FN Thomson Reuters Web of Science™ VR 1.0 PT B AU Bogner, MS AF Bogner, MS BE Zsambok, CE Klein, G TI Naturalistic decision making in health care SO NATURALISTIC DECISION MAKING SE EXPERTISE: RESEARCH AND APPLICATIONS LA English DT Proceedings Paper CT 2nd Naturalistic Decision Making Conference CY JUN, 1994 CL DAYTON, OH SP Klein Associates Inc, Armstrong Lab, Human Engn Div, USA Res Inst Behav & Social Sci, USA Res Lab, Human Res & Engn Directorate, Crew Syst Ergon Informat Anal Ctr, NASA, Ames Res Ctr, Naval Air Warfare Ctr, Training Syst Div, Naval Command, Control & Ocean Surveillance Ctr, USN, Off Naval Res C1 US FDA,ROCKVILLE,MD 20857. NR 0 TC 10 Z9 10 U1 2 U2 3 PU LAWRENCE ERLBAUM ASSOC PUBL PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430 BN 0-8058-1873-1 J9 EXP RES APPL PY 1997 BP 61 EP 69 PG 9 WC Psychology, Experimental SC Psychology GA BH21E UT WOS:A1997BH21E00006 ER PT S AU Binienda, Z AF Binienda, Z BE Slikker, W TI Compensatory long-term effect of perinatal hypoxia-ischemia - A possible mechanism for neuroprotection? SO NEUROPROTECTIVE AGENTS - THIRD INTERNATIONAL CONFERENCE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 3rd International Conference on Neuroprotective Agents - Clinical and Experimental Aspects CY SEP 09-12, 1996 CL VARENNA, ITALY SP New York Acad Sci, FDA, Natl Ctr Toxicol Res, Arkansas, Dept Vet Affairs Med Ctr, Togus, Maine ID 3-NITROPROPIONIC ACID; RAT HIPPOCAMPUS; BRAIN-LESIONS; NEONATAL RAT; KAINIC ACID; MODULATION; ADENOSINE; INCREASE; SEIZURES; TOXICITY RP Binienda, Z (reprint author), US FDA, NATL CTR TOXICOL RES, DIV NEUROTOXICOL, JEFFERSON, AR 72079 USA. NR 22 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 1-57331-093-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 825 BP 146 EP 151 DI 10.1111/j.1749-6632.1997.tb48425.x PG 6 WC Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BJ99G UT WOS:A1997BJ99G00014 PM 9369983 ER PT S AU Freyaldenhoven, TE Ali, SF AF Freyaldenhoven, TE Ali, SF BE Slikker, W TI Role of heat shock proteins in MPTP-induced neurotoxicity SO NEUROPROTECTIVE AGENTS - THIRD INTERNATIONAL CONFERENCE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 3rd International Conference on Neuroprotective Agents - Clinical and Experimental Aspects CY SEP 09-12, 1996 CL VARENNA, ITALY SP New York Acad Sci, FDA, Natl Ctr Toxicol Res, Arkansas, Dept Vet Affairs Med Ctr, Togus, Maine ID 1-METHYL-4-PHENYLPYRIDINIUM ION MPP+; MONOAMINE-OXIDASE; STRIATAL DOPAMINE; SUBSTANTIA-NIGRA; MOUSE-BRAIN; CHRONIC PARKINSONISM; PROTECTS CELLS; THERMAL-STRESS; MESSENGER-RNA; ATP LOSS C1 US FDA, NATL CTR TOXICOL RES, DIV NEUROTOXICOL, NEUROCHEM LAB, JEFFERSON, AR 72079 USA. UNIV ARKANSAS MED SCI, DEPT NEUROL, LITTLE ROCK, AR 72205 USA. UNIV ARKANSAS MED SCI, DEPT BIOCHEM & MOL BIOL, LITTLE ROCK, AR 72205 USA. NR 50 TC 10 Z9 12 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 1-57331-093-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 825 BP 167 EP 178 DI 10.1111/j.1749-6632.1997.tb48427.x PG 12 WC Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BJ99G UT WOS:A1997BJ99G00016 PM 9369985 ER PT S AU Scallet, AC Ye, XM AF Scallet, AC Ye, XM BE Slikker, W TI Excitotoxic mechanisms of neurodegeneration in transmissible spongiform encephalopathies SO NEUROPROTECTIVE AGENTS - THIRD INTERNATIONAL CONFERENCE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 3rd International Conference on Neuroprotective Agents - Clinical and Experimental Aspects CY SEP 09-12, 1996 CL VARENNA, ITALY SP New York Acad Sci, FDA, Natl Ctr Toxicol Res, Arkansas, Dept Vet Affairs Med Ctr, Togus, Maine ID NEONATAL MONOSODIUM GLUTAMATE; MONKEYS