FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Luo, WH Hansen, EB Ang, CYW Thompson, HC AF Luo, WH Hansen, EB Ang, CYW Thompson, HC TI Determination of lincomycin residue in salmon tissues by ion-pair reversed-phase liquid chromatography with electrochemical detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A method is described for detecting and quantitating lincomycin residue in salmon muscle and skin tissues by ion-pair reversed-phase liquid chromatography (LC) with electrochemical detection at +0.9 V. Lincomycin was extracted from tissues by homogenizing with 0.01M KH2PO4 buffer (pH 4.5) and centrifuging the mixture. Water-soluble proteins were precipitated by adding sodium tungstate and sulfuric acid and removed by centrifugation, The buffer extract was then passed through a C-18 solid-phase extraction cartridge, Lincomycin was eluted with 50% acetonitrile in water, and the eluate containing lincomycin was extracted with ethyl acetate, After the solvent had evaporated, the residue was redissolved in mobile phase and analyzed by LC, The method had a limit of detection of 7 ng/g lincomycin for salmon muscle and 12 ng/g for salmon skin, The limit of quantitation was 17 ng/g for salmon muscle and 24 ng/g for salmon skin, Average recoveries of lincomycin spiked at 50, 100, and 200 ng/g were greater than or equal to 85% for salmon muscle and greater than or equal to 80% for salmon skin. C1 US FDA,NATL CTR TOXICOL RES,DIV CHEM,JEFFERSON,AR 72079. NR 11 TC 10 Z9 12 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1996 VL 79 IS 4 BP 839 EP 843 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA UX853 UT WOS:A1996UX85300006 PM 8757439 ER PT J AU McNeilly, PJ Reeves, VB Deveau, EJI AF McNeilly, PJ Reeves, VB Deveau, EJI TI Determination of ceftiofur in bovine milk by liquid chromatography SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID CLEANUP; PLASMA; CATTLE AB A liquid chromatographic procedure is described for determination of ceftiofur (CEF) residues in milk, Milk samples were diluted with ammonium acetate solution and extracted on a C-18 solid-phase extraction (SPE) column, After the analyte was eluted from the SPE column with methanol, extract volumes were reduced under nitrogen, diluted to 2.0 mL with acetate buffer, and filtered. CEF was determined after separation of milk components by reversed-phase chromatography with UV detection at 293 nm, Recoveries of CEF from bovine milk fortified at 25, 50, and 100 ppb were 86.1, 90.8, and 92.0%, respectively, with coefficients of variation (CVs) of 6.4, 7.3, and 3.9%, respectively. Values of CEF obtained from analysis of milk containing 2 levels of biologically incurred residues were 26.1 and 67.3 ppb with CVs of 3.8 and 4.4%, respectively, The limits of detection and quantitation were estimated to be 4 and 7 ppb, respectively. C1 US FDA,AGR RES CTR E,CTR VET MED,BELTSVILLE,MD 20705. NR 9 TC 6 Z9 6 U1 0 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1996 VL 79 IS 4 BP 844 EP 847 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA UX853 UT WOS:A1996UX85300007 PM 8757440 ER PT J AU Amaguana, RM Sherrod, PS Hammack, TS June, GA Andrews, WH AF Amaguana, RM Sherrod, PS Hammack, TS June, GA Andrews, WH TI Usefulness of cellulase in recovery of Salmonella spp from guar gum SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID FOODS AB Most foods examined for Salmonella spp, by the procedure described in the U.S. Food and Drug Administration's Bacteriological Analytical Manual are preenriched at a 1:9 sample/broth ratio, However, 25 g guar gum (an emulsifying agent) is not wetted completely in 225 mt of preenrichment broth, and after a 24 h incubation at 35 degrees C, the product is transformed into a viscous, nonpipettable mass, The effects of 4 factors (inorganic salts, pH, temperature, and various enzymes) on the viscosity of the sample/preenrichment mixture during incubation were determined, Addition of various inorganic salts or adjustment of pH from 4.0 to 9.0 had no significant effect on the viscosity of the incubated mixture, Elevated incubation temperatures of 42 degrees, 44 degrees, and 46 degrees C reduced viscosity but were well above the optimal growth temperature for Salmonella, 35 degrees C, Addition of cellulase to lactose broth at a final concentration of 0.01% reduced viscosity of the mixture, making it readily pipettable. At least one Salmonella cell was consistently recovered from 25 g samples of guar gum, which represents a most probable number value of 0.04 cell per g. RP Amaguana, RM (reprint author), US FDA,DIV MICROBIOL STUDIES,200 C ST SW,WASHINGTON,DC 20204, USA. NR 12 TC 3 Z9 3 U1 1 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1996 VL 79 IS 4 BP 853 EP 857 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA UX853 UT WOS:A1996UX85300009 PM 8757442 ER PT J AU Cohen, AE Kerdahi, KF AF Cohen, AE Kerdahi, KF TI Evaluation of a rapid and automated enzyme-linked fluorescent immunoassay say for detecting Escherichia coli serogroup O157 in cheese SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; POLYMERASE CHAIN-REACTION; INFECTION AB The Vitek Immunodiagnostic Assay System (VI-DAS) for Escherichia coli O157, a rapid and fully automated test, was evaluated for use in detecting the foodborne pathogen E. coli O157:H7 in soft, semisoft, and hard cheeses. Sixty-five cheese samples were artificially contaminated at low (2-4 colony-forming units [cfu]/25 g) and high (7-10 cfu/25 g) levels with one of 2 strains of enterohemorrhagic E. coli O157:H7. Contamination at high levels was detected in all cheeses by VIDAS, whereas in 5 cheeses (7.7%) inoculated at low let els, contamination was not detected, In 15 additional cheeses inoculated with cold-stressed cells, both VIDAS and the Bacteriological Analytical Manual cultural assay detected all high and low levels of contamination. No false positives or interference from product background fluorescence was encountered in any of the cheeses tested by VIDAS. C1 US FDA,NE REG LAB,BROOKLYN,NY 11232. NR 13 TC 16 Z9 16 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1996 VL 79 IS 4 BP 858 EP 860 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA UX853 UT WOS:A1996UX85300010 PM 8757443 ER PT J AU Sciacchitano, CJ Hirshfield, IN AF Sciacchitano, CJ Hirshfield, IN TI Molecular detection of Clostridium botulinum type E neurotoxin gene in smoked fish by polymerase chain reaction and capillary electrophoresis SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID NUCLEOTIDE-SEQUENCE; E TOXIN; COMPONENT; MASHIKE; FOOD AB The polymerase chain reaction (PCR), a rapid, sensitive technique for amplifying target DNA sequences of pathogenic microorgansims, was used to amplify Clostridium botulinum type E neurotoxin gene fragments in smoked fish, Other botulinal neurotoxin-producing strains, nontoxigenic strains, and food-related microorganisms did not yield nonspecific amplification products with this PCR assay. PCR products were analyzed by capillary electrophoresis (CE) using a low-viscosity entangled polymer system, Resolution, sensitivity, and DNA sizing accuracy were improved, and analytical times were markedly shortened. The PCR/CE assay detected the C. botulinum type E neurotoxin gene in as few as 10 cells, The technique to other foods may also be a valuable tool for detecting foodborne pathogens. C1 ST JOHNS UNIV,JAMAICA,NY 11439. RP Sciacchitano, CJ (reprint author), US FDA,NE REG LAB,850 3RD AVE,BROOKLYN,NY 11232, USA. NR 20 TC 18 Z9 19 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1996 VL 79 IS 4 BP 861 EP 865 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA UX853 UT WOS:A1996UX85300011 PM 8757444 ER PT J AU Valdes, PA Ziobro, GC Ferrera, RS AF Valdes, PA Ziobro, GC Ferrera, RS TI Use of urease-bromothymol blue-agar method for large-scale testing of urine on grain and seeds SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB The current AOAC method (963.28) for large-scale (50 g) testing of urine on grain is basted on the reaction of sodium in urine with magnesium uranyl acetate, Detection of sodium suggests that urine is present and that a test. for urea is appropriate. Urea is detected with urease-bromothymol blue-paper and is confirmed through its reaction with xanthydrol to form dixanthylurea crystals, which are detected microscopically The initial nonspecific test for sodium can be influenced by the presence of salt or other sodium compounds, Furthermore, the magnesium uranyl acetate spray used in Method 963.28 potentially exposes the analyst to the aerosol of a volatile, toxic uranium compound, Excess reagents and analyzed test portions must be disposed of as radioactive waste. In addition, Method 963.28 requires several steps to determine the presence of urea, The alternative AOAC method (972.41) tests for the presence of urea from urine on individual seeds, Urea is enzymatically decomposed to ammonia and carbon dioxide by urease. Liberated ammonia shifts the pH, changing the color of the indicator in the agar from yellow to blue. This study adapts Method 972.41 to larger test samples. Up to 25 g grains and seeds are sprayed with urease test agar instead of being individually immersed in the urease test agar. The modified method was used to analyze urea on seeds and grains of 24 plants from 4 families. the method has a limit of defection of one seed contaminated with 1 mu g urea. RP Valdes, PA (reprint author), US FDA,DIV MICROANALYT EVALUAT,200 C ST SW,WASHINGTON,DC 20204, USA. NR 13 TC 2 Z9 2 U1 1 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1996 VL 79 IS 4 BP 866 EP 873 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA UX853 UT WOS:A1996UX85300012 PM 8757445 ER PT J AU Trucksess, MW Ready, DE Pender, MK Ligmond, CA Wood, GE Page, SW AF Trucksess, MW Ready, DE Pender, MK Ligmond, CA Wood, GE Page, SW TI Determination and survey of deoxynivalenol in white flour, whole wheat flour, and bran SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID DECONTAMINATION; ZEARALENONE; NIVALENOL; BAKING AB A liquid chromatographic (LC) method for determining deoxynivalenol (DON) in white flour, whole wheat flour, and bran was developed, A 25 g test portion was extracted with acetonitrile-water (84 + 16), and the extract was filtered and applied to a column containing a combination of charcoal, Celite, and other adsorbents, The eluate was then chromatographed on a silica-based, reversed-phase LC column by using a gradient of water and methanol, DON was measured at 220 nm, Average recoveries of DON from white flour, whole wheat flour, and bran spiked at 1 mu g/g were 88, 86, and 85%, respectively, The limit of determination of the method was <0.5 mu g/g, A total of 562 wheat-based products from the 1993 crop year were collected by 21 U.S. Food and Drug Administration District Offices and analyzed by this method in Kansas City, Seattle, and New Orleans District Laboratories, The numbers of samples with DON contamination 21 mu g/g from 163 bran, 272 white flour, 90 whole wheat flour, and 37 miscellaneous test samples were 20, 28, 14, and 2, respectively, About 52, 50, 40, and 27% of the same test samples were contaminated with DON at levels >0.1 mu g/g. RP Trucksess, MW (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV NAT PROD,WASHINGTON,DC 20204, USA. NR 12 TC 53 Z9 55 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1996 VL 79 IS 4 BP 883 EP 887 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA UX853 UT WOS:A1996UX85300014 PM 8757447 ER PT J AU Casanova, JA AF Casanova, JA TI Use of solid-phase extraction disks for analysis of moderately polar and nonpolar pesticides in high-moisture foods SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID RESIDUE DETERMINATION; CLEANUP; PARTITION; COLUMN AB This study investigated the use of solid-phase extraction (SPE) disks in analysis-of high-moisture (<2% fat) foods for organophosphorus and organochlorinated pesticides with low (<25 mg/mL) water solubilities. Five representative food were each spiked with one of 18 pesticides at 2 levels. Gas chromatography with flame photometric and electrolytic conductivity detection was used to quantitate organophosphates and organochlorinated pesticides, respectively, Essentially complete recoveries (greater than or equal to 80%) suggest that use of SPE disks can complement traditional liquid-liquid extraction procedures. RP Casanova, JA (reprint author), US FDA,60 8TH ST,ATLANTA,GA 30309, USA. NR 12 TC 27 Z9 29 U1 0 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1996 VL 79 IS 4 BP 936 EP 940 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA UX853 UT WOS:A1996UX85300021 PM 8757452 ER PT J AU Young, SJV Parfitt, CH Newell, RF Spittler, TD AF Young, SJV Parfitt, CH Newell, RF Spittler, TD TI Homogeneity of fruits and vegetables comminuted in a vertical cutter mixer SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB The homogeneity of comminuted composites of 20 lb samples of apples, cabbage, and green beans containing field-incurred residues of p,p'-methoxychlor was studied to determine whether a 5 min comminution in a 40 qt vertical cutter mixer produces a homogeneous composite and whether the size of test portions used accurately represents the composite. Duplicate test portions of 100, 50, 25, 10, 5, and 2 g taken from each of 6 separate sections of the mixer were analyzed by standard pesticide residue methodology for p,p'-methoxychlor. Results of this study confirmed that comminution of fresh produce in a 40 qt vertical cutter mixer, according to instructions described in the U.S. Food and Drug Administration's Pesticide. Analytical Manual, Volume I, section 203B, producer, a homogeneous composite, No significant differences were found in the data for the 3 crops taken from the 6 sections of the mixer, Test portion weights of 100, 50, and 25 g produced equivalent results for all 3 crops, Statistically significant differences were observed for cabbage at 2, 5, and 10 g and for green beans at 2 g. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,DIV PESTICIDES & IND CHEM,WASHINGTON,DC 20204. US FDA,CTR FOOD SAFETY & APPL NUTR,DIV MATH,WASHINGTON,DC 20204. CORNELL UNIV,NEW YORK STATE AGR EXPT STN,GENEVA,NY 14456. NR 4 TC 13 Z9 14 U1 0 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1996 VL 79 IS 4 BP 976 EP 980 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA UX853 UT WOS:A1996UX85300028 PM 8757457 ER PT J AU Kirchhoefer, RD Hamilton, JF AF Kirchhoefer, RD Hamilton, JF TI Effect of USP apparatus 1 and 2 at different rotational speeds on dissolution of niacin formulations SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Forty-four niacin formulations were examined by the United States Pharmacopeia dissolution test, consisting of 0.1N HCl with apparatus 1 and 2. Each formulation was tested with apparatus 1 (basket) at 100 rpm and apparatus 2 (paddle) at 50 and 100 rpm. Dissolution results varied widely among manufacturers. C1 US FDA,CTR DRUG EVALUAT & RES,DIV DRUG ANAL,ST LOUIS,MO 63101. NR 2 TC 1 Z9 1 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1996 VL 79 IS 4 BP 1005 EP 1008 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA UX853 UT WOS:A1996UX85300033 PM 8757459 ER PT J AU Hahn, DW Wolfarth, DL Parks, NL AF Hahn, DW Wolfarth, DL Parks, NL TI Characterization of submicron polyethylene wear debris from synovial-fluid samples of revised knee replacements using a light-scattering technique SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article ID JOINT AB The objectives of this study were to determine whether submicron-sized ultra-high-molecular-weight polyethylene (UHMWPE) wear debris was present in synovial fluid surrounding knee implants, and to report on the utility of a light-scattering technique for the in situ analysis of submicron-sized wear debris. The measured light-scattering coefficients of the implant synovial fluid samples were significantly larger than the coefficients of the control samples (p < 0.0001). The enhanced light scattering was attributed to the presence of submicron UHMWPE particles. This is consistent with light-scattering considerations and a Raman spectroscopy survey of synovial fluid. The mean particle volume fraction of UHMWPE was 1.11 x 10(-5) cm(3)/mL for the six implant samples, with mean particle diameters in the range of 200-300 nm. The UHMWPE volume fractions were found to differ by a factor of 2 between the osteolytic and nonosteolytic cases. The current findings warrant further work to determine the role of submicron polyethylene debris in the wear mechanisms of biomaterials and in the development of osteolysis following total knee replacement. (C) 1996 John Wiley & Sons, Inc. C1 US FDA, CTR DEVICES & RADIOL HLTH, ROCKVILLE, MD 20857 USA. ANDERSON ORTHOPAED RES INST, ARLINGTON, VA 22206 USA. NR 24 TC 23 Z9 24 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD JUL PY 1996 VL 31 IS 3 BP 355 EP 363 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA UU786 UT WOS:A1996UU78600009 PM 8806061 ER PT J AU Holcomb, M Thompson, HC AF Holcomb, M Thompson, HC TI Analysis of fumonisin B-1 in rodent feed by CE with fluorescence detection of the FMOC derivative SO JOURNAL OF CAPILLARY ELECTROPHORESIS LA English DT Article DE fumonisin B-1; mycotoxin; Fusarium moniliforme; FMOC derivative; CE ID FUSARIUM-MONILIFORME; MASS-SPECTROMETRY; CORN; HPLC; B1 AB A fast, simple, and environmentally friendly method has been developed for the analysis of fumonisin B-1 (FB1) in rodent feed using CE. FB1 is the major fumonisin metabolite produced by the fungus Fusarium moniliforme and has been implicated in human and animal diseases. FB1 was extracted from rodent feed with acetonitrile/water (50/50) (vol/vol) and cleaned up with a C-18 Sep-Pak Vac cartridge (Waters Corp., Milford, MA, U.S.A.). FB1 was quantitated after elution from the column using capillary electrophoresis with a 25-mM sodium berate buffer (pH 9.0) containing 10% acetonitrile and fluorescence detection of the (9-fluorenylmethyl) chloroformate (FMOC) derivative. The minimum detectable amount in rodent feed was 0.5 ppm. Recovery values in spiked rodent feed averaged more than 87% over the 2-20 ppm range. C1 US FDA,NATL CTR TOXICOL RES,DIV CHEM,JEFFERSON,AR 72079. NR 13 TC 6 Z9 9 U1 1 U2 4 PU I S C TECHNICAL PUBLICATIONS, INC PI SHELTON PA 30 CONTROLS DR, BOX 828, SHELTON, CT 06484-0828 SN 1079-5383 J9 J CAPILLARY ELECTROP JI J. Capillary Electrophor. PD JUL-AUG PY 1996 VL 3 IS 4 BP 205 EP 208 PG 4 WC Biochemistry & Molecular Biology; Electrochemistry SC Biochemistry & Molecular Biology; Electrochemistry GA WV567 UT WOS:A1996WV56700005 PM 9384738 ER PT J AU Gerstman, BB Jolson, HM Bauer, M Cho, P Livingston, JM Platt, R AF Gerstman, BB Jolson, HM Bauer, M Cho, P Livingston, JM Platt, R TI The incidence of depression in new users of beta-blockers and selected antihypertensives SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE depression; adrenergic beta receptor blockaders; propranolol; hypertension; central nervous system effects; information systems; ambulatory care ID BLOCKING-AGENTS; PROPRANOLOL; SYSTEM; THERAPY; TRIALS AB We studied the occurrence of depression in new users of propranolol (n = 704), other betablockers (n = 587), angiotensin-converting enzyme inhibitors (n = 976), calcium channel blockers (n = 742), and diuretics (n = 773) in the Harvard Community Health Plan population. The period of the study was from April 1988 to June 1991. All study subjects were followed for new or newly recurrent depression for up to 6 months after receiving their first study prescription, Case status was confirmed by blinded medical record review. We found 10 cases of depression that met DSM-III-R criteria (''major depression'') and an additional 18 cases that had one or more symptoms consistent with depression (''minor depression''). Rates of major depression in users of beta blockers and users of non beta-blocker study drugs were 5.8 per 1000 person-years of exposure and 9.6 per 1000 person-years, respectively. None of the cases of major depression was propranolol associated. Rates of major or minor depression (combined) in users of beta-blockers and users of non-beta-blockers were 20.2 per 1000 person-years and 25.2 per 1000 person years, respectively. The age- and sex-adjusted relative risk of major or minor depression associated with the use of beta-blockers compared to non-beta-blockers was 0.8 (95% CI, 0.3-1.9). The relative risk associated with propranolol compared to non-beta-blockers was also 0.8 (95% CI, 0.1-2.7), Therefore, depression occurred no more frequently in beta-blocker users than in other members of the study base. C1 US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. HARVARD PILGRIM HLTH CARE,BROOKLINE,MA. BRIGHAM & WOMENS HOSP,DEPT MED,CHANNING LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT AMBULATORY CARE & PREVENT,BOSTON,MA. RP Gerstman, BB (reprint author), SAN JOSE STATE UNIV,DEPT HLTH SCI,SAN JOSE,CA 95192, USA. FU FDA HHS [FD-U-000315] NR 31 TC 46 Z9 47 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JUL PY 1996 VL 49 IS 7 BP 809 EP 815 DI 10.1016/0895-4356(96)00017-0 PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA VA007 UT WOS:A1996VA00700016 PM 8691233 ER PT J AU Yu, CR Lin, JX Fink, DW Akira, S Bloom, ET Yamauchi, A AF Yu, CR Lin, JX Fink, DW Akira, S Bloom, ET Yamauchi, A TI Differential utilization of Janus kinase-signal transducer and activator of transcription signaling pathways in the stimulation of human natural killer cells by IL-2, IL-12, and IFN-alpha SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PERIPHERAL-BLOOD LYMPHOCYTES; HUMAN NK CELLS; INTERFERON-GAMMA; BETA-CHAIN; MEDIATED CYTOTOXICITY; HUMAN INTERLEUKIN-2; T-CELLS; INDUCTION; RECEPTOR; TYROSINE AB IL-2-, IL-12-, and IFN-alpha-mediated signaling pathways were analyzed in primary NK cells and in the NK3.3 cell line. Gel mobility shift and immunoprecipitation analyses revealed that in addition to activating STAT3 (signal transducer and activator of transcription-3) and STAT5, IL-2 induced tyrosine and serine phosphorylation of STAT1 alpha, which formed IFN-gamma-activated sequence-binding complexes by itself and with STAT3. Although IL-2 and IFN-alpha activated STAT1 alpha and STAT5, IL-2 predominantly activated STAT5, while IFN-alpha predominantly activated STAT1 alpha. IL-2 induced less STAT1 alpha activation and IFN-alpha induced greater STAT5 activation in NK3.3 cells compared with preactivated primary NK cells. In NK3.3 cells, IL-2 induced comparable formation of c-fos promoter sis-inducible element IFN-gamma-activated sequence-binding complexes containing STAT3 alone with complexes containing STAT3 and STAT1 alpha, while in preactivated primary NK cells, it preferentially induced complexes containing STAT3 and STAT1 alpha. Thus, signaling in NK3.3 cells is not always identical with that in primary NK cells. In contrast to IL-2 and IFN-alpha, IL-12 induced strong tyrosine phosphorylation of STAT4 and variable weak phosphorylation of STAT3. However, supershift analyses using the c-fos promoter sis-inducible element probe showed that IL-12 activated STAT4, STAT1 alpha, and STAT3, acid induced complexes containing STAT4 only, STAT4 with STAT1 alpha, STAT3 with STAT1 alpha, or STAT1 alpha only in preactivated primary NK cells. STAT1 alpha activation by IL-12 correlated with increased phosphorylation of serine, but not tyrosine. Finally, IL-2 induced tyrosine phosphorylation of JAK1 and JAK3, while IL-12 induced phosphorylation of JAK2 and TYK2 in both preactivated primary NK and NK3.3 cells. Differential phosphorylation and consequent differential activation of both separate and overlapping STAT proteins by IL-2, IL-12, and IFN-alpha may provide a molecular basis for the similarities and differences in the actions of these cytokines on NK cells. C1 US FDA,CELLULAR IMMUNOL LAB,DIV CELLULAR & GENE THERAPIES,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. US FDA,CELL BIOL LAB,DIV CYTOKINE BIOL,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,DEPT MICROBIOL & IMMUNOL,WASHINGTON,DC 20037. OSAKA UNIV,INST MOLEC & CELLULAR BIOL,DIV IMMUNOL,SUITA,OSAKA 565,JAPAN. NHLBI,LAB MOL IMMUNOL,NIH,BETHESDA,MD 20892. RI Akira, Shizuo/C-3134-2009 NR 73 TC 80 Z9 82 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1996 VL 157 IS 1 BP 126 EP 137 PG 12 WC Immunology SC Immunology GA UT109 UT WOS:A1996UT10900016 PM 8683106 ER PT J AU RiepenhoffTalty, M Gouvea, V Evans, MJ Svensson, L Hoffenberg, E Sokol, RJ Uhnoo, I Greenberg, SJ Schakel, K Zhaori, G Fitzgerald, J Chong, S ElYousef, M Nemeth, A Brown, M Piccoli, D Hyams, J Ruffin, D Rossi, T AF RiepenhoffTalty, M Gouvea, V Evans, MJ Svensson, L Hoffenberg, E Sokol, RJ Uhnoo, I Greenberg, SJ Schakel, K Zhaori, G Fitzgerald, J Chong, S ElYousef, M Nemeth, A Brown, M Piccoli, D Hyams, J Ruffin, D Rossi, T TI Detection of group C rotavirus in infants with extrahepatic biliary atresia SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID POLYMERASE CHAIN-REACTION; GROUP-A ROTAVIRUSES; NEONATAL HEPATITIS; ELECTRON-MICROSCOPY; REOVIRUS TYPE-3; FAMILY OUTBREAK; DIARRHEA; INFECTION; PARTICLES; ETIOLOGY AB The purpose of this retrospective study was to examine liver tissue from patients with cholestatic disease for the presence of group C rotavirus RNA. The reverse transcriptase-polymerase chain reaction (PCR) for genes 5 and 6 was used, and the PCR products were subjected to liquid hybridization with a P-32-labeled probe. A second amplification with nested primers was also used. Samples from 32 subjects (20 with biliary atresia or choledochal cyst and 12 controls) were tested. Ten of 20 biliary atresia patients were positive for group C rotavirus RNA; no controls were positive (P < .003). Three of the positive patients were positive for both genes 5 and 6. Six of the 10 had > 1 sample that was positive. These data suggest a possible relationship between group C rotavirus and extrahepatic biliary atresia in the 10 patients in whom virus RNA was detected. C1 SUNY BUFFALO,CHILDRENS HOSP BUFFALO,DEPT PEDIAT,BUFFALO,NY. SUNY BUFFALO,CHILDRENS HOSP BUFFALO,DEPT MICROBIOL,BUFFALO,NY. SUNY BUFFALO,CHILDRENS HOSP BUFFALO,DEPT NEUROL,BUFFALO,NY. ROSWELL PK CANC INST,DEPT CELLULAR & MOLEC BIOL,BUFFALO,NY. UNIV ROCHESTER,MED CTR,DIV PEDIAT GASTROENTEROL & NUTR,ROCHESTER,NY 14642. US FDA,WASHINGTON,DC 20204. UNIV COLORADO,SCH MED,DEPT PEDIAT PEDIAT GASTROENTEROL & NUTR,DENVER,CO. CHILDRENS HOSP,DENVER,CO 80218. JAMES WHITCOMB RILEY HOSP CHILDREN,DEPT PEDIAT GASTROENTEROL,INDIANAPOLIS,IN 46202. CHILDRENS MEM HOSP,DIV GASTROENTEROL,CHICAGO,IL 60614. CHILDRENS HOSP PHILADELPHIA,DIV GASTROENTEROL & NUTR,PHILADELPHIA,PA 19104. HARTFORD HOSP,DIV PEDIAT GASTROENTEROL,HARTFORD,CT 06115. KAROLINSKA INST,HUDDINGE HOSP,NATL BACTERIOL LAB,VIROL LAB,S-10401 STOCKHOLM,SWEDEN. KAROLINSKA INST,HUDDINGE HOSP,DEPT PEDIAT,S-10401 STOCKHOLM,SWEDEN. UNIV HOSP,DEPT INFECT DIS,UPPSALA,SWEDEN. UNIV GOTTINGEN,W-3400 GOTTINGEN,GERMANY. BEIJING CHILDRENS HOSP,BEIJING PEDIAT RES INST,BEIJING,PEOPLES R CHINA. FU NCRR NIH HHS [RR-00069] NR 39 TC 135 Z9 138 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL PY 1996 VL 174 IS 1 BP 8 EP 15 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UT468 UT WOS:A1996UT46800002 PM 8656017 ER PT J AU Goda, K Balkay, L Marian, T Tron, L Aszalos, A Szabo, G AF Goda, K Balkay, L Marian, T Tron, L Aszalos, A Szabo, G TI Intracellular pH does not affect drug extrusion by P-glycoprotein SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article DE multidrug resistance; intracellular pH; P-glycoprotein ID LARGE UNILAMELLAR VESICLES; MULTIDRUG-RESISTANCE; TUMOR-CELLS; CANCER-CELLS; CYTOSOLIC PH; TRANSPORT; ADRIAMYCIN; BINDING; LINES; DAUNORUBICIN AB The intracellular pH (pH(i)) of cells exhibiting multidrug resistance (MDR) related to the expression of the P-glycoprotein (Pgp) is often more alkaline than that of the parental cells, as also observed for the KB-V1/KB-3-1 system in this paper. The possible role of an elevated pH(i) in Pgp-related MDR has been investigated by shifting back the pH(i) of the MDR(+) cells to a more acidic value using the mobile proton ionophore carbonylcyanide m-chlorophenylhydrazone (CCCP). The influence of CCCP-evoked Delta pH(i) on relative daunorubicin (DNR) accumulation was similar in the case of several Pgp positive and negative cell lines, in view of flow cytometric and radioactive drug accumulation studies and measuring DNR levels in the medium in a flow-through system. Our data argue against a significant effect of pH(i) on Pgp pumping efficiency. However, an indirect connection between pH(i) regulation and the MDR phenotype is suggested by the fact that acidification of the external medium in the presence of verpamil could be observed exclusively in MDR(+) cells. C1 DEBRECEN UNIV MED,SCH MED,PET CTR,H-4012 DEBRECEN,HUNGARY. US FDA,CTR DRUG EVALUAT & RES,DIV RES & AGING,WASHINGTON,DC 20204. RP Goda, K (reprint author), DEBRECEN UNIV MED,SCH MED,DEPT BIOPHYS,H-4012 DEBRECEN,HUNGARY. NR 38 TC 20 Z9 21 U1 0 U2 4 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE 1 PA PO BOX 564, 1001 LAUSANNE 1, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD JUL PY 1996 VL 34 IS 2-3 BP 177 EP 182 DI 10.1016/1011-1344(95)07282-9 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VF409 UT WOS:A1996VF40900011 PM 8810535 ER PT J AU Chen, ETY HughesDillon, K Schroeder, LW AF Chen, ETY HughesDillon, K Schroeder, LW TI Development of analytical methods for quantification of residual powder on 'powderless' latex gloves SO JOURNAL OF TESTING AND EVALUATION LA English DT Article DE residual glove powder; aqueous phase modifier; beta-cyclodextrin; analytical method; latex glove ID ANTIGENS; ANAPHYLAXIS; PRODUCTS; CONTACT; ASTHMA AB This paper describes the validation of an analytical method to determine the minimum amount of residual corn starch powder that can reliably be detected on ''powderless'' gloves. Our procedures are similar to the ASTM D 11.40 method currently under development titled ''ASTM D 11.40, Section I Working Draft for Powder-free Glove Method.'' The various steps in the procedure were analyzed to determine their limitations and effects on the final results. The ability of the washing steps to remove residual powder from ''powderless'' gloves was ascertained by conducting recovery studies. An average powder recovery of 81.52% with a relative standard deviation (rsd) value of 8.12% (n = 15) was obtained by the draft ASTM D 11.40 procedure. The efficiency of the filtration and transfer steps was measured. A new device designed in this laboratory received an average yield of 1.51 +/- 0.13 mg/glove (n = 15) as compared to the updated draft ASTM D 11.40 method with 0.84 +/- 0.11 mg/glove (n = 15). Our new procedure gave an increase of 79% in yield with a rsd value of 8.5%. To enhance yield and powder recovery, it is crucial to rinse the glove surface effectively and reduce the washwater transfer steps. The use of beta-cyclodextrin (beta-CD) as an aqueous phase modifier was investigated. The results obtained with (beta-CD) increased the powder recovery per glove to 102% with a pooled standard deviation (psd) of 8% (n = 30, 10 level), corresponding to a rsd value of 8% when powder recovery was in the range of 0.5-10 mg. With water alone, the average recovery was 89% with a psd value of 16% in the same range. However, when the range was limited to 1-10 mg, the powder recovery per glove when using water alone was 95% with a psd value of 14%. The 2.7 mu m glass microfiber filter collects 96% of the powder applied to it. The degree of dependency to which the amount of powder on the glove affects powder recovery was studied using the relative error coefficient (rec). The rec values are less than 0.5%/mg/glove throughout the range of 0.5-10 mg using beta-CD. With water alone in the same study range, a rec value of less than 3%/mg/glove was obtained. The correlation coefficients for percent powder recovery versus amount of powder on the glove show much less correlation over these study ranges. beta-CD increased the recovery 15% and decreased the dependency of recovery on the amount of powder on the glove by 7.3-fold. The slopes and intercepts of recovered powder versus added powder were 1.01 +/- 0.02 and 1.0 X 10(-2) +/- 1.3 X 10(-1) mg for P-CD wash, and 0.95 +/- 0.04 and -6.0 X 10(-2) +/- 2.5 X 10(-1) mg for water wash in the range of 0.5-10 mg, respectively. C1 US FDA,CTR DEVICES & RADIOL HLTH,DIV MECH & MAT SCI,ROCKVILLE,MD 20857. NR 23 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 SN 0090-3973 J9 J TEST EVAL JI J. Test. Eval. PD JUL PY 1996 VL 24 IS 4 BP 229 EP 236 PG 8 WC Materials Science, Characterization & Testing SC Materials Science GA UW686 UT WOS:A1996UW68600004 ER PT J AU Martinez, MN Brown, SA Copeland, DD Haibel, GK Koritz, GD Riddell, MG Riviere, JE Rollins, LD AF Martinez, MN Brown, SA Copeland, DD Haibel, GK Koritz, GD Riddell, MG Riviere, JE Rollins, LD TI Developing a model of a professional veterinary drug label SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Editorial Material C1 PHARMACIA & UPJOHN INC,DIV ANIM HLTH,KALAMAZOO,MI 49001. BAYER ANIM HLTH,PHARMACEUT RES & DEV,MERRIAM,KS 66202. UNIV ILLINOIS,COLL VET MED,URBANA,IL 61801. AUBURN UNIV,COLL VET MED,AUBURN,AL 36849. N CAROLINA STATE UNIV,COLL VET MED,RALEIGH,NC 27606. RP Martinez, MN (reprint author), US FDA,CTR VET MED,7500 STANDISH PL,ROCKVILLE,MD 20855, USA. RI Riviere, Jim/A-9210-2008 OI Riviere, Jim/0000-0001-8412-9650 NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD JUL 1 PY 1996 VL 209 IS 1 BP 83 EP 91 PG 9 WC Veterinary Sciences SC Veterinary Sciences GA UU667 UT WOS:A1996UU66700024 PM 8926218 ER PT J AU Altaie, SS Penque, PH Mookherjee, S Evans, DT AF Altaie, SS Penque, PH Mookherjee, S Evans, DT TI Should laboratories test for toxin A-negative, toxin B-positive Clostridium difficile? SO LABORATORY MEDICINE LA English DT Article AB We evaluated 300 stool specimens from patients suspected of having Clostridium difficile-associated diarrhea to determine the prevalence of toxin A-negative, toxin B-positive C difficile isolates. Each specimen was cultured anaerobically on selective media using the heat-shock method and screened for C difficile toxins by two enzyme immunoassays-one that uses an anti-toxin A monoclonal antibody and one that uses a mixture of an anti-toxin A and an anti-toxin B monoclonal. The C difficile strains isolated from specimens were retested for production of toxin B by a tissue culture assay and for production of toxin A by a second toxin A immunoassay. Thirty-two specimens were positive and 234 specimens were negative for all assays. Thirty-four specimens had discrepant results. After discrepancy analysis, all of the isolated difficile strains were determined to be either nontoxigenic (producing neither of the toxins) or toxigenic (producing both toxins). These data indicate that the prevalence of toxin A-negative, toxin B-positive strains of C difficile is not of concern in routine diagnostic testing for C difficile toxins in our study population. RP Altaie, SS (reprint author), CTR DRUG EVALUAT & RES,DIV ANTI INFECT DRUG PROD,DOCUMENT CONTROL ROOM,5600 FISHERS LANE,HFD-520,ROCKVILLE,MD 20857, USA. NR 8 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 SN 0007-5027 J9 LAB MED JI Lab. Med. PD JUL PY 1996 VL 27 IS 7 BP 468 EP 471 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UV076 UT WOS:A1996UV07600024 ER PT J AU Oelschlaeger, TA Tall, BD AF Oelschlaeger, TA Tall, BD TI Uptake pathways of clinical isolates of Proteus mirabilis into human epithelial cell lines SO MICROBIAL PATHOGENESIS LA English DT Article DE Proteus mirabilis; invasion; internalization; microfilaments; microtubules; receptor-mediated endocytosis; endosome acidification ID URINARY-TRACT INFECTION; ESCHERICHIA-COLI; INVASION DETERMINANTS; CHLAMYDIA-TRACHOMATIS; MOLECULAR-CLONING; MAMMALIAN-CELLS; MOUSE MODEL; HELA-CELLS; ENDOCYTOSIS; SALMONELLA AB Proteus mirabilis isolates obtained from urine and faeces showed high invasion levels into several human epithelial cell lines in gentamicin assays. invasion efficiencies of isolate 102 from a monkey with diarrhoea equalled or even exceeded those of Salmonella typhi strain Ty2 (6.3 to 13.8% of the inoculum). Vegetative, non-swarming P. mirabilis invaded epithelial cells efficiently and were found in endosomes and free in the cytoplasm. Although inhibition of eukaryotic protein synthesis by cycloheximide did not reduce bacterial uptake, inhibition with bacteriostatic antibiotics of bacterial protein-, RNA-, or DNA-synthesis reduced invasion drastically. Involvement of eukaryotic structures and processes in internalization was determined by using various inhibitors in the invasion assay. Uptake of P. mirabilis isolated from urine into gut (INT407, HCT-8) cells and bladder (T24) cells was dramatically inhibited only by microfilament depolymerization. Internalization of faecal isolate 102 into gut or bladder epithelial cells was inhibited by depolymerization of microfilaments or microtubules. Engulfment of isolate 102 into T24 bladder cells was also reduced by inhibition of receptor-mediated endocytosis. Interference with endosome acidification decreased the number of intracellular bacteria of isolate 102 in all three cell lines. These results suggest that P. mirabilis isolates from different sources are internalized by epithelial cells by different eukaryotic processes, and that these processes can vary between cell lines. C1 WALTER REED ARMY INST RES,DEPT BACTERIAL DIS,WASHINGTON,DC 20307. US FDA,DIV MICROBIOL STUDIES,WASHINGTON,DC 20204. RI Oelschlaeger, Tobias/B-5624-2015; OI Tall, Ben/0000-0003-0399-3629 NR 54 TC 10 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD JUL PY 1996 VL 21 IS 1 BP 1 EP 16 DI 10.1006/mpat.1996.0037 PG 16 WC Immunology; Microbiology SC Immunology; Microbiology GA UW559 UT WOS:A1996UW55900001 PM 8827702 ER PT J AU Syin, C Goldman, ND AF Syin, C Goldman, ND TI Cloning of a Plasmodium falciparum gene related to the human 60-kDa heat shock protein SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE heat shock protein 60; mitochondrial targeting sequence; transcript; Plasmodium falciparum ID ESCHERICHIA-COLI; BACTERIAL; MITOCHONDRIA; ANTIGEN; HSP60; PLANT; DNA AB We have identified a gene encoding the 60 kDa heat shock protein (hsp60) from a Plasmodium falciparum blood stage cDNA library. The deduced protein sequence encodes for a polypeptide of 577 amino acids with a calculated molecular weight of 62158 Da. The primary structure of P. falciparum hsp60 contains a putative mitochondrial targeting peptide at its amino-terminus and a GGM motif at its carboxyl-terminus. The overall structure exhibits strong conservation (similar to 50%) to the hsp60 from human and other eukaryotes, but only low homology (<30%) to a recently reported P. falciparum chaperonin 60 gene. The P. falciparum hsp60 gene is located on chromosome 10. During heat shock, the level of hsp60 transcript in blood stage parasites increases significantly and its accumulation correlates with the duration of the induction. RP Syin, C (reprint author), US FDA,LAB PARASIT BIOL & BIOCHEM,DIV ALLERGEN PROD & PARASITOL,OFF VACCINE REVIEW & RES,ROCKVILLE,MD 20852, USA. NR 27 TC 26 Z9 26 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JUL PY 1996 VL 79 IS 1 BP 13 EP 19 DI 10.1016/0166-6851(96)02633-3 PG 7 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA VA645 UT WOS:A1996VA64500002 PM 8844668 ER PT J AU Eng, GD Binder, H Getson, P ODonnell, R AF Eng, GD Binder, H Getson, P ODonnell, R TI Obstetrical brachial plexus palsy (OBPP) outcome with conservative management SO MUSCLE & NERVE LA English DT Article DE brachial plexus palsy; newborn; nerve regeneration; electrodiagnosis rehabilitation ID BIRTH PALSY; ROOT AVULSION; TRAUMA AB Resurgence of neurosurgical intervention oi obstetrical brachial plexus palsy prompted our review of 186 patients evaluated between 1981 and 1993, correlating clinical examination, electrodiagnosis, and functional outcome with conservative management. Eighty-eight percent had upper brachial plexus palsies, and 63% were mild. Forty-two infants required no long-term follow-up because they rated 1 or 2 on initial physical examination, Comparing first and last follow-up clinical findings of the remaining 149 patients, there was high agreement (correlation r = 0.81; P <0.001). Pearson correlation of initial physical exam with electrodiagnosis at three intervals was relatively stable (r = 0.87, 0.88, 0.69). One hundred eight (72%) of the patients remained in their original severity groups. Thirty-three of 41 patients with discrepant follow-up scores improved by at least one category. Eight patients deteriorated. The natural pathophysiology and recovery of OBPP is presented. (C) 1996 John Wiley & Sons, Inc. C1 GEORGE WASHINGTON UNIV,CHILDRENS NATL MED CTR,DEPT PHYS MED & REHABIL,WASHINGTON,DC. MED CTR,WASHINGTON,DC. CTR BIOL EVALUAT & RES,DIV BIOSTAT & EPIDEMIOL,ROCKVILLE,MD. RP Eng, GD (reprint author), CHILDRENS NATL MED CTR,DIV BIOSTAT,RES INST,111 MICHIGAN AVE NW,WASHINGTON,DC 20010, USA. NR 29 TC 64 Z9 64 U1 0 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD JUL PY 1996 VL 19 IS 7 BP 884 EP 891 DI 10.1002/(SICI)1097-4598(199607)19:7<884::AID-MUS11>3.0.CO;2-J PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UQ394 UT WOS:A1996UQ39400012 PM 8965843 ER PT J AU Koch, WH Henrikson, EN Cebula, TA AF Koch, WH Henrikson, EN Cebula, TA TI Molecular analyses of Salmonella hisG428 ochre revertants for rapid characterization of mutational specificity SO MUTAGENESIS LA English DT Article ID OLIGODEOXYRIBONUCLEOTIDE COLONY HYBRIDIZATION; TESTER STRAIN TA102; ESCHERICHIA-COLI; BASE SUBSTITUTION; PLASMID PKM101; ALKYLATING-AGENTS; SEQUENCE-ANALYSIS; TYPHIMURIUM; DNA; MUTAGENESIS AB The Salmonella typhimurium tester strains TA104 and TA102 were developed primarily to aid in the detection of oxidative mutagens and other agents that react preferentially with AT base pairs. Reversion to prototrophy of strains harboring the hisG428 ochre allele can occur by (i) any of seven single base substitutions or (ii) several tandem double base substitutions at the ochre codon, (iii) in-frame deletions removing all or part of the ochre codon or (iv) mutations at several distinct tRNA extragenic suppressor loci. We have used allele-specific oligonucleotide probes and DNA sequence analysis to characterize 625 revertants of strain TA104 (hisG428, rfa, Delta uvrB/pKM101) arising spontaneously or after treatment with methyl methanesulfonate, glyoxal, streptonigrin or angelicin with UVA radiation, The reversion profiles obtained from these analyses distinguished readily each of the mutagen-treated populations from one another and from spontaneously derived revertants, Both GC and AT base pair-specific revertants were observed. Molecular analyses of S.typhimurium hisG428 revertants permitted rapid assessment of base pair substitution specificity of mutagens, especially the detection of AT base pair substitutions not recovered in strains carrying the complementary hisG46 allele. RP Koch, WH (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,MOL BIOL BRANCH,200 C ST SW HFS-237,WASHINGTON,DC 20204, USA. NR 58 TC 24 Z9 24 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD JUL PY 1996 VL 11 IS 4 BP 341 EP 348 DI 10.1093/mutage/11.4.341 PG 8 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA UX266 UT WOS:A1996UX26600005 PM 8671758 ER PT J AU Satchithanandam, S Klurfeld, DM Calvert, RJ Cassidy, MM AF Satchithanandam, S Klurfeld, DM Calvert, RJ Cassidy, MM TI Effects of dietary fibers on gastrointestinal mucin in rats SO NUTRITION RESEARCH LA English DT Article DE dietary fiber; ELISA; glycoprotein; mucin; rat ID WHEAT BRAN; RICE BRAN; CHOLESTEROL; CELLULOSE; PSYLLIUM; ACID AB Gastrointestinal mucin is believed to contribute to the intestinal diffusion barrier for nutrients. This study quantitated the effects of feeding three dietary fibers on gastrointestinal mucin production. Male Wistar rats (150-175 g) were fed, ad libitum, a diet containing 10 or 20% cellulose, psyllium, or rice bran or a control diet containing no fiber. After 4 weeks, the stomachs, small intestines, and colons were removed, and surface luminal mucin and tissue mucin were collected. Specimens were homogenized, the homogenates were centrifuged, and the supernatants were assayed for mucin by an enzyme-linked immunosorbent assay (ELISA) technique. The results of the dietary fiber feeding showed that levels of luminal and total (luminal plus tissue) gastric mucin were significantly higher in rats fed 20% psyllium than in rats fed the control diet. There were no significant differences in the levels of small intestinal mucin among groups. Colonic luminal and total mucin levels, however, were significantly increased in rats fed 10% psyllium compared with those of rats fed the control diet. The increase in colonic mucin levels was later confirmed by periodic acid Schiff(PAS) staining. It was observed that large amounts of mucus may have been lost in the feces of rats fed a diet containing 20% psyllium, and smaller amounts in the feces of those fed 10% psyllium. Reduced absorption of cholesterol and fatty acid was found previously in psyllium-fed rats. Thus, increases in gastric and colonic mucin levels caused by psyllium treatment may protect these organs as well as alter nutrient absorption. C1 WAYNE STATE UNIV,DEPT NUTR & FOOD SCI,DETROIT,MI 48202. GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,DEPT PHYSIOL,WASHINGTON,DC 20052. RP Satchithanandam, S (reprint author), US FDA,DIV SCI & APPL TECHNOL,OFF SPECIAL NUTR,MOD-1,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 27 TC 39 Z9 39 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD JUL PY 1996 VL 16 IS 7 BP 1163 EP 1177 DI 10.1016/0271-5317(96)00121-2 PG 15 WC Nutrition & Dietetics SC Nutrition & Dietetics GA UT760 UT WOS:A1996UT76000009 ER PT J AU Cote, CJ Kauffman, RE Troendle, GJ Lambert, GH AF Cote, CJ Kauffman, RE Troendle, GJ Lambert, GH TI Is the ''therapeutic orphan'' about to be adopted? SO PEDIATRICS LA English DT Editorial Material ID BUPIVACAINE TOXICITY SECONDARY; CAUDAL EPIDURAL INFUSION; CHILDREN; FENTANYL; ANESTHESIA; PHARMACOKINETICS; MIDAZOLAM; INFANTS; AGE C1 CHILDRENS MERCY HOSP,DEPT PEDIAT,KANSAS CITY,MO 64108. CHILDRENS MERCY HOSP,DEPT PHARMACOL,KANSAS CITY,MO 64108. US FDA,DIV METAB & ENDOCRINE DRUG PROD,ROCKVILLE,MD 20857. UNIV MED & DENT NEW JERSEY,CLIN RES CTR,DEPT PEDIAT,PISCATAWAY,NJ 08855. RP Cote, CJ (reprint author), NORTHWESTERN UNIV,CHILDRENS MEM HOSP,SCH MED,DEPT ANESTHESIA,2300 CHILDRENS PLAZA,CHICAGO,IL 60614, USA. NR 30 TC 55 Z9 56 U1 1 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 1996 VL 98 IS 1 BP 118 EP 123 PG 6 WC Pediatrics SC Pediatrics GA UU137 UT WOS:A1996UU13700023 PM 8668382 ER PT J AU Berlin, CM May, DG Notterman, DA Ward, RM Weismann, DN Wilson, GS Wilson, JT Bennett, DR Hoskins, IA Mulinare, J Kaufman, P Rieder, MJ Troendle, G Yaffe, SJ Cote, CJ Szefler, SJ AF Berlin, CM May, DG Notterman, DA Ward, RM Weismann, DN Wilson, GS Wilson, JT Bennett, DR Hoskins, IA Mulinare, J Kaufman, P Rieder, MJ Troendle, G Yaffe, SJ Cote, CJ Szefler, SJ TI Unapproved uses of approved drugs: The physician, the package insert, and the food and drug administration: Subject review SO PEDIATRICS LA English DT Article C1 AMER MED ASSOC,CHICAGO,IL 60610. US PHARMACOPEIA CONVENT,ROCKVILLE,MD 20852. AMER COLL OBSTETRICIANS & GYNECOLOGISTS,WASHINGTON,DC 20024. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. PHARMACEUT RES & MANUFACTURERS ASSOC AMER,WASHINGTON,DC. CANADIAN PAEDIAT SOC,OTTAWA,ON,CANADA. US FDA,WASHINGTON,DC 20204. NIH,BETHESDA,MD 20892. AMER ACAD PEDIAT,SECT ANESTHESIOL,ELK GROVE VILLAGE,IL 60009. AMER ACAD PEDIAT,SECT ALLERGY & IMMUNOL,ELK GROVE VILLAGE,IL 60009. AMER ACAD PEDIAT,COMM DRUGS,ELK GROVE VILLAGE,IL 60009. NR 0 TC 52 Z9 52 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 1996 VL 98 IS 1 BP 143 EP 145 PG 3 WC Pediatrics SC Pediatrics GA UU137 UT WOS:A1996UU13700031 ER PT J AU Halsey, NA Chesney, PJ Gerber, MA Gromisch, DS Kohl, S Marcy, SM Marks, MI Murray, DL Overall, JC Pickering, LK Whitley, RJ Yogev, R Peter, G Berkelman, RL Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Hadler, S Orenstein, WA Rabinovich, NR AF Halsey, NA Chesney, PJ Gerber, MA Gromisch, DS Kohl, S Marcy, SM Marks, MI Murray, DL Overall, JC Pickering, LK Whitley, RJ Yogev, R Peter, G Berkelman, RL Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Hadler, S Orenstein, WA Rabinovich, NR TI Recommended Childhood Immunization Schedule SO PEDIATRICS LA English DT Article C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. US FDA,WASHINGTON,DC 20204. NATL VACCINE PROGRAM OFF,ROCKVILLE,MD. AMER THORAC SOC,NEW YORK,NY. CANADIAN PAEDIAT SOC,OTTAWA,ON,CANADA. NIH,BETHESDA,MD 20892. RP Halsey, NA (reprint author), AMER ACAD PEDIAT,COMM INFECT DIS,POB 927,ELK GROVE VILLAGE,IL 60009, USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 1996 VL 98 IS 1 BP 158 EP 160 PG 3 WC Pediatrics SC Pediatrics GA UU137 UT WOS:A1996UU13700035 ER PT J AU Pentikis, HS Henderson, JD Tran, NL Ludden, TM AF Pentikis, HS Henderson, JD Tran, NL Ludden, TM TI Bioequivalence: Individual and population compartmental modeling compared to the noncompartmental approach SO PHARMACEUTICAL RESEARCH LA English DT Article DE modeling; NONMEM; bioequivalence; noncompartmental; population; compartmental ID BIOAVAILABILITY AB Purpose. The purposes of this study were to evaluate the use of individual compartmental and population compartmental methods for bioequivalence determination, and to determine their utility as adjuncts to the current methods used for bioequivalence assessment. Methods. Data from three bioequivalence studies of chlorthalidone were analyzed with PCNONLIN using individual compartmental modeling and NONMEM for population analyses. These results were compared with results obtained from the traditional noncompartmental or SHAM (slopes, heights, areas, and moments) approach for bioequivalence assessment and the 90% confidence interval procedure. Results. Individual compartmental modeling and population compartmental modeling techniques performed well on this routine set of bioequivalence data which displayed simple pharmacokinetic properties. A direct assessment of the analysis methods was made by comparing the final estimates and 90% confidence intervals for the test to reference ratios (T/R) of AUC and CMAX. The final estimates and 90% confidence intervals for AUC T/R and CMAX T/R were similar and suggest consistency of results, independent of the method used. Conclusions. These results demonstrate the utility of modeling techniques as adjuncts to the traditional noncompartmental approach for bioequivalence determination. C1 US FDA,CTR DRUG EVALUAT & RES,DIV BIOPHARMACEUT,ROCKVILLE,MD 20857. US FDA,CTR DRUG EVALUAT & RES,OFF GENER DRUGS,ROCKVILLE,MD 20857. NR 14 TC 22 Z9 22 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD JUL PY 1996 VL 13 IS 7 BP 1116 EP 1121 DI 10.1023/A:1016083429903 PG 6 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA UZ233 UT WOS:A1996UZ23300024 PM 8842055 ER PT J AU Kenyon, AS Layloff, TP AF Kenyon, AS Layloff, TP TI Weighing on an analytical balance SO PHARMACOPEIAL FORUM LA English DT Article RP Kenyon, AS (reprint author), US FDA,DIV DRUG ANAL,1114 MARKET ST,ROOM 1002,ST LOUIS,MO 63101, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU US PHARMACOPEIAL CONVENTION PI ROCKVILLE PA 12601 TWINBROOK PKWY, ROCKVILLE, MD 20852 SN 0363-4655 J9 PHARMACOPEIAL FORUM JI Pharmacop. Forum PD JUL-AUG PY 1996 VL 22 IS 4 BP 2686 EP 2689 PG 4 WC Medicine, Legal; Pharmacology & Pharmacy SC Legal Medicine; Pharmacology & Pharmacy GA UY566 UT WOS:A1996UY56600004 ER PT J AU Hansen, DK Dial, SL Terry, KK Grafton, TF AF Hansen, DK Dial, SL Terry, KK Grafton, TF TI In vitro embryotoxicity of carbamazepine and carbamazepine-10,11-epoxide SO TERATOLOGY LA English DT Article ID ANTIEPILEPTIC DRUGS; PROSTAGLANDIN SYNTHETASE; PHENYTOIN TERATOGENICITY; ANTICONVULSANT DRUGS; ACETYLSALICYLIC-ACID; EMBRYO CULTURE; SPINA-BIFIDA; RAT EMBRYOS; PREGNANCY; BIOACTIVATION AB Carbamazepine (Tegretol(R), CBZ) is an anticonvulsant drug that is very effective in the treatment of tonic-clonic seizures and is gaining acceptance as a treatment for various psychiatric disorders. The drug is embryotoxic in rodents and has been reported to produce neural tube defects in approximately 1% of prenatally exposed human offspring. It is metabolized by the cytochrome P-450 system to a stable, pharmacologically active epoxide intermediate, carbamazepine-10,11-epoxide. It is currently unknown whether the parent compound, the epoxide intermediate or some other metabolite is the embryotoxic agent. The present study was designed to determine the embryotoxicity of CBZ and its epoxide intermediate (CBZ-E) in a rodent whole embryo culture system. Rat embryos were cultured beginning on day 9 of gestation (GD 9), and mouse embryos were cultured beginning on GD 8. All embryos were cultured for 48 hr in medium containing various concentrations of either CBZ or CBZ-E. Mice were more sensitive to the effects of CBZ than were rats. The parent compound was embryotoxic to mouse embryos at concentrations as low as 12 mu g/ml, but it was only embryotoxic at 60 mu g/ml to rat embryos. CBZ-E was not embryotoxic to either species at concentrations as high as 48 mu g/ml. These results suggest that the parent compound is the embryotoxic agent and that the epoxide intermediate plays no role in the drug's embryotoxic mechanism. RP Hansen, DK (reprint author), US FDA,NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,DEPT HLTH & HUMAN SERV,3900 NCTR RD,HFT 130,JEFFERSON,AR 72079, USA. NR 42 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0040-3709 J9 TERATOLOGY JI Teratology PD JUL PY 1996 VL 54 IS 1 BP 45 EP 51 PG 7 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA VQ592 UT WOS:A1996VQ59200006 PM 8916369 ER PT J AU Donoghue, AM Garner, DL Donoghue, DJ Johnson, LA AF Donoghue, AM Garner, DL Donoghue, DJ Johnson, LA TI Assessment of the membrane integrity of fresh and stored turkey spermatozoa using a combination of hypo-osmotic stress fluorescent staining and flow cytometry SO THERIOGENOLOGY LA English DT Article DE flow cytometry; membrane integrity; osmolarity; poultry; spermatozoa ID HYPOOSMOTIC SWELLING TEST; HUMAN-SPERM MEMBRANE; FUNCTIONAL INTEGRITY; BOVINE SPERMATOZOA; WATER-TEST; VIABILITY; FERTILITY; FROZEN; FOWL; POULTRY AB A study was conducted to evaluate the integrity of turkey sperm plasma membrane subjected to various hypo-osmotic conditions, and to develop a test to determine the percentage of viable spermatozoa capable of withstanding hypo-osmotic stress after in vitro storage. Semen from 10 toms was collected and pooled twice weekly for 6 wk, and each trial was repeated 6 times. For Trial I, spermatozoa were subjected to varying osmotic solutions by suspension in 100, 80, 60, 40, 20 or 0% PBS in distilled water (297 to 19 mosm/kg H2O) and stained to assess membrane integrity with Calcein-AM (GAL) and propidium iodide (PI). The CAL detected viable spermatozoa (green fluorescence) while the PI shined dead cells (red fluorescence). Spermatozoa were evaluated microscopically and by flow cytometry. The percentage of viable spermatozoa, as determined by flow cytometry, was not different from that in 100% PBS (76.4+/-3.8) to 20% PBS (74.1+/-3.5). Fewer viable spermatozoa, however, were detected in 0% PBS (61.1+/-4.8, P < 0.05). The percentages of swollen tails observed for viable (green stained) spermatozoa were 0, 4.5, 6.5, 24.3, 50.5 and 100% for 100, 80, 60, 40, 20 and 0% PBS, respectively. Semen was also evaluated fresh or after 24 h in vitro storage at 5 degrees C in PBS or H2O (Trial II). The percentage of viable spermatozoa was not different for fresh or in vitro-stored spermatozoa in PBS. For spermatozoa stored 24 h in vitro, the percentage of viable cells was lower in H2O (48.0+/-5.1) than in PBS (66.1+/-5.6, P<0.05). Subjecting in vitro-stored sperm cells to hypo-osmotic stress before fluorescent staining resulted in detection of labile spermatozoa not accounted for by staining alone, indicating that the turkey sperm membrane is more susceptible to damage after cold storage. C1 UNIV NEVADA,SCH VET MED,RENO,NV 89557. US FDA,BIOCHEM PHARMACOL BRANCH,BELTSVILLE,MD 20705. RP Donoghue, AM (reprint author), USDA,ARS,GERMPLASM & GAMETE PHYSIOL LAB,BELTSVILLE,MD 20705, USA. NR 29 TC 28 Z9 29 U1 0 U2 3 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0093-691X J9 THERIOGENOLOGY JI Theriogenology PD JUL PY 1996 VL 46 IS 1 BP 153 EP 163 DI 10.1016/0093-691X(96)00150-1 PG 11 WC Reproductive Biology; Veterinary Sciences SC Reproductive Biology; Veterinary Sciences GA UW613 UT WOS:A1996UW61300015 ER PT J AU Freedman Simon Pocock DerSimonian Brown DeMets Louis Chalmers Collins Clemens George Feinstein Ellenberg Olkin AF Freedman Simon Pocock DerSimonian Brown DeMets Louis Chalmers Collins Clemens George Feinstein Ellenberg Olkin TI Meta-analysis in the design and monitoring of clinical trials - Discussion SO STATISTICS IN MEDICINE LA English DT Editorial Material ID ADJUVANT THERAPY; FLUOROURACIL; LEVAMISOLE; CARCINOMA C1 LONDON SCH HYG & TROP MED,LONDON WC1,ENGLAND. NICHHD,BETHESDA,MD. STANFORD UNIV,SCH MED,STANFORD,CA 94305. UNIV WISCONSIN,MADISON,WI 53706. UNIV MINNESOTA,SCH PUBL HLTH,MINNEAPOLIS,MN 55455. METAWORKS INC,LUDINGTON,MI 49431. RADCLIFFE INFIRM,OXFORD,ENGLAND. DUKE UNIV,MED CTR,DURHAM,NC 27706. YALE UNIV,SCH MED,NEW HAVEN,CT. US FDA,ROCKVILLE,MD. RP Freedman (reprint author), NCI,BETHESDA,MD 20892, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 30 PY 1996 VL 15 IS 12 BP 1249 EP 1252 PG 4 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 UU766 UT WOS:A1996UU76600003 ER PT J AU Meier Olkin Begg George Ellenberg Collins Freedman Pocock Chalmers AF Meier Olkin Begg George Ellenberg Collins Freedman Pocock Chalmers TI Meta-analysis: Current issues in research synthesis - Discussion SO STATISTICS IN MEDICINE LA English DT Editorial Material ID CORONARY THROMBOLYSIS C1 STANFORD UNIV,STANFORD,CA 94305. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. DUKE UNIV,MED CTR,DURHAM,NC. US FDA,ROCKVILLE,MD 20857. RADCLIFFE INFIRM,OXFORD OX2 6HE,ENGLAND. NCI,BETHESDA,MD 20892. LONDON SCH HYG & TROP MED,LONDON WC1,ENGLAND. METAWORKS INC,LUDINGTON,MI 49431. RP Meier (reprint author), COLUMBIA UNIV,NEW YORK,NY 10027, USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 30 PY 1996 VL 15 IS 12 BP 1259 EP 1262 PG 4 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 UU766 UT WOS:A1996UU76600005 ER PT J AU DeMets Temple Chalmers Begg Collins Olkin Freedman Ellenberg Geller Berendes Feinstein George Meier AF DeMets Temple Chalmers Begg Collins Olkin Freedman Ellenberg Geller Berendes Feinstein George Meier TI Changes in clinical trials mandated by the advent of meta-analysis - Discussion SO STATISTICS IN MEDICINE LA English DT Editorial Material C1 US FDA,ROCKVILLE,MD. METAWORKS INC,LUDINGTON,MI 49431. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. NICHHD,BETHESDA,MD. STANFORD UNIV,STANFORD,CA 94305. NCI,BETHESDA,MD 20892. NHLBI,BETHESDA,MD 20892. YALE UNIV,SCH MED,NEW HAVEN,CT. DUKE UNIV,MED CTR,DURHAM,NC. COLUMBIA UNIV,NEW YORK,NY. RP DeMets (reprint author), UNIV WISCONSIN,MADISON,WI 53706, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 30 PY 1996 VL 15 IS 12 BP 1269 EP 1272 DI 10.1002/(SICI)1097-0258(19960630)15:12<1269::AID-SIM306>3.0.CO;2-# PG 4 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 UU766 UT WOS:A1996UU76600007 ER PT J AU Ellenberg Pocock Lee Olkin Collins Meier Louis George Simon AF Ellenberg Pocock Lee Olkin Collins Meier Louis George Simon TI The role of external evidence in data monitoring of a clinical trial - Discussion SO STATISTICS IN MEDICINE LA English DT Editorial Material C1 LONDON SCH HYG & TROP MED,LONDON,ENGLAND. NICHHD,BETHESDA,MD. STANFORD UNIV,STANFORD,CA 94305. RADCLIFFE INFIRM,OXFORD OX2 6HE,ENGLAND. COLUMBIA UNIV,NEW YORK,NY. UNIV MINNESOTA,SCH PUBL HLTH,MINNEAPOLIS,MN. DUKE UNIV,MED CTR,DURHAM,NC. NCI,BETHESDA,MD 20892. RP Ellenberg (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 30 PY 1996 VL 15 IS 12 BP 1295 EP 1297 PG 3 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA UU766 UT WOS:A1996UU76600011 ER PT J AU Friedman Begg Feinstein Chalmers Meier Freedman Pocock Ellenberg Brown Louis Collins Olkin DerSimonian AF Friedman Begg Feinstein Chalmers Meier Freedman Pocock Ellenberg Brown Louis Collins Olkin DerSimonian TI The role of meta-analysis in monitoring clinical trials - Discussion SO STATISTICS IN MEDICINE LA English DT Editorial Material C1 METAWORKS INC,LUDINGTON,MI 49431. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. RADCLIFFE INFIRM,OXFORD,ENGLAND. US FDA,ROCKVILLE,MD 20857. YALE UNIV,SCH MED,NEW HAVEN,CT. COLUMBIA UNIV,NEW YORK,NY. LONDON SCH HYG & TROP MED,LONDON,ENGLAND. STANFORD UNIV,SCH MED,STANFORD,CA. UNIV MINNESOTA,SCH PUBL HLTH,MINNEAPOLIS,MN. NICHHD,BETHESDA,MD. RP Friedman (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 30 PY 1996 VL 15 IS 12 BP 1307 EP 1311 DI 10.1002/(SICI)1097-0258(19960630)15:12<1307::AID-SIM312>3.0.CO;2-J PG 5 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 UU766 UT WOS:A1996UU76600013 ER PT J AU Brown Friedman Temple Collins Simon Feinstein Chalmers Begg Pocock Freedman Meier George DeMets Ellenberg Clemens Berendes AF Brown Friedman Temple Collins Simon Feinstein Chalmers Begg Pocock Freedman Meier George DeMets Ellenberg Clemens Berendes TI Role of meta-analyses in design and monitoring of randomized clinical trials: Summary of first day of the workshop - Concluding discussion SO STATISTICS IN MEDICINE LA English DT Editorial Material C1 NCI,BETHESDA,MD 20892. NHLBI,BETHESDA,MD 20892. US FDA,ROCKVILLE,MD 20857. RADCLIFFE INFIRM,OXFORD OX2 6HE,ENGLAND. YALE UNIV,SCH MED,NEW HAVEN,CT. METAWORKS INC,LUDINGTON,MI 49431. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. LONDON SCH HYG & TROP MED,LONDON,ENGLAND. COLUMBIA UNIV,NEW YORK,NY. DUKE UNIV,MED CTR,DURHAM,NC. UNIV WISCONSIN,MADISON,WI 53706. NICHHD,BETHESDA,MD. RP Brown (reprint author), STANFORD UNIV,SCH MED,STANFORD,CA 94305, USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 30 PY 1996 VL 15 IS 12 BP 1317 EP 1323 DI 10.1002/(SICI)1097-0258(19960630)15:12<1317::AID-SIM314>3.0.CO;2-C PG 7 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA UU766 UT WOS:A1996UU76600015 ER PT J AU Kodell, RL Basu, AP Gaylor, DW AF Kodell, RL Basu, AP Gaylor, DW TI On interspecies correlations of carcinogenic potencies SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article AB It has been established in the literature that constraints on the designs of experiments used to estimate carcinogenic potencies cause overestimation of true biological inter-species correlations of such potencies. This article explores the potential for appreciable underestimation of interspecies correlations, due to the experimental error that occurs in the estimation of carcinogenic potencies. C1 UNIV MISSOURI,DEPT STAT,COLUMBIA,MO 65211. RP Kodell, RL (reprint author), NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,BIOMETRY BRANCH,3900 NCTR RD,HFT-20,JEFFERSON,AR 72079, USA. NR 12 TC 1 Z9 1 U1 1 U2 1 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD JUN 28 PY 1996 VL 48 IS 3 BP 231 EP 237 DI 10.1080/009841096161302 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA UR866 UT WOS:A1996UR86600002 PM 8656447 ER PT J AU Dale, EC Yang, XL Moore, SK Shyamala, G AF Dale, EC Yang, XL Moore, SK Shyamala, G TI Cloning and characterization of the promoter for murine 84-kDa heat-shock protein SO GENE LA English DT Article DE HSP-90; HSE; stress regulatory elements; transcription factors ID DEVELOPMENTAL REGULATION; GENE; EXPRESSION; SEQUENCE; ELEMENT; FAMILY; HSP82; CELLS AB The 90-kDa heat-shock (HS) proteins (HSP90) are members of the HSP family. Their synthesis is inducible by HS and a variety of stress signals. HSP90 is also abundant under normal physiological conditions and its synthesis can be regulated during growth and differentiation. Therefore, HSP90 is speculated to have important biological functions, in addition to its role in mediating stress responses. However, the mechanism(s) regulating hsp90 gene expression in nonstressed cells is poorly understood. As a prerequisite towards understanding the basis for hsp90 regulation, we have cloned and characterized the 5' flanking region of murine hsp84, one of two genes which code for HSP90 proteins. Full basal promoter activity of hsp84 was found to be associated with a 627-bp region immediately upstream from the transcription start point (tsp). Sequence analysis revealed several putative regulatory elements, including a HS element (HSE), an AP1-binding site (AP1), a cyclic AMP response element (CRE), and four stimulatory protein-1-binding sites (SP1). HS inducibility required the HSE which was bound by HS transcription factor-1 (HSF-l) present in extracts prepared from cells exposed to HS. The HSE was not required for basal (non-HS) expression, but, interestingly, two protein-HSE complexes, devoid of HSF-1 and HSF-2, were formed under these conditions. The potential significance of these findings to the expression of hsp84 under normal physiological conditions is discussed. C1 UNIV CALIF BERKELEY,LAWRENCE BERKELEY NATL LAB,DIV LIFE SCI,BERKELEY,CA 94720. US FDA,DIV METAB & ENDOCRINE DRUG PROD,ROCKVILLE,MD 20857. FU NCI NIH HHS [CA54828] NR 28 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUN 26 PY 1996 VL 172 IS 2 BP 279 EP 284 DI 10.1016/0378-1119(96)00191-6 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA UU734 UT WOS:A1996UU73400018 PM 8682317 ER PT J AU Ault, KT Dirksen, ML Jamrich, M AF Ault, KT Dirksen, ML Jamrich, M TI Novel homeobox gene PV.1 mediates induction of ventral mesoderm in Xenopus embryos SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE bone morphogenetic protein 4; mesodermal induction ID BONE MORPHOGENETIC PROTEIN-4; PEPTIDE GROWTH-FACTORS; LAEVIS EMBRYOS; BOX GENE; ORGANIZER; EXPRESSION; PATTERN; HOMOLOG AB The formation of ventral mesoderm has been traditionally viewed as a result of a lack of dorsal signaling and therefore assumed to be a default state of mesodermal development. The discovery that bone morphogenetic protein 4 (BMP4) can induce ventral mesoderm led to the suggestion that the induction of the ventral mesoderm requires a different signaling pathway than the induction of the dorsal mesoderm, However, the individual components of this pathway remained largely unknown. Here we report the identification of a novel Xenopus homeobox gene PV.1 (posterior-ventral 1) that is capable of mediating induction of ventral mesoderm. This gene is activated in blastula stage Xenopus embryos, its expression peaks during gastrulation and declines rapidly after neurulation is complete. PV:1 is expressed in the ventral marginal zone of blastulae and later in the posterior ventral area of gastrulae and neurulae, PV.1 is inducible in uncommited ectoderm by the ventralizing growth factor BMP4 and counteracts the dorsalizing effects of the dominant negative BMP4 receptor. Overexpression of PV.1 yields ventralized tadpoles and rescues embryos partially dorsalized by LiCl treatment, In animal caps, PV.1 ventralizes induction by activin and inhibits expression of dorsal specific genes, All of these effects mimic those previously reported for BMP4. These observations suggest that PV.1 is a critical component in the formation of ventral mesoderm and possibly mediates the effects of BMP4. RP Ault, KT (reprint author), US FDA,DIV CELLULAR & GENE THERAPEUT,DEV BIOL LAB,HFM-527,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 50 TC 63 Z9 64 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 25 PY 1996 VL 93 IS 13 BP 6415 EP 6420 DI 10.1073/pnas.93.13.6415 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UU367 UT WOS:A1996UU36700037 PM 8692829 ER PT J AU Desai, D Michalak, M Singh, NK Niles, RM AF Desai, D Michalak, M Singh, NK Niles, RM TI Inhibition of retinoic acid receptor function and retinoic acid-regulated gene expression in mouse melanoma cells by calreticulin - A potential pathway for cyclic AMP regulation of retinoid action SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CALCIUM-BINDING PROTEIN; THYROID-HORMONE; NUCLEAR RECEPTOR; ENDOPLASMIC-RETICULUM; RESPONSE ELEMENT; NONMUSCLE CELLS; CLONING; GAMMA; BETA; DIFFERENTIATION AB Calcium is a second messenger that controls a wide variety of cellular functions. Because of its multiple actions, there is a stringent requirement for calcium ho meostasis, and this is achieved in part by a system of transport and storage proteins such as calreticulin located in the endoplasmic reticulum, Calreticulin is also found in the nucleus, suggesting that it may have a role in transcriptional regulation. It has been reported that calreticulin can inhibit steroid-regulated gene transcription by preventing receptor binding to DNA, Here we report that overexpression of the calreticulin gene in B16 mouse melanoma cells resulted in a decrease in retinoic acid (RA)-stimulated reporter gene expression, Gel shift analysis showed that purified calreticulin inhibited the binding of endogenous RAR 60 a beta-RA response element oligonucleotide, only if added prior to the addition of the oligonucleotide. Co-immunoprecipitation studies suggest a physical interaction between RAR and calreticulin. Transfection of the calreticulin gene into B16 cells inhibited the RA induction of protein kinase C alpha, a marker of RA induced differentiation. We also found that cyclic AMP increased the expression of calreticulin, Cyclic AMP may act to antagonize RA action by both decreasing RAR expression (Y, Xiao, D, Desai, T, Quick, and R, M, Niles, J, Cell Physiol., in press) and stimulating calreticulin levels, C1 MARSHALL UNIV,SCH MED,DEPT BIOCHEM & MOLEC BIOL,HUNTINGTON,WV 25755. UNIV ALBERTA,DEPT BIOCHEM,MED RES COUNCIL GRP MOLEC BIOL MEMBRANES,EDMONTON,AB T6G 2S2,CANADA. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. FU NCI NIH HHS [CA 59530] NR 34 TC 33 Z9 34 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 21 PY 1996 VL 271 IS 25 BP 15153 EP 15159 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UT106 UT WOS:A1996UT10600075 PM 8662962 ER PT J AU Kuznetsov, VA AF Kuznetsov, VA TI ''Harpoon'' model for cell-cell adhesion and recognition of target cells by the natural killer cells SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Review ID MEDIATED CYTO-TOXICITY; COMPLEX CLASS-I; NK-CELLS; MEMBRANE FLUIDITY; PLASMA-MEMBRANE; LYMPHOCYTES-T; SIALIC-ACID; LETHAL HIT; EXPRESSION; LYSIS AB The mechanism of recognition by natural killer (NK) cells is still unknown. A dynamic model is formulated describing recognition of NK-sensitive target cells (TCs) by NK cells or NK-like cells. This model does not assume the presence of the specific NK-receptor(s) on the membrane of NK cells and corresponding specific ligands on the NK-sensitive TCs. We suggest: (1) the expression of various kinds of ''non-NK receptors'' and corresponding ligands (counter-receptors) on the plasma membrane of the same NK cell and, possibly, of TCs (e.g. LFA-I and ICAM-1-ICAM3, CD2 and LFA-3; receptors for TNF and corresponding ligand etc.); (2) the presence of multiple disorders in the organization of ''extracellular matrix-surface membrane-submembrane cytoskeleton'' assembly of the NK-sensitive TCs; (3) non-specific primary linking of NK cell with TCs, which induces a transfer of vesicles or membrane fragments from the NK surface to the target cell surface (and perhaps vice versa). These processes may also permit the transfer of many types of receptor and counter-receptor molecules from the surface of one conjugated cell to another by vesicles or membrane fragments. After transferral through the intercellular cleft, the free receptors and counter-receptors will be localized on both cell surfaces at the contact region between conjugated cells. By this model the NK cell can ''harpoon'' the TC and enhance the binding forces between cells up to the critical level and then switch on killing mechanisms for the TC. By means of this ''harpoon'' model of cell recognition, it seems possible to explain the nature of the wide polymorphism of TCs which are sensitive to the effect of NK and NK-like cells. A mathematical model of the NK cell cytotoxic reaction is described. The model describes many nonlinear peculiarities of the cytotoxic process and predicts some new phenomena. We suggest new approaches of manipulation of cell membranes which can transform NK-resistant target cells in NK sensitive cells and vice versa. (C) 1996 Academic Press Limited. RP Kuznetsov, VA (reprint author), US FDA,CTR BIOL EVALUAT & RES,LAB MOLEC TUMOR BIOL,BETHESDA,MD 20895, USA. NR 101 TC 9 Z9 9 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD JUN 21 PY 1996 VL 180 IS 4 BP 321 EP 342 DI 10.1006/jtbi.1996.0106 PG 22 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA UY868 UT WOS:A1996UY86800005 PM 8776465 ER PT J AU Tejeda, HA Green, SB Trimble, EL Ford, L High, JL Ungerleider, RS Friedman, MA Brawley, OW AF Tejeda, HA Green, SB Trimble, EL Ford, L High, JL Ungerleider, RS Friedman, MA Brawley, OW TI Representation of African-Americans, Hispanics, and whites in National Cancer Institute cancer treatment trials SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CLINICAL-TRIALS; PATIENT AB Background: The National Cancer Institute (NCI)-sponsored clinical trials cooperative groups place more than 25 000 American patients in treatment trials every year. Equal access and proportional representation of all races/ethnicities is desired. Purpose: Our objectives were to evaluate the inclusion of African-Americans, Hispanics, and non-Hispanic whites in NCI-sponsored treatment trials and to determine if there is proportional racial/ethnic representation. Methods: During the period of January 1, 1991, through June 30, 1994, 99 495 cancer patients were enrolled in clinical trials and declared themselves as non-Hispanic black, non-Hispanic white, or Hispanic (of any race). In the analysis, participants in NCI treatment trials were subdivided into three age groups: birth to 19 years, 20-49 years, and 50 or more years. The racial/ethnic composition of each of these age groups was compared with the racial/ethnic makeup of the American population with cancer. Estimates of the number of incident cancer cases per year were made for each racial/ethnic group within each age group using data from the Surveillance, Epidemiology, and End Results (SEER) Program and the 1990 Census. The percentage of all cancer patients who were in each racial/ethnic group were compared with the population that entered clinical trials. Comparisons are also made separately for patients with leukemia and breast, colorectal, lung, and prostate cancers. Results: Among patients 0-19 years old, 20-49 years old, and 50 years old or older there is relatively proportional representation of non-Hispanic blacks, Hispanics, and non-Hispanic whites in trials. It is noted that more than 70% of cancer patients aged 0-19 years are estimated to enter cooperative group clinical trials compared with 4.0% of cancer patients aged 20-49 years and 1.5% of patients aged 50 years or older. Conclusions: Accrual of American cancer patients to NCI-sponsored treatment trials generally parallels the incident burden of disease among non-Hispanic African-Americans, Hispanics, and non-Hispanic whites. Implications: This study shows that the NCI clinical trials are, as a whole, racially/ethnically representative of the American population and suggests that there is equal access to NCI clinical trials. C1 US FDA,ROCKVILLE,MD 20857. NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT & COMMUNITY ONCOL PROGRAM,BETHESDA,MD 20892. NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT DIAG & CTR,CANC TREATMENT EVALUAT PROGRAM,BETHESDA,MD 20892. NR 18 TC 147 Z9 147 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 19 PY 1996 VL 88 IS 12 BP 812 EP 816 DI 10.1093/jnci/88.12.812 PG 5 WC Oncology SC Oncology GA UR094 UT WOS:A1996UR09400011 PM 8637047 ER PT J AU Neenan, JP Opitz, SM Cooke, CL Ussery, MA Morrill, TC Eckel, LM AF Neenan, JP Opitz, SM Cooke, CL Ussery, MA Morrill, TC Eckel, LM TI Adenosine dialdehyde analogs .1. Regioselective synthesis of adenosine monoaldehydes SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID S-ADENOSYLHOMOCYSTEINE HYDROLASE AB Selective borohydride reduction of adenosine dialdehyde (1) gave the known adenosine 2'-monoaldehyde (2). Reaction of 1 with N,N'-diphenylethylenediamine, followed by reduction and deblocking gave adenosine 3'-monoaldehyde (5), a new compound. Unlike 2, compound 5 inhibited S-AdoHcy hydrolase and showed antiviral activity in vitro. Copyright (C) 1996 Elsevier Science Ltd C1 US FDA,PUBL HLTH SERV,DEPT HLTH & HUMAN SERV,ROCKVILLE,MD 20857. RP Neenan, JP (reprint author), ROCHESTER INST TECHNOL,DEPT CHEM,ROCHESTER,NY 14623, USA. NR 20 TC 2 Z9 2 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JUN 18 PY 1996 VL 6 IS 12 BP 1381 EP 1386 DI 10.1016/0960-894X(96)00234-X PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA UU381 UT WOS:A1996UU38100019 ER PT J AU Herman, EH Zhang, J Chadwick, DP Ferrans, VJ AF Herman, EH Zhang, J Chadwick, DP Ferrans, VJ TI Age dependence of the cardiac lesions induced by minoxidil in the rat SO TOXICOLOGY LA English DT Article DE minoxidil; aging; rat; myocardium; necrosis; inflammation; arteritis; hemorrhage ID HYPOTENSIVE AGENT; DRUG DISPOSITION; MINIATURE SWINE; DOGS; CARDIOTOXICITY; MYOCARDIUM; RESPONSIVENESS; PATHOGENESIS; HYPERTENSION; HEARTS AB To evaluate the age- and dose-dependence of the cardiotoxicity induced by minoxidil, histologic studies were made of the hearts of 3-, 6-, 15- and 24-month-old Sprague Dawley rats treated with either 10, 50 or 250 mg/kg of the drug p.o. daily for two consecutive days. The 10 mg/kg dose of minoxidil induced myocyte necrosis in each of the 24-month-old rats but only in one other animal (6-month-old). The 50 mg/kg dose produced necrosis in all the 15- and 24-month-old rats, but in only one of the other animals (6-month-old), while the 250 mg/kg dose induced necrosis in animals of all ages. Inflammation was present in all minoxidil-treated animals, but at each dose level it was most severe in the oldest rats. Interstitial hemorrhages were observed at all dose levels, but increased in frequency and severity with the dose of minoxidil, and at each dose level they were more severe in the oldest animals. Vascular lesions consisting of arteriolar damage and calcification were observed only in the 24-month-old animals. Thus, these data demonstrate that the cardiac lesions induced by minoxidil are more frequent and severe in older than in younger rats. C1 NHLBI,NIH,PATHOL SECT,BETHESDA,MD 20892. RP Herman, EH (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV RES & TESTING,HFD 472 MOD 1,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 37 TC 14 Z9 14 U1 0 U2 0 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 17 PY 1996 VL 110 IS 1-3 BP 71 EP 83 DI 10.1016/0300-483X(96)03337-9 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA UQ569 UT WOS:A1996UQ56900008 PM 8658561 ER PT J AU Whitehurst, VE Joseph, X Vick, JA Alleva, FR Zhang, J Balazs, T AF Whitehurst, VE Joseph, X Vick, JA Alleva, FR Zhang, J Balazs, T TI Reversal of acute theophylline toxicity by calcium channel blockers in dogs and rats SO TOXICOLOGY LA English DT Article DE theophylline; calcium ion; cardiovascular toxicity; verapamil; nifedipine; diltiazem ID NIFEDIPINE; PATIENT; ASTHMA; HEART AB Theophylline, widely used in the treatment of pulmonary diseases, has a narrow therapeutic index; the recommended plasma levels being 10-20 mu g/ml in humans. The misuse or abuse of theophylline can cause life-threatening central nervous system and cardiovascular effects. Increased intracellular Ca2+ levels are thought to play an important role in theophylline toxicity and death. The objective of this study was to determine whether Ca2+ channel blockers, e.g. verapamil, nifedipine, or diltiazem, prevent sudden death caused by theophylline treatment in rats and dogs. Groups of Sprague-Dawley rats were treated with theophylline alone (150 mg/kg i.p.) or with theophylline pretreatment followed by administration of verapamil (0.25 to 0.5 mg/kg i.p.), nifedipine (0.25 to 1.0 mg/kg i.p.), or diltiazem (0.5 to 1.0 mg/kg i.p.), 2.5 to 15 min later. The rats were observed for toxic signs and survival over a period of 15 days. All three calcium channel blockers significantly reduced the theophylline-induced sudden death in rats. In a separate study, neither verapamil (0.5 mg/kg i.p.) nor nifedipine (1.0 mg/kg i.p.) prevented the theophylline-induced myocardial necrosis in the rat. In beagle dogs, verapamil (0.5 mg/kg i.v.) prevented theophylline (15 mg/kg/min i.v. for 10 min)-induced hypotension, arrhythmias, and sudden death. Our results support previously reported findings that calcium plays a major role in theophylline-induced toxicity and death. C1 US FDA,DIV ONCOL & PULM DRUG PROD,WASHINGTON,DC 20204. US FDA,DIV RES & TESTING,WASHINGTON,DC 20204. NR 30 TC 8 Z9 8 U1 0 U2 2 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 17 PY 1996 VL 110 IS 1-3 BP 113 EP 121 DI 10.1016/0300-483X(96)03343-4 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA UQ569 UT WOS:A1996UQ56900012 PM 8658552 ER PT J AU DAquila, RT Hughes, MD Johnson, VA Fischl, MA Sommadossi, JP Liou, SH Timpone, J Myers, M Basgoz, N Niu, M Hirsch, MS Costanzo, L Ruben, S Berzins, B Martinez, A Fishman, I Kazial, K Cort, SN Robinson, P Hall, D Macy, H McLaren, C Rooney, J Warwick, J CavailleColl, M Valentine, F Booth, D Soeiro, R Stein, D Zingman, B Schliosberg, J Polsky, B Sepkowitz, K Sharpe, V Giordano, M Wanke, C Gulick, R Craven, D Grodman, C Fife, K Black, J Todd, K Nixon, H Sperber, K Gerits, P Mildvan, D Nicholas, P Murphy, RL Kessler, H Pulvirenti, J Squires, K Saag, M Weingarten, J Gnann, J Havlir, D Fegan, C Spector, S Richman, D Jacobson, M Dybeck, K Joseph, P Clanon, K McKenzie, S Daniel, P Dayton, D Leonard, J Schooley, R Kuritzkes, D Ray, G Putnam, B Jayaweera, D PatroneReese, J Tanner, T Moebus, J Reed, N StJacque, R Henry, K Swindells, S Eron, J Ragan, D Horton, J Lane, T Frank, I Norris, A Pomerantz, R Hauptman, S Geiseler, J Leedom, J Canchola, F Olson, C Deyton, L Pettinelli, C AF DAquila, RT Hughes, MD Johnson, VA Fischl, MA Sommadossi, JP Liou, SH Timpone, J Myers, M Basgoz, N Niu, M Hirsch, MS Costanzo, L Ruben, S Berzins, B Martinez, A Fishman, I Kazial, K Cort, SN Robinson, P Hall, D Macy, H McLaren, C Rooney, J Warwick, J CavailleColl, M Valentine, F Booth, D Soeiro, R Stein, D Zingman, B Schliosberg, J Polsky, B Sepkowitz, K Sharpe, V Giordano, M Wanke, C Gulick, R Craven, D Grodman, C Fife, K Black, J Todd, K Nixon, H Sperber, K Gerits, P Mildvan, D Nicholas, P Murphy, RL Kessler, H Pulvirenti, J Squires, K Saag, M Weingarten, J Gnann, J Havlir, D Fegan, C Spector, S Richman, D Jacobson, M Dybeck, K Joseph, P Clanon, K McKenzie, S Daniel, P Dayton, D Leonard, J Schooley, R Kuritzkes, D Ray, G Putnam, B Jayaweera, D PatroneReese, J Tanner, T Moebus, J Reed, N StJacque, R Henry, K Swindells, S Eron, J Ragan, D Horton, J Lane, T Frank, I Norris, A Pomerantz, R Hauptman, S Geiseler, J Leedom, J Canchola, F Olson, C Deyton, L Pettinelli, C TI Nevirapine, zidovudine, and didanosine compared with zidovudine and didanosine in patients with HIV-1 infection - A randomized, double-blind, placebo-controlled trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; COMBINATION THERAPY; MULTIDRUG-RESISTANCE; REPLICATION; INHIBITION; INTERFERON AB Objective: To study the addition of a third human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitor, nevirapine, to the combination of zidovudine and didanosine. Design: A 48-week, randomized, double-blind, placebo-controlled trial at 16 AIDS (acquired immunodeficiency syndrome) Clinical Trials Units. Patients: 398 adults who had HIV-1 infection, had 350 or fewer CD4(+) T lymphocytes/mm(3), and had had more than 6 months of previous nucleoside therapy. Intervention: 1) Either nevirapine or placebo (200 mg/d for 2 weeks, then 400 mg/d thereafter) and 2) open-label zidovudine (600 mg/d) and didanosine (400 mg/d for patients weighing greater than or equal to 60 kg). Measurements: CD4(+) T lymphocyte counts, time to first HIV-1 disease progression event or death, adverse events, and nevirapine levels in plasma samples taken at random were measured in all patients. Plasma levels of HIV-1 RNA; HIV-1 infectivity titer in peripheral blood mononuclear cells; serum p24 antigen levels; and plasma levels of zidovudine and didanosine were measured in patients enrolled at half the study sites. Results: After 48 weeks of study treatment, the patients assigned to the triple-combination regimen (nevirapine, zidovudine, and didanosine) had an 18% higher mean absolute CD4 cell count (95% CI, 7% to 29%; P = 0.001), a 0.32 log(10) lower mean infectious HIV-1 titer in peripheral blood mononuclear cells (CI, 0.05 to 0.59 log(10) infectious units per million cells; P = 0.023), and a 0.25 log(10) lower mean plasma HIV-1 RNA level (CI, 0.03 to 0.48 log(10) RNA copies/mL; P = 0.028) than did patients assigned to the double-combination regimen (zidovudine and didanosine). Severe rashes were more common among patients assigned to receive the triple combination (9% compared with 2%; P = 0.002). Risk for disease progression did not differ between the two groups (relative hazard of the triple-combination group, 1.24 [CI, 0.75 to 2.06]; P > 0.2), although the study had only moderate power to detect a major difference. Conclusions: Adding nevirapine to zidovudine and didanosine improved the long-term immunologic and virologic effects of therapy and was associated with severe rash among the patients studied, who had had extensive previous therapy. These results support 1) the continuing development of combinations of more than two antiretroviral drugs to increase and prolong HIV-1 suppression and 2) the potential utility of nevirapine in combination regimens. C1 AIDS CLIN TRIALS GRP OPERAT OFF,ROCKVILLE,MD. NORTHWESTERN UNIV,CHICAGO,IL 60611. NIAID,PHARMACEUT & REGULATORY AFFAIRS BRANCH,BETHESDA,MD 20892. FRONTIER SCI & TECHNOL RES FDN INC,STAT & DATA MANAGEMENT CTR,AMHERST,MA. BOEHRINGER INGELHEIM PHARMACEUT INC,RIDGEFIELD,CT 06877. BRISTOL MYERS SQUIBB CO,WALLINGFORD,CT 06492. GLAXO WELLCOME CO,RES TRIANGLE PK,NC. US FDA,BETHESDA,MD 20014. NYU,MED CTR,NEW YORK,NY. CLIN SITE MONITORING GRP,DURHAM,NC. ALBERT EINSTEIN COLL MED,NEW YORK,NY. CORNELL UNIV,NEW YORK,NY. BOSTON CITY HOSP,BOSTON,MA 02118. INDIANA UNIV,INDIANAPOLIS,IN 46204. MT SINAI MED CTR,NEW YORK,NY 10029. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV CINCINNATI,CINCINNATI,OH. UNIV COLORADO,HLTH SCI CTR,DENVER,CO. UNIV MIAMI,MIAMI,FL 33152. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. UNIV N CAROLINA,CHAPEL HILL,NC. UNIV PENN,PHILADELPHIA,PA 19104. UNIV SO CALIF,LOS ANGELES,CA. NIAID,DIV AIDS,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,AIDS CLIN TRIALS GRP STAT DATA & ANAL CTR,BOSTON,MA 02115. UNIV ALABAMA,SCH MED,DEPT MED,DIV INFECT DIS,BIRMINGHAM,AL 35294. VET AFFAIRS MED CTR,BIRMINGHAM,AL 35294. UNIV MIAMI,SCH MED,DEPT MED,MIAMI,FL 33101. UNIV ALABAMA,DEPT PHARMACOL,DIV CLIN PHARMACOL,SCH MED,BIRMINGHAM,AL 35294. GENENTECH INC,DEPT BIOSTAT,S SAN FRANCISCO,CA 94080. GEORGETOWN UNIV,MED CTR,DEPT MED,DIV INFECT DIS,WASHINGTON,DC 20007. BOEHRINGER INGELHEIM PHARMACEUT INC,RIDGEFIELD,CT 06877. US FDA,DIV BIOSTAT & EPIDEMIOL,ROCKVILLE,MD 20852. OI Murphy, Robert/0000-0003-3936-2052 NR 46 TC 234 Z9 237 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 15 PY 1996 VL 124 IS 12 BP 1019 EP 1030 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA UQ658 UT WOS:A1996UQ65800001 PM 8633815 ER PT J AU Yamauchi, A Taga, K Mostowski, HS Bloom, ET AF Yamauchi, A Taga, K Mostowski, HS Bloom, ET TI Target cell-induced apoptosis of interleukin-2-activated human natural killer cells: Roles of cell surface molecules and intracellular events SO BLOOD LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; SIGNAL TRANSDUCTION; GENE-EXPRESSION; NK CELLS; LYMPHOCYTES; CYTOTOXICITY; ACTIVATION; DEATH; GENERATION; INDUCTION AB We previously reported that natural killer (NK)-sensitive target cells, K562, kill interleukin-2-stimulated (lymphokine-activated killer [LAK]) but not unstimulated NK cells. We have now investigated the molecular basis of this phenomenon. Soluble monoclonal antibody (MoAb) to CD18 inhibited 75% of K562-induced DNA fragmentation and membrane disruption, whereas blocking MoAb to Fas partially inhibited only the DNA fragmentation. MoAbs to CD2, CD11a, CD11b, B7, or CD16 had limited or no effect on K562-induced death of LAK cells. Receptor ligation with either immobilized MoAb to CD18 or Fas induced membrane disruption and DNA degradation in LAK cells independently of K562, and MoAb to CD18, CD11a, or CD11b enhanced DNA fragmentation induced by anti-fas. Fas-L-transfected Raji cells also killed LAK cells, but only if Fast expression was amplified. K562 cells rapidly triggered protein phosphorylation in LAK cells, and the tyrosine kinase inhibitor, Herbimycin A, inhibited DNA fragmentation and membrane disruption. Protease inhibitors strongly suppressed K562-mediated DNA fragmentation of LAK cells, but not membrane disruption. In conclusion, (1) K562-induced death of LAK cells involves primarily CD18, although other molecules, such as Fas, may also be involved; (2) K562-mediated apoptosis of LAK cells requires tyrosine phosphorylation and protease activity; (3) engagement of Fas by immobilized MoAb or Fas-L on target cells can also kill LAK cells; and (4) Fas-immobilized MoAb synergizes with coimmobilized MoAb to CD11a, CD11b, or CD18 for LAK cell killing. Activation-induced death of NK cells may represent a mechanism for NK cell regulation. This is a US government work. There are no restrictions on its use. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GEN THERAPIES,LAB CELLULAR IMMUNOL HFM518,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. NR 53 TC 42 Z9 42 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1996 VL 87 IS 12 BP 5127 EP 5135 PG 9 WC Hematology SC Hematology GA UQ709 UT WOS:A1996UQ70900022 PM 8652825 ER PT J AU Chen, JJ AF Chen, JJ TI Global tests for analysis of multiple tumour data from animal carcinogenicity experiments SO STATISTICS IN MEDICINE LA English DT Article ID ENDPOINTS; SAMPLES AB This paper presents test procedures for testing of the overall dose effect at every tumour type/site simultaneously in a chronic animal carcinogenicity bioassay. I derive global tests of the tumour prevalence rates and the tumour onset rates using the generalized estimating equations approach. The test is based on the model of a common dose effect alternative. I used the logistic regression model for simultaneous testing of non-lethal tumours, and the Poly-3 test for testing of mixtures of lethal or non-lethal tumours of different types/sites. An application illustrating the proposed tests concerns analysis of a carcinogenicity experiment designed to study the dose response of hepatocellular and bladder tumours to 2-acetylaminofluorene (2-AAF) exposure. RP Chen, JJ (reprint author), US FDA,NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,JEFFERSON,AR 72079, USA. NR 27 TC 6 Z9 6 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 15 PY 1996 VL 15 IS 11 BP 1217 EP 1225 DI 10.1002/(SICI)1097-0258(19960615)15:11<1217::AID-SIM229>3.0.CO;2-4 PG 9 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA UR768 UT WOS:A1996UR76800010 PM 8804149 ER PT J AU Lu, ZB Asher, DM Levenbook, IS Chumakov, KM AF Lu, ZB Asher, DM Levenbook, IS Chumakov, KM TI Succession of mutations in the Sabin strain of type 3 poliovirus replicating in the central nervous system of monkeys SO VIROLOGY LA English DT Article ID VACCINE; NEUROVIRULENCE; SEQUENCE AB Sabin strains of oral poliovirus vaccine (OPV) undergo limited genetic changes during replication in cell cultures, the gastrointestinal tract of vaccinees, and the central nervous system of monkeys. Some of these changes are associated with loss of attenuation markers. Here we report the dynamics of mutant accumulation in the Sabin strain of poliovirus type 3 inoculated intraspinally into monkeys. Thr --> lie reversion in amino acid 6 of VPI (2493 C --> U) occurred within the first few days postinoculation (p.i.), but decreased on later days and completely disappeared by Day 17 p.i. 472 U --> C reversion in the 5'-untranslated region appeared to accumulate slower and by Day 17 completely substituted for the vaccine-type nucleotide at this site. These results indicate that experimental infection of the central nervous system of monkeys consists of early and late phases in which a different genetic constitution of the virus is favored. In several isolates one additional neurovirulent revertant was found: a Phe --> Ser at amino acid 91 of VP3 (2034 U --> C). Since this mutation was never detected in vaccine lots and is strongly selected against in cell cultures at temperatures below 38.5 degrees, it does not threaten the safety of OPV. (C) 1996 Academic Press, Inc. C1 US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852. NR 18 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 15 PY 1996 VL 220 IS 2 BP 285 EP 289 DI 10.1006/viro.1996.0316 PG 5 WC Virology SC Virology GA UT252 UT WOS:A1996UT25200004 PM 8661379 ER PT J AU Sherman, DR Mdluli, K Hickey, MJ Arain, TM Morris, SL Barry, CE Stover, CK AF Sherman, DR Mdluli, K Hickey, MJ Arain, TM Morris, SL Barry, CE Stover, CK TI Compensatory ahpC gene expression in isoniazid-resistant Mycobacterium tuberculosis SO SCIENCE LA English DT Article ID OXIDATIVE STRESS AB Mutations that eliminate KatG catalase-peroxidase activity prevent activation of isoniazid and are a major mechanism of resistance to this principal drug for the treatment of Mycobacterium tuberculosis infections. However, the loss of KatG activity in clinical isolates seemed paradoxical because KatG is considered an important factor for the survival of the organism. Expression of either KatG or the recently identified alkyl hydroperoxidase AhpC was sufficient to protect bacilli against the toxic effects of organic peroxides. To survive during infection, isoniazid-resistant KatG mutants have apparently compensated for the loss of KatG catalase-peroxidase activity by a second mutation, resulting in hyperexpression of AhpC. C1 PATHOGENESIS CORP,LAB TB & MOL MICROBIOL,SEATTLE,WA 98119. NIAID,TB RES UNIT,INTRACELLULAR PARASITES LAB,ROCKY MT LABS,HAMILTON,MT 59840. US FDA,LAB MYCOBACTERIA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. RI Barry, III, Clifton/H-3839-2012; OI Stover, Charles/0000-0002-7406-1696 FU Intramural NIH HHS [Z01 AI000783-11] NR 21 TC 272 Z9 288 U1 2 U2 8 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 14 PY 1996 VL 272 IS 5268 BP 1641 EP 1643 DI 10.1126/science.272.5268.1641 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UR093 UT WOS:A1996UR09300043 PM 8658136 ER PT J AU Stadel, BV Gueriguian, J Fleming, GA AF Stadel, BV Gueriguian, J Fleming, GA TI Metformin-associated mortality in US studies SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Stadel, BV (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 13 PY 1996 VL 334 IS 24 BP 1613 EP 1613 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UP663 UT WOS:A1996UP66300029 ER PT J AU Tanner, P Przekwas, G Clark, R Ginsberg, M Waterman, S AF Tanner, P Przekwas, G Clark, R Ginsberg, M Waterman, S TI Tetrodotoxin poisoning associated with eating puffer fish transported from Japan - California, 1996 (Reprinted from MMWR, vol 45 pg 389-391, 1996) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 UNIV CALIF SAN DIEGO,MED CTR,SAN DIEGO REG POISON CTR,SAN DIEGO,CA 92103. SAN DIEGO CTY HLTH DEPT,SAN DIEGO,CA. CALIF DEPT HLTH SERV,SACRAMENTO,CA. US FDA,ROCKVILLE,MD 20857. CDC,NATL CTR ENVIRONM HLTH,DIV ENVIRONM HAZARDS & HLTH EFFECTS,ATLANTA,GA. CDC,DIV FIELD EPIDEMIOL,EPIDEMIOL PROGRAM OFF,ATLANTA,GA. RP Tanner, P (reprint author), SAN DIEGO DEPT ENVIRONM HLTH,SAN DIEGO,CA, USA. NR 9 TC 7 Z9 7 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 5 PY 1996 VL 275 IS 21 BP 1631 EP 1631 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UN252 UT WOS:A1996UN25200007 ER PT J AU BallardBarbash, R Potosky, AL Harlan, LC Nayfield, SG Kessler, LG AF BallardBarbash, R Potosky, AL Harlan, LC Nayfield, SG Kessler, LG TI Factors associated with surgical and radiation therapy for early stage breast cancer in older women SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; SEGMENTAL-MASTECTOMY; GEOGRAPHIC-VARIATION; AXILLARY DISSECTION; ELDERLY WOMEN; AGE; SURGERY; CARE; RADIOTHERAPY; PATTERNS AB Background: In addition to demographic and health care-related characteristics, the age and physiologic status of women at the time of breast cancer diagnosis have been reported to influence receipt of standard treatments. Previous studies of the influence of age and comorbidity have not examined whether other patient-, region-, or health care-related characteristics altered the association of age and comorbidity with type of treatment received. Purpose: This study examined factors associated with receipt of breast-conserving surgery and radiation therapy, both of which are recommended treatments for breast cancer, among a cohort of 18 704 women aged 65 years or more who had breast cancer diagnosed during the period from 1985 through 1989. Methods: A data file linking Medicare claims records to data from the Surveillance, Epidemiology, and End Results (SEER) Program of the U.S. National Cancer Institute was utilized. Logistic regression analysis was used to examine associations between patient, region, and hospital characteristics and the receipt of specific treatments. The likelihood test was used to assess the significance of observed associations (expressed as odds ratios [ORs]). Because of multiple comparisons, only those ORs with two-sided P values <.01 were considered statistically significant. Results: The frequency of breast-conserving surgery was highest (54%) among women aged 80 years or more, who had two or more comorbid conditions and stage I disease. However, in general, the receipt of radiation therapy among women undergoing breast-conserving surgery declined markedly with age, irrespective of comorbidity status and disease stage. Between the ages of 65-69 years and 80 years or older, radiation therapy declined from 77% to 24% among women with no comorbid conditions and from 50% to 12% among women with two or more comorbid conditions. In regression models that included hospital, region, and patient characteristics as variables, age and comorbidity remained independently associated with the receipt of radiation therapy (OR = 0.12 and 95% confidence interval [CI] = 0.10-0.14 for women aged 80 years or more compared with women 65-69 years of age and OR of 0.33 [95 % CI = 0.24-0.46] for women with two or more comorbid conditions versus no comorbid conditions). Conclusions: After adjustment for multiple clinical and nonclinical factors influencing treatment, chronologic age remains an important independent factor associated with the receipt of radiation therapy after breast-conserving surgery among women aged 65 years or more who were diagnosed with early stage breast cancer. Implications: Future studies should determine whether these differences in treatment patterns among older women result in increased morbidity (e.g., from recurrence), shortened disease-free or overall survival, or decreased quality of life. C1 NCI,CHEMOPREVENT BRANCH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. OFF SURVEILLANCE & BIOMETR FOOD & DRUG ADM,CTR DEVICES & RADIOL HLTH,GAITHERSBURG,MD. RP BallardBarbash, R (reprint author), NCI,APPL RES BRANCH,DIV CANC PREVENT & CONTROL,EXECUT PLAZA N,RM 343,BETHESDA,MD 20892, USA. NR 60 TC 286 Z9 287 U1 1 U2 6 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 5 PY 1996 VL 88 IS 11 BP 716 EP 726 DI 10.1093/jnci/88.11.716 PG 11 WC Oncology SC Oncology GA UN481 UT WOS:A1996UN48100009 PM 8637025 ER PT J AU Kux, L AF Kux, L TI Looking back at existing rules: Agency perspectives on analysis requirements SO ADMINISTRATIVE LAW REVIEW LA English DT Article RP Kux, L (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER BAR ASSOC PI CHICAGO PA 750 N LAKE SHORE DR ATTN:ORDER FULFILLMENT, CHICAGO, IL 60611 SN 0001-8368 J9 ADMIN LAW REV JI Adm. Law Rev. PD SUM PY 1996 VL 48 IS 3 BP 375 EP 379 PG 5 WC Law SC Government & Law GA UR645 UT WOS:A1996UR64500019 ER PT J AU Bright, RA Moore, RM AF Bright, RA Moore, RM TI Estimating the prevalence of women with breast implants SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter C1 US DEPT HHS,OFF INT AFFAIRS,ROCKVILLE,MD 20852. RP Bright, RA (reprint author), US FDA,EPIDEMIOL BRANCH,CTR DEVICES & RADIOL HLTH,OFF SURVEILLANCE & BIOMETR,HFZ-541,ROCKVILLE,MD 20857, USA. RI Bright, Roselie/D-2240-2016 NR 4 TC 3 Z9 3 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 1996 VL 86 IS 6 BP 891 EP 891 DI 10.2105/AJPH.86.6.891 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UQ530 UT WOS:A1996UQ53000037 PM 8659677 ER PT J AU Doerge, DR Churchwell, MI Holder, CL Rowe, L Bajic, S AF Doerge, DR Churchwell, MI Holder, CL Rowe, L Bajic, S TI Detection and confirmation of beta-agonists in bovine retina using LC/APCI-MS SO ANALYTICAL CHEMISTRY LA English DT Article ID MASS-SPECTROMETRY; CLENBUTEROL; CHROMATOGRAPHY; RESIDUES; LIVER AB beta-Adrenergic receptor agonists are growth-promoting drugs with the potential far illegal use in livestock, and human toxicity has resulted from consumption of contaminated meat, On-line liquid chromatography with atmospheric pressure chemical ionization mass spectrometry (LC/APCI-MS) was used for sensitive detection of several beta-agonists in retina, a tissue reported to concentrate and retain such residues for extended periods, Multiresidue extraction, separation, detection, and confirmation procedures were developed for retinal tissue and applied to eyes from cattle treated with clenbuterol (69-201 ppb) and to control eyes spiked with salbutamol (100 ppb) and terbutaline (25-100 ppb). Rapid switching of the potential difference between sampling tone and skimmer in the transport region of the API source was used to optimize acquisition of the protonated molecules and characteristic fragment ions obtained by collision-induced dissociation reactions. The respective selected ions were simultaneously acquired using a single quadrupole mass spectrometer. The accurate and precise agreement observed for diagnostic ion intensity ratios between beta-agonists in retinal samples and authentic standards suggests that LC/APCI-MS can he used for confirmation of analyte structure at trace levels and does not require the use of a triple-stage quadrupole mass analyzer. C1 USDA ARS,COLLEGE STN,TX 77845. VG ORGAN,ALTRINCHAM WA14 5RZ,CHESHIRE,ENGLAND. RP Doerge, DR (reprint author), NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 18 TC 45 Z9 50 U1 2 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JUN 1 PY 1996 VL 68 IS 11 BP 1918 EP 1923 DI 10.1021/ac951174f PG 6 WC Chemistry, Analytical SC Chemistry GA UN470 UT WOS:A1996UN47000022 PM 8686914 ER PT J AU Pothuluri, JV Evans, FE Heinze, TM Cerniglia, CE AF Pothuluri, JV Evans, FE Heinze, TM Cerniglia, CE TI Formation of sulfate and glucoside conjugates of benzo[e]pyrene by Cunninghamella elegans SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; PHANEROCHAETE-CHRYSOSPORIUM; PHENANTHRENE; METABOLISM; OXIDATION AB Benzo[e]pyrene is a pentacyclic aromatic hydrocarbon, which, unlike its structural isomer benzo[a]pyrene, is not a potent carcinogen or mutagen. The metabolism of benzo[e]pyrene was studied using the filamentous fungus Cunninghamella elegans ATCC 36112.C. elegans metabolized 65% of the [9, 10, 11, 12-H-3]benzo[e]pyrene and unlabeled benzo[e]pyrene added to Sabouraud dextrose broth cultures after 120 h of incubation. Three major metabolites of benzo[e]pyrene were separated by reversed-phase high- performance liquid chromatography. These were identified by H-1 and C-13 NMR, and mass spectral analyses as 3-benzo [e] pyrenylsulfate, 10-hydroxy-3-benzo[e]pyrenyl sulfate, and benzo[e]pyrene 3-O-beta-glucopyranoside. RP Pothuluri, JV (reprint author), US FDA,NATL CTR TOXICOL RES,DIV MICROBIOL,HFT 250,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 22 TC 18 Z9 19 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD JUN PY 1996 VL 45 IS 5 BP 677 EP 683 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA UV891 UT WOS:A1996UV89100017 ER PT J AU Taurog, A Dorris, ML Doerge, DR AF Taurog, A Dorris, ML Doerge, DR TI Mechanism of simultaneous iodination and coupling catalyzed by thyroid peroxidase SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID CYTOCHROME-C PEROXIDASE; HORMONE SYNTHESIS; LACTOPEROXIDASE-H2O2 COMPOUNDS; THYROGLOBULIN IODINATION; HORSERADISH-PEROXIDASE; OXIDIZING EQUIVALENTS; LIGNIN PEROXIDASE; NATIVE ENZYME; OXIDATION; TYROSINE AB Thyroid peroxidase (TPO) simultaneously catalyzes two very different types of reaction in the thyroid gland-iodination and coupling, The present study addresses the mechanism of this simultaneous dual activity, Compound I, the two-electron oxidation product of TPO, exists in two different forms-an oxoferryl porphyrin pi-cation radical and an oxoferryl protein radical, It has been proposed that iodination is mediated by the porphyrin pi-cation radical form of TPO compound I, while coupling is mediated by the protein radical form, However, results obtained in the present study favor the view that both iodination and coupling are mediated by the porphyrin pi-cation radical form of compound I, In the first part of the study, we compared coupling and iodination activities of two peroxidases with very similar crystal structures-cytochrome c peroxidase (CcP) and lignin peroxidase (LiP), Although these two peroxidases have very similar three-dimensional structures, CcP forms a compound I only of the protein radical type, whereas compound I of LiP exists only as a porphyrin pi-cation radical, Comparison of the catalytic activities of the two enzymes showed that diiodotyrosine (DIT)-stimulated coupling activity of LiP was significantly greater than that of CcP, Moreover, lignin peroxidase displayed very significant iodinating activity at acid pHs, whereas iodination with CcP was negligible at all pHs tested, Our findings with these two structurally similar peroxidases suggested that TPO-catalyzed iodination and coupling could both be mediated by the porphyrin pi-cation radical form of compound I, More direct evidence in support of this view was obtained in the second part of this study, employing TPO and lactoperoxidase (LPO) model systems in which iodination and coupling occurred simultaneously, Heme spectral analysis was used to correlate formation of the protein radical form of compound I with the kinetics of the iodination and coupling reactions, Formation of the compound I protein radical was not observed until the iodination and coupling reactions had almost been completed, In separate experiments it was shown that the spontaneous conversion of the porphyrin pi-cation radical form of TPO or LPO compound I to the protein radical form was markedly inhibited by a low concentration of iodide, especially in the presence of an iodide acceptor, These studies provide compelling evidence that both iodination and coupling are mediated by the porphyrin pi-cation radical form of compound I, This was further substantiated by the finding that coupling was inhibited in the presence of excess iodide, an observation readily explained by competition between iodide and DIT residues in thyroglobulin for oxidation by the porphyrin pi-cation radical. (C) 1996 Academic Press, Inc. C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RP Taurog, A (reprint author), UNIV TEXAS,SW MED CTR,DEPT PHARMACOL,5323 HARRY HINES BLVD,DALLAS,TX 75235, USA. FU NIDDK NIH HHS [NIDDK-U3612] NR 32 TC 73 Z9 75 U1 2 U2 8 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN 1 PY 1996 VL 330 IS 1 BP 24 EP 32 DI 10.1006/abbi.1996.0222 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UP131 UT WOS:A1996UP13100005 PM 8651700 ER PT J AU Higley, JD Mehlman, PT Higley, SB Fernald, B Vickers, J Lindell, SG Taub, DM Suomi, SJ Linnoila, M AF Higley, JD Mehlman, PT Higley, SB Fernald, B Vickers, J Lindell, SG Taub, DM Suomi, SJ Linnoila, M TI Excessive mortality in young free-ranging male nonhuman primates with low cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MONKEYS MACACA-MULATTA; RHESUS-MONKEYS; METABOLITES; MONOAMINE; BEHAVIOR AB Background: The purpose of this study was to assess the impact of central serotonin turnover rate on survival to adulthood among nonhuman primates living in a large, free-ranging colony. Methods: The rate of mortality was ascertained over a 4-year period after obtaining blood and cisternal cerebrospinal fluid (CSF) samples from 49 free-ranging, 2-year-old prepubertal male rhesus monkeys. Cerebrospinal fluid was assayed for 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine, 3-methoxy-4-hydroxyphenylgycol, and homovanillic acid. Blood plasma was assayed for adrenocorticotropic hormone, cortisol, and testosterone. Following the sampling of body fluids, records of scars and wounds and aggressive encounters were used to rank the subjects from low to high in aggressiveness. Direct observations of aggressive behavior were collected from 27 of the subjects over a 3-month period. Results: Four years later, 6 of the 49 subjects were known to be dead and an additional 5 had been missing for more than 2 years and were presumed dead. The CSF 5-HIAA concentrations were predictive of which subjects died, with 46% of the subjects with low CSF 5-HIAA concentrations dead or presumed dead. None of the subjects from the highest CSF 5-HIAA concentration quartile were dead or missing. Indeed, 91% of the dead subjects came from the 2 lowest quartiles of CSF 5-HIAA concentrations. Direct observations of aggressive behavior showed that dead or missing subjects had initiated escalated aggression, a measure of unrestrained aggression that has a high probability of trauma or injury, at a higher rate than subjects that were known to be alive. The cause of death could be ascertained for 6 of the 11 missing subjects. The 4 subjects that were known to die as a consequence of aggressive encounters came from the lowest quartile of CSF 5-HIAA concentrations and had been rated as more aggressive during their initial capture. Subjects captured more than once possessed lower CSF 5-HIAA concentrations, were rated as more aggressive, and were more likely to suffer early death than those captured only once. Conclusion: These findings suggest that low CSF 5-HIAA concentrations quantified early in life is a powerful biological predictor of future excessive aggression, risk taking, and premature death among nonhuman primate males. C1 NIAAA,SECT NEUROCHEM & NEUROENDOCRINOL,CLIN STUDIES LAB,DIV INTRAMURAL CLIN & BIOL RES,BETHESDA,MD 20205. NICHHD,COMPARAT ETHOL LAB,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20014. LAB ANIM BREEDERS & SERV INC,YEMASSEE,SC. FU PHS HHS [223-89-1101] NR 25 TC 138 Z9 138 U1 1 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 1996 VL 53 IS 6 BP 537 EP 543 PG 7 WC Psychiatry SC Psychiatry GA UP723 UT WOS:A1996UP72300008 PM 8639037 ER PT J AU Katzper, M Neuner, R AF Katzper, M Neuner, R TI Susceptibility and therapeutic scenarios for rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 US FDA,CDER,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1996 VL 39 IS 6 SU S BP R25 EP R25 PG 1 WC Rheumatology SC Rheumatology GA UQ616 UT WOS:A1996UQ61600099 ER PT J AU Schwartz, PS Finbloom, DS AF Schwartz, PS Finbloom, DS TI Effects of dexamethasone (Dex) on interferon gamma induced activation of the stat transcription factor pathway and map kinase (MAPK) activity in rat basophilic leukemia (RBL) cells. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. US FDA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1996 VL 39 IS 6 SU S BP R25 EP R25 PG 1 WC Rheumatology SC Rheumatology GA UQ616 UT WOS:A1996UQ61600098 ER PT J AU Marriott, BM Smith, JC Jacobs, RM Jones, AOL Altman, JD AF Marriott, BM Smith, JC Jacobs, RM Jones, AOL Altman, JD TI Calcium, magnesium, and phosphorus content of hair from two populations of rhesus monkeys SO BIOLOGICAL TRACE ELEMENT RESEARCH LA English DT Article DE hair mineral content; monkeys; rhesus monkeys; Macaca mulatta ID MACACA-MULATTA; CAYO-SANTIAGO; TRACE; ZINC; NUTRITION; MINERALS; CATTLE; COPPER AB The use of hair for the assessment of human mineral nutritional status is controversial, yet has potential because of the ease of collection and storage, and the high concentration of minerals in hair. This study generated baseline values for hair macromineral content in the most commonly used primate model for human nutrition and disease, the rhesus monkey. Hair digests from monkeys in Maryland (n=98) and Puerto Rico (n=208) were analyzed by inductively coupled plasma atomic emission spectrometry (ICP-AES). Significant differences existed between the two populations for hair calcium (Ca), magnesium (Mg), and phosphorus (P) (P <0.01, P <0.001, P<0.02). Male hair had higher concentrations of Mg in specimens from the Puerto Rican population (P <0.001), whereas hair phosphorus was higher in female hair (P <0.02). There were no significant differences attributable to pregnancy status. Differences in hair content attributable to categorical age were found for Ca and Mg (P <0.001, P <0.01). Significant location differences paralleled dietary differences. These values therefore can be considered reference ranges for hair Ca, Mg, and P for free-ranging and caged rhesus monkeys. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT CELL BIOL & ANAT,BALTIMORE,MD 21205. USDA,HUMAN NUTR RES CTR,BELTSVILLE,MD 20705. US FDA,SAN FRANCISCO DIST OFF,PESTICIDE MET SECT,SAN FRANCISCO,CA. US FDA,CTR FOOD SAFETY & APPL NUTR,OFF BELTSVILLE TECH OPERAT,LAUREL,MD. RP Marriott, BM (reprint author), NIH,OFF DIETARY SUPPLEMENTS,FED BLDG,SUITE 610,7500 WISCONSIN AVE,BETHESDA,MD 20892, USA. FU NCRR NIH HHS [RR-01293, RR-7-2115]; NIMH NIH HHS [MH3079-01A2] NR 70 TC 3 Z9 3 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0163-4984 J9 BIOL TRACE ELEM RES JI Biol. Trace Elem. Res. PD SUM PY 1996 VL 53 IS 1-3 BP 147 EP 165 DI 10.1007/BF02784552 PG 19 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA VA909 UT WOS:A1996VA90900014 PM 8862745 ER PT J AU Marriott, BM Smith, JC Jacobs, RM Jones, AOL Altman, JD AF Marriott, BM Smith, JC Jacobs, RM Jones, AOL Altman, JD TI Copper, iron, manganese, and zinc content of hair from two populations of rhesus monkeys SO BIOLOGICAL TRACE ELEMENT RESEARCH LA English DT Article DE hair trace element content; trace elements; rhesus monkeys; monkeys; Macaca mulatta ID TRACE-ELEMENT CONCENTRATIONS; CHILDREN; AGE; SEX; DEFICIENCY; PROTEIN AB The concentrations of the elements copper (Cu), iron (Fe), manganese (Mn), and zinc (Zn) in hair of caged (in Maryland) and free-ranging (in Puerto Rico) rhesus monkey populations were determined. Significant chronological age-related decreases were evident for the trace elements Mn and Zn in both populations (P less than or equal to 0.01) and for Cu and Fe in free-ranging monkeys (P less than or equal to 0.005). The only overall gender difference was higher hair Mn concentration in free-ranging males than in females (P <0.03). There were no significant differences in hair Cu, Fe, or Mn related to pregnancy status. Hair Zn was lower in samples from pregnant than from nonpregnant monkeys from the caged monkeys (P less than or equal to 0.05), but did not differ in the free-ranging monkeys. Comparison of the two populations revealed that hair Zn levels were significantly higher in caged vs free-ranging animals (P <0.001). We attribute this higher hair Zn in the caged monkeys to contact and ingestion of Zn from their galvanized enclosures. Hair iron levels were significantly higher (P <0.001) in free-ranging monkeys, possibly as a result of Fe-rich soil ingestion from their environment. These data support continued investigation of the use of hair as an indicator of the exposure of large groups or populations to potentially high levels of specific minerals, and the use of nonhuman primates as models for the study of trace element deficiency and/or toxicity in humans. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT CELL BIOL & ANAT,BALTIMORE,MD 21205. USDA,HUMAN NUTR RES CTR,BELTSVILLE,MD 20705. US FDA,SAN FRANCISCO DIST OFF,PESTICIDE MET SECT,SAN FRANCISCO,CA. US FDA,CTR FOOD SAFETY & APPL NUTR,OFF BELTSVILLE TECH OPERAT,LAUREL,MD. RP Marriott, BM (reprint author), NIH,OFF DIETARY SUPPLEMENTS,FED BLDG,SUITE 610,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. FU NCRR NIH HHS [RR-01293, RR-7-2115]; NIMH NIH HHS [MH3079-01A2] NR 53 TC 4 Z9 4 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0163-4984 J9 BIOL TRACE ELEM RES JI Biol. Trace Elem. Res. PD SUM PY 1996 VL 53 IS 1-3 BP 167 EP 183 DI 10.1007/BF02784553 PG 17 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA VA909 UT WOS:A1996VA90900015 PM 8862746 ER PT J AU Dragunsky, E Taffs, R Chernokhvostova, Y Nomura, T Hioki, K Gardner, D Norwood, L Levenbook, I AF Dragunsky, E Taffs, R Chernokhvostova, Y Nomura, T Hioki, K Gardner, D Norwood, L Levenbook, I TI A poliovirus-susceptible transgenic mouse model as a possible replacement for the monkey neurovirulence test of oral poliovirus vaccine SO BIOLOGICALS LA English DT Article ID GENETIC STABILITY; MICE; RECEPTOR; STRAIN AB Two poliovirus-susceptible transgenic mouse (Tg PVR) strains, Tg1 and Tg21, were compared with the monkey test for their sensitivity to neurovirulence of live oral poliovirus vaccine (OPV). Intracerebral (i.c.) and intraspinal (i.s.) routes of inoculation were investigated to determine the most suitable combination of mouse strain and route. Evaluation of the mouse tests was performed using several indicators; clinical score and failure time were selected as the most efficient. Tg1 and Tg21 mice inoculated i.s. with type 2, and Tg21 mice inoculated i.s, with type 3 OPV were determined to be the most appropriate systems, whereas they are shown not to be suitable for type 1 OPV. The sensitivity of each of the two mouse models was at least equal to that of the monkey test, suggesting that these mouse systems might be considered as a potential replacement for the monkey test of OPV. However, more data are needed to establish regulatory criteria of acceptability for vaccine lots tested in Tg PVR mice. This is the first study conducted with Tg PVR mice with ail three types of poliovirus vaccine preparations. (C) 1996 The International Association of Biological Standardization C1 CENT INST EXPT ANIM,MIYAMAE,KAWASAKI 216,JAPAN. RP Dragunsky, E (reprint author), US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892, USA. NR 17 TC 28 Z9 28 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD JUN PY 1996 VL 24 IS 2 BP 77 EP 86 DI 10.1006/biol.1996.0010 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA VH437 UT WOS:A1996VH43700001 PM 8889053 ER PT J AU Progar, JJ May, JC Rains, TC Watters, RL Yu, L AF Progar, JJ May, JC Rains, TC Watters, RL Yu, L TI Preparation of an intra-laboratory reference material - Determination of the aluminum content of a pooled 5% albumin (human) solution by ETAAS, MFS and ICP-AES SO BIOLOGICALS LA English DT Article ID DIALYSIS ENCEPHALOPATHY SYNDROME; CONTAMINATION; TOXICITY; PLASMA; BONE AB Human albumin solutions as well as other biological products intended for human use may contain aluminum as a result of intentional addition due to manufacturing protocol or through inadvertent contamination occuring during the manufacturing process. Because of the implication of aluminum in human disease, it is desirable that aluminum levels in these products be monitored. To satisfy the need for a reference material that is representative of albumin products that are intended for therapeutic use, a pooled 5% human albumin solution was prepared in bulk to serve as a reference for aluminum during analytical procedures. Aliquots of the albumin pool were analyzed for their aluminum content by three independent analytical methods, namely, electrothermal atomic absorption, molecular fluorescence and inductively coupled plasma-atomic emission spectrometry. Measured values for aluminum in the albumin solution showed good agreement between the different analytical methods. The concentration of aluminum was determined to be 0.512 mu g Al/ml by the atomic absorption method, 0.502 mu g Al/ml by molecular fluorescence, and 0.498 mu g Al/ml by the inductively coupled plasma-atomic emission method. The overall average concentration was calculated to be 0.507 mu g/ml +/- 0.009 mu g Al/ml. The preparation of the albumin reference and its subsequent aluminum analysis is described. (C) 1996 The International Association of Biological Standardization C1 US DEPT COMMERCE,NATL INST STAND & TECHNOL,GAITHERSBURG,MD 20899. RP Progar, JJ (reprint author), US FDA,CTR BIOL EVALUAT & RES,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. RI Yu, Lee/N-7263-2015 OI Yu, Lee/0000-0002-8043-6853 NR 23 TC 6 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD JUN PY 1996 VL 24 IS 2 BP 87 EP 93 DI 10.1006/biol.1996.0011 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA VH437 UT WOS:A1996VH43700002 PM 8889054 ER PT J AU Sundaresan, PR Kaup, SM Wiesenfeld, PW Chirtel, SJ Hight, SC Rader, JI AF Sundaresan, PR Kaup, SM Wiesenfeld, PW Chirtel, SJ Hight, SC Rader, JI TI Interactions in indices of vitamin A, zinc and copper status when these nutrients are fed to rats at adequate and increased levels SO BRITISH JOURNAL OF NUTRITION LA English DT Article DE vitamin A; zinc; copper; nutrient interactions ID WEANLING RATS; A STATUS; CERULOPLASMIN; METABOLISM; EXCESS; SERUM; DIETS; LIVER AB The purpose of the present study was to determine the effects of feeding nutritionally adequate and increased levels of vitamin A (retinyl acetate at 1.4, 34.4, and 206.4 mg/kg diet) in combination with adequate or increased Zn (12 and 240 mg/kg) and Cu (5 and 50 mg/kg) on serum and tissue concentrations of retinol and retinyl palmitate and on indices of Cu and Zn status in female Sprague-Dawley rats, and to measure interactive effects of such nutrient imbalances, Rats fed on diets containing 34.4 and 206.4 mg vitamin A/kg had higher feed intakes and relative Liver weights than those fed on diets containing 1.4 mg vitamin A/kg. An interaction between dietary Cu and Zn and an independent effect of vitamin A affected serum ceruloplasmin oxidase (EC 1.16.3.1) activity, Rats fed on high Zn, adequate-Cu diets (240 and 5 mg Zn and Cu/kg respectively) had lower serum ceruloplasmin oxidase levels than rats fed on adequate-Zn, adequate-Cu diets(12 and 5 mg Zn and Cu/kg respectively), This effect was not observed in rats fed on high-Zn, high-Cu diets (240 and 50 mg Zn and Cu/kg respectively), Alterations in dietary levels of Cu and vitamin A independently affected haemoglobin levels, Serum cholesterol concentration was affected by interactions between Zn and vitamin A and Cu and vitamin A, Levels of retinol and retinyl palmitate in liver and kidney were significantly higher in rats fed on diets with increased dietary vitamin A than in those fed on diets with adequate vitamin A. Three-way interactions among Cu, Zn, and vitamin A affected levels of retinol in serum and liver, Two-way interactions between Cu and vitamin A affected liver retinyl palmitate and the sum of liver retinol+retinyl palmitate. An independent effect of dietary Zn on these variables was also observed. Interactions between Cu and vitamin A affected levels of Cu in liver and kidney while Fe and Zn in kidney were affected by interactions between Cu and Zn, This study demonstrates that differing interactions among variables of vitamin A metabolism and mineral status occur with higher dietary levels of vitamin A, Zn and Cu in the rat. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,OFF SCI ANAL & SUPPORT,WASHINGTON,DC 20204. US FDA,CTR FOOD SAFETY & APPL NUTR,OFF PLANT & DAIRY FOODS & BEVERAGES,WASHINGTON,DC 20204. US FDA,CTR FOOD SAFETY & APPL NUTR,OFF FOOD LABELING,WASHINGTON,DC 20204. RP Sundaresan, PR (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,OFF SPECIAL NUTR,200 C ST SW,WASHINGTON,DC 20204, USA. NR 29 TC 10 Z9 14 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0007-1145 J9 BRIT J NUTR JI Br. J. Nutr. PD JUN PY 1996 VL 75 IS 6 BP 915 EP 928 DI 10.1079/BJN19960197 PG 14 WC Nutrition & Dietetics SC Nutrition & Dietetics GA UY480 UT WOS:A1996UY48000012 PM 8774236 ER PT J AU Plakas, SM ElSaid, KR Stehly, GR Gingerich, WH Allen, JL AF Plakas, SM ElSaid, KR Stehly, GR Gingerich, WH Allen, JL TI Uptake, tissue distribution, and metabolism of malachite green in the channel catfish (Ictalurus punctatus) SO CANADIAN JOURNAL OF FISHERIES AND AQUATIC SCIENCES LA English DT Article ID PROLIFERATIVE KIDNEY-DISEASE; RAINBOW-TROUT; TRIPHENYLMETHANE DYE; FISH; RESIDUES AB The disposition of malachite green was determined in channel catfish (Ictalurus punctatus) after intravascular dosing (0.8 mg . kg(-1)) or waterborne exposure (0.8 mg . L(-1) for 1 h). After intravascular dosing, mean plasma concentrations of the parent compound exhibited a triphasic decline with a terminal elimination half-life of 6.2 h. Malachite green was rapidly absorbed and concentrated in the tissues during waterborne exposure. The rate of accumulation was directly related to pH of the exposure water. After waterborne exposure, elimination of the parent compound from plasma also was triphasic with a terminal half-life of 4.7 h. In muscle, the half-life of the parent compound was approximately 67 h. Malachite green and its metabolites were widely distributed in all tissues. In fish exposed to C-14-labeled malachite green, total drug equivalent concentrations were highest in abdominal fat and lowest in plasma. Malachite green was rapidly and extensively metabolized to its reduced form, leucomalachite green, which was slowly eliminated from the tissues. Leucomalachite green is an appropriate target analyte for monitoring exposure of channel catfish to this drug. C1 NATL BIOL SERV,UPPER MISSISSIPPI SCI CTR,LA CROSSE,WI 54602. RP Plakas, SM (reprint author), US FDA,GULF COAST SEAFOOD LAB,POB 158,DAUPHIN ISL,AL 36528, USA. NR 26 TC 58 Z9 66 U1 1 U2 12 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0706-652X J9 CAN J FISH AQUAT SCI JI Can. J. Fish. Aquat. Sci. PD JUN PY 1996 VL 53 IS 6 BP 1427 EP 1433 DI 10.1139/cjfas-53-6-1427 PG 7 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA VP799 UT WOS:A1996VP79900020 ER PT J AU Collins, JM Klecker, RW Chang, AE Kinsella, TJ AF Collins, JM Klecker, RW Chang, AE Kinsella, TJ TI Untitled SO CANCER RESEARCH LA English DT Letter ID IODODEOXYURIDINE C1 UNIV MICHIGAN,ANN ARBOR,MI 48109. UNIV WISCONSIN,MADISON,WI 53792. RP Collins, JM (reprint author), US FDA,RES CTR 4,ROCKVILLE,MD 20857, USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1996 VL 56 IS 11 BP 2677 EP 2677 PG 1 WC Oncology SC Oncology GA UN250 UT WOS:A1996UN25000042 ER PT J AU Scholl, P Musser, SM Kensler, TW Groopman, JD AF Scholl, P Musser, SM Kensler, TW Groopman, JD TI Inhibition of aflatoxin M(1) excretion in rat urine during dietary intervention with oltipraz SO CARCINOGENESIS LA English DT Article ID GLUTATHIONE S-TRANSFERASES; MOLECULAR DOSIMETRY; BUTYLATED HYDROXYANISOLE; HEPATIC TUMORIGENESIS; ETHOXYQUIN; HEPATOCARCINOGENESIS; AFLATOXIN-N7-GUANINE; ANTIOXIDANTS; PROTECTION; 1,2-DITHIOLE-3-THIONE AB 4-Methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione (oltipraz) is an effective chemopreventive agent against several classes of carcinogens in many target organs. Induction of carcinogen detoxication enzymes, particularly glutathione S-transferases, appears to be an important component of the protective actions of oltipraz. It has recently been observed that addition of oltipraz to rat liver microsomes or to cultured human hepatocytes blocks the oxidative metabolism of aflatoxin B-1 (AFB(1)) to its 8,9-oxide and the hydroxylated derivative aflatoxin M(1) (AFM(1)). Oltipraz is a competitive and perhaps irreversible inhibitor of cytochromes P450 1A2 and 3A4. To determine whether oltipraz can affect cytochrome P450-dependent metabolism of AFB(1) in vivo we have assessed the effect of oltipraz on the urinary excretion of oxidative metabolites of AFB(1) before, during and after a transient intervention. Male F344 rats, housed individually in glass metabolism cages, were gavaged daily with 25 mu g [H-3]AFB(1) for 28 consecutive days. Starting on day 6 and extending to day 16 half of the rats were fed a diet supplemented with 0.075 % oltipraz, Sequential 24 h urine samples were collected and a subset analyzed for AFB(1) metabolites. AFM(1) was the major metabolite detected in all urine samples, accounting for 2-6% of the administered dose. The excretion of AFM(1) was greatly reduced (77%) during the active phase of the intervention, when oltipraz was added to the diet, but rapidly returned to control levels after cessation of oltipraz administration. This inhibition of AFM(1) excretion was not seen in animals receiving oltipraz by gavage 24 h prior to dosing with AFB(1). Collectively these data are consistent with the view that oltipraz or a short-lived metabolite inhibits cytochrome P450 1A2 in vivo. C1 JOHNS HOPKINS UNIV,DEPT ENVIRONM HLTH SCI,SCH HYG & PUBL HLTH,BALTIMORE,MD 21205. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. RI Kensler, Thomas/D-8686-2014; OI Kensler, Thomas/0000-0002-6676-261X; Scholl, Peter/0000-0002-8870-3266 FU NIEHS NIH HHS [ES03819, ES06052, ES07141] NR 29 TC 21 Z9 21 U1 1 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1996 VL 17 IS 6 BP 1385 EP 1388 DI 10.1093/carcin/17.6.1385 PG 4 WC Oncology SC Oncology GA UT605 UT WOS:A1996UT60500030 PM 8681461 ER PT J AU Valentine, CR Valentine, JL Seng, J Leakey, J Casciano, D AF Valentine, CR Valentine, JL Seng, J Leakey, J Casciano, D TI The use of transgenic cell lines for evaluating toxic metabolites of carbamazepine SO CELL BIOLOGY AND TOXICOLOGY LA English DT Article DE carbamazepine; CYP3A4; cytotoxicity; human lymphoblastoid cells; MIT; transgenic cells ID XENOBIOTIC METABOLISM; CHILDREN; CARBAMAZEPINE-10,11-EPOXIDE; EPILEPSY; INVITRO; ASSAY; CYTOCHROMES-P450; CYTOTOXICITY; COMPETENT; PHENYTOIN AB Human lymphoblastoid cell lines transgenic for human CYP450s were evaluated for the identification of toxic metabolites of the anticonvulsant drug carbamazepine (CBZ). Human CYP450 isoforms expressed by these cell lines included 1A1, 1A2, 2E1, 2A6, and 3A4. A dose-dependent inhibition of population growth from 50-200 mu g/ml CBZ was detected by measuring cell number and respiration. The inhibition increased with the growth rate of the various lines, which correlated inversely with the presence of CYP450s, and may have been caused by CBZ itself. Cytotoxicity was observed only at the highest dose and in the line lacking transfected CYP450s. Microsomal preparations from hCYP3A4/OR cells converted CBZ into its principal oxidative metabolite, carbamazepine-10,11-epoxide (CBZ-E), at a rate of 630 pmol/min per mg protein, confirming a major role of CYP3A4 in this reaction. However, no CBZ-E (or any metabolite) was recovered from any whole-cell incubation even though hCYP3A4 cells readily converted testosterone to 6 beta-hydroxytestosterone. This suggests that differences exist between whole-cell and microsomal preparations of lymphoblastoid cells in their ability to metabolize CBZ. C1 NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,JEFFERSON,AR 72079. UNIV ARKANSAS MED SCI HOSP,DEPT PEDIAT,CLIN PHARMACOL SECT,LITTLE ROCK,AR. ARKANSAS CHILDRENS HOSP,LITTLE ROCK,AR 72202. RP Valentine, CR (reprint author), NATL CTR TOXICOL RES,DIV GENET TOXICOL,3900 NCTR RD,HFT-120,JEFFERSON,AR 72079, USA. FU NICHD NIH HHS [U10 HD 31324-01] NR 38 TC 18 Z9 19 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0742-2091 J9 CELL BIOL TOXICOL JI Cell Biol. Toxicol. PD JUN PY 1996 VL 12 IS 3 BP 155 EP 165 DI 10.1007/BF00148169 PG 11 WC Cell Biology; Toxicology SC Cell Biology; Toxicology GA UX424 UT WOS:A1996UX42400004 PM 8817061 ER PT J AU Miller, KG Poole, CF Pawlowski, TMP AF Miller, KG Poole, CF Pawlowski, TMP TI Classification of the botanical origin of cinnamon by solid-phase microextraction and gas chromatography SO CHROMATOGRAPHIA LA English DT Article DE gas chromatography; semivolatile flavor compounds; cinnamon; solid-phase microextraction; chemometric classification AB The conditions which affect the reproducibility of characteristic chromatographic profiles of semivolatile compounds from true cinnamon and cassia by headspace solid-phase microextraction are determined. Optimum conditions for sample amount, vial size, temperature, sampling time, and fiber type for steady state sampling conditions are identified. Vial size was an unexpected critical parameter possibly related to the build up of internal pressure during sample heating followed by expulsion of a portion of the vapor phase through the septum as it was punctured by the syringe. Gas chromatography with ion trap mass spectrometry was used to identify the major volatile compounds in cassia and true cinnamon. Reasonable semi-quantitative agreement (r(2) > 0.87 and generally greater than 0.93) was observed for the major semivolatile compounds isolated by headspace solid-phase microextraction and solvent-assisted supercritical fluid extraction. The extracts isolated by solid-phase microextraction contained relatively high concentrations of terpene-type compounds in low abundance in the solvent-assisted supercritical fluid extracts, but these compounds were of little value in distinguishing the botanical origin of authentic cinnamon and cassia samples. The latter were easily distinguished by the presence of eugenol and benzyl benzoate in true cinnamon, that was absent in cassia, and the presence of coumarin and delta-cadinene, in cassia, that was either absent or in low concentration in true cinnamon. Headspace solid-phase microextraction provides a rapid and simple method for establishing the botanical origin of the principal cinnamons of commerce. C1 UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,DEPT CHEM,LONDON SW7 2AY,ENGLAND. WAYNE STATE UNIV,DEPT CHEM,DETROIT,MI 48202. UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,CTR ANALYT CHEM,ZENECA SMITHKLINE BEECHAM,LONDON SW7 2AY,ENGLAND. US FDA,DETROIT,MI 48207. NR 19 TC 32 Z9 36 U1 2 U2 15 PU FRIEDR VIEWEG SOHN VERLAG GMBH PI WIESBADEN 1 PA PO BOX 5829, W-6200 WIESBADEN 1, GERMANY SN 0009-5893 J9 CHROMATOGRAPHIA JI Chromatographia PD JUN PY 1996 VL 42 IS 11-12 BP 639 EP 646 DI 10.1007/BF02267695 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA UX426 UT WOS:A1996UX42600005 ER PT J AU Hartman, NR OReilly, S Rowinsky, EK Collins, JM Strong, JM AF Hartman, NR OReilly, S Rowinsky, EK Collins, JM Strong, JM TI Murine and human in vivo penclomedine metabolism SO CLINICAL CANCER RESEARCH LA English DT Article ID PRECLINICAL ANTITUMOR-ACTIVITY; NSC-338720 AB Penclomedine is a multichlorinated alpha picoline derivative which has shown prominent activity in murine breast cancer models and is currently undergoing clinical development, Previous in vitro research has identified several penclomedine metabolites. In this study, human and murine in vivo penclomedine metabolism was examined, Upon i.v. administration to mice, no penclomedine was detectable in plasma at time points as early as 1 h postinfusion, The principle metabolite was demethyl-penclomedine [3,5-dichloro-2-methoxy-4-hydroxy-6-(trichloromethyl)pyridine]. Both penclomedine and demethyl-penclomedine could be recovered from tissues, Greater than 60% of the penclomedine dose remaining in the body at 22 h was indelibly bound to tissue and plasma proteins, Urinary metabolites of penclomedine consisted mainly of penclomic acid and additional polar metabolites, The results obtained after p.o. administration were nearly identical to i.v. administration with respect to the extent, level, and type of metabolites found in the plasma, tissues, and urine and with respect to the extent of protein binding, In human subjects administered penclomedine daily for 5 consecutive days, demethyl-penclomedine could be detected in plasma and accumulated with successive doses of penclomedine, reaching peak plasma concentrations of up to 10 times that of penclomedine itself and plasma exposures of nearly 400 times that of the parent drug, It appears that patients eliminate penclomedine largely through metabolism and that this drug may be amenable to p.o. administration. C1 US FDA,DIV CLIN PHARMACOL RES,OFF TESTING & RES,LAUREL,MD 20708. US FDA,CTR DRUG EVALUAT & RES,OFF PHARMACEUT SCI,LAUREL,MD 20708. JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21287. RP Hartman, NR (reprint author), US FDA,DIV CLIN PHARMACOL,ROOM 3406,MOD 1,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. FU NCI NIH HHS [CA 70095-02, N01 CM-07302]; NCRR NIH HHS [RR 00035] NR 8 TC 14 Z9 14 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN PY 1996 VL 2 IS 6 BP 953 EP 962 PG 10 WC Oncology SC Oncology GA UP184 UT WOS:A1996UP18400006 PM 9816256 ER PT J AU Cavalli, SA Otta, MI Hirata, RDC Nguyen, NY Hirata, MH AF Cavalli, SA Otta, MI Hirata, RDC Nguyen, NY Hirata, MH TI Apolipoprotein E genotyping in Brazilian normolipidemic individuals. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 UNIV SAO PAULO,FAC PHARMACEUT SCI,BR-05508 SAO PAULO,BRAZIL. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20014. RI Hirata, Mario/C-9718-2013 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 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1996 VL 42 IS 6 SU S BP 840 EP 840 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UR522 UT WOS:A1996UR52200839 ER PT J AU Wolfe, EJ Cavacini, LA Samore, MH Posner, MR Kozial, C Spino, C Trapnell, CB Ketter, N Hammer, S Gambertoglio, JG AF Wolfe, EJ Cavacini, LA Samore, MH Posner, MR Kozial, C Spino, C Trapnell, CB Ketter, N Hammer, S Gambertoglio, JG TI Pharmacokinetics of F105, a human monoclonal antibody, in persons infected with human immunodeficiency virus type 1 SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID NEUTRALIZING ANTIBODIES; HIV-1/GP120; BINDING; HIV-1 AB F105 is a human monoclonal antibody that binds to the CD4 binding site of human immunodeficiency virus type 1 gp120 and neutralizes clinical and laboratory isolates of the human immunodeficiency virus, This phase I study investigated the disposition of the antibody in humans. F105 was administered over a 60-minute period at two dose levels, 100 and 500 mg/m(2). Blood samples were obtained for up to 56 days, The clearance of the antibody was 0.33 ml/min with a corresponding half-life of approximately 13 days, Peak concentrations achieved at the higher dose level were 216.19 +/- 9.62 mu g/ml. The disposition of the drug mas linear for the doses studied, Simulations were performed to design future studies aimed at investigating the efficacy of the antibody, This study concluded that F105 can be administered as a bolus dose every 21 days. C1 UNIV CALIF SAN FRANCISCO,DEPT CLIN PHARM,SAN FRANCISCO,CA 94143. HARVARD UNIV,SCH MED,SCH PUBL HLTH,BOSTON,MA. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. US FDA,ROCKVILLE,MD 20857. NIAID,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-26926]; PHS HHS [A1-27663] NR 13 TC 18 Z9 19 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUN PY 1996 VL 59 IS 6 BP 662 EP 667 DI 10.1016/S0009-9236(96)90006-5 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UV547 UT WOS:A1996UV54700007 PM 8681491 ER PT J AU Cohn, J MacPhail, RC Paule, MG AF Cohn, J MacPhail, RC Paule, MG TI Repeated acquisition and the assessment of centrally acting compounds SO COGNITIVE BRAIN RESEARCH LA English DT Article DE repeated acquisition; learning; method ID INCREMENTAL REPEATED ACQUISITION; RADIAL-ARM MAZE; RESPONSE SEQUENCES; D-AMPHETAMINE; WORKING MEMORY; CEREBRAL-ISCHEMIA; PERFORMANCE; RATS; SCOPOLAMINE; MONKEYS AB Repeated acquisition (RA) procedures are behavioral preparations in which subjects learn new sequences of responses during each experimental session. They have been used with great success to assess the effects of drugs and other compounds on learning processes. As learning can be measured over many sessions in individual subjects, RA procedures can prove invaluable when conducting studies of the effects of chronic drug administration, aging and the long-term effects of exposure to toxic compounds. Analyzing the patterns of responding during acquisition can provide insights into the behavioral mechanisms underlying the effects of drugs and other centrally acting compounds on learning. Systematic comparisons are needed on the influence of many procedural variables on RA and the extent to which they may modulate the effects of chemicals. C1 US EPA,NATL HLTH & ENVIRONM EFFECTS RES LAB,DIV NEUROTOXICOL,RES TRIANGLE PK,NC 27711. NATL CTR TOXICOL RES,DIV NEUROTOXICOL,JEFFERSON,AR 72079. UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & TOXICOL,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT PEDIAT,LITTLE ROCK,AR 72205. RP Cohn, J (reprint author), UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC 27599, USA. NR 60 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6410 J9 COGNITIVE BRAIN RES JI Cognit. Brain Res. PD JUN PY 1996 VL 3 IS 3-4 BP 183 EP 191 DI 10.1016/0926-6410(96)00005-5 PG 9 WC Computer Science, Artificial Intelligence; Neurosciences; Neuroimaging SC Computer Science; Neurosciences & Neurology GA UU009 UT WOS:A1996UU00900004 ER PT J AU Dettmar, HP Barbour, GS Blackwell, KT Vogl, TP Alkon, DL Fry, FS Totah, JE Chambers, TL AF Dettmar, HP Barbour, GS Blackwell, KT Vogl, TP Alkon, DL Fry, FS Totah, JE Chambers, TL TI Orange juice classification with a biologically based neural network SO COMPUTERS & CHEMISTRY LA English DT Article ID RECOGNITION AB Dystal, an artificial neural network, was used to classify orange juice products. Nine varieties of oranges collected from six geographical regions were processed into single-strength, reconstituted or frozen concentrated orange juice. The data set represented 240 authentic and 173 adulterated samples of juices; 16 variables [8 flavone and flavanone glycoside concentrations measured by high-performance liquid chromatography (HPLC) and 8 trace element concentrations measured by inductively coupled plasma spectroscopy] were selected to characterize each juice and were used as input to Dystal. Dystal correctly classified 89.8% of the juices as authentic or adulterated. Classification performance increased monotonically as the percentage of pulpwash in the sample increased. Dystal correctly identified 92.5% of the juices by variety (Valencia vs non-Valencia). C1 ENVIRONM RES INST MICHIGAN,ARLINGTON,VA 22209. NINCDS,BETHESDA,MD 20892. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. FU NINDS NIH HHS [N01NS32304, N01NS02389] NR 22 TC 13 Z9 16 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0097-8485 J9 COMPUT CHEM JI Comput. Chem. PD JUN PY 1996 VL 20 IS 2 BP 261 EP 266 DI 10.1016/0097-8485(95)00015-1 PG 6 WC Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA UG116 UT WOS:A1996UG11600011 PM 8936424 ER PT J AU Unz, RF Shuttleworth, KL AF Unz, RF Shuttleworth, KL TI Microbial mobilization and immobilization of heavy metals SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Article AB Recent studies in the area of heavy metal biosorption and mobilization have addressed the selectivity of microbial sorbents in multimetal mixtures, the potential for metal uptake under natural environmental conditions, and the mechanisms of 'reactions' between metals and microbes. Results from these studies have provided a better understanding of the potential for interactive effects in complex systems and may aid in the development of predictive models. C1 NATL CTR TOXICOL RES,FOOD & DRUG ADM,DEPT HLTH & HUMAN SERV,JEFFERSON,AR 72079. RP Unz, RF (reprint author), PENN STATE UNIV,DEPT CIVIL & ENVIRONM ENGN,212 SACKETT BLDG,UNIVERSITY PK,PA 16802, USA. NR 35 TC 30 Z9 34 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD JUN PY 1996 VL 7 IS 3 BP 307 EP 310 DI 10.1016/S0958-1669(96)80035-8 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA UT526 UT WOS:A1996UT52600011 PM 8785435 ER PT J AU Schuger, L Johnson, GR Gilbride, K Plowman, GD Mandel, R AF Schuger, L Johnson, GR Gilbride, K Plowman, GD Mandel, R TI Amphiregulin in lung branching morphogenesis: Interaction with heparan sulfate proteoglycan modulates cell proliferation SO DEVELOPMENT LA English DT Article DE amphiregulin; lung development; extracellular matrix; heparan sulfate proteoglycan; cell proliferation; branching morphogenesis; mouse ID EPIDERMAL GROWTH-FACTOR; BASEMENT-MEMBRANE; EPITHELIAL-CELLS; POSSIBLE INVOLVEMENT; CHICK LUNG; EXPRESSION; SURFACE; LOCALIZATION; CARCINOMA; LAMININ AB Epithelial and mesenchymal cells isolated from mouse embryonic lungs synthesized and responded to amphiregulin (AR) in a different fashion. Mesenchymal cells produced and deposited 3- to 4-fold more AR than epithelial cells, proliferated in the presence of exogenous AR, and their spontaneous growth was blocked by up to 85% by anti-AR antibodies. In contrast, epithelial cells exhibited a broad response to this growth regulator factor depending on whether they were supplemented with extracellular matrix (ECM) and whether this ECM was of epithelial or mesenchymal origin. AR-treated epithelial cells proliferated by up to 3-fold in the presence of mesenchymal-deposited ECM, remained unchanged in the presence of epithelial-deposited ECM, and decreased in their proliferation rate below controls in the absence of ECM supplementation. This effect was abolished by treatment with the glycosaminoglycan-degrading enzymes heparinase and heparitinase suggesting the specific involvement of heparan sulfate proteoglycan (HSPG) in AR-mediated cell proliferation. In whole lung explants, branching morphogenesis was inhibited by antibodies against the AR heparan sulfate binding site and stimulated by exogenous AR. Since during development, epithelial cells are in contact with mesenchymal ECM at the tips of the growing buds and alongside the basement membrane, focal variations in the proportion of epithelial and mesenchymal HSPG will focally affect epithelial proliferation rates. Therefore, AR-HSPG interaction may underlie the process of branching morphogenesis by inducing differential cell proliferation. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. BOSTON UNIV,SCH MED,DEPT PATHOL & LAB MED,BOSTON,MA 02118. SUGEN INC,REDWOOD CITY,CA 94063. RP Schuger, L (reprint author), WAYNE STATE UNIV,SCH MED,DEPT PATHOL & LAB MED,DETROIT,MI 48201, USA. RI PLOWMAN, Greg/E-2012-2011 FU NHLBI NIH HHS [HL 48730-01] NR 42 TC 54 Z9 55 U1 1 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN PY 1996 VL 122 IS 6 BP 1759 EP 1767 PG 9 WC Developmental Biology SC Developmental Biology GA UT207 UT WOS:A1996UT20700009 PM 8674415 ER PT J AU Aoki, I Tanaka, S Ishii, N Minami, M Klinman, DM AF Aoki, I Tanaka, S Ishii, N Minami, M Klinman, DM TI Contribution of interleukin-3 to antigen-induced Th2 cytokine production SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Th2 cell; interleukin-3; non-B/non-T cell; mast cell; basophil ID CD4+ T-CELLS; BONE-MARROW; FC-EPSILON; INTERFERON-GAMMA; IMMUNE-RESPONSE; NON-B; MICE; IL-4; RECEPTORS; INFECTION AB Short-term stimulation of mouse spleen cells in vitro with interleukin (IL)-3 induces the secretion of the Th2 cytokines IL-4 and IL-6. Non-B/non-T cells were the target of this IL-3 effect. However, during long-term antigen-dependent culture, T cells are the major source of IL-4 and IL-6. The addition of IL-3 to such cultures also led to a significant increase in IL-4 and IL-6 production. This Th2 cytokine secretion was amplified by the addition of irradiated non-B/non-T cells at the initiation of culture, and was inhibited by anti-IL-4 antibodies. These findings suggest that IL-3 induces the rapid release of IL-4 and IL-6 by non-B/non-T cells, thereby creating an immune milieu conducive to the development of antigen-specific IL-4 and IL-6-secreting Th2 cells. C1 YOKOHAMA CITY UNIV,SCH MED,DEPT INTERNAL MED,YOKOHAMA,KANAGAWA 232,JAPAN. YOKOHAMA CITY UNIV,SCH MED,DEPT DERMATOL,YOKOHAMA,KANAGAWA 232,JAPAN. YOKOHAMA CITY UNIV,SCH MED,DEPT PARASITOL,YOKOHAMA,KANAGAWA 232,JAPAN. US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,SECT RETROVIRAL IMMUNOL,BETHESDA,MD. RP Aoki, I (reprint author), YOKOHAMA CITY UNIV,SCH MED,DEPT PATHOL,KANAZAWA KU,3-9 FUKU URA,YOKOHAMA,KANAGAWA 236,JAPAN. NR 38 TC 11 Z9 11 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUN PY 1996 VL 26 IS 6 BP 1388 EP 1393 DI 10.1002/eji.1830260631 PG 6 WC Immunology SC Immunology GA UQ062 UT WOS:A1996UQ06200030 PM 8647221 ER PT J AU SilvaAraujo, A Silva, MC Simon, A NguyenLegros, J Ali, SF Tavares, MA AF SilvaAraujo, A Silva, MC Simon, A NguyenLegros, J Ali, SF Tavares, MA TI The effects of prenatal exposure to cocaine on the dopaminergic cells in the rat retina. An immunocytochemical and neurochemical study SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE retina; cocaine; dopaminergic cells; tyrosine hydroxylase; prenatal exposure; immunocytochemistry; morphometry; neurochemistry; rat ID TYROSINE-HYDROXYLASE ACTIVITY; POSTNATAL-DEVELOPMENT; OPTIC-NERVE; VASCULAR DISRUPTION; BRAIN; NEURONS; SYSTEM; LIGHT; DRUGS; IMMUNOREACTIVITY AB There is a growing consensus that the development of the eye is affected by prenatal exposure to cocaine. Considering that the retina is affected by prenatal cocaine exposure, that this drug affects the dopaminergic systems, that the dopaminergic cells in the retina show a well-defined pattern of development and that they can be specifically stained in wholemounts by the antibody anti-tyrosine hydroxylase (TH), this study was undertaken to evaluate the effects of in utero cocaine exposure on the dopaminergic cells of the rat retina. Pregnant Wistar rats were given 60 mg (kg body weight)(-1) day(-1) of cocaine hydrochloride, subcutaneously, from gestational days 8 to 22. Control groups of pregnant rats were pair-fed. At PND14, 30 and 90, male offspring from different litters were perfused with fixative and the retinas processed as wholemounts and immunostained with the antibody anti-TH, Rats from other groups were decapitated at the same post-natal ages. the retinas dissected and processed by neurochemical techniques to measure the concentrations of dopamine, its metabolites and the turnover of dopamine. There was a significant increase of the retina surface area between PND14-30 in the control group, which was not found in the cocaine group. The density of the immunostained small TH cells was lower in the cocaine groups, No drug-effects were detected in the density of the large TH cells. The densities of the total large and small cells in the superior, inferior and nasal hemiretinas were similar to those found in the whole retinas: however, in the temporal hemiretinas of the cocaine groups, the density of the large TH cells was higher and of the small TH cells was lower than in controls, resulting in an absence of effects on the total density of TH-cells in this hemiretina. A transient increase in the level of dopamine metabolite (DOPAC) and of the turnover of dopamine at PND14 was detected in the cocaine groups. All quantitative parameters reached normal values, in all groups, at PND90. These results show that, during the critical periods in which catecholamines can influence the development of neurons, cocaine transiently affects the pattern of dopaminergic neurons in the retina. This may have functional importance due to the role of this neurotransmitter as a regulatory and/or trophic factor in developing neuronal circuitries. (C) 1996 Academic Press Limited C1 MED SCH PORTO, INST ANAT, P-4200 OPORTO, PORTUGAL. UNIV PORTO, INST MOLEC & CELLULAR BIOL, P-4100 OPORTO, PORTUGAL. UNIV PORTO, INST BIOMED SCI ABEL SALAZAR, LAB BIOMETRY, P-4100 OPORTO, PORTUGAL. INSERM U86, LAB NEUROCYTOL OCULAIRE, PARIS, FRANCE. NATL CTR TOXICOL RES, DIV NEUROTOXICOL, NEUROCHEM LAB, JEFFERSON, AR 72079 USA. OI Ferreira, Maria/0000-0001-6789-3796 NR 64 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JUN PY 1996 VL 62 IS 6 BP 697 EP 708 DI 10.1006/exer.1996.0080 PG 12 WC Ophthalmology SC Ophthalmology GA UT616 UT WOS:A1996UT61600012 PM 8983951 ER PT J AU Ndimbie, OK Kingsley, LA Nedjar, S Rinaldo, CR AF Ndimbie, OK Kingsley, LA Nedjar, S Rinaldo, CR TI Hepatitis C virus infection in a male homosexual cohort: Risk factor analysis SO GENITOURINARY MEDICINE LA English DT Article DE hepatitis C; STD; transmission ID HUMAN-IMMUNODEFICIENCY-VIRUS; MULTICENTER AIDS COHORT; VOLUNTEER BLOOD-DONORS; NON-B HEPATITIS; SEXUAL TRANSMISSION; LIVER-DISEASE; HEPATOCELLULAR-CARCINOMA; NATURAL-HISTORY; UNITED-STATES; HCV ANTIBODY AB Background: Hepatitis C virus (HCV) infection is a major cause of morbidity throughout the world. Parenteral exposure to infected blood accounts for the majority of cases. Sexual transmission is suggested by the higher prevalence of infection in sex workers and homosexual men. Sexual practices which contribute to HCV infection need to be identified. Methods: The social and medical history, and HCV serostatus of 1058 homosexual men in the Pittsburgh arm of the Multicenter AIDS Cohort Study were analysed. Multivariate analysis was used to determine risk factors for HCV seropositivity. Results: 31 men were HCV seropositive by enzyme immunoassay and recombinant immunoblot assay (2.9%). They were more likely to be HIV seropositive (39%) than the HCV seronegative men (19%). Needle sharing and illegal drug use were the most important risk factors for HCV seropositivity. Statistically significant sexual factors (p < 0.05) included a history of syphilis, rectal gonorrhea, anal insertive intercourse with ejaculation, and douche or enema use before anal receptive intercourse. The number of sexual partners was not a significant risk factor. Conclusions: HCV infection is associated with specific sexually transmitted diseases (STDs) and sexual practices in the male homosexual population. The evidence of high risk behavior should be incorporated into ongoing educational efforts to decrease the incidence of STDs. C1 UNIV PITTSBURGH,DEPT INFECT DIS & MICROBIOL,PITTSBURGH,PA 15260. UNIV PITTSBURGH,DEPT EPIDEMIOL,PITTSBURGH,PA 15260. US FDA,DIV TRANSFUS MED,HEPATATIS LAB,KENSINGTON,MD. RP Ndimbie, OK (reprint author), UNIV PITTSBURGH,MED CTR,DEPT PATHOL,200 LOTHROP ST,PITTSBURGH,PA 15213, USA. FU NIAID NIH HHS [U01-AI-35041, N01-AI-72632] NR 34 TC 48 Z9 48 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0266-4348 J9 GENITOURIN MED JI Genitourin. Med. PD JUN PY 1996 VL 72 IS 3 BP 213 EP 216 PG 4 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Urology & Nephrology SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Urology & Nephrology GA UR350 UT WOS:A1996UR35000014 PM 8707327 ER PT J AU Devi, SJN Hayat, U Powell, JL Morris, JG AF Devi, SJN Hayat, U Powell, JL Morris, JG TI Preclinical immunoprophylactic and immunotherapeutic efficacy of antisera to capsular polysaccharide-tetanus toxoid conjugate vaccines of Vibrio vulnificus SO INFECTION AND IMMUNITY LA English DT Article ID LIVER-DISEASE; LIPID-A; VIRULENCE; INFECTION; SEPTICEMIA; MICE; CYTOLYSIN; FEATURES; PROTEASE; ADJUVANT AB Vibrio vulnificus is an oyster-associated bacterial pathogen that causes life-threatening fulminating septicemia and necrotizing wound infections in humans. The capsular polysaccharide of V. vulnificus (VvPS) is critical for virulence. Previously we showed that active immunization of mice with a VvPS-tetanus toroid (VvPS-TTa) conjugate vaccine conferred significantly higher protection against subsequent lethal challenge than immunization with VvPS alone. In the current study, we examined the utility of immunoprophylaxis or immunotherapy with hyperimmune antisera elicited by VvPS-TTa and VvPS-TTb conjugate vaccines prepared by different synthetic schemes. First we demonstrated that the Ribi adjuvant significantly enhanced the murine antibody response (P less than or equal to 0.02) to both conjugates. Subsequently, high-titered polyclonal antisera were raised to VvPS-TTa and VvPS-TTb conjugate vaccines by using Ribi adjuvant or Freund's adjuvants. Antisera were observed to have protective effects when administered before and after acute lethal infection. All animals receiving prophylactic antisera intraperitoneally 24 h before lethal challenge with homologous carbotype 1 were protected, while 73 to 100% of control mice succumbed. Immunotherapy was also effective, with survival rates of 60 to 73% seen among mice when antisera were administered 2 h after bacterial challenge, at a time when symptoms of infection were already apparent. The protective effect of capsular antiserum appeared to be serotype specific. Antisera to the carbotype 1 VvPS-TTa vaccine did not confer cross-protection against lethal challenge with carbotype 2 V. vulnificus despite partial structural similarity and a weak serological cross-reaction between the two carbotypes. Immune globulins induced by a potential multivalent VvPS conjugate vaccine composed of clinically prevalent carbotypes may have utility in the management of V. vulnificus infections and deserve further evaluation. C1 VET AFFAIRS MED CTR,INFECT DIS SECT,BALTIMORE,MD 21201. US FDA,DIV BACTERIAL PROD,OFF VACCINE RES & REVIEW,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,CTR VACCINE DEV,BALTIMORE,MD 21201. NR 40 TC 20 Z9 20 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 1996 VL 64 IS 6 BP 2220 EP 2224 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UN189 UT WOS:A1996UN18900048 PM 8675330 ER PT J AU Fleckenstein, JM Kopecko, DJ Warren, RL Elsinghorst, EA AF Fleckenstein, JM Kopecko, DJ Warren, RL Elsinghorst, EA TI Molecular characterization of the tia invasion locus from enterotoxigenic Escherichia coli SO INFECTION AND IMMUNITY LA English DT Article ID UNDIFFERENTIATED HUMAN DIARRHEA; EPITHELIAL-CELL INVASION; TISSUE-CULTURE CELLS; CYTOPLASMIC MEMBRANE; ENHANCED TOXICITY; BACTERIOPHAGE-MU; DNA FRAGMENTS; PROTEIN; COLONIZATION; CLONING AB Enterotoxigenic Escherichia call (ETEC) shares with other diarrheal pathogens the capacity to invade epithelial cell lines originating from the human ileum or colon, although the role of invasion in ETEC pathogenesis remains undefined. Two distinct loci (tia and tib) that direct noninvasive E. coli to adhere to and invade intestinal epithelial cell lines have previously been isolated from cosmid libraries of the classical ETEC strain H10407. Here, we report the molecular characterization of the tia locus. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of cellular fractions of E. coli DH5 alpha carrying the tia-positive cosmids and recombinant plasmid subclones revealed that this locus directs the production of a 25-kDa protein (the Tia protein) that is localized to the outer membrane. The tia locus was subcloned to a maximum of 2 kb and mutagenized with bacteriophage Mud. Synthesis of this protein was directly correlated with the ability of subclones and Mud transposon mutants to adhere to and invade epithelial cells. Sequencing of the tia locus identified a 756-bp open reading frame. All transposon insertions resulting in an invasion-negative phenotype mapped to this open reading frame. The open reading frame was amplified and directionally cloned behind the inc promoter of pHG165. This construct directed DH5 alpha to express a 25-kDa protein and to adhere to and invade epithelial cells. The role of the tia gene in directing epithelial adherence and invasion was further assessed by the construction of chromosomal tia deletion derivatives of the parent ETEC strain, H10407. These tia deletion strains were noninvasive and lacked the ability to adhere to human ileocecal cells. The tia gene shares limited homology with the Yersinia ail locus and significant homology with the hra1 agglutinin gene cloned from a porcine ETEC strain. Additionally, tia probes hybridized to geographically diverse ETEC strains, as well as some enteropathogenic E. coli, enteroaggregative E. coli, and Shigella sonnei strains. C1 WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,WASHINGTON,DC 20307. US FDA,LAB ENTER & SEXUALLY TRANSMITTED DIS,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. UNIV KANSAS,DEPT MICROBIOL,LAWRENCE,KS 66045. RP Fleckenstein, JM (reprint author), WALTER REED ARMY MED CTR,DIV INFECT DIS,DEPT MED,WASHINGTON,DC 20307, USA. OI Fleckenstein, James/0000-0002-1148-697X NR 54 TC 76 Z9 76 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 1996 VL 64 IS 6 BP 2256 EP 2265 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UN189 UT WOS:A1996UN18900053 PM 8675335 ER PT J AU Snapper, CM Rosas, F Moorman, MA Jin, L Shanebeck, K Klinman, DM Kehry, MR Mond, JJ Maliszewski, CR AF Snapper, CM Rosas, F Moorman, MA Jin, L Shanebeck, K Klinman, DM Kehry, MR Mond, JJ Maliszewski, CR TI IFN-gamma is a potent inducer of Ig secretion by sort-purified murine B cells activated through the mIg, but not the CD40, signaling pathway SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE anti-Ig-dextran; CD40 ligand; IgA; granulocyte-macrophage colony stimulating factor (GM-CSF); IL-1; IL-2; IL-3 ID FOLLICULAR DENDRITIC CELLS; INTERFERON-GAMMA; IMMUNE-RESPONSE; LYMPHOCYTE-B; T-CELLS; DIFFERENTIATION; ANTIGEN; ANTIBODIES; PROLIFERATION; STIMULATION AB IFN-gamma has been shown to either stimulate or inhibit Ig secretion, No studies have yet addressed the basis for these seemingly conflicting properties nor whether IFN-gamma acted directly at the level of the B cell to mediate its effects, Thus, we studied the ability of IFN-gamma to regulate Ig secretion in sort-purified, resting murine B cells that were >99% Ig(+), activated either through membrane Ig using unconjugated or dextran-conjugated anti-IgD antibodies (as-dex) or through CD40 using soluble or membrane CD40 ligand (CD40L), B cells activated with alpha delta-dex proliferate but do not secrete Ig, even in the presence of IL-l + IL-2, We demonstrate that IFN-gamma only when added subsequent to B cell stimulation with alpha delta-dex, but not unconjugated anti-IgD antibody, plus IL-l + IL-2 induces up to 100-fold enhancements in Ig secretion and in the numbers of Ig-secreting cells, The predominant Ig isotype secreted is IgM, with IgG3 and IgG2a comprising the majority of non-IgM antibody, IFN-gamma must act in concert with IL-2 for stimulation of Ig secretion, Further, IFN-gamma synergizes with IL-3 + granulocyte-macrophage colony stimulating factor for induction of Ig synthesis, IFN-gamma also enhances IgA synthesis by transforming growth factor-beta-induced membrane IgA(+) cells, By contrast, IFN-gamma fails to stimulate Ig secretion in B cells activated with CD40L in the presence or absence of IL-l + IL-2 or IL-4, However, the combination of CD40L and alpha delta-dex is strongly synergistic for IFN-gamma-induced Ig secretion, Thus, these data establish that IFN-gamma can act directly on the B cell to induce Ig synthesis without the participation of any other cell and demonstrates that the mode of activation of the B cell plays an important role in directing the action of IFN-gamma. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,BIOMED INSTRUMENTAT CTR,BETHESDA,MD 20814. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. BOEHRINGER INGELHEIM PHARMACEUT INC,RIDGEFIELD,CT 06877. IMMUNEX RES & DEV CORP,SEATTLE,WA 98101. RP Snapper, CM (reprint author), UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,4301 JONES BRIDGE RD,BETHESDA,MD 20814, USA. FU NIAID NIH HHS [AI36588, AI32560] NR 53 TC 30 Z9 30 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUN PY 1996 VL 8 IS 6 BP 877 EP 885 DI 10.1093/intimm/8.6.877 PG 9 WC Immunology SC Immunology GA UU915 UT WOS:A1996UU91500008 PM 8671677 ER PT J AU Hitchins, AD AF Hitchins, AD TI Assessment of alimentary exposure to Listeria monocytogenes SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE foodborne Listeria monocytogenes; ready-to-eat foods; dietary intake; alimentary exposure ID SPORADIC LISTERIOSIS; FOODS; EPIDEMIOLOGY; BRITAIN AB Survey data on the frequency of foodborne occurrence and dietary exposure to Listeria monocytogenes were used to estimate the mininmal mean per person annual rate of exposure in the United States during the late 1980s. The estimate was restricted to ready-to-eat (RTE) foods because proper cooking was assumed to be listericidal. The mean amount of each food type per L. monocytogenes occurrence was calculated in about 100 sources, and dietary intake data were used to calculate the mean number of occurrences of L. monocytogenes consumption per person per year. The mean number of occurrences-consumed annually per person was determined to be 10 to 100 for RTE food values of 2 to 20% of the total dietary intake, respectively. The frequency of foodborne listeriosis (approximate to 10(-5)) was consistent with the estimated exposure rate only if the susceptible population was unexpectedly small or extremely high doses were necessary for;infection. Because little evidence is available to support a high rate of unreported non-severe infections, this study was concerned only with severe listeriosis cases. Published frequencies of L. monocytogenes concentrations in food were used to convert occurrences to colony forming units (CFU). Low L. monocytogenes concentrations (approximate to 1 CFU/g) were too frequent to be responsible for listeriosis in susceptible subjects, would have caused listeriosis only with extremely low probability in a one-cell threshold infection model. The probability of exposure to a higher dose (greater than or equal to 10(3) CFU) was large enough to account for the observed rate of listeriosis. RP Hitchins, AD (reprint author), US FDA, DIV MICROBIOL STUDIES HFS516, 200 C ST SW, WASHINGTON, DC 20204 USA. NR 40 TC 44 Z9 45 U1 1 U2 5 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 PY 1996 VL 30 IS 1-2 BP 71 EP 85 DI 10.1016/0168-1605(96)00992-0 PG 15 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA VB143 UT WOS:A1996VB14300007 PM 8856375 ER PT J AU Matchette, LS Vegella, TJ AF Matchette, LS Vegella, TJ TI Glutaraldehyde retains its disinfectant properties in presence of hydroxypropylmethyl cellulose(HPMC) gel SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article AB Explanted medical devices are routinely sent to laboratories at the Center for Devices and Radiological Health for analysis, The shipping of these devices presents potential hazards to personnel as well as an opportunity for damage to the devices. In an effort to address these concerns, a viscous disinfecting shipping medium that would limit splashing and cushion a suspended device was proposed, Consequently, we investigated the disinfectant properties of adding a gelling agent, hydroxypropylmethyl cellulose (HPMC) to common disinfectants, We found that the germicidal effectiveness of 2.5% glutaraldehyde in 0.05 M borax when tested against Bacillus subtilis spores was not changed by the addition of 2% HPMC, In addition, HPMC appears to be compatible with 70% ethanol and at least one commercial disinfectant containing a quaternary ammonium compound, Preliminary experiments indicate that an HPMC-disinfectant gel is a potentially useful packaging agent for minimizing the hazards to personnel and materials during shipping of explanted medical devices, The use of such a medium would be subject to guidelines within the context of a program for handling biologically contaminated materials. (C) 1996 John Wiley & Sons, Inc.* RP Matchette, LS (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,MAIL STOP HFZ-134,ROCKVILLE,MD 20857, USA. NR 3 TC 0 Z9 0 U1 1 U2 4 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD SUM PY 1996 VL 33 IS 2 BP 101 EP 105 DI 10.1002/(SICI)1097-4636(199622)33:2<101::AID-JBM6>3.0.CO;2-V PG 5 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA UN017 UT WOS:A1996UN01700006 PM 8736028 ER PT J AU Chapekar, MS Zaremba, TG Kuester, RK Hitchins, VM AF Chapekar, MS Zaremba, TG Kuester, RK Hitchins, VM TI Synergistic induction of tumor necrosis factor alpha by bacterial lipopolysaccharide and lipoteichoic acid in combination with polytetrafluoroethylene particles in a murine macrophage cell line RAW 264.7 SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article ID TISSUE-INJURY; INTERLEUKIN-1; CACHECTIN; INVITRO; SHOCK AB The induction of tumor necrosis factor alpha (TNF-alpha) by polytetrafluoroethylene (PTFE) particles (5-50 mu m) and by bacterial lipopolysaccharide (LPS) and lipoteichoic acid (LTA) was examined in RAW cell cultures. Twenty-four-hour culture supernatants from the treated and control cells were assayed for TNF-alpha using a mouse L929 cell cytotoxicity assay. Untreated RAW cells produced low levels of endogenous TNF-alpha in the culture supernatants. Addition of 0.5 ng to 1 mu g/mL LPS or 1 ng to 1 mu g/ml LTA increased the TNF-alpha production by 7-3570-fold and 2-815-fold, respectively. Addition of 1-5 mg PTFE increased the TNF-alpha production by 6-17-fold over the untreated control cell levels. The cells exposed to PTFE and 0.5 ng/mL LPS or 5 ng/mL LTA produced TNF-alpha levels that were significantly higher than those produced by any inducer alone. Thus, both LTA, a Gram-positive bacterial cell wall component and LPS, a Gram-negative bacterial cell wall component, can induce TNF-cr production, which is further enhanced by PTFE particles in RAW cells. (C) 1996 John Wiley & Sons, Inc. C1 US FDA, CTR DEVICES & RADIOL HLTH, ROCKVILLE, MD 20857 USA. RP Chapekar, MS (reprint author), CTR BIOL EVALUAT & RES, HFM 591, 1401 ROCKVILLE PIKE, ROCKVILLE, MD 20852 USA. NR 17 TC 33 Z9 33 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD JUN PY 1996 VL 31 IS 2 BP 251 EP 256 DI 10.1002/(SICI)1097-4636(199606)31:2<251::AID-JBM12>3.0.CO;2-O PG 6 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA UG003 UT WOS:A1996UG00300012 PM 8731214 ER PT J AU Sakatsume, M Finbloom, DS AF Sakatsume, M Finbloom, DS TI Modulation of the expression of the IFN-gamma receptor beta-chain controls responsiveness to IFN-gamma in human peripheral blood T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN INTERFERON-GAMMA; HUMAN-MONOCYTES; GENE; INDUCTION; PROMOTER; BINDING; LINES AB IFN-gamma has potent antiproliferative and apoptotic effects in T cells that are important in determining T cell development and polarized differentiation. Therefore, any event that enables T cells to become less responsive to IFN-gamma may potentially alter immune responsiveness to Ag, In this work, rye show that human peripheral blood T cells that are stimulated through the TCR and expanded with IL-2 are unresponsive to IFN-gamma, as determined by a lack of activation of Jak kinases and the transcription factor, STAT1 alpha, a signal transducer and activator of transcription, This nonresponsiveness occurs because of a lack of expression of the beta-chain (accessory factor) of the IFN-gamma receptor, while at the same time maintaining IFN-gamma receptor alpha-chain expression, Expression of the beta-chain can be restored by secondary TCR ligation or PMA treatment, T cell blasts treated with PMA are now responsive to IFN-gamma. When freshly isolated, highly enriched (>98%) T cells are examined for IFN-gamma responsiveness; these cells can respond to IFN-gamma and express beta-chain. Therefore, as T cells progress from primary TCR activation through IL-2-dependent proliferation, followed by secondary TCR stimulation, their responsiveness to IFN-gamma varies, and this may affect their ability to participate in an ongoing immune response. C1 US FDA,DIV CYTOKINE BIOL,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 28 TC 38 Z9 39 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 1996 VL 156 IS 11 BP 4160 EP 4166 PG 7 WC Immunology SC Immunology GA UM244 UT WOS:A1996UM24400014 PM 8666783 ER PT J AU Wahl, SM Feldman, GM McCarthy, JB AF Wahl, SM Feldman, GM McCarthy, JB TI Regulation of leukocyte adhesion and signaling in inflammation and disease SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article ID PROTEIN TYROSINE PHOSPHORYLATION; TUMOR-NECROSIS-FACTOR; CELL-ADHESION; ENDOTHELIAL-CELLS; GROWTH-FACTOR; P-SELECTIN; EXTRACELLULAR-MATRIX; ALPHA-4 INTEGRIN; HEPARAN-SULFATE; HUMAN MONOCYTES AB Cell adhesion molecules provide the foundation for cell communication, trafficking, and immune surveillance central to host defense, These adhesion molecules which include selectins, integrins and members of the Ig superfamily, provide a recognition system between leukocytes, endothelial cells and matrix molecules. Leukocyte-endothelial interactions initiate recruitment at sites of injury, infection and inflammation, Cell-cell and cell-matrix interactions also influence leukocyte phenotype and function. Dysregulation of these adhesion and signal transduction pathways can contribute to continued recruitment and persistent leukocyte activation with unresolved inflammation, Based on the pivotal role adhesive interactions play, the adhesion molecules provide potential targets for intervention, Selected synthetic fibronectin peptides, which inhibit leukocyte integrin binding and signal transduction in vibro, block recruitment and activation to limit inflammation in vivo. C1 US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20014. UNIV MINNESOTA,DEPT PATHOL & MED,MINNEAPOLIS,MN 55455. RP Wahl, SM (reprint author), NIDR,NIH,CELL IMMUNOL SECT,BLDG 30,RM 331,BETHESDA,MD 20892, USA. NR 94 TC 58 Z9 60 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUN PY 1996 VL 59 IS 6 BP 789 EP 796 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA UV313 UT WOS:A1996UV31300004 PM 8691062 ER PT J AU Weisz, A Andrzejewski, D Mandelbaum, A AF Weisz, A Andrzejewski, D Mandelbaum, A TI Fragmentation of isomeric N-quinolinylphthalimides on electron impact ionization SO JOURNAL OF MASS SPECTROMETRY LA English DT Article DE N-quinolinylphthalimides; electron impact ionization; collision-induced dissociation; positional isomers; fragmentation mechanism AB The isomeric 2, 3-, 5-, 6- and 8-quinolinylphthalimides give rise to different electron impact ionization mass spectra, which permit easy distinction, The specific fragmentation processes are rationalized in terms of proximity effects and stabilization of cyclic ion structures, Collision-induced dissociation spectra were used to support the proposed ion structures of major fragment ions. C1 US FDA,OFF SCI ANAL & SUPPORT,WASHINGTON,DC 20204. TECHNION ISRAEL INST TECHNOL,DEPT CHEM,IL-32000 HAIFA,ISRAEL. RP Weisz, A (reprint author), US FDA,OFF COSMET & COLORS,WASHINGTON,DC 20204, USA. NR 7 TC 6 Z9 6 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1076-5174 J9 J MASS SPECTROM JI J. Mass Spectrom. PD JUN PY 1996 VL 31 IS 6 BP 676 EP 680 DI 10.1002/(SICI)1096-9888(199606)31:6<676::AID-JMS342>3.3.CO;2-Z PG 5 WC Biophysics; Chemistry, Organic; Spectroscopy SC Biophysics; Chemistry; Spectroscopy GA UQ849 UT WOS:A1996UQ84900015 PM 8799302 ER PT J AU Holcomb, M Thompson, HC Cooper, WM Hopper, ML AF Holcomb, M Thompson, HC Cooper, WM Hopper, ML TI SFE extraction of aflatoxins (B-1, B-2, G(1), and G(2)) from corn and analysis by HPLC SO JOURNAL OF SUPERCRITICAL FLUIDS LA English DT Article DE aflatoxins; mycotoxins; SFE; HPLC ID SUPERCRITICAL-FLUID EXTRACTION AB A supercritical-fluid extraction (SFE) method has been developed that extracts aflatoxins B-1, B-2, G(1), and G(2) from spiked corn using modified supercritical carbon dioxide. Methanol is added to the SFE extraction cell containing the corn layered between Hydromatrix (a dispersing material) which helps to prevent the clogging of the frits and reduces the effect of moisture on the extraction. The corn is held in static extraction at 65 degrees C and 51.7 MPa for 15 min followed by a dynamic extraction with 20 mL of liquid carbon dioxide. The sample is depressurized and modifier re-added with a 10-min static extraction at 51.7 MPa followed by a dynamic extraction with 20 mt of liquid carbon dioxide. The SFE extract is collected in 10 mL of chloroform and further cleaned up with a Florisil Sep-Pak. The aflatoxins were analyzed by HPLC using fluorescence detection after post-column derivatization with iodine. Recoveries of the aflatoxins B-1, B-2, G(1), and G(2) over a range of 3 to 11 ng g(-1) averaged 77.3, 82.9, 75.4, and 80.3%, respectively. C1 US FDA,TOTAL DIET RES CTR,LENEXA,KS 66285. RP Holcomb, M (reprint author), US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 6 TC 25 Z9 25 U1 0 U2 0 PU PRA PRESS PI CINCINNATI PA POLYMER RES ASSOC INC 9200 MONTGOMERY RD, SUITE 23B, CINCINNATI, OH 45242 SN 0896-8446 J9 J SUPERCRIT FLUID JI J. Supercrit. Fluids PD JUN PY 1996 VL 9 IS 2 BP 118 EP 121 DI 10.1016/S0896-8446(96)90007-8 PG 4 WC Chemistry, Physical; Engineering, Chemical SC Chemistry; Engineering GA UZ737 UT WOS:A1996UZ73700008 ER PT J AU Culp, SJ Beland, FA AF Culp, SJ Beland, FA TI Malachite green: A toxicological review SO JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY LA English DT Article DE malachite green; leuco-malachite green; triphenylmethane dyes; gentian violet; carcinogenicity; mutagenicity ID HAMSTER EMBRYO CELLS; GENTIAN-VIOLET; RAINBOW-TROUT; TRIPHENYLMETHANE DYES; DNA; AQUACULTURE; TOXICITY; AZO; RAT AB Malachite green, an N-methylated diaminotriphenylmethane dye, is used primarily as a therapeutic agent in aquaculture. In solution, the dye exists as a mixture of the cation (chromatic malachite green) and its carbinol base, with the ratio depending on the pH of the solution; the dye also can undergo chemical and metabolic reduction to a leuco derivative. Analysis of fish tissue after exposure to malachite green indicates the presence of both chromatic and leuco forms, with the latter having a much longer tissue half-life. Malachite green intercalates with DNA, with a preference for A:T-rich regions, and the leuco derivative bears a structural resemblance to carcinogenic aromatic amines that can form covalent DNA adducts. Malachite green is mutagenic in Salmonella typhimurium TA98 in the presence of an exogenous metabolizing system. In mammalian cells, it shows marked cytotoxicity and the ability to induce cell transformation and lipid peroxidation. Results from carcinogenicity bioassays with malachite green have been equivocal; however, it appears to act as a tumor promoter, perhaps because of its ability to induce the formation of reactive oxygen species. These characteristics, plus its close structural similarity to carcinogenic triphenylmethane dyes (e.g., gentian violet) suggest that additional data are required to determine if human exposure to malachite green results in adverse health effects. RP Culp, SJ (reprint author), NATL CTR TOXICOL RES,HFT-110,JEFFERSON,AR 72079, USA. NR 80 TC 223 Z9 238 U1 9 U2 59 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0730-0913 J9 J AM COLL TOXICOL JI J. Am. Coll. Toxicol. PD JUN PY 1996 VL 15 IS 3 BP 219 EP 238 PG 20 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA UV103 UT WOS:A1996UV10300004 ER PT J AU Kolykhalov, AA Feinstone, SM Rice, CM AF Kolykhalov, AA Feinstone, SM Rice, CM TI Identification of a highly conserved sequence element at the 3' terminus of hepatitis C virus genome RNA SO JOURNAL OF VIROLOGY LA English DT Article ID NON-A; REGIONS; ORGANIZATION AB Previous reports suggest that the hepatitis C virus (HCV) genome RNA terminates with homopolymer tracts of either poly(U) or poly(A), By ligation of synthetic oligonucleotides followed by reverse transcription-PCR, cDNA cloning, and sequence analysis, we determined the 3'-terminal sequence of HCV genome RNA, Our results show that the HCV 3' nontranslated region consists of four elements (positive sense, 5' to 3'): (i) a short sequence with significant variability among genotypes, (ii) a homopolymeric poly(U) tract, (iii) a polypyrimidine stretch consisting of mainly U with interspersed C residues, (iv) a novel sequence of 98 bases, This latter nucleotide sequence is not present in human genomic DNA and is highly conserved among HCV genotypes, The 3'-terminal 46 bases are predicted to form a stable stem-loop structure, Using a quantitative competitive reverse transcription-PCR assay, we show that a substantial fraction of HCV genome RNAs from a high-specific-infectivity inoculum contain this 3'-terminal sequence element, These results indicate that the HCV genome RNA terminates with a highly conserved RNA element which is likely to be required for authentic HCV replication and recovery of infectious RNA from cDNA. C1 WASHINGTON UNIV,SCH MED,DEPT MOLEC MICROBIOL,ST LOUIS,MO 63110. US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,BETHESDA,MD 20892. FU NCI NIH HHS [CA57973] NR 40 TC 311 Z9 318 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1996 VL 70 IS 6 BP 3363 EP 3371 PG 9 WC Virology SC Virology GA UL104 UT WOS:A1996UL10400005 PM 8648666 ER PT J AU Guilfoyle, DE Hirshfield, IN AF Guilfoyle, DE Hirshfield, IN TI The survival benefit of short-chain organic acids and the inducible arginine and lysine decarboxylase genes for Escherichia coli SO LETTERS IN APPLIED MICROBIOLOGY LA English DT Article ID TOLERANCE RESPONSE; RESISTANCE; GROWTH AB The short-chain organic acids (SCOAs), acetic and propionic acids, are used widely as food preservatives, The production of these two acids plus butyric acid in the colon by anaerobes serves as a mechanism for controlling the numbers of enterobacteria (which can be pathogens) in this organ. It has been found in this study that the acid tolerance of cells initially grown at near neutral pH (6.5) to a lethal pH of 3.5 is enhanced by their exposure to 0.1% propionate or butyrate. The data also indicate that the inducible arginine and lysine decarboxylases are important for the survival of Escherichia coli exposed to a combination of mildly acidic pH (5.5) and 0.5% butyrate. This study suggests that the presence of SCOAs could trigger an adaptive survival response which may be important in the survival of food-borne pathogens. C1 ST JOHNS UNIV,DEPT BIOL SCI,JAMAICA,NY 11439. US FDA,NE REG LAB,BROOKLYN,NY. NR 18 TC 26 Z9 26 U1 0 U2 5 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0266-8254 J9 LETT APPL MICROBIOL JI Lett. Appl. Microbiol. PD JUN PY 1996 VL 22 IS 6 BP 393 EP 396 DI 10.1111/j.1472-765X.1996.tb01187.x PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA UQ741 UT WOS:A1996UQ74100002 PM 8695061 ER PT J AU Corfman, P Dutta, S Golden, L Price, P Rarick, L Stadel, B Troendle, G AF Corfman, P Dutta, S Golden, L Price, P Rarick, L Stadel, B Troendle, G TI Guidance for clinical evaluation of combination estrogen/progestin-containing drug products used for hormone replacement therapy (HRT) of postmenopausal women SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Letter RP Corfman, P (reprint author), US FDA,FDA HRT WORKING GRP,ROCKVILLE,MD 20857, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD SUM PY 1996 VL 3 IS 2 BP 117 EP 118 DI 10.1097/00042192-199603020-00009 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA UM133 UT WOS:A1996UM13300009 ER PT J AU Lin, DT Goldman, ND Syin, C AF Lin, DT Goldman, ND Syin, C TI Stage-specific expression of a Plasmodium falciparum protein related to the eukaryotic mitogen-activated protein kinases SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Plasmodium falciparum; PfMRP; mitogen-activated protein kinase; developmental regulation ID CONTINUOUS CULTURE; MALARIA PARASITES; PHOSPHORYLATION; CEREVISIAE; BERGHEI; FAMILY; DNA AB We have identified a putative protein kinase gene from both Plasmodium falciparum cDNA and genomic DNA libraries. The nucleotide sequence contains an open-reading frame of 2646 bp, which codes for a predicted protein of 882 amino acid residues. Comparison of the predicted amino acid sequence with those in GenBank suggests that this gene codes for a protein similiar to the mitogen-activated protein (MAP) kinase of other organisms. This MAP kinase-related protein, named PfMRP, contains the TDY dual phosphorylation site upstream of the highly conserved VATRWYRAPE sequence in subdomain VIII. PfMRP contains an unusually large and highly charged domain within its carboxyl-terminal segment, which includes two repetitive sequences of either a tetrapeptide or octapeptide motif. PfMRP gene is located on chromosome 14. Northern blot analysis of total RNA reveals the presence of a single mRNA transcript similar to 4.2 kb in length, which is predominantly expressed in gametocytes and gametes/zygotes. C1 US FDA, LAB PARASIT BIOL & BIOCHEM, DIV ALLERGEN PROD & PARASITOL, OFF VACCINE REVIEW & RES, ROCKVILLE, MD 20852 USA. NR 37 TC 37 Z9 37 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 EI 1872-9428 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JUN PY 1996 VL 78 IS 1-2 BP 67 EP 77 DI 10.1016/S0166-6851(96)02608-4 PG 11 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA UW159 UT WOS:A1996UW15900007 PM 8813678 ER PT J AU Brundage, JF Gunzenhauser, JD Longfield, JN Rubertone, MV Ludwig, SL Rubin, FA Kaplan, EL AF Brundage, JF Gunzenhauser, JD Longfield, JN Rubertone, MV Ludwig, SL Rubin, FA Kaplan, EL TI Epidemiology and control of acute respiratory diseases with emphasis on Group A beta-hemolytic Streptococcus: A decade of US Army experience SO PEDIATRICS LA English DT Article; Proceedings Paper CT Conference on Group-A Streptococcal Infections CY JAN 20-22, 1995 CL TAMPA, FL SP Wyeth Ayerst Labs, St Davids DE Streptococcus; surveillance; respiratory disease; US Army; benzathine penicillin ID PYOGENES INFECTION; PENICILLIN-G; PROPHYLAXIS; BENZATHINE AB Objective. To summarize the experiences of the U.S. Army regarding prevention and control, and frequencies, rates, trends, and determinants of febrile acute respiratory diseases (ARDs), particularly Group A beta-hemolytic streptococcus (GABHS). Methodology. Since 1966, the U.S. Army has conducted routine surveillance of ARDs among basic trainees. Since 1985, all trainees with fever and respiratory tract symptoms have been cultured for GABHS. Field investigations were conducted when outbreaks of acute respiratory or GABHS-associated illnesses were detected. Mass