Inc, Malvern, PA 19355 USA. NIOSH, Morgantown, WV USA. Procter & Gamble Co, Cincinnati, OH USA. ILSI Risk Sci Inst, Washington, DC USA. US FDA, CDER, Div Antiviral Drug Prod, Rockville, MD 20857 USA. RP Dean, JH (reprint author), Sanofi Res, Sanofi Pharmaceut Inc, 9 Great Valley Pkwy,POB 3026, Malvern, PA 19355 USA. NR 62 TC 0 Z9 1 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD MAY-JUN PY 1998 VL 17 IS 3 BP 277 EP 296 PG 20 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA ZP646 UT WOS:000073774300004 ER PT J AU Collins, TFX Sprando, RL Hansen, DL Shackelford, ME Welsh, JJ AF Collins, TFX Sprando, RL Hansen, DL Shackelford, ME Welsh, JJ TI Testing guidelines for evaluation of reproductive and developmental toxicity of food additives in females SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article AB The original Redbook issued by the Food and Drug Administration in 1982 provided guidelines for testing the effects of direct food additives and color additives on mothers and developing embryos. The tests included brief teratology/developmental toxicity studies and longer studies spanning several generations called multigeneration reproduction studies. In 1993, the draft version of Redbook II was made available for public comment. In it, the revised chapter on, reproduction and developmental toxicity is the result of extensive literature review and public comment. It includes discussions of the major manifestations of an effect on the developing organism-death, structural anomaly, altered or retarded growth, and functional deficiency-and evaluation of these manifestations with respect to dosage and other factors. Additional test endpoints and developmental landmarks are included and evaluated. The use of the degree of maternal toxicity in assessing fetotoxicity or embryotoxicity is discussed. FDA's revised guidelines for developmental toxicity and multigeneration reproduction studies are described and compared with current EPA draft guidelines and the guidelines issued by the OECD. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Ctr Food Safety & Appl Nutr, Washington, DC USA. RP Collins, TFX (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-507,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 14 TC 6 Z9 6 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD MAY-JUN PY 1998 VL 17 IS 3 BP 299 EP 325 PG 27 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA ZP646 UT WOS:000073774300006 ER PT J AU Sprando, RL Collins, TFX AF Sprando, RL Collins, TFX TI Testing guidelines for evaluation of food additives' effects on male reproduction SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article AB The revised FDA Redbook guidelines presented in this article reflect current thinking concerning male reproductive toxicology. A number of different endpoints to assess male reproductive function have been included in the present draft of the FDA Redbook II guidelines to better assess potential effects of direct food additives and color additives on male reproductive function. The guidelines reflect a harmony with the development of the guidelines of regulatory: agencies in this country and around the world. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Sprando, RL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-507,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD MAY-JUN PY 1998 VL 17 IS 3 BP 327 EP 336 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA ZP646 UT WOS:000073774300007 ER PT J AU Hattan, DG AF Hattan, DG TI In utero phase carcinogenicity testing SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article ID PERINATAL EXPOSURE; MICE; RATS; MOUSE; INDUCTION; TUMORS; SACCHARIN; QUINOLINE; NEWBORN; LIVER AB Early experimentation with transplacental exposure (1940s) demonstrated that expression of lung tuners in mice was enhanced when urethane was given. during development in utero. In 1970, a U.S. Food and Drug Administration (FDA) expert panel on the safety evaluation of food additives and pesticides met and recommended that an in utero exposure phase be added to carcinogenicity testing (U.S. FDA, 1971). An analysts was conducted of studies in the open scientific literature, in food additive studies available in FDA files and in studies performed by the National Institute of Environmental Health Sciences (NIEHS). While exposure to rodents during only the adult phase provided qualitatively similar results, early neonatal exposure typically provided slightly higher incidences of tumors, and decreased latency to tumor onset in certain scientific studies. In a series of studies recently performed by the NIEHS with three known animal carcinogens, neonatal or adult exposure produced similar tumors in similar tissues. The food additive saccharin,, which shows bladder tumors, and eugenol reliably produced tumors only with neonatal exposure. Implications for carcinogenicity testing of food additives are discussed in Light of these experimental findings. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Hattan, DG (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-507,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 46 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD MAY-JUN PY 1998 VL 17 IS 3 BP 337 EP 353 DI 10.1080/109158198226611 PG 17 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA ZP646 UT WOS:000073774300008 ER PT J AU Roth, WL Young, JF AF Roth, WL Young, JF TI Use of pharmacokinetic data under the FDAs Redbook II guidelines for direct food additives SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article ID AIR PARTITION-COEFFICIENTS; LINEAR MAMMILLARY MODELS; BLOOD-FLOW; ORGANIC-CHEMICALS; INVIVO; RAT; INVITRO; TISSUE; DRUG; HEPATOCYTES AB Experience with food additive petitions submitted after publication of the Food and Drug Administration's Redbook I(U.S. FDA, 1982) guidelines indicated a number of areas in which improvements were needed, and advances in toxicology testing during the last decade required additional revisions. In March 1993, the FDA's Center for Food Safety and Applied Nutrition (CFSAN) distributed copies of a draft of Redbook II for public comment. Since that time, revisions have been made based on comments received on the initial draft. This article describes the rationale for Redbook II guidance on the design of pharmacokinetic studies and discusses some common problems the FDA has encountered in reviewing pharmacokinetic data submitted as part of food additive petitions. Points emphasized are that (1) pharmacokinetic information is needed for the interpretation of toxicity studies and is most useful when conducted before major toxicity studies, (2) the use of whole-body autoradiography is encouraged as a means to select tissues of interest, and as a substitute for dissection and tissue sampling, (3) kinetic and mechanistic studies conducted with blood components, tissue slices, hepatocytes, and other cell types in vitro often provide more useful information on the fate of chemicals in specific tissues than information extracted from whole-animal studies. The intention of the new guidelines for pharmacohinetic studies is to increase the information content of data gathered and to encourage the use of pharmacokinetic models and results in the selection of doses for subchronic, chronic, and developmental toxicity studies. C1 US FDA, MOD I Lab, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Roth, WL (reprint author), US FDA, MOD I Lab, Ctr Food Safety & Appl Nutr, HFS-507,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 54 TC 2 Z9 2 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD MAY-JUN PY 1998 VL 17 IS 3 BP 355 EP 381 PG 27 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA ZP646 UT WOS:000073774300009 ER PT J AU Ciolino, LA AF Ciolino, LA TI Determination and classification of added caramel color in adulterated acerola juice formulations SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE caramel color; HPLC profiling; acerola; juice adulteration ID SUGAR COULEUR; CHROMATOGRAPHY; SPECIFICATIONS AB Four batches of acerola juice concentrate were suspected of being adulterated with caramel color from a specific caramel color raw material. Analyses of both the caramel color raw material and the finished acerola juice products were conducted. The detection of the caramel marker compounds 5-HMF and 4-MeI in the raw material was consistent with its classification as a class IV caramel color. A distinctive four-peak sequence in the HPLC-UV profile of the raw material was used to match the caramel color to its commercial source. The same four-peak sequence was used to detect and quantify added caramel color in the finished acerola juice products. This is the first report of an adulterated acerola juice product and the first report in which added caramel color has been matched to its commercial source. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45202 USA. RP Ciolino, LA (reprint author), US FDA, Forens Chem Ctr, 1141 Cent Pkwy, Cincinnati, OH 45202 USA. EM lciolino@ora.fda.gov NR 20 TC 14 Z9 14 U1 3 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 EI 1520-5118 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY PY 1998 VL 46 IS 5 BP 1746 EP 1753 DI 10.1021/jf970878i PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA ZP481 UT WOS:000073757800009 ER PT J AU Nasr, MM Reepmeyer, JC Tang, YB AF Nasr, MM Reepmeyer, JC Tang, YB TI In vitro study of nicotine release from smokeless tobacco SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ABSORPTION; SNUFF AB Four brands (Copenhagen Snuff, Skoal Bandit Classic, Skoal Wintergreen Long Cut, and Skoal Wintergreen Fine Cut) of smokeless tobacco products were tested for their rate of nicotine release into artificial saliva via direct contact or through a dialysis bag. Nicotine was determined by reversed-phase liquid chromatography. When samples were in direct contact with artificial saliva, most of the nicotine was released from the tobacco in the first minute. Nicotine release from Skoal Bandit Classic, marketed as smokeless tobacco in a sachet, was slower with the sachet intact than without the sachet, When smokeless tobacco and artificial saliva were placed inside a dialysis bag, nicotine release was much slower and primarily depended upon the permeability of the dialysis membrane. Although total nicotine was lowest for Skoal Bandit Classic, little difference was seen in nicotine release rates among the brands tested. When smokeless tobacco was placed in dialysis bags with artificial saliva outside, a significant difference was seen in rates of nicotine migration through the membrane. In this model, nicotine release from Copenhagen Snuff was much faster than from Skoal Bandit Classic with or without the sachet. This difference may be related to the pH of the smokeless tobacco products. C1 US FDA, Div Testing & Appl Analyt Dev, St Louis, MO 63101 USA. RP Nasr, MM (reprint author), US FDA, Div Testing & Appl Analyt Dev, 1114 Market St,Room 1002, St Louis, MO 63101 USA. NR 14 TC 7 Z9 7 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 MAY-JUN PY 1998 VL 81 IS 3 BP 540 EP 543 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA ZM875 UT WOS:000073585100008 PM 9606918 ER PT J AU Rupp, HS Turnipseed, SB Walker, CC Roybal, JE Long, AR AF Rupp, HS Turnipseed, SB Walker, CC Roybal, JE Long, AR TI Determination of ivermectin in salmon muscle tissue by liquid chromatography with fluorescence detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ATLANTIC SALMON; BOVINE-MILK; LIVER; RESIDUES; DERIVATIZATION; EXTRACTION; PLASMA; SALAR; HPLC AB A liquid chromatographic method was developed for determination of ivermectin B-1a (IVR) extracted from raw fortified and incurred Atlantic salmon muscle tissues. The method was also used to determine fortified doramectin (DOR) in Atlantic salmon. Tissue extract was applied to a C-8 solid-phase extraction (SPE) column, followed by a silica SPE column. Residues in the eluate were treated with trifluoroacetic anhydride and methylimidazole to dehydrate the IVR molecule and form an aromatic fluorescent moiety with a trifluoroacetic ester, This product was subsequently treated with ammonium acetate in methanol to cleave the ester and convert the functional group back to a stable alcohol form. The analytes were determined by fluorescence with excitation at 272 nm and emission at 465 nm. A C-18 Hypersil column was used for analysis with a mobile phase of acetonitrile-water (90 + 10, v/v) and an oven temperature of 65 degrees C, IVR and DOR were determined at 5 fortification levels (1, 5, 10, 20, and 40 ppb). Intra-assay absolute recoveries ranged from 75 to 89% for IVR and from 73 to 85% for DOR, Relative standard deviations (RSDs) were <7% in all cases. The limit of detection (3 x baseline noise) was 0.25 ppb extracted from tissue. Incurred tissues had an average concentration of 32 ppb, with an RSD of 3%. C1 US FDA, Seattle Dist Off, Bothell, WA 98021 USA. US FDA, Anim Drugs Res Ctr, Denver, CO 80225 USA. US EPA, Gulf Breeze, FL 32561 USA. US FDA, Atlant Ctr Nutr Anal, Atlanta, GA 30309 USA. RP Rupp, HS (reprint author), US FDA, Seattle Dist Off, 22201 23rd Dr SE, Bothell, WA 98021 USA. NR 16 TC 19 Z9 24 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1998 VL 81 IS 3 BP 549 EP 553 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA ZM875 UT WOS:000073585100010 PM 9606920 ER EF