MACACA-FASCICULARIS; KAINATE RECEPTOR ACTIVATION; CREUTZFELDT-JAKOB-DISEASE; DOMOIC ACID INTOXICATION; RAT DORSAL HIPPOCAMPUS; CENTRAL NERVOUS-SYSTEM; LH-RELEASING HORMONE; ANTI-ADDICTIVE DRUG; GROWTH-HORMONE RP Scallet, AC (reprint author), US FDA, NATL CTR TOXICOL RES, DIV NEUROTOXICOL, JEFFERSON, AR 72079 USA. NR 96 TC 26 Z9 26 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 1-57331-093-X; 1-57331-092-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 825 BP 194 EP 205 DI 10.1111/j.1749-6632.1997.tb48429.x PG 12 WC Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BJ99G UT WOS:A1997BJ99G00018 PM 9369987 ER PT S AU Slikker, W Sobotka, TJ AF Slikker, W Sobotka, TJ BE Slikker, W TI Current and future approaches to neurotoxicity risk assessment SO NEUROPROTECTIVE AGENTS - THIRD INTERNATIONAL CONFERENCE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 3rd International Conference on Neuroprotective Agents - Clinical and Experimental Aspects CY SEP 09-12, 1996 CL VARENNA, ITALY SP New York Acad Sci, FDA, Natl Ctr Toxicol Res, Arkansas, Dept Vet Affairs Med Ctr, Togus, Maine ID DEVELOPMENTAL NEUROTOXICITY C1 US FDA, CTR FOOD SAFETY & APPL NUTR, NEUROBEHAV TOXICOL TEAM, LAUREL, MD 20708 USA. RP Slikker, W (reprint author), US FDA, NATL CTR TOXICOL RES, DIV NEUROTOXICOL, 3900 NCTR DR, JEFFERSON, AR 72079 USA. NR 25 TC 0 Z9 0 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-093-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 825 BP 406 EP 418 DI 10.1111/j.1749-6632.1997.tb48452.x PG 13 WC Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BJ99G UT WOS:A1997BJ99G00036 PM 9370005 ER PT S AU Slikker, W Trembly, B AF Slikker, W Trembly, B BE Slikker, W TI Summary of survey results from the Third International Conference on Neuroprotective Agents SO NEUROPROTECTIVE AGENTS - THIRD INTERNATIONAL CONFERENCE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 3rd International Conference on Neuroprotective Agents - Clinical and Experimental Aspects CY SEP 09-12, 1996 CL VARENNA, ITALY SP New York Acad Sci, FDA, Natl Ctr Toxicol Res, Arkansas, Dept Vet Affairs Med Ctr, Togus, Maine C1 DEPT VET AFFAIRS MED CTR, DEPT NEUROSURG, TOGUS, ME 04330 USA. RP Slikker, W (reprint author), US FDA, NATL CTR TOXICOL RES, DIV NEUROTOXICOL, 3900 NCTR DR, JEFFERSON, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-093-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 825 BP 428 EP 430 DI 10.1111/j.1749-6632.1997.tb48454.x PG 3 WC Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BJ99G UT WOS:A1997BJ99G00037 ER PT J AU Frederick, DL Paule, MG AF Frederick, DL Paule, MG TI Effects of MDMA on complex brain function in laboratory animals SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE MDMA; brain function; neurotransmitter system; cognitive processes; short-term memory ID CONDITIONED PLACE PREFERENCE; SCHEDULE-CONTROLLED BEHAVIOR; CENTRAL SEROTONERGIC NEURONS; ORALLY-ADMINISTERED MDMA; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; D-AMPHETAMINE; METHYLENEDIOXYMETHAMPHETAMINE MDMA; NONHUMAN PRIMATE; CROSS-TOLERANCE; TASTE-AVERSIONS AB This review surveys experiments that have examined the effects of acute and chronic MDMA exposure on schedule-controlled operant behaviors thought to engender responses that reflect the expression of complex brain functions. Such functions include time estimation, short-term memory, learning, motivation, and color and position discrimination. Recent experiments conducted in the Behavioral Toxicology Laboratory at the National Center for Toxicological Research concerning MDMA's acute and long-term effects on rhesus monkey performance in