plus tandem benzathine penicillin prophylaxis were used to interdict and control training center GABHS outbreaks. Results. During the period 1985 to 1994, there were 65 184 hospitalizations for acute febrile respiratory illnesses among Army trainees. The crude hospitalization rate was 0.45 per 100 trainees per week. The rate consistently declined over the period. Incremental declines were temporally associated with increased use of adenovirus immunizations and broader use of benzathine penicillin prophylaxis. During the period, 10 789 of 59 818 (18%) pharyngeal cultures were positive for GABHS. GABHS outbreaks were associated with diverse clinical manifestations including streptococcal toxic shock, acute rheumatic fever, and pneumonia. The emergence of mucoid colony morphology in clinical isolates was a consistent indicator of circulating virulent strains with epidemic potential. Outbreak-associated M types were M1, M3, M5, and M18. In response to six GABHS outbreaks, mass plus tandem benzathine penicillin chemoprophylaxis produced rapid and sustained GABHS control. ARD and GABHS recovery rates were lowest when benzathine penicillin prophylaxis was widely used. Conclusions. ARD rates among Army trainees have consistently declined to unprecedented levels. GABHS has reemerged as an important threat to military trainees. Benzathine penicillin chemoprophylaxis is safe and effective for interdicting and preventing GABHS outbreaks in closed, healthy young adult populations. C1 MADIGAN ARMY MED CTR,PREVENT MED SERV,TACOMA,WA 98431. BROOKE ARMY MED CTR,DEPT CLIN INVEST,FT SAM HOUSTON,TX 78234. US FDA,ROCKVILLE,MD 20857. UNIV MINNESOTA,SCH MED,DEPT PEDIAT,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,SCH MED,WHO COLLABORATING CTR REFERENCE & RES STREPTOCOCC,MINNEAPOLIS,MN 55455. RP Brundage, JF (reprint author), USA,CTR HLTH PROMOT & PREVENT MED,EPIDEMIOL & DIS SURVEILLANCE DIRECTORATE,ABERDEEN PROVING GROUND,MD 21010, USA. NR 16 TC 37 Z9 37 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUN PY 1996 VL 97 IS 6 SU S BP 964 EP 970 PG 7 WC Pediatrics SC Pediatrics GA UQ090 UT WOS:A1996UQ09000006 PM 8637783 ER PT J AU Godar, DE AF Godar, DE TI Preprogrammed and programmed cell death mechanisms of apoptosis: UV-induced immediate and delayed apoptosis SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID INTERNUCLEOSOMAL DNA CLEAVAGE; CHEMOTHERAPEUTIC-AGENTS; THYMOCYTE APOPTOSIS; PROTEIN-SYNTHESIS; HL-60 CELLS; RADIATION; INDUCTION; FRAGMENTATION; CYCLOHEXIMIDE; LYMPHOCYTES AB Equitoxic doses (10% clonogenic survival) of UV radiation (UVR) from the three waveband regions, i.e. UVA1 (340-400 nm), UVB (290-320 nm) and UVC (200-290 nm), were shown to induce immediate or delayed apoptosis in L5178Y-R murine lymphoma cells, Membrane and DNA damage were shown to be the most probable initiators of UVA1-induced immediate or UVR-induced delayed apoptosis, respectively, These UV-induced apoptotic processes appeared to utilize two different ''core'' biochemical mechanisms; however, one core mechanism could be initiated at two distinct sites (e.g. membrane or DNA) and result in disparate kinetics, In an attempt to resolve this mechanistic issue, the dependence on macromolecular synthesis of each UV-induced apoptotic mechanism was investigated, In the absence of UVR, inhibition of either transcription (actinomycin D) or translation (cycloheximide) induced apoptosis in a concentration- and time-dependent manner. These results suggest that an apoptotic mechanism exists that does not require macromolecular synthesis postinsult (constitutive), The UVR data demonstrate that UVA1-induced immediate apoptosis utilizes this constitutive mechanism (preprogrammed), while UVR-induced delayed apoptosis utilizes the well-known inducible mechanism (programmed), Therefore, there are two different core biochemical mechanisms of apoptotic death available to each cell: preprogrammed (constitutive) and programmed (inducible) cell death. RP Godar, DE (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,12709 TWINBROOK PKWY,ROCKVILLE,MD 20857, USA. NR 38 TC 66 Z9 67 U1 0 U2 0 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUN PY 1996 VL 63 IS 6 BP 825 EP 830 DI 10.1111/j.1751-1097.1996.tb09638.x PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UQ162 UT WOS:A1996UQ16200023 PM 8992504 ER PT J AU Donoghue, AM Thistlethwaite, D Donoghue, DJ Kirby, JD AF Donoghue, AM Thistlethwaite, D Donoghue, DJ Kirby, JD TI A new method for rapid determination of sperm concentration in turkey semen SO POULTRY SCIENCE LA English DT Article DE sperm concentration; turkey; hemacytometer; photometer AB The routine determination of sperm concentration not only provides a measure of semen quality but also supplies a means of delivering precise sperm numbers in modern artificial insemination (Al) programs. Methods for estimating sperm numbers in laboratory settings (e.g., hemacytometer) are not practical for use in breeding facilities. A microprocessor-controlled semen analyzer (Densimeter, Model 534-B-Mod1, Animal Reproductive Systems) is commercially available for evaluating stallion semen. We calibrated and modified the semen analyzer to determine sperm concentration in turkey semen and to provide information on the required dilution for a constant Al dose. To calibrate the semen analyzer for turkeys, six samples of pooled semen (10 toms per sample) were collected by abdominal massage. A dilution curve of undiluted and 1:0.5, 1:1, 1:1.5, 1:2, 1:3, 1:5, and 1:10 diluted semen was established using Beltsville Poultry Semen Extender. Sperm concentration in diluted samples was determined by hemacytometer counts. The hemacytometer counts were used to develop an equation for estimating sperm concentration from the semen analyzer's absorbance readings and the equation programmed into the instrument. The newly developed program on the semen analyzer was subsequently validated by comparing instrument values for sperm concentrations with concurrent hemacytometer counts, which compared well to concentrations determined by a previously calibrated photoelectric colorimeter (Klett). Correlation coefficients between the semen analyzer and hemacytometer counts and the Klett and hemacytometer counts were r = 0.996 and r = 0.992, respectively (P < 0.001). The semen analyzer method was accurate and precise and could be beneficial to commercial turkey AI programs because it is easy to use, requires limited technological skills, and provides results for determining sperm concentration and AI dose in similar to 1 min. C1 ANIM REPROD SYST,CHINO,CA 91710. US FDA,BIOCHEM PHARMACOL BRANCH,BELTSVILLE,MD 20705. UNIV ARKANSAS,DEPT POULTRY SCI,FAYETTEVILLE,AR 72701. RP Donoghue, AM (reprint author), USDA ARS,GERMPLASM & GAMETE PHYSIOL LAB,BARC E BLDG 262,BELTSVILLE,MD 20705, USA. NR 10 TC 9 Z9 11 U1 0 U2 1 PU POULTRY SCIENCE ASSN INC PI CHAMPAIGN PA 309 W CLARK ST, CHAMPAIGN, IL 61802 SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PD JUN PY 1996 VL 75 IS 6 BP 785 EP 789 PG 5 WC Agriculture, Dairy & Animal Science SC Agriculture GA UP264 UT WOS:A1996UP26400016 PM 8737845 ER PT J AU Gaylor, DW Chen, JJ AF Gaylor, DW Chen, JJ TI A simple upper limit for the sum of the risks of the components in a mixture SO RISK ANALYSIS LA English DT Article ID CARCINOGENESIS; MODEL AB Natural or manufactured products may contain mixtures of carcinogens and the human environment certainly contains mixtures of carcinogens. Various authors have shown that the total risk of a mixture can be approximated by the sum of the risks of the individual components under a variety of conditions at low doses. Under these conditions, summing the individual estimated upper bound risks, as currently often done, is too conservative because it is unlikely that all risks for a mixture are at their maximum levels simultaneously. In the absence of synergism, a simple procedure is proposed for estimating a more appropriate upper bound of the additive risks for a mixture of carcinogens. These simple limits also apply to noncancer endpoints when the risks of the components are approximately additive. RP Gaylor, DW (reprint author), US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 8 TC 9 Z9 9 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD JUN PY 1996 VL 16 IS 3 BP 395 EP 398 DI 10.1111/j.1539-6924.1996.tb01473.x PG 4 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA UT121 UT WOS:A1996UT12100015 PM 8693164 ER PT J AU Carrington, CD AF Carrington, CD TI Trust in numbers: The pursuit of objectivity in science and public life - Porter,TM SO RISK ANALYSIS LA English DT Book Review RP Carrington, CD (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DEPT HLTH & HUMAN SERV,200 C ST SW,HFS-308,WASHINGTON,DC 20204, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD JUN PY 1996 VL 16 IS 3 BP 440 EP 441 PG 2 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA UT121 UT WOS:A1996UT12100022 ER PT J AU Taurog, A Dorris, ML Doerge, DR AF Taurog, A Dorris, ML Doerge, DR TI Minocycline and the thyroid: Antithyroid effects of the drug, and the role of thyroid peroxidase in minocycline-induced black pigmentation of the gland SO THYROID LA English DT Article ID PLACEBO-CONTROLLED TRIAL; CATALYZED IODINATION; RHEUMATOID-ARTHRITIS; RADICAL MECHANISM; NATIVE ENZYME; DOUBLE-BLIND; PROPYLTHIOURACIL; THERAPY; INHIBITION; METABOLISM AB Minocycline (MN), a member of the tetracycline family of antibiotics, is known to induce a black discoloration of the thyroid in several species, including humans. Antithyroid effects of MN have also been reported. The aim of the present study was two-fold: (1) to determine whether thyroid peroxidase (TPO) is involved in the MN-induced black thyroid, and (2) to obtain information on the effect of MN on TPO-catalyzed iodination and coupling in model systems containing highly purified TPO. Treatment of MN with TPO in the presence of the H2O2 generating system, glucose-glucose oxidase, resulted in the formation of a black product (or products). In phosphate buffer, pH 7.0, the color intensity reached its peak in about 90 min. Control samples without TPO showed little or no color change during this interval. Formation of the black product(s) did not require the presence of iodide. Other members of the tetracycline family were not oxidized to dark products by the TPO system. These results provide definitive evidence that TPO is involved in the MN-induced black thyroid. MN is an inhibitor of TPO-catalyzed iodination in model systems, with a potency comparable to that of MMI and PTU. At low drug concentrations (similar to 25 mu M), MN appeared to act as a competitive inhibitor, as previously shown for lower concentrations of MMT and PTU. However, when the drug concentration was increased, MN and the thioureylene drugs inhibited iodination by different mechanisms. With PTU and MMI, iodination was irreversibly inhibited through inactivation of TPO. However, inhibition of iodination by MN (100 mu M) was not associated with inactivation of TPO and was at least partially reversible. The most potent inhibitory effect of MN was on TPO-catalyzed coupling. This was demonstrated both in a coupling test system, designed to measure coupling in the absence of iodination, and in an iodination system, in which iodination and coupling occurred simultaneously. In both systems, MN was several times more potent than PTU and MMI, or other tetracycline drugs. Based on the potent antithyroid effects of MN observed in our in vitro studies, it seems advisable to monitor thyroid function in patients receiving long-term MN therapy. C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RP Taurog, A (reprint author), UNIV TEXAS,SW MED CTR,DEPT PHARMACOL,5323 HARRY HINES BLVD,DALLAS,TX 75235, USA. FU NIDDK NIH HHS [NIDDK-03612] NR 44 TC 32 Z9 33 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-7256 J9 THYROID JI Thyroid PD JUN PY 1996 VL 6 IS 3 BP 211 EP 219 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UZ441 UT WOS:A1996UZ44100010 PM 8837329 ER PT J AU Patriarca, PA AF Patriarca, PA TI Oral poliomyelitis vaccines SO LANCET LA English DT Letter RP Patriarca, PA (reprint author), US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD MAY 25 PY 1996 VL 347 IS 9013 BP 1495 EP 1495 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UM485 UT WOS:A1996UM48500077 PM 8676673 ER PT J AU Bai, RL Pei, XF Boye, O Getahun, Z Grover, S Bekisz, J Nguyen, NY Brossi, A Hamel, E AF Bai, RL Pei, XF Boye, O Getahun, Z Grover, S Bekisz, J Nguyen, NY Brossi, A Hamel, E TI Identification of cysteine 354 of beta-tubulin as part of the binding site for the A ring of colchicine SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 2,4-DICHLOROBENZYL THIOCYANATE; ANTIMITOTIC AGENT; TAXOL; PROTEIN; CHROMATOGRAPHY; CONFORMATIONS; SEPARATION; MUTANTS; NMR AB The colchicine analog 3-chloroacetyl-3-demethylthiocolchicine (3CTC) is a competitive inhibitor of colchicine binding to tubulin, binds to tubulin at 37 degrees C, but not at 0 degrees C, and covalently reacts with beta-tubulin at 37 degrees C, but not at 0 degrees C, in a reaction inhibited by colchicine site drugs. The approximate intramolecular distance be tween the oxygen at position C-3 in 3CTC and the chlorine atom of the 3-chloroacetyl group is 3 Angstrom. Using decylagarose chromatography, we purified beta-tubulin that had reacted with 3-(chloromethyl-[C-14]carbonyl)-3-demethylthiocolchicine ([C-14]3CTC). This beta-tubulin was digested with formic acid, cyanogen bromide, endoproteinase Glu-C, or endoproteinase Lys C, and the radiolabeled peptide(s) were isolated. The sequences of these peptides indicated that as much as 90% of the covalent reaction between the [C-14]3CTC and beta-tubulin occurred at cysteine 354. This finding indicates that the C-3 oxygen atom of colchicinoids is within 3 Angstrom of the sulfur atom of the Cys-354 residue, suggests that the colchicine A ring lies between Cys-354 and Cys-239, based on the known 9 Angstrom distance between these residues, and may indicate that the tropolone C ring lies between the peptide region containing Cys-239 and the amino-terminal beta-tubulin sequence, based on the labeling pattern observed following direct photoactivation of tubulin-bound colchicine. C1 NCI,MOLEC PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NIDDK,STRUCT BIOL LAB,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,DEPT CHEM,WASHINGTON,DC 20057. US FDA,CTR BIOL EVALUAT & RES,FACIL BIOTECHNOL RESOURCES,BETHESDA,MD 20892. NR 37 TC 82 Z9 90 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 24 PY 1996 VL 271 IS 21 BP 12639 EP 12645 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UL660 UT WOS:A1996UL66000078 PM 8647876 ER PT J AU Hardy, BJ Gutierrez, A Lesiak, K Seidl, E Widmalm, G AF Hardy, BJ Gutierrez, A Lesiak, K Seidl, E Widmalm, G TI Structural analysis of the solution conformation of methyl 4-O-beta-D-glucopyranosyl-alpha-D-glucopyranoside by molecular mechanics and ab initio calculation, stochastic dynamics simulation, and NMR spectroscopy SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID AQUEOUS-SOLUTION; DIRECT SCF; BETA-CELLOBIOSIDE; INTERNAL MOTIONS; FORCE-FIELD; D-GLUCOSE; WATER; OLIGOSACCHARIDES; OPTIMIZATION; RELAXATION AB Unambiguous determination of the solution conformation of carbohydrates is an important current research challenge. In general, we wish to test the hypothesis that the connecting linkages of these molecules may have significantly greater flexibility than in the crystalline state. In this study we specifically focus on the conformation of the disaccharide methyl 4-O-beta-D-glucopyranosyl-alpha-D-glucopyranoside using 1D and 2D NOESY experiments and molecular modeling. In particular we attempt to discover if ''folded'' conformations of this molecule exist in addition to the more expected crystalline ''extended'' conformations. The modeling calculations, both ab initio and molecular mechanics, indicate that the folded conformations are low in energy and can reasonably be expected to exist in solution if solvent effects, which are difficult to predict accurately, are not too large. The NMR data do not support the existence of the folded conformations in solution as a major population. Minor populations of folded conformations cannot, however, be clearly ruled out by the data. We assert that the glycosidic linkage flexibility hypothesis is not yet disproven for this linkage. C1 FDA BIOPHYS LAB, CTR BIOL EVALUAT & RES, BETHESDA, MD 20892 USA. NIH, DIV COMP RES & TECHNOL, BETHESDA, MD 20892 USA. UNIV STOCKHOLM, ARRHENIUS LAB, DEPT ORGAN CHEM, S-10691 STOCKHOLM, SWEDEN. RP Hardy, BJ (reprint author), UNIV OXFORD, PHYS & THEORET CHEM LAB, S PARKS RD, OXFORD OX1 3QZ, ENGLAND. NR 48 TC 21 Z9 21 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD MAY 23 PY 1996 VL 100 IS 21 BP 9187 EP 9192 DI 10.1021/jp953139i PG 6 WC Chemistry, Physical SC Chemistry GA UM677 UT WOS:A1996UM67700081 ER PT J AU Koch, WH Kopsidas, G Meffle, B Levine, AS Woodgate, R AF Koch, WH Kopsidas, G Meffle, B Levine, AS Woodgate, R TI Analysis of chimeric UmuC proteins: Identification of regions in Salmonella typhimurium UmuC important for mutagenic activity SO MOLECULAR & GENERAL GENETICS LA English DT Article DE Escherichia coli; Salmonella typhimurium; SOS mutagenesis; Chimeric proteins; UmuC ID DNA-REPAIR GENES; ESCHERICHIA-COLI; RECA PROTEIN; SOS MUTAGENESIS; CLEAVAGE; OPERON; PLASMID; LT2; UV; ENTEROBACTERIA AB Unlike Escherichia coli, the closely related bacterium Salmonella typhimurium is relatively unresponsive to the mutagenic effects of DNA-damaging agents. Previous experiments have suggested that these phenotypic differences might result from reduced activity of the S. typhimurium UmuC protein. To investigate this possibility, we have taken advantage of the high degree of homology between the UmuC proteins of E. coli and S. typhimurium and have constructed a series of plasmid-encoded chimeric proteins. The possibility that the phenotypic differences might be due to differential expression of the respective UmuC proteins was eliminated by constructing chimeric proteins that retained the first 25 N-terminal amino acids of either of the UmuC proteins (and presumably the same translational signals), but substituting the remaining 397 C-terminal amino acids with the corresponding segments from the reciprocal operon. Constructs expressing mostly E. coli UmuC were moderately proficient for mutagenesis whereas those expressing mostly S. typhimurium UmuC exhibited much lower frequencies of mutation, indicating that the activity of the UmuC protein of S. typhimurium is indeed curtailed. The regions responsible for this phenotype were more precisely localized by introducing smaller segments of the S. typhimurium UmuC protein into the UmuC protein of E. coli. While some regions could be interchanged with few or no phenotypic effects, substitution of residues 212-395 and 396-422 of E. coli UmuC with those from S. typhimurium resulted in reduced mutability, while substitution of residues 26-59 caused a dramatic loss of activity. We suggest, therefore, that the primary cause for the poor mutability of S. typhimurium can be attributed to mutations located within residues 26-59 of the S. typhimurium UmuC protein. C1 NICHHD,SECT DNA REPLICAT REPAIR & MUTAGENESIS,NIH,BETHESDA,MD 20892. US FDA,MOL BIOL BRANCH,WASHINGTON,DC 20204. NR 34 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0026-8925 J9 MOL GEN GENET JI Mol. Gen. Genet. PD MAY 23 PY 1996 VL 251 IS 2 BP 121 EP 129 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA UP515 UT WOS:A1996UP51500002 PM 8668121 ER PT J AU Nightingale, SL AF Nightingale, SL TI First antibiotic treatment to reduce the risk of duodenal ulcer recurrence SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP Nightingale, SL (reprint author), OFF HLTH AFFAIRS, FDA PARKLAWN BLDG, 5600 FISHERS LN, ROCKLAND, 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 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 22 PY 1996 VL 275 IS 20 BP 1534 EP 1534 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UL029 UT WOS:A1996UL02900004 ER PT J AU Nightingale, SL AF Nightingale, SL TI Important information regarding alendronate adverse reactions SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP Nightingale, SL (reprint author), OFF HLTH AFFAIRS, FDA PARKLAWN BLDG, 5600 FISHERS LN, ROCKLAND, 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 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 22 PY 1996 VL 275 IS 20 BP 1534 EP 1534 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UL029 UT WOS:A1996UL02900005 ER PT J AU Nightingale, SL AF Nightingale, SL TI Warning issued about street drugs containing botanical sources of ephedrine SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP Nightingale, SL (reprint author), OFF HLTH AFFAIRS, FDA PARKLAWN BLDG, 5600 FISHERS LN, ROCKLAND, 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 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 22 PY 1996 VL 275 IS 20 BP 1534 EP 1534 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UL029 UT WOS:A1996UL02900003 ER PT J AU Hennessy, TW Hedberg, CW Slutsker, L White, KE BesserWiek, JM Moen, ME Feldman, J Coleman, WW Edmonson, LM MacDonald, KL Osterholm, MT Belongia, E Boxrud, D Boyer, W Danila, R Korlath, J Leano, F Mills, W Soler, J Sullivan, M Deling, M Geisen, P Kontz, C Elfering, K Krueger, W Masso, T Mitchell, MF Vought, K Duran, A Harrell, F Jirele, K Krivitsky, A Manresa, H Mars, R Nierman, M Schwab, A Sedzielarz, F Tillman, F Wagner, D Wieneke, D Price, C AF Hennessy, TW Hedberg, CW Slutsker, L White, KE BesserWiek, JM Moen, ME Feldman, J Coleman, WW Edmonson, LM MacDonald, KL Osterholm, MT Belongia, E Boxrud, D Boyer, W Danila, R Korlath, J Leano, F Mills, W Soler, J Sullivan, M Deling, M Geisen, P Kontz, C Elfering, K Krueger, W Masso, T Mitchell, MF Vought, K Duran, A Harrell, F Jirele, K Krivitsky, A Manresa, H Mars, R Nierman, M Schwab, A Sedzielarz, F Tillman, F Wagner, D Wieneke, D Price, C TI A national outbreak of Salmonella enteritidis infections from ice cream SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID FOODBORNE OUTBREAK; UNITED-STATES; RAW-MILK; CONSUMPTION; GASTROENTERITIS; TRANSMISSION AB Background. In September 1994, the Minnesota Department of Health detected an increase in the number of reports of Salmonella enteritidis infections. After a case-control study implicated a nationally distributed brand of ice cream (Schwan's) in the outbreak, the product was recalled and further epidemiologic and microbiologic investigations were conducted. Methods. We defined an outbreak-associated case of S. enteritidis infection as one in which S. enteritidis was cultured from a person who became ill in September or October 1994. We established national surveillance and surveyed customers of the implicated manufacturer, The steps involved in the manufacture of ice cream associated with cases of S. enteritidis infection were compared with those of products not known to be associated with infection matched for the date of manufacture. Cultures for bacteria were obtained from ice cream samples, the ice cream plant, and tanker trailers that had transported the ice cream base (premix) to the plant. Results. estimate that S. enteritidis gastroenteritis developed in 224,000 persons in the United States after they ate Schwan's ice cream. The attack rate for consumers was 6.6 percent. Ice cream associated with infection contained a higher percentage of premix that had been transported by tanker trailers that had carried nonpasteurized eggs immediately before (P = 0.02). S. enteritidis was isolated from 8 of 266 ice cream products (3 percent), but not from environmental samples obtained from the ice cream plant (n = 157) or tanker trailers (n = 204). Conclusions. This nationwide outbreak of salmonellosis was most likely the result of contamination of pasteurized ice cream premix during transport in tanker trailers that had previously carried nonpasteurized liquid eggs containing S. enteritidis. To prevent further outbreaks, food products not destined for repasteurization should be transported in dedicated containers. C1 MINNESOTA DEPT HLTH,ACUTE DIS EPIDEMIOL SECT,MINNEAPOLIS,MN 55440. MINNESOTA DEPT HLTH,PUBL HLTH LAB,MINNEAPOLIS,MN 55440. MINNESOTA DEPT HLTH,EXECUT OFF,MINNEAPOLIS,MN 55440. CTR DIS CONTROL & PREVENT,DIV FIELD EPIDEMIOL,ATLANTA,GA 30341. CTR DIS CONTROL & PREVENT,EPIDEM INTELLIGENCE SERV,ATLANTA,GA 30341. CTR DIS CONTROL & PREVENT,FOODBORNE & DIARRHEAL DIS BRANCH,NATL CTR INFECT DIS,ATLANTA,GA 30341. MINNESOTA DEPT AGR,DIV DAIRY & FOOD INSPECT,ST PAUL,MN. US FDA,MINNEAPOLIS,MN. OLMSTED CTY HLTH DEPT,ROCHESTER,MN. US FDA,CHICAGO,IL. NR 26 TC 198 Z9 203 U1 3 U2 18 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 16 PY 1996 VL 334 IS 20 BP 1281 EP 1286 DI 10.1056/NEJM199605163342001 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA UK880 UT WOS:A1996UK88000001 PM 8609944 ER PT J AU Puri, RK Leland, P Obiri, NI Husain, SR Kreitman, RJ Haas, GP Pastan, I Debinski, W AF Puri, RK Leland, P Obiri, NI Husain, SR Kreitman, RJ Haas, GP Pastan, I Debinski, W TI Targeting of interleukin-13 receptor on human renal cell carcinoma cells by a recombinant chimeric protein composed of interleukin-13 and a truncated form of pseudomonas exotoxin A (PE38QQR) SO BLOOD LA English DT Article ID HUMAN B-CELLS; IGE SYNTHESIS; EXPRESSION; IL-13; PROLIFERATION; CYTOKINE; INVITRO; IGG4 AB We have previously shown that human renal cell carcinoma (RCC) cells express large numbers of interleukin-13 receptors (IL-13R), a newly described hemopoietic growth factor receptor. To target tumor cells that express IL-13R. we have produced a chimeric protein composed of human IL-13 and a derivative of Pseudomonas exotoxin A, termed PE38QQR. We report here that IL13-PE38QQR is highly cytotoxic to many human RCC cell lines. IL-13R-negative cell lines or cell lines expressing low numbers of IL-13R (<300 sites/cell) that include human bone marrow-derived cells were not susceptible to the cytotoxic effect of IL13-PE38QQR. The sensitivity of RCC cells to IL13-PE38QQR correlated positively with the density of IL-13R. The cytotoxic activity of IL13-PE38QQR was competed by an excess of IL-13 in a protein synthesis inhibition assay and confirmed by a clonogenic assay. Even though IL-13 and IL-4 are homologues and IL-4R and IL-13R have been proposed to share a receptor subunit, IL-4 did not compete for the cytotoxicity mediated by IL13-toxin on RCC. IL13-PE38QQR competes for [I-125]-lL-13 binding sites on RCC cells, although at a lower affinity than the wild-type recombinant cytokine. Human T-cell, B-cell, and monocytic cell lines are unresponsive to the cytotoxic action of IL13-PE38QQR. Thus, our results indicate that IL13-PE38QQR is highly cytotoxic to human RCC cells, although it is not cytotoxic to a variety of normal hematopoietic cells. IL13-PE38QQR should be further investigated preclinically for the treatment of human RCCs. This is a US government work. There are no restrictions on its use. C1 NCI,MOLEC BIOL LAB,DIV CANC BIOL DIAG & CTR,NIH,BETHESDA,MD 20892. PENN STATE UNIV,COLL MED,MILTON S HERSHEY MED CTR,DEPT SURG,DIV NEUROSURG,HERSHEY,PA. SUNY HLTH SCI CTR,DEPT UROL,SYRACUSE,NY 13210. RP Puri, RK (reprint author), US FDA,LAB MOL TUMOR BIOL,DIV CELLULAR & GENE THERAPIES,CTR BIOL EVALUAT & RES,NIH,BLDG 29B,BETHESDA,MD 20892, USA. NR 32 TC 95 Z9 96 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 1996 VL 87 IS 10 BP 4333 EP 4339 PG 7 WC Hematology SC Hematology GA UK879 UT WOS:A1996UK87900036 PM 8639793 ER PT J AU Zambon, M Hay, A Wood, J Gust, I Hampson, A Canas, L Guo, Y AF Zambon, M Hay, A Wood, J Gust, I Hampson, A Canas, L Guo, Y TI Update: Influenza activity - United States and worldwide, 1995-96 season, and composition of the 1996-97 influenza vaccine (Reprinted from MMWR, vol 45, pg 326-329, 1996) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 NATL INST MED RES,LONDON NW7 1AA,ENGLAND. NATL INST BIOL STAND & CONTROLS,POTTERS BAR EN6 3QG,HERTS,ENGLAND. COMMONWEALTH SERUM LABS,PARKVILLE,VIC 3052,AUSTRALIA. ARMSTRONG LAB,BROOKS AFB,TX. NATL CTR PREVENT MED,INST VIROL,BEIJING,PEOPLES R CHINA. WHO,NATL INFLUENZA CTR,DIV EMERGING & OTHER COMMUNICABLE DIS SURVEILLANC,CH-1211 GENEVA,SWITZERLAND. CDC,INFLUENZA BR,DIV VIRAL & RICKETTSIAL DIS,NATL CTR INFECT DIS,ATLANTA,GA 30333. US FDA,DIV VIROL,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20857. RP Zambon, M (reprint author), CENT PUBL HLTH LAB,LONDON NW9 5HT,ENGLAND. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 15 PY 1996 VL 275 IS 19 BP 1467 EP 1468 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA UJ937 UT WOS:A1996UJ93700009 ER PT J AU Johnson, GC Maddox, CW Fales, WH Wolff, WA Randle, RF Ramos, JA Schwartz, H Heise, KM Baetz, AL Wesley, IV Wagner, DE AF Johnson, GC Maddox, CW Fales, WH Wolff, WA Randle, RF Ramos, JA Schwartz, H Heise, KM Baetz, AL Wesley, IV Wagner, DE TI Epidemiologic evaluation of encephalitic listeriosis in goats SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article DE caprine species; epidemiology; listeriosis ID MONOCYTOGENES EXCRETION; DAIRY-CATTLE; ANIMALS; SHEEP; OUTBREAKS; HERD AB Objective-To evaluate host and environmental factors associated with the development of encephalitic listeriosis in goats, Design-Retrospective analysis of diagnostic laboratory records and survey of veterinarians and goat producers. Sample Population-355 goal herds accessible through laboratory records; 38 veterinarians who treated goats and 76 goat producers. Procedure-Data regarding breed and use for goats affected with encephalitic listeriosis were obtained from surveys and case follow-up information. Listeria monocytogenes isolates from the brains of 7 affected goats were serotyped and subjected to DNA restriction analysis. Results-Odds ratio for the development of encephalitis listeriosis in Angora (mohair-producing) goals was 22.9 by use of diagnostic laboratory records. Surveys also revealed a high prevalence in herds of Angora and other breeds that subsisted on woody browse, although Angora goats feeding predominantly on hay or pasture were not affected. listeria monocytogenes isolates from 4 Angora goats in 3 herds differed in DNA restriction patterns, although the pattern was identical in 3 other goals from another herd. Clinical Implications-Encephalitic listeriosis can be observed in all goat breeds, but a lifestyle of heavy browse consumption seems important to the development of disease in some herds. C1 UNIV MISSOURI,COLL VET MED,DEPT VET MED & SURG,COLUMBIA,MO 65211. UNIV MISSOURI,COLL VET MED,VET MED EXTENS,COLUMBIA,MO 65211. UNIV AUTONOMA BARCELONA,FAC VET MED,E-08193 BARCELONA,SPAIN. LINCOLN UNIV,AGR EXTENS SERV,JEFFERSON CITY,MO 65101. RIVER HILLS VET CLIN,VAN BUREN,MO 63965. NATL ANIM DIS CTR,AMES,IA 50010. PUBL HLTH SERV,DEPT HLTH & HUMAN SERV,US FDA,MINNEAPOLIS,MN 55455. RP Johnson, GC (reprint author), UNIV MISSOURI,COLL VET MED,VET MED DIAGNOST LAB,COLUMBIA,MO 65211, USA. NR 31 TC 10 Z9 11 U1 0 U2 2 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD MAY 15 PY 1996 VL 208 IS 10 BP 1695 EP & PG 6 WC Veterinary Sciences SC Veterinary Sciences GA UK946 UT WOS:A1996UK94600022 PM 8641953 ER PT J AU Myers, MJ Henderson, M AF Myers, MJ Henderson, M TI Assessment of two devices for measuring tympanic membrane temperature in swine, dairy cattle, and dairy calves SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article DE bovine species; porcine species; rectal temperature; tympanic membrane AB Objective-To compare tympanic membrane temperature readings obtained with 2 commercially available devices with rectal temperature readings obtained with a standard mercury thermometer in dairy cattle, dairy calves, and swine. Design-Clinical trial. Animals-6 Holstein calves (approx 6 months old), 6 Holstein cattle (approx 4 years old), and 5 Landrace-Poland China swine. Procedure-Tympanic membrane temperatures were measured, and results were compared with rectal temperatures obtained with a standard mercury thermometer. Tympanic membrane temperatures were obtained before and after insertion of the rectal thermometer. Temperature readings in swine were obtained following passive restraint in a cage-like device or restraint using a snare to assess the effect of stress on tympanic membrane temperature. Results-Tympanic membrane temperature readings from both devices were lower than those obtained using a rectal thermometer for all animals. Repealed measurement of tympanic membrane temperature of individual cattle resulted in consistent readings for both devices. Clinical Implications-Because all animals were visibly healthy, results suggest that tympanic membrane temperature readings obtained with either device may be an adequate assessment of health status. RP Myers, MJ (reprint author), US FDA,ANIM BIOL BRANCH,CTR VET MED,BLDG 328A,CTR RD,BELTSVILLE,MD 20705, USA. NR 4 TC 5 Z9 5 U1 0 U2 1 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD MAY 15 PY 1996 VL 208 IS 10 BP 1700 EP & PG 3 WC Veterinary Sciences SC Veterinary Sciences GA UK946 UT WOS:A1996UK94600023 PM 8641954 ER PT J AU Hinson, RM Williams, JA Shacter, E AF Hinson, RM Williams, JA Shacter, E TI Elevated interleukin 6 is induced by prostaglandin E(2) in a murine model of inflammation: Possible role of cyclooxygenase-2 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RHEUMATOID-ARTHRITIS; GROWTH-FACTOR; SYNTHASE CYCLOOXYGENASE; HUMAN MONOCYTES; CROHNS-DISEASE; INHIBITION; PLASMACYTOMAS; INDOMETHACIN; INVIVO AB Injection of mineral oils such as pristane into the peritoneal cavities of BALB/c mice results in a chronic peritonitis associated with high tissue levels of interleukin 6 (IL-6), Here we show that increased prostaglandin E(2) (PGE(2)) synthesis causes induction of IL-6 and that expression of an inducible cyclooxggenase, Cox-2, may mediate this process, Levels of both PGE(2) and IL-6 are elevated in inflammatory exudates from pristane-treated mice compared with lavage samples from untreated mice. The Cox-a gene is induced in the peritoneal macrophage fraction isolated from the mice, A cause and effect relationship between increased macrophage PGE(2) and IL-6 production is shown in vitro, When peritoneal macrophages are activated with an inflammatory stimulus (polymerized albumin), the Cox-2 gene is induced and secretion of PGE(2) and IL-6 increases, with elevated PGE(2) appearing before IL-6, Cotreatment with 1 mu M indomethacin inhibits PGE(2) production by the cells and reduces the induction of IL-6 mRNA but has no effect on Cox-2 mRNA, consistent with the fact that the drug inhibits catalytic activity of the cyclooxygenase but does not affect expression of the gene. Addition of exogenous PGE(2) to macrophages induces IL-6 protein and mRNA synthesis, indicating that the eicosanoid stimulates IL-6 production at the level of gene expression, PGE(2)-stimulated IL-6 production is unaffected by addition of indomethacin. Taken together with the earlier finding that indomethacin diminishes the elevation of IL-6 in pristane-treated mice, the results show that PGE(2) can induce IL-6 production in vivo and implicate expression of the Cox-2 gene in the regulation of this cytokine. C1 US FDA,CTR BIOL EVALUAT & RES,IMMUNOL LAB,BETHESDA,MD 20892. RP Hinson, RM (reprint author), UNIFORMED SERV UNIV HLTH SCI,DEPT PEDIAT,BETHESDA,MD 20814, USA. NR 61 TC 201 Z9 205 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 14 PY 1996 VL 93 IS 10 BP 4885 EP 4890 DI 10.1073/pnas.93.10.4885 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UL255 UT WOS:A1996UL25500067 PM 8643498 ER PT J AU Weisz, A Scher, AL Ito, Y AF Weisz, A Scher, AL Ito, Y TI Isolation of 4'-bromo-4,5,6,7-tetrachlorofluorescein from a synthetic mixture by pH-zone-refining counter-current chromatography with continuous pH monitoring SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; preparative chromatography; color additives; bromotetrachlorofluorescein AB A synthetic mixture containing mainly 4'-bromo-4,5,6,7-tetrachlorofluorescein (4'BrTCF, ca. 25% by high-performance liquid chromatography) was prepared by direct bromination of tetrachlorofluorescein in ethanol. The 4'BrTCF was isolated and purified by pH-zone-refining counter-current chromatography (CCC), using two different two-phase solvent systems: diethyl ether-acetonitrile-water (4:1:5, v/v) and tert.-butyl methyl ether-water (1:1, v/v). For each system, the upper organic phase was acidified and used as the stationary phase and the lower aqueous phase was made basic and used as the mobile phase. pH-Zone-refining CCC of two 5-g batches of the crude mixture yielded 1.65 g of 4'BrTCF that was ca. 95% pure by HPLC. For these separations, a commercial counter-current chromatograph was fitted with a pH electrode in a flow cell to record the pH of the effluent 'on-line,' thereby replacing the tedious and time-consuming manual measurement of the pH of each fraction. Additionally, UV spectra of the effluent were continuously monitored and stored by using a computerized scanning UV-Vis detector equipped with an adjustable short-pathlength flow cell. C1 US FDA,OFF COSMET & COLORS,WASHINGTON,DC 20204. NHLBI,BIOPHYS CHEM LAB,NIH,BETHESDA,MD 20892. NR 7 TC 30 Z9 30 U1 1 U2 6 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 MAY 3 PY 1996 VL 732 IS 2 BP 283 EP 290 DI 10.1016/0021-9673(95)01266-4 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA UL386 UT WOS:A1996UL38600012 PM 8653202 ER PT J AU Weaver, JL McKinney, L Schoenlein, PV Goldenberg, S Gottesman, MM Aszalos, A AF Weaver, JL McKinney, L Schoenlein, PV Goldenberg, S Gottesman, MM Aszalos, A TI MDR1/P-glycoprotein function .1. Effect of hypotonicity and inhibitors on rhodamine 123 exclusion SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE multidrug resistance; chloride channel; drug efflux; cyclosporine A; 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid; 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid; flufenamic acid ID SENSITIVE CHLORIDE CONDUCTANCE; RESISTANCE P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; CELLS; FORSKOLIN; IDENTIFICATION; TRANSPORTER; EXPRESSION; MEMBRANE; CHANNELS AB The MDR1 protein (P-glycoprotein) is a membrane ATPase whose expression results in resistance to several anti-tumor drugs. It has been proposed that the MDR1 protein, in addition to its pumplike properties, can function as (Gill et al. Cell 71: 23-32, 1992; Altenberg et al. Cancer Res. 54: 618-622, 1994) or mediate the activity of (Hardy et al. EMBO J. 14: 68-75, 1995) a hypotonic stress-induced Cl- current. In addition, one study found that drug transport and Cl- channel-associated functions of MDR1 were separable and mutually exclusive and that, when cells were swelled, the MDR1 protein could not transport substrate. This hypothesis was tested in four pairs of isogenic cell lines with MDR1 transfectants expressing 8,000-55,000 MDR1 antibody binding sites per cell. Cytoplasmic exclusion of rhodamine 123 was used as an indicator of MDR1 function to measure the effect of hypotonic stress, MDR1 inhibitors, and Cl- channel blockers on MDR1 transport function. It was found that MDR1 activity and its inhibition by cyclosporine A or flufenamic acid were unaffected by hypotonicity alone or in combination with Cl- channel blockers. C1 ARMED FORCES RADIAT RADIOBIOL INST, DEPT PHYSIOL, BETHESDA, MD 20892 USA. NCI, CELL BIOL LAB, NIH, BETHESDA, MD 20892 USA. MED COLL GEORGIA, DEPT ANAT & CELL BIOL, AUGUSTA, GA 30912 USA. RP Weaver, JL (reprint author), US FDA, CTR DRUG EVALUAT & RES,DIV RES & TESTING,MOD-1, RM 3309, 8301 MUIRKIRK RD, LAUREL, MD 20708 USA. NR 35 TC 13 Z9 13 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD MAY PY 1996 VL 270 IS 5 BP C1447 EP C1452 PG 6 WC Cell Biology; Physiology SC Cell Biology; Physiology GA UJ814 UT WOS:A1996UJ81400023 ER PT J AU Weaver, JL Aszalos, A McKinney, L AF Weaver, JL Aszalos, A McKinney, L TI MDR1/P-glycoprotein function .2. Effect of hypotonicity and inhibitors on Cl- efflux and volume regulation SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE multidrug resistance; P-glycoprotein; chloride channel; chloride efflux; cyclosporin; 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid; 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid; forskolin; 1,9-dideoxyforskolin ID RESISTANCE P-GLYCOPROTEIN; COMPLEMENTARY-DNA; LYMPHOCYTES; TRANSPORT; CELLS; CONDUCTANCE; LEUKOCYTES; CHANNELS; MEMBRANE AB Resistance to anti-tumor drugs can be mediated by overexpression of the multidrug resistance 1 (MDR1) protein (P-glycoprotein). In three MDR1-transfected cell lines (Gill et al. Cell 71: 23-32, 1992; Altenberg et al. Cancer Res. 54: 618-622, 1994), a hypotonic stress-induced Cl- current has been demonstrated that can be inhibited by MDR1 substrates and Cl- channel blockers. We tested the hypothesis that MDR1 expression confers additional Cl- conductance by measuring regulatory volume decrease (RVD) in four pairs of isogenic cell lines and Cl-36 efflux in two cell lines with and without hypotonic stress. The kinetics of RVD and response to Cl- channel blockers were indistinguishable in MDR and parental cells. Additionally, no significant difference was seen between Cl-36 efflux rate constants under hypotonic conditions between NIH/3T3 and L1210 parental and MDR cells. We conclude that, in intact cells, the expression of MDR1 does not alter the rate of volume regulation or the rate of Cl-36 efflux under hypotonic conditions between parental and MDR cells. C1 ARMED FORCES RADIAT RADIOBIOL INST, DEPT PHYSIOL, BETHESDA, MD 20889 USA. RP Weaver, JL (reprint author), US FDA, CTR DRUG EVALUAT & RES,DIV RES & TESTING,MOD-1, RM 3309, 5301 MUIRKIRK RD, LAUREL, MD 20708 USA. NR 29 TC 7 Z9 7 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD MAY PY 1996 VL 270 IS 5 BP C1453 EP C1460 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA UJ814 UT WOS:A1996UJ81400024 ER PT J AU Cherrington, JM Fuller, MD Mulato, AS Allen, SJW Kunder, SC Ussery, MA Lesnikowski, Z Schinazi, RF Sommadossi, JP Chen, MS AF Cherrington, JM Fuller, MD Mulato, AS Allen, SJW Kunder, SC Ussery, MA Lesnikowski, Z Schinazi, RF Sommadossi, JP Chen, MS TI Comparative kinetic analyses of interaction of inhibitors with rauscher murine leukemia virus and human immunodeficiency virus reverse transcriptases SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID BLOOD MONONUCLEAR-CELLS; 3'-AZIDO-3'-DEOXYTHYMIDINE; INVITRO; INFECTIVITY; CULTURE; AGENT AB The inhibitory effects of several nucleoside triphosphate analogs on Rauscher murine leukemia virus (RMuLV) and human immunodeficiency virus (HIV) type 1 reverse transcriptases (RTs) were studied. With RNA as the template, the apparent K-m and apparent K-i values of HIV RT toward its substrates and inhibitors are 12 to 500 times lower than the corresponding values for RMuLV RT. However, the K-i/K-m ratios (inhibition efficiencies) for HIV and RMuLV RTs are similar for AZTTP (zidovudine triphosphate), d4TTP [3'-deoxythymidine-2'-ene-(3'-deoxy-2',3'-didehydrothymidine) triphosphate], PMEADP [9-(2-phosphonylmethoxyethyl)adenine diphosphate], FIAUTP [1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)-5-iodouracil triphosphate], and HPMPCDP [(S)-1-(3-hydroxy-2-phosphylmethoxypropyl)cytosine diphosphate]. With DNA as the template, the K-m values are similar for HIV and RMuLV RTs. However, the K-i/K-m values of HIV and RMuLV RTs are significantly different for ddCTP, ddATP, and 3TCTP (2',3'-dideoxy-3'-thiacytidine). The RTs of RMuLV and HIV are sufficiently different from one another that the kinetic inhibition constants for a particular antiviral compounds should be determined to indicate whether anti-RMuLV activity is likely to be predictive for the anti-HIV activity of the compound. This information, in conjunction with species-specific drug metabolism differences and tissue culture antiviral activity, is important in determining the suitability of a particular animal model. C1 GILEAD SCI, FOSTER CITY, CA 94404 USA. US FDA, ROCKVILLE, MD 20857 USA. VET AFFAIRS MED CTR, GEORGIA RES CTR AIDS & HIV INFECT, DECATUR, GA 30033 USA. EMORY UNIV, SCH MED, DEPT PEDIAT, BIOCHEM PHARMACOL LAB, ATLANTA, GA 30322 USA. UNIV ALABAMA, CTR AIDS RES, DEPT PHARMACOL, DIV CLIN PHARMACOL, BIRMINGHAM, AL 35294 USA. RI Schinazi, Raymond/B-6777-2017 NR 23 TC 18 Z9 18 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 1996 VL 40 IS 5 BP 1270 EP 1273 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA UJ076 UT WOS:A1996UJ07600040 PM 8723481 ER PT J AU Khan, AA Wang, RF Nawaz, MS Cao, WW Cerniglia, CE AF Khan, AA Wang, RF Nawaz, MS Cao, WW Cerniglia, CE TI Purification of 2,3-dihydroxybiphenyl 1,2-dioxygenase from Pseudomonas putida OU83 and characterization of the gene (bphC) SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYCHLORINATED BIPHENYL DEGRADATION; NUCLEOTIDE-SEQUENCE; ESCHERICHIA-COLI; DIOXYGENASE GENE; DEGRADING STRAIN; RING-CLEAVAGE; EXPRESSION; CLONING; PSEUDOALCALIGENES; 4-CHLOROBIPHENYL AB The 2,3-dihydroxybiphenyl 1,2-dioxygenase (2,3-DBPD) of Pseudomonas putida OU83 was constitutively expressed and purified to apparent homogeneity. The apparent molecular mass of the native enzyme was 256 kDa, and the subunit molecular mass was 32 kDa. The data suggested that 2,3-DBPD was an octamer of identical subunits. The nucleotide sequence of a DNA fragment containing the bphC region was determined. The deduced protein sequence for 2,3-DBPD consisted of 292 amino acid residues, with a calculated molecular mass of 31.9 kDa, which was in agreement with data for the purified 2,3-DBPD. Nucleotide and amino acid sequence analyses of the bphC gene and its product, respectively, revealed that there was a high degree of homology between the OU83 bphC gene and the bphC genes of Pseudomonas cepacia LB400 and Pseudomonas pseudoalcaligenes KF707. C1 NATL CTR TOXICOL RES,FOOD & DRUG ADM,DIV MICROBIOL,JEFFERSON,AR 72079. NR 36 TC 20 Z9 20 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD MAY PY 1996 VL 62 IS 5 BP 1825 EP 1830 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA UJ228 UT WOS:A1996UJ22800058 PM 8633883 ER PT J AU Vanyushin, BF Poirier, LA AF Vanyushin, BF Poirier, LA TI Drosophila melanogaster genomic DNA sequence homologous to mammalian cytosine DNA-methyltransferase gene SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article DE CpG suppression; DNA-methyltransferase gene; Drosophila ID 5-METHYLCYTOSINE; ABSENCE; DOMAIN; BASES AB Using Southern blotting procedure we have shown that Drosophila genomic DNA hybridizes with 4423-bp C-terminal fragment of murine cytosine DNA-methyltransferase gene. Thus, the Drosophila genome has a sequence homologous to the mammalian cytosine DNA-methyltrasferase gene. We assume that DNA methylation most likely responsible for strong CpG suppression in the Drosophila genome mainly was catalyzed by a cytosine DNA-methyltransferase that has since been lost. C1 NATL CTR TOXICOL RES,DIV NUTR TOXICOL,JEFFERSON,AR 72079. NR 23 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE NSW 2204, AUSTRALIA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD MAY PY 1996 VL 39 IS 2 BP 353 EP 358 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UT736 UT WOS:A1996UT73600017 PM 8799463 ER PT J AU Sgadari, C Angiolillo, AL Tosato, G AF Sgadari, C Angiolillo, AL Tosato, G TI Inhibition of angiogenesis by interleukin-12 is mediated by the interferon-inducible protein 10 SO BLOOD LA English DT Article ID CELL STIMULATORY FACTOR; LYMPHOCYTE MATURATION FACTOR; NATURAL-KILLER-CELLS; CD4+ T-CELLS; GAMMA-INTERFERON; HETERODIMERIC CYTOKINE; ENDOTHELIAL-CELLS; BASEMENT-MEMBRANE; GROWTH-FACTOR; PROLIFERATION AB Interleukin 12 (IL-12), a multifunctional cytokine produced by macrophages and B-cell lines, induces interferon-gamma (IFN-gamma) production, stimulates growth of both T and natural killer cells, promotes Th1-type helper T-cell responses, and inhibits neovascularization. Because the human interferon-inducible protein 10 (IP-10) can also inhibit neovascularization, we tested whether IP-10, induced by IL-12 through the intermediate IFN-gamma, might be a mediator of IL-12 angiogenesis inhibition. We report here that murine IL-12 profoundly inhibited basic fibroblast growth factor (bFGF)-induced Matrigel neo-vascularization in vivo, and that this effect of IL-12 was neutralized by systemic administration of antibodies to either murine IFN-gamma or IP-10. Murine IL-12 induced murine IP-10 expression in mouse splenocytes, and human IFN-gamma induced human IP-10 expression in purified human endothelial cells, suggesting that IL-12 can induce IP-10 expression in certain cells. These results document the important role of IP-10 as a mediator of angiogenesis inhibition by IL-12, and raise the possibility that IP-10 may also contribute to the antitumor effect of IL-12. This is a US government work. There are no restrictions on its use. C1 CHILDRENS NATL MED CTR,DEPT HEMATOL ONCOL,WASHINGTON,DC 20010. RP Sgadari, C (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,HFM-535,BLDG 29A,ROOM 2D06,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Sgadari, Cecilia/H-4302-2016 OI Sgadari, Cecilia/0000-0003-0364-4912 NR 55 TC 355 Z9 365 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 1996 VL 87 IS 9 BP 3877 EP 3882 PG 6 WC Hematology SC Hematology GA UH142 UT WOS:A1996UH14200041 PM 8611715 ER PT J AU Freni, SC Eberhardt, MS Turturro, A Hine, RJ AF Freni, SC Eberhardt, MS Turturro, A Hine, RJ TI Anthropometric measures and metabolic rate in association with risk of breast cancer (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE anthropometry; breast cancer; elbow width; height; menopause; metabolic rate; risk factors; United States ID DIETARY-FAT; WEIGHT; HEIGHT; WOMEN; CALORIES AB To investigate whether cancer risk-reduction seen in calorie-restricted animals also applies to breast cancer in women, we have analyzed data from the first National Health and Nutrition Examination Survey in the United States and subsequent follow-up surveys. During the follow-up of one to 155 months, 182 out of 7,622 women developed breast cancer. Due to biased under-reporting of dietary intake, the analysis did not examine calorie intake as an exposure variable, but rather focused on anthropometric measures and metabolic rate as biomarkers of nutritional balance, Multiple Cox regression analysis showed elevated odds ratios (OR) for height, elbow width, and skinfolds among postmenopausal women. ORs for the fifth quintile were 2.0 (95 percent confidence interval [CI]=1.0-3.8), 2.3 (CI=1.2-4.7), and 2.0 (CI=1.0-4.0), respectively. Weight (OR=2.5, CI=1.2-5.1) and resting metabolic rate (OR=2.0, CI=1.0-4.0) were significant relative to the second quintile, Bitrochanteric breadth, sitting height, body fat, body mass index, or combination variables were not associated with cancer risk, It was concluded that in the analysis of breast cancer data, skeletal measures ought to be considered as routine potential confounders, and that using measured rather than estimated metabolic rates may improve risk prediction. C1 UNIV ARKANSAS MED SCI HOSP,LITTLE ROCK,AR 72205. US CTR DIS CONTROL,NATL CTR HLTH STAT,HYATTSVILLE,MD. RP Freni, SC (reprint author), US FDA,NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,HFT-20,JEFFERSON,AR 72079, USA. NR 34 TC 19 Z9 19 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 1996 VL 7 IS 3 BP 358 EP 365 DI 10.1007/BF00052942 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA UL406 UT WOS:A1996UL40600010 PM 8734830 ER PT J AU vanAcker, SABE Kramer, K Voest, EE Grimbergen, JA Zhang, J vanderVijgh, WJF Bast, A AF vanAcker, SABE Kramer, K Voest, EE Grimbergen, JA Zhang, J vanderVijgh, WJF Bast, A TI Doxorubicin-induced cardiotoxicity monitored by ECG in freely moving mice - A new model to test potential protectors SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE telemetry; ECG; cardiotoxicity; doxorubicin; mice ID GUINEA-PIG; ADRIAMYCIN; ICRF-187; MOUSE AB In laboratory animals, histology is most commonly used to study doxorubicin-induced cardiotoxicity, However, for monitoring during treatment, large numbers of animals are needed. Recently we developed a new method to measure ECG values in freely moving mice by telemetry. With this model we investigated the effect of chronic doxorubicin administration on the ECG of freely moving BALB/c mice and the efficacy of ICRF-187 as a protective agent. The ST interval significantly widened from 15.0 +/- 1.5 to 56.8 +/- 11.8 ms in week 10 (7 weekly doses of 4 mg/kg doxorubicin given i.v. plus 3 weeks of observation). The ECG of the control animals did not change during the entire study. After sacrifice the hearts of doxorubicin-treated animals were enlarged and the atria were hypertrophic. As this schedule exerted more toxicity than needed to investigate protective agents, the protection of ICRF-187 was determined using a dose schedule with lower general toxicity (6 weekly doses of 4 mg/kg doxorubicin given i.v. plus 2 weeks of observation). On this schedule, the animals' hearts appeared normal after sacrifice and ICRF-187 (50 mg/kg given i.p. 1 h before doxorubicin) provided almost full protection. These data were confirmed by histology. The results indicate that this new model is very sensitive and enables monitoring of the development of cardiotoxicity with time. These findings result in a model that allows the testing of protectors against doxorubicin-induced cardiotoxicity as demonstrated by the protection provided by ICRF-187. C1 FREE UNIV AMSTERDAM HOSP,DEPT ONCOL,1081 HV AMSTERDAM,NETHERLANDS. UNIV UTRECHT HOSP,DEPT INTERNAL MED,3584 CX UTRECHT,NETHERLANDS. VRIJE UNIV AMSTERDAM,FAC MED,CLIN ANIM LAB,1081 HV AMSTERDAM,NETHERLANDS. US FDA,TOXICOL & PHARMACOL BRANCH,DIV RES & TESTING,LAUREL,MD. RP vanAcker, SABE (reprint author), VRIJE UNIV AMSTERDAM,FAC CHEM,DEPT PHARMACOCHEM,DIV MOLEC PHARMACOL,DE BOELELAAN 1083,1081 HV AMSTERDAM,NETHERLANDS. RI Bast, Aalt/I-7809-2013 NR 21 TC 59 Z9 60 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAY PY 1996 VL 38 IS 1 BP 95 EP 101 DI 10.1007/s002800050453 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA UB308 UT WOS:A1996UB30800015 PM 8603459 ER PT J AU Chae, YH Delclos, KB Blaydes, B ElBayoumy, K AF Chae, YH Delclos, KB Blaydes, B ElBayoumy, K TI Metabolism and DNA binding of the environmental colon carcinogen 6-nitrochrysene in rats SO CANCER RESEARCH LA English DT Article ID CHEMICAL CARCINOGENESIS; HUMAN HEPATOCYTES; ADDUCT FORMATION; PRIMARY CULTURES; NEWBORN MICE; COOKED FOOD; CD RATS; INDUCTION; MOUSE; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE AB The environmental contaminant 6-nitrochrysene (6-NC) has been shown to induce adenomas and adenocarcinomas in the colons of rats, The present study aimed at providing a better understanding of mechanisms that are responsible for this effect, Three female CD rats were injected i.p. with [3,4,9,10-H-3]6-NC [9 mu mol/rat (316 mu Ci/rat)], and urine and feces were collected daily for 3 days, In the first 24 h, radioactivity corresponding to 1.3% of the dose was excreted in the urine, whereas 23.0% was recovered in the feces, After 3 days, the total excretions in urine and feces were 2.8% and 34.9% of the dose, respectively, Radioactivity measured in various organs 3 days after injection of [3,4,9,10-H-3]6-NC amounted to 24.8% of the administered dose, Fecal metabolites were identified, based on comparison of their chromatographic characteristics with those of standards, as trans-1,2-dihydro-1,2-dihydroxy-6-NC, chrysene-5,6-quinone, and 6-aminochrysene (6-AC); the structure of the latter was further confirmed by mass spectrometry and UV spectral analysis, Metabolites identified in the urine were 6-AC, trans-1,2-dihydro-1,2-dihydroxy-6-NC, and trans-9,10-dihydro-9,10-dihydroxy-6-NC in free forms and also as glucuronide and/or sulfate conjugates, The P-32-postlabeling assay was used to determine the metabolic pathways that were leading to DNA adduct formation in the target (colon) and nontarget (liver, lung, and mammary tissues) organs of female CD rats injected with 6-NC under conditions identical to those of the bioassay (total, 14.8 mu mol/rat; single i.p. injections on days 1, 8, 15, 22, and 29), Twenty-four h after the last carcinogen administration, the levels of the adduct derived from trans-1,2-dihydro-1,2-dihydroxy-6-AC were higher than those derived from N-hydroxg-6-AC in all organs examined; however, the highest levels of DNA adducts were found in the lung and not in the target organ, the colon, Although the role of each adduct in colon carcinogenesis needs to be determined, the results favor the ring oxidation and nitroreduction combination pathway as the primary contributor to the activation of 6-NC as a colon carcinogen in the rat. C1 AMER HLTH FDN,DIV CANC ETIOL & PREVENT,VALHALLA,NY 10595. NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079. FU NCI NIH HHS [CA 35519, CA 17613] NR 62 TC 9 Z9 10 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1996 VL 56 IS 9 BP 2052 EP 2058 PG 7 WC Oncology SC Oncology GA UG756 UT WOS:A1996UG75600021 PM 8616850 ER PT J AU Gutman, S AF Gutman, S TI Food and drug administration (FDA)'s impact on laboratory performance: FDA's perspective SO CLINICAL CHEMISTRY LA English DT Article DE premarket review; in vitro diagnostic devices; premarket application; premarket notification; 510(K) submissions AB The Division of Clinical Laboratory Devices is responsible for the premarket review of in vitro diagnostic devices (laboratory tests). We currently process >1000 diverse applications per year. New versions of old devices are handled as premarket notifications, so-called 510(k) submissions, The review objective is to establish that the new product is ''substantially equivalent'' to its predicate. Fundamentally new devices are handled as premarket applications, The review objective is to establish de novo that the product is ''safe and effective.'' A central regulatory issue over the past several years has been the development of a standardized model for scientific review. The Food and Drug Administration contributes to the quality of in vitro diagnostic devices by providing oversight and objective review, by setting thresholds for product safety and effectiveness, and by ensuring that organized data and appropriate labeling is present in support of a device's intended use. RP Gutman, S (reprint author), CTR DEVICES & RADIOL HLTH,US FDA,DIV CLIN LAB DEVICES,OFF DEVICE EVALUAT,2098 GAITHER RD,ROCKVILLE,MD 20850, USA. NR 5 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 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAY PY 1996 VL 42 IS 5 BP 786 EP 789 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UJ253 UT WOS:A1996UJ25300033 PM 8653915 ER PT J AU Pauken, CM LaBorde, JB Bolon, B AF Pauken, CM LaBorde, JB Bolon, B TI Malformations caused by exposure of gestational day (GD) 5 mouse embryos to all-trans retinoic acid. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079. PATHOL ASSOCIATES INT,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY 1 PY 1996 VL 175 IS 2 BP 89 EP 89 PG 1 WC Developmental Biology SC Developmental Biology GA UK435 UT WOS:A1996UK43500145 ER PT J AU Rajaratnam, VS Cerro, JA Pintar, JE Fishman, RB Webb, PJ Streck, RD AF Rajaratnam, VS Cerro, JA Pintar, JE Fishman, RB Webb, PJ Streck, RD TI Developmental expression of IGFBP-1 mRNA in the somites and urogenital ridge of the rat fetus. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT NEUROSCI & CELL BIOL,PISCATAWAY,NJ 08854. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY 1 PY 1996 VL 175 IS 2 BP 96 EP 96 PG 1 WC Developmental Biology SC Developmental Biology GA UK435 UT WOS:A1996UK43500152 ER PT J AU Baggio, MC MedeirosNeto, G Osawa, Y Nguyen, NY Santisteban, P Knobel, M Grollman, EF AF Baggio, MC MedeirosNeto, G Osawa, Y Nguyen, NY Santisteban, P Knobel, M Grollman, EF TI Amino acid composition of proteins extracted from endemic goiter glands SO ENDOCRINE PATHOLOGY LA English DT Article DE thyroid albumin; iodine-deficiency goiter; thyroglobulin; endemic goiter; amino acid composition ID CONGENITAL GOITER; THYROID PEROXIDASE; FAMILIAL GOITER; THYROGLOBULIN; ALBUMIN AB Proteins were isolated and characterized in thyroid tissue of six patients from Brazil with endemic goiter. Biochemical studies of these thyroidal proteins included gel filtration, electrophoresis, and amino acid analysis. In addition to thyroglobulin, two of the most abundant proteins found in all goiters studied had molecular weights of 68 and 14 kDa, One protein was identified as albumin based on its immunoreactivity with antibodies to serum albumin. The other protein was identified as a hemoglobin subunit using reverse-phase high-performance liquid chromatography (HPLC). Identification was confirmed by partial N-terminal amino acid sequencing that showed several nonconservative differences in thyroid albumin when compared to human serum albumin (HSA). Biochemical findings were correlated with iodine and hormone contents in serum and thyroglobulin from these patients. Based on these findings, we suggest that hemoglobin and albumin are taken up from the blood by the hyperplastic thyroid tissue, Albumin would be processed by the thyroid follicular cell, becoming iodinated and released into the circulation. C1 UNIV SAO PAULO,HOSP CLIN,SCH MED,DIV ENDOCRINOL,THYROID UNIT,BR-01065970 SAO PAULO,BRAZIL. NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NHLBI,NIH,MOLEC IMMUNOL LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,FACIL BIOTECHNOL RESOURCES,BETHESDA,MD. RI Santisteban, Pilar/E-7829-2016 OI Santisteban, Pilar/0000-0002-2758-796X NR 24 TC 3 Z9 3 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 1046-3976 J9 ENDOCR PATHOL JI Endocr. Pathol. PD MAY PY 1996 VL 7 IS 2 BP 137 EP 143 DI 10.1007/BF02739973 PG 7 WC Endocrinology & Metabolism; Pathology SC Endocrinology & Metabolism; Pathology GA UN720 UT WOS:A1996UN72000005 ER PT J AU Soriano, V Gutierrez, M Caballero, E Cilla, G Fernandez, JL Aguilera, A Tuset, C Dronda, F Martin, AM Carballo, E Lopez, I GonzalezLahoz, J deLejarazu, RO Eiros, JM Tor, J Muga, R Pujol, E Calderon, E Leal, M MartinezZapico, R Pozo, F delRomero, J Rodriguez, C Ulloa, F PerezTrallero, E Bravo, R Mas, A GarciaLerma, G PerezLabad, ML GomezCano, M Villalba, N Heredia, A Vallejo, A Hewlett, I AF Soriano, V Gutierrez, M Caballero, E Cilla, G Fernandez, JL Aguilera, A Tuset, C Dronda, F Martin, AM Carballo, E Lopez, I GonzalezLahoz, J deLejarazu, RO Eiros, JM Tor, J Muga, R Pujol, E Calderon, E Leal, M MartinezZapico, R Pozo, F delRomero, J Rodriguez, C Ulloa, F PerezTrallero, E Bravo, R Mas, A GarciaLerma, G PerezLabad, ML GomezCano, M Villalba, N Heredia, A Vallejo, A Hewlett, I TI Epidemiology of HIV-2 infection in Spain SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-2; POLYMERASE CHAIN-REACTION; HIGH-RISK INDIVIDUALS; WEST-AFRICA; INDETERMINATE SERA; TRANSMISSION; PREVALENCE; FRANCE; BISSAU; AIDS AB Human immunodeficiency virus type 2 (HIV-2) infection is endemic in West Africa, where it is responsible for many cases of AIDS. HIV-2-infected subjects have been described in other countries, mainly African immigrants, although infection in native individuals has been reported as well. The first cases of HIV-2 infection in Spain were identified in 1988. Through December 1995, 56 HIV-2-infected individuals have been diagnosed, primarily in large urban areas (23 cases in Madrid and 18 in Barcelona). All are African immigrants, except for 12 natives (21.4%), six of whom acquired the infection in endemic areas; the remaining six (2 women with numerous sexual partners and 4 homo/bisexual men) acquired the infection in Spain. Heterosexual transmission was probable in all but seven cases: five home/bisexual males, a subject who likely acquired infection through parenteral exposure, and a child born to an HIV-2-infected mother. Nine patients (all Spanish born) have developed AIDS (16%), six of whom have died. In conclusion, HIV-2 infection is present in Spain at a low rate, and there is little evidence supporting an emerging ongoing transmission outside the population of African immigrants. C1 HOSP GEN VALLE HEBRON,MICROBIOL SERV,BARCELONA,SPAIN. HOSP VIRGEN ARANZAZU,MICROBIOL SERV,SAN SEBASTIAN,SPAIN. CONSORCI HOSP,SERV TROP MED,MATARO,SPAIN. HOSP XERAL VIGO,INFECT DIS SERV,SANTIAGO COMPOSTE,SPAIN. HOSP XERAL VIGO,MICROBIOL SERV,SANTIAGO COMPOSTE,SPAIN. HOSP GEN UNIV,SERV IMMUNOL,VALENCIA,SPAIN. HOSP PENITENCIARIO,MICROBIOL SERV,MADRID,SPAIN. HOSP INSULAR,MICROBIOL SERV,LAS PALMAS,SPAIN. HOSP MEIXOEIRO,VIGO,SPAIN. HOSP CLIN,VALLADOLID,SPAIN. HOSP GERMANS TRIAS & PUJOL,BADALONA,SPAIN. HOSP JUAN RAMON JIMENEZ,HUELVA,SPAIN. HOSP VIRGEN ROCIO,SEVILLE,SPAIN. HOSP LA PAZ,MADRID,SPAIN. CTR SANDOVAL,MADRID,SPAIN. HOSP MUNICIPAL,VIGO,SPAIN. HOSP VIRGEN ARANZAZU,SAN SEBASTIAN,SPAIN. INST SALUD CARLOS III,MOLEC VIROL LAB,MADRID,SPAIN. US FDA,DIV TRANSFUS MED,BETHESDA,MD 20014. RP Soriano, V (reprint author), INST SALUD CARLOS III,CIC,INFECT DIS SERV,C SINESIO DELGADO 10,E-28029 MADRID,SPAIN. RI Leal, Manuel/C-8458-2015; IBIS, INMUNOVIROLOGI/O-9246-2015; Vallejo, Alejandro/I-5881-2015; IBIS, EPIDEMIOLOGIA/O-8791-2015; Mas, Antonio/F-2505-2011; OI Vallejo, Alejandro/0000-0001-5360-878X; Mas, Antonio/0000-0003-2563-570X; Calderon, Enrique/0000-0002-3166-5086 NR 46 TC 12 Z9 12 U1 0 U2 0 PU FRIEDR VIEWEG SOHN VERLAG GMBH PI WIESBADEN 1 PA PO BOX 5829, W-6200 WIESBADEN 1, GERMANY SN 0934-9723 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD MAY PY 1996 VL 15 IS 5 BP 383 EP 388 DI 10.1007/BF01690094 PG 6 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA UR493 UT WOS:A1996UR49300005 PM 8793396 ER PT J AU Chetty, M Pillay, VL Moodley, SV Miller, R AF Chetty, M Pillay, VL Moodley, SV Miller, R TI Response in chronic schizophrenia correlated with chlorpromazine, 7-OH-chlorpromazine and chlorpromazine sulfoxide levels SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE chlorpromazine; metabolite; therapeutic effect ID PLASMA-LEVEL; ANTIPSYCHOTIC-DRUGS; METABOLITES AB The relationship between chlorpromazine, six of its metabolites and therapeutic response in chronic schizophrenic patients was investigated in this study. Logistic regression revealed no correlation between therapeutic response and four metabolites viz. Nor, chlorpromazine, Nor, chlorpromazine, chlorpromazine-N-oxide and Nor, chlorpromazine sulfoxide. A good correlation was seen between CPZ (P=0.036), 7-hydroxychlorpromazine (P=0.004), chlorpromazine sulfoxide (P=0.002) and therapeutic response. Good therapeutic response was correlated to high levels of chlorpromazine and its 7-hydroxy metabolite while high levels of the sulfoxide metabolite appeared to have a negative effect on therapeutic response. Poor responders who had high levels of chlorpromazine also had high levels of the sulfoxide metabolite. This suggests that the difference in response may lie in the difference in the metabolism of the drug. C1 UNIV NATAL,DEPT CHEM ENGN,DURBAN,SOUTH AFRICA. US FDA,DEPT BIOPHARMACEUT,WASHINGTON,DC 20204. RP Chetty, M (reprint author), WITS UNIV,SCH MED,DEPT PHARM,7 YORK RD,JOHANNESBURG 2193,SOUTH AFRICA. NR 22 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD MAY PY 1996 VL 6 IS 2 BP 85 EP 91 DI 10.1016/0924-977X(95)00047-S PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA UT299 UT WOS:A1996UT29900001 PM 8791032 ER PT J AU Zhang, DL Yang, YF Leakey, JEA Cerniglia, CE AF Zhang, DL Yang, YF Leakey, JEA Cerniglia, CE TI Phase I and phase II enzymes produced by Cunninghamella elegans for the metabolism of xenobiotics SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE metabolism; enzyme; PAPS sulfotransferase; cytochrome P450; Cunninghamella elegans ID INTESTINAL BACTERIUM; CELL-EXTRACTS; SULFOTRANSFERASE; BAINIERI; RAT AB The filamentous fungus Cunninghamella elegans has the ability to metabolize xenobiotics, including polycyclic aromatic hydrocarbons and pharmaceutical drugs, by both phase I and II biotransformations. Cytosolic and microsomal fractions were assayed for activities of cytochrome P450 monooxygenase, aryl sulfotransferase, glutathione S-transferase, UDP-glucuronosyltransferase, UDP-glucosyltransferase, and N-acetyltransferase. The cytosolic preparations contained activities of an aryl sulfotransferase (15.0 nmol min(-1) mg(-1)), UDP-glucosyltransferase (0.27 nmol min(-1) mg(-1)) and glutathione S-transferase (20.8 nmol min(-1) mg(-1)). In contrast, the microsomal preparations contained cytochrome P450 monooxygenase activities for aromatic hydroxylation (0.15 nmol min(-1) mg(-1)) and N-demethylation (0.17 nmol min(-1) mg(-1)) of cyclobenzaprine. UDP-glucuronosyltransferase activity was detected in both the cytosol (0.09 nmol min(-1) mg(-1)) and the microsomes (0.13 nmol min(-1) mg(-1)). N-Acetyltransferase was not detected. The results from these experiments provide enzymatic mechanism data to support earlier studies and further indicate that C. elegans has a broad physiological versatility in the metabolism of xenobiotics. C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 26 TC 71 Z9 81 U1 4 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD MAY 1 PY 1996 VL 138 IS 2-3 BP 221 EP 226 DI 10.1016/0378-1097(96)00111-5 PG 6 WC Microbiology SC Microbiology GA UP376 UT WOS:A1996UP37600021 PM 9026450 ER PT J AU Hood, HL Wickett, RR Bronaugh, RL AF Hood, HL Wickett, RR Bronaugh, RL TI In vitro percutaneous absorption of the fragrance ingredient musk xylol SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID EXCISED HUMAN-SKIN; METABOLISM; PENETRATION; TOXICITY AB The percutaneous absorption of the fragrance fixative musk xylol was measured in vitro in human and hairless guinea pig skin. For comparison, musk xylol was applied to skin in an oil-in-water emulsion or the volatile solvent, methanol. After 24 hr, total absorption of musk xylol in hairless guinea pig skin was 55% from the emulsion vehicle and 45% from the methanol vehicle. With human skin, permeation of musk xylol from both vehicles decreased to 22% of the applied dose. When human studies were continued for an additional 6 days after skin surface washing, only 6% of the applied dose remained in skin. The data suggest that most of the absorbed musk xylol in skin at 24 hr will be systemically absorbed in vivo within 1 wk. Throughout the 24-hr absorption study, absorbed musk xylol was not metabolized. A permeability constant for musk xylol permeation through hairless guinea pig skin was determined by a modified procedure for the lipophilic compound. At each time point, some diffusion cells were terminated so that skin and receptor fluid levels could be determined. Under steady-state absorption the permeability constant was 6.86 x 10(-5) cm/hr. The amount of musk xylol penetrating skin from three types of cosmetic products was also calculated on the basis of actual conditions of use. Products that are applied to large areas of the body and remain on the skin for long periods will result in the greatest absorption of musk xylol. (C) 1996 Elsevier Science Ltd. C1 UNIV CINCINNATI,COLL PHARM,CINCINNATI,OH 45267. RP Hood, HL (reprint author), US FDA,OFF COSMET & COLORS,LAUREL,MD 20708, USA. NR 22 TC 30 Z9 31 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD MAY PY 1996 VL 34 IS 5 BP 483 EP 488 DI 10.1016/0278-6915(96)87359-5 PG 6 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA UQ161 UT WOS:A1996UQ16100007 PM 8655098 ER PT J AU Larkin, JW Spinak, SH AF Larkin, JW Spinak, SH TI Safety considerations for ohmically heated, aseptically processed, multiphase low-acid food products SO FOOD TECHNOLOGY LA English DT Article; Proceedings Paper CT IFT Biotechnology Symposium on Food Allergy, at the Annual Meeting of the Institute-of-Food-Technologists CY JUN 03-07, 1995 CL ANAHEIM, CA SP Inst Food Technologists ID MIXTURES AB The uniqueness of an ohmic heater requires an understanding of critical factors not typical to a conduction-heated food product C1 US FDA,WASHINGTON,DC 20204. RP Larkin, JW (reprint author), US FDA,NATL CTR FOOD SAFETY & TECHNOL,FOOD PROC HAZARD ANAL BRANCH,6502 S ARCHER RD,SUMMIT ARGO,IL 60501, USA. NR 17 TC 14 Z9 14 U1 0 U2 0 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA SUITE 300 221 N LASALLE ST, CHICAGO, IL 60601-1291 SN 0015-6639 J9 FOOD TECHNOL-CHICAGO JI Food Technol. PD MAY PY 1996 VL 50 IS 5 BP 242 EP 245 PG 4 WC Food Science & Technology SC Food Science & Technology GA UN005 UT WOS:A1996UN00500035 ER PT J AU Zhang, SD Kassis, J Olde, B Mellerick, DM Odenwald, WF AF Zhang, SD Kassis, J Olde, B Mellerick, DM Odenwald, WF TI Pollux, a novel Drosophila adhesion molecule, belongs to a family of proteins expressed in plants, yeast, nematodes, and man SO GENES & DEVELOPMENT LA English DT Article DE pollux; Drosophila; adhesion protein; trachea; CNS ID AMINO-ACID SEQUENCE; CELL-ADHESION; SEA-URCHIN; IMMUNOGLOBULIN SUPERFAMILY; EXTRACELLULAR-MATRIX; NEURAL DEVELOPMENT; RECOGNITION; RECEPTORS; GENE; IDENTIFICATION AB Adhesion molecules have pivotal roles in cellular processes critical to the development and maintenance of multicellular organisms. Here we describe a new member of the adhesive repertoire encoded by the Drosophila pollux (pix) gene. Marked by a novel 74-amino-acid domain, Pix belongs to a highly conserved family with members in plants, yeast, nematodes, and man, including the human oncoprotein TRE17. Essential for viability, pix mutant analysis indicates that larval death is attributable to asphyxiation brought on by fluid-congested tracheal tubes. Ultrastructural examination of mutant tracheae reveals defects in cell-extracellular matrix contacts. During embryogenesis, Pix uniformly covers the apical surface of cellular blastoderm cells. It is later found regionally concentrated along subsets of central nervous system axon pathways and on the apical surface of the trachea's tubular epithelium. Cell attachment assays demonstrate that pix can serve as a ligand for cell surface integrins. Pix also contains a motor neuron-selective adhesive site, multiple proteoglycan-binding motifs, and a leucine zipper: all suggest possible associations with additional components of the adhesion complex. C1 NINCDS,NIH,NEUROGENET UNIT,NEUROCHEM LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. NINCDS,NIH,NEUROGENET CTR,BETHESDA,MD 20892. OI Kassis, Judith/0000-0001-9268-3213 NR 67 TC 29 Z9 29 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 1 PY 1996 VL 10 IS 9 BP 1108 EP 1119 DI 10.1101/gad.10.9.1108 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA UL248 UT WOS:A1996UL24800006 PM 8654926 ER PT J AU Kurokohchi, K Carrington, M Mann, DL Simonis, TB AlexanderMiller, MA Feinstone, SM Akatsuka, T Berzofsky, JA AF Kurokohchi, K Carrington, M Mann, DL Simonis, TB AlexanderMiller, MA Feinstone, SM Akatsuka, T Berzofsky, JA TI Expression of HLA class I molecules and the transporter associated with antigen processing in hepatocellular carcinoma SO HEPATOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; HEPATOMA-CELL LINE; LYMPHOCYTE-T; GENES; MHC; RECOGNITION; SPECIFICITY; PEPTIDES; REGION AB The expression of the HLA class I molecules on the cell surface was investigated in hepatocellular carcinoma (HCC) cell lines using complement-mediated cytotoxicity (CMC) and flow cytometric analysis, Although HLA-A antigens were detected by CMC in all cell Lines tested, HLA-B and-C antigens were not detectable in six of seven HCC cell lines. These results were also confirmed by now cytometric analysis focusing on HLA-Bw4 and Bw6 public antigens, Furthermore, complementary DNA (cDNA) hom each cell line was tested for the expression of HLA-A, -B, -C and the transporter associated with antigen processing genes (TAP1 and TAP2). Two cell lines showed a reduced level of one or both of the TAP messenger RNAs (mRNAs), and one of these showed a reduction of HLA-B and -C gene expression as well, but the others had detectable mRNA levels. These results demonstrate that hepatocellular carcinoma cell lines tested in the current study lose or decrease the expression of HLA-B and -C alleles on the cell surface, even though mRNA encoding these alleles is present, suggesting that the loss of the HLA molecules might be caused by posttranscriptional events or failure to transport and load peptides necessary for HLA expression, The selective loss of HLA-B and -C, but not -A, molecules (which also excludes a beta(2)-microglobulin defect) is intriguing, and may be attributable to the ability of some of the HLA-A molecules to load signal peptides not requiring TAP transport, or to natural selection by HLA-B or -C locus-specific immune surveillance. C1 NCI,METAB BRANCH,MOLEC IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD. NIH,DEPT TRANSFUS MED,CTR CLIN,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,LAB HEPATITIS RES,BETHESDA,MD. NR 45 TC 54 Z9 58 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 1996 VL 23 IS 5 BP 1181 EP 1188 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UJ443 UT WOS:A1996UJ44300037 PM 8621152 ER PT J AU Conte, ED Miller, DW AF Conte, ED Miller, DW TI A solid phase microextraction-electrodeposition device for the determination of putrescine and cadaverine by high resolution gas chromatography SO HRC-JOURNAL OF HIGH RESOLUTION CHROMATOGRAPHY LA English DT Article DE solid phase microextraction; gas chromatography; thermionic detection; putrescine; cadaverine ID AMINES C1 NATL CTR TOXICOL RES,DEPT CHEM,JEFFERSON,AR 72079. NR 9 TC 16 Z9 16 U1 2 U2 3 PU DR ALFRED HUTHIG VERLAG GMBH PI HEIDELBERG 1 PA POSTFACH 102869, W-69018 HEIDELBERG 1, GERMANY SN 0935-6304 J9 HRC-J HIGH RES CHROM JI HRC-J. High Resolut. Chromatogr. PD MAY PY 1996 VL 19 IS 5 BP 294 EP 297 PG 4 WC Chemistry, Analytical SC Chemistry GA UP863 UT WOS:A1996UP86300011 ER PT J AU Waynant, RW AF Waynant, RW TI From the editor-in-chief SO IEEE CIRCUITS AND DEVICES MAGAZINE LA English DT Editorial Material RP Waynant, RW (reprint author), US FDA,1901 CHAPMAN AVE,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 8755-3996 J9 IEEE CIRCUIT DEVIC JI IEEE Circuit Devices Mag. PD MAY PY 1996 VL 12 IS 3 BP 2 EP 2 PG 1 WC Engineering, Electrical & Electronic; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA UL091 UT WOS:A1996UL09100001 ER PT J AU Waynant, RW Fuller, R AF Waynant, RW Fuller, R TI Software and the web SO IEEE CIRCUITS AND DEVICES MAGAZINE LA English DT Editorial Material RP Waynant, RW (reprint author), US FDA,1901 CHAPMAN AVE,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 8755-3996 J9 IEEE CIRCUIT DEVIC JI IEEE Circuit Devices Mag. PD MAY PY 1996 VL 12 IS 3 BP 53 EP 53 PG 1 WC Engineering, Electrical & Electronic; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA UL091 UT WOS:A1996UL09100014 ER PT J AU Oza, NB Weinberg, MS Oza, MN AF Oza, NB Weinberg, MS Oza, MN TI rK7-kallikrein in rat kidney and urine SO IMMUNOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 14th International Symposium on Bradykinin and Related Kinins (KININ 95) CY SEP 10-15, 1995 CL DENVER, CO DE kallikrein; kallikrein-like enzyme; kallikrein isoenzyme; kallikrein-kinin system; hypertension; renal hypertension ID KALLIKREIN-KININ SYSTEM AB Rat Kidney is reported to contain the rK7-kallikrein gene expressed at a high mRNA level. However, there is no diner evidence that the rK7 enzyme is present in kidney or urine. We have analyzed rat kidney and urine for rK7-like enzyme activity, using distinctive properties of purified rK7 enzyme (hydrolysis of specific substrate, inhibition by SBTI). Rat urine and kidney cortex contain substantial levels of rK7-like enzyme activity. Nearly 40% of the enzyme in urine is in an active form while nearly all of the rK7 in kidney cortex is in the inactive form. Treatment with low salt diet and mineralocorticoid increases rK7 in both kidney cortex and urine approximately 2-fold. The percentage of active enzyme in urine increases markedly on this regimen. C1 BROWN UNIV,ROGER WILLIAMS MED CTR,DEPT MED,SECT HYPERTENS & NEPHROL,PROVIDENCE,RI 02904. RP Oza, NB (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV CARDIORENAL DRUG PROD,USPHS,HFD-110,ROCKVILLE,MD 20857, USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0162-3109 J9 IMMUNOPHARMACOLOGY JI Immunopharmacology PD MAY PY 1996 VL 32 IS 1-3 BP 102 EP 104 DI 10.1016/0162-3109(95)00064-X PG 3 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA UR643 UT WOS:A1996UR64300026 PM 8796280 ER PT J AU HorvathArcidiacono, JA Mostowski, HS Bloom, ET AF HorvathArcidiacono, JA Mostowski, HS Bloom, ET TI IL-12 administered in vivo to young and aged mice. Discrepancy between the effects on tumor growth in vivo and cytotoxic T lymphocyte generation ex vivo: Dependence on IFN-gamma SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE aging; CD4(+); CD8(+); IL-4; IL-10; immunotherapy; NK cells; splenomegaly ID CELL STIMULATORY FACTOR; INTERFERON-GAMMA; HETERODIMERIC CYTOKINE; MATURATION FACTOR; FACTOR NKSF; INTERLEUKIN-12; PROLIFERATION; TH1; PURIFICATION; EXPRESSION AB Because IL-12 restores allogeneic cytotoxic T lymphocyte (CTL) activity by T cells of aged mice in vitro, we initially assessed whether IL-12 could overcome age-related deficits when given to aged mice in vivo. Growth of P815 (H-2(d)) was enhanced in aged compared with young BALB/c (H-2(d)) mice and tumor growth was curtailed by IL-12 in both age groups, Unexpectedly, secondary CTL stimulated ex vivo with P815 were reduced in IL-12-treated mice compared with controls. Primary CTL generated ex vivo across MHC differences in IL-12-treated BALB/c and C57BL/6 young mice were reduced by 90-99%, were dose- and time-dependent, and were associated with reduced allo-stimulated NK-like activity and [H-3]thymidine incorporation. IFN-gamma was elevated in sera and in supernatants from allo-stimulated cultures from IL-12-treated mice, while IL-4 was reduced in such supernatants, suggesting that, despite reduced CTL, IL-12 was associated with increased T(h)1- and reduced T(h)2-type cytokine production. IL-12 also induced splenomegaly, primarily due to increased numbers of cells lacking markers of mature T, B and NK cells, or macrophages, or polymorphonuclear leukocyte morphology. IFN-gamma mutant mice exhibited reduced splenic enlargement in response to IL-12, suggesting that the splenomegaly was due, in part, to IFN-gamma production, However, reduced CTL generation was not due entirely to dilution of CTL precursor cells because spleen cellularity and size increased 3-fold while CTL activity decreased 10- to 100-fold, and CTL generation normalized to CD8(+) T effector cells was still significantly reduced in IL-12-treated mice. Interestingly, purified CD4(+) and CD8(+) T cells from IL-12-treated normal mice exhibited greater proliferative and cytolytic activities respectively compared with controls, Thus, effector T cells in IL-12-treated mice were not impaired, but exhibited augmented responsiveness, suggesting that IL-12 induced complex interactions among spleen cell populations and that these effects, in part,are mediated by IFN-gamma. C1 CTR BIOL EVALUAT RES FOOD & DRUG ADM,LAB CELLULAR IMMUNOL HFM 518,DIV CELL & GENE THERAPIES,BETHESDA,MD 20892. NR 64 TC 6 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAY PY 1996 VL 8 IS 5 BP 661 EP 673 DI 10.1093/intimm/8.5.661 PG 13 WC Immunology SC Immunology GA UN188 UT WOS:A1996UN18800004 PM 8671653 ER PT J AU Shparago, N Zelazowski, P Jin, L McIntyre, TM Stuber, E Pecanha, LMT Kehry, MR Mond, JJ Max, EE Snapper, CM AF Shparago, N Zelazowski, P Jin, L McIntyre, TM Stuber, E Pecanha, LMT Kehry, MR Mond, JJ Max, EE Snapper, CM TI IL-10 selectively regulates murine Ig isotype switching SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE anti-Ig-dextran; CD40; CD40 ligand; digestion-circularization PCR; IL-4; IL-5; lipopolysaccharide; transforming growth factor-beta ID HUMAN B-CELLS; CYTOKINE PRODUCTION; IMMUNOGLOBULIN-A; LYMPHOCYTES-B; INTERLEUKIN-10; TRANSCRIPTS; ANTIBODY; GROWTH; RECOMBINATION; EXPRESSION AB A role for IL-10 in regulating Ig isotype switching directly at the level of the murine B cell has not been previously reported, In this report we show that IL-10 selectively up-regulated IgM to IgG3 class switching in lipopolysaccharide (LPS)-activated cultures through a direct effect on membrane (m) IgM(+)IgG3(-) B cells in vitro. IL-10 stimulated a 3- to 4-fold enhancement (from 6-8 to 20-30%) in membrane mIgG3(+) cells and a significant increase in S-mu-S(gamma)3 DNA rearrangement events as measured by digestion-circularization PCR (DC-PCR) over that observed with LPS alone, IL-10 induction of switching to lgG3 was not accompanied by a corresponding increase in the steady-state levels of germline C(H gamma)3 RNA, By contrast, IL-10 strongly inhibited the transforming growth factor-beta-mediated generation of mIgA(+) cells and S-mu-S-alpha DNA rearrangement events in LPS-, but not CD40 ligand (CD40L)-activated B cells, This effect was not accompanied by changes in the steady-state levels of germline C-H alpha RNA. IL-10 had no effect on IL-4-mediated switching to either IgG1 or IgE in either LPS- or CD40L-activated B cells, Thus, IL-10 can either enhance or suppress switching to particular murine Ig isotypes but it differs from most other murine cytokines in that its effects on switching do not appear to be associated with changes in the corresponding steady-state levels of germline C-H RNA. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. NIH,CLIN INVEST LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. IM UFRJ,DEPTO IMUNOL,RIO JANEIRO,BRAZIL. BOEHRINGER INGELHEIM PHARMACEUT INC,RIDGEFIELD,CT 06877. FU NIAID NIH HHS [AI32560, AI36588] NR 40 TC 35 Z9 35 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAY PY 1996 VL 8 IS 5 BP 781 EP 790 DI 10.1093/intimm/8.5.781 PG 10 WC Immunology SC Immunology GA UN188 UT WOS:A1996UN18800018 PM 8671667 ER PT J AU Fu, TJ AF Fu, TJ TI Kinetics of the formation and decomposition of 1,1'-ethylidenebis[L-tryptophan], an eosinophilia myalgia syndrome-associated compound SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE 1,1'-ethylidenebis[L-tryptophan]; peak E; L-tryptophan; eosinophilia myalgia syndrome; kinetics ID POSSIBLE CAUSATIVE SUBSTANCE; PEAK-E-SUBSTANCE; L-TRYPTOPHAN; 1-METHYL-1,2,3,4-TETRAHYDRO-BETA-CARBOLINE-3-CARBOXYLIC ACID; 1,1'-ETHYLIDENEBIS(L-TRYPTOPHAN); IDENTIFICATION; CONTAMINANTS; INGESTION; RATS; EMS AB 1, 1'-Ethylidenebis[L-tryptophan] (EBT), an impurity found in L-tryptophan associated with eosinophilia myalgia syndrome (EMS), has been suggested as one of the causative agents for EMS. Highperformance liquid chromatography was used to study the kinetics of EBT formation and decomposition in buffer systems. Initial EBT decomposition was first-order with respect to EBT and strongly pH-dependent. The pH profile suggested that decomposition involved the addition of one proton. The value of the critical pH, above which the rate of EBT decomposition remained constant, was determined to be 4.8. The rate of EBT decomposition increased with increasing temperature, and the activation energy was calculated to be 12.5 kcal/mol. The rate of EBT formation decreased with increasing pH and decreasing temperature. The presence of excess acetaldehyde increased EBT formation to a lesser extent than did the presence of excess L-tryptophan. The results of this study are consistent with the hypothesis that EBT was formed during the absorption stage of the cation exchange operation in the commercial process that resulted in the formation of EMS-associated L-tryptophan. RP Fu, TJ (reprint author), US FDA,NATL CTR FOOD SAFETY & TECHNOL,6502 S ARCHER RD,SUMMIT ARGO,IL 60501, USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY PY 1996 VL 44 IS 5 BP 1224 EP 1229 DI 10.1021/jf950421d PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA UL585 UT WOS:A1996UL58500010 ER PT J AU Akasawa, A Hsieh, LS Lin, Y AF Akasawa, A Hsieh, LS Lin, Y TI Comparison of latex-specific IgE binding among nonammoniated latex, ammoniated latex, and latex glove allergenic extracts by ELISA and immunoblot inhibition SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE latex allergens; latex proteins; latex glove AB Background: Nonammoniated latex, ammoniated latex, and latex glove extracts have been used as source materials for the preparation of allergenic extracts for the diagnosis of latex allergy. These materials showed different patterns of protein bands and immunoreactive bands. However, their IgE-reactive repertoires were not compared. Objective: The goals of this study were to compare the IgE reactivity and to define the common IgE-reactive epitopes among three latex allergenic extracts. Methods: Two serum pools were obtained from adults and children with latex allergy to evaluate the IgE reactivity among three latex extracts. IgE reactivity and IgE-reactive proteins were compared by inhibition ELISA and inhibition immunoblot methods, respectively. Results: In this study inhibition curves were similar for nonammoniated latex and ammoniated latex but were different when the latex glove extracts were used. Several protein bands of ammoniated latex and latex glove extracts could not be inhibited by the nonammoniated latex. The ammoniated latex and latex glove extracts were able to remove all the latex-specific IgE from the serum. Conclusion: The IgE-reactive proteins differ among different latex extracts. Ammoniated latex and latex glove extracts contain more complete immunoreactive repertoires for detecting IgE antibodies. Our study provide useful information for selecting the latex extract. C1 CBER,FD,DIV ALLERGEN PROD & PARASITOL,LAB IMMUNOCHEM,ROCKVILLE,MD 20852. NR 4 TC 20 Z9 20 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 1996 VL 97 IS 5 BP 1116 EP 1120 DI 10.1016/S0091-6749(96)70266-X PG 5 WC Allergy; Immunology SC Allergy; Immunology GA UL261 UT WOS:A1996UL26100013 PM 8626990 ER PT J AU Horwitz, W Albert, R AF Horwitz, W Albert, R TI Reliability of the determinations of polychlorinated contaminants (biphenyls, dioxins, furans) SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID DIBENZO-P-DIOXIN; CHROMATOGRAPHY-MASS-SPECTROMETRY; GAS-CHROMATOGRAPHY; PRECISION PARAMETERS; QUALITY ASSURANCE; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; MATRICES; LIMITS; PCDDS; PCDFS AB Precision performance parameters from results of 34 interlaboratory performance studies of polychlorinated aromatic ring compounds (biphenyls, dioxins, and furans) (PCCs) have been recalculated by using the International Union of Pure and Applied Chemistry-1987 harmonized protocol, Most studies of 1052 test samples, 56 analytes, 19 matrixes, and 2 types of detectors (electron capture and mass spectrometers) provide among-laboratories relative standard deviations (RSD(R)s), that are considerably better than those predicted from the Horwitz equation at fractional concentrations of 10(-6) down to 10(-15). The explanation suggested is that supplying common reference calibration solutions, as was done in many of these studies, does not reflect realistic operating conditions, Furthermore, the ability to repeat, discuss, and reassess aberrant reported values results in underestimating the true RSD(R). The commonly reported problems of preparation of standard calibrating solutions, instability of the detection system, and failure to follow quality control instructions and good laboratory practices may be important sources of interlaboratory variability in PCC determinations. RP Horwitz, W (reprint author), US FDA,200 C ST SW,WASHINGTON,DC 20204, USA. NR 53 TC 42 Z9 42 U1 1 U2 4 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1996 VL 79 IS 3 BP 589 EP 621 PG 33 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA UN110 UT WOS:A1996UN11000002 PM 8634528 ER PT J AU Doub, WH Ruhl, DD Hart, B Mehelic, PR Revelle, LK AF Doub, WH Ruhl, DD Hart, B Mehelic, PR Revelle, LK TI Gradient liquid chromatographic method for determination of chlorhexidine and its degradation products in bulk material SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID 4-CHLOROANILINE; DIGLUCONATE AB A liquid chromatographic method was developed for determination of chlorhexidine and its degradation products in unformulated drug substance. A nonlinear gradient from 80% 0.1 M ammonium acetate buffer, pH 5.0, to 20% buffer over 90 min (balance is acetonitrile) is applied to a 3 mu m octadecylsilane bonded-phase column. The drug and some of its degradation products are determined at 230 nm. Of 11 previously identified degradation products, 9 are determined with good precision (relative standard deviation of peak area is <2%). C1 US FDA,DIV DRUG ANAL,ST LOUIS,MO 63101. NR 21 TC 8 Z9 10 U1 0 U2 5 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1996 VL 79 IS 3 BP 636 EP 639 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA UN110 UT WOS:A1996UN11000005 PM 8634531 ER PT J AU Feng, P AF Feng, P TI Emergence of rapid methods for identifying microbial pathogens in foods SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID IDENTIFICATION; SALMONELLA; SYSTEMS AB Because of the complexities of food analysis, conventional microbiological methods must use time-consuming enrichment steps for culturing viable bacterial cells in foods. With rapid advancements in technology, however, numerous so-called rapid methods were introduced into the field of food microbiology in a relatively short time, Culture methods that were once used to obtain profiles for bacterial identification were simplified or automated, Many microbiological procedures were also streamlined or automated to reduce assay time, labor, and materials, Nucleic acid-based assays are used to identify gene sequences in foodborne bacteria, and antibody-based assays are used in numerous formats to detect bacterial pathogens and toxins in foods. The difficulties of analyzing food, however, remain challenging, and rapid methods need to be evaluated thoroughly before they are used for routine food analysis. RP Feng, P (reprint author), US FDA,DIV MICROBIOL STUDIES,200 C ST SW,WASHINGTON,DC 20204, USA. NR 14 TC 24 Z9 24 U1 1 U2 5 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1996 VL 79 IS 3 BP 809 EP 812 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA UN110 UT WOS:A1996UN11000032 PM 8634549 ER PT J AU Perfetti, GA AF Perfetti, GA TI Determination of heterocyclic aromatic amines in process flavors by a modified liquid chromatographic method SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MUTAGENS; FOOD AB A liquid chromatographic method for determining heterocyclic aromatic amines (HAAs) was modified so that it can be used to quantitate the following 5 HAAs in complex process flavors: 2-amino-3-methylimidazo[4,5-f]quinoline (IQ); 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ); 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx); 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (diMeIQx); and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). By changing the initial extraction procedure, PhIP recovery improved from 35 to 87%. An additional cleanup step using ion-exchange solid-phase extraction reduced the levels of interfering components, thus allowing determination of low levels of the amines. Recoveries from process flavors spiked at 25 ppb averaged 83-90%. RP Perfetti, GA (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,200 C ST SW,WASHINGTON,DC 20204, USA. NR 5 TC 20 Z9 20 U1 0 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1996 VL 79 IS 3 BP 813 EP 816 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA UN110 UT WOS:A1996UN11000033 ER PT J AU Prival, MJ AF Prival, MJ TI Isolation of glutamate-inserting ochre suppressor mutants of Salmonella typhimurium and Escherichia coli SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LINKAGE MAP; GLTT AB Glutamate-inserting ochre suppressors have been identified among late-arising, spontaneous revertants of a hisG428 mutant of Salmonella typhimurium and an argE3 mutant of Escherichia coli. The S. typhimurium suppressors mapped in the tRNA(2)(Glu) gene gltU at 82 min; those in E. coli were found to be in tRNA(2)(Glu) genes gltW at 56 min, gltU at 85 min, and gltT at 90 min. RP Prival, MJ (reprint author), US FDA,GENET TOXICOL BRANCH,HFS-226,200 C ST SW,WASHINGTON,DC 20204, USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 1996 VL 178 IS 10 BP 2989 EP 2990 PG 2 WC Microbiology SC Microbiology GA UL275 UT WOS:A1996UL27500037 PM 8631694 ER PT J AU Goldman, SA Lieberman, R Kausal, DJ AF Goldman, SA Lieberman, R Kausal, DJ TI Teaching healthcare professionals about drug-induced disease: An innovative clinical therapeutic approach SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID PHARMACOLOGY; CURRICULUM; ATTITUDES; EVENTS AB An innovative conference on the general principles of recognition and management of drug-induced disease was developed for healthcare professionals (particularly primary care). The full-day conference used a clinical therapeutic approach and was a cooperative effort of the United Stales Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) Staff College and Georgetown University Medical Center (GUMC). Linked with the FDA MedWatch postmarketing surveillance initiative, the conference used multiple formats, including didactic presentations, panel discussions, and case discussions led by faculty from various disciplines (e.g., internal and family medicine, psychiatry, clinical pharmacology, dentistry, clinical pharmacy, nursing, epidemiology). Conference topics included new drug approval, pharmacokinetic/pharmacodynamic considerations, and clinical assessment of adverse drug events. Tests were administered to participants before and after the conference, and participants completed a conference evaluation, Mean scores for the pre- and posttests were compared globally and by professional discipline. Conference evaluations were assessed for responses to eight standardized statements and elicited comments. After the conference, mean and median test scores were improved both globally and by discipline in comparison to pretest results, with improvement on almost all individual test questions. Comparison of median scores for the pre- and posttests showed small differences between physicians and pharmacists. Evaluations showed markedly positive response to standardized statements, including enhancement of professional growth; elicited comments were supportive of conference effectiveness and attendee acceptance. This conference, which utilized a combination of educational formats, was designed to present material of an innovative nature. Results indicate that the conference was well received and fulfilled specified learning objectives, including recognition of populations particularly vulnerable to adverse drug events and understanding of how individual providers can contribute to FDA postmarketing surveillance. Continuing educational efforts using this approach are encouraged. C1 US FDA,OFF COMMISSIONER,ROCKVILLE,MD 20857. US FDA,CTR DRUG EVALUAT & RES,DIV TRAINING & DEV,OFF TRAINING & COMMUN,ROCKVILLE,MD 20857. NR 19 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAY PY 1996 VL 36 IS 5 BP 386 EP 396 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UL678 UT WOS:A1996UL67800002 PM 8739016 ER PT J AU Webster, PA Roberts, DW Benson, RW Kearns, GL AF Webster, PA Roberts, DW Benson, RW Kearns, GL TI Acetaminophen toxicity in children: Diagnostic confirmation using a specific antigenic biomarker SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID INDUCED HEPATIC NECROSIS; COVALENT BINDING; YOUNG-CHILD; 3-(CYSTEIN-S-YL)ACETAMINOPHEN ADDUCTS; PARACETAMOL TOXICITY; LIVER PROTEINS; TREATED MICE; HEPATOTOXICITY; GLUTATHIONE; KINETICS AB Chronic acetaminophen (APAP) toxicity poses a difficult diagnostic challenge to the clinician. Signs and symptoms are nonspecific and no currently available laboratory study can confirm APAP as the causative agent of hepatic injury. In this study an antigenic biomarker for APAP toxicity was used to confirm the diagnosis of APAP-induced hepatic failure in two children with chronic APAP toxicity. APAP that has been metabolized to N-acetyl-benzoquinone imine (NAPQI) reacts with cellular proteins to form 3-(cystein-S-yl)-APAP protein adducts (3-Cys-A). Serum from both patients was submitted for quantitation of 3-Cys-A by a competitive inhibition enzyme-linked immunosorbent assay (ELISA). Concentrations of 3-Cys-A in the two patients were 1.97 and 2.77 nmol/mg protein, which are similar to concentrations found in adults with hepatic injury secondary to an overdose of APAP. Individuals with no exposure to APAP have no detectable 3-Cys-A in serum. It was concluded that 3-Cys-A is a useful marker of APAP intoxication after long-term ingestion of APAP when total dose and time course of ingestion are uncertain, and may prove to be a useful clinical and investigative tool in the study of APAP intoxication. C1 UNIV ARKANSAS MED SCI HOSP,DEPT PEDIAT,DIV PEDIAT CRIT CARE,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT PEDIAT,DIV PEDIAT CLIN PHARMACOL,LITTLE ROCK,AR 72205. NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079. NR 46 TC 34 Z9 34 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAY PY 1996 VL 36 IS 5 BP 397 EP 402 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UL678 UT WOS:A1996UL67800003 PM 8739017 ER PT J AU Guan, E Wang, JH Laborda, J Norcross, M Baeuerle, P Hoffman, T AF Guan, E Wang, JH Laborda, J Norcross, M Baeuerle, P Hoffman, T TI T cell leukemia-associated human notch translocation-associated notch homologue has I kappa B-like activity and physically interacts with nuclear Factor-kappa B proteins in T cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CANDIDATE PROTOONCOGENE BCL-3; DNA-BINDING; TRANSCRIPTION FACTORS; DROSOPHILA-NOTCH; REL ONCOGENE; CAENORHABDITIS-ELEGANS; ONCOPROTEIN BCL-3; ANKYRIN REPEATS; PRECURSOR P105; CYCLE CONTROL AB Translocation-associated Notch homologue (TAN-1), a gene originally cloned from the translocation breakpoint of a human T cell leukemia carrying a 9:7(q34.3) translocation, encodes a protein belonging to the Notch/Lin-12/Glp-1 receptor family. These receptors mediate the specification of numerous cell fates during development in invertebrates and vertebrates. The intracellular portion of Notch/TAN-1 contains six ankyrin repeats that are similar to those found in cytoplasmic I kappa B proteins. I kappa B proteins are specific inhibitors of nuclear factor (NF)-kappa B/Rel transcription factors. Here we show that TAN-1 has functional properties of an I kappa B-like regulator with specificity for the NF-kappa B p50 subunit. A recombinant polypeptide corresponding to the cytoplasmic portion of TAN-1 (TAN-1(C)) specifically inhibited the DNA binding of p50-containing NF-kappa B complexes. When overexpressed in an appropriate cell Line, TAN-le prevented kappa B-dependent transactivation in transient reporter gene assays in a fashion similar to the structurally related protein, Bcl-3. TAN-1(C) could activate kappa B-dependent gene expression by attenuating the inhibitory effect of an excess of p50 homodimers. Immunoprecipitation experiments showed that the TAN-1 from a T cell line is associated with NF-kappa B containing p50 and p65 subunits. These observations indicate that TAN-1(C) may directly engage NF-kappa B transcription factors and modulate nuclear gene expression. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,CELL BIOL LAB,BETHESDA,MD 20892. TULARIK INC,DEPT DRUG DISCOVERY,SAN FRANCISCO,CA 94080. RP Guan, E (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV MONOCLONAL ANTIBODIES,CELL BIOL LAB,BLDG 29B,ROOM 4G03,BETHESDA,MD 20892, USA. RI Laborda, Jorge/L-5726-2014 OI Laborda, Jorge/0000-0002-9210-838X NR 55 TC 107 Z9 112 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 1 PY 1996 VL 183 IS 5 BP 2025 EP 2032 DI 10.1084/jem.183.5.2025 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UM424 UT WOS:A1996UM42400011 PM 8642313 ER PT J AU Combadiere, B Freedman, M Chen, L Shores, EW Love, P Lenardo, MJ AF Combadiere, B Freedman, M Chen, L Shores, EW Love, P Lenardo, MJ TI Qualitative and quantitative contributions of the T cell receptor zeta chain to mature T cell apoptosis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ANTIGEN RECEPTOR; SIGNAL TRANSDUCTION; TYROSINE KINASE; CYTOPLASMIC TAIL; COMPLEX; ACTIVATION; PROTEIN; DEATH; INTERLEUKIN-2; MUTAGENESIS AB Engagement of the T cell receptor (TCR) of mature T lymphocytes can lead either to activation/proliferation responses or programmed cell death. To understand the molecular regulation of these two fundamentally different outcomes of TCR signaling, we investigated the participation of various components of the TCR-CD3 complex. We found that the TCR-zeta chain, while not absolutely required, was especially effective at promoting mature T cell apoptosis compared with the CD3 epsilon, gamma, or delta chains. We also carried out mutagenesis to address the role of the immunoreceptor tyrosine-based activation motifs (ITAMs) that are the principal signaling components found three times in the TCR-zeta chain and once in each of the CD3 epsilon, gamma, or delta chains. We found that the ability of the TCR-zeta chain to promote apoptosis results both from a quantitative effect of the presence of multiple ITAMs as well as qualitatively different contributions made by individual ITAMs. Apoptosis induced by single chain chimeras revealed that the first zeta ITAM stimulated greater apoptosis than the third zeta ITAM, and the second zeta ITAM was unable to trigger apoptosis. Because microheterogeneity in the amino acid sequence of the various ITAM motifs found in the TCR-zeta and CD3 chains predicts interactions with distinct src-homology-2-domain signaling proteins, our results suggest the possibility that individual ITAM motifs might play unique roles in TCR responses by engaging specific signaling pathways. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. NICHHD,NIH,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. RP Combadiere, B (reprint author), NIAID,NIH,IMMUNOL LAB,BLDG 10,BETHESDA,MD 20892, USA. RI Combadiere, Behazine/G-3881-2013 NR 45 TC 73 Z9 74 U1 1 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 1 PY 1996 VL 183 IS 5 BP 2109 EP 2117 DI 10.1084/jem.183.5.2109 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UM424 UT WOS:A1996UM42400019 PM 8642321 ER PT J AU Reddy, NR Paradis, A Roman, MG Solomon, HM Rhodehamel, EJ AF Reddy, NR Paradis, A Roman, MG Solomon, HM Rhodehamel, EJ TI Toxin development by Clostridium botulinum in modified atmosphere-packaged fresh tilapia fillets during storage SO JOURNAL OF FOOD SCIENCE LA English DT Article DE fish; tilapia; Clostridium botulinum; toxin development; modified atmospheres ID NONPROTEOLYTIC TYPE-B; SHELF-LIFE EXTENSION; GROWTH; VACUUM; FISH; PROBABILITY; RISK AB Potential for toxin development by Clostridium botulinum type E was investigated in retail-type packages of fresh tilapia fillets packaged in high barrier film under selected atmospheres [100% air, a modified atmosphere (MA) containing 75%CO2:25%N-2, and vacuum] and stored under refrigeration (4 degrees C) and abuse temperatures (8 and 16 degrees C). Toxin development coincided with sensory spoilage at 16 degrees C storage for fillets packaged in either MA, or vacuum. At 8 degrees C, toxin development in fillets packaged in either of the atmospheres occurred 7-23 days after sensory spoilage. At 4 degrees C, none of MA-packaged fillets became toxic until 10 days after onset of sensory spoilage. Toxin development did not precede sensory spoilage in any treatments or temperatures studied. C1 KRAFT GEN FOODS INC,CTR TECHNOL,GLENVIEW,IL 60025. US FDA,DIV MICROBIOL STUDIES,WASHINGTON,DC 20204. US FDA,DIV HACCP PROGRAMS,WASHINGTON,DC 20204. LIQUID CARBON IND CORP,CTR TECH,CHICAGO,IL 60626. RP Reddy, NR (reprint author), US FDA,NATL CTR FOOD SAFETY & TECHNOL,DIV FOOD PROC & PACKAGING,6502 S ARCHER RD,SUMMIT ARGO,IL 60501, USA. NR 25 TC 24 Z9 26 U1 1 U2 3 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA SUITE 300 221 N LASALLE ST, CHICAGO, IL 60601-1291 SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD MAY-JUN PY 1996 VL 61 IS 3 BP 632 EP 635 DI 10.1111/j.1365-2621.1996.tb13174.x PG 4 WC Food Science & Technology SC Food Science & Technology GA UQ367 UT WOS:A1996UQ36700038 ER PT J AU BroussardDiehl, C Bauer, SR Scheuermann, RH AF BroussardDiehl, C Bauer, SR Scheuermann, RH TI A role for c-myc in the regulation of thymocyte differentiation and possibly positive selection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR TRANSGENIC MICE; APOPTOTIC CELL-DEATH; NEGATIVE SELECTION; CD4+8+ THYMOCYTES; ANTIGEN RECEPTOR; T-LYMPHOCYTES; EXPRESSION; BCL-2; MURINE; MATURATION AB The purpose of thymocyte differentiation is to establish the T cell repertoire and eliminate nonfunctional and autoreactive T cells, In an analysis of potential regulators of this process, we have found that c-myc expression is down-regulated dramatically during early thymocyte differentiation and subsequently up-regulated along with TCR/CD3 in CD4(+)8(+) cells, Transgenic E beta-myc mice that constitutively express c-myc in thymocytes have a larger proportion of thymocytes with high TCR/CD3 and low heat-stable antigen-1 expression than controls, and an increase in the number of transitional cells with a CD4(+)CD8(low) phenotype, Mature E beta-myc T cells respond less vigorously than controls to activation through their TCR/CD3 complex, as measured by proliferation and induction of the activation marker CD69. These results are consistent with a hypothesis in which activation of immature T cells through TCR/CD3 induces c-myc up-regulation and drives thymocytes through the initial stage of positive selection. C1 UNIV TEXAS,SW MED CTR,DEPT PATHOL,LAB MOLEC PATHOL,GRAD PROGRAM IMMUNOL,DALLAS,TX 75235. US FDA,CTR BIOL EVALUAT & RES,LAB MOLEC IMMUNOL,BETHESDA,MD 20852. RI Bauer, Steven/G-5559-2012; OI Bauer, Steven/0000-0003-2831-846X FU NCI NIH HHS [CA09082-18] NR 62 TC 21 Z9 21 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1996 VL 156 IS 9 BP 3141 EP 3150 PG 10 WC Immunology SC Immunology GA UF742 UT WOS:A1996UF74200008 PM 8617934 ER PT J AU Hlady, WG Klontz, KC AF Hlady, WG Klontz, KC TI The epidemiology of Vibrio infections in Florida, 1981-1993 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID VULNIFICUS INFECTIONS; GULF-COAST; SURVEILLANCE; ASSOCIATION; COMMUNITY; SPECTRUM; FEATURES; CHOLERA; RISK; IRON AB The epidemiology of 690 Vibrio infections reported in Florida during 1981-1993 is described. Most infections resulted in one of three clinical syndromes: gastroenteritis (51%), wound infections (24%), or primary septicemia (17%). Case-fatality rates were 1% for gastroenteritis, 5% for wound infections, and 44% for primary septicemia. While gastroenteritis had little seasonal variation, 91% of primary septicemias and 86% of wound infections occurred from April through October, mostly due to the seasonality of Vibrio vulnificus and Vibrio parahaemolyticus infections. Infected wounds were largely a result of occupational activities around seawater. Some 68% of gastroenteritis cases and 83% of the primary septicemias were associated with raw oyster consumption. Preexisting liver disease was present in 48% of patients with primary septicemia and was associated with a fatal outcome in both wound infections (relative risk [RR], 28.3; 95% confidence interval [CI], 6.3-127.5; P <.0001) and primary septicemia (RR, 1.9; 95% CI, 1.2-3.1; P <.01). C1 FLORIDA DEPT HLTH & REHABIL SERV,EPIDEMIOL PROGRAM,TALLAHASSEE,FL 32399. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NR 30 TC 269 Z9 298 U1 2 U2 18 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1996 VL 173 IS 5 BP 1176 EP 1183 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UF867 UT WOS:A1996UF86700017 PM 8627070 ER PT J AU Levine, WC Bennett, RW Choi, Y Henning, KJ Rager, JR Hendricks, KA Hopkins, DP Gunn, RA Griffin, PM AF Levine, WC Bennett, RW Choi, Y Henning, KJ Rager, JR Hendricks, KA Hopkins, DP Gunn, RA Griffin, PM TI Staphylococcal food poisoning caused by imported canned mushrooms SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article AB From February through April 1989, four outbreaks of staphylococcal food poisoning in the United States were associated with eating mushrooms canned in the People's Republic of China (PRC), In the four outbreaks, 99 persons who ate at a suspect facility developed gastrointestinal symptoms within 24 h, including 18 who were hospitalized, Illness was associated with eating mushrooms at a university cafeteria (relative risk [RR] = 53.0), a hospital cafeteria (RR = 13.8), a pizzeria (odds ratio [OR] = infinity), and a restaurant (OR = infinity) (all P < .0001), Staphylococcal enterotoxin A was found by ELISA in mushrooms at the sites of two outbreaks and in unopened cans from the three plants thought to have produced mushrooms implicated in outbreaks, These investigations led to multistate recalls and a US Food and Drug Administration order to restrict entry into the United States of all mushrooms produced in the PRC; until this action, the United States imported similar to 50 million pounds yearly. C1 CDCP,NATL CTR INFECT DIS,DIV BACTERIAL & MYCOT DIS,FOODBORNE & DIARRHEAL DIS BRANCH,ATLANTA,GA 30341. CDCP,DIV FIELD EPIDEMIOL,EPIDEMIOL PROGRAM OFF,ATLANTA,GA 30341. ALLEGHENY CTY HLTH DEPT,PITTSBURGH,PA. MISSISSIPPI DEPT HLTH,JACKSON,MS. US FDA,DIV MICROBIOL STUDIES,WASHINGTON,DC 20204. NR 14 TC 27 Z9 27 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1996 VL 173 IS 5 BP 1263 EP 1267 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UF867 UT WOS:A1996UF86700030 PM 8627083 ER PT J AU Altekruse, S AF Altekruse, S TI Food and drug administration response SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT Symposium on Food Safety, at the 132nd Annual Meeting of the AVMA CY JUL 11, 1995 CL PITTSBURGH, PA SP Amer Vet Med Assoc RP Altekruse, S (reprint author), CTR DIS CONTROL & PREVENT,CTR FOOD SAFETY & APPL NUTR,FDA,M-S A-38,1600 CLIFTON RD,ATLANTA,GA 30333, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD MAY 1 PY 1996 VL 208 IS 9 BP 1399 EP 1399 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA UG889 UT WOS:A1996UG88900012 ER PT J AU Lapham, C Golding, B Inman, J Blackburn, R Manischewitz, J Highet, P Golding, H AF Lapham, C Golding, B Inman, J Blackburn, R Manischewitz, J Highet, P Golding, H TI Brucella abortus conjugated with a peptide derived from the V3 loop of human immunodeficiency virus (HIV) type 1 induces HIV-Specific cytotoxic T-cell responses in normal and in CD4(+) cell-depleted BALB/c mice SO JOURNAL OF VIROLOGY LA English DT Article ID GENE-EXPRESSION; LYMPHOCYTES-T; MOLECULES; PROTEINS; ANTIGENS; PRIMES; GAMMA AB We have previously shown that immunization of mice with human immunodeficiency virus (HIV)-derived proteins or peptides conjugated to inactivated Brucella abortus induces the secretion of virus-neutralizing antibodies, predominantly of the immunoglobulin G2a (IgG2a) isotype, In addition, B, abortus activates human CD4(+) and CD8(+) cells to secrete gamma interferon. Since these are both characteristics of a Th1-type immune response, which is associated with the development of cell-mediated immunity, it was important to determine if B. abortus conjugates would also act as a carrier to induce a cytotoxic T-lymphocyte (CTL) response, To test this hypothesis, we conjugated an 18-amino-acid peptide from the V3 loop of the MN strain of HIV-1 gp120 that contains both B- and cytotoxic T-cell epitopes to B, abortus (B. abortus-MN 18-mer), A 10-amino-acid fragment of this peptide has been shown to be the minimal CTE determinant presented by murine H-2D(d), It was found that two in vivo immunizations with 10(8) organisms of B. abortus-MN 18-mer followed by in vitro stimulation with peptide induced a virus-specific CTL response, Conjugation to B. abortus was required for in vive priming, since there was no induction of memory CTLs when B. abortus was only mixed with peptide, Targets pulsed with peptide as well as those infected with a vaccinia virus encoding HIV gp160 were killed, demonstrating recognition of naturally processed envelope, Also, major histocompatibility complex-incompatible L cells which were infected with vaccinia viruses that encoded H-2D(d) but not H-2k(d), and pulsed with peptide were lysed, This demonstrated the appropriate major histocompatibility complex class I restriction, Treatment of the mice with anti-L3T4 prior to immunization caused a severe depletion of CD4(+) lymphocytes, yet it did not decrease the CTL priming, Thus, inactivated B. abortus can induce non-CD4(+) cells to produce the cytokines required for CTL induction, We conclude that B, abortus stimulates a cellular as well as a humoral immune response, even in the relative absence of CD4(+) helper cells, It may be a particularly useful vaccine carrier in HIV-1-infected individuals or others with impaired CD4(+) T-cell function. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,LAB PLASMA DERIVAT,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. RP Lapham, C (reprint author), US FDA,CTR BIOL EVALUAT & RES,LAB RETROVIRUS RES,DIV VIRAL PROD,BLDG 29B,RM 3G21,HFM 454,BETHESDA,MD 20892, USA. NR 37 TC 26 Z9 28 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1996 VL 70 IS 5 BP 3084 EP 3092 PG 9 WC Virology SC Virology GA UF247 UT WOS:A1996UF24700048 PM 8627787 ER PT J AU Shuttleworth, KL Cerniglia, CE AF Shuttleworth, KL Cerniglia, CE TI Bacterial degradation of low concentrations of phenanthrene and inhibition by naphthalene SO MICROBIAL ECOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; DEGRADING BACTERIA; BIODEGRADATION; SOIL; WATER; MINERALIZATION; SURFACTANTS; EXPOSURE; PLASMID AB Phenanthrene-degrading bacteria were isolated from enrichment cultures of soils contaminated with creosote and jet fuel, The isolates from the creosote enrichments were classified by fatty acid methyl ester profiles as Acidovorax delafieldii and Sphingomonas paucimobilis; the bacterium from the jet fuel-contaminated soil was not identified and was designated strain JFD 11. All three isolates used phenanthrene as a sole carbon and energy source, and two of the isolates used fluoranthene as a sole carbon and energy source, Anthracene and fluorene were cometabolized by all three strains, but pyrene was not transformed, Naphthalene inhibited all of the strains, and 28-h cultures of A. delafieldii were inhibited by naphthalene concentrations as low as 5 ppm, Short-term degradation experiments were undertaken with center-well flasks and concentrations of phenanthrene ranging from 1.2 to 12.0 mu M. Since initial degradation rates were not a function of phenanthrene concentration, it was inferred that the half-saturation constants were less than the lowest phenanthrene concentration tested. C1 US FDA,NATL CTR TOXICOL RES,DIV MICROBIOL,JEFFERSON,AR 72079. NR 25 TC 43 Z9 43 U1 0 U2 7 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0095-3628 J9 MICROBIAL ECOL JI Microb. Ecol. PD MAY-JUN PY 1996 VL 31 IS 3 BP 305 EP 317 PG 13 WC Ecology; Marine & Freshwater Biology; Microbiology SC Environmental Sciences & Ecology; Marine & Freshwater Biology; Microbiology GA UH525 UT WOS:A1996UH52500006 ER PT J AU Chen, ZP Berkower, I Ching, WM Wang, RYH Alter, HJ Shih, JWK AF Chen, ZP Berkower, I Ching, WM Wang, RYH Alter, HJ Shih, JWK TI Identification of a murine CD4(+) T-lymphocyte response site in hepatitis C virus core protein SO MOLECULAR IMMUNOLOGY LA English DT Article DE HCV; truncated recombinant core proteins; immune responses; epitope mapping; H-2 congenic mice; T helper epitope ID NON-B-HEPATITIS; CHRONIC NON-A; POSTTRANSFUSION HEPATITIS; NUCLEOTIDE-SEQUENCE; IMMUNE-RESPONSE; ANTIGEN; INFECTION; ANTIBODY; CELLS; NUCLEOPROTEIN AB T cell response to a recombinant HCV truncated core protein (cp1-10) was measured in a proliferation assay. Based on a 10-fold greater response to this truncated core protein than to its shorter form (cp1-8), a predominant epitope was mapped to the carboxyl quarter of this sequence. This epitope was further mapped to a synthetic peptide corresponding to amino acids 121-140 of the core protein. The peptide was antigenic for T cells of all three H-2 types tested, H-2 r, b and d, and the proliferating T cells were CD4(+). Besides inducing specific proliferation in vitro, peptide aa121-140 can prime helper T cells in vivo. When boosted with core protein, mice primed with peptide produced 64-fold higher antibody titer than without priming in 1 week. The identification of a broadly immunogenic T cell helper epitope on core protein may be important for vaccine design against HCV. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,OFF VACCINE RES & REVIEW,IMMUNOREGULAT LAB,BETHESDA,MD 20852. USN,MED RES INST,DEPT INFECT DIS,BETHESDA,MD 20889. ARMED FORCES INST PATHOL,AMER REGISTRY PATHOL,WASHINGTON,DC 20306. NR 43 TC 4 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD MAY-JUN PY 1996 VL 33 IS 7-8 BP 703 EP 709 DI 10.1016/0161-5890(96)00010-7 PG 7 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA VA418 UT WOS:A1996VA41800014 PM 8760282 ER PT J AU Doig, P Yao, RJ Burr, DH Guerry, P Trust, TJ AF Doig, P Yao, RJ Burr, DH Guerry, P Trust, TJ TI An environmentally regulated pilus-like appendage involved in Campylobacter pathogenesis SO MOLECULAR MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; JEJUNI INFECTION; SALMONELLA-ENTERITIDIS; ANTIGENIC VARIATION; COLONIZATION FACTOR; GENE-EXPRESSION; IDENTIFICATION; MODEL; FLAGELLA; CLONING AB Examination of strains of Campylobacter jejuni, Campylobacter coli, and Campylobacter fetus by electron microscopy revealed that they produced peritrichous pilus-like appendages when the bacteria were grown in the presence of bile salts. Various bile-salt supplements were used and it was found that deoxycholate and chenodeoxycholic acid caused a significant enhancement of pilus production and resulted in a highly aggregative phenotype. Morphologically, the pili were between 4 and 7 nm in width and were greater than 1 mu m in length. A gene, termed pspA, which encodes a predicted protein resembling protease IV of Escherichia coli, was identified in C. jejuni strain 81-176. A site-specific insertional mutation within this gene resulted in the loss of pilus synthesis as determined by electron microscopy. Insertions upstream and downstream of the gene had no effect on pilus production. The non-piliated mutant of strain 81-176 showed no reduction in adherence to or invasion of INT 407 cells in vitro. However, this mutant, while still possessing the ability to colonize ferrets, caused significantly reduced disease symptoms in this animal model. C1 UNIV VICTORIA, DEPT BIOCHEM & MICROBIOL, VICTORIA, BC V8W 3P6, CANADA. UNIV VICTORIA, CANADIAN BACTERIAL DIS NETWORK, VICTORIA, BC V8W 3P6, CANADA. USN, MED RES INST, ENTER DIS PROGRAM, BETHESDA, MD 20889 USA. US FDA, WASHINGTON, DC 20204 USA. NR 56 TC 38 Z9 39 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 1996 VL 20 IS 4 BP 885 EP 894 DI 10.1111/j.1365-2958.1996.tb02526.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA UN988 UT WOS:A1996UN98800019 ER PT J AU Shaddock, JG Chou, MW Casciano, DA AF Shaddock, JG Chou, MW Casciano, DA TI Effects of age and caloric restriction on cell proliferation in hepatocyte cultures from control and hepatectomized Fischer 344 rats SO MUTAGENESIS LA English DT Article ID DNA-REPAIR ASSAY; LIVER-REGENERATION; DIETARY RESTRICTION; GROWTH-FACTORS; CARCINOGENESIS; CANCER; INDUCTION; EXPOSURE; MOUSE; MICE AB The effects of age and caloric restriction on cell proliferation, measured as scheduled DNA synthesis (SDS), were evaluated in primary hepatocyte cultures from control and partially hepatectomized (PH) young to old ad libitum (AL) and caloric-restricted (CR) male Fischer 344 (F344) rats, We reported significant age- or CR-related decreases in SDS in control cultures, PH-induced cultures exhibited significant increases in SDS compared with their control counterparts. Hepatocytes from PH-induced old CR diet-fed animals exhibited significant increases in SDS compared with cultures from control old CR, PH-induced young CR and PH-induced old AL animals, Alternatively, SDS rates for PH-induced young CR animals were significantly lower at 48 h and higher at 72 h than the rates we reported for cultures from PH-induced young AL F344 rats, These data suggest that CR decreases and preserves the proliferative capacity in hepatocytes from young animals and may permit animals to respond more efficiently with induced compensatory cellular replication in old age. C1 NATL CTR TOXICOL RES, DIV NUTR TOXICOL, JEFFERSON, AR 72079 USA. UNIV ARKANSAS MED SCI HOSP, DEPT BIOCHEM & MOLEC BIOL, LITTLE ROCK, AR 72205 USA. UNIV ARKANSAS MED SCI HOSP, DEPT TOXICOL, LITTLE ROCK, AR 72205 USA. RP Shaddock, JG (reprint author), NATL CTR TOXICOL RES, DIV GENET TOXICOL, HFT-120, 3900 NCTR DR, JEFFERSON, AR 72079 USA. NR 49 TC 9 Z9 9 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD MAY PY 1996 VL 11 IS 3 BP 281 EP 284 DI 10.1093/mutage/11.3.281 PG 4 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA UK072 UT WOS:A1996UK07200007 PM 8671749 ER PT J AU Timbo, B Altekruse, S Fowler, MG AF Timbo, B Altekruse, S Fowler, MG TI Breast-feeding and HIV transmission: Epidemiologic studies and their limitations SO NUTRITION RESEARCH LA English DT Article DE breast-feeding; breast milk; postnatal HIV transmission; epidemiology studies ID HUMAN-IMMUNODEFICIENCY-VIRUS; POSTNATAL TRANSMISSION; INFANTS BORN; PERINATAL TRANSMISSION; VERTICAL TRANSMISSION; CHILD TRANSMISSION; SEROPOSITIVE WOMEN; INFECTION; TYPE-1; MILK AB Postnatal human immunodeficiency virus (HIV) transmission from an HIV-infected mother to child has been attributed mostly to breast-feeding. However, the mechanism and timing of HIV transmission via breast-feeding and the risk factors for that mode of transmission are not well defined. A series of case reports and cohort studies have provided useful but incomplete information on the transmission of HIV through breast-feeding Various studies have yielded risk estimates of 15-40%. The stage of the HIV infection in the mother and the immunologic constituents of the breast milk have been suggested as important determinants of HIV transmission through breast-feeding. C1 NIAID, VACCINE TRIALS & EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA. RP Timbo, B (reprint author), US FDA, CTR FOOD SAFETY & APPL NUTR, EPIDEMIOL BRANCH, HFS-728, WASHINGTON, DC 20204 USA. NR 50 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 0271-5317 J9 NUTR RES JI Nutr. Res. PD MAY PY 1996 VL 16 IS 5 BP 759 EP 768 DI 10.1016/0271-5317(96)00067-X PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA UH279 UT WOS:A1996UH27900006 ER PT J AU Gutman, S AF Gutman, S TI Rapid streptococcal tests SO PEDIATRICS LA English DT Letter RP Gutman, S (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,DIV CLIN LAB DEVICES,OFF DEVICE EVALUAT,ROCKVILLE,MD 20857, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 1996 VL 97 IS 5 BP 783 EP 784 PG 2 WC Pediatrics SC Pediatrics GA UH758 UT WOS:A1996UH75800050 PM 8628638 ER PT J AU Moore, TW Shangraw, RF Habib, Y AF Moore, TW Shangraw, RF Habib, Y TI Dissolution calibrator tablets: A recommendation for new calibrator tablets to replace both current USP calibrator tablets SO PHARMACOPEIAL FORUM LA English DT Article C1 UNIV MARYLAND,BALTIMORE,MD 21201. RP Moore, TW (reprint author), US FDA,DIV DRUG ANAL,1114 MARKET ST,ROOM 1002,ST LOUIS,MO 63101, USA. NR 6 TC 11 Z9 11 U1 0 U2 0 PU US PHARMACOPEIAL CONVENTION PI ROCKVILLE PA 12601 TWINBROOK PKWY, ROCKVILLE, MD 20852 SN 0363-4655 J9 PHARMACOPEIAL FORUM JI Pharmacop. Forum PD MAY-JUN PY 1996 VL 22 IS 3 BP 2423 EP 2428 PG 6 WC Medicine, Legal; Pharmacology & Pharmacy SC Legal Medicine; Pharmacology & Pharmacy GA UV102 UT WOS:A1996UV10200003 ER PT J AU Seed, J Chapin, RE Clegg, ED Dostal, LA Foote, RH Hurtt, ME Klinefelter, GR Makris, SL Perreault, SD Schrader, S Seyler, D Sprando, R Treinen, KA Veeramachaneni, DNR Wise, LD AF Seed, J Chapin, RE Clegg, ED Dostal, LA Foote, RH Hurtt, ME Klinefelter, GR Makris, SL Perreault, SD Schrader, S Seyler, D Sprando, R Treinen, KA Veeramachaneni, DNR Wise, LD TI Methods for assessing sperm motility, morphology, and counts in the rat, rabbit, and dog: A consensus report SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE methods; sperm motility; sperm morphology; sperm counts; rat; rabbit; dog ID ETHANE DIMETHANESULFONATE; ADULT-RATS; FERTILITY; INVITRO AB Reproductive toxicity studies are increasingly including assessments of sperm parameters including motility, morphology, and counts, While these assessments can provide valuable information for the determination of potential reproductive toxicity, the methods for conducting the assessments have not been well developed in all laboratories and are continually evolving, The use of different methods in different laboratories makes comparison of data among laboratories difficult, To address the differences in methods, a working group was convened to discuss methods currently in use, share data, and try to reach consensus about optimal methods for assessing sperm parameters in rats, rabbits, and dogs, This article presents the consensus report, as well as future research needs, with the hope that optimized common methods will aid in the detection of reproductive effects and enhance interlaboratory comparisons. C1 NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. US EPA,WASHINGTON,DC 20460. CORNELL UNIV,ITHACA,NY 14853. WARNER LAMBERT PARKE DAVIS,PARKE DAVIS PHARMACEUT RES,ANN ARBOR,MI 48105. DUPONT CO INC,NEWARK,DE 19714. NIOSH,CINCINNATI,OH 45226. ELI LILLY & CO,LILLY RES LABS,GREENFIELD,IN 46140. US FDA,BELTSVILLE,MD. COLORADO STATE UNIV,FT COLLINS,CO 80523. MERCK RES LABS,W POINT,PA. RP Seed, J (reprint author), ILSI RISK SCI INST,1126 16TH ST NW,WASHINGTON,DC 20036, USA. RI Schrader, Steven/E-8120-2011; OI Chapin, Robert/0000-0002-5997-1261 NR 30 TC 139 Z9 144 U1 1 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD MAY-JUN PY 1996 VL 10 IS 3 BP 237 EP 244 DI 10.1016/0890-6238(96)00028-7 PG 8 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA UN191 UT WOS:A1996UN19100011 PM 8738562 ER PT J AU Kraeling, MEK Lipicky, RJ Bronaugh, RL AF Kraeling, MEK Lipicky, RJ Bronaugh, RL TI Metabolism of benzocaine during percutaneous absorption in the hairless guinea pig: Acetylbenzocaine formation and activity SO SKIN PHARMACOLOGY LA English DT Article DE percutaneous absorption; metabolism; benzocaine; hairless guinea pig ID SQUID GIANT-AXON; INVITRO AB The effect of dose and enzymatic inhibition on the percutaneous absorption and metabolism of benzocaine was studied in vitro in the hairless guinea pig, At the dose level of 2 mu g/cm(2), benzocaine was rapidly absorbed and extensively metabolized (80%) by acetyltransferase. As the applied dose of benzocaine was increased to 40 and 200 mu g/cm(2), N-acetylation of benzocaine decreased to 44 and 34%, respectively, suggesting saturation of the acetyltransferase system, Total C-14 absorption after benzocaine application was not significantly different between control and enzyme-inhibited skin and therefore does not appear to be affected by the extent of benzocaine metabolism during percutaneous penetration, Skin provides a significant first-pass metabolic effect for therapeutic doses of percutaneously absorbed benzocaine, and the primary metabolite formed, acetylbenzocaine, is biologically active. C1 US FDA,COSMET TOXICOL BRANCH,OFF COSMET & COLORS,CTR FOOD SAFETY & APPL NUTR,LAUREL,MD 20708. US FDA,OFF DRUG EVALUAT 1,CTR DRUG EVALUAT & RES,LAUREL,MD 20708. NR 12 TC 10 Z9 11 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-0283 J9 SKIN PHARMACOL JI Skin Pharmacol. PD MAY-JUN PY 1996 VL 9 IS 3 BP 221 EP 230 PG 10 WC Dermatology; Pharmacology & Pharmacy SC Dermatology; Pharmacology & Pharmacy GA UN793 UT WOS:A1996UN79300008 PM 8737920 ER PT J AU Hastings, KL AF Hastings, KL TI Regulatory issues of importance to developing anti-HIV therapeutics SO TOXICOLOGIC PATHOLOGY LA English DT Article DE Pre-Investigational New Drug (pre-IND) program ID DRUG DEVELOPMENT AB In the United States, before clinical trials with new drugs can proceed, an Investigational New Drug (IND) application must be submitted to the Food and Drug Administration. Applications for drugs intended for the treatment of HIV-related diseases are reviewed by the Division of Anti-Viral Drug Products (DAVDP) within the Center for Drug Evaluation and Research. IND applications must contain adequate preclinical studies to support the safety of the proposed clinical trials. Essential for demonstrating safety are animal toxicology studies in which the drug has been administered in doses, by the route(s) of administration, and over a length of time equivalent to the corresponding parameters proposed for clinical trials. Reproductive toxicology/teratology studies should be conducted early in the development of the drug. Other nonclinical toxicology studies, such as carcinogenicity bioassays, are usually conducted concurrently with clinical trials. The DAVDP has developed a Pre-IND program to assist sponsors in preparing the best preclinical research to support the development of new drugs. RP Hastings, KL (reprint author), US FDA,DIV ANTIVIRAL DRUG PROD,CTR DRUG EVALUAT & RES,HFD-530,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAY-JUN PY 1996 VL 24 IS 3 BP 278 EP 280 PG 3 WC Pathology; Toxicology SC Pathology; Toxicology GA UN140 UT WOS:A1996UN14000003 PM 8736383 ER PT J AU Andrews, WH AF Andrews, WH TI AOAC Internationals three validation programs for methods used in the microbiological analysis of foods SO TRENDS IN FOOD SCIENCE & TECHNOLOGY LA English DT Article AB The sheer number of microbiological methods, both rapid and conventional, that have become available during the past ten years has underscored the need for methods validation. The Association or Official Analytical Chemists INTERNATIONAL has responded by offering a variety of validation programs, each with different objectives, approaches, requirements and advantages. The harmonization of these validation efforts with those of other international organizations is needed to achieve uniformity of methods in an expedient and cost-effective manner. RP Andrews, WH (reprint author), US FDA,DIV MICROBIOL STUDIES,200 C ST SW,WASHINGTON,DC 20204, USA. NR 14 TC 13 Z9 13 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0924-2244 J9 TRENDS FOOD SCI TECH JI Trends Food Sci. Technol. PD MAY PY 1996 VL 7 IS 5 BP 147 EP 151 DI 10.1016/0924-2244(96)10017-0 PG 5 WC Food Science & Technology SC Food Science & Technology GA UN342 UT WOS:A1996UN34200001 ER PT J AU Scott, DE Agranovich, I Golding, B AF Scott, DE Agranovich, I Golding, B TI B72 costimulation is required for Th2 but not Th1-mediated responses to ovabumin. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 208 EP 208 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100438 ER PT J AU Zaitseva, M Mojcik, C Shevach, E Golding, H AF Zaitseva, M Mojcik, C Shevach, E Golding, H TI Protective role of the VLA4 integrin in dexamethasone-induced apoptosis in human thymocytes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,BETHESDA,MD 20892. NIAID,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 260 EP 260 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100491 ER PT J AU BroussardDiehl, C Bauer, S Scheuermann, R AF BroussardDiehl, C Bauer, S Scheuermann, R TI A role for c-myc in the regulation of thymocyte differentiation and possibly positive selection. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV TEXAS,SW MED CTR,LAB MOLEC PATHOL,DEPT PATHOL,DALLAS,TX 75235. US FDA,CTR BIOL EVALUAT & RES,LAB MOLEC IMMUNOL,BETHESDA,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 264 EP 264 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100496 ER PT J AU Donnelly, RP Freeman, SL Dickensheets, HL AF Donnelly, RP Freeman, SL Dickensheets, HL TI Interleukin-12 (IL-12) coamplifies production of interferon-gamma and IL-10 in activated human T cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CBER,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 313 EP 313 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100544 ER PT J AU Lee, C Wang, T Kosaka, T AF Lee, C Wang, T Kosaka, T TI Binding characteristics and protective immunity of monoclonal antibodies to pneumococcal type 9V conjugate SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 472 EP 472 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100700 ER PT J AU Berkower, I Patterson, LJ AF Berkower, I Patterson, LJ TI Chimeric HIV-1 envelope GP120-hepatitis B core antigen (HBcAg) fusion proteins for HIV-1 vaccines SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CTR BIOL,OFF VACCINE RES,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 485 EP 485 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100715 ER PT J AU Mills, F Harindranath, N Max, E AF Mills, F Harindranath, N Max, E TI An elk-1 related sequence flanks the human psi gamma immunoglobulin pseudogene. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 992 EP 992 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86101220 ER PT J AU Saikh, KU Conlon, K Ulrich, RG AF Saikh, KU Conlon, K Ulrich, RG TI Functional maturation of human dendritic cells proceeds through a MHC class II negative precursor. SO FASEB JOURNAL LA English DT Meeting Abstract C1 USA,MED RES INST INFECT DIS,FREDERICK,MD 21702. US FDA,OTRR,CTR BIOL EVAL RES,ROCKVILLE,MD 20853. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 1238 EP 1238 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86101465 ER PT J AU Honkanen, RE Dickey, RW AF Honkanen, RE Dickey, RW TI Assessment of a protein phosphatase based assay for the detection of DSP-toxins in shellfish. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV S ALABAMA,DEPT BIOCHEM & MOLEC BIOL,MOBILE,AL 36688. US FDA,OFF SEAFOOD,DAUPHIN ISL,AL 36528. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 1459 EP 1459 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86101690 ER PT J AU James, SJ Poirier, LA Pogribny, IP AF James, SJ Poirier, LA Pogribny, IP TI Transition to malignancy is associated with de novo methylation and reduced expression of the p53 gene in tumors from folate/methyl deficient rats. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 2472 EP 2472 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86102700 ER PT J AU Schneck, JP Sechler, J OHerrin, SM Bieler, JG Barnes, N Rosenberg, A AF Schneck, JP Sechler, J OHerrin, SM Bieler, JG Barnes, N Rosenberg, A TI Specific inhibition of graft rejection by soluble MHC superdimers. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,BETHESDA,MD 20892. JOHNS HOPKINS UNIV HOSP,SCH MED,BALTIMORE,MD 21205. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 2729 EP 2729 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86102955 ER PT J AU Myers, MJ Farrell, DE Howard, KD Kawalek, JC AF Myers, MJ Farrell, DE Howard, KD Kawalek, JC TI Identification of swine cytochrome P450 isozymes SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CTR VET MED,DIV ANIM RES,BELTSVILLE,MD 20705. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 2874 EP 2874 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86103100 ER PT J AU Nightingale, SL AF Nightingale, SL TI New cancer therapy initiatives SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP Nightingale, SL (reprint author), US FDA,OFF HLTH AFFAIRS,PARKLAWN BLDG,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 24 PY 1996 VL 275 IS 16 BP 1224 EP 1224 DI 10.1001/jama.275.16.1224 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UF478 UT WOS:A1996UF47800009 PM 8601942 ER PT J AU Nightingale, SL AF Nightingale, SL TI Important new safety information for tramadol hydrochloride SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP Nightingale, SL (reprint author), US FDA,OFF HLTH AFFAIRS,PARKLAWN BLDG,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 24 PY 1996 VL 275 IS 16 BP 1224 EP 1224 DI 10.1001/jama.275.16.1224 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UF478 UT WOS:A1996UF47800008 PM 8601942 ER PT J AU Nightingale, SL AF Nightingale, SL TI Nicotine nasal spray approved for smoking cessation SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP Nightingale, SL (reprint author), US FDA,OFF HLTH AFFAIRS,PARKLAWN BLDG,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 24 PY 1996 VL 275 IS 16 BP 1224 EP 1224 DI 10.1001/jama.275.16.1224 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UF478 UT WOS:A1996UF47800007 PM 8601942 ER PT J AU Ogretmen, B Ratajczak, H Gendel, SM Stark, BC AF Ogretmen, B Ratajczak, H Gendel, SM Stark, BC TI Effects of sodium saccharin and linoleic acid on mRNA levels of Her2/neu and p53 in a human breast epithelial cell line SO CANCER LETTERS LA English DT Article DE sodium saccharin; linoleic acid; phorbol 12-myristate 13-acetate; Her2/neu; p53 ID MAMMARY CARCINOGENESIS; ONCOGENE EXPRESSION; TUMOR PROMOTION; PROTO-ONCOGENE; DIFFERENT AGES; DOSE-RESPONSE; DIETARY-FAT; MOUSE SKIN; 2200 MICE; CANCER AB The effects of two food-related chemicals (sodium saccharin and linoleic acid) on the levels of Her2/neu and p53 mRNA in a non-cancerous human breast epithelial cell line (HBL-100) were tested in comparison with the effects of the known tumor promoter phorbol 12-myristate 13-acetate (TPA). Treatments were made both with and without prior treatment with two well-known tumor initiators, N-nitroso-N-methylurea (NMU) or 7,12-dimethylbenz[a]anthracene (DMBA). The effects in general were small, the greatest being increases of 46-67% in Her2/neu mRNA levels in response to treatments with TPA or sodium saccharin following NMU treatments. These results demonstrate that sodium saccharin following NMU treatments might be involved in transcriptional regulation of Her2/neu in HBL-100 cells and suggest that its effects may not be limited to urinary bladder. C1 IIT,IIT CTR,DEPT BIOL CHEM & PHYS SCI,CHICAGO,IL 60616. IIT,IIT CTR,RES INST,DEPT LIFE SCI,CHICAGO,IL 60616. US FDA,NATL CTR FOOD SAFETY & TECHNOL,SUMMIT ARGO,IL 60501. NR 49 TC 4 Z9 4 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD APR 19 PY 1996 VL 102 IS 1-2 BP 91 EP 99 DI 10.1016/0304-3835(96)04170-5 PG 9 WC Oncology SC Oncology GA UB974 UT WOS:A1996UB97400013 PM 8603385 ER PT J AU David, M Wong, L Flavell, R Thompson, SA Wells, A Larner, AC Johnson, GR AF David, M Wong, L Flavell, R Thompson, SA Wells, A Larner, AC Johnson, GR TI STAT activation by epidermal growth factor (EGF) and amphiregulin - Requirement for the EGF receptor kinase but not for tyrosine phosphorylation sites or JAK1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE; PROMOTER; CELLS AB The epidermal growth factor (EGF) receptor activates several signaling cascades in response to the ligands EGF and amphiregulin (AR). One of these signaling events involves the tyrosine phosphorylation of STATs (signal transducers and activators of transcription), a process believed to require the activation of a tyrosine kinase of the JAK family, In this report we demonstrate that EGF- and AR-induced STAT activation requires the intrinsic kinase activity of the receptor but not the presence of Jak1. We show that both wild type (WT) and truncated EGF receptors lacking all autophosphorylation sites activate STAT 1, 3, and 5 in response to either EGF or AR. Furthermore, relative to cells expressing WT receptor, ligand-induced tyrosine phosphorylation of the STATs was enhanced in cells expressing only the truncated receptor, These results provide the first evidence that (i) EGF receptor-mediated STAT activation occurs in a Jak1-independent manner, (ii) the intrinsic tyrosine kinase activity of the receptor is essential for STAT activation, and (iii) tyrosine phosphorylation sites within the EGF receptor are not required for STAT activation. C1 YALE UNIV,HOWARD HUGHES MED INST,NEW HAVEN,CT 06510. BERLEX BIOSCI,DEPT PROT CHEM & BIOPHYS,RICHMOND,CA 94804. UNIV ALABAMA,DEPT PATHOL,BIRMINGHAM,AL 35294. VET ADM MED CTR,BIRMINGHAM,AL 35294. RP David, M (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BLDG 29A,RM 2B06,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Wells, Alan/0000-0002-1637-8150 NR 24 TC 132 Z9 133 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 19 PY 1996 VL 271 IS 16 BP 9185 EP 9188 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UG044 UT WOS:A1996UG04400004 PM 8621573 ER PT J AU Braden, BC Fields, BA Ysern, X Goldbaum, FA DallAcqua, W Schwarz, FP Poljak, RJ Mariuzza, RA AF Braden, BC Fields, BA Ysern, X Goldbaum, FA DallAcqua, W Schwarz, FP Poljak, RJ Mariuzza, RA TI Crystal structure of the complex of the variable domain of antibody D1.3 and turkey egg white lysozyme: A novel conformational change in antibody CDR-L3 selects for antigen SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE monoclonal antibody; protein structure; antibody-antigen interaction; X-ray diffraction; CDR conformation AB The crystal structure of the Fv fragment of the murine monoclonal anti-lysozyme antibody D1.3, complexed with turkey egg-white lysozyme (TEL), is presented. D1.3 (IgG1, kappa) is a secondary response antibody specific for hen egg-white lysozyme (HEL). TEL and HEL are homologous and differ in amino acid sequence in the antibody-antigen interface only at position 121. The side-chain of HEL residue Gln121 makes a pair of hydrogen bonds to main-chain atoms of the antibody light chain. In the D1.3-TEL structure, TEL residue His121 makes only one hydrogen bond with the light chain as a result of 129 degrees and 145 degrees change in peptide torsion angles for residues Trp92 and Ser93. Probably as a consequence of this conformational change, the D1.3-TEL association occurs at a much slower rate than the D1.3-HEL association. The D1.S-TEL complex is destabilized with respect to the D1.3-HEL interaction by the loss of two hydrogen bonds, exclusively due to the substitution of histidine for glutamine. While antibodies of secondary responses are indeed highly specific for antigen, this work demonstrates that by undergoing subtle conformational change antibodies can still recognize mutated protein antigens, albeit at a cost to affinity. (C) 1996 Academic Press Limited C1 NATL INST STAND & TECHNOL,ROCKVILLE,MD 20850. US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. RP Braden, BC (reprint author), UNIV MARYLAND,MARYLAND BIOTECHNOL INST,CTR ADV RES BIOTECHNOL,ROCKVILLE,MD 20850, USA. FU NIGMS NIH HHS [GM52801] NR 29 TC 33 Z9 33 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 19 PY 1996 VL 257 IS 5 BP 889 EP 894 DI 10.1006/jmbi.1996.0209 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UG014 UT WOS:A1996UG01400001 PM 8632472 ER PT J AU Pothuluri, JV Evans, FE Heinze, TM Fu, PP Cerniglia, CE AF Pothuluri, JV Evans, FE Heinze, TM Fu, PP Cerniglia, CE TI Fungal metabolism of 2-nitrofluorene SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; AIR POLLUTANT 2-NITROFLUORENE; DETOXIFICATION; RAT; FLUORANTHENE AB Nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) are direct-acting mutagens and carcinogens that are considered a risk to human health. We investigated the metabolism of 2-nitrofluorene by the fungus Cunninghamella elegans ATCC 36112. Ar 144 h of incubation, C. elegans had metabolized about 81% of the [9-C-14]-2-nitrofluorene, resulting in 6 metabolites. The major metabolites were separated by reversed-phase high-performance liquid chromatography and identified by H-1 NMR, ultraviolet (UV)-visible, and mass spectral analyses as 2-nitro-9-fluorenol, 2-nitro-9-fluorenone, 6-hydroxy-2-nitrofluorene, and sulfate conjugates of 7-hydroxy-2-nitro-9-fluorenone and 7-hydroxy-2-nitrofluorene. 2-Nitro-9-fluorenol accounted For about 62% of the total metabolism. For comparison with the microbial system, experiments with liver microsomes of rats pretreated with 3-methylcholanthrene were conducted. Microsomal incubations indicated formation of phenolic and ring-hydroxylated products of 2-nitrofluorene. 2-Nitrofluorene and hydroxylated metabolites have been previously implicated as direct-acting mutagens in bacterial assays and have shown sister chromatid exchanges in vivo in bone marrow cells and in vitro in ovary cells and unscheduled DNA synthesis in mammalian studies. Previous studies with other PAHs using C. elegans have shown that the phenols and glucoside and sulfate conjugates of phenols are generally less mutagenic than the parent. The results From the metabolism of 2-nitrofluorene by C. elegans suggest the detoxification potential of this fungus. RP Pothuluri, JV (reprint author), US FDA, NATL CTR TOXICOL RES, HFT 250, DIV MICROBIOL, 3900 NCTR RD, JEFFERSON, AR 72079 USA. NR 24 TC 11 Z9 11 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD APR 19 PY 1996 VL 47 IS 6 BP 587 EP 599 DI 10.1080/009841096161555 PG 13 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA UG504 UT WOS:A1996UG50400006 PM 8614025 ER PT J AU Panyi, G Gaspar, R Krasznai, Z terHorst, JJ Ameloot, M Aszalos, A Steels, P Damjanovich, S AF Panyi, G Gaspar, R Krasznai, Z terHorst, JJ Ameloot, M Aszalos, A Steels, P Damjanovich, S TI Immunosuppressors inhibit voltage-gated potassium channels in human peripheral blood lymphocytes SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CYCLOSPORINE-A; ACTIVATION; RAPAMYCIN; FK-506; CELLS; SITE AB The effects of immunosuppressive agents on the potassium current of human peripheral blood lymphocytes have been studied using the whole-cell patch-clamp technique. Cyclosporin A(10 mu g/ml), rapamycin (10 mu g/ml) and FK-506 (2.5 mu g/ml) reduced the peak K+ current by approximately 40, 30 and 40% of the control, respectively, without any change in the reversal potential of the current. The current inhibition was similar at all membrane potentials studied and was accompanied with an increase in the rate of K+ current inactivation Membrane potential measurements in current-clamp showed a marked depolarization of the membrane (>10 mV) upon the addition of either immunosuppressor to the cells. Our findings revealed that the voltage-dependent potassium current in human peripheral blood lymphocytes is inhibited by Cyclosporin A and other immunosuppressors, resulting in a depolarized membrane potential. (C) 1996 Academic Press, Inc. C1 DEBRECEN UNIV MED,SCH MED,DEPT BIOPHYS,H-4102 DEBRECEN,HUNGARY. LIMBURGS UNIV CENTRUM,DEPT PHYSIOL,DIEPENBEEK,BELGIUM. US FDA,DIV RES & TESTING,WASHINGTON,DC 20204. RI Damjanovich, Sandor/A-9284-2011; Panyi, Gyorgy/H-4406-2013 NR 17 TC 18 Z9 19 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 16 PY 1996 VL 221 IS 2 BP 254 EP 258 DI 10.1006/bbrc.1996.0582 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UF911 UT WOS:A1996UF91100008 PM 8619842 ER PT J AU Silverman, BG Brown, SL Bright, RA Kaczmarek, RG ArrowsmithLowe, JB Kessler, DA AF Silverman, BG Brown, SL Bright, RA Kaczmarek, RG ArrowsmithLowe, JB Kessler, DA TI Reported complications of silicone gel breast implants: An epidemiologic review SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID CONNECTIVE-TISSUE DISEASE; CAPSULAR CONTRACTURE; AUGMENTATION MAMMAPLASTY; DEFINITIVE DIAGNOSIS; CANCER; MAMMOGRAPHY; PROSTHESES; RUPTURE; SMOOTH; RECONSTRUCTION AB Data Sources: Epidemiologic studies of the potential risks of silicone breast implants identified by MEDLINE search and literature review. Study Selection: Epidemiologic studies with cohort, Ease-control, and cross-sectional designs. When epidemiologic studies were unavailable (as for estimates of local complications), case series were reviewed. Data Extraction: Epidemiologic studies evaluated for methodologic quality, including such characteristics as study design, sample size and selection, determination of silicone exposure and outcome variables, and duration of follow-up. Data Synthesis: The epidemiologic literature on the potential complications of silicone breast implants has concentrated primarily on connective tissue disorders and cancer. Estimates of the true incidence of local complications, such as rupture, capsular contracture, and breast pain, are unavailable. Studies of scleroderma and other defined connective tissue diseases suggest that implant recipients have no substantially increased risk for these disorders; however, the epidemiologic literature is insufficient to rule out an association between breast implants and connective tissue disease-like syndromes. Overall, the rate of breast cancer does not seem to be increased in women with silicone breast implants. However, the risk to women as they reach the postmenopausal years is not yet known. Conclusions: Information is insufficient to adequately advise women who currently have or are seeking to obtain breast implants about the overall risk of these devices. Mo epidemiologic study has indicated that the rate of well-defined connective tissue disease or breast cancer has greatly increased in women with silicone breast implants, but no studies have ruled out a moderately increased risk for these diseases. No studies have adequately addressed the crucial issue of local complications such as rupture and capsular contracture, although evidence increasingly points to a higher risk for rupture as implants age. C1 US FDA,HF 1,ROCKVILLE,MD 20857. US FDA,CTR BIOL EVALUAT & RES,HFM 380,ROCKVILLE,MD 20852. RP Silverman, BG (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,HFZ 541,1350 PICCARD DR,ROCKVILLE,MD 20850, USA. RI Bright, Roselie/D-2240-2016; OI Silverman, Barbara/0000-0002-0337-4919 NR 103 TC 110 Z9 112 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 15 PY 1996 VL 124 IS 8 BP 744 EP 756 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA UD936 UT WOS:A1996UD93600008 PM 8633836 ER PT J AU Schneck, JP Sechler, J OHerrin, SM Bieler, JG Barnes, N Rosenberg, A AF Schneck, JP Sechler, J OHerrin, SM Bieler, JG Barnes, N Rosenberg, A TI Specific inhibition of graft rejection by soluble MHC superdimers. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD APR 15 PY 1996 VL 47 IS 1-2 BP O809 EP O809 PG 1 WC Immunology SC Immunology GA UM455 UT WOS:A1996UM45500810 ER PT J AU Murata, T Noguchi, PD Puri, RK AF Murata, T Noguchi, PD Puri, RK TI IL-13 induces phosphorylation and activation of JAK2 Janus kinase in human colon carcinoma cell lines - Similarities between IL-4 and IL-13 signaling SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR GAMMA-CHAIN; HUMAN B-CELLS; INTERLEUKIN-4 RECEPTOR; TRANSDUCTION; SUPERFAMILY; EXPRESSION; COMPONENT; PROTEINS; CYTOKINE; BINDING AB We have recently reported that IL-13R may share a component with IL-4R, Here we report that both IL-4 and IL-13 share signaling events in human colon carcinoma cell lines (HT-29 and WiDr). IL-13 caused rapid phosphorylation of the three out of four members of the known Janus family of kinases (JAKs). We shaw that JAK2 kinase is rapidly phosphorylated and activated in response to IL-13, Within 1 min of activation, JAK2 was phosphorylated, and peaked in 10 min. In addition, IL-13 phosphorylated insulin response substrate-1, IL-4R p140, JAK1, and Tyk2, but not JAK3 kinase. IL-4 also stimulated all three kinases and substrates, but unlike in immune cells, IL-4 did not involve JAK3 activation for its signaling in colon cancer cell lines, Furthermore, JAK2 associated with the IL-4R p140 before and after stimulation with IL-13, Both IL-13 and IL-4 induced phosphorylation of IL-4 STAT (STAT6) but not STAT1, STAT3, or STAT5, I-125-IL-13 did not bind to colon cancer cell lines, but unlabeled IL-13 competed for the binding of I-125-IL-4, Our data suggest that IL-13 utilizes IL-4R and its signaling pathway, and JAK2 may play an important role in the function of IL-4R and IL-13R in colon cancer cells. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,LAB MOLEC TUMOR BIOL,BETHESDA,MD 20892. NR 45 TC 114 Z9 117 U1 2 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1996 VL 156 IS 8 BP 2972 EP 2978 PG 7 WC Immunology SC Immunology GA UE192 UT WOS:A1996UE19200041 PM 8609418 ER PT J AU Mazzola, EP Turujman, SA Bell, SJ Barrows, JN Bailey, JE Mouchahoir, EG Prescott, S Archer, MD Oliver, M Reynolds, WF Nielsen, KW AF Mazzola, EP Turujman, SA Bell, SJ Barrows, JN Bailey, JE Mouchahoir, EG Prescott, S Archer, MD Oliver, M Reynolds, WF Nielsen, KW TI Nuclear magnetic resonance investigations of azo-hydrazone, acid-base equilibria of FD&C Yellow No 6 SO TETRAHEDRON LA English DT Article ID N-15 AB Azo-hydrazone, acid-base equilibria were examined for the water-soluble dye FD&C Yellow No. 6 (Y6), with the observation of dynamic NMR effects near, and at, pH 12, where the dye converts from a predominantly hydrazone tautomer (acidic to moderately basic pH) to a prevailing azo-anion resonance hybrid (high pH). Semilogarithmatic pH-C-13 chemical shift plots and a 2-bond, N-15(beta)-C-13(8a) coupling constants vs. pH relationship both indicate that the midpoint of the azo-hydrazone equilibrium occurs at ca. pH 12. Potentiometric titrations further indicate that the pK(a) of Y6 is ca. 12. These data suggest that the observed NMR line broadening is due to slow proton transfer between the hydrazone-NH and water. (C) 1996 Elsevier Science Ltd. C1 UNIV TORONTO,DEPT CHEM,TORONTO,ON M5S 1A1,CANADA. RP Mazzola, EP (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,200 C ST SW,WASHINGTON,DC 20204, USA. NR 24 TC 9 Z9 9 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD APR 15 PY 1996 VL 52 IS 16 BP 5691 EP 5698 DI 10.1016/0040-4020(96)00205-0 PG 8 WC Chemistry, Organic SC Chemistry GA UF167 UT WOS:A1996UF16700004 ER PT J AU Lackritz, EM Janssen, RS Epstein, JS AF Lackritz, EM Janssen, RS Epstein, JS TI The rise of HIV transmission by screened blood - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA,ROCKVILLE,MD 20857. RP Lackritz, EM (reprint author), CTR DIS CONTROL & PREVENT,ATLANTA,GA 30333, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 11 PY 1996 VL 334 IS 15 BP 993 EP 993 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UD596 UT WOS:A1996UD59600025 ER PT J AU Mireskandari, A Reid, RL Kashanchi, F Dittmer, J Li, WB Brady, JN AF Mireskandari, A Reid, RL Kashanchi, F Dittmer, J Li, WB Brady, JN TI Isolation of a cDNA clone, TRX, encoding a human T-cell lymphotrophic virus type-I Tax(1) binding protein SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE HTLV-1 Tax(1); Tax(1) binding protein ID TRANSCRIPTIONAL ACTIVATOR TAX; HTLV-I; REGULATORY ELEMENTS; TRANSACTIVATION; MYELOPATHY; SEQUENCES; PROMOTER; ENHANCER; REPEATS; BLOOD AB Tax, is essential for human T-cell lymphotropic virus type I (HTLV-I) virus replication and transformation. We have identified and characterized a Tax(1) binding protein, TRX, by cDNA screening of a Jurkat T-cell cDNA library. TRX mRNA is ubiquitously expressed in human tissues tested and cell lines analyzed. C1 NCI,MOLEC VIROL LAB,NIH,BETHESDA,MD 20892. US FDA,ONCOL BRANCH,DIB CLIN TRIAL DESIGN & ANAL,CTR BIOL & RES,ROCKVILLE,MD 20852. LIFE TECHNOL,GAITHERSBURG,MD. RI Dittmer, Juergen/G-1160-2011 NR 19 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD APR 10 PY 1996 VL 1306 IS 1 BP 9 EP 13 DI 10.1016/0167-4781(96)00012-7 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UF670 UT WOS:A1996UF67000003 PM 8611628 ER PT J AU Bencsath, FA Shartava, A Monteiro, CA Goodman, SR AF Bencsath, FA Shartava, A Monteiro, CA Goodman, SR TI Identification of the disulfide-linked peptide in irreversibly sickled cell beta-actin SO BIOCHEMISTRY LA English DT Article ID MASS-SPECTROMETRY; ASSIGNMENT; OCCLUSION; ADHESION; SPECTRIN; PROTEIN; DISEASE AB We have previously demonstrated that the membrane skeletons of irreversibly sickled cells (ISCs) dissociate more slowly at 37 degrees C, in high ionic strength Triton X-100 buffer, than do the membrane skeletons of reversibly sickled cells or control erythrocytes [Shartava et al. (1995) J. Cell. Biol. 128, 805-818], Furthermore, we demonstrated that the major cause of this' slow dissociation was a single posttranslational modification in ISC beta-actin. Two sulfhydryl groups (Cys(284) and Cys(373)) became inaccessible to thiol reagents because of this modification. We suggested the possibility that the modification was a disulfide bridge between Cys(284) and Cys(373) since the reducing agent dithiothreitol restored the sulfhydryl groups. In this article, we directly demonstrate the existence of the disulfide bridge between cysteine(284) and cysteine(373) in ISC beta-actin. We synthesized the associated ISC beta-actin tryptic cystine-peptide (KCF-CDVDIR), characterized it by HPLC, MS, and MSMS, and identified it in the tryptic digest of the ISC beta-actin. These results support our earlier suggestion that the oxidative change in ISC beta-actin is a major cause of the irreversible sickling phenomenon. C1 UNIV SO ALABAMA,COLL MED,USA COMPREHENS SICKLE CELL CTR,MOBILE,AL 36688. UNIV SO ALABAMA,COLL MED,DEPT BIOCHEM,MOBILE,AL 36688. US FDA,GULF COAST SEAFOOD LAB,DAUPHIN ISL,AL 36258. FU NHLBI NIH HHS [3P60 HL38639] NR 29 TC 32 Z9 33 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 9 PY 1996 VL 35 IS 14 BP 4403 EP 4408 DI 10.1021/bi960063n PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UE612 UT WOS:A1996UE61200017 PM 8605189 ER PT J AU Desai, VG Feuers, RJ Hart, RW Ali, SF AF Desai, VG Feuers, RJ Hart, RW Ali, SF TI MPP(+)-induced neurotoxicity in mouse is age-dependent: Evidenced by the selective inhibition of complexes of electron transport SO BRAIN RESEARCH LA English DT Article DE 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); 1-methyl-4-phenylpyridine (MPP(+)); neurotoxicity; NADH-ubiquinone oxidoreductase; succinate-ubiquinone oxidoreductase; ubiquinol-cytochrome c reductase; cytochrome c oxidase ID 1-METHYL-4-PHENYLPYRIDINIUM ION MPP+; MITOCHONDRIAL-DNA MUTATIONS; INDUCED PARKINSONS-DISEASE; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; SUPEROXIDE FORMATION; BRAIN MITOCHONDRIA; MONOAMINE-OXIDASE; SUBSTANTIA NIGRA; DOPAMINERGIC-NEURONS; REDUCTION REACTIONS AB 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), has been demonstrated to cause selective neurotoxicity by inhibiting complex I in mitochondria, through its toxic metabolite 1-methyl-4-phenylpyridine (MPP(+)) which is formed during the bioactivation of MPTP by monoamine oxidase B. In this report, we have evaluated the effect of MPP(+) on the 4 mitochondrial respiratory chain complexes by incubating brain mitochondria of mice at 3 different age groups with MPP(+) (200 mu M) and monitoring enzyme activities of complexes I, II, III, and IV at 5, 10, 15, 30, 60, and 120 min. Complexes I, III, and IV showed significant inhibition within 15 min in all the age groups studied, followed by some recovery in enzyme activities upon further incubation for complexes I and IV. However, complex II was not affected by MPP(+) at any age. Our data suggest that inhibition of complexes I, III and IV by MPP(+) efficiently restrict the transport of electrons down the respiratory chain which ultimately leads to decreased ATP production. This could further aggravate oxidative stress as ATP is required for the synthesis of glutathione (GSH), one of the important scavengers of free radicals. In this study, inhibition was more severe in mitochondrial preparations from older rather than younger mice. Additionally, young animals showed faster recovery following inhibition than old animals for complex I. Impaired respiratory chain function in older animals compared to younger ones supports the hypothesis of accumulation of age-related mitochondrial DNA mutations which partly encode for subunits of complexes I, III, and IV. From this study, it seems that inhibition of complexes I, III and IV may be the underlying cause of neurotoxicity due to MPP(+) which could be intensified by age-associated dysfunction of electron transport. C1 US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,NEUROCHEM LAB,JEFFERSON,AR 72079. US FDA,NATL CTR TOXICOL RES,DIV GENET TOXICOL,JEFFERSON,AR 72079. US FDA,NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,JEFFERSON,AR 72079. UNIV ARKANSAS MED SCI HOSP,DEPT ANAT,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT MED,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM & MOLEC BIOL,LITTLE ROCK,AR 72205. NR 60 TC 64 Z9 66 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 9 PY 1996 VL 715 IS 1-2 BP 1 EP 8 DI 10.1016/0006-8993(95)01255-9 PG 8 WC Neurosciences SC Neurosciences & Neurology GA UK609 UT WOS:A1996UK60900001 PM 8739616 ER PT J AU Delclos, KB Blaydes, B Heflich, RH Smith, BA AF Delclos, KB Blaydes, B Heflich, RH Smith, BA TI Assessment of DNA adducts and the frequency of 6-thioguanine resistant T-lymphocytes in F344 rats fed 2,4-toluenediamine or implanted with a toluenediisocyanate-containing polyester polyurethane foam SO MUTATION RESEARCH-GENETIC TOXICOLOGY LA English DT Article DE 2.4-toluenediamine; polyurethane; breast implant; DNA adduct; P-32-postlabeling; T-lymphocyte hprt mutations ID COVERED BREAST IMPLANTS; ETHYL-N-NITROSOUREA; FISCHER-344 RATS; MUTAGENIC NONCARCINOGEN; MANUFACTURING-INDUSTRY; LARGE DELETIONS; ANIMAL-MODEL; HPRT LOCUS; 2,4-DIAMINOTOLUENE; 2,6-DIAMINOTOLUENE AB Toluenediamines have been of toxicological concern because of their industrial use as intermediates in polyurethane synthesis and because of the potential of their release from degradation of the Microthane (TM) polyesterurethane covering of some breast implants. In this study, we have assessed the extent of DNA damage in rats treated with a carcinogenic toluenediamine isomer, 2,4-toluenediamine (2,4-TDA), under conditions that result in tumor induction, and in rats implanted with Microthane (TM) polyesterurethane foam. Time and dose-dependent formation of adducts was observed in DNA from the liver and mammary gland of rats fed 10, 40, 80 and 180 ppm 2,4-TDA for up to 6 weeks. In assays conducted 1 to 32 weeks after the start of treatment, no adducts were detected in the DNA of T-lymphocytes isolated from the spleens of animals fed 40 or 180 ppm 2,4-TDA, nor was there an increase in mutations at the hprt locus in these lymphocytes. In rats fed 40 or 180 ppm 2,4-TDA for 6 weeks, adducts were detectable in DNA isolated from liver and mammary gland for 26 to 43 weeks after termination of the treatment. No DNA damage, as assessed by both DNA adduct measurement and induction of T-lymphocyte hprt mutations, was observed in rats up to 42 weeks after receiving subcutaneous implants of polyesterurethane foam (67 or 267 mg/kg). Although 2,4-TDA is clearly capable of damaging DNA, the results of this study are consistent with the conclusion that Microthane (TM) foam-containing implants present a minimal risk of genotoxicity through release and subsequent metabolic activation of 2,4-TDA. The study also indicates that DNA adduct formation and mutation induction in lymphocytes are inadequate biomonitors for measuring exposure to toluenediamines. C1 NATL CTR TOXICOL RES,DIV GENET TOXICOL,JEFFERSON,AR 72079. RP Delclos, KB (reprint author), NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,HFT-110,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 48 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1218 J9 MUTAT RES-GENET TOX JI Mutat. Res.-Genet. Toxicol. PD APR 6 PY 1996 VL 367 IS 4 BP 209 EP 218 DI 10.1016/S0165-1218(96)90079-8 PG 10 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA UG798 UT WOS:A1996UG79800005 ER PT J AU Klinman, DM Yi, AK Beaucage, SL Conover, J Krieg, AM AF Klinman, DM Yi, AK Beaucage, SL Conover, J Krieg, AM TI CpG motifs present in bacterial DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon gamma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CELLS; DIFFERENTIATION; INVITRO; GROWTH; MICE; CD4+ AB Bacterial infection stimulates the host to mount a rapid inflammatory response, A 6-base DNA motif consisting of an unmethylated CpG dinucleotide flanked by two 5' purines and two 3' pyrimidines was shown to contribute to this response by inducing polyclonal B-cell activation, This stimulatory motif is 20 times more common in the DNA of bacteria than higher vertebrates. The current work shows that the same motif induces the rapid and coordinated secretion of interleukin (IL) 6, IL-12, and interferon gamma (but not IL-2, IL-3, IL-4, IL-5, or IL-10) in vivo and in vitro. Stimulatory CpG DNA motifs induced B, T, and natural killer cells to secrete cytokine more effectively than did lipopolysaccharide. Thus, Immune recognition of bacterial DNA may contribute to the cytokine as well as the antibody production characteristic of an Innate inflammatory response. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. UNIV IOWA,COLL MED,DEPT INTERNAL MED,DIV RHEUMATOL,IOWA CITY,IA 52242. VET AFFAIRS MED CTR,IOWA CITY,IA 52242. RP Klinman, DM (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,SECT RETROVIRAL IMMUNOL,BETHESDA,MD 20892, USA. FU NIAMS NIH HHS [R29-AR42556-01] NR 33 TC 1194 Z9 1254 U1 3 U2 12 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 2 PY 1996 VL 93 IS 7 BP 2879 EP 2883 DI 10.1073/pnas.93.7.2879 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UD375 UT WOS:A1996UD37500048 PM 8610135 ER PT J AU Rheinstein, PH AF Rheinstein, PH TI Significant FDA approvals in 1995 SO AMERICAN FAMILY PHYSICIAN LA English DT Article RP Rheinstein, PH (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD APR PY 1996 VL 53 IS 5 BP 1871 EP 1874 PG 4 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA UE743 UT WOS:A1996UE74300032 PM 8623703 ER PT J AU Wang, RF Cao, WW Cerniglia, CE AF Wang, RF Cao, WW Cerniglia, CE TI PCR detection and quantitation of predominant anaerobic bacteria in human and animal fecal samples SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; INTESTINAL MICROFLORA; METABOLISM; PROBES AB PCR procedures based on 16S rRNA gene sequences specific for 12 anaerobic bacteria that predominate in the human intestinal tract were developed and used for quantitative detection of these species in human (adult and baby) feces and animal (rat, mouse, cat, dog, monkey, and rabbit) feces, Fusobacterium prausnitzii, Peptostreptococcus productus, and Clostridium clostridiiforme had high PCR titers (the maximum dilutions for positive PCR results ranged from 10(-3) to 10(-8)) in all of the human and animal fecal samples tested, Bacteroides thetaiotaomicron, Bacteroides vulgatus, and Eubacterium limosum also showed higher PCR titers (10(-2) to 10(-6)) in adult human feces, The other bacteria tested, including Escherichia coli, Bifidobacterium adolescentis, Bifidobacterium longum, Lactobacillus acidophilus, Eubacterium biforme, and Bacteroides distasonis, were either at low PCR titers (less than 10(-2)) or not detected by PCR, The reported PCR procedure including the fecal sample preparation method is simplified and rapid and eliminates the DNA isolation steps. C1 US FDA,NATL CTR TOXICOL RES,DIV MICROBIOL,JEFFERSON,AR 72079. NR 28 TC 278 Z9 302 U1 6 U2 19 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD APR PY 1996 VL 62 IS 4 BP 1242 EP 1247 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA UD950 UT WOS:A1996UD95000019 PM 8919784 ER PT J AU McClure, GYH Freeman, JP Lay, JO Hinson, JA AF McClure, GYH Freeman, JP Lay, JO Hinson, JA TI Haemoglobin adducts as biomarkers of exposure to the herbicides propanil and fluometuron SO BIOMARKERS LA English DT Article DE haemoglobin adducts; herbicides; propanil; fluometuron; agricultural biomonitoring ID MONOCYCLIC AROMATIC-AMINES; HEMOGLOBIN BINDING; MOLECULAR DOSIMETRY; 4-AMINOBIPHENYL; METHEMOGLOBINEMIA; METABOLITES; PESTICIDES; SMOKING; RATS AB Aromatic amine herbicides, including propanil, fluometuron, alachlor, trifluralin, and pendimethalin, were examined for their ability to form haemoglobin adducts in rats as potential biomarkers of exposure, Many aromatic amines are known to form haemoglobin adducts via conversion to the nitroso metabolite and binding of this metabolite to cysteinyl groups on haemoglobin, Since red blood cells are long lived, adducts formed with these cells may be reliable biomarkers of exposure with the potential for showing progressive accumulation, Gas chromatographic-mass spectrometric analyses of haemoglobin revealed that adducts were formed in rats treated with the rice herbicide propanil and the cotton herbicide fluometuron, Adducts were not detected with the herbicides alachlor, trifluralin, or pendamethalin. C1 NATL CTR TOXICOL RES,DIV CHEM,JEFFERSON,AR 72079. RP McClure, GYH (reprint author), UNIV ARKANSAS MED SCI HOSP,DIV TOXICOL,LITTLE ROCK,AR 72205, USA. RI Lay, Jackson/G-1007-2011 OI Lay, Jackson/0000-0003-3789-2527 NR 22 TC 5 Z9 5 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 1354-750X J9 BIOMARKERS JI Biomarkers PD APR-JUN PY 1996 VL 1 IS 2 BP 136 EP 140 DI 10.3109/13547509609088681 PG 5 WC Biotechnology & Applied Microbiology; Toxicology SC Biotechnology & Applied Microbiology; Toxicology GA VV685 UT WOS:A1996VV68500009 PM 23888924 ER PT J AU Wang, D Weghorst, CM Calvert, RJ Stoner, GD AF Wang, D Weghorst, CM Calvert, RJ Stoner, GD TI Mutations in the p53 tumor suppressor gene in rat esophageal papillomas induced by N-nitrosomethylbenzylamine SO CARCINOGENESIS LA English DT Article ID POLYMERASE CHAIN-REACTION; POINT MUTATIONS; CANCER; DNA; RISK; O-6-METHYLDEOXYGUANOSINE; METHYLBENZYLNITROSAMINE; CARCINOGENESIS; EPIDEMIOLOGY; METHYLATION AB Mutations in the p53 tumor suppressor gene have been implicated in the pathogenesis of a wide variety of human neoplasms, The location and type of p53 gene mutation can reflect exposure of humans to certain types of carcinogenic agents, Much less is known about the role of p53 mutational inactivation in rodent tumors, Using both 'Hot' (radioactive) and 'Cold' (non-radioactive) single strand conformation polymorphism (SSCP) analyses, the present study analyzed exons 5-8 and the exon-intron junction of the p53 gene from rat esophageal papillomas induced by N-nitsosomethylbenzylamine (NMBA) for mutations, Nine of 30 (30%) esophageal papillomas contained SSCP mobility shifts, principally within exons 5 and 7, These positive SSCP findings were further validated by direct DNA sequencing analysis, Eight of the nine mutations were G:C-->A:T transitions in codons 131, 149, 153, 242 (2), 243, 248, and the 5 end of intron 7, None of these G:C-->A:T mutations occurred at the CPG sites, The other mutation was a frameshift mutation in codon 176, The G:C-->A:T transitions observed in this study are consistent with the documented formation of O-6-methylguanine adducts in DNA by N-nitroso compounds, These results suggest that point mutations of the p53 gene are involved in the development of approximately one-third of NMBA-induced rat esophageal papillomas, 'Hot' and 'Cold' SSCP methods were equally sensitive for the identification of mutations in the rat p53 gene. C1 OHIO STATE UNIV,DEPT PATHOL,COLUMBUS,OH 43210. OHIO STATE UNIV,CANC ETIOL & CHEMOPREVENT LAB,COLUMBUS,OH 43210. OHIO STATE UNIV,SCH PUBL HLTH,COLUMBUS,OH 43210. US FDA,CLIN RES & REVIEW STAFF,OFFF SPECIAL NUTRITIONALS,LAUREL,MD 20708. NR 58 TC 41 Z9 42 U1 1 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 1996 VL 17 IS 4 BP 625 EP 630 DI 10.1093/carcin/17.4.625 PG 6 WC Oncology SC Oncology GA UG814 UT WOS:A1996UG81400002 PM 8625469 ER PT J AU Butcher, NJ Minchin, RF Kadlubar, FF Ilett, KF AF Butcher, NJ Minchin, RF Kadlubar, FF Ilett, KF TI Uptake of the food-derived heterocyclic amine carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and its N-hydroxy metabolite into rat pancreatic acini and hepatocytes in vitro SO CARCINOGENESIS LA English DT Article ID EXOCRINE PANCREAS; PHIP; PHENYLALANINE; ACTIVATION; TRANSPORT; MUTAGENS; PROTEIN; CANCER; INFLUX; CELLS AB Since DNA adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are formed at relatively high levels in the fat pancreas but not liver, we examined the uptake of PhIP and its N-hydroxy metabolite (N-OH-PhIP) into pancreatic acini and hepatocytes to determine if differential tissue uptake was a factor modulating the formation of PhIP-DNA adducts, Pn addition, since the precursors of PhIP formation are two amino acids and since various amino acid transporters have been identified in the pancreas, the possible involvement of these transporters in the uptake of PhIP and N-OH-PhIP was investigated. The uptake of both heterocyclic compounds into both tissue preparations was rapid, with maximal uptake occurring within 1-2 min, However, PhIP uptake into pancreatic acini was significantly (2-way ANOVA, P < 0.05) greater than uptake of N-OH-PhIP into pancreatic acini and the uptake of both PhIP and N-OH-PhIP into hepatocytes. Although uptake was rapid, efflux of both compounds from both tissue preparations was also rapid. However, the efflux rate constant (1.86 +/- 0.6/min, mean +/- SEM) for PhIP was significantly lower (Student's t-test, P < 0.05) than that for N-OH-PhIP (4.14 +/- 0.04/min) from pancreatic acini. This, combined with the increased uptake of PhIP into pancreatic acini, suggests that there is substantial but reversible binding of PhIP in the pancreas, The uptake of both PhIP and N-OH-PhIP into pancreatic acini acid hepatocytes was not affected by the presence of various amino acids in the incubation buffer, indicating that amino acid transporters are not involved in uptake of these compounds, Furthermore, uptake of both compounds did not appear to be dependent on metabolic energy supply. The above data, together with the high octanol:buffer partition coefficients (logP = 1.322 and 1.301 for PhIP and N-OH-PhIP respectively) suggest that both uptake and efflux of PhIP and N-OH-PhIP are consistent with a process of passive diffusion, The tissue binding characteristics for PhIP in the pancreas may create conditions whereby pancreatic cytochrome P450 1A1 can catalyse the formation of N-OH-PhIP. While N-OH-PhIP is not the ultimate reactive DNA binding species, it has been shown to directly bind to and form DNA adducts, Therefore, it is possible that the apparent selective accumulation of PhIP may contribute to the high level of PhIP-DNA adducts formed in the rat pancreas. C1 UNIV WESTERN AUSTRALIA,DEPT PHARMACOL,NEDLANDS,WA 6907,AUSTRALIA. NATL CTR TOXICOL RES,DIV MOLEC EPIDEMIOL,JEFFERSON,AR 72079. WESTERN AUSTRALIA INST PATHOL & MED RES,CLIN PHARMACOL & TOXICOL LAB,NEDLANDS,WA 6907,AUSTRALIA. OI Butcher, Neville/0000-0002-0709-5589 NR 27 TC 10 Z9 10 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 1996 VL 17 IS 4 BP 889 EP 892 DI 10.1093/carcin/17.4.889 PG 4 WC Oncology SC Oncology GA UG814 UT WOS:A1996UG81400040 PM 8625507 ER PT J AU Aidoo, A Feuers, RJ LynCook, LE Bishop, ME Casciano, DA AF Aidoo, A Feuers, RJ LynCook, LE Bishop, ME Casciano, DA TI Characterization of rat lymphocyte primary culture for the development of an in-vitro mutagenesis assay: Effect of interleukin-2 and 2-mercaptoethanol on the activities of intermediary metabolism enzymes and cell proliferation SO CELL BIOLOGY AND TOXICOLOGY LA English DT Article DE intermediary metabolism enzymes; mitogen stimulation; rat lymphocytes ID PERIPHERAL-BLOOD; PROTEIN; MODULATION; ACTIVATION; INDUCTION; INVIVO; PHYTOHEMAGGLUTININ; CARCINOGENICITY; PHOSPHORYLATION; RESPONSIVENESS AB Efficient energy utilization is essential for cell growth; in an attempt to improve the growth conditions of the rat T-lymphocyte culture model for potential use in studying the mutagenic activity of carcinogens in vitro, we have investigated the effects of phytohemagglutinin (PHA), interleukin-2 (IL-2) and 2-mercaptoethanol (2-ME) on the activities of intermediary metabolism enzymes and cell proliferation. Isolated lymphocytes were cultured in the presence and absence of PHA, IL-2, or 2-ME. The intermediary metabolism enzymes investigated were glutamate dehydrogenase, glutamate-pyruvate transaminase, malate dehydrogenase, isocitrate dehydrogenase, lactate dehydrogenase, pyruvate kinase, and fatty acid synthetase (FAS). Measurable activity of all enzymes investigated, except for FAS, was detected in PHA-stimulated cells cultured with IL-2 or 2-ME. The unstimulated lymphocytes had significantly lower enzyme activity than stimulated cells. The combination of all three agents showed increased enzyme activity. This increase in activity brought about by the combination of the three agents was not reproduced by either agent acting alone. In general, the increase in enzyme activity correlated with cell proliferation as measured by [H-3]thymidine uptake in PHA-stimulated cultures containing IL-2 and/or 2-ME. The results suggest that the addition of exogenous IL-2 and 2-ME enhances metabolic function and may be beneficial in in vitro culture of rat lymphocytes. RP Aidoo, A (reprint author), US FDA,NATL CTR TOXICOL RES,DIV GENET TOXICOL,HFT 120,JEFFERSON,AR 72079, USA. NR 34 TC 4 Z9 4 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0742-2091 J9 CELL BIOL TOXICOL JI Cell Biol. Toxicol. PD APR PY 1996 VL 12 IS 2 BP 79 EP 87 DI 10.1007/BF00143358 PG 9 WC Cell Biology; Toxicology SC Cell Biology; Toxicology GA UL450 UT WOS:A1996UL45000003 PM 8738477 ER PT J AU Ahn, HS AF Ahn, HS TI Log-normal regression modeling through recursive partitioning SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE bootstrap; censoring; cross-validation; parametric regression; regression tree; survival analysis ID CENSORED SURVIVAL-DATA; LINEAR-REGRESSION; TREES AB This article discusses a method for fitting log-normal regression models to censored survival data through binary decision trees. Recursive partitioning is performed by analysis of the distributions of residuals and cross-validation estimates of the average squared error. Several forms of strata selection and bootstrapping are examined to study their relative effectiveness. If the Newton - Raphson method for determining the maximum likelihood estimates fails because of heavy censoring, a method relying only on the first derivatives of the log likelihood function is used. The proposed method helps to identify the local effect of the covariates. The methods are illustrated with real and simulated data. Especially, a data set having categorical variables and missing values is used for modeling the tree-structured log-normal regression. C1 US FDA,NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,JEFFERSON,AR 72079. NR 32 TC 6 Z9 6 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD APR PY 1996 VL 21 IS 4 BP 381 EP 398 DI 10.1016/0167-9473(95)00023-2 PG 18 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA UC911 UT WOS:A1996UC91100001 ER PT J AU Free, MJ Srisamang, V Vail, J Mercer, D Kotz, R Marlowe, DE AF Free, MJ Srisamang, V Vail, J Mercer, D Kotz, R Marlowe, DE TI Latex rubber condoms: Predicting and extending shelf life SO CONTRACEPTION LA English DT Article DE latex condoms; latex stability; aging; shelf life; condom quality ID STRENGTH AB Condoms from five manufacturers were subjected to controlled exposures of heat, humidity, and air and to different natural environments in five countries. Under aerobic conditions (condoms in permeable packages or unpackaged), stress properties declined. The relationship between rate of decline as a function of temperature was quadratic. Under oxygen-restricted conditions (foil-wrapped packages) at average storage temperatures of 30 degrees C and lower, strain properties declined with Little or no significant change in stress properties. The effect is to cause condoms to become stiffer; high-breakage rates in use have been correlated with product stiffening. A new rationale for accelerated-aging tests to predict condom shelf stability is suggested, including a test to control the trend of condoms to stiffen. Silicone lubricant, impermeable packaging, and inclusion of antioxidants in the condom formulation can prevent or minimize aerobic breakdown of latex condoms. Specifying low-modulus condoms can prevent excessive stiffening. C1 PROGRAM APPROPRIATE TECHNOL & HLTH,SEATTLE,WA 98109. US FDA,CTR DEVICES & RADIOL HLTH,OFF SCI & TECHNOL,ROCKVILLE,MD 20850. NR 5 TC 12 Z9 12 U1 1 U2 3 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0010-7824 J9 CONTRACEPTION JI Contraception PD APR PY 1996 VL 53 IS 4 BP 221 EP 229 DI 10.1016/0010-7824(96)00041-8 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA UE914 UT WOS:A1996UE91400006 PM 8706440 ER PT J AU Raza, H King, RS Squires, RB Guengerich, FP Miller, DW Freeman, JP Lang, NP Kadlubar, FF AF Raza, H King, RS Squires, RB Guengerich, FP Miller, DW Freeman, JP Lang, NP Kadlubar, FF TI Metabolism of 2-amino-alpha-carboline - A food-borne heterocyclic amine mutagen and carcinogen by human and rodent liver microsomes and by human cytochrome P4501A2 SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID CIGARETTE-SMOKE CONDENSATE; ALPHA-CARBOLINES; AROMATIC-AMINES; ACTIVATION; RAT; OXIDATION AB 2-Amino-alpha-carboline (A alpha C) is a mutagenic and carcinogenic heterocyclic amine that is formed as a pyrolysis product during the high temperature cooking of food and the burning of tobacco. Human, rat, and mouse hepatic microsomes each catalyzed the NADPH-dependent oxidation of A alpha C to form six products separable by HPLC. The two major metabolites, which together accounted for similar to 85% of the total metabolism, were characterized by UV, fluorescence, proton magnetic resonance, and mass spectral analyses as 3-hydroxy-A alpha C and 6-hydroxy-A alpha C. The remaining 15% were judged to be N-hydroxy-A alpha C and its oxidation products, based on chromatographic and spectral comparisons with a standard, whose synthesis and characterization are also described. Although the proportions of each metabolite were similar across species and individuals, the overall rate of metabolism of A alpha C by human hepatic microsomes showed a wide interindividual variation (37-fold), with a mean activity that was comparable with that observed with rat or mouse liver microsomes. alpha-Naphthoflavone, a selective inhibitor for cytochromes P4501A1 and P4501A2, strongly inhibited formation of both ring-hydroxylation and N-oxidation products by human, rat, or mouse liver hepatic microsomes. In addition, A alpha C oxidation was strongly correlated (r = 0.98; p < 0.001) with the oxidation of 4-aminobiphenyl, a known selective substrate for human and rodent cytochromes P4501A2. Immunoblot analyses confirmed the presence of cytochromes P4501A2, and not P4501A1, in human liver microsomes. Additional studies using recombinant human cytochromes P450 show that high catalytic activity for A alpha C metabolism was associated with human cytochrome P4501A2. Lower, but significant activity was also noted for P4501A1 and P4502C10, which could have important implications for the metabolic activation of A alpha C in extrahepatic tissues. Neither