an operant test battery are compared to previous studies involving the effects of MDMA on operant behaviors. Results of these experiments suggest that when given acutely, MDMA disrupts complex brain functions associated with learning and time estimation more than those associated with short-term memory and visual discrimination, and that behavioral tasks requiring relatively high rates of responding are particularly sensitive to the disruptive effects of MDMA. Repeated exposure to doses of MDMA sufficient to produce long-lasting changes in brain neurotransmitter systems results in residual effects (e.g. tolerance, sensitivity) on behavioral task performance when subjects are subsequently challenged with acute MDMA, whereas baseline (non-challenged) performance of these tasks after such exposure generally remains unchanged. Although the experiments described herein were conducted on a relatively small number of non-human subjects, they raise the possibility that long-term effects on cognitive processes may also occur in humans exposed to repeated or acute high doses of MDMA. C1 UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & TOXICOL,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT PEDIAT,LITTLE ROCK,AR 72205. RP Frederick, DL (reprint author), US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,JEFFERSON,AR 72079, USA. NR 70 TC 45 Z9 45 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD JAN PY 1997 VL 21 IS 1 BP 67 EP 78 DI 10.1016/0149-7634(95)00064-X PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA WB590 UT WOS:A1997WB59000007 PM 8994210 ER PT J AU Lazarovici, P Oshima, M Shavit, D Shibutani, M Jiang, H Monshipouri, M Fink, D Movsesyan, V Guroff, G AF Lazarovici, P Oshima, M Shavit, D Shibutani, M Jiang, H Monshipouri, M Fink, D Movsesyan, V Guroff, G TI Down-regulation of epidermal growth factor (EGF) receptors by nerve growth factor (NGF) in PC12 cells is P140(TRK)-, Ras-, and Src-dependent SO NEUROSCIENCE LETTERS LA English DT Meeting Abstract C1 Hebrew Univ Jerusalem, Sch Pharm, Dept Pharmacol, IL-91120 Jerusalem, Israel. NICHD, Growth Factors Sect, NIH, Bethesda, MD USA. US FDA, Div Cytokines Biol, Bethesda, MD 20892 USA. RI Shibutani, Makoto/C-2510-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PY 1997 SU 48 BP S31 EP S31 PG 1 WC Neurosciences SC Neurosciences & Neurology GA ZB328 UT WOS:000072460000127 ER PT J AU Ye, X Scallet, AC Carp, RI AF Ye, X Scallet, AC Carp, RI TI The 139H scrapie agent produces hypothalamic neurotoxicity and pancreatic islet histopathology: Electron microscopic studies SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 13th International Neurotoxicology Conference on Developmental Neurotoxicity of Endocrine Disrupters - Dioxins, PCBs, Pesticides and Metals CY OCT 29-NOV 01, 1995 CL HOT SPRINGS, AR SP Agcy Tox Subst & Dis Registry, Natl Ctr Environm Assessment, Natl Hlth & Environm Effects Res Lab, US EPA, NIH, NIEHS, Cranmer & Assoc Inc, Eastman Kodak Co, Environm Hlth Fdn, Redfield Labs, TSI Genzyme Transegen, Univ Arkansas Med Sci, Arkansas Childrens Hosp, US FDA, Natl Ctr Toxicol Res DE scrapie; islet of Langerhans; necrosis; PrPSc; hamster ID CENTRAL-NERVOUS-SYSTEM; PRION PROTEIN-FRAGMENT; INDUCED OBESITY; MOUSE SCRAPIE; MICE; HAMSTERS; STRAIN; APOPTOSIS; BRAIN; RAT AB Neuronal degeneration, along with astrocytosis, spongiform vacuolation, and amyloid (PrPSc) formation, have long been regarded as neuropathological hallmarks of transmissible spongiform encephalopathies (TSEs). In animals, these diseases include; scrapie, transmissible mink encephalopathy, chronic wasting disease, bovine and feline spongiform encephalopathies, and in humans; kuru, Creutzfeldt-Jakob disease (CJD) and Gerstmann-Straussler-Scheinker syndrome (GSS). The abnormal amyloid protein, (PrPSc) is toxic to neurons. Our previous studies showed that hamsters treated with 139H scrapie strain developed obesity, and generalized endocrinopathy, including lesions in hypothalamus, pituitary and pancreas. Histochemical and immunocytochemical studies revealed extensive pathological changes in the islets of Langerhans in 139H-infected hamsters, but not in hamsters infected with 263K scrapie strain. Using routine electron microscopy (EM) we have observed more details of lesions in the beta cells of islets of Langerhans in these animals. Cytoplasmic vacuolation occurred, cytoplasmic organelles were found damaged and disrupted, and membranes were occasionally ruptured. The width of endoplasmic reticulum (ER) lumina were 50-150 nm in controls, whereas in 139H-infected hamsters, they were occasionally increased up to 4000 nm in diameter. Most beta cells showed degranulation. These EM observations suggest that the cellular death seen in the islets of Langerhans in 139H-infected hamsters is due to necrosis, not apoptosis. Since there were no amyloid deposits found in the islet of Langerhans at the EM level, and there were extremely low scrapie infectivity levels and PrP S' levels in pancreas, it is suggested that the changes noted in pancreas were not a direct toxic effect of PrPSc. Instead, our study suggests that scrapie prion protein PrP S', acting as a neurotoxicant, alters the hypothalamic neuroendocrine regulation of the pancreas. (C) 1997 Inter Press, Inc. C1 NYS INST BASIC RES DEV DISABIL,STATEN ISL,NY. RP Ye, X (reprint author), NATL CTR TOXICOL RES,DIV NEUROTOXICOL,3900 NCTR DR,JEFFERSON,AR 72079, USA. FU NIA NIH HHS [AG0907] NR 53 TC 16 Z9 16 U1 0 U2 0 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PY 1997 VL 18 IS 2 BP 533 EP 545 PG 13 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA XU979 UT WOS:A1997XU97900022 PM 9291501 ER PT J AU Ferguson, SA StOmer, VEV Kwon, OS Holson, RR Houston, RJ Rottinghaus, GE Slikker, W AF Ferguson, SA StOmer, VEV Kwon, OS Holson, RR Houston, RJ Rottinghaus, GE Slikker, W TI Prenatal fumonisin (FB1) treatment in rats results in minimal maternal or offspring toxicity SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 13th International Neurotoxicology Conference on Developmental Neurotoxicity of Endocrine Disrupters - Dioxins, PCBs, Pesticides and Metals CY OCT 29-NOV 01, 1995 CL HOT SPRINGS, AR SP Agcy Tox Subst & Dis Registry, Natl Ctr Environm Assessment, Natl Hlth & Environm Effects Res Lab, US EPA, NIH, NIEHS, Cranmer & Assoc Inc, Eastman Kodak Co, Environm Hlth Fdn, Redfield Labs, TSI Genzyme Transegen, Univ Arkansas Med Sci, Arkansas Childrens Hosp, US FDA, Natl Ctr Toxicol Res DE fumonisin; developmental toxicity; mycotoxin; neurobehavioral toxicity; rodent ID MONILIFORME CULTURE MATERIAL; FUSARIUM-MONILIFORME; ESOPHAGEAL CANCER; DEVELOPMENTAL TOXICITY; CORN; B-1; B1; MYCOTOXINS; HAMSTERS; EXTRACT AB To investigate the neurobehavioral and developmental effects of the mycotoxin, FB1, Sprague-Dawley rats were treated with FB1 on gestational days 13-20. In Experiment I, FB1 was obtained from culture material and pregnant rats were gavaged with 0, 0.8 or 1.6 mg/kg. In Experiment 2, pregnant rats were gavaged with purified FB1 at doses of 0, 1.6 or 9.6 mg/kg. Offspring were evaluated on a battery of behavioral tests as well as measures of whole and regional brain weight. There were no effects on maternal weight gain, reproductive outcomes, or offspring body weight through