A alpha C metabolism nor immunoreactive cytochrome P4501A2 (or P4501A1) was detected in human pancreatic microsomes. Although further carcinogenicity and biomarker studies for A alpha C are needed, the high rate of A alpha C metabolism by human liver cytochrome P4501A2 suggests that humans with the rapid P4501A2 phenotype with may be more susceptible than rodents to this heterocyclic amine carcinogen. C1 NATL CTR TOXICOL RES,DIV MOL EPIDEMIOL,JEFFERSON,AR 72079. VANDERBILT UNIV,SCH MED,CTR MOLEC TOXICOL,NASHVILLE,TN 37240. VANDERBILT UNIV,SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37240. JOHN L MCCLELLAN MEM VET ADM MED CTR,MED CTR,LITTLE ROCK,AR 72205. UNITED ARAB EMIRATES UNIV,FAC MED & HLTH SCI,DEPT CHEM,AL AIN,U ARAB EMIRATES. RI King, Roberta/A-1749-2010 OI King, Roberta/0000-0002-3550-4255 NR 36 TC 53 Z9 53 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD APR PY 1996 VL 24 IS 4 BP 395 EP 400 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UE830 UT WOS:A1996UE83000004 PM 8801053 ER PT J AU Lampel, KA Keasler, SP Hanes, DE AF Lampel, KA Keasler, SP Hanes, DE TI Specific detection of Salmonella enterica serotype Enteritidis using the polymerase chain reaction SO EPIDEMIOLOGY AND INFECTION LA English DT Article ID PLASMID-ASSOCIATED VIRULENCE; NUCLEOTIDE-SEQUENCE; TYPHIMURIUM; GENE; DNA; IDENTIFICATION; DUBLIN; REGION AB An assay was developed for the specific detection of Salmonella enterica serotype Enteritidis, using a novel application of the polymerase chain reaction (PCR). This PCR assay is based on the mismatch amplification mutation assay, an allele-specific reaction, and can discriminate Enteritidis from all other salmonella. PCR primers were selected to amplify a 351-base pair (bp) DNA fragment from the salmonella plasmid virulence A (spvA) gene of Enteritidis. A single base difference at position 272 is present between the nucleotide sequence of the spvA gene of Enteritidis and other salmonellae. The downstream PCR primer, that encompasses position 272 of the Enteritidis spvA gene, was designed to contain a single base mismatch at the penultimate position, resulting in a 1-base mismatch with Enteritidis and a 2-base mismatch with other salmonellae that harbour the virulence plasmid. The upstream primer was completely homologous with the region immediately 5' to the spvA gene. When these primers were used and the annealing and extension reactions were performed at the same temperature, the PCR assay was specific for Enteritidis; no PCR product was detected for 40 other serotypes and 28 different genera examined. In pure culture, 120 colony forming units (c.f.u.) could be detected; a PCR product was observed from template derived from a 5 h enrichment broth culture of chicken seeded with 1 c.f.u, per gram of Enteritidis. This PCR assay is specific, reproducible, and less time consuming than the standard bacteriological methods used to detect Enteritidis. C1 US FDA,DIV VIRULENCE ASSESSMENT,WASHINGTON,DC 20204. RP Lampel, KA (reprint author), US FDA,DIV MOLEC BIOL RES & EVALUAT,HFS 237,200 C ST SW,WASHINGTON,DC 20204, USA. NR 43 TC 20 Z9 20 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD APR PY 1996 VL 116 IS 2 BP 137 EP 145 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA UH255 UT WOS:A1996UH25500005 PM 8620904 ER PT J AU Patnaik, R Lesko, LJ Chan, K Williams, RL AF Patnaik, R Lesko, LJ Chan, K Williams, RL TI Bioequivalence assessment of generic drugs: An American point of view SO EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS LA English DT Article; Proceedings Paper CT 6th European Congress of Biopharmaceutics and Pharmacokinetics CY APR 22-24, 1996 CL ATHENS, GREECE SP FIP DE bioequivalence; bioavailability ID INDIVIDUAL BIOEQUIVALENCE; ABSORPTION; BIOAVAILABILITY; EQUIVALENCE RP Patnaik, R (reprint author), US FDA,CTR DRUG EVALUAT & RES,OFF PHARMACEUT SCI,ROCKVILLE,MD 20855, USA. NR 20 TC 21 Z9 23 U1 0 U2 1 PU MEDECINE ET HYGIENE PI GENEVA 4 PA 78 AVE ROSERALE, 1211 GENEVA 4, SWITZERLAND SN 0378-7966 J9 EUR J DRUG METAB PH JI Eur. J. Drug Metabol. Pharmacokinet. PD APR-JUN PY 1996 VL 21 IS 2 BP 159 EP 164 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UY209 UT WOS:A1996UY20900012 PM 8839690 ER PT J AU Feinstone, SM AF Feinstone, SM TI Hepatitis A: Epidemiology and prevention SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Review DE hepatitis A; vaccine; epidemiology; risk factors; prevention ID A VACCINE H2-STRAIN; SERONEGATIVE VOLUNTEERS; CELL-CULTURE; VIRUS; OUTBREAK; LIVE; IMMUNOGENICITY; TRANSMISSION; SHELLFISH; INFECTION AB Hepatitis A is a disease with worldwide distribution. Conditions of sanitation and hygiene determine the overall epidemiological situation in any area, but risk behaviour determines an individual's chance of exposure. The recent licensing of formalin-inactivated vaccines for the prevention of hepatitis A requires an understanding of the epidemiology in order to devise how best to use this the vaccine in individuals or populations. Although higher-risk groups can be identified in developed countries, and vaccine will be useful to those groups, it is not likely that the vaccine will have a large effect on the prevalence of hepatitis A until it becomes a part of the routine childhood immunization schedule. RP Feinstone, SM (reprint author), CTR BIOL EVALUAT & RES,DIV VIRAL PROD,BETHESDA,MD 20892, USA. NR 67 TC 13 Z9 17 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0954-691X J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD APR PY 1996 VL 8 IS 4 BP 300 EP 305 DI 10.1097/00042737-199604000-00002 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UN977 UT WOS:A1996UN97700002 PM 8781894 ER PT J AU Sprando, RL Black, TN Ames, MJ Rorie, JI Collins, TFX AF Sprando, RL Black, TN Ames, MJ Rorie, JI Collins, TFX TI Effect of intratesticular injection of sodium fluoride on spermatogenesis SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID REPRODUCTIVE-ORGANS; VAS-DEFERENS; STERILITY; AGENTS; MOUSE; MICE AB The potential of sodium fluoride to affect spermatogenesis in the rat was assessed by intratesticular injection. Experimental rats' left testis was injected with sodium fluoride (50, 175 and 250 ppm) in vehicle (0.9% physiological saline); control testes were injected with vehicle. The right testis served as a non-injected control. Testicular tissues collected 'at' and 'distal ts' the injection site and from the non-injected control testes were evaluated microscopically 24 hr and 1, 2 and 3 wk post-injection. Testicular tissues obtained at and distal to the injection site in all fluoride-injected groups resembled tissues collected from corresponding areas in the controls. Seminiferous tubule damage observed in both the vehicle-injected control testes and the fluoride-injected testes but not in the non-injected testes was attributed to injection trauma. Polymorphonuclear leucocyte infiltration was observed 24 hr post injection only at the injection site in the vehicle- and fluoride-injected groups. Leydig cells were unaffected. Leucocyte infiltration with seminiferous tubule damage was not considered to be a fluoride treatment-related effect because it was observed in both vehicle- and fluoride-injected testes. The results demonstrate that spermatogenesis in the rat is not adversely affected by direct exposure to fluoride at levels 200 times greater than those under normal conditions. Published by Elsevier Science Ltd. RP Sprando, RL (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV TOXICOL RES,8301 MUIRKIRK RD,BELTSVILLE,MD 20708, USA. NR 22 TC 13 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD APR PY 1996 VL 34 IS 4 BP 377 EP 384 DI 10.1016/0278-6915(96)84542-X PG 8 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA UJ873 UT WOS:A1996UJ87300007 PM 8641664 ER PT J AU Hopkins, RJ Girardi, LS Turney, EA AF Hopkins, RJ Girardi, LS Turney, EA TI Relationship between Helicobacter pylori eradication and reduced duodenal and gastric ulcer recurrence: A review SO GASTROENTEROLOGY LA English DT Article ID FOLLOW-UP; TRIPLE THERAPY; RELAPSE RATES; INFECTION; RANITIDINE; OMEPRAZOLE; TRIAL; AMOXICILLIN; BLIND; CURE AB Background & Aims: The aim of this study was to determine whether the current literature supports the use of Helicobacter pylori cure as the primary efficacy end point in peptic ulcer clinical trials. This could potentially reduce the complexity of future trials. Methods: Published articles containing information on both H. pylori eradication and ulcer recurrence were searched with MEDLINE. Abstracts were found by reviewing references from both primary and review articles. Results: Fourteen duodenal ulcer and five gastric ulcer studies satisfied requisite inclusion criteria. Ulcer recurrence was significantly less common among H. pylori-cured patients vs. noncured patients (6% vs. 67% for patients with duodenal ulcers; 4% vs. 59% for patients with gastric ulcers). For H. pylori-cured patients, duodenal ulcer recurrence was higher in studies using two endoscopic tests compared with three tests (9% vs. 3%) and higher in abstracts compared with published articles (14% vs. 4%). Timing of H. pylori eradication (4 weeks vs. less than or equal to 12 weeks) and ulcer recurrence assessment (6 months vs. less than or equal to 12 months) was not significantly related to duodenal ulcer recurrence. Conclusions: The current literature strongly suggests that H. pylori eradication 4 weeks after therapy should be used as the primary efficacy end point for reduced gastric and duodenal ulcer recurrence for the purpose of clinical trial design. C1 US DEPT HHS,US FDA,CTR DRUG EVALUAT & RES,DIV BIOMETR,ROCKVILLE,MD 20850. RP Hopkins, RJ (reprint author), US DEPT HHS,US FDA,CTR DRUG EVALUAT & RES,DIV ANTIINFECT DRUG PROD,HFD-520,ROOM S323,ROCKVILLE,MD 20850, USA. NR 48 TC 422 Z9 436 U1 1 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1996 VL 110 IS 4 BP 1244 EP 1252 DI 10.1053/gast.1996.v110.pm8613015 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UD846 UT WOS:A1996UD84600033 PM 8613015 ER PT J AU Ridge, J Terle, DA Dragunsky, E Levenbook, I AF Ridge, J Terle, DA Dragunsky, E Levenbook, I TI Effects of gamma-IFN and NGF on subpopulations in a human neuroblastoma cell line: Flow cytometric and morphological analysis SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE neuroblastoma; gamma-IFN; NGF; differentiation; FACS analysis ID NERVE GROWTH-FACTOR; NEURO-BLASTOMA CELLS; FACTOR-INDUCED DIFFERENTIATION; RETINOIC ACID; INTERFERON-GAMMA; GENE-EXPRESSION; SCHWANN-CELLS; TRK GENE; CREST; RECEPTORS AB Neuroblastomas are neural crest-derived tumors that contain neuronal, melanocyte, and Schwann cell precursors. We examined the effects of treatment with gamma-interferon (gamma-IFN) and nerve growth factor (NGF), alone, and in combination, on these progenitor subpopulations in the human neuroblastoma cell line, SH-SY5Y. Using fluorescence-activated flow cytometry (FAGS), changes in expression of three differentiation-specific or -associated marker proteins, the 200 kD neurofilament protein, the myelin basic protein, and the S-100 protein, were analyzed. Growth rates and morphological changes associated with each treatment over the 2-wk incubation period were noted. The greatest effects were observed with combined IFN + NGF treatment. These were significant increases in expression of all three proteins, distinctive morphological signs of differentiation, and extensive inhibition of proliferation compared to control cultures. Treatment with NGF alone resulted in increased neurofilament protein expression and in the length and number of neurite extensions, but there was no effect on the growth rate. IFN induced striking morphological changes, significant inhibition of growth, and changes in protein expression that correlated with neuronal to non-neuronal subpopulation shifts due to the death of differentiated cells. When treatment was discontinued after 15 d, the morphological changes induced by NGF were reversed within 2-3 d, while those induced by IFN +/- NGF were present up to ii wk post-treatment. Small, neuroblastic colonies were observed throughout the treatment period and within 4-6 wk after the cessation of treatment this cell-type fully reconstituted the cultures suggesting the presence of a stem cell. Our results indicate that treatment with gamma-IFN +/- NGF can regulate growth and induce, either stem cells or progenitor neuronal, Schwann and melanocyte subpopulations in the SH-SY5Y cell line to irreversibly differentiate. RP US FDA, CTR BIOL EVALUAT & RES,NLRC,ROOM 119,HFM255, 8800 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 59 TC 8 Z9 8 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 EI 1543-706X J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD APR PY 1996 VL 32 IS 4 BP 238 EP 248 PG 11 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA UQ430 UT WOS:A1996UQ43000011 PM 8727049 ER PT J AU Soriano, V Gutierrez, M Vallejo, A Aguilera, A Pujol, E Calderon, E GonzalezLahoz, J deLejarazu, O Eiros, JM Tor, J Ribera, JM Esparza, B Merino, F Leal, M Tuset, C MartinezZapico, R Caballero, E Ribera, M Bouza, E Llibre, JM Dronda, F Carballo, E RodriguezIglesias, M DelRomero, J Rodriguez, C Martin, AM Castro, A Pedreira, J Ulloa, F Heredia, A Hewlett, I Cilla, G PerezTrallero, E Calatayud, T Adelantado, M Bravo, R Mas, A AF Soriano, V Gutierrez, M Vallejo, A Aguilera, A Pujol, E Calderon, E GonzalezLahoz, J deLejarazu, O Eiros, JM Tor, J Ribera, JM Esparza, B Merino, F Leal, M Tuset, C MartinezZapico, R Caballero, E Ribera, M Bouza, E Llibre, JM Dronda, F Carballo, E RodriguezIglesias, M DelRomero, J Rodriguez, C Martin, AM Castro, A Pedreira, J Ulloa, F Heredia, A Hewlett, I Cilla, G PerezTrallero, E Calatayud, T Adelantado, M Bravo, R Mas, A TI Epidemiology of HTLV-I infection in Spain SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE HTLV-I; epidemiology; Spain; HIV-1; PCR ID VIRUS TYPE-I; CELL LEUKEMIA-VIRUS; RETROVIRUS INFECTION; SPASTIC PARAPARESIS; BLOOD-TRANSFUSION; SCREENING ASSAYS; DRUG-ABUSERS; I/II; ANTIBODIES; DONORS AB Background. The human T-lymphotropic virus type I (HTLV-I) has been implicated in the genesis of tropical spastic paraparesis (TSP), adult T-cell lymphoma (ATL), and some cases of uveitis, subacute arthropathies, chronic dermatitis and lymphocytic alveolitis. The virus is endemic in some areas of the Caribbean basin, Japan, subSaharan Africa, Central and South America, Middle East and Melanesia. Given that HTLV-I is transmitted through similar ways to HIV, screening in blood donors is recommended in some countries. Material and Methods. The clinical, epidemiological and virological characteristics of 27 patients with HTLV-I infection were identified in Spain up to September 1995. Results. Eighteen cases were Spanish natives and 9 were immigrants from endemic areas. Fifteen were male and 12 were female. The majority (12/18; 66.7%) of subjects born in Spain had resided in endemic areas or had had sexual partners from these regions. Four patients had TSP, three had ATL and one developed lymphomatous granulomatosis and T-cell lymphoma. The remaining HTLV-I subjects were asymptomatic at the time of diagnosis. Four cases were identified from screening of blood donors. Conclusion. HTLV-I is present in Spain, affecting natives and, less frequently, immigrants from endemic areas. Both neurological and lymphoproliferative diseases have been recognized in a quarter of patients. C1 HOSP CLIN UNIV, VALLADOLID, SPAIN. HOSP GERMANS TRIAS & PUJOL, BADALONA, SPAIN. UNIV BASQUE COUNTRY, FAC MED, E-48080 BILBAO, SPAIN. HOSP JUAN RAMON JIMENEZ, HUELVA, SPAIN. HOSP UNIV VIRGEN ROCIO, SEVILLE, SPAIN. UNIV VALENCIA, GEN HOSP, VALENCIA, SPAIN. UNIV BARCELONA, HOSP VALL HEBRON, BARCELONA, SPAIN. HOSP LA PAZ, MADRID, SPAIN. HOSP GEN GREGORIO MARANON, MADRID, SPAIN. HOSP CALELLA, BARCELONA, SPAIN. HOSP PENITENCIARIO, MADRID, SPAIN. HOSP XERAL VIGO, SANTIAGO DE COMPOSTELA, SPAIN. UNIV HOSP, CADIZ, SPAIN. CTR SANITARIO SANDOVAL, MADRID, SPAIN. HOSP INSULAR, LAS PALMAS, SPAIN. HOSP JUAN CANALEJO, LA CORUNA, SPAIN. HOSP MUNICIPAL, VIGO, SPAIN. US FDA, DIV TRANSFUS SCI, BETHESDA, MD 20014 USA. HOSP VIRGEN ARANZAZU, SAN SEBASTIAN, SPAIN. HOSP CABUENAS, GIJON, SPAIN. CTR TRANSFUS GALICIA, SANTIAGO DE COMPOSTELA, SPAIN. INST SALUD CARLOS III, CTR INVEST CLIN, MADRID, SPAIN. RI Leal, Manuel/C-8458-2015; IBIS, INMUNOVIROLOGI/O-9246-2015; Vallejo, Alejandro/I-5881-2015; Mas, Antonio/F-2505-2011; Bouza, Emilio/D-8661-2014; IBIS, EPIDEMIOLOGIA/O-8791-2015; OI Vallejo, Alejandro/0000-0001-5360-878X; Mas, Antonio/0000-0003-2563-570X; Bouza, Emilio/0000-0001-6967-9267; Calderon, Enrique/0000-0002-3166-5086 NR 56 TC 6 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD APR PY 1996 VL 25 IS 2 BP 443 EP 449 DI 10.1093/ije/25.2.443 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VE063 UT WOS:A1996VE06300026 PM 9119572 ER PT J AU Khan, AA Wang, RF Cao, WW Franklin, W Cerniglia, CE AF Khan, AA Wang, RF Cao, WW Franklin, W Cerniglia, CE TI Reclassification of a polycyclic aromatic hydrocarbon-metabolizing bacterium, Beijerinckia sp strain B1, as Sphingomonas yanoikuyae by fatty acid analysis, protein pattern analysis, DNA-DNA hybridization, and 16S ribosomal DNA sequencing SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID PSEUDOMONAS-PAUCIMOBILIS; OXIDATION; BENZANTHRACENE; BIODEGRADATION; DIHYDRODIOLS; CARCINOGENS; GENE AB A bacterium isolated from a polluted stream, capable of metabolizing biphenyl, naphthalene, phenanthrene, and higher-molecular-weight polycyclic aromatic hydrocarbons (D. Gibson, V. Mahadevan, D. Jerina, H. Yagi, and H. Yeh, Science 189:295-297, 1975), was previously identified as Beijerinckia sp strain B1. In this investigation, 16S rRNA gene sequencing, biochemical tests, fatty acid methyl ester analysis, polyacrylamide gel electrophoresis of protein, and DNA-DNA hybridization were used to determine the taxonomic relationship of Beijerinckia sp strain B1. The sequence of the 16S rRNA gene of B1 was identical to that of Sphingomonas yanoikuyae ATCC 51230(T). The biochemical tests, fatty acid analysis, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis profile of soluble proteins of strain B1 showed results similar to those of S-yanoikuyae. DNA-DNA hybridization indicated that B1 and S-yanoikuyae ATCC 51230(T) are 75% homologous at the DNA level. We propose that Beijerinckia sp strain B1 be reclassified as S-yanoikuyae. C1 US FDA,NATL CTR TOXICOL RES,DIV MICROBIOL,JEFFERSON,AR 72079. NR 23 TC 63 Z9 66 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD APR PY 1996 VL 46 IS 2 BP 466 EP 469 PG 4 WC Microbiology SC Microbiology GA UE640 UT WOS:A1996UE64000016 PM 8934904 ER PT J AU Liu, HY Montaser, A Dolan, SP Schwartz, RS AF Liu, HY Montaser, A Dolan, SP Schwartz, RS TI Evaluation of a low sample consumption, high-efficiency nebulizer for elemental analysis of biological samples using inductively coupled plasma mass spectrometry SO JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY LA English DT Article DE nebulizer; elemental analysis; biological samples; inductively coupled plasma mass spectrometry ID DIRECT-INJECTION NEBULIZATION; GLASS FRIT NEBULIZER; ICP-MS; LIQUID-CHROMATOGRAPHY; MULTIELEMENT ANALYSIS; PNEUMATIC NEBULIZERS; ATOMIC SPECTROMETRY; SPRAY CHAMBERS; SPECIATION; IODINE AB The applications of a pneumatically driven high-efficiency nebulizer (HEN), operated at a solution uptake rate of 85 mu l min(-1), are reported for the analysis of digested biological standard reference materials using argon ICP-MS. Laser Fraunhofer diffraction also is used to acquire droplet-size distributions for the tertiary aerosol from the HEN. Three Standard Reference Materials (SRM 1566 Oyster Tissue, 1577a Bovine Liver and 1571 Orchard Leaves, National Institute of Standards and Technology) are microwave/nitric acid digested and analysed by external calibration with four internal standards. Results for the measurement of 10 elements in the SRMs are presented. In general, good agreement is obtained between the measured and certified values. The droplet-size distributions of the tertiary aerosol of biological materials tested are nearly identical to that of the digestion blank solution consisting of 10% HNO3. C1 GEORGE WASHINGTON UNIV,DEPT CHEM,WASHINGTON,DC 20052. US FDA,ELEMENTAL RES BRANCH,WASHINGTON,DC 20204. US CUSTOMS SERV,WASHINGTON,DC 20229. NR 40 TC 42 Z9 43 U1 0 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0267-9477 J9 J ANAL ATOM SPECTROM JI J. Anal. At. Spectrom. PD APR PY 1996 VL 11 IS 4 BP 307 EP 311 DI 10.1039/ja9961100307 PG 5 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA UF871 UT WOS:A1996UF87100011 ER PT J AU Nawaz, MS Khan, AA Bhattacharayya, D Siitonen, PH Cerniglia, CE AF Nawaz, MS Khan, AA Bhattacharayya, D Siitonen, PH Cerniglia, CE TI Physical, biochemical, and immunological characterization of a thermostable amidase from Klebsiella pneumoniae NCTR 1 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SULFHYDRYL-GROUPS; ACETONITRILE; DEGRADATION; METABOLISM; PURIFICATION; ACRYLAMIDE; PROTEINS AB An amidase capable of degrading acrylamide and aliphatic amides was purified to apparent homogeneity from klebsiella pneumoniae NCTR 1, The enzyme is a monomer with an apparent molecular weight of 62,000, The pH and temperature optima of the enzyme were 7.0 and 65 degrees C, respectively. The purified amidase contained 11 5,5-dithiobis (2-nitrobenzoate) (DTNB)-titratable sulfhydryl (SH) groups, In the native enzyme 1.0 SH group readily reacted with DTNB with no detectable loss of activity, Titration of the next 3.0 SH groups with DTNB resulted in a loss of activity of more than 70%, The remaining seven inaccessible SH groups could be titrated only in the presence of 8 M guanidine hydrochloride, Titration of SH groups was strongly inhibited by carboxymethylation and KMnO4, suggesting the presence of SH groups at the active site(s). Inductively coupled plasma-atomic emission spectrometry analysis indicated that the native amidase contains 0.33 mol of cobalt and 0.33 moi of iron per mol of the native enzyme, Polyclonal antiserum against X. pneumoniae amidase was raised in rabbits, and immunochemical comparisons were made with amidases from Rhodococcus sp,, Mycobacterium smegmatis, Pseudomonas chlororaphis B23, and Methylophilus methylotrophus. The antiserum immunoprecipitated and immunoreacted with the amidases of K. pneumoniae and P. chlororaphis B23, The antiserum failed to immunoreact or immunoprecipitate with other amidases. C1 US FDA,NATL CTR TOXICOL RES,DIV MICROBIOL,JEFFERSON,AR 72079. US FDA,NATL CTR TOXICOL RES,DIV CHEM,JEFFERSON,AR 72079. NR 39 TC 28 Z9 30 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 1996 VL 178 IS 8 BP 2397 EP 2401 PG 5 WC Microbiology SC Microbiology GA UF036 UT WOS:A1996UF03600031 PM 8636044 ER PT J AU Dahut, W Harold, N Takimoto, C Allegra, C Chen, A Hamilton, JM Arbuck, S Sorensen, M Grollman, F Nakashima, H Lieberman, R Liang, M Corse, W Grem, J AF Dahut, W Harold, N Takimoto, C Allegra, C Chen, A Hamilton, JM Arbuck, S Sorensen, M Grollman, F Nakashima, H Lieberman, R Liang, M Corse, W Grem, J TI Phase I and pharmacologic study of 9-aminocamptothecin given by 72-hour infusion in adult cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TOPOISOMERASE-I; MALIGNANT-MELANOMA; CAMPTOTHECIN; TOPOTECAN; NSC-100880; XENOGRAFTS; INHIBITION; ANALOGS; TRIAL AB Purpose: To conduct a phase I and pharmacologic study of the new topoisomerase I inhibitor, 9-aminocamptothecin (9-AC). Patients and Methods: A 72-hour infusion of 9-AC was administered every 14 days to 48 solid-tumor patients at doses of 5 to 59 mu g/m(2)/h without granulocyte colony-stimulating factor (G CSF) and 47 to 74 mu g/m(2)/ h with G-CSF. Results: Without G-CSF, two of eight patients who received 47 mu g/m(2)/h had dose-limiting neutropenia in their initial cycle, as did both patients who received 59 mu g/m(2)/h (with a platelet count < 25,000/mu L in one). With G-CSF, zero of seven patients treated with 47 mu g/ m(2)/h had dose-limiting neutropenia in their first cycle, while dose-limiting neutropenia occurred in six of 14 patients (with platelet count < 25,000/mu L in five) entered at 59 mu g/m(2)/h. Among 39 patients entered at greater than or equal to 25 mu g/ m(2)/h 9-AC with or without G CSF, fatigue, diarrhea, and navsea/vomiting of grade 2 severity ultimately occurred in 54%, 30%, and 38%, respectively, while grade 3 toxicity of each type occurred in 8% of patients. Steady-state 9-AC lactone concentration (Css) increased linearly from 0.89 to 10.6 nmol/L, and correlated strongly with leukopenia (r = .85). Conclusion: The recommended phase II dose of 9-AC given by 72-hour infusion every 2 weeks is 35 mu g/m(2)/h without G-CSF or 47 mu g/m(2)/h with G-CSF support. Dose escalation in individual patients may be possible according to their tolerance. C1 NATL NAVAL MED CTR, NAVY MED ONCOL BRANCH, DEPT RADIOL, BETHESDA, MD 20889 USA. NCI, DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM, CLIN ONCOL PROGRAM,NCI,NAVY MED ONCOL BRANCH, BETHESDA, MD USA. US FDA, CTR DRUG EVALUAT & RES, ROCKVILLE, MD 20857 USA. NR 26 TC 66 Z9 67 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1996 VL 14 IS 4 BP 1236 EP 1244 PG 9 WC Oncology SC Oncology GA UF068 UT WOS:A1996UF06800025 PM 8648379 ER PT J AU Peeler, JT Bunning, VK AF Peeler, JT Bunning, VK TI Hazard assessment of Listeria monocytogenes in the processing of bovine milk - Response SO JOURNAL OF FOOD PROTECTION LA English DT Letter C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NR 3 TC 2 Z9 2 U1 0 U2 0 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2838 SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD APR PY 1996 VL 59 IS 4 BP 342 EP 343 PG 2 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA UG822 UT WOS:A1996UG82200002 ER PT J AU Casillas, RP Crow, SA Heinze, TM Deck, J Cerniglia, CE AF Casillas, RP Crow, SA Heinze, TM Deck, J Cerniglia, CE TI Initial oxidative and subsequent conjugative metabolites produced during the metabolism of phenanthrene by fungi SO JOURNAL OF INDUSTRIAL MICROBIOLOGY LA English DT Article DE phenanthrene; fungi; degradation; conjugates; metabolism ID POLYCYCLIC AROMATIC-HYDROCARBONS; HUMAN CYTOCHROME-P-450 ENZYMES; CUNNINGHAMELLA-ELEGANS; K-REGION; PHANEROCHAETE-CHRYSOSPORIUM; ARENE OXIDES; TRANSFORMATION; DETOXIFICATION; IDENTIFICATION; DIHYDRODIOLS AB Three filamentous fungi were examined for the ability to biotransform phenanthrene to oxidative (phase I) and conjugative (phase II) metabolites. Phenanthrene metabolites were purified by high-performance liquid chromatography (HPLC) and identified by UV/visible absorption, mass, and H-1 NMR spectra. Aspergillus niger ATCC 6275, Syncephalastrum racemosum UT-70, and Cunninghamella elegans ATCC 9245 initially transformed [9-C-14]phenanthrene to produce metabolites at the 9,10-, 1,2-, and 3,4- positions. Subsequently, sulfate conjugates of phase I metabolites were formed by A. niger, S. racemosum, and C. elegans, Minor glucuronide conjugates of 9-phenanthrol and phenanthrene trans-9,10-dihydrodiol were formed by S. racemosum and A. niger, respectively, In addition, C. elegans produced the glucose conjugates 1-phenanthryl beta-D-glucopyranoside and 2-hydroxy-1-phenanthryl beta-D-glucopyranoside, a novel metabolite. [9-C-14]Phenanthrene metabolites were not detected in organic extracts from biotransformation experiments with the yeasts, Candida lipolytica 37-1, Candida tropicalis ATCC 32113, and Candida maltosa R-42. C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. GEORGIA STATE UNIV,DEPT BIOL,ATLANTA,GA 30303. NR 36 TC 37 Z9 53 U1 1 U2 12 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0169-4146 J9 J IND MICROBIOL JI J. Indust. Microbiol. PD APR PY 1996 VL 16 IS 4 BP 205 EP 215 DI 10.1007/BF01570023 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA UK811 UT WOS:A1996UK81100001 PM 8652115 ER PT J AU Krawczynski, K Alter, MJ Tankersley, DL Beach, M Robertson, BH Lambert, S Kuo, G Spelbring, JE Meeks, E Sinha, S Carson, DA AF Krawczynski, K Alter, MJ Tankersley, DL Beach, M Robertson, BH Lambert, S Kuo, G Spelbring, JE Meeks, E Sinha, S Carson, DA TI Effect of immune globulin on the prevention of experimental hepatitis C virus infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID POST-TRANSFUSION HEPATITIS; NON-B HEPATITIS; NON-A; ANTIBODY; CHIMPANZEES; EFFICACY; ANTIGEN; RNA; HCV AB The efficacy of postexposure prophylaxis for the prevention of hepatitis C virus (HCV) infection was studied in experimentally infected chimpanzees, Three chimpanzees were inoculated with HCV: Two were treated 1 h later with anti-HCV-negative intravenous immune globulin (IGIV) or hepatitis C immune globulin (HCIG), and a third animal was not treated, HCV infection was detected in all 3 animals within a few days of inoculation, Once passively transferred anti-HCV declined in the HCIG-treated animal, there was an increase of HCV antigen (Ag)-positive hepatocytes followed by reappearance of anti-HCV; HCVAg disappeared concordant with the development of acute hepatitis, Acute hepatitis C developed in both the IGIV-treated and untreated chimpanzees, with peak liver enzyme activity on day 59, but was delayed in the HCIG-treated animal until day 146, Postexposure HCIG treatment markedly prolonged the incubation period of acute hepatitis C but did not prevent or delay HCV infection, IGIV had no effect on the course of HCV infection. C1 US FDA,CTR BIOL EVALUAT & RES,OFF BLOOD RES & REVIEW,DIV HEMATOL,ROCKVILLE,MD 20857. CHIRON CORP,EMERYVILLE,CA 94608. RP Krawczynski, K (reprint author), CTR DIS CONTROL & PREVENT,HEPATITIS BRANCH,DVRD,NCID,A-33,BLDG 6,ROOM 157,1600 CLIFTON RD,ATLANTA,GA 30333, USA. NR 28 TC 124 Z9 125 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1996 VL 173 IS 4 BP 822 EP 828 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UB274 UT WOS:A1996UB27400006 PM 8603959 ER PT J AU Berkower, I Mostowski, H Bull, TE Murphy, D AF Berkower, I Mostowski, H Bull, TE Murphy, D TI CD4-IgG binding threshold for inactivation of human immunodeficiency virus type 1 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; RECOMBINANT SOLUBLE CD4; ENVELOPE GLYCOPROTEIN-GP120; NEUTRALIZING ANTIBODIES; CELL RECEPTORS; AIDS VIRUS; HTLV-III; T-CELLS; GP120; HIV AB The stoichiometry of human immunodeficiency virus type 1 (HIV-1) inactivation by soluble receptor CD4-IgG hybrid dimers (CD4-IgG) was examined. The extent of HIV-1 inactivation was measured in a sensitive plaque-forming assay, and the corresponding level of CD4-IgG binding was determined by immunofluorescence of infected cells, Ninety percent virus inactivation occurred at relatively low levels of CD4-IgG binding (10% of the saturating level). At even lower binding levels (1.4% of maximum binding), virus survival was 44%. Over a broad range of binding conditions, the survival curve followed a model in which viruses binding more than a threshold level of CD4-IgG were completely inactivated, while viruses binding less remained infectious, The data indicate that CD4-IgG binding to 1.4% of gp120 binding sites equals the threshold for inactivation, Thus, virus inactivation can begin when 3 CD4-IgG (of similar to 216 gp120 sites) bind per virion. C1 NIH,BIOPHYS LAB,OFF VACCINE RES,CTR BIOL,FDA,BETHESDA,MD 20892. RP Berkower, I (reprint author), NIH,IMMUNOREGULAT LAB,OFF VACCINE RES,CTR BIOL,FDA,BLDG 29,ROOM 523,NIH CAMPUS,BETHESDA,MD 20892, USA. NR 34 TC 4 Z9 4 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1996 VL 173 IS 4 BP 863 EP 869 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UB274 UT WOS:A1996UB27400011 PM 8603964 ER PT J AU Calvo, MS Park, YK AF Calvo, MS Park, YK TI Changing phosphorus content of the US diet: Potential for adverse effects on bone SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT 1995 American-Institute-of-Nutrition Annual Meeting CY APR 09-13, 1995 CL ATLANTA, GA SP Amer Inst Nutr DE dietary phosphorus; dietary calcium; calcitriol; osteoporosis ID IMMUNOREACTIVE PARATHYROID-HORMONE; SERUM IONIZED CALCIUM; VITAMIN-D AXIS; POSTMENOPAUSAL WOMEN; ENERGY-INTAKE; PHOSPHATE THERAPY; YOUNG-ADULTS; 1,25-DIHYDROXYVITAMIN-D; METABOLISM; SECRETION AB The dietary intake of phosphorus in the United States is high relative to calcium. Intake estimates from the 1989-1991 Continuing Surveys of Food Intakes by Individuals conducted by the U.S. Department of Agriculture show that for both men and women, median calcium intakes do not meet the 1989 Recommended Dietary Allowances (RDAs) for most age groups over 10 y of age, whereas phosphorus intakes exceed the RDAs for most age groups. The use of phosphorus-containing food additives in the processing of foods contributes substantially to the daily phosphorus intake, and their use is increasing. Because much of the phosphorus through food additive use is not reflected in the estimates of phosphorus intakes derived from national food consumption surveys, these estimates underestimate true dietary intakes of phosphorus. High phosphorus intake has been shown to cause secondary hyperparathyroidism and bone loss in several animal models. High phosphorus, low calcium consumption consistent with current observed intake levels resulted in changes in calcium regulating hormones that were not conducive to optimizing peak bone mass in young women. Evidence that such high phosphorus intakes may impair synthesis of the active metabolite of vitamin D and disrupt calcium homeostasis particularly in older women are discussed. RP Calvo, MS (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,OFF SPECIAL NUTR,WASHINGTON,DC 20204, USA. NR 71 TC 112 Z9 113 U1 2 U2 4 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD APR PY 1996 VL 126 IS 4 SU S BP S1168 EP S1180 PG 13 WC Nutrition & Dietetics SC Nutrition & Dietetics GA UD167 UT WOS:A1996UD16700032 ER PT J AU Mahmood, I Balian, JD AF Mahmood, I Balian, JD TI Interspecies scaling: Predicting pharmacokinetic parameters of antiepileptic drugs in humans from animals with special emphasis on clearance SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID ANTIPYRINE INTRINSIC CLEARANCE; DOG; BINDING; TIME; RAT AB The objective of this study was to test the interspecies-scaling approach in a series of antiepileptic drugs. Clearance, volume of distribution, and elimination half-life were scaled up from animal data obtained from literature. Four different methods were utilized to generate plots to scale up the clearance values: (i) clearance vs body weight (simple allometric equation); (ii) the product of clearance and maximum life-span potential (MLP) vs body weight (an approach recommended in literature); (iii) the two-term power equation which incorporates both body weight and brain weight suggested by Boxenbaum; and (iv) the product of clearance and brain weight vs body weight (a new approach being introduced in this study). When the predicted values for clearance were qualitatively compared with the observed values in humans, it was found that our proposed method predicted the clearance better than the other three methods. Using the simple allometric equation, the prediction of volume of distribution as a function of body weight was found to be satisfactory. The elimination half-life could not be predicted from simple allometric equations for any of the drugs studied; however, utilizing the equation CL = VK, prediction for half-life was feasible. The results of this study indicate that it is possible to predict reliably the pharmacokinetic parameters of these antiepileptic drugs in humans from animal data using an allometric approach. C1 US FDA,NEUROPHARMACOL DRUG PROD,ROCKVILLE,MD 20852. RP Mahmood, I (reprint author), US FDA,OFF CLIN PHARMACOL & BIOPHARMACEUT,DIV PHARMACEUT EVALUAT 1,HFD-860,WOODMONT OFF CTR 2,ROCKVILLE,MD 20852, USA. NR 24 TC 72 Z9 72 U1 0 U2 5 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD APR PY 1996 VL 85 IS 4 BP 411 EP 414 DI 10.1021/js950400y PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA UD668 UT WOS:A1996UD66800013 PM 8901079 ER PT J AU Muller, J Khan, AS Li, M Rao, V Hearing, VJ Gorelik, E AF Muller, J Khan, AS Li, M Rao, V Hearing, VJ Gorelik, E TI Phenotypic changes and loss of melanoma-specific endogenous C-type retroviruses in BL6 melanoma cells transfected with the H-2K(b) gene SO MELANOMA RESEARCH LA English DT Article DE BL6 melanoma; control of retrovirus production; melanoma-associated antigen; MHC class I; MuLV ID LEUKEMIA-VIRUS DNA; CLASS-I GENE; B-16 MELANOMA; INCREASED SENSITIVITY; MHC GENES; EXPRESSION; MOUSE; ANTIGEN; SEQUENCES; IDENTIFICATION AB The murine B16 melanoma and its sublines are low or totally deficient in expression of the H-2K(b) class I major histocompatibility complex (MHC) gene. In clones derived from the B16F10BL6 subline, expression of the transfected or endogenous H-2K(b) gene resulted in alterations of various phenotypic properties of these melanoma cells, among which was the loss of melanoma-associated antigen (MAA) expression. Because our previous immunoelectron microscopy studies showed that MAA was associated with a C-type ecotropic retrovirus specific for melanomas of C57BL/6 origin, we examined the effect of class I H-2K(b) as well as class II H-21A(k) gene expression on retrovirus production in subclones of BL6 melanoma cells, Here we have shown that expression of the transfected or endogenous H-2K(b) gene resulted in the loss of production of budding, MAA-specific, C-type retrovirus particles. Northern blot analysis demonstrated expression of ecotropic retroviral mRNAs in both particle-producing and non-producing BL6 melanoma clones. Southern blot analysis of high-molecular-weight cellular DNAs using an ecotropic env-specific DNA probe indicated that the parental BL6-8 melanoma cells contained the C57BL/6 endogenous ecotropic MuLV (Emv-2) and at least three additional, novel ecotropic retroviral DNAs. Restriction enzyme analysis of the proviral DNA suggests that the loss of retrovirus production in the H-2K(b)-expressing melanoma clones is the result of multiple rearrangements in the novel proviral DNAs. Thus, phenotypic changes observed in the H-2K(b) gene-transfected BL6 melanoma cells were associated with loss of endogenous melanoma-specific ecotropic retrovirus production. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,BETHESDA,MD 20892. FU NCI NIH HHS [R01 CA59903-01] NR 33 TC 7 Z9 7 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD APR PY 1996 VL 6 IS 2 BP 101 EP 111 DI 10.1097/00008390-199604000-00004 PG 11 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA UQ060 UT WOS:A1996UQ06000004 PM 8791267 ER PT J AU Petricoin, E David, M Igarashi, K Benjamin, C Ling, L Goelz, S Finbloom, DS Larner, AC AF Petricoin, E David, M Igarashi, K Benjamin, C Ling, L Goelz, S Finbloom, DS Larner, AC TI Inhibition of alpha interferon but not gamma interferon signal transduction by phorbol esters is mediated by a tyrosine phosphatase SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DNA-BINDING PROTEINS; TRANSCRIPTION FACTOR; INVITRO ACTIVATION; HUMAN-MONOCYTES; INDUCIBLE GENE; E1A ONCOGENE; KINASE; RECEPTOR; ELEMENT; PHOSPHORYLATION AB Previous studies have indicated that the expression of viral oncoproteins, cell transformation, or phorbol ester treatment of cells can inhibit alpha/beta interferon (IFN-alpha/beta)-induced gene expression, The mechanisms by which these promoters of cell growth exert their inhibitory effects vary, but in most instances they involve a disruption of the IFN-alpha/beta-induced transcription complex ISGF3 such that the DNA-binding component of this complex (the 48-kDa ISGF3 gamma protein) does not bind to the interferon-stimulated response element (ISRE). In this report, we demonstrate that phorbol ester treatment of human peripheral blood monocytes dramatically inhibits activation of IFN alpha/beta-stimulated early response genes but by a mechanism which does not involve abrogation of the ISRE binding of ISGF3 gamma. Phorbol ester treatment of monocytes inhibited IFN alpha-stimulated tyrosine phosphorylation of the transcription factors Stat1 alpha, Stat2, and Stat3 and of the tyrosine kinase Tyk2 but had no effect on IFN-gamma activation of Stat1 alpha. IFN alpha-stimulated tyrosine phosphorylation of Jak1 and the alpha subunit of the IFN-alpha receptor were unaffected by phorbol 12-myristate 13-acetate (PMA), Moreover, PMA caused the dephosphorylation of Tyk2 but not of Jak1, which was activated by IFN, Pretreatment of cells with vanadate prevented the effects of PMA with regard to PMA-induced Tyk2 dephosphorylation. These observations suggest that PMA exerts its inhibitory effects by activation of a tyrosine phosphatase which selectively regulates Tyk2 but not Jak1 activity. C1 CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,ROCKVILLE,MD 20892. BIOGEN INC,CAMBRIDGE,MA 02142. NR 36 TC 35 Z9 36 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 1996 VL 16 IS 4 BP 1419 EP 1424 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UB562 UT WOS:A1996UB56200015 PM 8657115 ER PT J AU Chang, H AF Chang, H TI Genetic engineering to enhance microbial interference and related therapeutic applications SO NATURE BIOTECHNOLOGY LA English DT Article ID BACTERIAL VAGINOSIS; GROWTH-FACTOR; STREPTOCOCCUS-MUTANS; ESCHERICHIA-COLI; CANDIDA-ALBICANS; VIRUS; COLONIZATION; LACTOBACILLI; INFECTIONS; EXPRESSION RP Chang, H (reprint author), US FDA,HFM-573,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 66 TC 5 Z9 5 U1 0 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD APR PY 1996 VL 14 IS 4 BP 444 EP 447 DI 10.1038/nbt0496-444 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA UL588 UT WOS:A1996UL58800026 PM 9630918 ER PT J AU Lawrence, RA Friedman, LR Roghmann, KJ Howard, CR Fein, S AF Lawrence, RA Friedman, LR Roghmann, KJ Howard, CR Fein, S TI Breastfeeding in the US: Findings from the infant feeding practice SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 US FDA,WASHINGTON,DC 20204. UNIV ROCHESTER,SCH MED & DENT,DEPT PEDIAT,ROCHESTER,NY 14642. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 715 EP 715 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800716 ER PT J AU Asher, DM Chumakov, KM Dragunsky, EM Ridge, JS Taffs, RE Rezapkin, GV Norwood, LP Chernokhvostova, YV Douthitt, MP Levenbook, IS AF Asher, DM Chumakov, KM Dragunsky, EM Ridge, JS Taffs, RE Rezapkin, GV Norwood, LP Chernokhvostova, YV Douthitt, MP Levenbook, IS TI Recent advances in safety testing of live oral poliovirus vaccines. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 979 EP 979 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800979 ER PT J AU Pichichero, ME Deloria, MA Rennels, MB Anderson, EL Edwards, KM Englund, JA Decker, MD Steinhoff, MC Deforest, A Meade, BD AF Pichichero, ME Deloria, MA Rennels, MB Anderson, EL Edwards, KM Englund, JA Decker, MD Steinhoff, MC Deforest, A Meade, BD TI A comparison of whole cell DPT (DTwP) with 12 acellular pertussis vaccines (DTaP) as a booster in 15- to 20-month-old children. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 UNIV ROCHESTER,ROCHESTER,NY. NIAID,BETHESDA,MD 20892. UNIV MARYLAND,BALTIMORE,MD 21201. ST LOUIS UNIV,ST LOUIS,MO 63103. VANDERBILT UNIV,NASHVILLE,TN. BAYLOR UNIV,HOUSTON,TX 77030. JOHNS HOPKINS UNIV,BALTIMORE,MD. TEMPLE UNIV,PHILADELPHIA,PA 19122. US FDA,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1075 EP 1075 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801075 ER PT J AU Frederick, DL Allen, JD AF Frederick, DL Allen, JD TI Effects of selective dopamine D-1- and D-2-agonists and antagonists on timing performance in rats SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE time estimation; peak procedure; dopamine agonists; dopamine antagonists; SKF 38393; quinpirole; SCH 23390; eticlopride; D-1-receptors; D-2-receptors ID INTERNAL CLOCK; TIME PERCEPTION; RECEPTORS; D1; METHAMPHETAMINE; DISCRIMINATION; STIMULATION; INCREASES; BEHAVIOR; SYSTEM AB Dopamine (DA) D-1- and D-2-agonists and antagonists were administered at fixed doses to assess putative dopaminergic involvement in timing behavior in rats performing under a peak-interval schedule. Significant shifts in response distributions to the left (consistent with the overestimation of the passage of time) were observed after treatment with the D-1- and D-2-agonists SKF 38393 and quinpirole, respectively. Both DA antagonists, eticlopride (D-2) and SCH 23390 (D-1), shifted the response distributions to the right (consistent with the underestimation of the passage of time), but neither drug produced statistically significant shifts. Based on percent shift in peak time from predrug baseline values, no significant differences were detected between agents as a function of their reported affinities for the D-1- or D-2-receptors. Results indicate the need for a systematic evaluation of each drug at various doses and a more derailed examination of the use of temporal schedules in predicting the efficacy of psychotherapeutic agents. C1 UNIV GEORGIA,DEPT PSYCHOL,ATHENS,GA 30602. RP Frederick, DL (reprint author), US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,HFT-132,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 36 TC 33 Z9 33 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD APR PY 1996 VL 53 IS 4 BP 759 EP 764 DI 10.1016/0091-3057(95)02103-5 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA UC055 UT WOS:A1996UC05500001 PM 8801575 ER PT J AU Osterberg, RE Szarfman, A AF Osterberg, RE Szarfman, A TI Assessment of risk for photocarcinogenesis: Regulatory reviewer viewpoint SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article RP Osterberg, RE (reprint author), US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857, USA. NR 4 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD APR PY 1996 VL 63 IS 4 BP 362 EP 365 DI 10.1111/j.1751-1097.1996.tb03042.x PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UE400 UT WOS:A1996UE40000003 PM 8934736 ER PT J AU Houn, F AF Houn, F TI Is the mammography quality standards act worth the cost? SO RADIOLOGY LA English DT Letter RP Houn, F (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,US DEPT HHS,PHS,1350 PICCARD DR,ROCKVILLE,MD 20850, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 1996 VL 199 IS 1 BP 285 EP 286 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UB584 UT WOS:A1996UB58400051 PM 8633166 ER PT J AU Basu, AP Gaylor, DW Chen, JJ AF Basu, AP Gaylor, DW Chen, JJ TI Estimating the probability of occurrence of tumor for a rare cancer with zero occurrence in a sample SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID PROPORTIONS; TREND AB In many physical situations one needs to estimate the probability of occurrence of a rare event based on a random sample when the event has not occurred at all. For example, if the true Lifetime incidence of a tumor at a particular tissue site is less than 1%, it is not uncommon to observe no tumors in a typical sample size of 50 animals. This paper explores the suitability of nonzero Bayesian estimation procedures to replace zero maximum likelihood estimates for tissue sites with nonzero background tumor incidences. (C) 1996 Academic Press, Inc. C1 US FDA,NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,JEFFERSON,AR 72079. RP Basu, AP (reprint author), UNIV MISSOURI,DEPT STAT,COLUMBIA,MO 65211, USA. NR 13 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD APR PY 1996 VL 23 IS 2 BP 139 EP 144 DI 10.1006/rtph.1996.0035 PG 6 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA UV471 UT WOS:A1996UV47100006 PM 8661332 ER PT J AU Gaylor, DW Zheng, Q AF Gaylor, DW Zheng, Q TI Risk assessment of nongenotoxic carcinogens based upon cell proliferation death rates in rodents SO RISK ANALYSIS LA English DT Article DE carcinogens; cell proliferation; Moolgavkar-Venzon-Knudson model ID MODELS AB Increased cell proliferation increases the opportunity for transformations of normal cells to malignant cells via intermediate cells. Nongenotoxic cytotoxic carcinogens that increase cell proliferation rates to replace necrotic cells are likely to have a threshold dose for cytotoxicity below which necrosis and hence, carcinogenesis do not occur. Thus, low dose cancer risk estimates based upon nonthreshold, linear extrapolation are inappropriate for this situation. However, a threshold dose is questionable if a nongenotoxic carcinogen acts via a cell receptor. Also, a nongenotoxic carcinogen that increases the cell proliferation rate, via the cell division rate and/or cell removal rate by apoptosis, by augmenting an existing endogenous mechanism is not likely to have a threshold dose. Whether or not a threshold dose exists for nongenotoxic carcinogens, it is of interest to study the relationship between lifetime tumor incidence and the cell proliferation rate. The Moolgavkar-Venzon-Knudson biologically based stochastic two-stage clonal expansion model is used to describe a carcinogenic process. Because the variability in cell proliferation rates among animals often makes it impossible to detect changes of less than 20% in the rate, it is shown that small changes in the cell proliferation rate, that may be obscured by the background noise in rates, can produce large changes in the lifetime tumor incidence as calculated from the Moolgavkar-Venzon-Knudson model. That is, dose response curves for cell proliferation and tumor incidence do not necessarily mimic each other. This makes the use of no observed effect levels (NOELs) for cell proliferation rates often inadmissible for establishing acceptable daily intakes (ADIs) of nongenotoxic carcinogens. In those cases where low dose linearity is not likely, a potential alternative to a NOEL is a benchmark dose corresponding to a small increase in the cell proliferation rate, e.g., 1%, to which appropriate safety (uncertainty) factors can be applied to arrive at an ADI. RP Gaylor, DW (reprint author), US FDA,DIV BIOMETRY & RISK ASSESSMENT,NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 17 TC 16 Z9 16 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD APR PY 1996 VL 16 IS 2 BP 221 EP 225 PG 5 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA UK610 UT WOS:A1996UK61000010 PM 8638041 ER PT J AU Anderson, JG Katzper, M AF Anderson, JG Katzper, M TI Simulation in health sciences SO SIMULATION LA English DT Editorial Material C1 US FDA,DIV ANTIINFLAMMATORY ANALGES & OPHTHALMOL DRUG PR,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. RP Anderson, JG (reprint author), PURDUE UNIV,INST SOCIAL RES,DEPT SOCIOL & ANTHROPOL,W LAFAYETTE,IN 47907, USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SIMULATION COUNCILS INC PI SAN DIEGO PA PO BOX 17900, SAN DIEGO, CA 92117 SN 0037-5497 J9 SIMULATION JI Simulation PD APR PY 1996 VL 66 IS 4 BP 205 EP 206 DI 10.1177/003754979606600403 PG 2 WC Computer Science, Interdisciplinary Applications; Computer Science, Software Engineering SC Computer Science GA UM650 UT WOS:A1996UM65000003 ER PT J AU Singh, N Gayowski, T Ndimbie, OK Nedjar, S Wagener, MM Yu, VL AF Singh, N Gayowski, T Ndimbie, OK Nedjar, S Wagener, MM Yu, VL TI Recurrent hepatitis C virus hepatitis in liver transplant recipients receiving tacrolimus: Association with rejection and increased immunosuppression after transplantation SO SURGERY LA English DT Article ID CHRONIC ACTIVE HEPATITIS; INFECTION; THERAPY; CYCLOSPORINE; MARKERS AB Background. Recurrent hepatitis C virus hepatitis is associated with significant morbidity and mortality after liver transplantation. However, the risk factors for clinical recurrence including the role of rejection and immunosuppression have nor been defined in patients receiving tacrolimus (FK506) as primary immunosuppression. Methods. Sixty-six consecutive adult liver transplant recipients receiving tacrolimus as primary immunosuppression were monitored; 31 of 66 underwent transplantation for end-stage liver disease caused by hepatitis C virus. Median follow-up for the patients in the study was 3 1/2 years. Recurrent hepatitis C virus hepatitis determined on histopathologic evaluation developed in 58% (18 of 31). A number of clinical variables including rejection and intensity of immunosuppression were assessed for patients with and without recurrence. Results. Rejection episodes preceding recurrence were documented in 72% (13 of 18) of patients with recurrence compared with 23% (3 of 13) in those without recurrence (p = 0.007). A total of 33% (5 of 15) of patients with no rejection experienced recurrence versus 83% (5 of 6) with one episode of rejection (p = 0.06) and 80% (8 of 10) with more than one episode of rejection (p = 0.04). The mean number of steroid boluses for the treatment of rejection was higher for patients with recurrence (2.3 versus 0.77, p = 0.01). Overall immunosuppression (as measured by steroid boluses, recycles, OKT3, and azathioprine) was significantly more intense for patients with recurrence (p = 0.013). Conclusions. Greater rejection concurrent with increased immunosuppression was associated with a higher recurrence of hepatitis C in liver transplant recipients. C1 VET AFFAIRS MED CTR,INFECT DIS SECT,PITTSBURGH,PA 15240. UNIV PITTSBURGH,PITTSBURGH,PA. CENT BLOOD BANK PITTSBURGH,PITTSBURGH,PA. US FDA,HEPATITIS LAB,KENSINGTON,MD. NR 23 TC 58 Z9 58 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD APR PY 1996 VL 119 IS 4 BP 452 EP 456 DI 10.1016/S0039-6060(96)80147-4 PG 5 WC Surgery SC Surgery GA UD512 UT WOS:A1996UD51200015 PM 8644012 ER PT J AU Lambert, LA Wamer, WG Kornhauser, A AF Lambert, LA Wamer, WG Kornhauser, A TI Animal models for phototoxicity testing (Reprinted from Dermatotoxicology, 1996) SO TOXICOLOGY METHODS LA English DT Reprint ID GUINEA-PIG; MOUSE; RADIATION; PHOTOSENSITIZATION; 5-METHOXYPSORALEN; DERIVATIVES; INVITRO; FILTERS; INVIVO; SKIN C1 US FDA,CTR FOOD SAFETY & APPL NUTR,DIV SCI & APPL TECHNOL,COSMET TOXICOL BRANCH,WASHINGTON,DC 20204. NR 56 TC 4 Z9 5 U1 0 U2 1 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 1051-7235 J9 TOXICOL METHOD JI Toxicol. Method. PD APR-JUN PY 1996 VL 6 IS 2 BP 99 EP 114 DI 10.3109/15376519609068456 PG 16 WC Toxicology SC Toxicology GA VD507 UT WOS:A1996VD50700004 ER PT J AU Williamson, LC Halpern, JL Montecucco, C Brown, JE Neale, EA AF Williamson, LC Halpern, JL Montecucco, C Brown, JE Neale, EA TI Clostridial neurotoxins and substrate proteolysis in intact neurons - Botulinum neurotoxin C acts on synaptosomal-associated protein of 25 kDa SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SPINAL-CORD NEURONS; TETANUS-TOXIN; NEUROTRANSMITTER RELEASE; SYNAPTIC TRANSMISSION; MEMBRANE-PROTEIN; CULTURE; SNAP-25; FUSION; IDENTIFICATION; SYNAPTOBREVIN AB Clostridial neurotoxins are zinc endopeptidases that block neurotransmission and have been shown to cleave, in vitro, specific proteins involved in synaptic vesicle docking and/or fusion. We have used immunohistochemistry and immunoblotting to demonstrate alterations in toxin substrates in intact neurons under conditions of toxin-induced blockade of neurotransmitter release. Vesicle-associated membrane protein, which colocalizes with synaptophysin, is not detectable in tetanus toxin-blocked cultures. Syntaxin, also concentrated in synaptic sites, is cleaved by botulinum neurotoxin C. Similarly, the carboxyl terminus of the synaptosomal-associated protein of 25 kDa (SNAP-25) is not detectable in botulinum neurotoxin A-treated cultures. Unexpectedly, tetanus toxin exposure causes an increase in SNAP-25 immunofluorescence, reflecting increased accessibility of antibodies to antigenic sites rather than increased expression of the protein. Furthermore, botulinum neurotoxin C causes a marked loss of the carboxyl terminus of SNAP-25 when the toxin is added to living cultures, whereas it has no action on SNAP-25 in in vitro preparations, This study is the first to demonstrate in functioning neurons that the physiologic response to these toxins is correlated with the proteolysis of their respective substrates, Furthermore, the data demonstrate that botulinum neurotoxin C, in addition to cleaving syntaxin, exerts a secondary effect on SNAP-25. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. UNIV PADUA,CTR CNR BIOMEMBRANE,I-35121 PADUA,ITALY. UNIV PADUA,DIPARTIMENTO SCI BIOMED SPERIMENTALI,I-35121 PADUA,ITALY. USA,INST INFECT DIS,FT DETRICK,MD 21701. RP Williamson, LC (reprint author), NICHHD,DEV NEUROBIOL LAB,NIH,BLDG 49,RM 5A38,BETHESDA,MD 20892, USA. FU Telethon [473] NR 43 TC 155 Z9 157 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 29 PY 1996 VL 271 IS 13 BP 7694 EP 7699 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UC774 UT WOS:A1996UC77400076 PM 8631808 ER PT J AU Fenichel, RR AF Fenichel, RR TI Drug-induced hepatotoxicity SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Fenichel, RR (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 28 PY 1996 VL 334 IS 13 BP 864 EP 864 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UB950 UT WOS:A1996UB95000020 PM 8596562 ER PT J AU Chang, HC Compadre, RL Lloyd, RV Freeman, JP Samokyszyn, VM AF Chang, HC Compadre, RL Lloyd, RV Freeman, JP Samokyszyn, VM TI Nonenzymatic reduction of tetrachloro-1,4-benzoquinone by reduced nicotinamide adenine dinucleotide phosphate in an aqueous system SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MICROSOMAL METABOLISM; COVALENT BINDING; PENTACHLOROPHENOL; PROTEIN AB NADPH was shown to reduce tetrachloro-1,4-benzoquinone (TCBQ) to tetrachloro-1,4-benzene diol which was identified on the basis of cochromatography with synthetic standard in a reverse phase HPLC system, electronic absorption spectroscopy, and mass spectrometry. Conversely, NADPH was shown to undergo TCBQ-dependent oxidation as evidenced by uv spectroscopic analysis. ESR spectroscopy demonstrated that NADPH-dependent reduction of TCBQ proceeds through the intermediacy of a semiquinone radical intermediate. In addition, molecular mechanics and molecular orbital calculations were carried out on TCBQ to obtain partial atomic charges and the results suggest that the first electron transfer from the reduced nicotinamide moiety to TCBQ occurs at a carbonyl carbon. Kinetic analysis indicated that the rate of NADPH oxidation is first order with respect to [TCBQ], second order with respect to [NADPH], and an Arrhenius plot yielded an activation energy of 26 kJ . mol(-1) for the rate limiting step. Mechanisms are proposed which are consistent with these results. (C) 1996 Academic Press, Inc. C1 UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & TOXICOL,DIV TOXICOL,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT BIOPHARMACEUT SCI,LITTLE ROCK,AR 72205. MEMPHIS UNIV,DEPT CHEM,MEMPHIS,TN 38152. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 12 TC 3 Z9 3 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 27 PY 1996 VL 220 IS 3 BP 1043 EP 1048 DI 10.1006/bbrc.1996.0529 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UE853 UT WOS:A1996UE85300100 PM 8607788 ER PT J AU Nightingale, SL AF Nightingale, SL TI National surveillance program for changes in antimicrobial susceptibilities SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP Nightingale, SL (reprint author), OFF HLTH AFFAIRS,FDA PARKLAWN BLDG,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 1 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 27 PY 1996 VL 275 IS 12 BP 902 EP 902 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UA563 UT WOS:A1996UA56300011 PM 8598604 ER PT J AU Nightingale, SL AF Nightingale, SL TI Nicorette gum approved for over-the-counter marketing SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP Nightingale, SL (reprint author), OFF HLTH AFFAIRS,FDA PARKLAWN BLDG,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 27 PY 1996 VL 275 IS 12 BP 902 EP 902 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UA563 UT WOS:A1996UA56300010 PM 8598604 ER PT J AU Nightingale, SL AF Nightingale, SL TI First product available for preventing serious RSV disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP Nightingale, SL (reprint author), OFF HLTH AFFAIRS,FDA PARKLAWN BLDG,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 27 PY 1996 VL 275 IS 12 BP 902 EP 902 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UA563 UT WOS:A1996UA56300009 PM 8598604 ER PT J AU Den, R Nichols, C AF Den, R Nichols, C TI Persistent lack of detectable HIV-1 antibody in a person with HIV infection - Utah, 1995 (reprinted from MMWR, vol 45, pg 181-185, 1996) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 UNIV UTAH,SALT LAKE CITY,UT 84112. UTAH DEPT HLTH,SALT LAKE CITY,UT 84116. US FDA,SALT LAKE CITY RESIDENT POST & OFF BLOOD RES & RE,SALT LAKE CITY,UT. CDC,NATL CTR PREVENT SERV,DIV HIV AIDS PREVENT,ATLANTA,GA 30333. CDC,NATL CTR INFECT DIS,DIV HIV SEXUALLY TRANSMITTED DIS & TB LAB RES,ATLANTA,GA 30333. RP Den, R (reprint author), VET AFFAIRS MED CTR,SALT LAKE CITY,UT 84148, USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 27 PY 1996 VL 275 IS 12 BP 903 EP 904 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA UA563 UT WOS:A1996UA56300012 ER PT J AU DaSilva, L Rui, H Erwin, RA Howard, OMZ Kirken, RA Malabarba, MG Hackett, RH Larner, AC Farrar, WL AF DaSilva, L Rui, H Erwin, RA Howard, OMZ Kirken, RA Malabarba, MG Hackett, RH Larner, AC Farrar, WL TI Prolactin recruits STAT1, STAT3 and STAT5 independent of conserved receptor tyrosines TYR402, TYR479, TYR515 and TYR580 SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE prolactin; prolactin receptor; janus kinase; STAT transcription factor; signal transduction ID ERYTHROPOIETIN RECEPTOR; HUMAN MONOCYTES; EXPRESSION; REGION; GENE AB The present study of prolactin (PRL) receptor-mediated recruitment of signal transducers and activators of transcription (STATs) demonstrates that PRL activates STAT3, in addition to STAT1 and STAT5 as previously reported, and that STAT1, STAT3 and STAT5 are mediators of PRL effects in cells whether of lymphoid, myeloid or mammary epithelial origin. Furthermore, receptor mutants M240 and T280 that do not mediate PRL-induced JAK2 activation and cell proliferation, are also unable to mediate STAT activation, supporting the proposed model of JAK2 as the initial effector protein used by PRL receptors. On the other hand, tyrosine phosphorylation analysis and electrophoretic mobility shift assays showed that receptor mutant G328, which lacks four of the five conserved cytoplasmic tyrosine residues of PRL receptors, retained the ability to activate JAK2 and STAT1, STAT3 and STAT5. These results support the notion that phosphotyrosyl residues other than those of the receptor, i.e., JAK2, are involved in recruiting STAT proteins to the activated PRL receptor complex. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,BETHESDA,MD 20814. NCI,MOLEC IMMUNOREGULAT LAB,CYTOKINE MOL MECHANISMS SECT,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20814. RP DaSilva, L (reprint author), NCI,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. RI Howard, O M Zack/B-6117-2012; Malabarba, Maria Grazia/L-4805-2015 OI Howard, O M Zack/0000-0002-0505-7052; Malabarba, Maria Grazia/0000-0002-9457-2047 NR 46 TC 121 Z9 122 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD MAR 25 PY 1996 VL 117 IS 2 BP 131 EP 140 DI 10.1016/0303-7207(95)03738-1 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA UF453 UT WOS:A1996UF45300002 PM 8737372 ER PT J AU Welsh, WJ Lin, W Tersigni, SH Collantes, ER Duta, R Zielinski, WL Brower, J Layloff, TP AF Welsh, WJ Lin, W Tersigni, SH Collantes, ER Duta, R Zielinski, WL Brower, J Layloff, TP TI Pharmaceutical fingerprinting using neural networks and related chemometric techniques. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV MISSOURI,DEPT CHEM,ST LOUIS,MO 63121. US FDA,DIV DRUG ANAL,ST LOUIS,MO 63101. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 7 EP CINF PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48201795 ER PT J AU Shank, FR Carson, KL AF Shank, FR Carson, KL TI The chemist as a member of the food safety team SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 16 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48200014 ER PT J AU Miller, DW Shen, CY Conte, ED Takenaka, NE AF Miller, DW Shen, CY Conte, ED Takenaka, NE TI Measurement of seafood quality: The relationship of indole and total volatile base formation during the decomposition of shrimp. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,NATL CTR TOXICOL RES,DIV CHEM,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 23 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48200021 ER PT J AU Beyer, EB AF Beyer, EB TI FDA food regulations. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,DHHS,NEW ORLEANS,LA 70122. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 35 EP CHAL PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48201953 ER PT J AU Shank, FR Carson, KL AF Shank, FR Carson, KL TI HACCP: Assuming chemical safety. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 35 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48200033 ER PT J AU Beatrice, MG AF Beatrice, MG TI The role of pilot facilities in biologics manufacturing SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 37 EP BIOT PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48200492 ER PT J AU Staruszkiewicz, WF AF Staruszkiewicz, WF TI Scombroid poisonings and biogenic amines: A chemical hazard. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,WASHINGTON SEAFOOD LAB,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 45 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48200043 ER PT J AU Hall, S AF Hall, S TI Natural toxins in seafoods: Options for detection and management. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,OFF SEAFOOD,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 47 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48200045 ER PT J AU Mulligan, KJ Fricke, FL Satzger, RD Wolnik, KA AF Mulligan, KJ Fricke, FL Satzger, RD Wolnik, KA TI Analytical approaches to the characterization of product tampering. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,FORENS CHEM CTR,CINCINNATI,OH 45202. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 51 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48200049 ER PT J AU Calvey, EM Block, E AF Calvey, EM Block, E TI Supercritical fluid extraction of Allium species. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 SUNY ALBANY,DEPT CHEM,ALBANY,NY 12222. US FDA,WASHINGTON,DC 20204. RI Block, Eric/D-3989-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 57 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48200055 ER PT J AU Warner, CR Daniels, DH JOe, FL Diachenko, GW AF Warner, CR Daniels, DH JOe, FL Diachenko, GW TI The role of analytical chemistry in HACCP programs for sulfites SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 60 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48200058 ER PT J AU Trucksess, MW AF Trucksess, MW TI Methods used in testing for mycotoxins in grains and grain products. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,DIV NAT PROD,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 61 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48200059 ER PT J AU Jackson, LS AF Jackson, LS TI Analytical methods for monitoring fumonisin levels in food and feed. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,NATL CTR FOOD SAFETY & TECHNOL,SUMMIT ARGO,IL 60501. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 62 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48200060 ER PT J AU Collantes, ER Tong, W Welsh, WJ Zielinski, WL AF Collantes, ER Tong, W Welsh, WJ Zielinski, WL TI Quantitative structure-retention relationships (QSRRs) for polycyclic aromatic hydrocarbons (PAHs) derived from comparative molecular field analysis (CoMFA). SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV MISSOURI,DEPT CHEM,ST LOUIS,MO 63121. US FDA,DIV DRUG ANAL,ST LOUIS,MO 63101. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 69 EP COMP PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48202260 ER PT J AU Mopper, B Hamid, J AF Mopper, B Hamid, J TI Separation and identification of several penicillins in milk by capillary electrophoresis. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,NE REG LAB,BROOKLYN,NY 11232. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 109 EP AGRO PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48200182 ER PT J AU Pardue, JR Bong, R AF Pardue, JR Bong, R TI Multiresidue method for the determination of triazine herbicides and their metabolites in raw agricultural products SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,SE REG LAB,ATLANTA,GA 30309. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 138 EP AGRO PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48200210 ER PT J AU Coelho, JA Mendes, RL Cabral, JS Novais, JM Palavra, AF Provost, MC AF Coelho, JA Mendes, RL Cabral, JS Novais, JM Palavra, AF Provost, MC TI Supercritical CO2 extraction modelling of rosemary volatile compounds SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Tecn Lisboa, DEPT ENGN QUIM, INST SUPER TECN, P-1096 LISBON, PORTUGAL. US FDA, CTR DEVICES & RADIOL HLTH, ROCKVILLE, MD 20855 USA. RI Cabral, Joaquim /G-2052-2010; Palavra, Antonio/H-9235-2012 OI Cabral, Joaquim /0000-0002-2405-5845; Palavra, Antonio/0000-0003-4838-1589 NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 163 EP IEC PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48202961 ER PT J AU Conte, ED Miller, DW AF Conte, ED Miller, DW TI A solid-phase microextraction device for the determination of putrescine and cadaverine by high resolution gas chromatography SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NATL CTR TOXICOL RES,DEPT CHEM,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 176 EP ANYL PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48200443 ER PT J AU Fletcher, JV LynCook, B AF Fletcher, JV LynCook, B TI Effect of dietary agents on cytochrome P401A2 activity in rat hepatic microsomes. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 TUSKEGEE UNIV,DEPT CHEM,TUSKEGEE,AL 36088. NATL CTR TOXICOL RES,JEFFERSON,AR 72205. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 231 EP CHED PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48201243 ER PT J AU Bao, JZ Swicord, ML Davis, CC AF Bao, JZ Swicord, ML Davis, CC TI Microwave dielectric characterization of binary mixtures of water, methanol, and ethanol SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID ENDED COAXIAL LINE; BIOLOGICAL SUBSTANCES; RICH REGION; RELAXATION; PERMITTIVITY; LIQUID; ERYTHROCYTES; FREQUENCIES; CONSTANT; EQUATION AB The complex dielectric constants of binary mixtures of water-methanol and water-ethanol in the frequency range from 45 MHz to 26.5 GHz, and binary mixtures of methanol-ethanol in the range from 200 MHz to 26.5 GKz have been measured with various volume fractions around room temperature by means of an open-ended coaxial sensor and a network analyzer. Methanol-ethanol mixtures display a near-Debye dispersion while water-alcohol mixtures show a Cole-Davidson dispersion. The logarithm of relaxation time log tau and dielectric decrement Delta epsilon for methanol-ethanol mixtures show a good linear relation with the volume fraction of methanol, while log tau and Delta epsilon extracted with the Debye function for water-alcohol mixtures display a near-linear relation with volume fraction of water. Two simple formulas are proposed for identifying the volume fractions of the components in binary mixtures of alcohol-alcohol and water-alcohol from a knowledge of tau and Delta epsilon for the pure liquids and the mixtures. The validity of these formulas has been demonstrated with three blind tests. The relation between the mole fraction of water and log tau for water-methanol and water-ethanol mixtures extracted by the use of a Cole-Davidson function clearly shows two linear regions, which implies a change of relaxation mechanism with mole fraction. (C) 1996 American Institute of Physics. C1 UNIV MARYLAND,DEPT ELECT ENGN,COLLEGE PK,MD 20742. US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857. NR 38 TC 89 Z9 90 U1 1 U2 22 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD MAR 22 PY 1996 VL 104 IS 12 BP 4441 EP 4450 DI 10.1063/1.471197 PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA UA381 UT WOS:A1996UA38100012 ER PT J AU Fu, PP VonTungeln, LS Zhan, DJ Bucci, T AF Fu, PP VonTungeln, LS Zhan, DJ Bucci, T TI Potent tumorigenicity of 7-chlorobenz[a]anthracene and 7-bromobenz[a]anthracene in the neonatal B6C3F(1) male mouse SO CANCER LETTERS LA English DT Article DE liver tumors; 7-chlorobenz[a]anthracene; 7-bromobenz[a]anthracene; neonatal mouse ID POLYNUCLEAR AROMATIC-HYDROCARBONS; RAT-LIVER MICROSOMES; STEREOSELECTIVE METABOLISM; URBAN AIR AB The tumorigenicity of 7-chlorobenz[alpha]anthracene (7-Cl-BA), an environmental contaminant, and 7-bromobenz[alpha]anthracene (7-Br-BA) was determined in the male B6C3F(1) newborn mouse. Mice receiving 7-Cl-BA and 7-Br-BA by i.p. injec tions at a dose of 1600 nmol per mouse on 1, 8, and 15 days after birth developed 92 and 96% hepatocellular adenomas, and 100 and 83% hepatocellular carcinoma, respectively. Metabolism by liver microsomes of 15-day-old mice each produced the corresponding trans-3,4-dihydrodiol. Analysis by P-32-postlabeling/HPLC indicated the presence of DNA adducts derived from 7-Cl-BA trans-3,4-dihydrodiol and 7-Br-BA trans-3,4-dihydrodiol. Our results indicate that both 7-Cl-BA and 7-Br-BA are potent carcinogens and that bay-region diol epoxides are the ultimate metabolites that lead to DNA adduct formation and tumor initiation. RP Fu, PP (reprint author), NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 12 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD MAR 19 PY 1996 VL 101 IS 1 BP 37 EP 42 DI 10.1016/0304-3835(96)04111-0 PG 6 WC Oncology SC Oncology GA TW797 UT WOS:A1996TW79700007 PM 8625280 ER PT J AU Bowyer, JF Clausing, P Schmued, L Davies, DL Binienda, Z Newport, GD Scallet, AC Slikker, W AF Bowyer, JF Clausing, P Schmued, L Davies, DL Binienda, Z Newport, GD Scallet, AC Slikker, W TI Parenterally administered 3-nitropropionic acid and amphetamine can combine to produce damage to terminals and cell bodies in the striatum SO BRAIN RESEARCH LA English DT Article DE 3-nitropropionic acid; amphetamine; neurotoxicity; dopamine; caudate-putamen ID DOPAMINE RELEASE; RAT STRIATUM; NITRIC-OXIDE; METHAMPHETAMINE; NEUROTOXICITY; GLUTAMATE; PARKINSONISM; TEMPERATURE; METABOLITE; MECHANISMS AB The combined effects of amphetamine (AMPH) and 3-nitropropionic acid (3-NPA) were investigated to determine how the energy depletion proposed to be produced by AMPH interacts with an inhibitor of mitochondrial respiration to produce striatal neurotoxicity. Neither two doses (2 h apart) of 3.75 mg/kg AMPH alone nor a single dose of 30 mg/kg 3-NPA i.p. produced neurotoxicity in the striatum or lowered striatal dopamine content in rat. Administration of 40 mg/kg of 3-NPA alone almost invariably produced either lethality or did not produce neurotoxicity in the striatum of surviving animals. However, 30 mg/kg of 3-NPA administered along with 2 doses of 3.75 mg/kg AMPH to 47 animals produced striatal damage in the 31 survivors with 15 of the surviving rats showing muscle rigidity/catatonia for several days after dosing, along with decreased food consumption. Thirteen of these 15 rats showed degeneration of axons and cell bodies in the medial caudate-putamen with minimal damage to the globus pallidus. However, two rats exhibited hindlimb paralysis and signs of axonal and neuronal soma degeneration in the thalamus and cerebellar nuclei as well as striatum. Sixteen of the rats given both AMPH and 3-NPA exhibited only torpidity and loss of muscle tone 1-3 h after dosing. Such rats showed no signs of neuronal cell degeneration in the striatum, but did show significant dopamine depletions (60% of control) and reductions in tyrosine hydroxylase immunoreactivity at 14 days postexposure. The mitochondrial dysfunction produced by 3-NPA combined with activation of neuronal pathways by AMPH may have predisposed terminals, axons and cell bodies in striatum to degeneration. RP Bowyer, JF (reprint author), NATL CTR TOXICOL RES,DIV NEUROTOXICOL,HFT-132,JEFFERSON,AR 72079, USA. NR 42 TC 32 Z9 32 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 18 PY 1996 VL 712 IS 2 BP 221 EP 229 DI 10.1016/0006-8993(95)01417-9 PG 9 WC Neurosciences SC Neurosciences & Neurology GA UD435 UT WOS:A1996UD43500006 PM 8814896 ER PT J AU Trapnell, CB Narang, PK Li, R Lavelle, JP AF Trapnell, CB Narang, PK Li, R Lavelle, JP TI Increased plasma rifabutin levels with concomitant fluconazole therapy in HIV-infected patients SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; AEROSOLIZED PENTAMIDINE; PROPHYLAXIS; TRIALS; AGENT; AIDS AB Objective: To determine the effect of fluconazole on rifabutin pharmacokinetics. Design: An open-label, crossover, phase 1 trial. Setting: Outpatient clinical research center at a university medical center in Washington, D.C. Patients: 12 persons with human immunodeficiency virus (HIV) infection whose CD4 lymphocyte counts were between 200 and 500 cells/mm(3) and who were receiving maintenance therapy with zidovudine. Intervention: Fluconazole, 200 mg/d for 2 weeks; then a combination of fluconazole, 200 mg/d, and rifabutin, 300 mg/d, for 2 weeks; and then rifabutin, 300 mg/d, for the final 2 weeks of the study. Measurements: Blood and urine samples were obtained at regular intervals for 24 hours at the end of each 2-week dosing period to ascertain concentrations of fluconazole and rifabutin and the 25-desacetyl metabolite of rifabutin, LM565. Results: Fluconazole significantly increased the plasma concentrations of both rifabutin and LM565. Mean increases in the area under the plasma concentration curve compared with the time curve over a 24-hour dosing interval were 82% (5442 +/- 2404 ng . h/mL compared with 3025 +/- 1117 ng . h/mL; P less than or equal to 0.05) for rifabutin and 216% (959 +/- 529 ng . h/mL compared with 244 +/- 141 ng . h/mL; P less than or equal to 0.05) for LM565. Conclusions: Fluconazole significantly increases the systemic exposure of both rifabutin and LM565. This pharmacokinetic interaction offers a mechanism that may explain the changes reported in both the efficacy and toxicity of rifabutin with concomitant fluconazole therapy. C1 GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. PHARMACIA INC,COLUMBUS,OH 43216. RP Trapnell, CB (reprint author), US FDA,CTR DRUG EVALUAT & RES,5600 FISHERS LANE,HFD-900,ROOM 13B-16,ROCKVILLE,MD 20857, USA. NR 19 TC 46 Z9 46 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 15 PY 1996 VL 124 IS 6 BP 573 EP 576 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA TZ529 UT WOS:A1996TZ52900007 PM 8597321 ER PT J AU Taga, K Yamauchi, A Kabashima, K Bloom, ET Muller, J Tosato, G AF Taga, K Yamauchi, A Kabashima, K Bloom, ET Muller, J Tosato, G TI Target-induced death by apoptosis in human lymphokine-activated natural killer cells SO BLOOD LA English DT Article ID HUMAN PERIPHERAL-BLOOD; C-MYC; IMMUNE-SYSTEM; BCL-2; THYMOCYTES; SURVIVAL; P53; INTERLEUKIN-2; ANTIBODIES; SELECTION AB Activated human natural killer (NK) cells undergo rapid apoptotic cell death after ligand binding to the Fc receptor (CD16). We examined whether human NK cells die after engagement in cytolytic functions. Peripheral blood NK cells, with and without prior activation in vitro with interleukin-2 (1L-2), were tested for the occurrence of cell death after incubation with K562, the prototype NK-sensitive target cell. A proportion (15.2%) of MK cells that were stimulated for 3 days with IL-2 and then incubated for 4 hours with K562 cells showed rapid cell death, but NK cells not stimulated with 1L-2 did not. This cell death was found to involve nuclear condensation and fragmentation and DNA cleavage, all of which are characteristic of apoptosis. These data indicate that a proportion of activated human NK cells undergo apoptosis as they engage in target cell lysis. Target-induced Nh cell death may represent an important mechanism for regulation of inflammatory processes involving NK cells. government work. There are no restrictions on its use. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,ROCKVILLE,MD 20852. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,ROCKVILLE,MD 20852. US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,ROCKVILLE,MD 20852. RI Kabashima, Kenji/G-2521-2014 OI Kabashima, Kenji/0000-0002-0773-0554 NR 44 TC 34 Z9 34 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 1996 VL 87 IS 6 BP 2411 EP 2418 PG 8 WC Hematology SC Hematology GA UA957 UT WOS:A1996UA95700034 PM 8630405 ER PT J AU Misiewicz, B Griebler, C Gomez, M Raybourne, R Zelazowska, E Gold, PW Sternberg, EM AF Misiewicz, B Griebler, C Gomez, M Raybourne, R Zelazowska, E Gold, PW Sternberg, EM TI The estrogen antagonist tamoxifen inhibits carrageenan induced inflammation in LEW/N female rats SO LIFE SCIENCES LA English DT Letter DE carrageenan; tamoxifen; inflammation; LEW/N rat hypothalamus ID WALL INDUCED POLYARTHRITIS; BREAST-CANCER; ANTIESTROGENS; CELLS AB Carrageenan induces a measurable inflammatory response in susceptible animals, and mature females are more responsive to carrageenan, than males. In the present study, we tested whether the estrogen antagonist tamoxifen influences carrageenan-induced inflammatory responses. Female LEW/N rats were treated with tamoxifen and compared to a control group of animals injected with vehicle. Tamoxifen significantly reduced estrous phase of estrous cycle during treatment, consistent with its functional anti-estrogen effects. Moreover, tamoxifen significantly decreased exudate volume but did not significantly influence relative white blood cell counts in the exudate. Interestingly, tamoxifen induced differential dose-dependent alterations in peripheral blood lymphocyte subpopulations. Low dose of tamoxifen increased CD25 cells. The high tamoxifen dose significantly increased CD8 blood lymphocyte counts. Our data indicate that tamoxifen treatment decreases carrageenan-induced inflammatory response in female LEW/N rats and suggest therefore that this inflammatory response is, at least in part, estrogen related. Moreover, our results suggest a possible role for tamoxifen in,treatment of inflammatory disorders. C1 US FDA,LAUREL,MD 20708. RP Misiewicz, B (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892, USA. NR 20 TC 9 Z9 9 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD MAR 15 PY 1996 VL 58 IS 16 BP PL281 EP PL286 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA UA675 UT WOS:A1996UA67500012 ER PT J AU Krauthamer, Y AF Krauthamer, Y TI Optical measurements of intracellular calcium and voltage dynamics in cultured heart cells exposed to high-voltage shock SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 382 EP 382 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400383 ER PT J AU Scariati, P GrummerStrawn, L Fein, S AF Scariati, P GrummerStrawn, L Fein, S TI A longitudinal analysis of infant morbidity and the extent of breast-feeding, United States SO FASEB JOURNAL LA English DT Meeting Abstract C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30333. US FDA,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 1100 EP 1100 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28401100 ER PT J AU Ellwood, KC Loo, G Chen, C Obermeyer, W AF Ellwood, KC Loo, G Chen, C Obermeyer, W TI Ability of ferulic acid to inhibit oxidation of low density lipoprotein. SO FASEB JOURNAL LA English DT Meeting Abstract C1 USDA,CSREES,WASHINGTON,DC 20250. UNIV N CAROLINA,DEPT FOOD NUTR & FOOD SERV MGT,GREENSBORO,NC 27412. US FDA,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 1155 EP 1155 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28401157 ER PT J AU Whittaker, P Robl, MG Hines, FA Dunkel, VC AF Whittaker, P Robl, MG Hines, FA Dunkel, VC TI Histopathological evaluation of dietary iron overload in the rat. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 1447 EP 1447 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28401447 ER PT J AU Wamer, W Yurawecz, MP Wei, R Schat, N Ku, Y AF Wamer, W Yurawecz, MP Wei, R Schat, N Ku, Y TI In vitro assessment of the cytotoxicity and antioxidant activity of a furan fatty acid, a novel oxidation product of conjugated linoleic acid. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 1565 EP 1565 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28401566 ER PT J AU Misiewicz, B Poltorak, M Wright, R Raybourne, R Szczepanowski, R Freed, WJ Sternberg, EM AF Misiewicz, B Poltorak, M Wright, R Raybourne, R Szczepanowski, R Freed, WJ Sternberg, EM TI Intracerebroventricular transplantation of F344/N hypothalamic tissue alters the course of experimental allergic encephalomyelitis in LEW/N rats SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH,CNE,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,WASHINGTON,DC 20052. NIMH,PRECLIN NEUROSCI SECT,WASHINGTON,DC 20032. US FDA,IMMUNOBIOL BRANCH,LAUREL,MD 20708. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 1624 EP 1624 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28401622 ER PT J AU Brase, DA Chapdelaine, P HajilooAbedi, L Edeki, TI AF Brase, DA Chapdelaine, P HajilooAbedi, L Edeki, TI TI Sex-specific difference in the rate of decline of plasma phenytoin between African Americans and Caucasians SO FASEB JOURNAL LA English DT Meeting Abstract C1 MEHARRY MED COLL,NASHVILLE,TN 37208. US FDA,ROCKVILLE,MD 20857. NR 1 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 1628 EP 1628 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28401627 ER PT J AU Onwere, I Chakrabarti, A Ali, SF Onaivi, ES AF Onwere, I Chakrabarti, A Ali, SF Onaivi, ES TI Effect of Ibogaine on cocaine withdrawal anxiogenesis in mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 MEHARRY MED COLL,NASHVILLE,TN 37208. OAKWOOD COLL,HUNTSVILLE,AL 35896. US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 2595 EP 2595 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28402597 ER PT J AU Friedman, L Gaines, DW Eppley, R Smith, MC Chi, RK Braunberg, RC AF Friedman, L Gaines, DW Eppley, R Smith, MC Chi, RK Braunberg, RC TI Effects of T-2 toxin (T2), deoxynivalenol (DON), zearalenone (Z) and DON+Z on macromolecular synthesis by male rat spleen slices. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CFSAN,WASHINGTON,DC 20201. US FDA,CFSAN,LAUREL,MD 20708. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 2642 EP 2642 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28402641 ER PT J AU Wiesenfeld, PL Babu, US AF Wiesenfeld, PL Babu, US TI In vitro fatty acid uptake by WEHI-3 and J774A1 cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,DIV SCI & APPL TECHNOL,LAUREL,MD 20708. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 2747 EP 2747 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28402748 ER PT J AU Gallo, L Satchithanandam, S Nayar, S AF Gallo, L Satchithanandam, S Nayar, S TI Role of cholesterol esterase (CE'ASE) and ACAT on cholesterol ((C)under-bar) absorption in rats fed increasing cholesterol loads SO FASEB JOURNAL LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. US FDA,BELTSVILLE,MD 20708. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 2933 EP 2933 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28402932 ER PT J AU Satchithanandam, S WadsworthHla, J Gallo, L Kritchevsky, D AF Satchithanandam, S WadsworthHla, J Gallo, L Kritchevsky, D TI Comparison of absorption of cholesterol and dihydrolanosterol in the rat SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,LAUREL,MD. GEORGE WASHINGTON UNIV,WASHINGTON,DC. WISTAR INST ANAT & BIOL,PHILADELPHIA,PA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 2945 EP 2945 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28402944 ER PT J AU Sundaresan, PR Lakshman, MR Liu, QH Sapp, R AF Sundaresan, PR Lakshman, MR Liu, QH Sapp, R TI Effect of dietary taurocholate on the distribution and metabolism of dietary beta-carotene to vitamin A in ferrets. SO FASEB JOURNAL LA English DT Meeting Abstract C1 VET ADM MED CTR,WASHINGTON,DC 20422. US FDA,LAUREL,MD 20708. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3032 EP 3032 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403033 ER PT J AU Mitchell, GV Grundel, E Jenkins, MY AF Mitchell, GV Grundel, E Jenkins, MY TI Nutritional responses in Sprague-Dawley rats to the replacement of dietary fat with margarine-like products. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,LAUREL,MD 20708. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3048 EP 3048 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403047 ER PT J AU Rader, JI Weaver, CM Patrascu, L Ali, LH Angyal, G AF Rader, JI Weaver, CM Patrascu, L Ali, LH Angyal, G TI Vitamin E (alpha-tocopherol) content of margarines and new reduced-fat margarine-like products. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3049 EP 3049 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403050 ER PT J AU Mondoro, TH Shafer, BC Vostal, JG AF Mondoro, TH Shafer, BC Vostal, JG TI Tyrosine nitration of platelet proteins by peroxynitrite does not alter thrombin-induced tyrosine, phosphorylation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3819 EP 3819 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403817 ER PT J AU Frederick, DL Ferguson, SA Fogle, CM Paule, MG AF Frederick, DL Ferguson, SA Fogle, CM Paule, MG TI A novel operant task designed to assess auditory, visual, and position discrimination ability: Acute effects of drugs. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4131 EP 4131 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404133 ER PT J AU Morris, P Hand, BT Lundy, PM AF Morris, P Hand, BT Lundy, PM TI Effects of atropine and HI-6 on avoidance behavior in the rat. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. DEF RES ESTAB SUFFIELD,DND,MEDICINE HAT,AB T1A 8K6,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4134 EP 4134 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404132 ER PT J AU Pennington, JAT AF Pennington, JAT TI Dietary assessment based on core foods. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4178 EP 4178 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404178 ER PT J AU Jenkins, MY Satchithanandam, S Grundel, E Mitchell, GV AF Jenkins, MY Satchithanandam, S Grundel, E Mitchell, GV TI Effect of dietary canthaxanthin on the lymphatic absorption of alpha-tocopherol in rats SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,OFF FOOD LABELING,LAUREL,MD 20708. US FDA,OFF SPECIAL NUTR,LAUREL,MD 20708. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4226 EP 4226 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404225 ER PT J AU Rapier, SH Holson, RR Turner, BB AF Rapier, SH Holson, RR Turner, BB TI Dexamethasone exposure on postnatal day 7 alters multiple aspects of rat cerebellar development. SO FASEB JOURNAL LA English DT Meeting Abstract C1 E TENNESSEE STATE UNIV,JAMES H QUILLEN COLL MED,JOHNSON CITY,TN 37614. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4415 EP 4415 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404415 ER PT J AU Casterline, JI Oles, C Ku, Y AF Casterline, JI Oles, C Ku, Y TI Determination of ''other carbohydrate'' in foods by an enzymatic-HPLC procedure.. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4584 EP 4584 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404584 ER PT J AU Ali, L Angyal, G Weaver, C Rader, J AF Ali, L Angyal, G Weaver, C Rader, J TI Determination of saturated and cis and trans unsaturated fatty acids in foods using capillary column-gas chromatography. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,OFF FOOD LABELING,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4588 EP 4588 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404589 ER PT J AU Lakshman, MR Satchithanandam, S AF Lakshman, MR Satchithanandam, S TI Effect of chronic ethanol feeding on gastrointestinal mucins in rats. SO FASEB JOURNAL LA English DT Meeting Abstract C1 DEPT VET AFFAIRS MED CTR,WASHINGTON,DC 20422. US FDA,LAUREL,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4614 EP 4614 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404614 ER PT J AU Sagripanti, JL Lightfoote, MM AF Sagripanti, JL Lightfoote, MM TI Cupric and ferric ions inactivate HIV SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID LYMPHADENOPATHY-ASSOCIATED VIRUS; DNA DAMAGE; COPPER; PEROXIDE; STRAND; IRON; LAV AB Human immunodeficiency virus (HIV-1) was inactivated by either cupric or ferric ions when the virus uas free in solution and also 3 hr after cell infection. Fifty percent inactivation of cell-free HIV was achieved with Cu(II) at a concentration between 0.16 and 1.6 mM, or by 1.8 to 18 mM Fe(III). Thus, the dose to inactivate 50% of infectious HIV (D-50) by Cu(II) or Fe(III) is higher than that reported for glutaraldehyde (0.1 mM): between the D-50 reported for sodium hypochlorite (1.3 mM)and sodium hydroxide (11.5 mM), and significantly lower than that required for HIV inactivation by ethanol (360 mM). Treatment of infected cells for 30 min at 20 degrees C with 6 mM Cu(II) or Fe(III) completely inhibited the formation of syncytia and the synthesis of virus-specific p24 antigen in HIV-infected cells, while still preserving cell viability, The virucidal properties of cupric and ferric ions could be exploited for the development of novel virucidal formulations efficient against HIV. RP Sagripanti, JL (reprint author), US FDA, CTR DEVICES & RADIOL HLTH, MOLEC BIOL BRANCH HFZ 113, ROCKVILLE, MD 20857 USA. NR 16 TC 21 Z9 21 U1 0 U2 7 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAR 1 PY 1996 VL 12 IS 4 BP 333 EP 336 DI 10.1089/aid.1996.12.333 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA UD140 UT WOS:A1996UD14000009 PM 8906994 ER PT J AU Rothman, N Li, GL Dosemeci, M Bechtold, WE Marti, GE Wang, YZ Linet, M Xi, LQ Lu, W Smith, MT TitenkoHolland, N Zhang, LP Blot, W Yin, SN Hayes, RB AF Rothman, N Li, GL Dosemeci, M Bechtold, WE Marti, GE Wang, YZ Linet, M Xi, LQ Lu, W Smith, MT TitenkoHolland, N Zhang, LP Blot, W Yin, SN Hayes, RB TI Hematotoxicity among Chinese workers heavily exposed to benzene SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE benzene; hematotoxicity; phenol; muconic acid; hydroquinone; catechol ID HUMAN-LYMPHOCYTES; METABOLITES; TOXICITY; HYDROQUINONE; MICE; CHROMOSOME; TOLUENE; INVITRO; MYELOTOXICITY; STIMULATION AB Benzene is a well-established hematotoxin. However, reports of its effects on specific blood cells have been somewhat inconsistent and the relative toxicity of benzene metabolites on peripheral blood cells in humans has not been evaluated. We compared hematologic outcomes in a cross-sectional study of 44 workers heavily exposed to benzene (median: 31 parts permillion [ppm] as an 8-hr time-weighted average [TWA] and 44 age and gender-matched unexposed controls from Shanghai, China. All hematologic parameters (total white blood cells [WBC], absolute lymphocyte count, platelets, red blood cells, and hematocrit) were decreased among exposed workers compared to controls, with the exception of the red blood cell mean corpuscular volume (MCV), which was higher among exposed subjects. In a subgroup of workers who were not exposed to more than 31 ppm benzene on any of 5 sampling days (n = 11, median 8 hr TWA = 7.6 ppm, range = 1-20 ppm), only the absolute lymphocyte count was significantly different between exposed workers (mean [sd] 1.6 [0.4] x 10(3) mu L) and controls (1.9 [0.4] x 10(3) mu L, p = 0.03). Among exposed subjects, a dose-response relationship with various measures of current benzene exposure (i.e., personal air monitoring, benzene metabolites in urine) was present only for the total WBC count, the absolute lymphocyte count, and the MCV. Correlations between benzene metabolites and hematologic parameters were generally similar, although hydroquinone was somewhat more strongly associated with a decrease in the absolute lymphocyte count, and catechol was more strongly associated with an increase in MCV. Morphologic review of peripheral blood slides demonstrated and excess of red blood cell abnormalities (i.e., stomatocytes and target cells) only in the most heavily exposed workers, with no differences in granulocyte, lymphocyte, or platelet morphology noted. Although benzene can affect all the major peripheral blood elements, our results support the use of the absolute lymphocyte count as the most sensitive indicator of benzene-induced hematotoxicity. (C) 1995 Wiley-Liss, Inc. C1 CHINESE ACAD PREVENT MED,INST OCCUPAT MED,BEIJING 100050,PEOPLES R CHINA. LOVELACE INHALAT TOXICOL RES INST,ALBUQUERQUE,NM. US FDA,CTR BIOL RES & EVALUAT,BETHESDA,MD. SHANGHAI HYG & ANTIEPIDEM CTR,DEPT OCCUPAT HLTH,SHANGHAI,PEOPLES R CHINA. UNIV CALIF BERKELEY,SCH PUBL HLTH,BERKELEY,CA 94720. RP Rothman, N (reprint author), NCI,NIH,EPIDEMIOL & BIOSTAT PROGRAM 418,BETHESDA,MD 20892, USA. FU NIEHS NIH HHS [P30ES01896, P42ES04705] NR 50 TC 114 Z9 121 U1 1 U2 10 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD MAR PY 1996 VL 29 IS 3 BP 236 EP 246 DI 10.1002/(SICI)1097-0274(199603)29:3<236::AID-AJIM3>3.0.CO;2-O PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TX830 UT WOS:A1996TX83000003 PM 8833776 ER PT J AU Black, PL Ussery, MA Barney, S Wittrock, R DeMarsh, P Dreyer, GB Petteway, SR DalMonte, P Baldoni, J Lambert, DM AF Black, PL Ussery, MA Barney, S Wittrock, R DeMarsh, P Dreyer, GB Petteway, SR DalMonte, P Baldoni, J Lambert, DM TI Effects of SKF 108922, an HIV-1 protease inhibitor, on retrovirus replication in mice SO ANTIVIRAL RESEARCH LA English DT Article DE protease inhibitor; animal model; murine retrovirus; murine leukemia virus ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; FOCUS-FORMING VIRUS; REVERSE-TRANSCRIPTASE; VIRAL INFECTIVITY; ASPARTIC PROTEASE; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; RATIONAL DESIGN; INFECTED-CELLS AB Rationally designed synthetic inhibitors of retroviral proteases inhibit the processing of viral polypeptides in cultures of human T lymphocytes infected with human immunodeficiency virus type 1 (HIV-1) and therefore suppress the infectivity of HIV-1 in vitro. We have previously reported the antiviral activity in vitro of HIV-1 protease inhibitors against the C-type retrovirus Rauscher murine leukemia virus (RMuLV) and the lentivirus simian immunodeficiency virus (SIV). The same compounds which blocked the infectivity of HIV-1 also inhibited the infectivity of RMuLV and SIV in vitro. This report extends these findings by testing the antiviral activity of HIV-1 protease inhibitors in vivo in the RMuLV model. RMuLV-infected mice were treated twice a day (bid) with either an active (SKF 108922) or inactive (SKF 109273) compound for fourteen days by the intraperitoneal (IF) route. Compared with excipient control, SKF 108922, formulated with hydroxypropyl-beta-cyclodextrin (HPB), reduced virus-induced splenomegaly, viremia, and serum reverse transcriptase (RT) levels, while SKF 109273 was inactive. The HPB vehicle by itself enhanced replication of RMuLV. The effects of changing the formulation and the route of administration were examined. SKF 108922, formulated in HPB, had similar antiviral activity when administered by the IP or subcutaneous (SC) routes. However, SKF 108922 administered as a colloidal suspension in cholesterol sulfate (CS) had no detectable antiviral effect. Measurements of the circulating levels of the protease inhibitor in plasma explained this result. Plasma concentrations of SKF 108922 exceeded 1000 nM within 10 min after SC administration of the compound solubilized in HPB, but SKF 108922 was not detected in plasma after SC administration of the same dose formulated with CS. Information on optimal conditions for administering these agents should prove useful in guiding their clinical application Therefore, RMuLV should provide a good model for the preclinical evaluation and development of this class of agents for the treatment of HIV. C1 SMITHKLINE BEECHAM PHARMACEUT,RES & DEV,KING OF PRUSSIA,PA 19406. RP Black, PL (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV ANTIVIRAL DRUG PROD,HFD-535,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. FU NIAID NIH HHS [1UO1AI25617] NR 43 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD MAR PY 1996 VL 29 IS 2-3 BP 175 EP 186 DI 10.1016/0166-3542(95)00831-4 PG 12 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA UJ976 UT WOS:A1996UJ97600005 PM 8739597 ER PT J AU Zhang, DL Freeman, JP Sutherland, JB Walker, AE Yang, YF Cerniglia, CE AF Zhang, DL Freeman, JP Sutherland, JB Walker, AE Yang, YF Cerniglia, CE TI Biotransformation of chlorpromazine and methdilazine by Cunninghamella elegans SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID N-DEMETHYLATION; METABOLISM; EXTRACTS; CYTOCHROME-P-450; MECHANISM; BAINIERI AB When tested as a microbial model for mammalian drug metabolism, the filamentous fungus Cunninghamella elegans metabolized chlorpromazine and methdilazine within 72 h. The metabolites were extracted by chloroform, separated by high-performance liquid chromatography, and characterized by proton nuclear magnetic resonance, mass, and UV spectroscopic analyses. The major metabolites of chlorpromazine were chlorpromazine sulfoxide (36%), N-desmethylchlorpromazine (11%), N-desmethyl-7-hydroxychlorpromazine (6%), 7-hydroxychlorpromazine sulfoxide (5%), and chlorpromazine N-oxide (2%), all of which have been found in animal studies. The major metabolites of methdilazine were 3-hydroxymethdilazine (35%), methdilazine sulfoxide (30%), methdilazine N-oxide (4%), phenothiazine (3%), and 2-hydroxymethdilazine (3%). O-18(2) labeling experiments indicated that the oxygen atoms in methdilazine sulfoxide, methdilazine N-oxide, and 3-hydroxymethdilazine were all derived from molecular oxygen. The production of methdilazine sulfoxide and 3-hydroxymethdilazine was inhibited by the cytochrome P-450 inhibitors metyrapone and proadifen. An enzyme activity for the sulfoxidation of methdilazine was found in microsomal preparations of C. elegans. These experiments suggest that the sulfoxidation and hydroxylation of methdilazine and chlorpromazine by C. elegans are catalyzed by cytochrome P-450. C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 29 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD MAR PY 1996 VL 62 IS 3 BP 798 EP 803 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA TY365 UT WOS:A1996TY36500009 PM 8975609 ER PT J AU Hagiwara, E Gourley, MF Lee, S Klinman, DM AF Hagiwara, E Gourley, MF Lee, S Klinman, DM TI Disease severity in patients with systemic lupus erythematosus correlates with an increased ratio of interleukin-10:Interferon-gamma-secreting cells in the peripheral blood SO ARTHRITIS AND RHEUMATISM LA English DT Article ID GROWTH-FACTOR; B-CELLS; IL-6; PATHOGENESIS; EXPRESSION; RESPONSES; MICE; SLE; TH1 AB Objective. To compare the phenotype and frequency of cells that actively secrete type 1 and type 2 cytokines in systemic lupus erythematosus (SLE) patients (n = 46), versus normal controls (n = 60). Methods. ELISPOT analysis of freshly isolated peripheral blood mononuclear cells (PBMC). Results. T cells were the major source of interleukin-2 (IL-2), IL-4, and interferon-gamma (IFN gamma), whereas monocytes were the primary source of IL-6 and IL-10 in the PB of lupus patients. Significantly fewer PBMC spontaneously secreted IFN gamma and IL-2 (P less than or equal to 0.03), while significantly more PBMC produced IL-6 and IL-10 (P < 0.001), in lupus patients versus controls. Disease severity in lupus patients correlated with an elevated ratio of IL-10:IFN gamma-secreting cells (P < 0.001). Conclusion. SLE is characterized by an imbalance in the ratio of type 1:type 2 cytokine-secreting PBMC. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,BETHESDA,MD 20892. NIAMSD,NIH,BETHESDA,MD 20892. NR 36 TC 245 Z9 262 U1 0 U2 5 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAR PY 1996 VL 39 IS 3 BP 379 EP 385 DI 10.1002/art.1780390305 PG 7 WC Rheumatology SC Rheumatology GA TZ599 UT WOS:A1996TZ59900004 PM 8607886 ER PT J AU Gribaldo, L Bueren, J Deldar, A Hokland, P Meredith, C Moneta, D Mosesso, P Parchment, R ParentMassin, D Pessina, A SanRoman, J Schoeters, G AF Gribaldo, L Bueren, J Deldar, A Hokland, P Meredith, C Moneta, D Mosesso, P Parchment, R ParentMassin, D Pessina, A SanRoman, J Schoeters, G TI The use of in vitro systems for evaluating haematotoxicity - The report and recommendations of ECVAM workshop 141 SO ATLA-ALTERNATIVES TO LABORATORY ANIMALS LA English DT Editorial Material ID HEMATOPOIETIC PROGENITOR CELLS; MARROW STROMAL CELLS; HUMAN-BONE-MARROW; PRECLINICAL DRUG DEVELOPMENT; TOPOISOMERASE-I INHIBITOR; COLONY-STIMULATING FACTOR; SEVERE APLASTIC-ANEMIA; STEM-CELLS; PHASE-I; INVITRO MYELOTOXICITY C1 CONSORZIO MILANO RES, I-20129 MILAN, ITALY. CIEMAT, INST ENVIRONM, E-28040 MADRID, SPAIN. ELI LILLY & CO, LILLY RES LABS, TOXICOL RES LABS, GREENFIELD, IN 46140 USA. AARHUS UNIV HOSP, DEPT HEMATOL, DK-8000 AARHUS, DENMARK. BIBRA TOXICOL INT, CARSHALTON SM5 4DS, SURREY, ENGLAND. PHARMACIA, TOXICOL & SAFETY ASSESSMENT DEPT, HEMATOL & CLIN CHEM SECT, I-20014 NERVIANO, ITALY. UNIV TUSCIA, DABAC, I-01100 VITERBO, ITALY. US FDA, CTR DRUG EVALUAT & RES, LAUREL, MD 20708 USA. UNIV BRETAGNE OCCIDENTALE, ECOLE SUPER MICROBIOL, TECHNOPOLE BREST IROISE, F-29280 PLOUZANE, FRANCE. UNIV MILAN, INST MED MICROBIOL, CELL CULTURE LAB, I-20133 MILAN, ITALY. ADV TISSUE SCI, LA JOLLA, CA 92037 USA. VLAAMSE INSTELLING TECHNOL ONDERZOEK, DEPT ENVIRONM, B-2400 MOL, BELGIUM. RP Gribaldo, L (reprint author), ECVAM, JRC INST ENVIRONM, TP 580, I-21020 ISPRA, ITALY. RI Bueren, Juan/L-6112-2014 OI Bueren, Juan/0000-0002-3228-7013 NR 116 TC 51 Z9 52 U1 0 U2 2 PU FRAME PI NOTTINGHAM PA RUSSELL & BURCH HOUSE 96-98 NORTH SHERWOOD ST, NOTTINGHAM, NOTTS, ENGLAND NG1 4EE SN 0261-1929 J9 ATLA-ALTERN LAB ANIM JI ATLA-Altern. Lab. Anim. PD MAR-APR PY 1996 VL 24 IS 2 BP 211 EP 231 PG 21 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UG490 UT WOS:A1996UG49000016 ER PT J AU West, RW Hinson, WG Swicord, ML AF West, RW Hinson, WG Swicord, ML TI Anchorage-independent growth with JB6 cells exposed to 60 Hz magnetic fields at several flux densities SO BIOELECTROCHEMISTRY AND BIOENERGETICS LA English DT Article DE magnetic fields; JB6 cells; anchorage-independent growth; cancer promotion ID FREQUENCY ELECTROMAGNETIC-FIELDS; MECHANISMS AB JB6 clone 41 cells have previously been shown to respond to a 1.1 mT magnetic field with increased growth under anchorage-independent (Al) conditions. Here we have examined the Al growth-response simultaneously at three lower flux densities and without an applied field. Fields were generated with Helmholtz coils held in water-jacketed CO2 incubators. Colony growth (60 mu m diameter) was scored at 8 and 14 days after seeding cells in soft agar. Zero-field experiments conducted simultaneously in several incubators produced uniform counts (about 1 per 10(3) cells seeded). For 14-day exposures at 100 mu T, 10 mu T and 1 mu T, four of four, six of six, and two of three experiments, respectively, showed a significantly increased colony number (p < 0.02), with the ratio of field-exposed to control colonies varying from 1.2 to 3.2. Thus, an effect of magnetic fields at flux densities approaching environmental levels of exposure has been demonstrated. C1 US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857. RP West, RW (reprint author), US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 17 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE 1 PA PO BOX 564, 1001 LAUSANNE 1, SWITZERLAND SN 0302-4598 J9 BIOELECTROCH BIOENER JI Bioelectrochem. Bioenerg. PD MAR PY 1996 VL 39 IS 2 BP 175 EP 179 DI 10.1016/0302-4598(95)05038-8 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UG704 UT WOS:A1996UG70400004 ER PT J AU Williams, PB Akasawa, A Dreskin, S Selner, JC AF Williams, PB Akasawa, A Dreskin, S Selner, JC TI Respirable tire fragments contain specific IgE-binding and bridging latex antigens SO CHEST LA English DT Article; Proceedings Paper CT Symposium on Environmental Lung Disease in Exposures and Mechanisms, at the Thomas-L-Petty-Aspen-Lung-Conference 38th Annual Meeting CY JUL 07-10, 1995 CL ASPEN, CO SP Thomas L Petty Aspen Lung Conf C1 US FDA,CDER,ROCKVILLE,MD 20857. RP Williams, PB (reprint author), UNIV COLORADO,HLTH SCI CTR,ALLERGY RESP INST COLORADO,4200 E 9TH AVE,DENVER,CO 80262, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD MAR PY 1996 VL 109 IS 3 SU S BP S13 EP S13 DI 10.1378/chest.109.3_Supplement.13S PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA UA472 UT WOS:A1996UA47200008 PM 8598133 ER PT J AU OReilly, S Hartman, NR Grossman, SA Strong, JM Struck, RF Eller, S Lesser, GJ Donehower, RC Rowinsky, EK AF OReilly, S Hartman, NR Grossman, SA Strong, JM Struck, RF Eller, S Lesser, GJ Donehower, RC Rowinsky, EK TI Tissue and tumor distribution of C-14-penclomedine in rats SO CLINICAL CANCER RESEARCH LA English DT Article ID PRECLINICAL ANTITUMOR-ACTIVITY; PENCLOMEDINE; NSC-338720 AB Penclomedine, a lipophilic cy-picoline derivative, is undergoing clinical development presently because of its pronounced antitumor activity against intracerebral (i.c.) tumor xenografts. Penclomedine may be metabolized in vivo to a more potent compound. Although it may be useful in the treatment of brain tumors, the drug has caused significant neurotoxicity in early clinical trials. The possibility that antitumor activity and neurotoxicity may be mediated by different mechanisms prompted a study assessing the differential distribution of penclomedine and penclomedine metabolites to brain and i.c.-implanted tumors in rats. In the present study, quantitative autoradiographic analysis demonstrated a homogenous distribution of C-14-penclomedine in all organs within 1 h of administration. Levels of C-14-penclomedine in both i.c. and s.c. tumors were three times higher than in normal brain tissue. High-performance liquid chromatography combined with gas chromatography and mass spectrophotometry demonstrated that two metabolites, O-demethyl penclomedine and penclomic acid, were responsible for most of the plasma radioactivity. Penclomic acid was also the most common urinary metabolite of penclomedine. In liver samples, although a large number of metabolite peaks were detected, no parent compound could be identified. However, in tumors and all other tissues, penclomedine was the main compound detected. The finding of penclomedine in normal brain tissue indicates not only that this drug may be useful in tumors with normal blood-brain barrier function, but also that it may be directly neurotoxic. C1 US FDA,CTR DRUG EVALUAT & RES,DIV CLIN PHARMACOL,LAUREL,MD 20708. SO RES INST,BIRMINGHAM,AL 35255. RP OReilly, S (reprint author), JOHNS HOPKINS ONCOL CTR,DIV MED ONCOL,ROOM 137,600 N WOLFE ST,BALTIMORE,MD 21287, USA. FU NCI NIH HHS [CA 1709-03] NR 11 TC 10 Z9 10 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 1996 VL 2 IS 3 BP 541 EP 548 PG 8 WC Oncology SC Oncology GA TY620 UT WOS:A1996TY62000014 PM 9816201 ER PT J AU Normanno, N Bianco, C Damiano, V deAngelis, E Selvam, MP Grassi, M Magliulo, G Tortora, G Bianco, AR Mendelsohn, J Salomon, DS Ciardiello, F AF Normanno, N Bianco, C Damiano, V deAngelis, E Selvam, MP Grassi, M Magliulo, G Tortora, G Bianco, AR Mendelsohn, J Salomon, DS Ciardiello, F TI Growth inhibition of human colon carcinoma cells by combinations of anti-epidermal growth factor-related growth factor antisense oligonucleotides SO CLINICAL CANCER RESEARCH LA English DT Article ID RECEPTOR MONOCLONAL-ANTIBODIES; FACTOR-ALPHA; COLORECTAL TUMORS; CANCER-CELLS; EXPRESSION; AMPHIREGULIN; LINE; PROLIFERATION; GENE; MICE AB GEO is a well-differentiated colon cancer cell line that coexpresses the epidermal growth factor-like growth factors CRTPTO (CR), amphiregulin (AR), and transforming growth factor alpha. (TGF-alpha). Antisense 20-mer phosphorothioate oligodeoxynucleotides (AS S-oligos) directed against CR, AR, and TGF-alpha mRNAs were equipotent in their ability to inhibit both the anchorage-dependent growth and the anchorage-independent growth (AIG) of GEO cells, with a 50% inhibitory concentration of about 5 mu M in the AIG assay. A supraadditive effect was observed when a combination of S-oligos was used. For example, a combination of two different AS S-oligos (either AR + CR, or TGF-alpha + CR, or TGF-alpha + AR) at a concentration of 1 mu M each (total concentration, 2 mu M) resulted in 50% inhibition of GEO cells AIG, whereas the use of each AS S-Oligo at a 1 or 2 mu M concentration resulted respectively in about 10 and 20% growth inhibition. A combination of the three AS S-oligos was even more effective, resulting in about 60% inhibition of GEO cells AIG at a concentration of 1 mu M each (3 mu M total concentration). The AS S-oligos were also able to inhibit specifically the expression of either AR, CR, or TGF-alpha proteins in GEO cells, as assessed using immunocytochemistry or Western blot analysis. Finally, a supraadditive growth inhibitory effect of the AS S-oligos and an epidermal growth factor receptor-blocking antibody (monoclonal antibody 528) was observed. These data suggest that the use of a combination of AS S-oligos directed against different growth factors and antibodies directed against their receptors might result in an efficient inhibition of colon carcinoma cell growth. C1 UNIV FREDERICO II, FAC MED & CHIRURG, DIPARTIMENTO ENDOCRINOL & ONCOL MOL & CLIN, I-80131 NAPLES, ITALY. NCI, TUMOR IMMUNOL & BIOL LAB, TUMOR GROWTH FACTOR SECT, NIH, BETHESDA, MD USA. US FDA, ROCKVILLE, MD 20852 USA. MEM SLOAN KETTERING CANC CTR, DEPT MED, NEW YORK, NY 10021 USA. RP Normanno, N (reprint author), FDN PASCALE, ITN, I-80131 NAPLES, ITALY. OI Ciardiello, Fortunato/0000-0002-3369-4841; Normanno, Nicola/0000-0002-7158-2605 NR 53 TC 59 Z9 60 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 1996 VL 2 IS 3 BP 601 EP 609 PG 9 WC Oncology SC Oncology GA TY620 UT WOS:A1996TY62000022 PM 9816209 ER PT J AU Choudary, J Contrera, JF DeFelice, A DeGeorge, JJ Farrelly, JG Fitzgerald, G Goheer, MA Jacobs, A Jordan, A Meyers, L Osterberg, R Resnick, C Sun, CJ Temple, RJ AF Choudary, J Contrera, JF DeFelice, A DeGeorge, JJ Farrelly, JG Fitzgerald, G Goheer, MA Jacobs, A Jordan, A Meyers, L Osterberg, R Resnick, C Sun, CJ Temple, RJ TI Response to Monro and Mehta proposal for use of single-dose toxicology studies to support single-dose studies of new drugs in humans SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material C1 US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. NR 2 TC 8 Z9 8 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 1996 VL 59 IS 3 BP 265 EP 267 DI 10.1016/S0009-9236(96)80003-8 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UD420 UT WOS:A1996UD42000003 PM 8653988 ER PT J AU Pipkin, JL Hinson, WG LynCook, LE Aidoo, A Feuers, RJ Anson, JF Casciano, DA AF Pipkin, JL Hinson, WG LynCook, LE Aidoo, A Feuers, RJ Anson, JF Casciano, DA TI Comparison of the cell cycle regulated synthesis and phosphorylation of stress proteins, actin isoforms and a novel actin-like protein following drug administration in cultured rat lymphocytes SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE actin isoforms; cell cycle regulated; cell sorting; rat lymphocytes; stress proteins; ultra-microelectrophoresis ID HEAT-SHOCK PROTEINS; POLYACRYLAMIDE GELS; NUCLEAR-PROTEIN; BETA-ACTIN; CARDIAC MYOCYTES; RNA-POLYMERASE; INDUCTION; DROSOPHILA; PROLIFERATION; MYOSIN AB Administration of phytohemagglutinin initiated cycling of rat lymphocytes in vitro, and following treatment with this drug and other drugs in combination, lymphocytes were pulse labeled with [H-3] leucine or [P-32] phosphate. The nuclei were isolated from lymphocytes and collected from partitions of the cell cycle, and the proteins analyzed from fluorographs following gel electrophoresis for protein biomarkers after drug exposure. Stress proteins (sps) were dependent on a specific drug or drugs in combination (i.e., interleukin-2, bleomycin) for their synthesis that occurred only during the G(1)-phase of the cell cycle. An ''actin-like'' protein (A(4)) With electrophoretic mobilities similar to the actin complex, was synthesized in S and G(2) phases and phosphorylated in all phases of the cell cycle only following the administration of drugs in combination. A(4) exhibited a binding affinity for sp 24 that was cell cycle regulated (i.e., A(4) from S phase did not bind with sp 24, but A(4) from G(2) phase did bind with the sp. Protein A(4) appeared similar in some structural aspects to the nonmuscular actin isoform family but differed in epitope, suggesting a unique relationship and represented a stable protein, perhaps a product from the mutation of an actin gene. The dependence of certain sps and protein A(4) for their induction by drugs in combination may serve as biomarkers of chemical interaction and toxicity. RP Pipkin, JL (reprint author), US FDA,NATL CTR TOXICOL RES,DIV GENET TOXICOL,JEFFERSON,AR 72079, USA. NR 68 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0305-0491 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD MAR PY 1996 VL 113 IS 3 BP 549 EP 559 DI 10.1016/0305-0491(95)02090-X PG 11 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA UC564 UT WOS:A1996UC56400015 PM 8829805 ER PT J AU Blout, E AF Blout, E TI Polaroid: Dreams to reality SO DAEDALUS LA English DT Article C1 US FDA,ROCKVILLE,MD 20857. RP Blout, E (reprint author), AMER ACAD ARTS & SCI,CAMBRIDGE,MA 02138, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DAEDALUS PI CAMBRIDGE PA 136 IRVING ST, STE 100, CAMBRIDGE, MA 02138 SN 0011-5266 J9 DAEDALUS JI Daedalus PD SPR PY 1996 VL 125 IS 2 BP 39 EP 53 PG 15 WC Humanities, Multidisciplinary; Social Sciences, Interdisciplinary SC Arts & Humanities - Other Topics; Social Sciences - Other Topics GA UD991 UT WOS:A1996UD99100005 ER PT J AU Basnakian, AG James, SJ AF Basnakian, AG James, SJ TI Quantification of 3'OH DNA breaks by random oligonucleotide-primed synthesis (ROPS) assay SO DNA AND CELL BIOLOGY LA English DT Article ID TOPOISOMERASE-I; FRAGMENTATION; ENDONUCLEASE; INHIBITION; INSITU AB A simple and precise assay is presented for quantification of the relative number of 3'OH ends (breaks) present in DNA molecules. The assay is based on the ability of the Klenow fragment polymerase to initiate random oligonucleotide-primed synthesis from the reannealed 3'OH ends of single-stranded (ss) DNA. After a denaturation-reassociation step, the ssDNA serves as its own primer by randomly reassociating itself or to other ssDNA molecules. Under strictly defined reaction conditions (time, temperature, concentration of precursors) the incorporation of [P-32]dNTP into newly synthesized DNA will be proportional to the initial number of 3'OH ends (breaks). The assay is specific for the detection of 3'OH ends and requires only 0.25 mu g of DNA for analysis, It has application for the detection of the relative number of breaks per DNA molecule generated in vitro by endonucleases or in vivo during normal processes of DNA repair and also for the detection of DNA strand breaks from genotoxic DNA damaging agents. Although specific for 3'OH DNA ends, the assay can be adapted to measure 3'P (5'OH) DNA ends or breaks induced by oxidative DNA damaging agents by pretreatment of the DNA with alkaline phosphatase or Escherichia coli exonuclease In. The assay is capable of quantifying first several breaks per 10(5) bp. RP Basnakian, AG (reprint author), US FDA, DIV NUTR TOXICOL, NATL CTR TOXICOL RES, 3900 NCTR RD, JEFFERSON, AR 72079 USA. NR 26 TC 47 Z9 47 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5498 EI 1557-7430 J9 DNA CELL BIOL JI DNA Cell Biol. PD MAR PY 1996 VL 15 IS 3 BP 255 EP 262 DI 10.1089/dna.1996.15.255 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA UC256 UT WOS:A1996UC25600008 PM 8634154 ER PT J AU Chen, JJ Gaylor, DW Laborde, JB AF Chen, JJ Gaylor, DW Laborde, JB TI Dose-response modelling of growth for developmental toxicity SO ENVIRONMETRICS LA English DT Article DE foetal growth model; exponential growth; quasi-likelihood ID 2,4,5-TRICHLOROPHENOXYACETIC ACID 2,4,5-T; RISK ASSESSMENT; MICE; MALFORMATIONS; EXPOSURE AB A biologically-based dose-response model for predicting developmental malformation effects from exposure to a toxic substance during pregnancy is developed. The biological basis of this model arises from the expectation of exponential growth in rodents during gestation, and the exponential growth rate assumed to be reduced by dose raised to a power when a toxic substance is administered during gestation. The prenatal foetal weight is used as a biomarker to link the incidence of cleft palate to the dose level. A dose-response growth model for prenatal foetal weight as a function of both time and dose is established. This dose-response function is then combined with a dose-response function between the incidence of cleft palate and the prenatal foetal weight to form a dose-response function between the cleft palate and dose. Two experiments, a dexamethasone (DEX) exposure in rats and a 2,4,5-trichlorophenoxyacetic (2,4,5-T) acid exposure in mice, were conducted for purpose of checking the models empirically and for demonstration of modelling process. The proposed dose-response growth model for prenatal foetal weight fits adequately to both experimental data, but the model from prenatal foetal weight and incidence of cleft palate combined seems inadequate to describe the relationship between the dose and incidence of cleft palate fully. C1 US FDA,NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079. RP Chen, JJ (reprint author), US FDA,NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,JEFFERSON,AR 72079, USA. NR 17 TC 4 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1180-4009 J9 ENVIRONMETRICS JI Environmetrics PD MAR-APR PY 1996 VL 7 IS 2 BP 135 EP 144 PG 10 WC Environmental Sciences; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Environmental Sciences & Ecology; Mathematics GA UD795 UT WOS:A1996UD79500002 ER PT J AU Chu, I Dick, D Bronaugh, R Tryphonas, L AF Chu, I Dick, D Bronaugh, R Tryphonas, L TI Skin reservoir formation and bioavailability of dermally administered chemicals in hairless guinea pigs SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID PERCUTANEOUS-ABSORPTION; STRATUM-CORNEUM; INVITRO; METABOLISM AB There is concern as to whether dermally applied chemicals that remain in the skin after exposure are bioavailable and should be included as part of the systemic dose; this study was conducted to investigate the temporal relationship between the skin depot and absorbed dose. Single doses of C-14-labelled phenanthrene, benzo[a]pyrene or di(2-ethylhexyl) phthalate were administered dermally to groups of four female, Hartley hairless guinea pigs which were housed individually in metabolism cages to collect urine and faeces for radioassay. The animals were sacrificed at 6 hr, 24 hr, 48 hr, 7 days or 14 days after dosing to harvest skin specimens for the determination of radioactivity by autoradiographic and liquid scintillation methods, and to determine the dose that remained in the body. It was found that for all three compounds the amount of chemical left in the skin decreased over time while the cumulative percent dose excreted in urine and faeces increased. The autoradiographic results were consistent with those obtained from the liquid scintillation method showing a gradual decrease in radioactivity grain accumulation over the time periods for the three compounds, with the highest grain density observed around hair follicles of the skin. The results of this study indicate that the chemicals left in the skin after surface washing eventually enter the systemic circulation and should be considered as part of the total dose absorbed, and that the hair follicle may play an important role in percutaneous penetration. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. RP Chu, I (reprint author), DEPT HLTH & WELF,ENVIRONM HLTH DIRECTORATE,BLDG 8,TUNNEYS PASTURE,OTTAWA,ON K1A 0L2,CANADA. NR 17 TC 32 Z9 33 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD MAR PY 1996 VL 34 IS 3 BP 267 EP 276 DI 10.1016/0278-6915(95)00112-3 PG 10 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA UC259 UT WOS:A1996UC25900004 PM 8621108 ER PT J AU Wodicka, VO AF Wodicka, VO TI Regulation of food: Where have we been? SO FOOD TECHNOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Institute-of-Food-Technologists CY JUN 03-07, 1995 CL ANAHEIM, CA SP Inst Food Technologists RP Wodicka, VO (reprint author), US FDA,BUR FOODS,1307 NORMAN PL,FULLERTON,CA 92631, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA SUITE 300 221 N LASALLE ST, CHICAGO, IL 60601-1291 SN 0015-6639 J9 FOOD TECHNOL-CHICAGO JI Food Technol. PD MAR PY 1996 VL 50 IS 3 BP 106 EP 109 PG 4 WC Food Science & Technology SC Food Science & Technology GA UB389 UT WOS:A1996UB38900015 ER PT J AU Halsted, CH Villanueva, J Chandler, CJ Stabler, SP Allen, RH Muskhelishvili, L James, SJ Poirier, L AF Halsted, CH Villanueva, J Chandler, CJ Stabler, SP Allen, RH Muskhelishvili, L James, SJ Poirier, L TI Ethanol feeding of micropigs alters methionine metabolism and increases hepatocellular apoptosis and proliferation SO HEPATOLOGY LA English DT Article ID ONE-CARBON METABOLISM; FOLATE-DEFICIENCY; RAT-LIVER; FOLIC-ACID; COBALAMIN; ACETALDEHYDE; SERUM; DNA; METHYLTRANSFERASE; DYSPLASIA AB Chronic alcoholism is associated with increased cancer risk that may be related to ethanol-induced alterations in methionine and deoxynucleotide metabolism. These metabolic relationships were studied in micropigs fed diets for 12 months that contained 40% ethanol or cornstarch control with adequate folate, Ethanol feeding altered methionine metabolism without changing mean terminal liver folate levels. After initial equilibration to diet, ethanol feeding significantly increased monthly serum homocysteine levels while reducing serum methionine levels over the time course of the experiment. After 12 months, hepatic methionine synthase activity and the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) were significantly reduced in ethanol-fed animals, whereas the ratio of liver deoxyuridine triphosphate (dUTP) to deoxythymidine triphosphate (dTTP) was increased and correlated inversely with methionine synthase activity, These findings were associated with increased frequency of hepatocytes with apoptotic bodies and positivity for pro liferating cell nuclear antigen (PCNA) in livers from ethanol-fed minipigs, These studies suggest that chronic ethanol feeding perturbs methionine metabolism by impairment of methionine synthase activity, resulting in deoxynucleoside triphosphate (dNTP) imbalance, increased apoptosis, and regenerative proliferation, These biochemical alterations may provide a promoting environment for carcinogenesis during long-term ethanol exposure. C1 UNIV COLORADO,SCH MED,DEPT MED,DENVER,CO. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RP Halsted, CH (reprint author), UNIV CALIF DAVIS,DEPT INTERNAL MED,DIV CLIN NUTR & METAB,TB-156,DAVIS,CA 95616, USA. FU NIA NIH HHS [AG 09834-01]; NIAAA NIH HHS [AA 06938]; NIDDK NIH HHS [DK 35747] NR 50 TC 134 Z9 136 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 1996 VL 23 IS 3 BP 497 EP 505 DI 10.1002/hep.510230314 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA TZ788 UT WOS:A1996TZ78800014 PM 8617429 ER PT J AU Carrington, CD AF Carrington, CD TI Logical probability and risk assessment SO HUMAN AND ECOLOGICAL RISK ASSESSMENT LA English DT Article DE model uncertainty; probability ID METHYLMERCURY AB A risk assessment is intended to provide a statement of current knowledge which is intended to inform a decision-maker of the current state of knowledge in response to a particular concern. Because answering the concerns of decision-makers often requires inferences to be drawn, doubt often arises over how the inference is to be drawn. In quantitative risk assessment, where a mathematical equation or model is used to draw the inference, this uncertainty is referred to as model uncertainty. A two-step process, which is referred to as logical probability, is proposed as a technique for representing model uncertainty in a risk assessment. The first step involves assigning model weights in which the degree of evidential support for each of the alternative models is considered. The second step involves assigning a unique interval in the range of 0 to 1 for each model which reflects the models' weight, to form a probability distribution. While the second step is straightforward, the first step is not. Assigning model weights requires consideration of any line of evidence that may reasonably impact the validity of the assertion of a model. While the development of a procedure for doing so may be expected to be a process which reflects the subjective preferences of whomever is involved in creating it, there are some historical precedents on which to build. Foremost among these are (1) the use of a correlation coefficient or other goodness-of-fit criteria to measure the degree of correspondence between a given model and a set of observations which are used as evidence to support it, and (2) preference given to models which are simpler, which may be ascertained as the number of adjustable parameters the model contains. Additional principles, which have little or no tradition to stand on, must be used to reflect the impact of other empirically supported beliefs on model preference. The procedure proposed is comparable to the procedure known as decision analysis, in which probabilities are assigned to alternative models based on expert or subjective input. The principal difference in the present case is that it is suggested that principles which transcend the decision at hand should be sought and articulated in order to generate a consistent measure of uncertainty arising from interpretation. RP Carrington, CD (reprint author), US FDA,200 C ST,SW HFS-308,WASHINGTON,DC 20204, USA. NR 20 TC 20 Z9 20 U1 0 U2 0 PU AMHERST SCIENTIFIC PUBL PI AMHERST PA PO BOX 2308, AMHERST, MA 01004-2308 SN 1080-7039 J9 HUM ECOL RISK ASSESS JI Hum. Ecol. Risk Assess. PD MAR PY 1996 VL 2 IS 1 BP 62 EP 78 DI 10.1080/10807039.1996.10387462 PG 17 WC Biodiversity Conservation; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA UR815 UT WOS:A1996UR81500012 ER PT J AU Waynant, RW AF Waynant, RW TI Surf's up SO IEEE CIRCUITS AND DEVICES MAGAZINE LA English DT Editorial Material RP Waynant, RW (reprint author), US FDA,1901 CHAPMAN AVE,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 8755-3996 J9 IEEE CIRCUIT DEVIC JI IEEE Circuit Devices Mag. PD MAR PY 1996 VL 12 IS 2 BP 4 EP 4 PG 1 WC Engineering, Electrical & Electronic; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA UA785 UT WOS:A1996UA78500001 ER PT J AU Waynant, RW Fuller, R AF Waynant, RW Fuller, R TI Changes, changes ... SO IEEE CIRCUITS AND DEVICES MAGAZINE LA English DT Editorial Material RP Waynant, RW (reprint author), US FDA,1901 CHAPMAN AVE,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 8755-3996 J9 IEEE CIRCUIT DEVIC JI IEEE Circuit Devices Mag. PD MAR PY 1996 VL 12 IS 2 BP 48 EP & PG 2 WC Engineering, Electrical & Electronic; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA UA785 UT WOS:A1996UA78500014 ER PT J AU Liu, YJ Malisan, F deBouteiller, O Guret, C Lebecque, S Banchereau, J Mills, FC Max, EE MartinezValdez, H AF Liu, YJ Malisan, F deBouteiller, O Guret, C Lebecque, S Banchereau, J Mills, FC Max, EE MartinezValdez, H TI Within germinal centers, isotype switching of immunoglobulin genes occurs after the onset of somatic mutation SO IMMUNITY LA English DT Article ID CONSTANT REGION GENE; PRIMARY IMMUNE-RESPONSE; CENTER B-CELLS; CIRCULAR DNA; RECOMBINATION; EXPRESSION; ANTIGEN; MATURATION; (4-HYDROXY-3-NITROPHENYL)ACETYL; INTERLEUKIN-4 AB Human tonsillar B cells were separated into naive IgD(+)CD38(-)CD23(-) (Bm1) and IgD(+)CD38(-)CD23(+) (Bm2), germinal center IgD(-)CD38(+)CD23(-) centroblasts (Bm3) and IgD(-)CD38(+)CD77(-) centrocytes (Bm4), and memory IgD(-)CD38(-) (Bm5) subsets. Previous IgV(H) sequence analysis concluded that the triggering of somatic mutations occurs during the transition from Bm2 subset into the Bm3 subset. To determine the initiation of isotype switching, sterile transcript expression was analyzed by amplification, cloning, and sequencing. A selective sterile I gamma, I alpha, and I epsilon expression was observed at centrocyte (Bm4) stage, suggesting that isotype switch is triggered within germinal centers, after somatic mutation is initiated within centroblasts (Bm3). Finally, the high level of 5'S gamma-S mu 3' DNA switching circles observed in germinal center B cells indicates that within human tonsils, germinal center is a major location for isotype switching. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. RP Liu, YJ (reprint author), SCHERING PLOUGH CORP,LAB IMMUNOL RES,F-69571 DARDILLY,FRANCE. OI MALISAN, FLORENCE/0000-0002-0213-9407 NR 61 TC 228 Z9 233 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 1996 VL 4 IS 3 BP 241 EP 250 DI 10.1016/S1074-7613(00)80432-X PG 10 WC Immunology SC Immunology GA UC018 UT WOS:A1996UC01800005 PM 8624814 ER PT J AU Conte, ED Shen, CY Perschbacher, PW Miller, DW AF Conte, ED Shen, CY Perschbacher, PW Miller, DW TI Determination of geosmin and methylisoborneol in catfish tissue (Ictalurus punctatus) by microwave-assisted distillation-solid phase adsorbent trapping SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE off-flavors; methylisoborneol; geosmin; catfish; microwave-assisted distillation ID CHANNEL CATFISH; 2-METHYLISOBORNEOL; FLAVOR; PONDS; WATER AB Methylisoborneol (MIB) and geosmin (GEO) are algal off-flavor compounds, which when present in catfish tissue create undesirable taste and odors in the prepared products. These undesirable taste and odor problems are not limited to catfish aquaculture. A procedure was developed for the determination of off-flavor compounds in channel catfish tissue that involves microwave radiation distillation with solid phase trapping. This is a modification of a microwave distillation-cold trapping procedure but without the need of a cryogen or a liquid-liquid extraction step. A channel catfish fillet sample is placed in a container located within a microwave oven. This container, which is directly connected to a thermostated condenser containing a solid phase adsorbent, is continually purged with argon gas. The trapped distillate components are eluted with ethyl acetate and then injected into a gas chromatograph-ion trap mass spectrometer for analysis. This technique offers a rapid and sensitive means of off-flavor analysis in fish tissue and improved recovery for MIB from 73 +/- 3% (50 ppb) to 85 +/- 5% (10 ppm) compared to 62 +/- 6% for microwave-cold trap collection. The method detection limits are 1.7 and 1.1 ppb for MIB and GEO, respectively. C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. UNIV ARKANSAS,PINE BLUFF,AR 71601. NR 9 TC 18 Z9 19 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAR PY 1996 VL 44 IS 3 BP 829 EP 835 DI 10.1021/jf9505032 PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA UB130 UT WOS:A1996UB13000033 ER PT J AU Jackson, LS Hlywka, JJ Senthil, KR Bullerman, LB Musser, SM AF Jackson, LS Hlywka, JJ Senthil, KR Bullerman, LB Musser, SM TI Effects of time, temperature, and pH on the stability of fumonisin B-1 in an aqueous model system SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Fumonisin B-1; thermal processing; decomposition ID FUSARIUM-MONILIFORME; CONTAMINATED CORN; NATURAL OCCURRENCE; ESOPHAGEAL CANCER; MYCOTOXINS; METABOLITE; TOXICITY; PRODUCTS; TRANSKEI; RATS AB Fumonisins, mycotoxins produced by Fusarium moniliforme in corn, have been implicated in several animal. and human diseases. The effects of processing time and temperature on fumonisin B-1 (FB1) stability (5 ppm) in aqueous solutions at pH 4, 7, and 10 were determined. Analysis of the thermally processed solutions by liquid chromatography/mass spectrometry indicated the predominant presence of hydrolysis products of FB1. The rate and extent of FB1 decomposition increased with processing temperature. After processing at less than or equal to 125 degrees C for 60 min, (27% of FB1 was lost; after 60 min at 150 degrees C, 18-90% was lost, depending on buffer pH. Overall, FB1 was least stable at pH 4 followed by pH 10 and 7, respectively. At greater than or equal to 175 degrees C, >90% of FB1 was lost after processing for 60 min, regardless of pH. FB1 levels may be substantially reduced in foods that reach greater than or equal to 150 degrees C during processing. C1 UNIV NEBRASKA,DEPT FOOD SCI & TECHNOL,LINCOLN,NE 68583. IIT,NATL FOOD CTR SAFETY & TECHNOL,SUMMIT ARGO,IL 60501. US FDA,WASHINGTON,DC 20204. RP Jackson, LS (reprint author), US FDA,NATL FOOD CTR SAFETY & TECHNOL,SUMMIT ARGO,IL 60501, USA. NR 36 TC 46 Z9 46 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAR PY 1996 VL 44 IS 3 BP 906 EP 912 DI 10.1021/jf950364o PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA UB130 UT WOS:A1996UB13000046 ER PT J AU Ang, CYW Luo, WH Hansen, EB Freeman, JP Thompson, HC AF Ang, CYW Luo, WH Hansen, EB Freeman, JP Thompson, HC TI Determination of amoxicillin in catfish and salmon tissues by liquid chromatography with precolumn formaldehyde derivatization SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID POST-COLUMN DERIVATIZATION; MASS-SPECTROMETRY; BODY-FLUIDS; AMPICILLIN; AMOXYCILLIN; PLASMA; EXTRACTION; MILK AB A liquid chromatographic (LC) method with fluorescence detection was developed for analysis of amoxicillin in catfish and salmon tissues, The tissue was extracted with phosphate buffer (pH 4.5), followed by trichloroacetic acid (TCA) precipitation of proteins and solid-phase (C-18) extraction, Trace amounts of nonpolar interfering substances present after solid-phase extraction were removed by ether liquid-liquid extraction, The extract was reacted with formaldehyde and TCA at 100 degrees C for 30 min. A fluorescent derivative was extracted with ether, concentrated, and analyzed by reversed-phase LC with fluorescence detection, Average recoveries of amoxicillin spiked at 2.5-20 ppb were >80% for catfish and >75% for salmon muscle tissue, with coefficients of variation of <6%. Limits of detection (LOD) and quantitation (LOQ) for catfish tissue were 0.5 and 1.2 ppb, respectively. LOD and LOQ for salmon muscle tissue were 0.8 and 2.0 ppb, respectively. RP Ang, CYW (reprint author), US FDA,NATL CTR TOXICOL RES,DIV CHEM,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 22 TC 31 Z9 35 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1996 VL 79 IS 2 BP 389 EP 396 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA UD268 UT WOS:A1996UD26800007 PM 8920125 ER PT J AU MacNeil, JD Martz, VK Korsrud, GO Salisbury, CDC Oka, H Epstein, RL Barnes, CJ AF MacNeil, JD Martz, VK Korsrud, GO Salisbury, CDC Oka, H Epstein, RL Barnes, CJ TI Chlortetracycline, oxytetracycline, and tetracycline in edible animal tissues, liquid chromatographic method: Collaborative study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID RESIDUES AB Thirteen laboratories analyzed samples of edible animal tissues for tetracycline residues, The method included extraction of analytes into buffer, elution from a C-18 solid-phase extraction (SPE) cartridge, and reversed-phase liquid chromatographic (LC) analysis, including use of a confirmation column, An additional laboratory, using an alternative LC assay based on a different sample cleanup, also analyzed the samples, Results showed the 2 methods are comparable, The LC method for determination of cholortetracycline, oxytetracycline, and tetracycline in edible animal tissues has been adopted by AOAC INTERNATIONAL, Results from 13 laboratories indicate that the method under study provides generally better results at the higher concentrations tested than at concentrations near the detection limit and that there is less problem with interferences in muscle tissue than in kidney, The method can achieve reliable results for analytes and matrixes studied at concentrations from 0.1 to 0.6 ppm and above, depending on the analyte-matrix combination, with generally better performance to be expected with muscle than with kidney, The poorer performance for fortified samples, particularly kidney, was attributed to additional homogenization steps required to prepare these samples, Recovery of analytes from different lots of solid-phase extraction (SPE) cartridges was an important variable. C1 AICHI PREFECTURAL INST PUBL HLTH,LAB FOOD & DRUG CHEM,KITA KU,NAGOYA,AICHI 462,JAPAN. USDA,AGR MARKETING SERV,DIV SCI,WASHINGTON,DC 20090. US FDA,OFF SCI,BELTSVILLE,MD 20705. RP MacNeil, JD (reprint author), AGR & AGRI FOOD CANADA,HLTH ANIM LAB,SASKATOON,SK S7N 2R3,CANADA. NR 3 TC 44 Z9 46 U1 1 U2 5 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1996 VL 79 IS 2 BP 405 EP 417 PG 13 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA UD268 UT WOS:A1996UD26800009 PM 8920127 ER PT J AU Walker, ST AF Walker, ST TI Liquid chromatographic determination of nalidixic acid in pharmaceutical preparations SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A simple, rapid, and environmentally safe liquid chromatographic (LC) method was developed for the qualitative and quantitative determination of pharmaceutical preparations of nalidixic acid, The new method was applied to commercial preparations of tablets and a suspension of nalidixic acid and found to be satisfactory for both quantitative and qualitative determinations, Previous LC methods either used chloroform to extract, which we were trying to eliminate, or used a mobile phase of about pH 2.5, which will destroy the column coating, The LC system for the new method uses sulfanilic acid as internal standard, a mu-Bondapak C-18 column, and a mobile phase of methanol, 0.0045M dibasic potassium phosphate, and 0.0072M hexadecyltrimethylammmonium bromide. The detection wavelength is 254 nm, The sample is dissolved in methanol, and an aliquot is injected through a 20 mu L injection loop, Average recoveries ranged from 99.4 to 101.3%. RP Walker, ST (reprint author), US FDA,DRUG CHEM BRANCH,NE REG LAB,850 3RD AVE,BROOKLYN,NY 11232, USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1996 VL 79 IS 2 BP 431 EP 433 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA UD268 UT WOS:A1996UD26800013 PM 8920129 ER PT J AU Brause, AR Trucksess, MW Thomas, FS Page, SW AF Brause, AR Trucksess, MW Thomas, FS Page, SW TI Determination of patulin in apple juice by liquid chromatography: Collaborative study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB An AOAC International-International Union of Pure acid Applied Chemistry-International Fruit Juice Union (AOAC-IUPAG-IFJU) collaborative study was conducted to evaluate a liquid chromatographic (LC) procedure for determination of patulin in apple juice, Patulin is a mold metabolite found naturally in rotting apples. Patulin is extracted with ethyl acetate, treated with sodium carbonate solution, and determined by reversed-phase LC with UV detection al 254 or 276 nm, Water, water-tetrahydrofuran, or water-acetonitrile was used as mobile phase, Levels determined in spiked test samples were 20, 50, 100, and 200 mu g/L. A test sample naturally contaminated at 31 mu g/L was also included. Twenty-two collaborators in 10 countries analyzed 12 test samples of apple juice. Recoveries averaged 96%, with a range of 91-108%. Repeatability relative standard deviations (RSD(r)) ranged from 10.9 to 53.8%. The reproducibility relative standard deviation (RSD(R)) ranged from 15.1 to 68.8%. The LC method for determination of patulin in apple juice has been adopted first action by AOAC INTERNATIONAL. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. RP Brause, AR (reprint author), COLUMBIA INC,ANALYT CHEM SERV,9151 RUMSEY RD,COLUMBIA,MD 21045, USA. NR 8 TC 69 Z9 69 U1 0 U2 8 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1996 VL 79 IS 2 BP 451 EP 455 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA UD268 UT WOS:A1996UD26800016 PM 8920132 ER PT J AU Carman, AS Kuan, SS Ware, GM Umrigar, PP Miller, KV Guerrero, HG AF Carman, AS Kuan, SS Ware, GM Umrigar, PP Miller, KV Guerrero, HG TI Robotic automated analysis of foods for aflatoxin SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LIQUID-CHROMATOGRAPHIC DETERMINATION; IMMUNOAFFINITY COLUMN CLEANUP; AFFINITY-CHROMATOGRAPHY; PEANUT BUTTER; PRODUCTS; CORN; MILK; M1 AB Immunoaffinity column-based sample preparation procedures for determination of aflatoxins B-1, B-2, G(1), and G(2) in several food matrixes and aflatoxin M(1) in milk have been automated by using flexible automation, or robotics, Components used to assemble the system were purchased commercially or developed and built in-house. A liquid-level sensor developed in-house to assist elution of the immunoaffinity column is described. After immunoaffinity column cleanup, aflatoxins are separated by reversed-phase liquid chromatography and determined by fluorescence without derivatization. Mean recoveries of aflatoxins B-1, B-2, and G(1) added to corn and nuts at 9-36 ng/g total aflatoxins were >85% (coefficient of variation [CV] = 16%). Recoveries of aflatoxin G(2) averaged 50% (CV = 28%). Recoveries of aflatoxin M(1) added to milk at 0.12-0.50 ng/mL averaged 78% (CV = 19%). The ability of the automated system to reproduce its results is demonstrated by the fact that the CV of replicate assays is generally better than 10%. Comparability between the automated procedure and the AOAC official method is demonstrated. C1 US FDA,NEW ORLEANS DIST LAB,NEW ORLEANS,LA 70122. RP Carman, AS (reprint author), US FDA,NAT TOXINS RES CTR,4298 ELYSIAN FIELDS AVE,NEW ORLEANS,LA 70122, USA. NR 18 TC 13 Z9 13 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1996 VL 79 IS 2 BP 456 EP 464 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA UD268 UT WOS:A1996UD26800017 PM 8920133 ER PT J AU Whitaker, T Horwitz, W Albert, R Nesheim, S AF Whitaker, T Horwitz, W Albert, R Nesheim, S TI Variability associated with analytical methods used to measure aflatoxin in agricultural commodities SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A total of 1019 analytical precision estimates obtained from method-performance (collaborative) studies for mycotoxins published through 1991 were sorted by type of variance measurement, type of analytical method, and type of agricultural commodity, Precision estimates for total aflatoxin were sorted into 2 precision measurements (among-laboratories and within-laboratory), 3 analytical methods (thin-layer chromatography [TLC], liquid chromatography [LC], and enzyme-linked immunosorbent assay [ELISA]), and 11 agricultural commodities. Sufficient data existed to study the analytical variability (precision) associated with 36 sorted combinations (of a possible 66). In all but one combination (within-laboratory, barley and TLC), the variance (V) was a function of total aflatoxin concentration (C). A power function of the form V = aC(b), where a and b are constants, describes the relationship between variance and aflatoxin concentration, The coefficients a and b were determined from regression analysis, When results were pooled across all agricultural commodities, LC had the lowest analytical variability while ELISA had the highest, For a given method, among-laboratories variability was approximately double the within-laboratory variability. These analytical variability estimates can be coupled with previously determined variability estimates of sampling and sample preparation to determine the performance associated with specific test procedures used to inspect agricultural commodities for aflatoxin. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. RP Whitaker, T (reprint author), N CAROLINA STATE UNIV,DEPT BIOL & AGR ENGN,USDA ARS,BOX 7625,RALEIGH,NC 27695, USA. NR 13 TC 35 Z9 37 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1996 VL 79 IS 2 BP 476 EP 485 PG 10 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA UD268 UT WOS:A1996UD26800020 PM 8920136 ER PT J AU Lovell, RA McChesney, DG Price, WD AF Lovell, RA McChesney, DG Price, WD TI Organohalogen and organophosphorus pesticides in mixed feed rations: Findings from FDA's domestic surveillance during fiscal years 1989-1994 SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB During Fiscal Years 1989-1994, the U.S. Food and Drug Administration (FDA) collected and analyzed 545 domestic surveillance samples of mixed feed rations (172 for cattle, 125 for poultry, 83 for swine, 61 for pets, 56 for fish, and 48 miscellaneous). All samples were analyzed by gas-liquid chromatography for organohalogen and organophosphorus pesticides. Of the 545 samples, 88 (16.1%) did not contain detectable pesticide residues. In the 457 samples with detectable pesticide levels, 804 residues (654 quantitable and 150 trace) were found. None of these 804 residues exceeded regulatory guidance. Malathion, chlorpyrifos-methyl, diazinon, chlorpyrifos, and pirimiphos-methyl were the most commonly detected pesticides. These 5 organophosphorus pesticides accounted for 93.4% of all pesticide residues detected (malathion, 52.9%; chlorpyrifos-methyl, 25.2%; diazinon, 7.7%; chlorpyrifos, 4.9%; and pirimiphos-methyl, 2.7%). Their median values in samples containing quantitable levels ranged from 0.014 to 0.098 ppm. The most commonly detected organohalogen compounds were methoxychlor, DDE, PCB, dieldrin, pentachloronitrobenzene, and lindane, These 6 compounds combined accounted for only 4.1 of of all residues detected. FDA is continuing its pesticide surveillance of feeds to help ensure animal safety and prevent violative residues in food derived from animals. C1 US FDA,CTR VET MED,DIV ANIM FEEDS,ROCKVILLE,MD 20857. NR 3 TC 14 Z9 14 U1 3 U2 11 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1996 VL 79 IS 2 BP 544 EP 548 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA UD268 UT WOS:A1996UD26800029 PM 8920144 ER PT J AU David, M Petricoin, E Larner, AC AF David, M Petricoin, E Larner, AC TI Activation of protein kinase A inhibits interferon induction of the Jak/Stat pathway in U266 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA; RECEPTOR; CAMP AB Activation of early response genes by interferons (IFNs) requires tyrosine phosphorylation of the Stat transcription factors and is mediated by the Jak family of tyrosine kinases, Recent evidence suggests that ERK2 serine/threonine kinase modulates the IFN-stimulated Jak/Stat pathway. In this report we show that in the myeloma cell line U266 protein kinase A specifically interacts with the cytoplasmic domain of the IFN alpha/beta receptor, Treatment of cells with the adenylate cyclase activator forskolin inhibits IFN beta-, IFN gamma-, and hydrogen peroxide/vanadate-induced formation of complexes that bind to enhancers known to stimulate the expression of IFN-regulated genes. Immunoprecipitations followed by anti-phosphotyrosine immunoblots indicate that tyrosine phosphorylation of the alpha chain of the IFN alpha/beta receptor, Jak1, Trk2, as well as Stat1 and Stat2 is reduced as a consequence of incubation of cells with forskolin. In contrast, dideoxyforskolin, which fails to activate adenylate cyclase, has no effect on IFN induction of the Jak/Stat pathway. These results indicate a novel regulatory mechanism by which protein kinase A can modulate the Jak/Stat signaling cascade. C1 NIH,DIV CYTOKINE BIOL,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 20 TC 62 Z9 64 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 1 PY 1996 VL 271 IS 9 BP 4585 EP 4588 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TX697 UT WOS:A1996TX69700005 PM 8617715 ER PT J AU Sun, JX Walter, B Sandefer, EP Page, RC Digenis, GA Ryo, UY Cipriano, A Maniara, WM Powell, ML Chan, K AF Sun, JX Walter, B Sandefer, EP Page, RC Digenis, GA Ryo, UY Cipriano, A Maniara, WM Powell, ML Chan, K TI Explaining variable absorption of a hypolipidemic agent (CGP 43371) in healthy subjects by gamma scintigraphy and pharmacokinetics SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID DRUG DELIVERY AB The gastrointestinal absorption of a hypolipidemic agent (CGP 43371) was investigated using an external scintigraphy technique in six healthy men. After an overnight fast, subjects received a single 800-mg oral dose of CCP 43371 (4 capsules of 200 mg each) and one capsule of radioactive samarium-153 oxide (100-130 mu Ci) as a nonabsorbable marker of gastrointestinal transit and fecal recovery for CGP 43371. In vivo gastrointestinal transit of samarium-153 was monitored via gamma scintigraphy for 48 hours after administration to coincide with blood sampling. Samarium-153 content in whole fecal samples was determined by external gamma scintigraphy, and CGP 43371 content in both fecal and plasma samples was determined using high-performance liquid chromatography (HPLC). The results of fecal analysis indicated that transit of the two compounds in the gastrointestinal tract were similar, and bioavailability of CGP 43371 was calculated to be 9% based on the difference between the cumulative amounts of the nonabsorbable radioactive marker and CGP 43371 found in the feces. The onset of drug absorption occurred 4 hours after administration when radioactive samarium-153 was in the distal small bowel, and peak plasma drug level occurred 6 hours after administration, which corresponded with the arrival of samarium-153 in the terminal ileum and ileal/cecal junction. This observation supported the concept that primary absorption of this compound was in the distal to terminal portion of the ileum. Although the onset of drug absorption was delayed, it was curious that the rate of gastric emptying also affected the extent of absorption. A positive correlation (r = 0.91) between area under the drug curve (AUG) and area under the transit curve (AUTC) of the gastric emptying showed that longer gastric residence improved oral absorption of CGP 43371. C1 BOEHRINGER INGELHEIM PHARMACEUT INC,RIDGEFIELD,CT 06877. UNIV KENTUCKY,COLL PHARM,LEXINGTON,KY 40506. CIBA GEIGY CORP,DIV PHARMACEUT,BIOANALYT & PHARMACOKINET RES DEPT,SUMMIT,NJ 07901. US FDA,ROCKVILLE,MD 20857. RP Sun, JX (reprint author), BAKER NORTON PHARMACEUT INC,50 NW 176TH ST,MIAMI,FL 33169, USA. NR 18 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAR PY 1996 VL 36 IS 3 BP 230 EP 237 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UC842 UT WOS:A1996UC84200007 PM 8690816 ER PT J AU Lavelle, J Follansbee, S Trapnell, CB Buhles, WC Griffy, KG Jung, D Dorr, A Conner, J AF Lavelle, J Follansbee, S Trapnell, CB Buhles, WC Griffy, KG Jung, D Dorr, A Conner, J TI Effect of food on the relative bioavailability of oral ganciclovir SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID ABSORPTION AB The steady-state pharmacokinetics of oral ganciclovir in the fasting versus fed state were studied in 20 patients infected with human immunodeficiency virus and with a seropositive test result for cytomegalovirus in a two-way crossover study. Patients received oral ganciclovir at a dose of 1000 mg every 8 hours for 8 days. On days 4 and 8, subjects were randomly assigned to receive the morning dose either after an overnight fast or after a standardized 602-calorie, high-fat (46.5%) breakfast. Serial blood samples were obtained over the 8-hour morning dose interval. The mean time to maximum concentration (t(max)) was increased from 1.8 hours in the fasting state to 3.0 hours in the fed state. Mean maximum serum concentration (C-max) and area under the concentration-time curve from time 0 to 8 hours (AUC(0-8)) of ganciclovir were significantly higher in the fed state than after an overnight fast. Because food could potentially increase the bioavailability of oral ganciclovir, patients should be instructed to take each dose of oral ganciclovir with food. C1 GEORGETOWN UNIV,MED CTR,DEPT MED,WASHINGTON,DC 20007. DAVIES MED CTR,SAN FRANCISCO,CA. US FDA,ROCKVILLE,MD 20857. SYNTEX INC,RES,PALO ALTO,CA 94304. UNIV CALIF SAN DIEGO,DEPT PEDIAT,SAN DIEGO,CA 92103. NR 8 TC 18 Z9 19 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAR PY 1996 VL 36 IS 3 BP 238 EP 241 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UC842 UT WOS:A1996UC84200008 PM 8690817 ER PT J AU Malisan, F Briere, F Bridon, JM HArindranath, N Mills, FC Max, EE Banchereau, J MartinezValdez, H AF Malisan, F Briere, F Bridon, JM HArindranath, N Mills, FC Max, EE Banchereau, J MartinezValdez, H TI Interleukin-10 induces immunoglobulin G isotype switch recombination in human CD40-activated naive B lymphocytes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID X-LINKED IMMUNODEFICIENCY; HUMAN IGE SYNTHESIS; CD40 LIGAND; HYPER-IGM; CIRCULAR DNA; CELLS; EXPRESSION; SEQUENCES; EPSILON; GAMMA AB Upon activation, B lymphocytes can change the isotype of the antibody they express by immunoglobulin (Ig) isotype switch recombination. In previous studies on the regulation of human IgG expression, we demonstrated that interleukin 10 (IL-10) could stimulate IgG1 and IgG3 secretion by human CD40-activated naive (sIgD(+)) tonsillar B cells. To assess whether IL-10 actually promotes the DNA recombination underlying switching to these isotypes, we examined the effect of IL-10 on the generation of reciprocal products that form DNA circles as by-products of switch recombination. The content of reciprocal products characteristic of mu-gamma recombination was elevated after culture of CD40-activated tonsillar sIgD(+) B cells with either IL-4 or IL-10, although high levels of IgG secretion were observed only with IL-10. Unlike IL-4, IL-10 did not induce reciprocal products of mu-epsilon and gamma-epsilon switch recombination. These results demonstrate that IL-10 promotes both switching to gamma and IgG secretion. C1 SCHERING PLOUGH SPA,LAB IMMUNOL RES,F-69571 DARDILLY,FRANCE. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. OI MALISAN, FLORENCE/0000-0002-0213-9407 NR 41 TC 108 Z9 110 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1996 VL 183 IS 3 BP 937 EP 947 DI 10.1084/jem.183.3.937 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UC775 UT WOS:A1996UC77500025 PM 8642297 ER PT J AU Altekruse, SF Street, DA Fein, SB Levy, AS AF Altekruse, SF Street, DA Fein, SB Levy, AS TI Consumer knowledge of foodborne microbial hazards and food-handling practices SO JOURNAL OF FOOD PROTECTION LA English DT Article DE consumer; food handling; Salmonella; survey ID UNITED-STATES; SAFETY; DISEASE AB A national telephone survey was conducted of 1,620 randomly selected U.S. residents who spoke English, were at least 18 years old, and resided in households with kitchen facilities. Respondents were interviewed about their recognition of foodborne pathogens, foods at risk for transmitting infection, knowledge of safe food handling, and food-handling practices. One-third of the respondents who prepared meals reported unsafe food hygiene practices: e.g., they did not wash hands or take precautions to prevent cross-contamination from raw meat. Unsafe practices were reported more often by men, adults 18 to 29 years of age, and occasional food preparers than by women, persons 30 years old or older, and frequent food preparers. Respondents who identified a food vehicle for Salmonella spp. were more likely to report washing their hands and cleaning cutting boards after preparing raw meat and poultry. The results raise concerns about consumer food-handling practices. The influence of food safety training, food-handling experience, and age on food-handling practices should be studied further. Awareness of a food vehicle for Salmonella spp., for example, may indicate knowledge of the etiology of foodborne disease that promotes safe food handling. Understanding the factors associated with safe food handling will assist in development of effective safe-food instruction programs. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,OFF SCI ANAL & SUPPORT,DIV MARKET STUDIES,WASHINGTON,DC 20204. NR 21 TC 143 Z9 149 U1 3 U2 13 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2838 SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD MAR PY 1996 VL 59 IS 3 BP 287 EP 294 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA UA875 UT WOS:A1996UA87500012 PM 10463448 ER PT J AU Rosen, R Winestock, K Liu, X Hennighausen, L Finbloom, DS AF Rosen, R Winestock, K Liu, X Hennighausen, L Finbloom, DS TI Differential activation of STAT5A and STAT5B by granulocyte-macrophage colony stimulating factor (GMCSF) in human peripheral blood monocytes. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIDDK,NIH,BETHESDA,MD. US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A230 EP A230 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700198 ER PT J AU Styrt, BA AF Styrt, BA TI Cooling blanket use in fever: A survey of critical care providers. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 US FDA,CTR DRUG EVALUAT & RES,OFF EPIDEMIOL & BIOSTAT,ROCKVILLE,MD 20857. HARVARD UNIV,SCH PUBL HLTH,MPH PROGRAM,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A324 EP A324 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700731 ER PT J AU Perrin, PJ Scott, D Davis, TA Gray, GS Doggett, MJ Abe, R June, CH Racke, MK AF Perrin, PJ Scott, D Davis, TA Gray, GS Doggett, MJ Abe, R June, CH Racke, MK TI Opposing effects of CTLA4-Ig and anti-CD80 (B7-1) plus anti-CD86(B7-2) on experimental allergic encephalomyelitis SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE B7 receptors; CD80; CD86; CTLA-4; experimental allergic encephalomyelitis; interleukin-10; interleukin-2; interferon-gamma; tumor necrosis factor-alpha ID T-CELL ACTIVATION; MYELIN BASIC-PROTEIN; AUTOIMMUNE DEMYELINATION; CLONAL ANERGY; LYMPHOCYTE-T; CTLA-4; ANTIGEN; LIGAND; CD28; ANTIBODIES AB The roles of the B7 receptors, CD80 and CD86, during actively induced experimental allergic encephalomyelitis were examined with specific monoclonal antibodies and CTLA4-Ig. Injection of CTLA4-Ig on day 2 post-immunization resulted in decreased incidence and severity of resultant disease. Anti-CD80 injection on day 2 blocked development of the first disease episode. Subsequent relapses were unaffected. In contrast, injection of anti-CD86 alone had no effect. Surprisingly, combined anti-CD80 + anti-CD86 monoclonal antibody injection on day 2 resulted in marked exacerbation of disease. Examination of cytokine production in the draining lymph node cells demonstrated a reduction in both interferon (IFN)-gamma and interleukin (IL)-2 producing cells, but a dramatic increase in tumor necrosis factor (TNF)-alpha secretion in animals receiving both monoclonal antibodies. These results suggest distinct roles for CD80 and CD86 in the initiation of EAE, resulting in the diverse clinical outcomes observed in this model of EAE. C1 US FDA,BETHESDA,MD 20892. REPLIGEN CORP,CAMBRIDGE,MA 02139. WASHINGTON UNIV,SCH MED,DEPT NEUROL,ST LOUIS,MO 63110. RP Perrin, PJ (reprint author), USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,MAIL STOP 06,BETHESDA,MD 20889, USA. NR 48 TC 37 Z9 37 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD MAR PY 1996 VL 65 IS 1 BP 31 EP 39 DI 10.1016/0165-5728(95)00172-7 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA UL418 UT WOS:A1996UL41800004 PM 8642061 ER PT J AU Shank, FR Carson, K Glinsmann, WH AF Shank, FR Carson, K Glinsmann, WH TI Putting things in perspective: Building on our experience SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Ceres Forum Program on Making Health Claims Work, Fortifying Policy with Science - The Case of Folate CY JUN 04, 1995 CL GEORGETOWN UNIV, WASHINGTON, DC SP Ceres Forum, Amer Inst Nutr HO GEORGETOWN UNIV DE health claims; folic acid; food labeling; food fortification AB The science and policy underlying food labeling and food fortification have evolved over the past 30 years to a point where dietary guidance and nutrition labeling now provide consumers with highly sophisticated, very specific information about links between diet and health. The focus was once on prevention of nutrient deficiency diseases, but today it is on reducing the risk of chronic diseases and health-related conditions. The Nutrition Labeling and Education Act of 1990, with its provisions for authorization of health claims on food labels, has provided a gateway through which a broader realm of nutrition and health information can be made available to consumers. However, the interpretation and implementation of the health claim provisions must evolve, based on a strong foundation of supporting science, so that industry may more readily make health information available to consumers in a form that is easily understood and effectively used in making their dietary choices. We must develop a database to support claims of beneficial effects of food components. We must be assured that the beneficial effects are not outweighed by safety concerns. And we must develop an environment that is conducive to conducting the research to develop these data. This can only be accomplished through the collaborative efforts of industry, academia, consumers and public health agencies. RP Shank, FR (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DEPT HLTH & HUMAN SERV,200 C ST SW,WASHINGTON,DC 20204, USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAR PY 1996 VL 126 IS 3 BP S781 EP S787 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA TZ111 UT WOS:A1996TZ11100024 PM 8598565 ER PT J AU Yetley, EA Rader, JI AF Yetley, EA Rader, JI TI The challenge of regulating health claims and food fortification SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Ceres Forum Program on Making Health Claims Work, Fortifying Policy with Science - The Case of Folate CY JUN 04, 1995 CL GEORGETOWN UNIV, WASHINGTON, DC SP Ceres Forum, Amer Inst Nutr HO GEORGETOWN UNIV DE fortification; health claims; folic acid; neural tube defects; public policy ID NEURAL-TUBE DEFECTS; VITAMIN; RISK; PREVENTION AB The Food and Drug Administration has several options that will assist the Public Health Service in implementing its September 1992 recommendation that all women of childbearing age consume 0.4 mg of folic acid daily to reduce their risk of having a pregnancy affected with a neural tube defect. The FDA can authorize the use of a health claim on labels and in the labeling of foods that characterizes the relationship between a nutrient and a health-related condition. Fortification of cereal-grain products with folic acid is a second option that has the potential for reaching most women of childbearing age without requiring them to change their food selection patterns. Consideration of these options has been intertwined with rapid developments in the scientific database that is the foundation of the health claim, by conflicting opinions regarding the effectiveness for women in the target population of FDA's proposed level of cereal-grain fortification, by lack of systematic safety data regarding the impact of fortification on persons in the general population and by changes in the regulatory environment in which the agency acts. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,OFF SPECIAL NUTR,WASHINGTON,DC 20204. RP Yetley, EA (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,OFF FOOD LABELING,HFS-175,200 C ST SW,WASHINGTON,DC 20204, USA. NR 19 TC 7 Z9 7 U1 1 U2 2 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAR PY 1996 VL 126 IS 3 BP S765 EP S772 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA TZ111 UT WOS:A1996TZ11100022 PM 8598563 ER PT J AU Levy, AS Fein, SB Schucker, RE AF Levy, AS Fein, SB Schucker, RE TI Performance characteristics of seven nutrition label formats SO JOURNAL OF PUBLIC POLICY & MARKETING LA English DT Article ID INFORMATION AB The authors evaluate seven nutrition label formats to determine consumer comprehension and acceptance of displayed information. They test comprehension on five tasks: comparing two products, judging healthfulness, verifying claims, estimating servings needed to meet the daily requirement for a nutrient, and balancing nutrients in a daily diet. Performance scores were higher on some tasks-particularly dietary management ones-for formats that displayed nutrient amounts in percentages than for those that displayed nutrient amounts in metric units, even when interpretational aids were included on the metric formats. The two most preferred formats were metric formats with an interpretational aid. The findings have an important impact on decisions about the final nutrition label format required by the Food and Drug Administration. C1 US FDA,DIV MARKET STUDIES,CTR FOOD SAFETY & APPL NUTR,ROCKVILLE,MD 20857. RP Levy, AS (reprint author), US FDA,CONSUMER STUDIES BRANCH,ROCKVILLE,MD 20857, USA. NR 43 TC 70 Z9 70 U1 0 U2 3 PU AMER MARKETING ASSN PI CHICAGO PA 250 SOUTH WACKER DRIVE SUITE 200, CHICAGO, IL 60606-5819 SN 0743-9156 J9 J PUBLIC POLICY MARK JI J. Public Policy Mark. PD SPR PY 1996 VL 15 IS 1 BP 1 EP 15 PG 15 WC Business SC Business & Economics GA UL677 UT WOS:A1996UL67700002 ER PT J AU Mackey, EA Anderson, DL ChenMayer, H Downing, RG Greenberg, RR Lamaze, GP Lindstrom, RM Mildner, DFR Paul, RL AF Mackey, EA Anderson, DL ChenMayer, H Downing, RG Greenberg, RR Lamaze, GP Lindstrom, RM Mildner, DFR Paul, RL TI Use of neutron beams for chemical analysis at NIST SO JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY-ARTICLES LA English DT Article ID RAY ACTIVATION-ANALYSIS; PROMPT-GAMMA ACTIVATION; CAPILLARY OPTICS; SCATTERING; BORON; FACILITY; GUIDANCE; RATES AB At the National Institute of Standards and Technology, there are two techniques for chemical analysis that use neutron beams from the reactor for target irradiation: neutron depth profiling (NDP) and prompt gamma-ray activation analysis (PGAA). There are two facilities for each technique, one equipped with a thermal neutron beam and the other, with a cold neutron beam. In addition, focused beams of cold neutrons will be used to measure the two-dimensional element distributions by PGAA and three-dimensional distributions by NDP. This paper includes a brief description of the facilities, the measurement capabilities of each, some recent applications of NDP and PGAA, and neutron focusing as applied to these techniques. C1 US FDA,ELEMENTAL RES BRANCH HFS338,WASHINGTON,DC 20204. RP Mackey, EA (reprint author), NIST,DIV ANALYT CHEM,GAITHERSBURG,MD 20899, USA. NR 70 TC 2 Z9 2 U1 1 U2 2 PU AKADEMIAI KIADO PI BUDAPEST PA PO BOX 245, H-1519 BUDAPEST, HUNGARY SN 0236-5731 J9 J RADIOAN NUCL CH AR JI J. Radioanal. Nucl. Chem.-Artic. PD MAR PY 1996 VL 203 IS 2 BP 413 EP 427 DI 10.1007/BF02041520 PG 15 WC Chemistry, Analytical; Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA UM201 UT WOS:A1996UM20100014 ER PT J AU Yoshikawa, T Stanberry, LR Bourne, N Krause, PR AF Yoshikawa, T Stanberry, LR Bourne, N Krause, PR TI Downstream regulatory elements increase acute and latent herpes simplex virus type 2 latency-associated transcript expression but do not influence recurrence phenotype or establishment of latency SO JOURNAL OF VIROLOGY LA English DT Article ID TRIGEMINAL GANGLIA; INFECTED NEURONS; MESSENGER-RNA; PROMOTER; REACTIVATION; SEQUENCE; REGION; INVIVO; GENE; SITE AB The role of putative promoter or activator sequences downstream of the herpes simplex virus ape 2 latency-associated transcript (LAT) promoter and upstream of the LAT intron was investigated in vivo by constructing and evaluating mutant viruses with deletions in this region. The deletion of LAT promoter sequences upstream of the primary LAT transcript reduced levels of LAT expression during productive infections, compared with the LAT expression level of wild-type virus, and abolished LAT expression during latency. The deletion of the putative downstream regulatory elements reduced but did not eliminate LAT expression during productive and latent infections. The deletion of both regions almost completely eliminated acute LAT transcription, although additional acute LAT-region transcription directed by sequences upstream of either region was detected by reverse transcriptase PCR. The deletion of the downstream elements did not influence the ability of the virus to reactivate from latently infected guinea pigs relative to the ability of the wild-type virus to reactivate; thus, decreased LAT expression did not affect the frequency of recurrence. The deletion of both regions did not affect the ability of the virus to establish latency. We conclude that downstream regulatory elements are necessary for maximal acute LAT expression but do not constitute an independent promoter during latency and do not play an obvious role in the establishment of or reactivation from latency. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,BETHESDA,MD. UNIV CINCINNATI,COLL MED,CHILDRENS HOSP RES FDN,DEPT PEDIAT,DIV INFECT DIS,CINCINNATI,OH. FU NIAID NIH HHS [AI2266] NR 43 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1996 VL 70 IS 3 BP 1535 EP 1541 PG 7 WC Virology SC Virology GA TV696 UT WOS:A1996TV69600025 PM 8627672 ER PT J AU Volmer, DA Vollmer, DL Wilkes, JG AF Volmer, DA Vollmer, DL Wilkes, JG TI Multiresidue analysis of pesticides by electrospray LC-MS and LC-MS-MS SO LC GC-MAGAZINE OF SEPARATION SCIENCE LA English DT Article ID CHROMATOGRAPHY MASS-SPECTROMETRY; AQUEOUS ENVIRONMENTAL-SAMPLES; METHYL CARBAMATE PESTICIDES; POLAR PESTICIDES; TEMPERATURE; WATERS RP Volmer, DA (reprint author), US FDA,NATL CTR TOXICOL RES,HFT-233,3900 NCTR DR,JEFFERSON,AR 72079, USA. RI Volmer, Dietrich/G-7900-2012 OI Volmer, Dietrich/0000-0003-2820-1480 NR 20 TC 11 Z9 11 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 SN 0888-9090 J9 LC GC-MAG SEP SCI JI LC GC-Mag. Sep. Sci. PD MAR PY 1996 VL 14 IS 3 BP 216 EP & PG 5 WC Chemistry, Analytical SC Chemistry GA VG467 UT WOS:A1996VG46700004 ER PT J AU Volmer, DA Vollmer, DL AF Volmer, DA Vollmer, DL TI Interfacing liquid chromatography with mass spectrometry and tandem mass spectrometry SO LC GC NORTH AMERICA LA English DT Article ID ION-SOURCE; THERMOSPRAY RP Volmer, DA (reprint author), US FDA, NATL CTR TOXICOL RES, HFT-233, 3900 NCTR DR, JEFFERSON, AR 72079 USA. RI Volmer, Dietrich/G-7900-2012 OI Volmer, Dietrich/0000-0003-2820-1480 NR 16 TC 8 Z9 8 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS INC PI DULUTH PA 131 W 1ST STREET, DULUTH, MN 55802 USA SN 1527-5949 EI 1939-1889 J9 LC GC N AM JI LC GC N. AM. PD MAR PY 1996 VL 14 IS 3 BP 236 EP + PG 0 WC Chemistry, Analytical SC Chemistry GA VG467 UT WOS:A1996VG46700007 ER PT J AU Sutherland, JB Evans, FE Freeman, JP Williams, AJ AF Sutherland, JB Evans, FE Freeman, JP Williams, AJ TI Biotransformation of quinoxaline by Streptomyces badius SO LETTERS IN APPLIED MICROBIOLOGY LA English DT Article ID PSEUDOMONAS-PUTIDA; CONSTITUENTS; METABOLISM AB Quinoxaline, a mutagenic azaarene produced in foods during cooking, was added to cultures of Streptomyces badius ATCC 39117. After 24 h, the cultures were extracted with ethyl acetate. Two major metabolites were purified by liquid chromatography and identified by mass spectrometry and nuclear magnetic resonance spectroscopy as 3,4-dihydro-2(1H)-quinoxalinone and 2(1H)-quinoxalinone. RP Sutherland, JB (reprint author), US FDA,NATL CTR TOXICOL RES,DIV MICROBIOL,JEFFERSON,AR 72079, USA. NR 15 TC 8 Z9 8 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0266-8254 J9 LETT APPL MICROBIOL JI Lett. Appl. Microbiol. PD MAR PY 1996 VL 22 IS 3 BP 199 EP 201 DI 10.1111/j.1472-765X.1996.tb01142.x PG 3 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA TZ232 UT WOS:A1996TZ23200004 PM 8852347 ER PT J AU Kuznetsov, VA Ivshina, AV Senko, OV Kuznetsova, AV AF Kuznetsov, VA Ivshina, AV Senko, OV Kuznetsova, AV TI Syndrome approach for computer recognition of fuzzy systems and its application to immunological diagnostics and prognosis of human cancer SO MATHEMATICAL AND COMPUTER MODELLING LA English DT Article DE fuzzy systems; pattern recognition; lymphocytes; cancer; prognosis ID MONOCLONAL-ANTIBODIES; HUMAN OSTEOSARCOMA; OSTEO-SARCOMA; CELLS AB We propose a novel pattern recognition method for the processing of a great number of ''fuzzy'' features in small groups of objects with small differences of features among the groups and with the missing of some data. Our algorithm dealing with statistical weighted syndromes (SWS) is based on the three-level feedback processing of fuzzy sets: recasting procedures of continual features to the gradations, optimization procedures of selection of the informative subareas (syndromes) in the feature space, and statistically weighted calculation of these subareas for prognosis of the class number function. At the training phase of the SWS method, the special likelihood function for the distribution of objects on the subareas is constructed. At all algorithm steps for control of stabilization and reproducing of the results, the jackknife procedure is used. The SWS method has been applied to analysis of flow cytometry measurements of the lymphocyte subpopulations in blood before treatment of osteosarcoma patients. We selected the small sets of the features from among. about 40 immunological features which allowed us to predict correctly the widespread metastases and to forecast successfully the outcome of preoperation chemotherapy of the patients with osteosarcoma. Thus, for the first time, the information about lymphocyte subpopulations in the blood is effectively used for individual diagnostics, staging and prognosis of patients with the low-immunogeneic solid human tumor. C1 RUSSIAN CANC RES CTR,LAB CLIN RADIOIMMUNOL,MOSCOW 115478,RUSSIA. RUSSIAN ACAD SCI,CTR COMP,MOSCOW 117964,RUSSIA. RUSSIAN ACAD SCI,INST CHEM PHYS,LAB MATH IMMUNOBIOPHYS,MOSCOW 117977,RUSSIA. RP Kuznetsov, VA (reprint author), US FDA,LAB MOL TUMOR BIOL,CTR BIOL EVALUAT & RES,BLDG 29B,ROOM 2G07,BETHESDA,MD 20892, USA. NR 43 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-7177 J9 MATH COMPUT MODEL JI Math. Comput. Model. PD MAR PY 1996 VL 23 IS 6 BP 95 EP 119 DI 10.1016/0895-7177(96)00021-0 PG 25 WC Computer Science, Interdisciplinary Applications; Computer Science, Software Engineering; Mathematics, Applied SC Computer Science; Mathematics GA UD577 UT WOS:A1996UD57700007 ER PT J AU McCarthy, SA AF McCarthy, SA TI Effects of temperature and salinity on survival of toxigenic Vibrio cholerae O1 in seawater SO MICROBIAL ECOLOGY LA English DT Article ID CHESAPEAKE BAY; COASTAL WATERS; GULF-COAST; NON-O1; ECOLOGY; ENVIRONMENTS; GROWTH; BANGLADESH; MICROCOSMS; ESTUARIES AB In 1991 and 1992, the Latin American epidemic strain of Vibrio cholerae 01 was isolated from ballast water, bilge water, and sewage taken from cargo ships docked in Mobile Bay, Alabama. The findings raised questions regarding the organism's ability to survive long-term aboard ships and to withstand the exchange of ballast at sea. The effects of temperature (6, 18, and 30 degrees C) and salinity (8, 16, and 32 ppt) on survival of V. cholerae 01 strains C6706 and C6707 and a ballast water isolate in sterile seawater were determined. The ballast water isolate, which had a D-value (number of days required to produce a 1 log(10) reduction in colony-forming units per milliliter) of 240 days at 18 degrees C, 32 ppt salinity, had the longest survival time. The range of D-values was 36-240 days at 18 degrees C, 60-120 days at 30 degrees C, and 5-20 days at 6 degrees C. In sterile seawater short-term survival was temperature dependent, whereas long-term survival was salinity dependent. In raw seawater, survival time of the ballast water isolate was reduced to 12-27 days, implying the existence of biological influences. As also shown in our previous work, the organism appeared to be able to survive for several months under relatively stable conditions in ballast water aboard ships; however, viability may be reduced to only a few weeks after the organism is introduced into estuarine or marine environments. RP McCarthy, SA (reprint author), US FDA,GULF COAST SEAFOOD LAB,POB 158,DAUPHIN ISL,AL 36528, USA. NR 38 TC 11 Z9 13 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0095-3628 J9 MICROBIAL ECOL JI Microb. Ecol. PD MAR-APR PY 1996 VL 31 IS 2 BP 167 EP 175 PG 9 WC Ecology; Marine & Freshwater Biology; Microbiology SC Environmental Sciences & Ecology; Marine & Freshwater Biology; Microbiology GA TX481 UT WOS:A1996TX48100005 PM 24185740 ER PT J AU Misiewicz, B Zelazowska, E Raybourne, RB Cizza, G Sternberg, EM AF Misiewicz, B Zelazowska, E Raybourne, RB Cizza, G Sternberg, EM TI Inflammatory responses to carrageenan injection in LEW/N and F344/N rats: LEW/N rats show sex- and age-dependent changes in inflammatory reactions SO NEUROIMMUNOMODULATION LA English DT Article DE corticotropin-releasing hormone; hypothalamus; carrageenan; inflammation ID CD4+ T-CELLS; TYROSINE-PHOSPHATASE; SIGNAL-TRANSDUCTION; ANIMAL-MODELS; IMMUNE; AUTOIMMUNITY; ACTIVATION; EXPRESSION; RECEPTOR; SUBSETS AB We studied the inflammatory responses of LEW/N and F344/N inbred rat strains after peripheral injection of carrageenan. The inflammatory responses were assessed in terms of volume, relative and total white blood cell counts of the exudates. Moreover, in both strains, blood CD4, CD8, CD25, naive CD4 (CD4/CD45RC) cell and B (CD45R) cell counts and plasma corticosterone levels, constituents of systemic inflammatory responses to carrageenan were evaluated. In general, LEW/N rats are highly responsive to challenge with carrageenan, whereas F344 rats are not. The strong local inflammatory responses to carrageenan are primarily exhibited by female LEW/N rats. The intensity of local inflammatory responses of LEW/N rats changes with the rat age, the highest exhibited by LEW/N rats up to 3 months of age, thereafter the carrageenan-induced inflammatory responses decline. Our results indicate that peripheral injection of carrageenan induces strong systemic immune component. After carrageenan injection, increases in CD8 and naive CD4 blood lymphocytes are seen. Although the carrageenan challenge does not change CD4 blood lymphocytes in both LEW/N and F344/N rat strains, LEW/N rats exhibit higher levels of CD4 cells than F344/N rats, Additionally, LEW/N rats demonstrated lower levels of B cells and higher naive CD4 lymphocytes. Carrageenan challenges induce significant increases in plasma corticosterone response in F344/N rats, as well as increases in LEW/N rats 1 h after injection. Our data stress the importance of rat age and gender in experiments studying inflammatory responses. C1 US FDA,LAUREL,MD. RP Misiewicz, B (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,SECT NEUROENDOCRINE IMMUNOL & BEHAV,BLDG 10,RM 3S 231,BETHESDA,MD 20892, USA. NR 40 TC 15 Z9 15 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PD MAR-JUN PY 1996 VL 3 IS 2-3 BP 93 EP 101 DI 10.1159/000097233 PG 9 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA VT878 UT WOS:A1996VT87800005 PM 8945724 ER PT J AU Morris, P Binienda, Z Gillam, MP Harkey, MR Zhou, C Henderson, GL Paule, MG AF Morris, P Binienda, Z Gillam, MP Harkey, MR Zhou, C Henderson, GL Paule, MG TI The effect of chronic cocaine exposure during pregnancy on maternal and infant outcomes in the rhesus monkey SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE rhesus; cocaine; pregnancy; mother; infant; outcome ID OPERANT TEST BATTERY; PROGRESSIVE RATIO; DRUG-USE; FETAL; HAIR; GROWTH; ABUSE; PHARMACOKINETICS; PERFORMANCE; PARAMETERS AB To explore the effects of gestational cocaine exposure in a nonhuman primate model, pregnant rhesus monkeys were treated from about 1 month of gestation until term with either 0 (N = 3), 0.3 (N = 3), 1.0 (N = 3), or escalating doses up to 8.5 (N = 3) mg/kg (IM), three times per day, 5 consecutive days per week. Despite these differences in cocaine exposure, the experimental groups did not differ significantly with respect to maternal outcome, as measured by body weight gain during pregnancy and length of pregnancy. A clear dose-response relationship was observed between the cumulative dose of cocaine administered during gestation and the levels of both cocaine and its major metabolite, benzoylecgonine, in samples of infant hair taken at birth. However, the experimental groups did not differ significantly with respect to infant outcome, as measured at birth by body weight, overall length, crown-to-rump length, rump-to-heel length, biparietal diameter, and crown circumference. Furthermore, the experimental groups did not differ significantly with respect to the integrity of a variety of infant reflexes tested at birth. It was concluded that, in a rhesus monkey model, chronic cocaine exposure during pregnancy had no significant effect on maternal and infant outcomes as assessed in this investigation. C1 UNIV CALIF DAVIS,DEPT MED PHARMACOL & TOXICOL,DAVIS,CA 95616. UNIV ARKANSAS MED SCI HOSP,DEPT PEDIAT,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & TOXICOL,LITTLE ROCK,AR 72205. RP Morris, P (reprint author), US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,3900 NCTR RD HFT-132,JEFFERSON,AR 72079, USA. FU PHS HHS [224-89-003] NR 48 TC 26 Z9 27 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAR-APR PY 1996 VL 18 IS 2 BP 147 EP 154 DI 10.1016/0892-0362(95)02030-6 PG 8 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA UC066 UT WOS:A1996UC06600004 PM 8709926 ER PT J AU Morris, P Gillam, MP Allen, RR Paule, MG AF Morris, P Gillam, MP Allen, RR Paule, MG TI The effect of chronic cocaine exposure during pregnancy on the acquisition of operant behaviors by rhesus monkey offspring SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE rhesus; cocaine; pregnancy; offspring; operant; behavior ID TEST BATTERY; NEONATAL GROWTH; MATERNAL-FETAL; DRUG-USE; PERFORMANCE; ABUSE; PHARMACOKINETICS; TOXICOLOGY; INTRANASAL; KINETICS AB To explore possible long-term effects of gestational cocaine exposure in a nonhuman primate model, pregnant rhesus monkeys were treated from about 1 month of gestation until term with either 0 (N = 3), 0.3 (N = 3), 1.0 (N = 3), or escalating doses up to 8.5 (N = 3) mg/kg (IM), three times per day, 5 consecutive days per week. Despite these differences in cocaine exposure, the experimental groups did not differ significantly with respect to the postnatal growth of offspring over an 18-month period following birth. Beginning at 6 months of age, the behavior of offspring was monitored using an operant test battery that included five food reinforced tasks designed to model aspects of learning, color and position discrimination, rime estimation, short-term memory and attention, and motivation. Although the acquisition of each operant behavior by offspring progressed significantly during training between 6 and 18 months of age, this acquisition was not differentially affected by gestational cocaine exposure. It was concluded that, in a rhesus monkey model, chronic cocaine exposure during pregnancy had no significant effect on the offsprings' acquisition of operant behaviors. C1 US FDA,NATL CTR TOXICOL RES,COMP BASED SYST INC,JEFFERSON,AR 72079. UNIV ARKANSAS MED SCI HOSP,DEPT PEDIAT,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & TOXICOL,LITTLE ROCK,AR 72205. RP Morris, P (reprint author), US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,3900 NCTR RD HFT-132,JEFFERSON,AR 72079, USA. FU PHS HHS [224-89-003] NR 74 TC 19 Z9 19 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAR-APR PY 1996 VL 18 IS 2 BP 155 EP 166 DI 10.1016/0892-0362(95)02031-4 PG 12 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA UC066 UT WOS:A1996UC06600005 PM 8709927 ER PT J AU Ferguson, SA Felipa, HN Bowman, RE AF Ferguson, SA Felipa, HN Bowman, RE TI Effects of acute treatment with dopaminergic drugs on open field behavior of adult monkeys treated with lead during the first year postpartum SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE monkey; open field; lead treatment; haloperidol; apomorphine; dopaminergic drugs ID STIMULUS PROPERTIES; RHESUS-MONKEYS; APOMORPHINE; EXPOSURE; HALOPERIDOL; AGONISTS AB A pharmacological challenge of nonhuman primate open field behavior, similar to that which pre previously assessed the cholinergic system (10), was used here to measure potential lead-induced alterations in the dopaminergic system. Monkeys that had been treated with lead during the first year postpartum were assessed at 7 years of age in the open field after acute intramuscular injection of apomorphine (0.0-0.3 mg/kg) or haloperidol (0.0-30 mu g/kg). Duration of environmental exploration indicated a possible greater responsivity to 0.2 mg/kg apomorphine in the lead-treated monkeys; however, in all other behaviors, lead-treated monkeys responded to both drugs similarly to controls. Regardless of lead treatment, apomorphine administration decreased duration of inactivity and increased environmental exploration; the latter possibly included an increase in stereotypical behavior that might have been recorded as environmental exploration. Haloperidol had no significant effects on open field behavior over the dose range tested. Open field behavioral alterations previously reported for these monkeys at 4-6 years of age were no longer strongly exhibited by the lead-treated monkeys in any portion of the current study. Latency to enter the open field was marginally increased in the lead-treated group but levels of environmental exploration were comparable to controls. These results indicate an attenuation of lead-related effects with maturity and/or familiarity with the open field. C1 UNIV WISCONSIN,DEPT PSYCHOL,HARLOW PRIMATE LAB,MADISON,WI 53715. RP Ferguson, SA (reprint author), NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,HFT-130,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 24 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAR-APR PY 1996 VL 18 IS 2 BP 181 EP 188 DI 10.1016/0892-0362(95)02050-0 PG 8 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA UC066 UT WOS:A1996UC06600008 PM 8709930 ER PT J AU Hall, CB Chesney, PJ Gromisch, DS Halsey, NA Kohl, S Marcy, SM Marks, MI Nankervis, GA Overall, JC Pickering, LK Steele, RW Yogev, R Peter, G Berkelman, RL Orenstein, WA Hardegree, MC Jacobs, RF MacDonald, NE Rabinovich, NR Hall, MS Boucher, F Delage, G FordJones, E King, SE Speert, DP Tan, BJK Friesen, FR Marchessault, V Carlson, JAK Scheifele, DW Waters, JR AF Hall, CB Chesney, PJ Gromisch, DS Halsey, NA Kohl, S Marcy, SM Marks, MI Nankervis, GA Overall, JC Pickering, LK Steele, RW Yogev, R Peter, G Berkelman, RL Orenstein, WA Hardegree, MC Jacobs, RF MacDonald, NE Rabinovich, NR Hall, MS Boucher, F Delage, G FordJones, E King, SE Speert, DP Tan, BJK Friesen, FR Marchessault, V Carlson, JAK Scheifele, DW Waters, JR TI Meningococcal disease prevention and control strategies for practice-based physicians SO PEDIATRICS LA English DT Article ID CAPSULAR POLYSACCHARIDE VACCINE; SINGLE-DOSE CIPROFLOXACIN; A NEISSERIA-MENINGITIDIS; NASOPHARYNGEAL CARRIERS; EPIDEMIC; POPULATION; CHILDREN; INFANTS; OUTBREAK; CONTACTS AB Localized outbreaks of meningococcal disease in the United States and Canada continue to cause serious alarm within communities as a result of the fulminating pattern of the disease, high mortality rate, and high incidence among adolescents. The increasing number of outbreaks since 1991 has raised questions about the management and prevention of further cases during an outbreak. The purpose of this statement is to guide primary-care physicians in their role in infection control and prevention of both sporadic cases and outbreaks of invasive meningococcal disease. This statement provides information on the epidemiology of meningococcal disease, including definitions of sporadic, secondary, and coprimary cases, clusters of cases, and outbreaks. Data are presented on identification of cases, disease risk of contacts, and agents for chemoprophylaxis, and recommendations are given for: (I) risk assessment of contacts, (2) administration of chemoprophylaxis, (3) appropriate use of meningococcal. vaccine, (4) appropriate use of the microbiology laboratory, (5) the necessity for timely and appropriate reporting of invasive meningococcal disease to local public health authorities, and (6) information on counseling and public education that may be helpful during an outbreak to minimize public anxiety. An additional section, ''Information for Sharing,'' which uses a question-and-answer format and which may be helpful to parents and community and health care workers during an outbreak, is also provided. C1 CDCP,ATLANTA,GA. US FDA,ROCKVILLE,MD 20857. AMER THORAC SOC,NEW YORK,NY. NIH,BETHESDA,MD 20892. AMER ACAD PEDIAT,EVANSTON,IL. NR 69 TC 23 Z9 25 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 1996 VL 97 IS 3 BP 404 EP 412 PG 9 WC Pediatrics SC Pediatrics GA TY580 UT WOS:A1996TY58000023 ER PT J AU Klish, WJ Baker, SS Flores, CA Georgieff, MK Lake, AM Leibel, RL Udall, JN Cheney, M Daniels, PN Harris, SS Hubbard, VS Levin, E Prendergast, A Smith, AE Yetley, E Yip, R Zlotkin, S Lauer, RM Bell, EF AF Klish, WJ Baker, SS Flores, CA Georgieff, MK Lake, AM Leibel, RL Udall, JN Cheney, M Daniels, PN Harris, SS Hubbard, VS Levin, E Prendergast, A Smith, AE Yetley, E Yip, R Zlotkin, S Lauer, RM Bell, EF TI Aluminum toxicity in infants and children SO PEDIATRICS LA English DT Article ID CHRONIC-RENAL-FAILURE; PARENTERAL-NUTRITION; CALCIUM ACETATE; ENCEPHALOPATHY; DIALYSIS; INTOXICATION; ACCUMULATION; HYDROXIDE; UREMIA; BONE C1 BUR NUTR SCI,OTTAWA,ON,CANADA. USDA,WASHINGTON,DC 20250. NIDDKD,BETHESDA,MD 20892. NICHHD,BETHESDA,MD 20892. AMER DIETET ASSOC,CHICAGO,IL. US FDA,ROCKVILLE,MD 20857. CDCP,ATLANTA,GA 30341. NR 35 TC 35 Z9 36 U1 1 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 1996 VL 97 IS 3 BP 413 EP 416 PG 4 WC Pediatrics SC Pediatrics GA TY580 UT WOS:A1996TY58000024 ER PT J AU Tozer, TN Bois, FY Hauck, WW Chen, ML Williams, RL AF Tozer, TN Bois, FY Hauck, WW Chen, ML Williams, RL TI Absorption rate vs exposure: Which is more useful for bioequivalence testing? SO PHARMACEUTICAL RESEARCH LA English DT Article DE absorption rate; bioequivalence; C-max/AUC(lqc); C-max; AUC; exposure AB Purpose. The goals were to evaluate the usefulness of C-max/AUC(1qc), ratio of the maximum plasma drug concentration to the area under the plasma concentration-time curve to the time of the last quantifiable concentration, in bioequivalence testing and to explore the use of exposure as a replacement for the concepts of rate and extent of drug absorption. Methods. The bioequivalence of products differing in both rate (ka) and extent (F) of absorption was assessed under conditions similar to those encountered in a typical trial. A one-compartment model drug with first-order absorption (rate constant = ka) and elimination was used. Variability was introduced in all model parameters using Monte Carlo techniques. The results were expressed in terms of the probability of declaring bioequivalence in a cross-over trial with 24 subjects using C-max/AUC(1qc), AUC(1qc), and C-max as bioequivalence measures. Results. The outcome of a bioequivalence trial was shown to depend on the measure. C-max/AUC(1qc) reflected changes in ka, but not in F. AUC(1qc) showed dependence on F, but virtually no dependence on ka. For C-max a 3- to 4-fold increase in ka and a concomittant 20% decrease in F, as well as corresponding changes in the opposite directions, resulted in bioequivalent outcomes. Conclusions. It was concluded that use of Cmax/AUC(1qc) should be discouraged and that defining bioequivalence in terms of rate and extent of absorption has major problems. The goal of bioequivalence trials should be to assure that the shape of the concentration-time curve of the test product is sufficiently similar to that of the reference product. To this end, the use of ''exposure'' rather than ''rate and extent of absorption'' concepts is encouraged. C1 UNIV CALIF BERKELEY,LAWRENCE BERKELEY LAB,INDOOR ENVIRONM PROGRAM,BERKELEY,CA 94720. THOMAS JEFFERSON UNIV,BIOSTAT SECT,DIV CLIN PHARMACOL,PHILADELPHIA,PA 19107. US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. RP Tozer, TN (reprint author), UNIV CALIF SAN FRANCISCO,SCH PHARM,DEPT PHARM,SAN FRANCISCO,CA 94143, USA. RI Bois, Frederic/E-9241-2012 OI Bois, Frederic/0000-0002-4154-0391 NR 15 TC 47 Z9 47 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD MAR PY 1996 VL 13 IS 3 BP 453 EP 456 DI 10.1023/A:1016061013606 PG 4 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA UB418 UT WOS:A1996UB41800019 PM 8692741 ER PT J AU Matchette, LS Grossman, LW Hahn, DW Cooney, C AF Matchette, LS Grossman, LW Hahn, DW Cooney, C TI Induction of lambda prophage by 213 nm laser radiation: A quantitative comparison with 193 nm excimer radiation using image analysis SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID ASSAY; AGENTS AB We compared the DNA damage produced by radiation from two UV laser wavelengths, 213 nm and 193 nm, with that produced by noncoherent 254 nm radiation, Following irradiation of Escherichia coli BR339, a bacteriophage lambda lysogen containing the lacZ gene, prophage induction was measured by assaying for beta-galactosidase, Because of the limited penetration by UV laser wavelengths an agar overlay of the lysogen was used as the irradiation target, Irradiation of 254 nm was performed in buffer suspension followed by transfer of 5 mu L spots onto assay plants, Computer image analysis was used to monitor the rate of product formation, observed as an increase in optical density of the irradiated zones on assay plates, We found that the rate of product formation was a more reproducible unit of comparison than the optical density present at the end of the reaction. Although the rate of product formation was not linearly related to enzyme concentration, the data could be fit to a simple logarithmic function, Using this method, we concluded that the DNA damaging ability of 213 nm radiation was 10 times more efficient than 193 nm radiation and about 100 times less efficient than 254 nm noncoherent radiation. RP Matchette, LS (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,MAIL STOP HFZ-134,1901 CHAPMAN AVE,ROOM 6,ROCKVILLE,MD 20857, USA. NR 17 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAR PY 1996 VL 63 IS 3 BP 281 EP 285 DI 10.1111/j.1751-1097.1996.tb03026.x PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TZ947 UT WOS:A1996TZ94700006 PM 8881331 ER PT J AU Donoghue, DJ Hairston, H Gaines, SA Bartholomew, MJ Donoghue, AM AF Donoghue, DJ Hairston, H Gaines, SA Bartholomew, MJ Donoghue, AM TI Modeling residue uptake by eggs .1. Similar drug residue patterns in developing yolks following injection with ampicillin or oxytetracycline SO POULTRY SCIENCE LA English DT Article DE drug residues; ampicillin; oxytetracycline; model; eggs AB This study was conducted to model the pattern of antibiotic drug uptake within yolks of developing follicles. In two separate experiments, 16 hens were divided into equal groups (n = 8) and injected only once with either 400 mg/kg ampicillin or 200 mg/kg oxytetracycline (OTC: total hens = 32) approximately 1 h after oviposition. Twenty-four hours following injections, hens were euthanatized and the ovaries were collected. Yolks were dissected free from the individual follicles with a blunt probe. Individual large yellow yolks (greater than or equal to 0.2 g) and a pool of 5 small yellow yolks (< 0.2 g) were collected for determination of ampicillin or OTC content. Samples were prepared and assayed using an agar diffusion microbiological method. Selected parameters were not different (P > 0.05) between Experiments 1 and 2 and the data were combined. Results indicate that short-term drug exposure in hens produced incorporation of drug residues in developing yolks in a specific pattern that does not appear to be drug dependent (P > 0.05). These incurred residues are contained in developing yolks that are days to weeks from being ovulated. Drug residues were greater (total microgram content) in some of the less mature yolks vs the largest preovulatory yolk. This may lead to a sequential release of eggs with increasing residue content, even after drug withdrawal. These data were used to construct a model to predict the pattern of incurred residues in formed eggs following a hen's exposure to drugs or other contaminants. C1 US FDA,CTR VET MED,BIOMETR BRANCH,ROCKVILLE,MD 20855. USDA,GERMPLASM & GAMETE PHYSIOL LAB,AGR RES SERV,BELTSVILLE,MD 20705. RP Donoghue, DJ (reprint author), US FDA,AGR RES CTR,CTR VET MED,PHARMACOL & BIOCHEM BRANCH,BLDG 328-A,BELTSVILLE,MD 20705, USA. NR 16 TC 22 Z9 22 U1 0 U2 3 PU POULTRY SCIENCE ASSN INC PI CHAMPAIGN PA 309 W CLARK ST, CHAMPAIGN, IL 61802 SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PD MAR PY 1996 VL 75 IS 3 BP 321 EP 328 PG 8 WC Agriculture, Dairy & Animal Science SC Agriculture GA UB862 UT WOS:A1996UB86200006 PM 8778723 ER PT J AU Henck, JW Hilbish, KG Serabian, MA Cavagnaro, JA Hendrickx, AG Agnish, ND Kung, AHC Mordenti, J AF Henck, JW Hilbish, KG Serabian, MA Cavagnaro, JA Hendrickx, AG Agnish, ND Kung, AHC Mordenti, J TI Reproductive toxicity testing of therapeutic biotechnology agents SO TERATOLOGY LA English DT Article ID CD4; PHARMACOKINETICS; IMMUNOASSAYS; DISPOSITION; VIRUS; MOUSE; MODEL; ACID C1 MILES INC,ELKHART,IN 46515. US FDA,ROCKVILLE,MD 20852. UNIV CALIF DAVIS,CALIF REG PRIMATE RES CTR,DAVIS,CA 95616. HOFFMANN LA ROCHE INC,NUTLEY,NJ 07110. SKYLINE TECHNOL CONSULTING GRP INC,SAN FRANCISCO,CA 94133. GENENTECH INC,S SAN FRANCISCO,CA 94080. RP Henck, JW (reprint author), WARNER LAMBERT PARKE DAVIS,PARKE DAVIS PHARMACEUT RES,2800 PLYMOUTH RD,ANN ARBOR,MI 48105, USA. NR 33 TC 23 Z9 25 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0040-3709 J9 TERATOLOGY JI Teratology PD MAR PY 1996 VL 53 IS 3 BP 185 EP 195 DI 10.1002/(SICI)1096-9926(199603)53:3<185::AID-TERA6>3.0.CO;2-3 PG 11 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA UP045 UT WOS:A1996UP04500006 PM 8761886 ER PT J AU Nightingale, SL AF Nightingale, SL TI Fat substitute Olestra approved SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP Nightingale, SL (reprint author), US FDA,OFF HLTH AFFAIRS,PARKLAWN BLDG,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 28 PY 1996 VL 275 IS 8 BP 585 EP 585 DI 10.1001/jama.275.8.585 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA TW627 UT WOS:A1996TW62700031 PM 8594230 ER PT J AU Nightingale, SL AF Nightingale, SL TI New Reporting requirements for device user facilities SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP Nightingale, SL (reprint author), US FDA,OFF HLTH AFFAIRS,PARKLAWN BLDG,5611 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 28 PY 1996 VL 275 IS 8 BP 585 EP 585 DI 10.1001/jama.275.8.585 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA TW627 UT WOS:A1996TW62700030 PM 8594230 ER PT J AU Nightingale, SL AF Nightingale, SL TI New tuberculosis test approved SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP Nightingale, SL (reprint author), US FDA,OFF HLTH AFFAIRS,PARKLAWN BLDG,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 28 PY 1996 VL 275 IS 8 BP 585 EP 585 DI 10.1001/jama.275.8.585 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA TW627 UT WOS:A1996TW62700005 PM 8594230 ER PT J AU Wong, WK Lachenbruch, PA AF Wong, WK Lachenbruch, PA TI Tutorial in biostatistics designing studies for dose response SO STATISTICS IN MEDICINE LA English DT Article ID REGRESSION AB 'Dose response' refers to the regression of a response on a stimulus. We review a number of options for dose-response designs, and compare various designs which may be used in practice. We start with two group designs. Next, we introduce basic optimal approximate design theory for simple linear and quadratic regression illustrating different criteria of optimality and their effect on the allocation of the levels of the dose. Then we obtain the efficiencies of these optimal. approximate designs and some simple designs which have intuitive appeal (symmetry, equal spacing of treatments, reduced numbers of observations at the highest and lowest doses). C1 US FDA,CBER,OELPS,HFM 215,ROCKVILLE,MD 20852. RP Wong, WK (reprint author), UNIV CALIF LOS ANGELES,DEPT BIOSTAT,LOS ANGELES,CA 90024, USA. NR 16 TC 19 Z9 19 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD FEB 28 PY 1996 VL 15 IS 4 BP 343 EP 359 DI 10.1002/(SICI)1097-0258(19960229)15:4<343::AID-SIM163>3.0.CO;2-F PG 17 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 TY774 UT WOS:A1996TY77400002 PM 8668866 ER PT J AU Sotomayor, RE Washington, MC AF Sotomayor, RE Washington, MC TI Formation of etheno and oxoethyl adducts in liver DNA from rats exposed subchronically to urethane in drinking water and ethanol SO CANCER LETTERS LA English DT Article DE DNA adducts; ethanol; urethane ID ETHYL CARBAMATE; VINYL CARBAMATE; MOUSE; MICE; ACTIVATION; METABOLISM; INHIBITION; TUMORS AB Exposure of Fisher-344 male rats to 10 000 ppm of urethane in drinking water for up to 90 days or in 5% ethanol for up to 14 days caused the formation of 7-[2'-oxoethyl]guanine (OEG) and 1,N-6-ethenoadenine (epsilon A) in liver DNA. Mild-acid DNA hydrolysates were analyzed by high-performance liquid chromatography with photodiode array detection and fluorometry. The identification of OEG and epsilon A was confirmed by coelution with the authentic standards. Forty and 67% of rats showed OEG and epsilon A adducts at 2 and 90 days of treatment with urethane in drinking water, respectively. In comparison, only 0 and 10% of rats showed adducts at 2 and 14 days of treatment with urethane in 5% ethanol, respectively, Neither OEG nor epsilon A was observed in control rats receiving water or 5% ethanol. Although these data are still preliminary, they appear to suggest that ethanol may inhibit formation of DNA adducts by urethane. Studies designed to produce more conclusive information about the role of ethanol in modifying DNA damage induced by urethane in vivo are in progress. RP Sotomayor, RE (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR HFS 509,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 26 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD FEB 27 PY 1996 VL 100 IS 1-2 BP 155 EP 161 DI 10.1016/0304-3835(95)04083-8 PG 7 WC Oncology SC Oncology GA TW796 UT WOS:A1996TW79600025 PM 8620436 ER PT J AU Freese, SJ Vann, WF AF Freese, SJ Vann, WF TI Synthesis of 2-acetamido-3-O-acetyl-2-deoxy-D-mannose phosphoramidites SO CARBOHYDRATE RESEARCH LA English DT Article DE N-acetylmannosamine phosphoramidites; N-acetylmannosamine; meningococcal polysaccharide C1 US FDA,CTR BIOL EVALUAT & RES,LAB BACTERIAL POLYSACCHARIDES,BETHESDA,MD 20892. NR 14 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD FEB 23 PY 1996 VL 281 IS 2 BP 313 EP 319 DI 10.1016/0008-6215(95)00345-2 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA TX992 UT WOS:A1996TX99200011 ER PT J AU Potterf, SB Muller, J Bernardini, I Tietze, F Kobayashi, T Hearing, VJ Gahl, WA AF Potterf, SB Muller, J Bernardini, I Tietze, F Kobayashi, T Hearing, VJ Gahl, WA TI Characterization of a melanosomal transport system in murine melanocytes mediating entry of the melanogenic substrate tyrosine SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEUKOCYTE GRANULAR FRACTIONS; LYSOSOMAL MEMBRANE-TRANSPORT; HUMAN FIBROBLAST LYSOSOMES; RAT-THYROID CELLS; CYSTINE TRANSPORT; AMINO-ACIDS; STIMULATION; NUTRITION; MELANOMA; DISEASE AB In this study, we identify a transport system for tyrosine, the initial precursor of melanin synthesis, in the melanosomes of murine melanocytes. Melanosomes preloaded with tyrosine demonstrated countertransport of 10 mu M [H-3]tyrosine, indicating carrier-mediated transport. Melanosomal tyrosine transport was saturable, with an apparent K-m for tyrosine transport of 54 mu M and a maximal velocity of 15 pmol of tyrosine/unit of hexosaminidase/min. Transport was temperature-dependent (E(alpha) = 7.5 kcal/mol) and showed stereospecificity for the L-isomer of tyrosine. Aromatic, neutral hydrophobic compounds (such as tryptophan and phenylalanine), as well as the small, bulky neutral amino acids (such as leucine, isoleucine, and methionine) competed for tyrosine transport. Tyrosine transport was inhibited by the classical system L analogue, 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid and by monoiodotyrosine, but not by cystine, lysine, glutamic acid, or 2-(methylamino)isobutyric acid. Tyrosine transport showed no dependence on Na+ or K+, and did not require an acidic environment or the availability of free thiols. These results demonstrate the existence of a neutral amino acid carrier in murine melanocyte melanosomes which resembles the rat thyroid FRTL-5 lysosomal system h. This transport system is critical to the function of the melanosome since tyrosine is the essential substrate required for the synthesis of the pigment melanin. C1 NICHHD,SECT HUMAN BIOCHEM GENET,HERITABLE DISORDERS BRANCH,BETHESDA,MD 20892. NCI,CELL BIOL LAB,BETHESDA,MD 20892. US FDA,DIV VIRAL PROD,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852. NIDDK,MOL & CELLULAR BIOL LAB,BETHESDA,MD 20892. NR 35 TC 38 Z9 38 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 23 PY 1996 VL 271 IS 8 BP 4002 EP 4008 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TW960 UT WOS:A1996TW96000010 PM 8626732 ER PT J AU Stancato, LF David, M CarterSu, C Larner, AC Pratt, WB AF Stancato, LF David, M CarterSu, C Larner, AC Pratt, WB TI Preassociation of STAT1 with STATE and STAT3 in separate signalling complexes prior to cytokine stimulation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-FREE SYSTEM; INTERFERON-ALPHA; TRANSCRIPTIONAL ACTIVATOR; GLUCOCORTICOID RECEPTOR; PROTEINS; ISGF-3 AB A variety of cytokines and growth factors act through an induction of gene expression mediated by a family of latent transcription factors called STAT (signal transducers and activators of transcription) proteins. Ligand-induced tyrosine phosphorylation of the STATs promotes their homodimer and heterodimer formation and subsequent nuclear translocation. We demonstrate here that STAT protein heterocomplexes exist prior to cytokine treatment, When unstimulated HeLa cells are ruptured in hypotonic buffer without salt or detergent, immunoadsorption of either STAT1 or STAT2 from the resulting cytosol yields coimmunoadsorption of the other STAT protein, Similarly, STAT1-STAT3 heterocomplexes are coimmunoadsorbed from hypotonic cytosol, STAT1 and STAT2 or STAT1 and STAT3 translated in reticulocyte lysate spontaneously form heterocomplexes when the translation lysates are mixed at 0 degrees C, Our data suggest that interferon-alpha/beta-induced tyrosine phosphorylation increases the stability of a preexisting, latent, STAT1-STAT2 signaling complex. Newly translated STAT1 binds in equilibrium fashion to STAT2 and STAT3, but we show that STAT2 and STAT3 exist in separate heterocomplexes with STAT1, consistent with a model in which STAT1 contains a common binding site for other STAT proteins. C1 UNIV MICHIGAN,SCH MED,DEPT PHARMACOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,SCH MED,DEPT PHYSIOL,ANN ARBOR,MI 48109. US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20892. FU NCI NIH HHS [CA28010, R01 CA028010]; NIDDK NIH HHS [DK34171, R01 DK034171] NR 21 TC 99 Z9 100 U1 3 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 23 PY 1996 VL 271 IS 8 BP 4134 EP 4137 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TW960 UT WOS:A1996TW96000030 PM 8626752 ER PT J AU LaBorde, JB Bates, HK Dacre, JC Young, JF AF LaBorde, JB Bates, HK Dacre, JC Young, JF TI Developmental toxicity of sarin in rats and rabbits SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article AB Sarin (Agent GB, isopropyl methylphosphonofluoridate) is an organophosphate cholinesterase inhibitor. Sarin (Type I or Type II) was administered by gavage to CD rats on d 6-15 of gestation at dose levels of 0, 100, 240, or 380 mu g/kg/d and to New Zealand White (NZW) rabbits on d 6-19 of gestation at dose levels of 0, 5, 10, or 15 mu g/kg/d. Females were weighed on gestational days (GD) 0, 6-16 for rats and 6-20 for rabbits, and immediately prior to termination (GD 20 for rats and GD 29 for rabbits). All animals were monitored daily for clinical signs of toxicity throughout dosing and until sacrifice. At necropsy, gravid uteri were weighed and examined for the number and status of implants (live, resorbed, or dead). Individual fetal body weight, malformations, and variations (external, visceral, and skeletal) were recorded. Rat and rabbit dams in the high-dose groups exhibited significant signs of maternal toxicity and increased maternal mortality. Examination of gravid uteri revealed no statistical differences among treatment groups in the incidence of resorptions or of dead or malformed fetuses, or in average body weight of live fetuses per litter. These results show no evidence of developmental toxicity in the CD rat or NZW rabbit following exposure to either Type I or Type II sarin during embryonic differentiation and major organogenesis, even at a dose that produced maternal toxicity. C1 NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079. PATHOL ASSOCIATES INC,JEFFERSON,AR. USA,BIOMED RES & DEV LAB,FT DETRICK,MD. NR 14 TC 8 Z9 8 U1 0 U2 0 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD FEB 23 PY 1996 VL 47 IS 3 BP 249 EP 265 DI 10.1080/009841096161771 PG 17 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA TW555 UT WOS:A1996TW55500004 PM 8604149 ER PT J AU Danielson, JW Thompson, RD AF Danielson, JW Thompson, RD TI Determination of glutaraldehyde and phenol in germicide products by capillary gas chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE glutaraldehyde; phenol; germicides AB A capillary gas chromatographic procedure is described for the analysis of glutaraldehyde and phenol present in germicidal formulations. Glutaraldehyde breaks down over time following activation with alkaline-buffered media and products must be used within certain time limits. Some germicidal products contain either glutaraldehyde or phenol and these are also used in combination. It is necessary to have suitable methodology for determining the concentration of glutaraldehyde and phenol as a means of evaluating the effective levels of these active ingredients. Various analytical methods are described in the literature for the determination of either glutaraldehyde or phenol. Using capillary gas chromatography with a column for compounds of intermediate polarity, both ingredients can be assayed from a single determination. RP Danielson, JW (reprint author), US FDA,240 HENNEPIN AVE,MINNEAPOLIS,MN 55401, USA. NR 13 TC 5 Z9 5 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD FEB 16 PY 1996 VL 724 IS 1-2 BP 398 EP 402 DI 10.1016/0021-9673(95)01035-1 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA TX704 UT WOS:A1996TX70400047 ER PT J AU Nelson, R Schaffner, AE Li, YX Walton, MK AF Nelson, R Schaffner, AE Li, YX Walton, MK TI Glutamate and cGMP sensitivities of rat retinal neurons assayed by fluorescent potentiometric probe SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NINCDS,NIH,NEUROPHYSIOL LAB,BETHESDA,MD. US FDA,CBER,OTRR,DCTDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 2910 EP 2910 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39702906 ER PT J AU Kenyon, K Moody, SA Jamrich, M AF Kenyon, K Moody, SA Jamrich, M TI A novel forkhead gene is the earliest specific marker for lens epidermis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,NEUROSCI PROGRAM,WASHINGTON,DC. US FDA,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4530 EP 4530 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704523 ER PT J AU Lafrenie, RM Wahl, LM Epstein, JS Hewlett, IK Yamada, KM Dhawan, S AF Lafrenie, RM Wahl, LM Epstein, JS Hewlett, IK Yamada, KM Dhawan, S TI HIV-1-Tat modulates the function of monocytes and alters their interactions with microvessel endothelial cells - A mechanism of HIV pathogenesis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN VASCULAR ENDOTHELIUM; TAT PROTEIN; IV COLLAGENASE; AIDS PATIENTS; T-CELLS; INFECTION; MACROPHAGES; EXPRESSION; TYPE-1 AB Monocytes are major targets of HIV infection in patients with AIDS. In vitro infection of monocytes with HIV is associated with increased expression of beta(2) integrins, which increases both monocyte aggregation and monocyte/endothelial adhesion as well as monocyte metalloproteinase (MMP-9) expression. Treatment of primary monocytes with soluble HIV-Tat protein mimicked many of the properties of HIV infection of monocytes. Tat treatment up-regulated the expression of the beta(2) integrins, which was associated with the formation of large aggregates of monocytes and increased adhesion to endothelial monolayers. Treatment of monocytes with Tat increased their adhesion to both untreated and TNF-alpha-treated endothelial monolayers, and adhesion was inhibited by inclusion of anti-beta(2) and anti-ICAM-1 Abs. The increased adhesion of activated monocytes was accompanied by substantial disruption of the endothelial monolayers, with retraction or detachment of individual endothelial cells. Tat treatment of monocytes up-regulated the synthesis and release of the protease MMP-9, providing a potential mechanism to explain endothelial cell/basement membrane detachment. Thus, extracellular Tat is capable of activating monocytes even in the absence of HIV infection, Our studies demonstrate that many of the effects of HIV infection on monocyte homotypic and heterotypic adhesion, protease secretion, and disruption of the endothelium can be mimicked by treatment with HIV-Tat protein alone. These results suggest a mechanism where monocytes could be inappropriately activated by HIV-Tat, secreted by HIV-infected cells, causing them to extravasate into underlying tissues and ultimately contribute to tissue damage as seen during the progression of AIDS. C1 US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,MOLEC VIROL LAB,ROCKVILLE,MD 20852. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NIDR,IMMUNOL LAB,BETHESDA,MD 20892. OI Yamada, Kenneth/0000-0003-1512-6805 NR 50 TC 111 Z9 115 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 1996 VL 156 IS 4 BP 1638 EP 1645 PG 8 WC Immunology SC Immunology GA TU692 UT WOS:A1996TU69200042 PM 8568270 ER PT J AU Zhang, YH Venable, RM Pastor, RW AF Zhang, YH Venable, RM Pastor, RW TI Molecular dynamics simulations of neat alkanes: The viscosity dependence of rotational relaxation SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; SYMMETRIC TOP MACROMOLECULES; MULTIPLE INTERNAL ROTATIONS; LIPID BILAYER-MEMBRANES; FRICTION COEFFICIENTS; STOCHASTIC DYNAMICS; CIRCULAR-CYLINDERS; LANGEVIN DYNAMICS; NMR RELAXATION; ISOMERIZATION AB Molecular dynamics simulations of neat octane, dodecane, hexadecane, and eicosane at 323 K are compared with experiment and analyzed with respect to terms that contribute to reorientational relaxation of CH vectors. Agreement with experiment for translational diffusion constants and rotational relaxational times is excellent. It is found that gauche-trans isomerization rates, while weakly dependent on chain position, are essentially independent of chain length and, hence, shear viscosity. In contrast, rotational correlation times of the symmetry. (or ''long'') axis of the instantaneous moment of inertia tensor increase monotonically with chain length, and, taking the shape dependence into account with a hydrodynamic cylinder model, are proportional to viscosity. Rotation about the long axis is strongly coupled with isomerization. Using an approximate separation of internal and overall motion, reorientation of octane is shown to be largely ''rigid body''. For the central carbons in eicosane flexibility contributes at most 40% to the total relaxation time that would be observed in, for example, NMR T-1 measurements. C1 US FDA,CTR BIOL EVALUAT & RES,BIOPHYS LAB,ROCKVILLE,MD 20852. NR 49 TC 41 Z9 41 U1 1 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD FEB 15 PY 1996 VL 100 IS 7 BP 2652 EP 2660 DI 10.1021/jp952745a PG 9 WC Chemistry, Physical SC Chemistry GA TV694 UT WOS:A1996TV69400025 ER PT J AU Tollefson, L AF Tollefson, L TI FDA reveals plans for antimicrobial susceptibility monitoring SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT News Item RP Tollefson, L (reprint author), US FDA,CTR VET MED,DIV VOLUNTARY COMPLIANCE,ROCKVILLE,MD 20857, USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD FEB 15 PY 1996 VL 208 IS 4 BP 459 EP 460 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA TU762 UT WOS:A1996TU76200001 PM 8603884 ER PT J AU Hung, HMJ AF Hung, HMJ TI Global tests for combination drug studies in factorial trials SO STATISTICS IN MEDICINE LA English DT Article AB To test the hypothesis that there are some studied dose combinations more effective in treating a disease than their respective component doses of two drugs, Hung, Chi and Lipicky proposed two alpha-level tests for normally distributed data. This paper extends the utilities of these tests to the outcome variable that has variance as a function of its mean, such as with a binomially distributed outcome, and to incomplete factorial design settings where some cells are not studied. I explore the impacts of excluding cells from study on the power performances of these tests. RP Hung, HMJ (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV BIOMETR,STAT EVALUAT & RES BRANCH,HFD-713,ROOM 6060,ROCKVILLE,MD 20852, USA. NR 9 TC 9 Z9 9 U1 2 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD FEB 15 PY 1996 VL 15 IS 3 BP 233 EP 247 DI 10.1002/(SICI)1097-0258(19960215)15:3<233::AID-SIM167>3.0.CO;2-H PG 15 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 TQ473 UT WOS:A1996TQ47300001 PM 8643882 ER PT J AU Ruymann, FB Krill, CE Halpin, TJ Churchill, WH Ewenstein, B DeMaria, A MancoJohnson, MJ Hoffman, RE AF Ruymann, FB Krill, CE Halpin, TJ Churchill, WH Ewenstein, B DeMaria, A MancoJohnson, MJ Hoffman, RE TI Hepatitis A among persons with hemophilia who received clotting factor concentrate - United States, September-December 1995 (Reprinted from MMWR, vol 45, pg 29-32, 1996) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 CHILDRENS HOSP,MED CTR,HEMOPHILIA TREATMENT CTR,AKRON,OH. OHIO DEPT HLTH,COLUMBUS,OH 43266. BRIGHAM & WOMENS HOSP,COMPREHENS HEMOPHILIA TREATMENT CTR,BOSTON,MA 02115. MASSACHUSETTS DEPT PUBL HLTH,BOSTON,MA 02111. UNIV COLORADO,HLTH SCI CTR,DENVER,CO. NATL HEMOPHILIA FDN,DEPT PUBL HLTH & ENVIRONM,NEW YORK,NY. CDC,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,HEMATOL DIS BRANCH,DIV AIDS STD & TB LAB RES,ATLANTA,GA. US FDA,CTR BIOL EVALUAT & RES,OFF BLOOD RES & REVIEW,ROCKVILLE,MD 20857. RP Ruymann, FB (reprint author), CHILDRENS HOSP,DIV PEDIAT HEMATOL ONCOL,COLUMBUS,OH 43205, USA. NR 11 TC 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 14 PY 1996 VL 275 IS 6 BP 427 EP 428 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA TU638 UT WOS:A1996TU63800008 ER PT J AU Harris, RZ Tsunoda, SM AF Harris, RZ Tsunoda, SM TI Timing of drug administration to prevent drug interactions SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NORTHEASTERN UNIV,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Harris, RZ (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 14 PY 1996 VL 275 IS 6 BP 445 EP 446 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA TU638 UT WOS:A1996TU63800026 PM 8627963 ER PT J AU Kim, CS Virella, A Braunberg, RC Ross, IA Matthews, RN Johnson, W Friedman, L AF Kim, CS Virella, A Braunberg, RC Ross, IA Matthews, RN Johnson, W Friedman, L TI Kinetic analysis of glutamate transport by the miniswine choroid plexus in vitro SO BRAIN RESEARCH LA English DT Article DE glutamic acid; choroid plexus; active transport; miniswine ID HIGH AFFINITY UPTAKE; AMINO-ACIDS; ASPARTIC-ACID; QUINOLINIC ACID; SPINAL-CORD; RAT-BRAIN; NEURONS AB Transport of glutamic acid by the choroid plexus, the blood-cerebrospinal fluid (CSF) barrier, was investigated by using the isolated choroid plexi from the fourth (FVCP) and lateral ventricles (LVCP) of the young adult miniswine in vitro. Glutamic acid uptake was very pronounced, with concentrations 7-fold (LVCP) and 2.4-fold (FVCP) higher in tissue than in medium after only 5 min of incubation with 1 mu M glutamic acid. Tissue/medium ratios reached steady state by 15 min at 30-fold (LVCP) and 11-fold (FVCP). Uptake was energy-dependent and inhibited by ouabain and hypothermia. L-Aspartic acid was shown to be inhibitory in a concentration-dependent manner, suggesting that it shares a common transport system, whereas neither octanoic acid nor okadaic acid (transported by a separate fatty acid system) inhibited glutamic acid transport. At the same temperature, the labeled metabolite of glutamate (glutamine) in the tissue was 64.7%, 73.2%, and 72.5% of total radioactivity at 5, 30, and 60 min, respectively. The estimated K-m values for glutamate uptake by the choroid plexus are 264 mu M (FVCP) and 196 mu M (LVCP); V-max values are 87 (FVCP) and 147 (LVCP) nmol/g/min, respectively. These results indicate that, in addition to the metabolism of glutamate to glutamine, an active uptake mechanism is present in the choroid plexus of miniswine which may serve to regulate glutamic acid concentration in the CSF. RP Kim, CS (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV TOXICOL RES HFS 506,WASHINGTON,DC 20204, USA. NR 31 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD FEB 12 PY 1996 VL 709 IS 1 BP 59 EP 64 DI 10.1016/0006-8993(95)01263-X PG 6 WC Neurosciences SC Neurosciences & Neurology GA TX909 UT WOS:A1996TX90900008 PM 8869557 ER PT J AU Manjanatha, MG Li, EE Fu, PP Heflich, RH AF Manjanatha, MG Li, EE Fu, PP Heflich, RH TI H- and K-ras mutational profiles in chemically induced liver tumors from B6C3F(1) and CD-1 mice SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article ID GUANINE PHOSPHORIBOSYLTRANSFERASE GENE; DOSE-DEPENDENT DIFFERENCES; DIPLOID HUMAN FIBROBLASTS; HPRT GENE; CODING REGION; ACTIVATED ONCOGENES; EXCISION REPAIR; MOUSE SKIN; 61ST CODON; CARCINOGENESIS AB Liver tumors from mice treated with genotoxic carcinogens often possess mutations in ras protooncogenes, and these sequence alterations in ras frequently reflect the mutational specificity of the carcinogen. Previous studies suggest that the mouse model used for tumor induction may affect ras mutational patterns. In order to explore this possibility, H- and K-ras mutational profiles were established in liver tumors from male B6C3F(1) and CD-I mice administered benzo[a]pyrene (BaP) 6-nitrochrysene (6-NC), and 4-aminobiphenyl (4-ABP). With the exception of B-NC-induced tumors in B6C3F(1) mice, a high proportion of the tumors induced in both types of mice contained ras mutations. In CD-1 mice, 6-NC predominantly induced C-->A mutations in H-ras codon 61 (90% of tumors analyzed), whereas 4-ABP mainly induced A-->T mutations in H-ras codon 61 (50%) and BaP induced both A-->T (27%) and G-->C (50%) mutations in H-ras codon 61 and K-ras codon 13, respectively. In B6C3F, mice, 85% of BaP tumors had G-->C mutations in K-ras codon 13 and 85% of 4-ABP tumors had C-->A mutations in H-ras codon 61, while among 6-NC tumors, only 4% had G-->C mutations in K-ras codon 13 and none had H-ras mutations. Statistical analysis of these results indicates that the patterns of tumor ras mutations induced by BaP in CD-1 and B6C3F(1) mice were indistinguishable, while 6-NC and 4-ABP produced different tumor ras profiles in the two mouse models. Published mutational profiles for active metabolites of BaP and 6-NC from in vitro reporter gene systems were inconsistent with both the CD-1 and B6C3F(1) tumor ras mutational responses. C1 US FDA,NATL CTR TOXICOL RES,DEPT HLTH & HUMAN SERV,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079. RP Manjanatha, MG (reprint author), US FDA,NATL CTR TOXICOL RES,DEPT HLTH & HUMAN SERV,DIV GENET TOXICOL,HFT-120,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 58 TC 34 Z9 35 U1 0 U2 2 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD FEB 9 PY 1996 VL 47 IS 2 BP 195 EP 208 DI 10.1080/009841096161898 PG 14 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA TV554 UT WOS:A1996TV55400009 PM 8598575 ER PT J AU Volmer, DA Lay, JO Billedeau, SM Vollmer, DL AF Volmer, DA Lay, JO Billedeau, SM Vollmer, DL TI Detection and confirmation of N-nitrosodialkylamines using liquid chromatography electrospray ionization coupled on-line with a photolysis reactor SO ANALYTICAL CHEMISTRY LA English DT Article ID MASS-SPECTROMETRY; NITROSAMINES; BEER AB Simultaneous detection and confirmation of several N-nitrosodialkylamines are accomplished by on-line coupling of a photolysis reactor with an HPLC-electrospray ionization mass spectrometer. Several parameters such as irradiation wavelength, irradiation time, mobile-phase composition, and pH, as well as different organic acid modifiers are investigated, and their impact on the detection of the N-nitrosodialkylamine-acid complex and its dissociative photolysis products is presented here, Additionally, the type of structural information obtained from the photolytic processes of N-nitrosodialkylamines is compared to that obtained by using in-source collision-induced dissociation. To demonstrate the potential of this technique, six N-nitrosodialkylamines are studied to determine the linearity of the response, the limits of detection and confirmation, and the reproducibility, The technique's versatility is also exhibited by utilizing negative-ion mode as a complementary means for analysis of the compounds, Finally, an illustrative application for N-nitrosodimethylamine analysis in beer is described. C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RI Lay, Jackson/G-1007-2011; Volmer, Dietrich/G-7900-2012 OI Lay, Jackson/0000-0003-3789-2527; Volmer, Dietrich/0000-0003-2820-1480 NR 36 TC 14 Z9 14 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD FEB 1 PY 1996 VL 68 IS 3 BP 546 EP 552 DI 10.1021/ac9508614 PG 7 WC Chemistry, Analytical SC Chemistry GA TR964 UT WOS:A1996TR96400020 PM 21619088 ER PT J AU Sagripanti, JL Bonifacino, A AF Sagripanti, JL Bonifacino, A TI Comparative sporicidal effects of liquid chemical agents SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID HYDROGEN-PEROXIDE; GLUTARALDEHYDE; COPPER; DISINFECTION; DNA AB We compared the effectiveness of glutaraldehyde, formaldehyde, hydrogen peroxide, peracetic acid, cupric ascorbate (plus a sublethal amount of hydrogen peroxide), sodium hypochlorite, and phenol to inactivate Bacillus subtilis spores under various conditions, Each chemical agent was distinctly affected by pH, storage time after activation, dilution, and temperature, Only three of the preparations (hypochlorite, peracetic acid, and cupric ascorbate) studied here inactivated more than 99.9% of the spore load after a 30-min incubation at 20 degrees C at concentrations generally used to decontaminate medical devices, Under similar conditions, glutaraldehyde inactivated approximately 90%, and hydrogen peroxide, formaldehyde, and phenol produced little killing of spores in suspension, By kinetic analysis at different temperatures, we calculated the rate of spore inactivation (k) and the activation energy of spore killing (Delta E) for each chemical agent. Rates of spore inactivation had a similar Delta E value of approximately 20 kcal/mol (ca, 83.68 kJ/mol) for every substance tested, The variation among k values allowed a quantitative comparison of liquid germicidal agents. RP Sagripanti, JL (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,MOLEC BIOL BRANCH HFZ113,OFF SCI & TECHNOL,DIV LIFE SCI,ROCKVILLE,MD 20857, USA. NR 35 TC 82 Z9 85 U1 1 U2 16 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD FEB PY 1996 VL 62 IS 2 BP 545 EP 551 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA TT690 UT WOS:A1996TT69000037 PM 8593054 ER PT J AU Alayash, AI Ryan, BAB Osawa, Y Cashon, RE Eich, R Olson, JS AF Alayash, AI Ryan, BAB Osawa, Y Cashon, RE Eich, R Olson, JS TI Oxidative reactions of sperm whale myoglobin and its distal pocket mutants with hydrogen peroxide SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NHLBI,NIH,BETHESDA,MD 20892. UNIV MAINE,ORONO,ME 04469. RICE UNIV,HOUSTON,TX 77251. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP MP371 EP MP371 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201253 ER PT J AU Pine, PS Weaver, JL Aszalos, A AF Pine, PS Weaver, JL Aszalos, A TI Proximity of CD4 and TcR/CD3 on activated and resting T4 cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 US FDA,CDER,DIV RES & TESTING,LAUREL,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP SU503 EP SU503 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68200686 ER PT J AU Goldberg, EM Lester, DS Borchardt, DB Zidovetzki, R AF Goldberg, EM Lester, DS Borchardt, DB Zidovetzki, R TI Dipalmitin- and unsaturated fatty acid-induced lipid bilayer perturbations correlate with synergistic activation of protein kinase C. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 UNIV CALIF RIVERSIDE,DEPT BIOL,RIVERSIDE,CA 92521. UNIV CALIF RIVERSIDE,DEPT CHEM,RIVERSIDE,CA 92521. US FDA,CDER,DRT,LAUREL,MD 20708. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP WP237 EP WP237 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202425 ER PT J AU Lewis, EN Levin, IW Hanig, JP Lester, DS AF Lewis, EN Levin, IW Hanig, JP Lester, DS TI Infrared chemical imaging of drug-induced neurotoxicity in the rat cerebellum SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK,NIH,CHEM PHYS LAB,BETHESDA,MD 20892. US FDA,CTR DRUG EVALUAT & RES,LAUREL,MD 20708. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP WP180 EP WP180 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202366 ER PT J AU Wessels, BW Breitz, H Mills, G Siegel, J Stabin, M Wessels, BW AF Wessels, BW Breitz, H Mills, G Siegel, J Stabin, M Wessels, BW TI The 10th international conference on monoclonal antibody immunoconjugates for cancer: Radiodosimetry and radiopharmaceuticals for therapy SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Editorial Material C1 VIRGINIA MASON MED CTR,DEPT NUCL MED,SEATTLE,WA 98101. US FDA,DIV CLIN TRIALS DESIGN & ANAL,ROCKVILLE,MD 20857. UNIV MED & DENT NEW JERSEY,COOPER HOSP,MED CTR,DEPT RADIAT ONCOL,CAMDEN,NJ 08103. OAK RIDGE ASSOCIATED UNIV,RADIAT INTERNAL DOSE INFORMAT CTR,OAK RIDGE,TN. RP Wessels, BW (reprint author), GEORGE WASHINGTON UNIV,MED CTR,DIV RADIAT ONCOL & BIOPHYS,WASHINGTON,DC 20037, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD FEB PY 1996 VL 11 IS 1 BP 25 EP 42 DI 10.1089/cbr.1996.11.25 PG 18 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA UR855 UT WOS:A1996UR85500005 ER PT J AU Tolleson, WH Melchior, WB Morris, SM McGarrity, LJ Domon, OE Muskhelishvili, L James, SJ Howard, PC AF Tolleson, WH Melchior, WB Morris, SM McGarrity, LJ Domon, OE Muskhelishvili, L James, SJ Howard, PC TI Apoptotic and anti-proliferative effects of fumonisin B-1 in human keratinocytes, fibroblasts, esophageal epithelial cells and hepatoma cells SO CARCINOGENESIS LA English DT Article ID PAPILLOMAVIRUS TYPE-16 DNA; FUSARIUM-MONILIFORME; TERMINAL DIFFERENTIATION; SPHINGOLIPID BIOSYNTHESIS; MURINE KERATINOCYTES; EPIDERMAL-CELLS; TUMOR PROMOTER; MYCOTOXINS; LINE; TRANSGLUTAMINASE AB Fumonisin B-1 is associated with various animal and human carcinomas and toxicoses, including leukoencelphalomalacia, hepatocarcinoma, pulmonary edema and esophageal carcinoma, We have examined the cellular effects of fumonisin B-1 in vitro using cellular model systems relevant to potential human target tissues, Although fumonisin B-1 has been described as a mitogen in Swiss 3T3 cells based on stimulation of [H-3]thymidine incorporation, in the current work it was found that fumonisin B-1 inhibited incorporation of [H-3]thymidine by cultured neonatal human keratinocytes and HepG2 human hepatocarcinoma cells at 10(-7) and 10(-4) M respectively, Fumonisin B-1 also inhibited clonal expansion of normal human keratinocytes and HET-IA human esophageal epithelial cells at 10(-5) M and growth in mass culture of normal human fibroblasts at 10(-7) M. The clonogenicity of normal human keratinocytes decreased to 45.5% of controls after exposure to 10(-4) M fumonisin B-1 for 2 days, However, no differences in the cell cycle distribution of cultured keratinocytes was noted after exposure to 10(-5) M fumonisin B-1 for 40 h., The viability of normal human keratinocytes and HET-1A cells decreased as a result of fumonisin B-1 treatment, as determined by a fluorescein diacetate/propidium iodide flow cytometric cell viability assay, Fumonisin B1-treated keratinocytes released nucleosomal DNA fragments into the medium 2-3 days after exposure to 10(-4) M fumonisin B-1 and increased DNA strand breaks were detected in attached keratinocytes exposed to 0-10(-4) M fumonisin B-1 using a terminal deoxynucleotidyl transferase-based immunochemical assay system, Furthermore, fumonisin B-1-treated keratinocytes and HET-1A cells developed morphological features consistent with apoptosis, as determined by phase contrast microscopy, fluorescent microscopy of acridine orange stained cells and electron microscopy, These results are consistent with the occurrence of fumonisin B-1-mediated apoptosis in vitro. C1 US FDA,DIV BIOCHEM TOXICOL,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. US FDA,DIV GENET TOXICOL,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. US FDA,DIV NUTR TOXICOL,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. FU NIA NIH HHS [IAG 224-93-0001] NR 54 TC 99 Z9 100 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 1996 VL 17 IS 2 BP 239 EP 249 DI 10.1093/carcin/17.2.239 PG 11 WC Oncology SC Oncology GA UC149 UT WOS:A1996UC14900011 PM 8625445 ER PT J AU Hertelendy, ZI Patel, DG Knittel, JJ AF Hertelendy, ZI Patel, DG Knittel, JJ TI Pancreastatin inhibits insulin secretion in RINm5F cells through obstruction of G-protein mediated, calcium-directed exocytosis SO CELL CALCIUM LA English DT Article ID ISOLATED RAT ISLETS; PANCREATIC-ISLETS; HORMONE-RELEASE; METABOLISM; MECHANISM; GALANIN; PEPTIDE; CA-2+ AB To elucidate the regulatory pathway through which pancreastatin inhibits insulin secretion, RINm5F insulinoma cells were challenged with physiological and pharmacological probes known to stimulate insulin release through different mechanisms. Utilizing the electrophysiological technique of capacitance measurements as a correlate to exocytosis, pancreastatin was found to significantly diminish maximum capacitance changes evoked by glyceraldehyde, an effect which was attenuated in pertussis toxin-treated cells. In static incubations of this cell line, pancreastatin significantly inhibited insulin secretion stimulated by glyceraldehyde, carbachol and A23187, secretagogues known to directly elevate beta-cell cytosolic Ca2+. This peptide also inhibited insulin secretion stimulated by phorbol myristate acetate (PMA), but only at incubation times less than or equal to 15 min. It was without effect on insulin secretion stimulated by mastoparan and longer incubations (30 min) with PMA, where the secretory mechanisms are not necessarily Ca2+-dependent. Additionally. pancreastatin had no effect on carbachol-generated inositol phosphate accumulation but inhibited simultaneously stimulated insulin secretion. All inhibitory effects of pancreastatin were pertussis toxin sensitive. These results suggest that pancreastatin inhibits insulin secretion in RINm5F cells through a G-protein regulated mechanism at a control point involved in the Ca2+-directed exocytotic machinery, a feature shared by other physiologic inhibitors of insulin secretion. C1 UNIV CINCINNATI,COLL PHARM,DIV PHARMACEUT SCI,CINCINNATI,OH 45267. UNIV CINCINNATI,COLL MED,DEPT MOLEC & CELLULAR PHYSIOL,CINCINNATI,OH 45267. US FDA,DCRDP,ROCKVILLE,MD 20857. FU NHLBI NIH HHS [HL07571] NR 31 TC 9 Z9 9 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD FEB PY 1996 VL 19 IS 2 BP 125 EP 132 DI 10.1016/S0143-4160(96)90081-0 PG 8 WC Cell Biology SC Cell Biology GA UA341 UT WOS:A1996UA34100004 PM 8689670 ER PT J AU Kowtha, VC Bryant, HJ Krauthamer, V Iwasa, KH Stenger, DA AF Kowtha, VC Bryant, HJ Krauthamer, V Iwasa, KH Stenger, DA TI Spontaneous firing of NG108-15 cells induced by transient exposure to ammonium chloride SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE NG108-15; serum-free media; ammonium chloride; intracellular pH ID INTRACELLULAR PH; NEURONS; INACTIVATION; AXONS AB 1. We report that NG108-15 (neuroblastoma x glioma) cells differentiated in defined serum-free media are capable of exhibiting stable automaticity (the spontaneous occurrence of regenerative action potentials) following exposure to extracellular perfusates containing NH4Cl. 2. Membrane depolarization (4-5 mV) concomitant with an increased pH(i) during NH4Cl exposure are followed by hyperpolarization (5-7 mV), subthreshold oscillations, and spontaneous firing after the removal of NH4Cl. 3. Cells cultured in 10% serum did not exhibit automaticity. Cells cultured in serum-free media are twice as likely to show automaticity as those cultured in reduced (1.5%) serum media. 4. We have examined factors that contribute to the events following NH4Cl exposure, namely, membrane depolarization and hyperpolarization, subthreshold oscillations, and automaticity, The inward currents activated at more negative potentials and the ionic currents associated with pronounced afterhyperpolarization in NG108-15 cells cultured in serum-free media provide a basis for the repetitive activity in general and automaticity in particular. C1 USN,RES LAB,CTR BIOMOLEC SCI & ENGN,WASHINGTON,DC 20375. UNIFORMED SERV UNIV HLTH SCI,DEPT PHYSIOL,BETHESDA,MD 20814. US FDA,ELECTROPHYS BRANCH,DPS,OST,CDRH,ROCKVILLE,MD 20857. NIDCD,NATL INST HLTH,SECT BIOPHYS SENSORY PROC,LCB,BETHESDA,MD 20892. OI Iwasa, Kuni/0000-0002-9397-7704 NR 14 TC 5 Z9 5 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD FEB PY 1996 VL 16 IS 1 BP 1 EP 9 DI 10.1007/BF02578382 PG 9 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA TV608 UT WOS:A1996TV60800001 PM 8714555 ER PT J AU Lee, SC Vincent, R Prosky, L Sullivan, DM AF Lee, SC Vincent, R Prosky, L Sullivan, DM TI Evaluating an analytical method for complex carbohydrate determinations SO CEREAL FOODS WORLD LA English DT Article C1 US FDA,WASHINGTON,DC 20204. CORNING HAZLETON INC,MADISON,WI. RP Lee, SC (reprint author), KELLOGG CO,BATTLE CREEK,MI, USA. NR 18 TC 5 Z9 5 U1 0 U2 1 PU AMER ASSOC CEREAL CHEMISTS PI ST PAUL PA 3340 PILOT KNOB RD, ST PAUL, MN 55121-2097 SN 0146-6283 J9 CEREAL FOOD WORLD JI Cereal Foods World PD FEB PY 1996 VL 41 IS 2 BP 64 EP 70 PG 7 WC Food Science & Technology SC Food Science & Technology GA TZ727 UT WOS:A1996TZ72700003 ER PT J AU Lee, SC Prosky, L AF Lee, SC Prosky, L TI Perspectives on complex carbohydrate definition SO CEREAL FOODS WORLD LA English DT Editorial Material C1 US FDA,WASHINGTON,DC 20204. RP Lee, SC (reprint author), KELLOGG CO,BATTLE CREEK,MI, USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CEREAL CHEMISTS PI ST PAUL PA 3340 PILOT KNOB RD, ST PAUL, MN 55121-2097 SN 0146-6283 J9 CEREAL FOOD WORLD JI Cereal Foods World PD FEB PY 1996 VL 41 IS 2 BP 88 EP 89 PG 2 WC Food Science & Technology SC Food Science & Technology GA TZ727 UT WOS:A1996TZ72700008 ER PT J AU Starkebaum, G Kenyon, CM Simrell, CR Creamer, JI Rubin, RL AF Starkebaum, G Kenyon, CM Simrell, CR Creamer, JI Rubin, RL TI Procainamide-induced agranulocytosis differs serologically and clinically from procainamide-induced lupus SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID PATIENTS RECEIVING PROCAINAMIDE; SUSTAINED-RELEASE PROCAINAMIDE; DRUG-INDUCED LUPUS; IMMUNE-COMPLEXES; ANTIBODIES; NEUTROPHILS; METABOLISM; ERYTHEMATOSUS; LEUKOCYTES; AMIDE AB Agranulocytosis is a well recognized but uncommon complication of procainamide (PA) therapy, whereas a lupus-like syndrome occurs in approximately 20% of patients treated chronically with PA. In order to gain insight into the immunopathogenic relationships among these conditions, we compared the humoral immune abnormalities in these patient groups as well as in asymptomatic PA-treated patients, A relatively uniform profile of IgM but not IgG autoantibody reactivity with a set of chromatin-related antigens was observed in eight elderly men who developed agranulocytosis after treatment with PA. In contrast PA-induced lupus patients had predominant reactivity with [(H2A-H2B)-DNA] in both IgM and IgG classes. Five of eight patients with agranulocytosis had elevated levels of neutrophil-reactive IgG which appeared to be due to immune complexes based on Fc gamma receptor blocking studies. However, 12 of 15 patients with PA-induced lupus, none of whom had neutropenia, had similar levels of neutrophil-reactive IgG, suggesting that this reactivity was not causally related to agranulocytosis. Agranulocytosis developed after less than 3 months treatment with PA in six of eight patients. This time course was similar to that seen in 77 PA-induced agranulocytosis patients reported in the literature plus 127 patients reported to the U.S. Food and Drug Administration in whom 90% developed agranulocytosis within 3 months of starting PA. In contrast, the mode duration of treatment with PA before lupus-like symptoms develop is 10-12 months. These findings, together with the different profiles of autoantibodies and clinical presentations, suggest that agranulocytosis arises from a different mechanism than that underlying PA-induced lupus. (C) 1996 Academic Press, Inc. C1 UNIV WASHINGTON, SCH MED, DEPT MED, DIV RHEUMATOL, SEATTLE, WA 98195 USA. UNIV WASHINGTON, SCH MED, DEPT PATHOL, SEATTLE, WA 98195 USA. US FDA, OFF EPIDEMIOL & BIOSTAT, REPORTS EVALUAT BRANCH, ROCKVILLE, MD 20857 USA. SCRIPPS RES INST, DEPT MOL & EXPTL MED, LA JOLLA, CA 92037 USA. RP Starkebaum, G (reprint author), VET ADM MED CTR, ARTHRIT SECT 111, 1660 S COLUMBIAN WAY, SEATTLE, WA 98108 USA. FU NIA NIH HHS [AG-09574] NR 66 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD FEB PY 1996 VL 78 IS 2 BP 112 EP 119 DI 10.1006/clin.1996.0020 PG 8 WC Immunology; Pathology SC Immunology; Pathology GA TX989 UT WOS:A1996TX98900003 PM 8625553 ER PT J AU Salcedo, J Narang, PK Sweeny, J Boone, S Young, M Trapnell, CB AF Salcedo, J Narang, PK Sweeny, J Boone, S Young, M Trapnell, CB TI Alteration of dapsone metabolism by rifabutin in HIV(+) subjects. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 GEORGETOWN UNIV,DIV CLIN PHARMACOL & INFORMAT DIS,WASHINGTON,DC. PHAMACIA INC,COLUMBUS,OH. US FDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP OIB3 EP OIB3 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100118 ER PT J AU Surr, H Wang, D Zhu, G Machado, S Ludden, TM AF Surr, H Wang, D Zhu, G Machado, S Ludden, TM TI A pharmacokmetic pharmacodynamic (PK/PD) model describing the combined effects of feedback, regulation and complexation (FRC) process. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 ORR,DIV BIOPHARM,ROCKVILLE,MD. US FDA,CDER,OEB,RAMP,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP OIA4 EP OIA4 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100115 ER PT J AU Balian, JD Flockhart, DA Harris, JW AF Balian, JD Flockhart, DA Harris, JW TI Utility of the acid-labile metabolite (ALM) of mephenytoin (MP) as a probe for the CYP2C19 metabolic polymorphism SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,DIV CLIN PHARMACOL,ROCKVILLE,MD 20857. GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20057. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP PI26 EP PI26 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100026 ER PT J AU BarditchCrovo, P Witter, F Hamzeh, F McPherson, J Stratton, P Alexander, N Trapnell, CB Hopkins, J AF BarditchCrovo, P Witter, F Hamzeh, F McPherson, J Stratton, P Alexander, N Trapnell, CB Hopkins, J TI Quantitation of vaginally administered nonoxynol-9 (N9) in premenopausal women. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,BALTIMORE,MD. US FDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP PII97 EP PII97 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100216 ER PT J AU Coyne, PE Ajayi, F Harris, J Wiley, T Wortham, D Cantilena, LR AF Coyne, PE Ajayi, F Harris, J Wiley, T Wortham, D Cantilena, LR TI ECG pharmacodynamics and pharmacokinetics of halofantrine and mefloquine. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 UNIFORMED SERV UNIV HLTH SCI,DIV CLIN PHARMACOL,BETHESDA,MD 20814. US FDA,CDER,ROCKVILLE,MD 20857. WRAMC,WASHINGTON,DC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP PII7 EP PII7 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100126 ER PT J AU Elte, EI Sahajwalla, C AF Elte, EI Sahajwalla, C TI Population pharmacokinetic model stability and performance SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,CDER,DIV BIOPHARMACEUT,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP PI93 EP PI93 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100093 ER PT J AU Fang, CL Stein, RA Widmark, RM AF Fang, CL Stein, RA Widmark, RM TI Mis-timed and missing data in analgesic trials SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,CDER,DIV PILOT DRUG EVALUAT,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP PI5 EP PI5 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100005 ER PT J AU Ludden, LK Pentikis, HS Ludden, TM Collins, JM Strong, JM AF Ludden, LK Pentikis, HS Ludden, TM Collins, JM Strong, JM TI The addition of albumin, in vitro, yields meaningful free drug Km values for phenytoin metabolism. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,CDER,DIV CLIN PHARMACOL,ROCKVILLE,MD. US FDA,CDER,DIV BIOPHARMACEUT,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP PII45 EP PII45 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100163 ER PT J AU Marinac, JS Flockhart, DA Foxworth, JW Willsie, SK Daus, JC Balian, JD AF Marinac, JS Flockhart, DA Foxworth, JW Willsie, SK Daus, JC Balian, JD TI Omeprazole (OPZ) as a probe for the CYP2C19 polymorphism in an African-American (AA) population SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 UNIV MISSOURI,SCH MED,KANSAS CITY,MO 64108. GEORGETOWN UNIV,MED CTR,DIV CLIN PHARMACOL,WASHINGTON,DC 20057. US FDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP PI19 EP PI19 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100019 ER PT J AU McMichael, J Lieberman, R McCauley, J Irish, W Doyle, H AF McMichael, J Lieberman, R McCauley, J Irish, W Doyle, H TI Concentration controlled trials (CCT) of tacrolimus (TAC) in autoimmunity (Al); PK-PD correlations SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 UNIV PITTSBURGH,TRANSPLANT INST,US FDA,CDER,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP PI100 EP PI100 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100335 ER PT J AU Nakashima, H Lieberman, R Karato, A Saijo, N AF Nakashima, H Lieberman, R Karato, A Saijo, N TI Bayesian estimation for TDM of anticancer drugs: Evaluation of different population methods SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,CDER,ROCKVILLE,MD 20857. NATL CANC CTR,TOKYO 104,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP PI105 EP PI105 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100340 ER PT J AU Singh, GJP Piacquadio, DJ Pershing, LK Willick, K Lambert, LD Adams, WP Schuirmann, DJ Shrivastava, S Shah, VP Lesko, LJ Williams, RL AF Singh, GJP Piacquadio, DJ Pershing, LK Willick, K Lambert, LD Adams, WP Schuirmann, DJ Shrivastava, S Shah, VP Lesko, LJ Williams, RL TI Pharmacodynamic (PD) bioequivalence (BE) studies on betamethasone dipropionate cream (BPC) SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,CDER,ROCKVILLE,MD 20857. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. UNIV UTAH,SALT LAKE CITY,UT. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP PII72 EP PII72 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100307 ER PT J AU Spyker, DA Alderfer, RJ Goetsch, RA Armstrong, GD Longmire, AW Kramer, ED AF Spyker, DA Alderfer, RJ Goetsch, RA Armstrong, GD Longmire, AW Kramer, ED TI Post-marketing adverse events associated with the nicotine patch and polacrilex resin in the United States. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP PII1 EP PII1 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100120 ER PT J AU Wachsman, M BarditchCrovo, P Petty, BG Trapnell, CB Brusilow, S Lietman, PS AF Wachsman, M BarditchCrovo, P Petty, BG Trapnell, CB Brusilow, S Lietman, PS TI Screening for beta-oxidation abnormalities as an indicator of drug-induced impaired mitochondrial function in people receiving zidovudine (ZDV) SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,BALTIMORE,MD. US FDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP PI50 EP PI50 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100050 ER PT J AU Wang, D Zhu, GR Ludden, T AF Wang, D Zhu, GR Ludden, T TI Enhance population pharmacokinetic (PPK) knowledge for a sparsely sampled population by borrowing strength of information from different populations SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP PII68 EP PII68 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100303 ER PT J AU Yasuda, SU Zannikos, P Sale, M Barbey, JT Woosley, RL AF Yasuda, SU Zannikos, P Sale, M Barbey, JT Woosley, RL TI Stereoselectivity of H-1 receptor occupancy following administration of chlorpheniramine (CPM) in humans. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 GEORGETOWN UNIV,MED CTR,DIV CLIN PHARMACOL,WASHINGTON,DC 20007. US FDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP PII35 EP PII35 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100153 ER PT J AU Lunsford, RD Nguyen, N London, J AF Lunsford, RD Nguyen, N London, J TI DNA-binding activities in Streptococcus gordonii: Identification of a receptor-nickase and a histonelike protein SO CURRENT MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; MOLECULAR-CLONING; HU; PURIFICATION; GENE AB Extraction of Streptococcus gordonii cells with the mild chaotropic agent, LiCl, drastically decreased DNA transforming ability, had little effect on viability, and released both DNA nicking and binding activities, Both activities were Mg2+ and Ca2+ independent and were not competence specific. Southwestern blot analysis of the extract identified putative surface proteins of 56 kDa and 68 kDa in strain Challis and Wicky, respectively. Extracts also contained a 10-kDa DNA-binding protein, designated HSgo, that belongs to the eubacterial histonelike class of proteins. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. RP Lunsford, RD (reprint author), NIDR,MICROBIAL ECOL LAB,BLDG 30,RM 312,30 CONVENT DR,BETHESDA,MD 20892, USA. NR 28 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0343-8651 J9 CURR MICROBIOL JI Curr. Microbiol. PD FEB PY 1996 VL 32 IS 2 BP 95 EP 100 DI 10.1007/s002849900017 PG 6 WC Microbiology SC Microbiology GA TM932 UT WOS:A1996TM93200008 PM 8574134 ER PT J AU Flurer, CL AF Flurer, CL TI Analysis of macrolide antibiotics by capillary electrophoresis SO ELECTROPHORESIS LA English DT Article DE glycoconjugated antibiotics; macrolide antibiotics; capillary electrophoresis; sodium cholate ID LIQUID-CHROMATOGRAPHY; ZONE ELECTROPHORESIS; ERYTHROMYCIN ESTOLATE; MASS-SPECTROMETRY; ORGANIC-SOLVENT; DOSAGE FORMS; SEPARATION; POLY(STYRENE-DIVINYLBENZENE); IDENTIFICATION; OPTIMIZATION AB Capillary electrophoresis was utilized in the study of the macrolide antibiotics (i.e. pharmaceutical glycoconjugates) clarithromycin, erythromycin, oleandomycin, troleandomycin, and spiramycin. In order to assist in analyte solubilization, two buffer systems using acetonitrile were developed. The first system involved 30 mM sodium cholate and 20% acetonitrile in 80 mM sodium phosphate, pH 6. This buffer permitted the baseline resolution of all five glycoconjugated antibiotics. In addition, erythromycin was separated from its derivatives estolate and ethylsuccinate. In the absence of surfactants, a higher acetonitrile quantity, 65%, was used in the second buffer system, with 35 mM sodium phosphate, pH 6. Selectivity between oleandomycin and clarithromycin was reversed in this system compared to the cholate buffer, indicating solute interaction with the cholate micelles in the previous system. Calibration linearity and detection sensitivity were improved in the high acetonitrile buffer, due to decreased background absorbance. It was demonstrated that both buffer systems can be utilized for the visualization of minor components that may be present in bulk pharmaceuticals. RP Flurer, CL (reprint author), US FDA,FORENS CHEM CTR,1141 CENT PKWY,CINCINNATI,OH 45202, USA. NR 22 TC 19 Z9 22 U1 0 U2 7 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD FEB PY 1996 VL 17 IS 2 BP 359 EP 366 DI 10.1002/elps.1150170212 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA UP014 UT WOS:A1996UP01400012 PM 8900943 ER PT J AU Hart, RW Leakey, J Duffy, PH Feuers, RJ Turturro, A AF Hart, RW Leakey, J Duffy, PH Feuers, RJ Turturro, A TI The effects of dietary restriction on drug testing and toxicity SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY LA English DT Article; Proceedings Paper CT 2nd Conference of the International-Federation-of-Societies-of-Toxicologic-Pathologists (IFSTP) CY APR 23-26, 1995 CL TOURS, FRANCE SP IFSTP DE dietary restriction, drug testing and toxicity; drug testing; toxicity testing; testing, drug, toxicity ID CHRONIC CALORIC RESTRICTION; MALE FISCHER-344 RAT; METABOLIZING-ENZYMES; CYTOCHROME-P-450; SYSTEM; AGE RP Hart, RW (reprint author), NATL CTR TOXICOL RES, HFT-020, 3900 NCTR RD, JEFFERSON, AR 72079 USA. NR 32 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0940-2993 J9 EXP TOXICOL PATHOL JI Exp. Toxicol. Pathol. PD FEB PY 1996 VL 48 IS 2-3 BP 121 EP 127 PG 7 WC Pathology; Toxicology SC Pathology; Toxicology GA TY331 UT WOS:A1996TY33100005 PM 8672865 ER PT J AU Lorentzen, RJ AF Lorentzen, RJ TI Impact of the Delaney Clause at the FDA SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY LA English DT Article; Proceedings Paper CT 2nd Conference of the International-Federation-of-Societies-of-Toxicologic-Pathologists (IFSTP) CY APR 23-26, 1995 CL TOURS, FRANCE SP IFSTP DE Delaney Clause; carcinogens, risk; food, safety; nutrition, safety RP Lorentzen, RJ (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,200 C ST SW,WASHINGTON,DC 20204, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GUSTAV FISCHER VERLAG JENA PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0940-2993 J9 EXP TOXICOL PATHOL JI Exp. Toxicol. Pathol. PD FEB PY 1996 VL 48 IS 2-3 BP 198 EP 198 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA TY331 UT WOS:A1996TY33100016 PM 8672876 ER PT J AU Hitchins, AD AF Hitchins, AD TI The International Dairy Federation's procedure for the validation of microbiological analytical methods for dairy foods SO FOOD CONTROL LA English DT Article DE dairy; microbiology methods; validation ID LISTERIA-MONOCYTOGENES AB The International Dairy Federation (IDF/FIL) empirically validates standard microbiological methods for the international dairy industry by using groups of qualified experts. Typically, a logical progression of interlaboratory performance studies conducted by several laboratories leads to a validated method. Control of dairy food matrices and analytes in interlaboratory studies, however, is not rigid. Interlaboratory reproducibility is not usually considered of paramount importance because of the difficulty of establishing test sample homogeneity with low numbers of microorganisms. However, the recent Listeria monocytogenes standard was validated by testing identical inoculated samples after preliminary interlaboratory studies. In the past, IDF/FIL preferred to validate only conventional methods that are widely used in dairy microbiology laboratories rather than novel vapid commercial kit methods. IDF/FIL Standards are internationally recognized. RP Hitchins, AD (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204, USA. NR 8 TC 2 Z9 2 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0956-7135 J9 FOOD CONTROL JI Food Control PD FEB PY 1996 VL 7 IS 1 BP 13 EP 18 DI 10.1016/0956-7135(96)00006-0 PG 6 WC Food Science & Technology SC Food Science & Technology GA UU986 UT WOS:A1996UU98600003 ER PT J AU Andrews, WH AF Andrews, WH TI Validation of modern methods in food microbiology by AOAC INTERNATIONAL collaborative study SO FOOD CONTROL LA English DT Article DE AOAC INTERNATIONAL; collaborative studies; validation AB There is a common misperception that the validation of a microbiological method by an AOAC collaborative study is an arduous undertaking. This paper attempts to dispel that notion by explaining how the system works, identifying the key players, and delineating their responsibilities. Criteria useful in selecting a procedure to be studied collaboratively and the clearance procedures for proposed study protocols and reports of completed studies are discussed. The author offers his views on the evolving internationality of AOAC and suggests that the harmonization of method validation by AOAC and other international organizations would be to the benefit of all. RP Andrews, WH (reprint author), US FDA,DIV MICROBIOL STUDIES,WASHINGTON,DC 20204, USA. NR 14 TC 9 Z9 9 U1 0 U2 4 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0956-7135 J9 FOOD CONTROL JI Food Control PD FEB PY 1996 VL 7 IS 1 BP 19 EP 29 DI 10.1016/0956-7135(96)00007-2 PG 11 WC Food Science & Technology SC Food Science & Technology GA UU986 UT WOS:A1996UU98600004 ER PT J AU Jackson, GJ Wachsmuth, IK AF Jackson, GJ Wachsmuth, IK TI The US food and drug administration's selection and validation of tests for foodborne microbes and microbial toxins SO FOOD CONTROL LA English DT Article DE food safety; microbial contaminants; testing methods; validated methods; peer-reviewed methods; FDA Bacteriological Analytical Manual (BAM); risk assessment; hazard analysis critical control points (HACCP) AB To accomplish its mission in regulating the safety of the national food supply, the US Food and Drug Administration (FDA) must have testing methods that cart be defended in a court of law. These methods must, at minimum, be reproducible. Whenever possible, the methods are validated according to procedures recommended by such international organizations as the AOAC INTERNATIONAL, the International Organization for Standardization (ISO) and the International Dairy Federation (IDF/FIL). Whenever it is not possible to validate a method fully prior to its use, FDA relies on the peer-reviewed scientific literature and the results of its own peer-reviewed research. FDA publishes its preferred methods to test foods for microbial pathogens and toxins in the FDA Bacteriological Analytical Manual (BAM), currently in its 8th edition (1995) and issued by AOAC INTERNATIONAL. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NR 13 TC 2 Z9 2 U1 2 U2 2 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0956-7135 J9 FOOD CONTROL JI Food Control PD FEB PY 1996 VL 7 IS 1 BP 37 EP 39 DI 10.1016/0956-7135(96)84938-3 PG 3 WC Food Science & Technology SC Food Science & Technology GA UU986 UT WOS:A1996UU98600006 ER PT J AU Gendel, SM AF Gendel, SM TI Computational analysis of the specificity of 16S rRNA-derived signature sequences for identifying food-related microbes SO FOOD MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; RIBOSOMAL-RNA; LISTERIA-MONOCYTOGENES; OLIGONUCLEOTIDE PROBES; RAPID DETECTION; HELICOBACTER-PYLORI; IDENTIFICATION; HYBRIDIZATION; CAMPYLOBACTER; CLOSTRIDIUM AB The efficacy of oligonucleotide-based molecular diagnostics for the identification of food-related microbes is critically dependent on the sequences of the gene probes or amplification primers used. Computational specificity analysis was used to evaluate and compare the apparent specificity of ribosomal small subunit (SSU)-derived signature sequences from a wide range of food-related microbes. Nine signature sequences were obtained from the SSU sequences of each of 40 species, the apparent specificity of each signature sequence was determined by using the Ribosomal Database Project (RDP) microbial SSU dataset. Use of the RDP database made if possible to compare results from a phylogenetically heterogeneous group of microbes. At least one species-specific signature sequence was found for 39 of the 40 species. Signature sequences derived from the SSU VI and V2 variable regions were the most specific. The apparent specificity of each of 77 SSU-based identification sequences obtained from the literature was also tested. Although a relatively large number of the published sequences were either non-specific or could not be matched to homologous sequences in the RDP database, most species-specific published sequences also originated from the VI and V2 variable regions. These results show that computational specificity analysis and sequence databases can be used to assess and compare the specificity of SSU-derived signature sequences for any food-related microbe, but that the addition of new sequences to the databases necessitates periodic reassessment of specificity. (C) 1996 Academic Press Limited. RP Gendel, SM (reprint author), US FDA,BIOTECHNOL STUDIES BRANCH,NATL CTR FOOD SAFETY & TECHNOL,6502 S ARCHER RD,SUMMIT ARGO,IL 60501, USA. NR 46 TC 11 Z9 11 U1 0 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD FEB PY 1996 VL 13 IS 1 BP 1 EP 15 DI 10.1006/fmic.1996.0001 PG 15 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA UC260 UT WOS:A1996UC26000001 ER PT J AU Wolff, GL AF Wolff, GL TI Variability in gene expression and tumor formation within genetically homogeneous animal populations in bioassays SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID VY F1-HYBRID MICE; PHENOBARBITAL PROMOTION; HEPATOTUMORIGENESIS; CARCINOGENICITY AB Considerable variation in susceptibility to tissue-specific tumor formation in response to chronic treatment with low or intermediate dose levels of putative carcinogens is observed within populations of genetically homogeneous test animals under controlled environmental conditions. Experimental evidence from National Toxicology Program studies is reviewed, as are studies of differing degrees of carcinogenic response and tumor promotion among iso-and congenic mice carrying the A(vy) (viable yellow) mutation. The data suggest that individual variations in carcinogenic response among genetically homogeneous animals may derive primarily from differences in regulation of gene transcription. Differences in posttranscriptional and posttranslational processing of gene products are probably also contributing factors. The viable yellow A(vy)/a mouse model system is uniquely suited for investigating the developmental and molecular bases of this phenotypic variability in genetically homogeneous populations since various degrees of carcinogenic response and promotion of tumor formation can be predicted, a priori, at least as early as 7 days of age by correlation with coat color patterns. Ectopic expression of the agouti protein results in enhanced susceptibility to tumor formation in tissues which are already sensitized to neoplastic transformation by their strain genome. The differences in tumorigenic response and coat color pattern among A(vy)/- mice appear to be associated with different DNA methylation states of the promoter of an intracisternal A particle inserted into exon 1A of the agouti gene. C1 UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL TOXICOL,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM MOLEC BIOL,LITTLE ROCK,AR 72205. RP Wolff, GL (reprint author), US FDA,US DEPT HHS,NATL CTR TOXICOL RES,DIV NUTR TOXICOL,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 30 TC 13 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD FEB PY 1996 VL 29 IS 2 BP 176 EP 184 DI 10.1006/faat.1996.0019 PG 9 WC Toxicology SC Toxicology GA TX206 UT WOS:A1996TX20600003 PM 8742313 ER PT J AU Greenman, DL Morrissey, RL Blakemore, W Crowell, J Siitonen, P Felton, P Allen, R Cronin, G AF Greenman, DL Morrissey, RL Blakemore, W Crowell, J Siitonen, P Felton, P Allen, R Cronin, G TI Subchronic toxicity of triethylenetetramine dihydrochloride in B6C3F1 mice and F344 rats SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID HYDROXYLASE-ACTIVITY; COPPER DEFICIENCY; TETRAMINE DIHYDROCHLORIDE; D-PENICILLAMINE; DIET; METABOLISM; ESTRADIOL; SUCROSE AB Triethylenetetramine dihydrochloride (trien-2HCl; CAS No. 38260-01-04), a chelating agent used to treat Wilson's disease patients who are intolerant of the drug of choice, was tested for subchronic toxicity in B6C3F1 mice and F344 rats. Mice and rats received trien-2HCl in the drinking water at concentrations of 0, 120, 600, or 3000 ppm for up to 92 days. Twenty mice and 18 rats of each sex were assigned to each dose group fed either a cereal-based (NIH-31) or a purified (AIN-76A) diet, both containing nutritionally adequate levels of copper. An additional control group of rats and mice received a Cu-deficient AIN-76A diet. This low copper diet resulted in Cu-deficiency symptoms, such as anemia, liver periportal cytomegaly, pancreatic atrophy and multifocal necrosis, spleen hematopoietic cell proliferation, and increased heart weight, together with undetectable levels of plasma copper in rats but not in mice. Trien-2HCl lowered plasma copper levels somewhat (at 600 and 3000 ppm) in rats fed the AIN-76A diet, but did not induce the usual signs of copper deficiency. Trien-2HCl caused an increased frequency of uterine dilatation at 3000 ppm in rats fed AIN-76A diet that was not noted in females fed the Cu-deficient diet. Trien-2HCl toxicity occurred only in mice in the highest dose group fed an AIN-76A diet. Increased frequencies of inflammation of the lung interstitium and liver periportal fatty infiltration were seen in both sexes, and hematopoietic cell proliferation was seen in the spleen of males. Kidney and body weights were reduced in males as was the incidence of renal cytoplasmic vacuolization. There were no signs of copper deficiency in mice exposed to trien-2HCl. The only effect of trien-2HCl in animals fed the NIH-31 diet was a reduced liver copper level in both rat sexes, noted at 3000 ppm. (C) 1996 Society of Toxicology C1 NATL CTR TOXICOL RES,DIV NUTR TOXICOL,JEFFERSON,AR 72079. NATL CTR TOXICOL RES,PATHOL ASSOCIATES INC,JEFFERSON,AR 72079. NATL CTR TOXICOL RES,DIV CHEM,JEFFERSON,AR 72079. NATL CTR TOXICOL RES,SYST DEV CORP,JEFFERSON,AR 72079. RP Greenman, DL (reprint author), NATL CTR TOXICOL RES,OFF ASSOCIATE DIRECTOR SCI COORDINAT,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 35 TC 9 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD FEB PY 1996 VL 29 IS 2 BP 185 EP 193 DI 10.1006/faat.1996.0020 PG 9 WC Toxicology SC Toxicology GA TX206 UT WOS:A1996TX20600004 PM 8742314 ER PT J AU Shimizu, YK Feinstone, SM Kohara, M Purcell, RH Yoshikura, H AF Shimizu, YK Feinstone, SM Kohara, M Purcell, RH Yoshikura, H TI Hepatitis C virus: Detection of intracellular virus particles by electron microscopy SO HEPATOLOGY LA English DT Article ID NON-B HEPATITIS; NON-A; CHIMPANZEES; INDUCTION AB We previously demonstrated that a human T-cell Line, HPBMa10-2 derived from HPBALL, was capable of supporting a productive infection of hepatitis C virus (HCV). We subsequently found Daudi cells, a human B-cell line, to be susceptible to HCV infection. Employing these cell Lines infected with HCV as well as liver obtained during the acute phase of hepatitis C from a chimpanzee, we observed intracellular HCV particles by electron microscopy (EM). We detected viruslike particles with a diameter of approximately 50 nm in the cytoplasmic vesicles. In Daudi cells harvested 15 days after virus inoculation, the appearance of cytoplasmic tubular structures which we originally described for chimpanzee hepatocytes in association with HCV infection was noted. Immunoperoxidase EM using antibodies against HCV core and envelope demonstrated that the particles contained the viral antigens. C1 TOKYO METROPOLITAN INST MED SCI,DEPT MICROBIOL,TOKYO 113,JAPAN. NIH,INFECT DIS LAB,BETHESDA,MD. US FDA,DIV VIROL,BETHESDA,MD. RP Shimizu, YK (reprint author), UNIV TOKYO,FAC MED,DEPT BACTERIOL,BUNKYO KU,7-3-1 HONGO,TOKYO 113,JAPAN. NR 14 TC 140 Z9 143 U1 0 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 1996 VL 23 IS 2 BP 205 EP 209 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA TU856 UT WOS:A1996TU85600002 PM 8591842 ER PT J AU Styrt, BA AF Styrt, BA TI Risks of infection and protective strategies for the asplenic patient SO INFECTIOUS DISEASES IN CLINICAL PRACTICE LA English DT Review ID SICKLE-CELL DISEASE; STREPTOCOCCUS-PNEUMONIAE; POSTSPLENECTOMY SEPSIS; SPLENECTOMY; CHILDREN; PROPHYLAXIS; PENICILLIN; EFFICACY RP US FDA, EPIDEMIOL BRANCH, DIV EPIDEMIOL & SURVEILLANCE, CTR DRUG EVALUAT & RES, HFD-733, ROCKVILLE, MD 20857 USA. NR 42 TC 7 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1056-9103 EI 1536-9943 J9 INFECT DIS CLIN PRAC JI Infect. Dis. Clin. Pract. PD FEB PY 1996 VL 5 IS 2 BP 94 EP 100 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TX441 UT WOS:A1996TX44100008 ER PT J AU Myers, MR AF Myers, MR TI A numerical investigation into factors affecting anesthetic distribution during spinal anesthesia SO JOURNAL OF BIOMECHANICS LA English DT Article DE anesthetic transport; anesthesia modeling; numerical simulation ID MODEL AB The factors affecting distribution of anesthetic within the spinal column are of current interest due to recent reports of neurological injury occurring during spinal anesthesia. This paper describes a numerical model for simulating anesthetic dispersion, and applies the model to the evaluation of spinal-column size, anesthetic injection rate, and catheter orientation as factors influencing the anesthetic distribution. The model is based upon the finite-element method and incorporates a three-dimensional geometry derived from images of human spinal columns. Simulation results show that the ratio of the cross-sectional dimension of the subarachnoid space within the spinal column to the diameter of the catheter is a critical parameter, with low values of this ratio producing the most uniform anesthetic distributions. Increasing injection rate is found to produce a less uniform distribution in a global sense (higher total volume of anesthetic in the 'sacral' half) but a more uniform distribution in a localized sense (lower concentrations at critical points). Finally, the anesthetic distribution is demonstrated to be highly sensitive to orientation angle at high injection rates. RP Myers, MR (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,HYDRODYNAM & ACOUST BRANCH,HFZ-132,12721 TWINBROOK PKWY,ROCKVILLE,MD 20852, USA. NR 8 TC 7 Z9 9 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD FEB PY 1996 VL 29 IS 2 BP 139 EP & DI 10.1016/0021-9290(95)00043-7 PG 10 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA TP161 UT WOS:A1996TP16100001 PM 8849807 ER PT J AU Pastakia, KB Brownson, NE Terle, DA Harvath, L AF Pastakia, KB Brownson, NE Terle, DA Harvath, L TI Adhesion of platelets to chemotactically responsive and non-responsive neutrophils SO JOURNAL OF CLINICAL PATHOLOGY-CLINICAL MOLECULAR PATHOLOGY EDITION LA English DT Article DE platelets; neutrophils; migrate ID STIMULATED PLATELETS; ACTIVATED PLATELETS; HUMAN-BLOOD; MONOCYTES; LEUKOCYTES; RECEPTORS; BINDING AB Aims-To investigate the heterotypic adhesion of unactivated platelets to chemotactically responsive (migrated) and non-responsive (non-migrated) polymorphonuclear neutrophils (PMN). Methods-Platelets and PMN were isolated from autologous, normal blood. Migrated and non-migrated PMN were separated after N-formylmethionyl-leucylphenylalanine (FMLP) stimulation. Platelets were labelled with a fluorescent monoclonal antibody directed against CD41 (GPIIb-IIIa). Platelets (3x10(8)/ml) and PMN (3 x 10(6)/ml) were incubated together. Heterotypic cell adhesion was measured in isolated PMN and PMN co-incubated with platelets by flow cytometric analysis of platelet marker fluorescence in PMN gated events. Platelet-PMN adhesion was also visualised by fluorescence microscopy. Results-In studies of isolated PR IN, contaminating platelets were bound to 16-34% of unstimulated PMN, 7-22% of stimulated PMN, 2-4% of migrated PMN, and 17-24% of non-migrated PMN. When platelets were co-incubated with migrated or non-migrated PMN, 15-78% of PMN bound one or two platelets. Conclusions-Unactivated platelets adhere to isolated PMN in vitro. Fewer unactivated platelets were adhered to migrated PMN than to non-migrated PMN in isolated PMN preparations. These results indicate that platelets adhering to PMN are removed during PMN migration. RP Pastakia, KB (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,LAB CELLULAR HEMATOL,BLDG 29,ROOM 329,BETHESDA,MD 20892, USA. NR 20 TC 3 Z9 3 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 1355-2910 J9 J CLIN PATHOL-CL MOL JI J. Clin. Pathol.