adulthood in either experiment. Complex maze performance, open field and running wheel activity were not altered by prenatal FB1 treatment. In Experiment 2, acoustic startle response was depressed at two ages during the first or second block of 9 trials in males treated with purified FB1. Females exhibited no such alterations. Play behavior at PND 33, but not PND 26, was increased in males prenatally treated with 9.6 mg/kg relative to those treated with 1.6 mg/kg. There were no substantive treatment effects on regional brain weight. These results suggest that doses of less than or equal to 9.6 mg purified FB1/kg and/or less than or equal to 1.6 mg FB1/kg obtained from culture material cause minimal maternal toxicity and produce few developmental functional alterations. In addition, potential FB1-related functional alterations were evident only in males providing further support for a mild sex-specific effect for fumonisin. (C) 1997 Inter Press, Inc. C1 UNIV MISSOURI,COLL VET MED,DEPT VET BIOMED SCI,COLUMBIA,MI 65211. NATL CTR TOXICOL RES,DIV NEUROTOXICOL,JEFFERSON,AR 72079. UNIV ARKANSAS,DEPT PSYCHOL,LITTLE ROCK,AR 72204. RP Ferguson, SA (reprint author), NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,HFT-130,2900 NCTR RD,JEFFERSON,AR 72079, USA. NR 26 TC 7 Z9 7 U1 0 U2 2 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PY 1997 VL 18 IS 2 BP 561 EP 569 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA XU979 UT WOS:A1997XU97900025 PM 9291504 ER PT J AU Kwon, OS Schmued, LC Slikker, W AF Kwon, OS Schmued, LC Slikker, W TI Fumonisin B-1 in developing rats alters brain sphinganine levels and myelination SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 13th International Neurotoxicology Conference on Developmental Neurotoxicity of Endocrine Disrupters - Dioxins, PCBs, Pesticides and Metals CY OCT 29-NOV 01, 1995 CL HOT SPRINGS, AR SP Agcy Tox Subst & Dis Registry, Natl Ctr Environm Assessment, Natl Hlth & Environm Effects Res Lab, US EPA, NIH, NIEHS, Cranmer & Assoc Inc, Eastman Kodak Co, Environm Hlth Fdn, Redfield Labs, TSI Genzyme Transegen, Univ Arkansas Med Sci, Arkansas Childrens Hosp, US FDA, Natl Ctr Toxicol Res DE fumonisin B-1; mycotoxin; sphinganine; sphingosine; hypomyelination; 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase, E.C.3.1.4.37) ID FUSARIUM-MONILIFORME; SPHINGOLIPID BIOSYNTHESIS; MYCOTOXINS; INHIBITION; CANCER; SPHINGOSINE; AREAS; LEUKOENCEPHALOMALACIA; CYTOTOXICITY; TRANSKEI AB Objectives of this study were to test the hypothesis that fumonisin B-1 (FB1) alters sphinganine (Sa) levels and myelin synthesis in the central nervous system of developing rats. FB1 (subcutaneous, 0.4 or 0.8 mg/kd/day) from postnatal days (PND) 3 to PND 72 resulted in a significant reduction of body weight gain and decreased survival rates. Both Sa levels and Sa/sphingosine (So) ratios were significantly increased in the brain of rats given 0.8 mg FB1/kg/day. To confirm the effect of limited nutrition on changes in the Sa levels and myelinogenesis, rats given 0.8 mg FB1/kg/day or treated by limited nutrition (temporary removal from dam during postnatal period) were compared to those in saline controls. Sa levels and Sa/So ratios were increased significantly in the 0.8 FB1-treated, but were not altered in the limited nutrition group. Myelin deposition in the corpus callosum and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) activities were decreased significantly in both nutritionally limited and FB1-exposed rats. These data indicate that sphingolipid metabolism in the central nervous system of developing rats is vulnerable to FB, exposure. The hypomyelination associated with FB1-treatment may be mediated by limited nutrition. (C) 1997 Inter Press, Inc. C1 UNIV ARKANSAS,DEPT PHARMACOL & TOXICOL,LITTLE ROCK,AR 72205. US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,JEFFERSON,AR 72079. NR 36 TC 20 Z9 21 U1 0 U2 3 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PY 1997 VL 18 IS 2 BP 571 EP 579 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA XU979 UT WOS:A1997XU97900026 PM 9291505 ER PT J AU Morris, P Binienda, Z Gillam, MP Klein, J McMartin, K Koren, G Duhart, HM Slikker, W Paule, MG AF Morris, P Binienda, Z Gillam, MP Klein, J McMartin, K Koren, G Duhart, HM Slikker, W Paule, MG TI The effect of chronic cocaine exposure throughout pregnancy on maternal and infant outcomes in the rhesus monkey SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE rhesus; cocaine; pregnancy; mother; infant; outcomes ID OPERANT TEST BATTERY; NEONATAL GROWTH; FOLLOW-UP; DRUG-USE; FETAL; PHARMACOKINETICS; CONSEQUENCES; PARAMETERS; MARIJUANA; ALCOHOL AB To explore the effects of gestational cocaine exposure in a nonhuman primate model, pregnant rhesus monkeys were either treated (N = 10) with escalating doses of cocaine up to 7.5 mg/kg (IM), three times per day, 5 consecutive days per week, prior to conception and throughout gestation, or were not treated (N = 10) with cocaine at all. Substantial levels of both cocaine and its major metabolite, benzoylecgonine, were observed in samples of hair taken at birth from mothers and infants of the cocaine-treated group. 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. On the other hand, the experimental groups did differ significantly with respect to infant outcome, as measured at birth by body weight, overall length, and crown circumference, all of which were decreased in the cocaine-treated group. A variety of reflexes tested at birth were normal in the cocaine-treated group. It was concluded that, in a rhesus monkey model, chronic cocaine exposure throughout pregnancy had no significant effect on maternal outcome, but did significantly affect infant outcome as assessed in this investigation. (C) 1997 Elsevier Science Inc. C1 HOSP SICK CHILDREN,DIV CLIN PHARMACOL & TOXICOL,TORONTO,ON M5G 1X8,CANADA. 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 63 TC 17 Z9 17 U1 1 U2 1 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 JAN-FEB PY 1997 VL 19 IS 1 BP 47 EP 57 DI 10.1016/S0892-0362(96)00187-0 PG 11 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA WP695 UT WOS:A1997WP69500008 PM 9088010 ER PT J AU Desai, VG Lyn-Cook, LE Aidoo, A Casciano, DA Feuers, RJ AF Desai, VG Lyn-Cook, LE Aidoo, A Casciano, DA Feuers, RJ TI Modulation of antioxidant enzymes in bleomycin-treated rats by vitamin C and beta-carotene SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID HUMAN-BLOOD PLASMA; SUPEROXIDE-DISMUTASE; METABOLIZING-ENZYMES; HYDROXYL RADICALS; ASCORBIC-ACID; CANTHAXANTHIN; GENOTOXICITY; GLUTATHIONE; PEROXIDASE; CANCER AB Bleomycin (BLM), an antineoplastic drug, is known to induce DNA strand breaks and is also mutagenic in mammalian cells, however, its mechanism of action is not well understood. It has been proposed that BLM cytotoxicity is mediated through the generation of reactive oxygen species. We have determined the effects of BLM on endogenous hepatic antioxidant enzymes such as glutathione peroxidase (GPx), glutathione reductase, and glucose-6-phosphate dehydrogenase in rats exposed to BLM in conjunction with dietary vitamins, vitamin C and beta-carotene (BC). Male Fischer 344 rats of two different age groups were treated with BLM in the presence or absence of antioxidant