-Clin. Mol. Pathol. Ed. PD FEB PY 1996 VL 49 IS 1 BP M17 EP M22 PG 6 WC Pathology SC Pathology GA TV766 UT WOS:A1996TV76600004 ER PT J AU Lu, ZB Rezapkin, GV Douthitt, MP Ran, YX Asher, DM Levenbook, IS Chumakov, KM AF Lu, ZB Rezapkin, GV Douthitt, MP Ran, YX Asher, DM Levenbook, IS Chumakov, KM TI Limited genetic changes in the Sabin 1 strain of poliovirus occurring in the central nervous system of monkeys SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID POLYMERASE ERROR FREQUENCY; 5' NONCODING REGION; TYPE-2 POLIOVIRUS; RNA; VACCINE; NEUROVIRULENCE; DETERMINANTS; IDENTIFICATION; TEMPERATURE; ATTENUATION AB Replication of attenuated poliovirus strains results in their partial deattenuation. Recently we identified mutations accumulating in the Sabin 1 poliovirus in cell cultures. Here we report genetic changes occurring in this virus during replication in the central nervous system (CNS) of monkeys. Viruses isolated from different parts of the CNS of rhesus monkeys (inoculated into the spinal cord) were screened for sequence heterogeneities and newly identified mutations were independently confirmed and quantified using mutant analysis by PCR and restriction enzyme cleavage (MAPREC). All consistently accumulating mutations identified in this study were located in untranslated regions: GU --> AU or GU --> GC substitution at a complementary pair formed by nucleotides 480 and 525, U --> C substitution at nucleotide 612, and GU --> AU or GU --> GC substitution of a base pair formed by the nucleotides 7427/7441 immediately preceding the poly(A) tract. All these mutations except one (7427) were previously identified in cell culture passages or stool isolates from vaccinees. Sequencing of 11 CNS isolates also identified a few random silent mutations that accumulated as neutral 'passengers', passively coselected with genuinely selectable mutations present on the same RNA molecule. One isolate also contained the wild-type base at nucleotide 2741 (Ala(88) --> Thr in VPI). Our results demonstrate a remarkable genetic stability of the Sabin 1 poliovirus in the CNS of monkeys, suggesting that deattenuation is determined by a very limited number of mutations. These mutations can be assayed by MAPREC to monitor the consistency of oral poliovirus vaccine (OPV) production. C1 US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852. NR 27 TC 9 Z9 10 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD FEB PY 1996 VL 77 BP 273 EP 280 DI 10.1099/0022-1317-77-2-273 PN 2 PG 8 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA TT842 UT WOS:A1996TT84200015 PM 8627231 ER PT J AU Smith, JF Dennis, JE AF Smith, JF Dennis, JE TI Toward harmonized laser product standards SO JOURNAL OF LASER APPLICATIONS LA English DT Article AB This article traces the history of efforts to harmonize the requirements of the Center for Devices and Radiological Health's (CDRH) Federal Performance Standard for Laser Products in the United States with those of the International Electrotechnical Commission's (IEC) International Standard, Safety of Laser Products, IEC 825-1. C1 US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857. RP Smith, JF (reprint author), ROCKWELL LASER IND,JACKSON SPRINGS,NC 27281, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU LASER INST AMER PI ORLANDO PA 12424 RESEARCH PARKWAY SUITE 125, ORLANDO, FL 32826 SN 1042-346X J9 J LASER APPL JI J. Laser Appl. PD FEB PY 1996 VL 8 IS 1 BP 9 EP 12 PG 4 WC Materials Science, Multidisciplinary; Optics; Physics, Applied SC Materials Science; Optics; Physics GA UG055 UT WOS:A1996UG05500004 ER PT J AU Freiman, JP FitzSimmons, SC AF Freiman, JP FitzSimmons, SC TI Colonic strictures in patients with cystic fibrosis: Results of a survey of 114 cystic fibrosis care centers in the United States SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE cystic fibrosis; pancreatic enzymes; colonic strictures AB We describe 15 cases of stricture of the colon requiring surgery in cystic fibrosis patients identified from a survey of 114 cystic fibrosis care centers in the United States. Patient ages ranged from 2 to 8 years, seven of the 15 patients were female. A history of meconium ileus was reported in nine of the 15 cases. Fibrosis of the submucosa was described in 14 surgical pathology reports. Pancreatic enzyme use history was available from 14 reports. All had taken delayed-release products for 6-96 months at average doses ranging from 6,700 to 29,100 units lipase/kg/meal, but only eight of them used products containing >20,000 units lipase per capsule prior to surgery. C1 CYST FIBROSIS FDN,BETHESDA,MD 20814. US FDA,CTR DRUG EVALUAT & RES,OFF EPIDEMIOL & BIOSTAT,DIV EPIDEMIOL & SURVEILLANCE,ROCKVILLE,MD 20857. NR 9 TC 28 Z9 28 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD FEB PY 1996 VL 22 IS 2 BP 153 EP 156 DI 10.1097/00005176-199602000-00005 PG 4 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA TU356 UT WOS:A1996TU35600005 PM 8642487 ER PT J AU Schall, R Williams, RL AF Schall, R Williams, RL TI Towards a practical strategy for assessing individual bioequivalence SO JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS LA English DT Article DE bootstrap; individual bioequivalence; moment-based criteria; population bioequivalence; probability-based criteria; scaled criteria; unsealed criteria AB Bioequivalence of two drug formulations is currently defined by drug regulatory authorities in terms of the mean responses following administration of the test and reference formulations (average bioequivalence). However, the various potential shortcomings of average bioequivalence are now understood, and switchability, and thus individual bioequivalence, has become a reasonable expectation when changing from one pharmaceutically equivalent drug product to another. Progress has been made in developing criteria for individual bioequivalence, and an overview and classification of most of the different approaches to the assessment of individual bioequivalence have been achieved. As a consequence of this classification, the different character of scaled and unscaled bioequivalence measures has been recognized and, in turn, this leads to the proposal, made in this paper, or using both scaled and unscaled criteria for bioequivalence assessment of different classes of drugs, depending on their within-subject variability and therapeutic range. This strategy addresses the shortcomings of average bioequivalence, and, when applied to data sets from bioequivalence studies with four-period replicate crossover designs, turns out to have some satisfactory properties. Open questions and areas for further research are discussed. C1 US FDA, CDER, ROCKVILLE, MD 20587 USA. RP Schall, R (reprint author), UNIV ORANGE FREE STATE, DEPT PHARMACOL, DIV BIOMETRY, POB 339 G6, BLOEMFONTEIN 9300, SOUTH AFRICA. RI Schall, Robert/A-9174-2012 NR 16 TC 57 Z9 59 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-466X J9 J PHARMACOKINET BIOP JI J. Pharmacokinet. Biopharm. PD FEB PY 1996 VL 24 IS 1 BP 133 EP 149 DI 10.1007/BF02353513 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UW532 UT WOS:A1996UW53200006 PM 8827586 ER PT J AU Booth, SL Pennington, JAT Sadowski, JA AF Booth, SL Pennington, JAT Sadowski, JA TI Food sources and dietary intakes of vitamin K-1 (phylloquinone) in the American diet: Data from the FDA Total Diet Study SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID HUMAN-MILK; K DEFICIENCY; COWS MILK; OSTEOCALCIN; INFANTS AB Objective To identify important food sources and estimate dietary intake of vitamin K-1 (phylloquinone) in the American can diet. Design Core foods from the US Food and Drug Administration (FDA) Total Diet Study (TDS), which was based on the 1987-88 Nationwide Food Consumption Survey (NFCS), were analyzed for vitamin K-1. These nutrient values were then applied to the FDA TDS consumption model. Subjects Of the NFCS participants within the 14 selected age-gender groups, 3,634 who had 3 days of dietary data were included in the FDA TDS consumption model. Main outcome measures Vitamin K-1 intakes were estimated for each of the age-gender groups. the percentage contribution of each food item to total intake of vitamin K-1 was calculated from the FDA TDS model. Results Of the 14 age-gender groups selected, the 25- to 30-year-old women and men consumed less than the current Recommended Dietary Allowance (RDA) for vitamin K. In contrast, formula-fed infants had estimated vitamin K-1 intakes six times greater than the RDA. All other groups consumed amounts within the recommended daily intakes but lower than 90 mu g/day. The top contributors to total vitamin K-1 intake were dark-green vegetables, although the fats and oils added to mixed dishes and desserts were also important contributors. The proportion of vitamin K-1 obtained horn vegetables increased with age. Applications The data identify important dietary sources of vitamin K-1 in the American diet. This knowledge can be used to develop dietary assessment instruments for use in epidemiologic studies. C1 TUFTS UNIV,SCH NUTR,BOSTON,MA 02111. US FDA,DIV NUTR,WASHINGTON,DC 20204. RP Booth, SL (reprint author), TUFTS UNIV,USDA,JEAN MAYER HUMAN NUTR RES CTR AGING,711 WASHINGTON ST,BOSTON,MA 02111, USA. NR 39 TC 86 Z9 88 U1 0 U2 3 PU AMER DIETETIC ASSN PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD FEB PY 1996 VL 96 IS 2 BP 149 EP 154 DI 10.1016/S0002-8223(96)00044-2 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA UQ841 UT WOS:A1996UQ84100012 PM 8557941 ER PT J AU Boyd, RK Henion, JD Alexander, M Budde, WL Gilbert, JD Musser, SM Palmer, C Zurek, EK AF Boyd, RK Henion, JD Alexander, M Budde, WL Gilbert, JD Musser, SM Palmer, C Zurek, EK TI Mass spectrometry and good laboratory practices SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Editorial Material C1 CORNELL UNIV,ITHACA,NY. SANDOZ PHARMACEUT CORP,E HANOVER,NJ. US EPA,ENVIRONM MONITORING SYST LAB,CINCINNATI,OH 45268. MERCK SHARP & DOHME RES LABS,W POINT,PA. US FDA,WASHINGTON,DC 20204. GOLDMAN ASSOCIATES INT,HERNDON,VA. RP Boyd, RK (reprint author), NATL RES COUNCIL CANADA,INST MARINE BIOSCI,1411 OXFORD ST,HALIFAX,NS B3H 3Z1,CANADA. NR 11 TC 4 Z9 4 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD FEB PY 1996 VL 7 IS 2 BP 211 EP 218 DI 10.1016/1044-0305(95)00631-1 PG 8 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA TX747 UT WOS:A1996TX74700013 PM 24203245 ER PT J AU Bour, S Schubert, U Peden, K Strebel, K AF Bour, S Schubert, U Peden, K Strebel, K TI The envelope glycoprotein of human immunodeficiency virus type 2 enhances viral particle release: A Vpu-like factor? SO JOURNAL OF VIROLOGY LA English DT Article ID PROTEIN INDUCES DEGRADATION; CYTOPLASMIC DOMAIN; CELL-LINES; HIV-1 GAG; CD4; EXPRESSION; GENE; ENV; MORPHOGENESIS; INFECTIVITY AB The Vpu protein is a human immunodeficiency virus type 1 (HIV-1)-specific accessory protein that is required for the efficient release of viral particles from infected cells, Even though HIV-2 does not encode Vpu, we found that this virus is nevertheless capable of efficiently releasing virus particles. In fact, the rate of virus release from HeLa cells transfected with a full-length molecular clone of HIV-2, ROD10, was comparable to that observed for the vpr(+) HIV-1 NL4-3 isolate and was not further enhanced by expression of Vpu in trans. However, consistent with previous observations showing that HIV-2 particle release is Vpu responsive in the context of HIV-1/HIV-2 chimeric constructs, exchanging the gag-pol region of NL4-3 with the corresponding region from pROD10 rendered the resulting chimeric virus Vpu responsive, Our finding that the responsiveness of HIV-2 particle release to Vpu is context dependent suggested the presence of a Vpu-like factor(s) encoded by HIV-2. Using chimeric proviruses encoding HIV-2 gag and pol in the context of the HIV-1 provirus that were coexpressed with subgenomic HIV-2 constructs, we found that the HIV-2 envelope glycoprotein had the ability to enhance HIV-2 particle release with an efficiency comparable to that of the HIV-I Vpu protein, Conversely, inactivation of the HIV-2 env gene in the original ROD10 clone resulted in a decrease in the rate of viral particle release to a level that was comparable to that of Vpu-deficient HIV-1 isolates. Providing the wild-type envelope in trans rescued the particle release defect of the ROD10 envelope mutant, Thus, unlike HIV-1, which encodes two separate proteins to regulate virus release or to mediate viral entry, the HIV-2 Env protein has evolved to perform both functions. C1 US FDA,CTR BIOL EVALUAT & RES,LAB RETROVIRUS RES,BETHESDA,MD 20892. RP Bour, S (reprint author), NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892, USA. NR 58 TC 86 Z9 87 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1996 VL 70 IS 2 BP 820 EP 829 PG 10 WC Virology SC Virology GA TP526 UT WOS:A1996TP52600018 PM 8551620 ER PT J AU Eiden, MV Farrell, KB Wilson, CA AF Eiden, MV Farrell, KB Wilson, CA TI Substitution of a single amino acid residue is sufficient to allow the human amphotropic murine leukemia virus receptor to also function as a gibbon ape leukemia virus receptor SO JOURNAL OF VIROLOGY LA English DT Article ID SUBGROUP-B; INFECTION; CELLS AB We have previously reported the unique properties of a receptor for amphotropic murine leukemia viruses (A-MuLVs) expressed on Chinese hamster E36 cells (C. A. Wilson, K. B. Farrell, and M. V. Eiden, J. Virol. 68:7697-7703, 1994). This receptor, HaPiT2 (formerly designated EAR), in contrast to the human form of the A-MuLV receptor (PiT2), functions as a receptor not only for A-MuLVs but also for gibbon ape leukemia virus (GALV). Comparison of the deduced amino acid sequences of the HaPiT2 and PiT2 proteins suggested that differences in the amino acid composition of the extracellular region(s) of the hamster and human proteins account for their functional differences, We substituted extracellular regions of HaPiT2 for those of PiT2 to map the region of the HaPiT2 protein required for GALV receptor function, Only those PiT2-HaPiT2 chimeric receptors containing the fourth and fifth extracellular regions of HaPiT2 functioned as GALV receptors, We have now determined that the substitution of a single amino acid residue, glutamic acid, for the lysine residue at position 522 in the fourth extracellular region of the PiT2 protein is sufficient to render PiT2 functional as a GALV receptor. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. US FDA,DIV CELLULAR & GENE THERAPIES,LAB MOLEC TUMOR BIOL,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20892. NR 22 TC 43 Z9 43 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1996 VL 70 IS 2 BP 1080 EP 1085 PG 6 WC Virology SC Virology GA TP526 UT WOS:A1996TP52600048 PM 8551566 ER PT J AU Wang, RF Campbell, W Cao, WW Summage, C Steele, RS Cerniglia, CE AF Wang, RF Campbell, W Cao, WW Summage, C Steele, RS Cerniglia, CE TI Detection of Pasteurella pneumotropica in laboratory mice and rats by polymerase chain reaction SO LABORATORY ANIMAL SCIENCE LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; INFECTION AB A 16S rDNA-based polymerase chain reaction (PCR) method specific for Pasteurella pneumotropica was developed. The PCR product, a 395-base pair DNA fragment, was amplified from P. pneumotropica and not from 42 other bacterial species tested, including four other Pasteurella species and Actinobacillus ureae, The PCR method was used to identify 13 previously isolated strains that had been identified as P. pneumotropica by conventional methods: 12 were confirmed by PCR; one that was PCR-negative was re-examined by biochemical methods and determined to be A. ureae. The PCR detection of P. pneumotropica in nasopharyngeal swab specimens from 121 surveillance animals (15 inbred mice and 5 inbred rats from 29 animal rooms) had a high carrier state in healthy laboratory animals; for example, rat swab specimens were 89.6% (43/48) positive by PCR, 8.3% were positive by the direct culture-biochemical method, and 16.7% were positive by the enrichment culture-biochemical method. The positive rate for mice (21.9% [16/73]) was lower than that for rats. C1 US FDA,NATL CTR TOXICOL RES,DIV MICROBIOL,JEFFERSON,AR 72079. NR 21 TC 30 Z9 32 U1 0 U2 3 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD FEB PY 1996 VL 46 IS 1 BP 81 EP 85 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA TW872 UT WOS:A1996TW87200017 PM 8699827 ER PT J AU Jones, SB Tiffany, LJ Garmestani, K Gansow, OA Kozak, RW AF Jones, SB Tiffany, LJ Garmestani, K Gansow, OA Kozak, RW TI Evaluation of dithiol chelating agents as potential adjuvants for anti-IL-2 receptor lead or bismuth alpha radioimmunotherapy SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE dithiol chelating; radiotoxicity; DMPS ID TAC MONOCLONAL-ANTIBODY; SODIUM 2,3-DIMERCAPTOPROPANE-1-SULFONATE; ACID; RAT; METABOLISM; STABILITY; EXCRETION; THERAPY AB The dithiol chelating agents 2,3-dimercapto-1-propanesulfonic acid (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) were evaluated for use as potential adjuvants to reduce or prevent radiotoxicity in anti interleukin 2 receptor (IL-2R) Lead-212 or Bismuth-212 alpha-radioimmunotherapy. DMPS was less toxic than DMSA to tumor cell lines in culture. No adverse effects on the ability of an anti-IL-2R monoclonal antibody (MAb) to bind to its specific antigen were detected using DMPS or DMSA at concentrations up to 600 ug/mL in 10% or 100% mouse serum. After a 5-day oral administration of chelating agent, neither acute nor chronic toxicities on blood hematology, blood chemistry or organ weights were observed for treated mice. DMPS and DMSA were effective in accelerating whole body clearance of the gamma-emitting tracer Bismuth-206. Both chelates significantly reduced femur uptake of tracer when compared to nontreated control mice. However, only DMPS prevented early (2 h postinjection) renal accumulation. These studies support the use of DMPS as a potential adjuvant chelation therapy in Lead-212 or Bismuth-212 radioimmunotherapy protocols. C1 NATL NAVAL MED CTR, DEPT OTOLARYNGOL HEAD & NECK SURG, BETHESDA, MD 20889 USA. US FDA, CTR BIOL EVALUAT & RES, DIV MONOCLONAL ANTIBODIES, BETHESDA, MD 20892 USA. NCI, NIH, RADIAT ONCOL BRANCH, BETHESDA, MD 20892 USA. NR 27 TC 11 Z9 12 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD FEB PY 1996 VL 23 IS 2 BP 105 EP 113 DI 10.1016/0969-8051(95)02006-3 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TW682 UT WOS:A1996TW68200001 PM 8868281 ER PT J AU Halsey, NA Chesney, PJ Gerber, MA Gromisch, DS Kohl, S Marcy, SM Marks, MI Murray, DL Overall, JC Pickering, LK Whitley, RJ Yogev, R Peter, G Berkelman, RL Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR AF Halsey, NA Chesney, PJ Gerber, MA Gromisch, DS Kohl, S Marcy, SM Marks, MI Murray, DL Overall, JC Pickering, LK Whitley, RJ Yogev, R Peter, G Berkelman, RL Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR TI The relationship between pertussis vaccine and central nervous system sequelae: Continuing assessment SO PEDIATRICS LA English DT Article ID IMMUNIZATION AB Reassessment of the role of whole-cell pertussis vaccine as a cause of permanent neurologic damage is necessitated by the 10-year follow-up of the National Childhood Encephalopathy Study (NCES) in Great Britain. The findings of this study demonstrate that infants and young children with serious acute neurologic disorders are at an increased risk of later neurologic impairment or death, irrespective of the initial precipitating event. The results, however, do not establish a causal relationship between pertussis vaccination and chronic neurologic abnormalities. The Academy reaffirms its earlier conclusion that whole-cell pertussis vaccine has not been proven to be a cause of brain damage and continues to recommend pertussis vaccination in accordance with the guidelines in the 1994 Red Book.(1) C1 US FDA,ROCKVILLE,MD 20857. AMER THORAC SOC,NEW YORK,NY. NIH,BETHESDA,MD 20892. RP Halsey, NA (reprint author), CTR DIS CONTROL & PREVENT,WASHINGTON,DC, USA. NR 13 TC 13 Z9 13 U1 0 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD FEB PY 1996 VL 97 IS 2 BP 279 EP 281 PG 3 WC Pediatrics SC Pediatrics GA TU284 UT WOS:A1996TU28400027 ER PT J AU Halsey, NA Chesney, PJ Gerber, MA Gromisch, DS Kohl, S Marcy, SM Marks, MI Murray, DL Overall, JC Pickering, LK Whitley, RJ Yogev, R Peter, G Berkelman, RL Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR AF Halsey, NA Chesney, PJ Gerber, MA Gromisch, DS Kohl, S Marcy, SM Marks, MI Murray, DL Overall, JC Pickering, LK Whitley, RJ Yogev, R Peter, G Berkelman, RL Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR TI Update on tuberculosis skin testing of children SO PEDIATRICS LA English DT Article C1 US FDA, ROCKVILLE, MD 20857 USA. AMER THORAC SOC, NEW YORK, NY USA. NIH, BETHESDA, MD USA. RP CTR DIS CONTROL & PREVENT, WASHINGTON, DC USA. NR 11 TC 37 Z9 37 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD FEB PY 1996 VL 97 IS 2 BP 282 EP 284 PG 3 WC Pediatrics SC Pediatrics GA TU284 UT WOS:A1996TU28400028 ER PT J AU Caputo, FA Ali, SF Wolff, GL Scallet, AC AF Caputo, FA Ali, SF Wolff, GL Scallet, AC TI Neonatal MSG reduces hypothalamic DA, beta-endorphin, and delays weight gain in genetically obese (A(viable yellow)/a) mice SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE MSG; development; obesity; food intake; genetic; mice hypothalamus; viable yellow; beta-endorphin; dopamine(DA); serotonin(5-HT); (A(vy)); agouti ID MELANOCYTE-STIMULATING HORMONE; MONOSODIUM GLUTAMATE TREATMENT; MEDIOBASAL HYPOTHALAMUS; MOUSE; LESIONS; RATS; METABOLISM; BRAIN; HYPERINSULINEMIA; CORTICOSTERONE AB Neonatal treatment with monosodium glutamate (MSG) decreases proopiomelanocortin (POMC) peptides and results in obesity. The yellow mouse is a model of obesity induced by the viable yellow (A(vy)) gene at the agouti locus on Chromosome 2, which results in overproduction of a POMC receptor antagonist. Thus we hypothesized that MSG, when imposed on the genetically susceptible model, would alter the development of obesity. Both yellow obese (A(vy)) and black lean (a/a) males were injected on Postnatal Days 1, 3, 5, 7, and 9 with 2.0 mg/g body weight MSG or saline SC. Their food intake, growth parameters, and neurochemical status were examined. Paradoxically, MSG interacted with the yellow phenotype to delay the rapid rate of weight gain characteristic of this model (p < 0.05). Food intake was decreased (p < 0.05) in both phenotypes treated with MSG, as was hypothalamic content of dopamine (p < 0.05) and of the POMC peptide, beta-endorphin (p < 0.001). The yellow obese phenotype was more sensitive than the black lean phenotype to the neurochemical effects of early postnatal MSG administration. Recent reports suggest the agouti locus protein is an antagonist of the receptor for another POMC peptide, melanocyte-stimulating hormone (MSH). Therefore, the balance of functional activity between various POMC peptides appears to be an important factor in the development of both acquired and genetic obesity. C1 US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,JEFFERSON,AR 72079. US FDA,NATL CTR TOXICOL RES,DIV NUTR TOXICOL,JEFFERSON,AR 72079. NR 43 TC 10 Z9 10 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD FEB PY 1996 VL 53 IS 2 BP 425 EP 432 DI 10.1016/0091-3057(95)02009-8 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA TT772 UT WOS:A1996TT77200028 PM 8808153 ER PT J AU Sobotka, TJ Whittaker, P Sobotka, JM Brodie, RE Quander, DY Robl, M Bryant, M Barton, CN AF Sobotka, TJ Whittaker, P Sobotka, JM Brodie, RE Quander, DY Robl, M Bryant, M Barton, CN TI Neurobehavioral dysfunctions associated with dietary iron overload SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE iron; dietary overload; dietary deficiency; neurobehavior; rodent ID GAMMA-AMINOBUTYRIC ACID; BRAIN IRON; LIPID-PEROXIDATION; RAT-BRAIN; REGIONAL DISTRIBUTION; DEFICIENT RATS; INJECTION; DOPAMINE; SEIZURES; BIOCHEMISTRY AB Excessive dietary Fe is known to be toxic, but the extent of neurobiological involvement is not clear. In the present study male weanling rats were fed diets containing Fe at 35 (control), 350, 3500, or 20000 ppm for 12 wk. An Fe-deficient group (4 ppm) was included for comparison. Rats were tested for behavioral and body weight changes at various times after initiation of diets, and liver and brain nonheme Fe were measured at term. Excess dietary Fe, primarily at 20000 ppm, significantly decreased activity, habituation, reflex startle, and conditioned avoidance response performance, and enhanced prepulse modulation of startle. Body weights were also markedly decreased. Fe-deficient animals showed similar behavioral effects but more moderate body weight changes. Liver nonheme Fe varied directly with dietary levels. Whole-brain nonheme Fe was significantly reduced in Fe-deficient animals but increased only at the 20000-ppm level. Homeostatic mechanisms appear to regulate whole-brain Fe more effectively under conditions of dietary Fe overload than under conditions of Fe deficiency. The behavioral changes associated with dietary Fe overload may represent secondary consequences of systemic toxicity. RP Sobotka, TJ (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,HFS-507,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 67 TC 42 Z9 42 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD FEB PY 1996 VL 59 IS 2 BP 213 EP 219 DI 10.1016/0031-9384(95)02030-6 PG 7 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA VG962 UT WOS:A1996VG96200001 PM 8838597 ER PT J AU Lutz, WK Gaylor, D AF Lutz, WK Gaylor, D TI Significance of DNA adducts at low dose: Shortening the time to spontaneous tumor occurrence SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID CHOLINE-DEFICIENT DIET; MOLECULAR DOSIMETRY; RAT-LIVER; EXPOSURE; CANCER; CARCINOGENESIS; ALKYLATION; MICE AB Formation and repair of adducts from DNA-reactive carcinogens as well as induction of genetic changes is expected to be proportional to dose as long as the rates of the enzymatic reactions are proportional to the substrate concentration and as long as the kinetics of cell division are not affected, Deviations from linearity are expected in situations of saturated or induced kinetics and whenever toxicity stimulates regenerative processes and accelerates the fixation and accumulation of mutations resulting from primary DNA lesions. Background DNA damage is postulated to drive the process of carcinogenesis resulting in what is called ''spontaneous'' tumor formation. Exposure to a low dose of a DNA-reactive carcinogen can result in a dose-dependent acceleration of the spontaneous process but it cannot induce cancer ''out of the blue.'' The shortening of the time to occurrence of a tumor is estimated for different situations using the multistage model. For a tumor which has a high background rate and a large number of steps, life shortening is small, while at a low background incidence rate and a small number of stages, life shortening can be larger. For the majority of tumors, therefore, the approach presented should be able to relieve hom the idea that a low dose of a carcinogen could induce cancer early in the life of an individual who without exposure would have lived a much longer, tumor-free Life. (C) 1996 Academic Press, Inc. C1 US FDA,NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,JEFFERSON,AR 72079. RP Lutz, WK (reprint author), UNIV WURZBURG,DEPT TOXICOL,VERSBACHER STR 9,D-97078 WURZBURG,GERMANY. NR 40 TC 20 Z9 21 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD FEB PY 1996 VL 23 IS 1 BP 29 EP 34 DI 10.1006/rtph.1996.0005 PN 1 PG 6 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA UH194 UT WOS:A1996UH19400005 PM 8628917 ER PT J AU Borzelleca, JF Cheney, M Davidson, MH Degnan, FH Derfler, PS Forbes, AL Glinsmann, W Heckman, JH Miller, SA Rulis, AM Masten, LW AF Borzelleca, JF Cheney, M Davidson, MH Degnan, FH Derfler, PS Forbes, AL Glinsmann, W Heckman, JH Miller, SA Rulis, AM Masten, LW TI Panel discussion: What is the future of macronutrient substitutes in North America? SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Editorial Material C1 CHICAGO CTR CLIN RES & PREVENT MED,CHICAGO,IL. US FDA,ROCKVILLE,MD 20857. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. ARCO CHEM CO,HOUSTON,TX. RP Borzelleca, JF (reprint author), VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,RICHMOND,VA 23298, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD FEB PY 1996 VL 23 IS 1 BP S51 EP S59 DI 10.1006/rtph.1996.0028 PN 2 PG 9 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA UH196 UT WOS:A1996UH19600017 PM 8801619 ER PT J AU Rulis, AM AF Rulis, AM TI Review of macronutrient substitutes by the food and drug administration SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT Workshop on Safety and Regulatory Aspects of Macronutrient Substitutes CY NOV 16, 1994 CL WASHINGTON, DC SP ILSI N Amer Tech Comm Macronutrient Substitut, Int Soc Regulatory Toxicol & Pharmacol RP Rulis, AM (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,OFF PREMARKET APPROVAL,WASHINGTON,DC 20204, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD FEB PY 1996 VL 23 IS 1 BP S47 EP S50 DI 10.1006/rtph.1996.0027 PN 2 PG 4 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA UH196 UT WOS:A1996UH19600016 PM 8801618 ER PT J AU Razzaghi, M Gaylor, DW AF Razzaghi, M Gaylor, DW TI On the correlation coefficient between the TD50 and the MTD SO RISK ANALYSIS LA English DT Article DE carcinogenic potency; maximum tolerated dose; carcinogen bioassay; correlation coefficient; toxicity ID CARCINOGENIC POTENCY; RISK ASSESSMENT AB The existence of correlation between the carcinogenic potency and the maximum tolerated dose has been the subject of many investigations in recent years. Several attempts have been made to quantify this correlation in different bioassay experiments. By using some distributional assumptions, Krewski et al.((1)) derive an analytic expression for the coefficient of correlation between the carcinogenic potency TD,, and the maximum tolerated dose. Here, we discuss the deviation that may result in using their analytical expression. By taking a more general approach we derive an expression for the correlation coefficient which includes the result of Krewski et al.((1)) as a special case, and show that their expression may overestimate the correlation in some instances and yet underestimate the correlation in other instances. The proposed method is illustrated by application to a real dataset. C1 US FDA,NATL CTR TOXICOL RES,ROCKVILLE,MD 20857. RP Razzaghi, M (reprint author), BLOOMSBURG UNIV,DEPT MATH,BLOOMSBURG,PA 17815, USA. NR 14 TC 5 Z9 5 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD FEB PY 1996 VL 16 IS 1 BP 107 EP 113 DI 10.1111/j.1539-6924.1996.tb01440.x PG 7 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA TZ844 UT WOS:A1996TZ84400011 PM 8868225 ER PT J AU Freeman, SM Whartenby, KA Freeman, JL Abboud, CN Marrogi, AJ AF Freeman, SM Whartenby, KA Freeman, JL Abboud, CN Marrogi, AJ TI In situ use of suicide genes for cancer therapy SO SEMINARS IN ONCOLOGY LA English DT Review ID TUMOR-INFILTRATING LYMPHOCYTES; THYMIDINE KINASE GENE; BRAIN-TUMORS; CYTOSINE DEAMINASE; GLIOMA-CELLS; RAT-BRAIN; HERPES; EXPRESSION; REGRESSION; SELECTION C1 US FDA,CTR BIOL,ROCKVILLE,MD 20857. CANC CARE CONSULTANTS,DEPT ONCOL,REDDING,CA. UNIV ROCHESTER,MED CTR,DEPT MED,ROCHESTER,NY 14642. RP Freeman, SM (reprint author), TULANE UNIV,SCH MED,CTR CANC,DIV ONCOL,MED SCH,SL78,1430 TULANE AVE,NEW ORLEANS,LA 70112, USA. NR 119 TC 146 Z9 151 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 1996 VL 23 IS 1 BP 31 EP 45 PG 15 WC Oncology SC Oncology GA TY194 UT WOS:A1996TY19400008 PM 8607030 ER PT J AU Kim, CS Binienda, Z Sandberg, JA AF Kim, CS Binienda, Z Sandberg, JA TI Construction of a physiologically based pharmacokinetic model for 2,4-dichlorophenoxyacetic acid dosimetry in the developing rabbit brain SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID CHOROID-PLEXUS; FETAL; RATS; ACCUMULATION; NEWBORN; BARRIER; ADULT; 2,4-D; MICE AB A physiologically based pharmacokinetic (PBPK) model that describes the kinetics of organic anions by using 2,4-dichlorophenoxyacetic acid (2,4-D) as a representative compound was constructed for the developing rabbit brain at near-term pregnancy (Gestation Day 30). The model consisted of brain, body, and venous and arterial compartments for the mother which were linked to the fetus by a placenta. Maternal brain compartments in the model were brain plasma, cerebrospinal fluid (CSF), and brain tissue including hypothalamus, caudate nucleus, hippocampus, forebrain, brainstem, and cerebellum, The fetus consisted of brain, body, amniotic fluid, and venous and arterial compartments, The maternal body had both a central and a deep compartment; the fetal body had only one compartment, Maternal blood flow to the fetus was modeled as blood flowing to the placenta, where it was equilibrated before it reached the fetus. The brain uptake was membrane-limited by the blood-brain barrier, with saturable clearance from the CSF into the venous blood by the choroid plexus in both fetus and mother. The model was used to compare concentrations of 2,4-D in maternal and fetal brain, maternal and fetal plasma, and amniotic fluid over time with experimental data from pregnant rabbits given 2,4-D intravenously (1, 10, or 40 mg/kg). The model adequately simulated the 2-hr time course of 2,4-D concentrations in both mother and fetus. With continued development, this generic PBPK model should be a useful tool for evaluating the safety of organic acid neurotoxicants in the developing brain. (C) 1996 Academic Press, Inc. C1 CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. NATL CTR TOXICOL RES,DIV NEUROTOXICOL HFT 132,JEFFERSON,AR 72079. RP Kim, CS (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV TOXICOL RES HFS 506,WASHINGTON,DC 20204, USA. NR 28 TC 18 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD FEB PY 1996 VL 136 IS 2 BP 250 EP 259 DI 10.1006/taap.1996.0032 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA TW998 UT WOS:A1996TW99800006 PM 8619233 ER PT J AU Winans, SC Burns, DL Christie, PJ AF Winans, SC Burns, DL Christie, PJ TI Adaptation of a conjugal transfer system for the export of pathogenic macromolecules SO TRENDS IN MICROBIOLOGY LA English DT Article ID SINGLE-STRANDED-DNA; PERTUSSIS TOXIN SECRETION; GRAM-NEGATIVE BACTERIA; AGROBACTERIUM-TUMEFACIENS; T-DNA; VIRB PROTEINS; MEMBRANE; OPERON; GENES; LOCALIZATION AB Conjugal transfer of bacterial plasmids requires a pore through which DNA can traverse the envelopes of the donor and recipient cells. Recent studies indicate that these pores, which are composed of approximately ten proteins, are evolutionarily related to the transport systems required for the transfer of oncogenic T-DNA from Agrobacterium tumefaciens to plant cells and for toxin secretion from Bordetella pertussis. C1 CORNELL UNIV,MICROBIOL SECT,ITHACA,NY 14853. US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,BETHESDA,MD 20892. UNIV TEXAS,HLTH SCI CTR,DEPT MICROBIOL & MOLEC GENET,HOUSTON,TX 77030. FU NIGMS NIH HHS [R01 GM048746] NR 46 TC 143 Z9 153 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD FEB PY 1996 VL 4 IS 2 BP 64 EP 68 DI 10.1016/0966-842X(96)81513-7 PG 5 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA TY295 UT WOS:A1996TY29500010 PM 8820569 ER PT J AU Hwang, M Ahn, CH Pine, PS Yin, JJ Hrycyna, CA Licht, T Aszalos, A AF Hwang, M Ahn, CH Pine, PS Yin, JJ Hrycyna, CA Licht, T Aszalos, A TI Effect of combination of suboptimal, concentrations of p-glycoprotein blockers on the proliferation of MDR1 gene expressing cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID EHRLICH ASCITES TUMOR; MULTIDRUG-RESISTANCE; CREMOPHOR-EL; DAUNORUBICIN; VERAPAMIL; REVERSAL; DRUGS; CONFORMATION; TRANSPORTER; MEMBRANES AB Pharmacologically active in vivo doses of P-glycoprotein (Pgp) blockers, specifically verapamil, Cremophor EL and PSC833 cause toxicity in addition to that from the concomitantly used cancer chemotherapeutic drugs. It was shown before that these blockers cause different types of toxicities in vivo. We found that these 3 chemically distinct Pgp blockers exert different biophysical effects on the membranes of L1210 MDR cells. They also affect the general metabolism of these cells differently, but all block affinity labeling of Pgp. We could also show that the combination of suboptimal doses of these blockers can restore the uptake of the Pgp substrate rhodamine 123 into L1210MDR, 3T3MDR and KB-VI cells and can reduce the survival rate of these cells when treated in combination with daunorubicin. Our results suggest that the combination of suboptimal doses of these Pgp blockers may be advantageous in clinical practice. (C) 1996 Wiley-Liss, Inc.* C1 US FDA,CTR DRUG EVALUAT & RES,WASHINGTON,DC 20204. US FDA,CTR FOOD SAFETY & NUTR,WASHINGTON,DC 20204. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,CELL BIOL LAB,BETHESDA,MD 20892. RI Yin, Jun Jie /E-5619-2014 NR 31 TC 26 Z9 26 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 26 PY 1996 VL 65 IS 3 BP 389 EP 397 DI 10.1002/(SICI)1097-0215(19960126)65:3<389::AID-IJC19>3.0.CO;2-5 PG 9 WC Oncology SC Oncology GA TT513 UT WOS:A1996TT51300019 PM 8575863 ER PT J AU Gueriguian, J Green, L Misbin, RI Stadel, B Fleming, GA AF Gueriguian, J Green, L Misbin, RI Stadel, B Fleming, GA TI Efficacy of metformin in non-insulin-dependent diabetes mellitus SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID LACTIC-ACIDOSIS RP Gueriguian, J (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 4 TC 4 Z9 4 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 25 PY 1996 VL 334 IS 4 BP 269 EP 269 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA TQ755 UT WOS:A1996TQ75500017 PM 8532012 ER PT J AU Nightingale, SL AF Nightingale, SL TI Progress in international harmonization of drug approval requirements SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP Nightingale, SL (reprint author), US FDA,OFF HLTH AFFAIRS,PARKLAWN BLDG,5600 FISHERS LN,ROCKVILLE,MD 20857, 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 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 24 PY 1996 VL 275 IS 4 BP 273 EP 273 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA TP965 UT WOS:A1996TP96500007 PM 8544255 ER PT J AU Nightingale, SL AF Nightingale, SL TI First protease inhibitor approved for treatment of HIV SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material 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 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 24 PY 1996 VL 275 IS 4 BP 273 EP 273 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA TP965 UT WOS:A1996TP96500005 PM 8544255 ER PT J AU Nightingale, SL AF Nightingale, SL TI Guidance on industry dissemination of textbooks and reprints SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material 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 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 24 PY 1996 VL 275 IS 4 BP 273 EP 273 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA TP965 UT WOS:A1996TP96500006 PM 8544255 ER PT J AU Scremin, CL Boal, JH Wilk, A Phillips, LR Beaucage, SL AF Scremin, CL Boal, JH Wilk, A Phillips, LR Beaucage, SL TI [(2-deoxy-alpha- and beta-D-erythro-pentofuranosyl)thymin-1-yl] methane derivatives as potential conformational probes for altDNA oligonucleotides SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article AB The previously unknown deoxyribonucleoside analogues 2a,b have been efficiently synthesized from commercial 1-O-methyl-2-deoxy-3,5-di-O-p-toluoyl-D-erythro-pentofuranose. The conversion of these nucleosides to the phosphoramidite derivatives 13a,b and 14a,b for subsequent incorporation into oligodeoxyribonucleotide analogues is also described. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV ALLERGEN PROD & PARASITOL,BETHESDA,MD 20892. NCI,DEV THERAPEUT PROGRAM,LAB PHARMACEUT CHEM,FREDERICK,MD 21701. NR 11 TC 11 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JAN 23 PY 1996 VL 6 IS 2 BP 207 EP 212 DI 10.1016/0960-894X(95)00589-L PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA TU582 UT WOS:A1996TU58200019 ER PT J AU Hagiwara, E Sacks, T LeitmanKlinman, SF Klinman, DM AF Hagiwara, E Sacks, T LeitmanKlinman, SF Klinman, DM TI Effect of HIV infection on the frequency of cytokine-secreting cells in human peripheral blood SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID ACQUIRED IMMUNE-DEFICIENCY; HOMOSEXUAL MEN; IMMUNODEFICIENCY SYNDROME; ACTIVATION; EXPRESSION; ABNORMALITIES; INTERLEUKIN-2; RESPONSES; RECEPTOR; HELPER AB A selective decrease in type 1 cytokine secretion by in vitro stimulated peripheral blood cells is reportedly associated with disease progression in HIV-infected individuals, To examine whether a similar change in cytokine secretion occurs under physiologic conditions in vivo, sensitive and specific ELIspot assays were used to compare the phenotype and frequency of PBMC spontaneously producing interleukin (IL)-2, IL-4, IL-10, and interferon-gamma (IFN-gamma) in 83 HIV-infected subjects and 60 normal controls, Phenotypic analysis of freshly isolated cytokine-secreting cells showed that T cells were the primary source of IL-2, IL-4, and IFN-gamma while CD14(+) macrophages/monocytes were the dominant source of IL-10 in vivo, The number of peripheral blood mononuclear cells (PBMC) spontaneously secreting both type 1 and type 2 cytokines was significantly reduced in HIV-infected patients versus controls, The magnitude of this decrease did not correlate with disease severity, Changes in IL-2-secreting cell number correlated with CD4 count, while changes in the frequency of IFN-gamma-secreting cells correlated with disease duration, These findings do not support the contention that a selective reduction in type 1 cytokine production correlates with disease progression. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,LAB RETROVIRAL RES,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 44 TC 26 Z9 26 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN 20 PY 1996 VL 12 IS 2 BP 127 EP 133 DI 10.1089/aid.1996.12.127 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA TV295 UT WOS:A1996TV29500006 PM 8834462 ER PT J AU Prater, DA Bertone, JJ Letonja, T Vaughn, SD AF Prater, DA Bertone, JJ Letonja, T Vaughn, SD TI Clinical investigation of new animal drugs by veterinary practitioners SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article C1 US FDA,CTR VET MED,ROCKVILLE,MD 20855. VIRGINIA MARYLAND REG COLL VET MED,BLACKSBURG,VA 24061. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD JAN 15 PY 1996 VL 208 IS 2 BP 190 EP 194 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA TP474 UT WOS:A1996TP47400006 PM 8567369 ER PT J AU Liu, HY Clifford, RH Dolan, SP Montaser, A AF Liu, HY Clifford, RH Dolan, SP Montaser, A TI Investigation of a high-efficiency nebulizer and a thimble glass frit nebulizer for elemental analysis of biological materials by inductively coupled plasma-atomic emission spectrometry SO SPECTROCHIMICA ACTA PART B-ATOMIC SPECTROSCOPY LA English DT Article DE biological material; core nebulizer; demountable thimble glass frit nebulizer; detection limit; high-efficiency nebulizer; inductively coupled plasma atomic emission spectrometry; thimble frit nebulizer ID NOISE POWER SPECTRA; MASS-SPECTROMETRY; ULTRASONIC NEBULIZERS; PNEUMATIC NEBULIZERS; SIGNAL FLUCTUATIONS; SPRAY CHAMBERS; DROPLETS; AEROSOLS; SIZE; FLOW AB A high-efficiency nebulizer (HEN) and a demountable thimble glass frit nebulizer are evaluated for argon inductively coupled plasma-atomic emission spectrometry (Ar ICP-AES). Aerosol characteristics for the HEN and the thimble frit are studied using laser Fraunhofer diffraction. Analyte transport efficiencies, mass transport rates, detection limits, and short- and long-term stabilities are measured. Four standard reference materials (trace elements in water, oyster tissue, bovine liver, and orchard leaves) are analyzed. For comparison, results obtained by a high-solid pneumatic nebulizer (conespray nebulizer) are also presented. Transport efficiencies of up to 50-60% are obtained for the HEN and the thimble frit nebulizer at an uptake rate of 11 mu l min(-1). For the elements tested. short- and long-term precisions and detection limits obtained with the thimble frit are comparable to those of a commonly used pneumatic nebulizer. Good agreement with certified values is obtained for six trace elements in a standard reference material (SRM) water sample nebulized by the thimble frit. However, signal suppression is observed when the biological or plant SRMs are nebulized with the thimble frit nebulizer. In contrast, satisfactory results are obtained for the same matrices when the HEN and the conespray nebulizer are used. C1 GEORGE WASHINGTON UNIV,DEPT CHEM,WASHINGTON,DC 20052. US FDA,ELEMENTAL RES BRANCH,WASHINGTON,DC 20204. NR 43 TC 39 Z9 40 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0584-8547 J9 SPECTROCHIM ACTA B JI Spectroc. Acta Pt. B-Atom. Spectr. PD JAN 15 PY 1996 VL 51 IS 1 BP 27 EP 40 DI 10.1016/0584-8547(95)01423-3 PG 14 WC Spectroscopy SC Spectroscopy GA UH063 UT WOS:A1996UH06300004 ER PT J AU Currier, RW Goddard, J Buechler, K Quinlisk, MP Wolfe, SL Spencer Carroll, TJ Bennett, T Stokes, J AF Currier, RW Goddard, J Buechler, K Quinlisk, MP Wolfe, SL Spencer Carroll, TJ Bennett, T Stokes, J TI Unexplained severe illness possibly associated with consumption of Kombucha tea - Iowa, 1995 (Reprinted from MMWR, vol 44, pg 892-893, 1995) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 OFF MED EXAMINER,SIOUX CITY,IA. UNIV IOWA,IOWA CITY,IA 52242. CDC,NATL CTR ENVIRONM HLTH,DIV ENVIRONM HAZARDS & HLTH EFFECTS,HLTH STUDIES BRANCH,ATLANTA,GA 30333. US FDA,CTR FOOD SAFETY,ROCKVILLE,MD 20857. RP Currier, RW (reprint author), IOWA DEPT PUBL HLTH,DES MOINES,IA 50319, USA. NR 9 TC 9 Z9 9 U1 3 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 10 PY 1996 VL 275 IS 2 BP 96 EP 98 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA TN280 UT WOS:A1996TN28000006 ER PT J AU Sell, DR Lane, MA Johnson, WA Masoro, EJ Mock, OB Reiser, KM Fogarty, JF Cutler, RG Ingram, DK Roth, GS Monnier, VM AF Sell, DR Lane, MA Johnson, WA Masoro, EJ Mock, OB Reiser, KM Fogarty, JF Cutler, RG Ingram, DK Roth, GS Monnier, VM TI Longevity and the genetic determination of collagen glycoxidation kinetics in mammalian senescence SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE life-span; oxidation; glycation; Maillard reaction; skin ID DIETARY RESTRICTION; DIABETES-MELLITUS; OXIDATIVE STRESS; CROSS-LINKING; AGE; GLUCOSE; HYPOTHESIS; DISEASE AB A fundamental question in the basic biology of aging is whether there is a universal aging process. If indeed such a process exists, one would expect that it develops at a higher rate in short- versus long-lived species, We have quantitated pentosidine, a marker of glycoxidative stress in skin collagen from eight mammalian species as a function of age. A curvilinear increase was modeled for all species, and the rate of increase correlated inversely with maximum life-span. Dietary restriction, a potent intervention associated with increased life-span, markedly inhibited glycoxidation rate in the rodent. On the assumption that collagen turnover rate is primarily influenced by the crosslinking due to glycoxidation, these results suggest that there is a progressive age-related deterioration of the process that controls the collagen glycoxidation rate, Thus, the ability to withstand damage due to glycoxidation and the Maillard reaction may be under genetic control. C1 NIA, GERONTOL RES CTR, BALTIMORE, MD 21224 USA. US FDA, DEPT HLTH & HUMAN SERV, LAUREL, MD 20708 USA. UNIV TEXAS, HLTH SCI CTR, DEPT PHYSIOL, SAN ANTONIO, TX 78284 USA. KIRKSVILLE COLL OSTEOPATH MED, DEPT ANAT, KIRKSVILLE, MO 63501 USA. UNIV CALIF DAVIS, CALIF REG PRIMATE RES CTR, DAVIS, CA 95616 USA. RP Sell, DR (reprint author), CASE WESTERN RESERVE UNIV, INST PATHOL, 2085 ADELBERT RD, CLEVELAND, OH 44106 USA. RI Monnier, Vincent/B-1371-2009 FU NIA NIH HHS [AG05601, AG11080]; NIAMS NIH HHS [P30 AR39750] NR 46 TC 140 Z9 144 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 9 PY 1996 VL 93 IS 1 BP 485 EP 490 DI 10.1073/pnas.93.1.485 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TP367 UT WOS:A1996TP36700097 PM 8552666 ER PT B AU Honstead, J Graber, G AF Honstead, J Graber, G GP SUNY, NEW YORK STATE COLL AGR & LIFE SCI TI FDA update on bovine spongiform encephalopathy SO 1996 CORNELL NUTRITION CONFERENCE FOR FEED MANUFACTURERS, PROCEEDINGS LA English DT Proceedings Paper CT 1996 Cornell Nutrition Conference for Feed Manufacturers CY OCT 22-24, 1996 CL ROCHESTER, NY SP Cornell Univ, New York State Coll Agr & Life Sci, Dept Anim Sci & Div Nutr, Sci RP Honstead, J (reprint author), US FDA,CTR VET MED,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CORNELL UNIV DEPT ANIMAL SCIENCE PI ITHACA PA 272 MORRISON HALL, ITHACA, NY 14853-4801 PY 1996 BP 75 EP 82 PG 8 WC Agriculture, Dairy & Animal Science; Agronomy; Nutrition & Dietetics SC Agriculture; Nutrition & Dietetics GA BG68X UT WOS:A1996BG68X00011 ER PT J AU Malinowski, HJ AF Malinowski, HJ GP CONTROLLED RELEASE SOC TI FDA guidance - Developing in vitro in vivo correlations for use as a surrogate for bioequivalency testing SO 23RD INTERNATIONAL SYMPOSIUM ON CONTROLLED RELEASE OF BIOACTIVE MATERIALS, 1996 PROCEEDINGS SE CONTROLLED RELEASE SOCIETY. INTERNATIONAL SYMPOSIUM ON CONTROLLED RELEASE OF BIOACTIVE MATERIALS LA English DT Proceedings Paper CT 23rd International Symposium on Controlled Release of Bioactive Materials CY JUL 07-10, 1996 CL KYOTO, JAPAN SP Controlled Release Soc Inc, Japan Soc Drug Delivery Syst RP Malinowski, HJ (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CONTROLLED RELEASE SOCIETY INC PI DEERFIELD PA 1020 MILWAUKEE AVE SUITE 235, DEERFIELD, IL 60015 SN 1022-0178 J9 CRS BUI NAT PY 1996 BP 151 EP 152 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BH42C UT WOS:A1996BH42C00078 ER PT J AU Aziz, KJ AF Aziz, KJ TI Clinical molecular biology: Concepts and applications SO ADVANCES IN CLINICAL CHEMISTRY, VOL 32 SE ADVANCES IN CLINICAL CHEMISTRY LA English DT Review ID ACUTE LYMPHOBLASTIC-LEUKEMIA; DUCHENNE MUSCULAR-DYSTROPHY; CHRONIC MYELOGENOUS LEUKEMIA; POLYMERASE CHAIN-REACTION; T-CELL RECEPTOR; CYSTIC-FIBROSIS; GENE REARRANGEMENTS; DNA; DIAGNOSIS; SEQUENCES RP Aziz, KJ (reprint author), US FDA,DIV CLIN LAB DEVICES,ROCKVILLE,MD 20857, USA. NR 32 TC 1 Z9 1 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0065-2423 J9 ADV CLIN CHEM PY 1996 VL 32 BP 39 EP 72 DI 10.1016/S0065-2423(08)60425-4 PG 34 WC Medical Laboratory Technology SC Medical Laboratory Technology GA BH78B UT WOS:A1996BH78B00002 PM 8899070 ER PT S AU Schultz, WB AF Schultz, WB BE Corfman, KP Lynch, JG TI Food and Drug Administration's suggested consumer research ideas SO ADVANCES IN CONSUMER RESEARCH, VOL 23: RESEARCH FRAME SYNERGIES SE ADVANCES IN CONSUMER RESEARCH LA English DT Article; Proceedings Paper CT 23rd Annual Conference of the Association-for-Consumer-Research CY OCT 19-22, 1995 CL MINNEAPOLIS, MN SP Assoc Consumer Res RP Schultz, WB (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC CONSUMER RESEARCH PI PROVO PA GRAD SCHOOL MANAGEMENT, BRIGHAM YOUNG UNIV, PROVO, UT 84602 SN 0098-9258 BN 0-915552-36-1 J9 ADV CONSUM RES PY 1996 VL 23 BP 316 EP 316 PG 1 WC Business SC Business & Economics GA BF97L UT WOS:A1996BF97L00073 ER PT B AU Ikeda, GJ Michel, TC Gaines, DW Olivito, VL Sapienza, PP Friedman, L Barton, CN ODonnell, MW AF Ikeda, GJ Michel, TC Gaines, DW Olivito, VL Sapienza, PP Friedman, L Barton, CN ODonnell, MW BE Tumbleson, ME Schook, LB TI A comparison of physiological and biochemical parameters in fully conscious Hormel-Hanford and Yucatan strains of miniature pig SO ADVANCES IN SWINE IN BIOMEDICAL RESEARCH, VOLS 1 AND 2 LA English DT Proceedings Paper CT International Symposium on Swine in Biomedical Research CY OCT 22-25, 1995 CL UNIV MARYLAND, COLLEGE PK, MD HO UNIV MARYLAND RP Ikeda, GJ (reprint author), US FDA,BELTSVILLE RES FACIL,CTR FOOD SAFETY & APPL NUTR,HFS-506,8501 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45495-5 PY 1996 BP 543 EP 555 PG 13 WC Medicine, Research & Experimental; Veterinary Sciences; Zoology SC Research & Experimental Medicine; Veterinary Sciences; Zoology GA BH12G UT WOS:A1996BH12G00046 ER PT B AU Friedman, L Panepinto, L Gaines, DW Chi, R Braunberg, RC Terris, J AF Friedman, L Panepinto, L Gaines, DW Chi, R Braunberg, RC Terris, J BE Tumbleson, ME Schook, LB TI Biochemical indices of stress associated with short-term restraint in Hormel and Yucatan miniature swine SO ADVANCES IN SWINE IN BIOMEDICAL RESEARCH, VOLS 1 AND 2 LA English DT Proceedings Paper CT International Symposium on Swine in Biomedical Research CY OCT 22-25, 1995 CL UNIV MARYLAND, COLLEGE PK, MD HO UNIV MARYLAND RP Friedman, L (reprint author), US FDA,DIV TOXICOL RES,8501 MUIKIRK RD,LAUREL,MD 20708, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45495-5 PY 1996 BP 557 EP 570 PG 14 WC Medicine, Research & Experimental; Veterinary Sciences; Zoology SC Research & Experimental Medicine; Veterinary Sciences; Zoology GA BH12G UT WOS:A1996BH12G00047 ER PT J AU Attallah, AM ElDidi, M Seif, F ElMohamady, H Dalbagni, G AF Attallah, AM ElDidi, M Seif, F ElMohamady, H Dalbagni, G TI Comparative study between cytology and dot-ELISA for early detection of bladder cancer SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE bladder cancer cytology; MoAb; cytokeratin; Dot-ELISA; urine ID TRANSITIONAL CELL-CARCINOMA; URINE; ANTIBODY AB Schistosomiasis remains one of the major public health problems of the tropics. Conservative estimates place the number of infected individuals at about 200 millions. In Egypt carcinoma of the urinary bladder associated with schistosomiases is the foremost oncologic problem, because of its high frequency and the late presentation of cases. A newly developed monoclonal antibody CK1K10 to keratinized grade 1 squamous cell carcinoma was used in a dot enzyme-linked immunosorbent assay (Dot ELISA) to test urine samples of 118 patients with bladder carcinoma, 291 patients with genitourinary pathology other than bladder carcinoma, in addition to 550 healthy controls. The overall sensitivity of the dot ELISA was 90% among 118 patients with bladder carcinoma, Twenty-seven of 33 transitional cell carcinoma cases (82%), 68 of the 71 squamous cell carcinoma cases (96%), 7 of 10 undifferentiated tumors cases (70%), and 4 of 4 adenocarcinoma were positive with this assay. The specificity was 90% in our sample population. A comparative study of diagnosis by cytology and dot ELISA was carried out in 57 patients with bladder carcinoma. Dot ELISA was found to be superior as a screening tool for high risk groups (P < .001 using chi-square test). Cytology detected 21% of transitional cell carcinoma, 68% of squamous cell carcinoma, 50% of adenocarcinoma, and 86% of undifferentiated tumors. The dot ELISA assay should be useful for screening high-risk groups because it does not require sophisticated equipment, is noninvasive, does not require highly trained staff, and can be performed in less than 30 minutes. C1 US FDA,OFF BIOL RES & REVIEW,BETHESDA,MD 20014. CAIRO UNIV,BIOTECHNOL RES CTR,CAIRO,EGYPT. CAIRO UNIV,NATL CANC INST,CAIRO,EGYPT. NR 21 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 1996 VL 105 IS 1 BP 109 EP 114 PG 6 WC Pathology SC Pathology GA TQ290 UT WOS:A1996TQ29000017 PM 8561075 ER PT B AU Ponnapalli, RM AF Ponnapalli, RM GP AMER STAT ASSOC TI On testing statistical hypotheses in biomedical experiments SO AMERICAN STATISTICAL ASSOCIATION 1996 PROCEEDINGS OF THE BIOMETRICS SECTION LA English DT Proceedings Paper CT Annual Meeting of the American-Statistical-Association CY AUG 04-08, 1996 CL CHICAGO, IL SP Amer Stat Assoc DE tests for equivalence and superiority; sample size RP Ponnapalli, RM (reprint author), US FDA,HFZ-542,1350 PICCARD DR,ROCKVILLE,MD 20850, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 BN 1-883276-37-3 PY 1996 BP 239 EP 243 PG 5 WC Statistics & Probability SC Mathematics GA BH98G UT WOS:A1996BH98G00037 ER PT B AU Arani, RB Chen, JJ Freni, SC AF Arani, RB Chen, JJ Freni, SC GP AMER STAT ASSOC TI Collinearity in the context of proportional hazards model SO AMERICAN STATISTICAL ASSOCIATION 1996 PROCEEDINGS OF THE BIOMETRICS SECTION LA English DT Proceedings Paper CT Annual Meeting of the American-Statistical-Association CY AUG 04-08, 1996 CL CHICAGO, IL SP Amer Stat Assoc DE proportional hazards model; collinearity; information matrix RP Arani, RB (reprint author), NATL CTR TOXICOL RES,HFT-20,3900 NCTR DR,JEFFERSON,AR 72079, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 BN 1-883276-37-3 PY 1996 BP 422 EP 427 PG 6 WC Statistics & Probability SC Mathematics GA BH98G UT WOS:A1996BH98G00072 ER PT B AU Silliman, NP AF Silliman, NP GP AMER STAT ASSOC TI Hidden issues concerning laboratory data evaluation: Discussion SO AMERICAN STATISTICAL ASSOCIATION - 1996 PROCEEDINGS OF THE BIOPHARMACEUTICAL SECTION LA English DT Proceedings Paper CT Symposium of the Biopharmaceutical Section, at the Annual Meeting of the American-Statistical-Association CY AUG 04-08, 1996 CL CHICAGO, IL SP Amer Stat Assoc, Biopharm Sect DE safety analysis; reference range; tolerance limit; Genie score; O'Brien extended tests; Conover-Salsburg test RP Silliman, NP (reprint author), US FDA,DIV BIOMETR 4 HFD 725,9201 CORP BLVD,ROCKVILLE,MD 20850, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 BN 1-883276-38-1 PY 1996 BP 23 EP 24 PG 2 WC Statistics & Probability SC Mathematics GA BJ14X UT WOS:A1996BJ14X00004 ER PT B AU Hung, HMJ AF Hung, HMJ GP AMER STAT ASSOC TI On evaluation of multiple-dose combination drugs in factorial clinical trials SO AMERICAN STATISTICAL ASSOCIATION - 1996 PROCEEDINGS OF THE BIOPHARMACEUTICAL SECTION LA English DT Proceedings Paper CT Symposium of the Biopharmaceutical Section, at the Annual Meeting of the American-Statistical-Association CY AUG 04-08, 1996 CL CHICAGO, IL SP Amer Stat Assoc, Biopharm Sect DE dose response; global test; synergism; interim analysis RP Hung, HMJ (reprint author), US FDA,CDER,DIV BIOMETR 1,HFD-710,1451 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 BN 1-883276-38-1 PY 1996 BP 25 EP 32 PG 8 WC Statistics & Probability SC Mathematics GA BJ14X UT WOS:A1996BJ14X00005 ER PT B AU Balch, AH Parchment, RE AF Balch, AH Parchment, RE GP AMER STAT ASSOC TI Modeling murine tumor growth and its stimulation SO AMERICAN STATISTICAL ASSOCIATION - 1996 PROCEEDINGS OF THE BIOPHARMACEUTICAL SECTION LA English DT Proceedings Paper CT Symposium of the Biopharmaceutical Section, at the Annual Meeting of the American-Statistical-Association CY AUG 04-08, 1996 CL CHICAGO, IL SP Amer Stat Assoc, Biopharm Sect RP Balch, AH (reprint author), US FDA,CDER,OEB,QMR,HFD 705,5600 FISHERS LANE,ROCKVILLE,MD 20878, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 BN 1-883276-38-1 PY 1996 BP 40 EP 44 PG 5 WC Statistics & Probability SC Mathematics GA BJ14X UT WOS:A1996BJ14X00007 ER PT B AU Berger, V Gnecco, G Chi, G Hirschfeld, S AF Berger, V Gnecco, G Chi, G Hirschfeld, S GP AMER STAT ASSOC TI Perspectives on tumor response and other ordinal data SO AMERICAN STATISTICAL ASSOCIATION - 1996 PROCEEDINGS OF THE BIOPHARMACEUTICAL SECTION LA English DT Proceedings Paper CT Symposium of the Biopharmaceutical Section, at the Annual Meeting of the American-Statistical-Association CY AUG 04-08, 1996 CL CHICAGO, IL SP Amer Stat Assoc, Biopharm Sect DE ordered categorical data; protocol AB A recent FDA initiative has made accelerated approval, based on (objective) tumor response, more accessible for new cancer drugs. For many types of malignancies, tumor response is a measure of the growth or shrinkage of solid tumors in response to treatment. Tumor response records the best response attained by each patient as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). Ordinality is the salient feature of these data, as CR is preferred to PR, which is preferred to either SD or PD. Far several reasons, including the fact that there is often no duration required for a patient to be classified as SD, there may be some reluctance to treat SD as being categorically better than PD. There may thus be a tendency to combine these two outcome levels into a single non-responder (NR) outcome level. With the new prominence afforded to tumor response data by the recent initiative, it becomes more important than ever to analyze such data with an appropriate method. Section 1 of this paper provides specific recommendations regarding what to include in the study protocol. Section 2 formulates the problem statistically in terms of a hypothesis testing problem. Section 3 addresses the controversy of conditioning on the margins. Section 4 considers what constitutes a ''good'' analysis, or what properties we would hope that an analysis would satisfy. We explore the most common approaches to the analysis of objective tumor response (binomial tests based on dichotomizing the outcome variable, scores tests based on assigning numerical scores to the outcome levels, the proportional hazards test, and the proportional odds test), as well as some newer approaches (the Smirnov test and the convex hull test). In Section 5, we offer recommendations regarding the choice of statistical analysis for tumor response data. RP Berger, V (reprint author), US FDA,CDER HFM 215,1401 ROCKVILLE PIKE 200S,ROCKVILLE,MD 20852, USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 BN 1-883276-38-1 PY 1996 BP 112 EP 117 PG 6 WC Statistics & Probability SC Mathematics GA BJ14X UT WOS:A1996BJ14X00021 ER PT B AU Nuri, WA Dubey, SD AF Nuri, WA Dubey, SD GP AMER STAT ASSOC TI Testing for treatment effect against placebo in multicenter trials SO AMERICAN STATISTICAL ASSOCIATION - 1996 PROCEEDINGS OF THE BIOPHARMACEUTICAL SECTION LA English DT Proceedings Paper CT Symposium of the Biopharmaceutical Section, at the Annual Meeting of the American-Statistical-Association CY AUG 04-08, 1996 CL CHICAGO, IL SP Amer Stat Assoc, Biopharm Sect DE multicenter trials; treatment by center interaction; multiple comparisons RP Nuri, WA (reprint author), US FDA,DIV BIOMETR 1,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 BN 1-883276-38-1 PY 1996 BP 118 EP 123 PG 6 WC Statistics & Probability SC Mathematics GA BJ14X UT WOS:A1996BJ14X00022 ER PT B AU Mahjoob, K Fenichel, RR Chi, GYH Lipicky, RJ AF Mahjoob, K Fenichel, RR Chi, GYH Lipicky, RJ GP AMER STAT ASSOC TI Statistical issues in measuring the agreement between diagnostic methods for disease detection SO AMERICAN STATISTICAL ASSOCIATION - 1996 PROCEEDINGS OF THE BIOPHARMACEUTICAL SECTION LA English DT Proceedings Paper CT Symposium of the Biopharmaceutical Section, at the Annual Meeting of the American-Statistical-Association CY AUG 04-08, 1996 CL CHICAGO, IL SP Amer Stat Assoc, Biopharm Sect DE sensitivity; specificity; concordance; kappa RP Mahjoob, K (reprint author), US FDA,CDER,5600 FISHERS LANE HFD-710,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 BN 1-883276-38-1 PY 1996 BP 124 EP 128 PG 5 WC Statistics & Probability SC Mathematics GA BJ14X UT WOS:A1996BJ14X00023 ER PT B AU Tsong, Y Sathe, P Shah, VP AF Tsong, Y Sathe, P Shah, VP GP AMER STAT ASSOC TI Comparing two dissolution data sets for similarity SO AMERICAN STATISTICAL ASSOCIATION - 1996 PROCEEDINGS OF THE BIOPHARMACEUTICAL SECTION LA English DT Proceedings Paper CT Symposium of the Biopharmaceutical Section, at the Annual Meeting of the American-Statistical-Association CY AUG 04-08, 1996 CL CHICAGO, IL SP Amer Stat Assoc, Biopharm Sect DE dissolution data; similarity test; bootstrap RP Tsong, Y (reprint author), US FDA,CDER,DIV BIOMETR 3,HFD-720,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 BN 1-883276-38-1 PY 1996 BP 129 EP 134 PG 6 WC Statistics & Probability SC Mathematics GA BJ14X UT WOS:A1996BJ14X00024 ER PT B AU Wang, SJ Hung, HMJ AF Wang, SJ Hung, HMJ GP AMER STAT ASSOC TI Evaluation of utilities of two-stage test and maximum test in two-period crossover trials SO AMERICAN STATISTICAL ASSOCIATION - 1996 PROCEEDINGS OF THE BIOPHARMACEUTICAL SECTION LA English DT Proceedings Paper CT Symposium of the Biopharmaceutical Section, at the Annual Meeting of the American-Statistical-Association CY AUG 04-08, 1996 CL CHICAGO, IL SP Amer Stat Assoc, Biopharm Sect DE carryover; maximum test; Monte Carlo; precision RP Wang, SJ (reprint author), US FDA,CDER,DIV BIOMETR 1,HFD-710,RM 2034,1451 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 BN 1-883276-38-1 PY 1996 BP 145 EP 150 PG 6 WC Statistics & Probability SC Mathematics GA BJ14X UT WOS:A1996BJ14X00027 ER PT B AU Campbell, G AF Campbell, G GP AMER STAT ASSOC TI Statistical issues in medical devices: A regulatory perspective SO AMERICAN STATISTICAL ASSOCIATION - 1996 PROCEEDINGS OF THE BIOPHARMACEUTICAL SECTION LA English DT Proceedings Paper CT Symposium of the Biopharmaceutical Section, at the Annual Meeting of the American-Statistical-Association CY AUG 04-08, 1996 CL CHICAGO, IL SP Amer Stat Assoc, Biopharm Sect DE clinical trials; statistical methodology; substantial equivalence; design of experiments AB The role of the Center for Devices and Radiological Health in the Food and Drug Administration (FDA) in the regulation of medical devices is to ensure that they are safe and effective. Scientific evidence needs to be provided to the FDA to substantiate such claims. Statistical designs and analyses are integral parts of the submission of applications of new devices for pre-market approval and for substantial equivalence to an already marketed device. In contrast to pharmaceutical trials, there are several unique problems that arise in device clinical trials; these issues are relevant in both the design and the analysis stages. A number of tips to streamline the approval process are discussed from the statistical viewpoint. In addition, there are several challenges to statistical theory and methodological development that medical devices pose. RP Campbell, G (reprint author), US FDA,HFZ-542,1350 PICCARD DR,ROCKVILLE,MD 20850, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 BN 1-883276-38-1 PY 1996 BP 224 EP 229 PG 6 WC Statistics & Probability SC Mathematics GA BJ14X UT WOS:A1996BJ14X00041 ER PT B AU Chiou, WJ AF Chiou, WJ GP AMER STAT ASSOC TI The two one-sided tests procedure for McNemar's test SO AMERICAN STATISTICAL ASSOCIATION - 1996 PROCEEDINGS OF THE BIOPHARMACEUTICAL SECTION LA English DT Proceedings Paper CT Symposium of the Biopharmaceutical Section, at the Annual Meeting of the American-Statistical-Association CY AUG 04-08, 1996 CL CHICAGO, IL SP Amer Stat Assoc, Biopharm Sect DE equivalence; bioequivalence; power; sample size RP Chiou, WJ (reprint author), US FDA,HFZ-542,1350 PICCARD DR,ROCKVILLE,MD 20850, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 BN 1-883276-38-1 PY 1996 BP 230 EP 232 PG 3 WC Statistics & Probability SC Mathematics GA BJ14X UT WOS:A1996BJ14X00042 ER PT B AU Blodgett, RJ AF Blodgett, RJ GP AMER STAT ASSOC TI An algorithm for L(p)-regression for 13.0.CO;2-Z PG 14 WC Biology; Biophysics SC Life Sciences & Biomedicine - Other Topics; Biophysics GA UU599 UT WOS:A1996UU59900005 PM 8809359 ER PT S AU Gazzara, RA Holson, RR Clausing, P Gough, B Slikker, W Bowyer, JF AF Gazzara, RA Holson, RR Clausing, P Gough, B Slikker, W Bowyer, JF BE Moncada, S Stamler, J Gross, S Higgs, EA TI Investigations into nitric oxide modulation of methamphetamine-stimulated dopamine release SO BIOLOGY OF NITRIC OXIDE, PT 5 SE PORTLAND PRESS PROCEEDINGS LA English DT Proceedings Paper CT 4th International Meeting on the Biology of Nitric Oxide CY SEP, 1995 CL AMELIA ISL, FL C1 NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA 59 PORTLAND PL, LONDON, ENGLAND W1N 3AJ SN 0966-4068 BN 1-85578-102-6 J9 PORTL PR P PY 1996 VL 10 BP 309 EP 309 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Chemistry, Medicinal; Pharmacology & Pharmacy; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Pharmacology & Pharmacy; Physiology GA BE95M UT WOS:A1996BE95M00304 ER PT J AU Branham, WS Fishman, R Streck, RD Medlock, KL DeGeorge, JJ Sheehan, DM AF Branham, WS Fishman, R Streck, RD Medlock, KL DeGeorge, JJ Sheehan, DM TI ICI 182,780 inhibits endogenous estrogen-dependent rat uterine growth and tamoxifen-induced developmental toxicity SO BIOLOGY OF REPRODUCTION LA English DT Article ID HUMAN-BREAST-CANCER; DNA-BINDING; TRACT ABNORMALITIES; CLOMIPHENE CITRATE; POSTNATAL ONTOGENY; PURE ANTIESTROGEN; UP-REGULATION; RECEPTOR; ENDOMETRIAL; THERAPY AB To assess the effects of the steroidal antiestrogen ICI 182,780 on postnatal uterine development, female Sprague-Dawley rats were given s.c. injections of ICI 182,780 (0.1-100 mu g/rat) on each of postnatal days (PND) 10-14. ICI 182,780 inhibited uterine growth, as measured by uterine weight, in a dose-dependent manner but had no effect on either uterine luminal epithelium hypertrophy or gland genesis., Immunohistochemical analysis revealed that ICI 182,780 (10 mu g) markedly reduced uterine estrogen receptor (ER) immunoreactivity in all uterine cell types while tamoxifen (10 mu g) increased ER immunoreactivity, most notably in the luminal epithelium. In addition, tamoxifen increased uterine weight and induced luminal epithelium hypertrophy but inhibited uterine gland genesis-outcomes also seen with synthetic estrogens such as diethylstilbestrol. To test the hypothesis that these effects are a consequence of the estrogen agonist activity of tamoxifen, rats were cotreated with ICI 182,780 (10 mu g, PND 8-14) and tamoxifen (10 pg, PND 10-14). ICI 182,780 greatly reduced or completely blocked tamoxifen-induced uterine weight gain, luminal epithelium hypertrophy, tamoxifen-induced ER immunoreactivity, and the inhibition of uterine gland genesis. ICI 182,780 given daily on PND 1-5 did not alter PND 5 uterine weight or uterine differentiation on PND 26. We conclude that postnatal exposure to ICI 182,780 does not affect uterine growth or differentiation at an age when the uterus is not dependent on estrogen for growth, i.e., PND 1-5, but does inhibit later endogenous estrogen-dependent uterine growth. The blockade of tamoxifen-induced uterine developmental alterations by ICI 182,780 demonstrates that these tamoxifen effects result from its estrogen agonist activity. C1 US FDA,CTR DRUG EVALUAT & RES,DIV ONCOL DRUG PROD,ROCKVILLE,MD 20852. RP Branham, WS (reprint author), US FDA,NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079, USA. NR 49 TC 35 Z9 36 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JAN PY 1996 VL 54 IS 1 BP 160 EP 167 DI 10.1095/biolreprod54.1.160 PG 8 WC Reproductive Biology SC Reproductive Biology GA TK644 UT WOS:A1996TK64400021 PM 8838013 ER PT B AU Gannot, I Waynant, R AF Gannot, I Waynant, R BE Katzir, A Harrington, JA TI Experiments in transmission of free electron laser radiation by flexible waveguides SO BIOMEDICAL FIBER OPTICS, PROCEEDINGS OF SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Biomedical Fiber Optics CY JAN 31, 1996 CL SAN JOSE, CA SP Soc Photo Opt Instrumentat Engineers C1 US FDA,CTR DEVICES & RADIOL HLTH,ELECTROOPT BRANCH,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2051-4 J9 P SOC PHOTO-OPT INS PY 1996 VL 2677 BP 99 EP 102 DI 10.1117/12.237553 PG 4 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BF35A UT WOS:A1996BF35A00012 ER PT J AU Chen, JJ Ahn, HS AF Chen, JJ Ahn, HS TI Fitting mixed Poisson regression models using quasi-likelihood methods SO BIOMETRICAL JOURNAL LA English DT Article DE extended quasi-likelihood; negative binomial; Poisson-lognormal; Poisson-inverse-Gaussian pseudo-likelihood ID LINEAR-MODELS; ROBUST ESTIMATION; VARIANCE AB This paper is to investigate the use of the quasi-likelihood, extended quasi-likelihood, and pseudo-likelihood approach to estimating and testing the mean parameters with respect to two variance models, M1: psi = mu(theta)(1 + mu phi) and M2: psi = mu(theta)(1 + tau). Simulation was conducted to compare the bias and standard deviation, and type I error of the Wald tests, based on the model-based and robust variance estimates, using the three semi-parametric approaches under four mixed Poisson models, two variance structures, and two sample sizes. All methods perform reasonably well in terms of bias. Type I error of the Wald test, based on either the model-based or robust estimate, tends to be larger than the nominal level when over-dispersion is moderate. The extended quasi-likelihood method with the variance model M1 performs more consistently in terms of the efficiency and controlling the type I error than with the model M2, and better than the pseudo-likelihood approach with either the M1 or M2 model. The model-based estimate seems to perform better than the robust estimate when the sample size is small. C1 US FDA,NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,JEFFERSON,AR 72079. NR 21 TC 4 Z9 5 U1 0 U2 0 PU AKADEMIE VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 1996 VL 38 IS 1 BP 81 EP 96 DI 10.1002/bimj.4710380108 PG 16 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA TX162 UT WOS:A1996TX16200006 ER PT J AU Liu, PT Chow, LP AF Liu, PT Chow, LP TI An application of renewal theory to contraceptive follow-up studies, exemplified by an intrauterine device study SO BIOMETRICAL JOURNAL LA English DT Article DE follow-up study; life table; renewal theory; contraception; intrauterine device; family planning; stochastic process AB Contraceptive practice consists of a series of recurrent events of use and nonuse. Application of the life table technique for analysis of multiple-segment contraceptive usage is not entirely satisfactory. In this paper the renewal process approach is applied to the results of contraceptive follow-up studies involving all segments of use. By means of this model it is possible to estimate the proportion of current users, the average duration of actual use, and the average number of segments used by the accepters. The practical importance of these parameters for the evaluation of family planning programs is considered. C1 CFSAN,FOOD & DRUG ADM,DIV MATH,WASHINGTON,DC. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT POPULAT DYNAM,BALTIMORE,MD 21205. NR 18 TC 0 Z9 0 U1 0 U2 0 PU AKADEMIE VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 1996 VL 38 IS 4 BP 393 EP 403 DI 10.1002/bimj.4710380403 PG 11 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA VB070 UT WOS:A1996VB07000002 ER PT J AU Garthright, WE Blodgett, RJ AF Garthright, WE Blodgett, RJ TI Confidence intervals for microbial density using serial dilutions with MPN estimates SO BIOMETRICAL JOURNAL LA English DT Article DE most probable number; MPN; confidence interval; dilution method; serial dilutions AB An alteration to Woodward's methods is recommended for deriving a I - alpha confidence interval for microbial density using serial dilutions with most-probable-number (MPN) estimates. Outcomes of the serial dilution test are ordered by their MPNs. A lower limit for the confidence interval corresponding to an outcome y is the density for which y and all higher ordered outcomes have total probability alpha/2. An upper limit is derived in the analogous way. An alteration increases the lowest lower limits and decreases the highest upper limits. For comparison, a method that is optimal in the sense of null hypothesis rejection is described. This method ranks outcomes dependent upon the microbial density in question, using proportional first derivatives of the probabilities. These and currently used methods are compared. The recommended method is shown to be more desirable in certain respects, although resulting in slightly wider confidence intervals than DE MAN'S (1983) method. C1 US FDA,DIV MATH,WASHINGTON,DC 20204. NR 10 TC 6 Z9 6 U1 1 U2 3 PU AKADEMIE VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 1996 VL 38 IS 4 BP 489 EP 505 DI 10.1002/bimj.4710380415 PG 17 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA VB070 UT WOS:A1996VB07000010 ER PT J AU Wong, WK Lachenbruch, PA Clements, PJ AF Wong, WK Lachenbruch, PA Clements, PJ TI On choice of subjects and replicates in estimating among and within subject variation SO BIOMETRICAL JOURNAL LA English DT Article DE cost; nested design; power; random effects model; sample size ID SAMPLE-SIZE REQUIREMENTS; SKIN THICKNESS SCORE; SYSTEMIC-SCLEROSIS; VARIABILITY AB We consider the problem of choosing the number of replicates and number of subjects in a components of variance problem which optimizes various criteria. The case study here involves patients suffering from systemic sclerosis (Scleroderma), a form of rheumatic disease that is potentially disabling. Under the physical constraints imposed on the study, we find that using 2 or 3 replicates with as many patients as possible is the optimal strategy for several criteria. C1 US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT BIOSTAT,LOS ANGELES,CA 90095. NR 12 TC 0 Z9 0 U1 0 U2 0 PU AKADEMIE VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 1996 VL 38 IS 7 BP 767 EP 777 DI 10.1002/bimj.4710380702 PG 11 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA WD389 UT WOS:A1996WD38900001 ER PT J AU Larner, A Reich, NC AF Larner, A Reich, NC TI Interferon signal transduction SO BIOTHERAPY LA English DT Article DE gene expression; cytokines; JAK; STAT ID PROTEIN-TYROSINE KINASE; DNA-BINDING PROTEIN; TRANSCRIPTION FACTOR; CYTOPLASMIC ACTIVATION; RAPID ACTIVATION; RESPONSE ELEMENT; IFN-GAMMA; ALPHA; PHOSPHORYLATION; RECEPTOR AB The interferon signal transduction pathway initiates at a cell surface receptor and mediates the activation of target genes in the nucleus. The binding of interferon to a transmembrane receptor stimulates the activation of associated tyrosine kinases of the Janus kinase (JAK) family. Subsequently latent cytoplasmic transcription factors are activated by tyrosine phosphorylation and function as signal transducers and activators of transcription (STATs). Advances in the held of interferon research have contributed to our understanding of signal transduction induced by many cytokines that also use JAK/STAT signaling pathways to activate early response genes. The specificity of signal activation by distinct cytokines that share these signaling components, and the molecular interaction of the signaling components with each other and their respective cytokine receptors represent major areas of research that are beginning to be elucidated. Signaling molecules other than the JAKs and STATs have also been found to be activated following interferon binding. In addition, the induction of type I interferon stimulated genes by double-stranded RNA in the absence of interferon provides another pathway of specific gene activation. C1 SUNY STONY BROOK,DEPT PATHOL,STONY BROOK,NY 11794. RP Larner, A (reprint author), CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,8800 ROCKVILLE PK,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA50773] NR 60 TC 14 Z9 14 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0921-299X J9 BIOTHERAPY JI Biotherapy PY 1996 VL 8 IS 3-4 BP 175 EP 181 DI 10.1007/BF01877202 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA UV952 UT WOS:A1996UV95200005 PM 8813329 ER PT J AU Bart, KJ Foulds, J Patriarca, P AF Bart, KJ Foulds, J Patriarca, P TI Global eradication of poliomyelitis: Benefit-cost analysis SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Article AB A benefit-cost analysis of the Poliomyelitis Eradication Initiative was undertaken to facilitate national and international decision-making with regard to financial support. The base case examined the net costs and benefits during the period 1986-2040; the model assumed differential costs for oral poliovirus vaccine (OPV) and vaccine delivery in industrialized and developing countries, and ignored all benefits aside from reductions in direct costs for treatment and rehabilitation. The model showed that the ''break-even'' point at which benefits exceeded costs was the year 2007, with a saving of US$ 13 600 million by the year 2040. Sensitivity analyses revealed only small differences in the break-even point and in the dollars saved, when compared with the base case, even with large variations in the target age group for vaccination, the proportion of case-patients seeking medical attention, and the cost of vaccine delivery. The technical feasibility of global eradication is supported by the availability of an easily administered, inexpensive vaccine (OPV), the epidemiological characteristics of poliomyelitis, and the successful experience in the Americas with elimination of wild poliovirus infection. This model demonstrates that the Poliomyelitis Eradication Initiative is economically justified. C1 US DEPT HHS,NIAID,DIV MICROBIOL & INFECT DIS,NIH,BETHESDA,MD. US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,OFF VACCINES,BETHESDA,MD. RP Bart, KJ (reprint author), US DEPT HHS,OFF INT HLTH,OFF SECRETARY,ROOM 18-74,5600 FISHERS LANE,ROCKVILLE,MD 20878, USA. NR 23 TC 49 Z9 50 U1 0 U2 0 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA DISTRIBUTION AND SALES, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PY 1996 VL 74 IS 1 BP 35 EP 45 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN911 UT WOS:A1996UN91100004 PM 8653814 ER PT S AU Takimoto, CH Dahut, W Harold, N Nakashima, H Lieberman, R Liang, MD Arbuck, SG Chen, AP Hamilton, JM Cantilena, LR Allegra, CJ Grem, JL AF Takimoto, CH Dahut, W Harold, N Nakashima, H Lieberman, R Liang, MD Arbuck, SG Chen, AP Hamilton, JM Cantilena, LR Allegra, CJ Grem, JL BE Pantazis, P Giovanella, BC Rothenberg, ML TI Clinical pharmacology of 9-aminocamptothecin SO CAMPTOTHECINS: FROM DISCOVERY TO THE PATIENT SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on the Camptothecins - From Discovery to the Patient CY FEB 07-10, 1996 CL BETHESDA, MD SP New York Acad Sci, Pharmacia & Upjohn Inc, Janssen Pharm, NCI, Rhone Poulenc Rorer, SmithKline Beecham Pharm, RGK Fdn, Yakult Honsha Co Ltd, Boehringer Ingelheim KG, Daiichi Pharm Corp, Genentech Inc, Marion Merrell Dow Inc, Rhone Poulenc Rorer Fdn, Stehlin Fdn Canc Res ID PHASE C1 US FDA, CTR DRUG EVALUAT & RES, ROCKVILLE, MD 20857 USA. NCI, CANC THERAPY EVALUAT PROGRAM, BETHESDA, MD 20892 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT INTERNAL MED, DIV CLIN PHARMACOL, BETHESDA, MD 20814 USA. RP Takimoto, CH (reprint author), USN, BETHESDA HOSP,NCI,MED ONCOL BRANCH,DIV CLIN SCI, BLDG 8, ROOM 5101, BETHESDA, MD 20889 USA. NR 3 TC 6 Z9 6 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-057-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 803 BP 324 EP 326 DI 10.1111/j.1749-6632.1996.tb26407.x PG 3 WC Oncology; Multidisciplinary Sciences; Pharmacology & Pharmacy SC Oncology; Science & Technology - Other Topics; Pharmacology & Pharmacy GA BH28S UT WOS:A1996BH28S00037 PM 8993530 ER PT B AU Abeyta, C Tenge, BJ Hunt, JM Trost, PA Bark, DH Kaysner, CA Wekell, MM AF Abeyta, C Tenge, BJ Hunt, JM Trost, PA Bark, DH Kaysner, CA Wekell, MM BE Newell, DG Ketley, JM Feldman, RA TI Comparison of selective media for primary isolation of Campylobacters SO CAMPYLOBACTERS, HELICOBACTERS, AND RELATED ORGANISMS LA English DT Proceedings Paper CT 8th International Workshop on Campylobacters, Helicobacters, and Related Organisms CY JUL 10-13, 1996 CL WINCHESTER, ENGLAND SP NIAID, US, NIDDK, US, NCI, US, US FDA, Dept Hlth, UK, Minist Agr Fisheries & Food, GB, US Dept Def, Naval Res Inst, Public Hlth Lab Serv Board, England & Wales, USDA AR, US, USDA FSIS, US, Cent Vet Labs, UK, Brit Soc Immunol, UK, Unipath Ltd, Orion Ltd, Coca Cola Ltd, Glaxo Ltd, Bayer, UK, Don Whitley Sci, Winchester City Council RP Abeyta, C (reprint author), US FDA,SEAFOOD PROD RES CTR,22201 23RD DR SE,BOTHELL,WA 98041, USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45312-6 PY 1996 BP 13 EP 18 PG 6 WC Microbiology SC Microbiology GA BH72E UT WOS:A1996BH72E00004 ER PT J AU Solimando, DA Phillips, ET Weiss, RB Dawson, NA Diehl, LF Rickles, NM AF Solimando, DA Phillips, ET Weiss, RB Dawson, NA Diehl, LF Rickles, NM TI Hypertensive reactions associated with paclitaxel SO CANCER INVESTIGATION LA English DT Article C1 US FDA,OFF ESTAB LICENSING & PROD SURVEILLANCE,ROCKVILLE,MD 20857. WALTER REED ARMY MED CTR,DEPT MED,HEMATOL ONCOL SERV,WASHINGTON,DC 20307. RP Solimando, DA (reprint author), THOMAS JEFFERSON UNIV HOSP,DEPT PHARM,ROOM 1830G,111 S 11TH ST,PHILADELPHIA,PA 19107, USA. NR 3 TC 4 Z9 4 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 1996 VL 14 IS 4 BP 340 EP 342 DI 10.3109/07357909609012161 PG 3 WC Oncology SC Oncology GA UY225 UT WOS:A1996UY22500008 PM 8689429 ER PT S AU Sheng, PL Cerruti, C Ali, S Cadet, JL AF Sheng, PL Cerruti, C Ali, S Cadet, JL BE Ali, SF Takahashi, Y TI Nitric oxide is a mediator of methamphetamine (METH)-induced neurotoxicity - In vitro evidence from primary cultures of mesencephalic cells SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY JUN 29-30, 1995 CL NIIGATA, JAPAN SP Int Soc Neurochem, Niigata Univ, Niigata City, Niigate Prefecture Med Assoc, Niigate Prefecture, Denkaseiken Ltd, Jujisawa Pharm Co, Perkin Elmer Japan, ABI Div, Ikeda Med Electr Co, Kyowa Hakko Co, Sumitomo Pharm Co, Pfizer Pharm Co, Brain Res Inst, Dept Neuropharm, Colleagues, Niigate Univ Sch Med, Dept Psychiat, Colleagues, Servier Amer, Matsuhama Hosp, Seki Hosp, Itsukamachi Hosp, Shima Hosp, Natl Saigata Hosp, Niigata & Niitsu Shinai Hosp, Suehirobashi Hosp, Tamiya Hosp, Mishima Hosp, Sagatasoh Hosp, Murakami Hosp, Haryugaoka Hosp, Ohshima Hosp, Nagaoka Hoyoin Hosp, Usuki Hosp, Lizuka Hosp, Kurokawa Hosp, Inazuki Hosp, Sanko Hosp, Minamihama Hosp, Aska Hoyoen Hosp, Hoshi Hosp, Ichiyokai Hosp, Arita Hosp, US FDA, Natl Ctr Toxicol Res ID TYROSINE-HYDROXYLASE ACTIVITY; DNA STRAND-BREAKS; DOPAMINERGIC-NEURONS; STRIATAL DOPAMINE; RAT-BRAIN; INDUCED DEPRESSION; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; TRANSGENIC MICE; UPTAKE SITES C1 NIDA, IRP, Mol Neuropsychiat Sect, NIH, Baltimore, MD 21224 USA. Natl Ctr Toxicol Res, Neurochem Lab, Jefferson, AR 72079 USA. RP Cadet, JL (reprint author), NIDA, IRP, Mol Neuropsychiat Sect, NIH, POB 5180, Baltimore, MD 21224 USA. NR 42 TC 39 Z9 40 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-036-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 801 BP 174 EP 186 DI 10.1111/j.1749-6632.1996.tb17440.x PG 13 WC Substance Abuse; Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BK04B UT WOS:000070968400014 PM 8959032 ER PT S AU Ali, SF Newport, GD Slikker, W AF Ali, SF Newport, GD Slikker, W BE Ali, SF Takahashi, Y TI Methamphetamine-induced dopaminergic toxicity in mice - Role of environmental temperature and pharmacological agents SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY JUN 29-30, 1995 CL NIIGATA, JAPAN SP Int Soc Neurochem, Niigata Univ, Niigata City, Niigate Prefecture Med Assoc, Niigate Prefecture, Denkaseiken Ltd, Jujisawa Pharm Co, Perkin Elmer Japan, ABI Div, Ikeda Med Electr Co, Kyowa Hakko Co, Sumitomo Pharm Co, Pfizer Pharm Co, Brain Res Inst, Dept Neuropharm, Colleagues, Niigate Univ Sch Med, Dept Psychiat, Colleagues, Servier Amer, Matsuhama Hosp, Seki Hosp, Itsukamachi Hosp, Shima Hosp, Natl Saigata Hosp, Niigata & Niitsu Shinai Hosp, Suehirobashi Hosp, Tamiya Hosp, Mishima Hosp, Sagatasoh Hosp, Murakami Hosp, Haryugaoka Hosp, Ohshima Hosp, Nagaoka Hoyoin Hosp, Usuki Hosp, Lizuka Hosp, Kurokawa Hosp, Inazuki Hosp, Sanko Hosp, Minamihama Hosp, Aska Hoyoen Hosp, Hoshi Hosp, Ichiyokai Hosp, Arita Hosp, US FDA, Natl Ctr Toxicol Res ID TYROSINE-HYDROXYLASE ACTIVITY; DISMUTASE TRANSGENIC MICE; STRIATAL DOPAMINE; SUBSTITUTED AMPHETAMINES; INDUCED NEUROTOXICITY; C57BL/6J MOUSE; UPTAKE SITES; RELEASE; ANTAGONISTS; INJURY C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, US FDA, Jefferson, AR 72079 USA. RP Ali, SF (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, US FDA, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 30 TC 60 Z9 60 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-036-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 801 BP 187 EP 198 DI 10.1111/j.1749-6632.1996.tb17441.x PG 12 WC Substance Abuse; Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BK04B UT WOS:000070968400015 PM 8959033 ER PT S AU Scallet, AC Ye, X Rountree, R Nony, P Ali, SF AF Scallet, AC Ye, X Rountree, R Nony, P Ali, SF BE Ali, SF Takahashi, Y TI Ibogaine produces neurodegeneration in rat, but not mouse, cerebellum - Neurohistological biomarkers of Purkinje cell loss SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY JUN 29-30, 1995 CL NIIGATA, JAPAN SP Int Soc Neurochem, Niigata Univ, Niigata City, Niigate Prefecture Med Assoc, Niigate Prefecture, Denkaseiken Ltd, Jujisawa Pharm Co, Perkin Elmer Japan, ABI Div, Ikeda Med Electr Co, Kyowa Hakko Co, Sumitomo Pharm Co, Pfizer Pharm Co, Brain Res Inst, Dept Neuropharm, Colleagues, Niigate Univ Sch Med, Dept Psychiat, Colleagues, Servier Amer, Matsuhama Hosp, Seki Hosp, Itsukamachi Hosp, Shima Hosp, Natl Saigata Hosp, Niigata & Niitsu Shinai Hosp, Suehirobashi Hosp, Tamiya Hosp, Mishima Hosp, Sagatasoh Hosp, Murakami Hosp, Haryugaoka Hosp, Ohshima Hosp, Nagaoka Hoyoin Hosp, Usuki Hosp, Lizuka Hosp, Kurokawa Hosp, Inazuki Hosp, Sanko Hosp, Minamihama Hosp, Aska Hoyoen Hosp, Hoshi Hosp, Ichiyokai Hosp, Arita Hosp, US FDA, Natl Ctr Toxicol Res ID NMDA RECEPTOR COMPLEX; ANTI-ADDICTIVE DRUG; INVIVO MICRODIALYSIS; MORPHINE-WITHDRAWAL; PARASAGITTAL ZONES; LOCOMOTOR-ACTIVITY; MK-801 BINDING; MOTOR BEHAVIOR; D-AMPHETAMINE; COCAINE C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Scallet, AC (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Dr, Jefferson, AR 72079 USA. NR 27 TC 21 Z9 21 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-036-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 801 BP 217 EP 226 DI 10.1111/j.1749-6632.1996.tb17444.x PG 10 WC Substance Abuse; Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BK04B UT WOS:000070968400018 PM 8959036 ER PT S AU Scallet, AC Ye, X Ali, SF AF Scallet, AC Ye, X Ali, SF BE Ali, SF Takahashi, Y TI NOS and fos in rat and mouse brain regions - Possible relation to ibogaine-induced Purkinje cell loss SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY JUN 29-30, 1995 CL NIIGATA, JAPAN SP Int Soc Neurochem, Niigata Univ, Niigata City, Niigate Prefecture Med Assoc, Niigate Prefecture, Denkaseiken Ltd, Jujisawa Pharm Co, Perkin Elmer Japan, ABI Div, Ikeda Med Electr Co, Kyowa Hakko Co, Sumitomo Pharm Co, Pfizer Pharm Co, Brain Res Inst, Dept Neuropharm, Colleagues, Niigate Univ Sch Med, Dept Psychiat, Colleagues, Servier Amer, Matsuhama Hosp, Seki Hosp, Itsukamachi Hosp, Shima Hosp, Natl Saigata Hosp, Niigata & Niitsu Shinai Hosp, Suehirobashi Hosp, Tamiya Hosp, Mishima Hosp, Sagatasoh Hosp, Murakami Hosp, Haryugaoka Hosp, Ohshima Hosp, Nagaoka Hoyoin Hosp, Usuki Hosp, Lizuka Hosp, Kurokawa Hosp, Inazuki Hosp, Sanko Hosp, Minamihama Hosp, Aska Hoyoen Hosp, Hoshi Hosp, Ichiyokai Hosp, Arita Hosp, US FDA, Natl Ctr Toxicol Res ID NITRIC-OXIDE SYNTHASE; PARASAGITTAL ZONES; NUCLEUS-ACCUMBENS; NADPH DIAPHORASE; STRIATUM; DOPAMINE; MORPHINE; NEURONS; ACID C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Scallet, AC (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Dr, Jefferson, AR 72079 USA. NR 20 TC 7 Z9 7 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-036-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 801 BP 227 EP 238 DI 10.1111/j.1749-6632.1996.tb17445.x PG 12 WC Substance Abuse; Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BK04B UT WOS:000070968400019 PM 8959037 ER PT S AU Benson, KA Ali, SF Wilson, MC AF Benson, KA Ali, SF Wilson, MC BE Ali, SF Takahashi, Y TI The effects of prenatal cocaine exposure on dopaminergic challenge and receptor binding in Wistar rats SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY JUN 29-30, 1995 CL NIIGATA, JAPAN SP Int Soc Neurochem, Niigata Univ, Niigata City, Niigate Prefecture Med Assoc, Niigate Prefecture, Denkaseiken Ltd, Jujisawa Pharm Co, Perkin Elmer Japan, ABI Div, Ikeda Med Electr Co, Kyowa Hakko Co, Sumitomo Pharm Co, Pfizer Pharm Co, Brain Res Inst, Dept Neuropharm, Colleagues, Niigate Univ Sch Med, Dept Psychiat, Colleagues, Servier Amer, Matsuhama Hosp, Seki Hosp, Itsukamachi Hosp, Shima Hosp, Natl Saigata Hosp, Niigata & Niitsu Shinai Hosp, Suehirobashi Hosp, Tamiya Hosp, Mishima Hosp, Sagatasoh Hosp, Murakami Hosp, Haryugaoka Hosp, Ohshima Hosp, Nagaoka Hoyoin Hosp, Usuki Hosp, Lizuka Hosp, Kurokawa Hosp, Inazuki Hosp, Sanko Hosp, Minamihama Hosp, Aska Hoyoen Hosp, Hoshi Hosp, Ichiyokai Hosp, Arita Hosp, US FDA, Natl Ctr Toxicol Res ID BRAIN; SYSTEM C1 Univ Mississippi, Sch Pharm, Dept Pharmacol, University, MS 38677 USA. Univ Mississippi, Sch Pharm, Pharmaceut Sci Res Inst, University, MS 38677 USA. US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Benson, KA (reprint author), Armed Forces Radiobiol Res Inst, Dept Behav Sci, Bethesda, MD 20889 USA. NR 16 TC 7 Z9 7 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-036-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 801 BP 289 EP 300 DI 10.1111/j.1749-6632.1996.tb17449.x PG 12 WC Substance Abuse; Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BK04B UT WOS:000070968400023 PM 8959041 ER PT S AU Paule, MG Gillam, MP Binienda, Z Morris, P AF Paule, MG Gillam, MP Binienda, Z Morris, P BE Ali, SF Takahashi, Y TI Chronic cocaine exposure throughout gestation in the rhesus monkey - Pregnancy outcomes and offspring behavior SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY JUN 29-30, 1995 CL NIIGATA, JAPAN SP Int Soc Neurochem, Niigata Univ, Niigata City, Niigate Prefecture Med Assoc, Niigate Prefecture, Denkaseiken Ltd, Jujisawa Pharm Co, Perkin Elmer Japan, ABI Div, Ikeda Med Electr Co, Kyowa Hakko Co, Sumitomo Pharm Co, Pfizer Pharm Co, Brain Res Inst, Dept Neuropharm, Colleagues, Niigate Univ Sch Med, Dept Psychiat, Colleagues, Servier Amer, Matsuhama Hosp, Seki Hosp, Itsukamachi Hosp, Shima Hosp, Natl Saigata Hosp, Niigata & Niitsu Shinai Hosp, Suehirobashi Hosp, Tamiya Hosp, Mishima Hosp, Sagatasoh Hosp, Murakami Hosp, Haryugaoka Hosp, Ohshima Hosp, Nagaoka Hoyoin Hosp, Usuki Hosp, Lizuka Hosp, Kurokawa Hosp, Inazuki Hosp, Sanko Hosp, Minamihama Hosp, Aska Hoyoen Hosp, Hoshi Hosp, Ichiyokai Hosp, Arita Hosp, US FDA, Natl Ctr Toxicol Res ID MATERNAL-FETAL; DRUG-USE; HAIR; GROWTH; PHARMACOKINETICS; METHYLMERCURY; PERFORMANCE; PARAMETERS; MARIJUANA; ADDICTION C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Arkansas, Dept Pediat, Little Rock, AR 72205 USA. Univ Arkansas, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. RP Paule, MG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 47 TC 7 Z9 7 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-036-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 801 BP 301 EP 309 DI 10.1111/j.1749-6632.1996.tb17450.x PG 9 WC Substance Abuse; Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BK04B UT WOS:000070968400024 PM 8959042 ER PT S AU Binienda, Z Sandberg, JA Slikker, W Ali, SF AF Binienda, Z Sandberg, JA Slikker, W Ali, SF BE Ali, SF Takahashi, Y TI Alterations in electroencephalographic signals and monoamine concentrations in the rat brain following cocaine and methamphetamine treatment SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY JUN 29-30, 1995 CL NIIGATA, JAPAN SP Int Soc Neurochem, Niigata Univ, Niigata City, Niigate Prefecture Med Assoc, Niigate Prefecture, Denkaseiken Ltd, Jujisawa Pharm Co, Perkin Elmer Japan, ABI Div, Ikeda Med Electr Co, Kyowa Hakko Co, Sumitomo Pharm Co, Pfizer Pharm Co, Brain Res Inst, Dept Neuropharm, Colleagues, Niigate Univ Sch Med, Dept Psychiat, Colleagues, Servier Amer, Matsuhama Hosp, Seki Hosp, Itsukamachi Hosp, Shima Hosp, Natl Saigata Hosp, Niigata & Niitsu Shinai Hosp, Suehirobashi Hosp, Tamiya Hosp, Mishima Hosp, Sagatasoh Hosp, Murakami Hosp, Haryugaoka Hosp, Ohshima Hosp, Nagaoka Hoyoin Hosp, Usuki Hosp, Lizuka Hosp, Kurokawa Hosp, Inazuki Hosp, Sanko Hosp, Minamihama Hosp, Aska Hoyoen Hosp, Hoshi Hosp, Ichiyokai Hosp, Arita Hosp, US FDA, Natl Ctr Toxicol Res ID DOPAMINE; EEG; NEUROTOXICITY; SEROTONIN C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Binienda, Z (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 15 TC 1 Z9 1 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-036-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 801 BP 394 EP 400 DI 10.1111/j.1749-6632.1996.tb17461.x PG 7 WC Substance Abuse; Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BK04B UT WOS:000070968400035 PM 8959053 ER EF