vitamins. In control animals, an age-associated decrease in GPx activity was noted (p < 0.05). The decrease in GPx activity observed in BLM-treated old animals given vitamin C was significant (p < 0.05) compared with BLM-treated young animals fed vitamin C. BC moderately induced GPx and glutathione reductase activities in old BLM-treated animals; however the increase in GPx was statistically significant (p < 0.05) only compared with old controls. A similar increase was noted in the activities of all the enzymes examined in young animals. Our results indicate that BLM exposure was accompanied by alterations in the activities of endogenous antioxidant enzymes, with a profound increase in activities occurring in old animals. In addition, the observed enzyme activities were modulated by antioxidant vitamin administration. The observation that both vitamins displayed differential effects on the enzyme activities also suggests that vitamin C and BC exert their effects by separate mechanisms. C1 US FDA, Div Genet Toxicol, Natl Ctr Toxicol Res, US Dept HHS, Jefferson, AR 72079 USA. RP Feuers, RJ (reprint author), US FDA, Div Genet Toxicol, Natl Ctr Toxicol Res, US Dept HHS, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 39 TC 7 Z9 7 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 1997 VL 29 IS 2 BP 127 EP 132 PG 6 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA YM124 UT WOS:000071031100005 PM 9427975 ER PT S AU Rulis, AM Pellicore, LS Thorsheim, HR AF Rulis, AM Pellicore, LS Thorsheim, HR BE Anderson, GH Rolls, BJ Steffen, DG TI Regulatory aspects of the introduction of new macronutrient substitutes SO NUTRITIONAL IMPLICATIONS OF MACRONUTRIENT SUBSTITUTES SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Nutritional Implications of Macronutrient Substitutes CY OCT 27-29, 1996 CL ARLINGTON, VA SP New York Acad Sci, Int Life Sci Inst, N Amer Tech Comm Macronutrient Substitut RP Rulis, AM (reprint author), US FDA, CTR FOOD SAFETY & APPL NUTR, OFF PREMARKET APPROVAL, HFS-200, 200 C ST SW, WASHINGTON, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-084-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 819 BP 22 EP 28 DI 10.1111/j.1749-6632.1997.tb51795.x PG 7 WC Food Science & Technology; Multidisciplinary Sciences; Nutrition & Dietetics SC Food Science & Technology; Science & Technology - Other Topics; Nutrition & Dietetics GA BH98L UT WOS:A1997BH98L00003 PM 9186757 ER PT S AU Mitchell, GV Grundel, E Jenkins, MY AF Mitchell, GV Grundel, E Jenkins, MY BE Anderson, GH Rolls, BJ Steffen, DG TI Replacement of dietary fat with fat-free margarine alters vitamin E storage in rats SO NUTRITIONAL IMPLICATIONS OF MACRONUTRIENT SUBSTITUTES SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Nutritional Implications of Macronutrient Substitutes CY OCT 27-29, 1996 CL ARLINGTON, VA SP New York Acad Sci, Int Life Sci Inst, N Amer Tech Comm Macronutrient Substitut RP Mitchell, GV (reprint author), US FDA, OFF FOOD LABELING, CTR FOOD SAFETY & APPL NUTR, LAUREL, MD 20708 USA. NR 3 TC 2 Z9 2 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 1-57331-084-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 819 BP 236 EP 238 DI 10.1111/j.1749-6632.1997.tb51812.x PG 3 WC Food Science & Technology; Multidisciplinary Sciences; Nutrition & Dietetics SC Food Science & Technology; Science & Technology - Other Topics; Nutrition & Dietetics GA BH98L UT WOS:A1997BH98L00020 PM 9186771 ER PT S AU Rader, JI AF Rader, JI BE Anderson, GH Rolls, BJ Steffen, DG TI Oil-soluble vitamin content of new reduced-fat and fat-free margarines - Potential implications for vitamin E intake SO NUTRITIONAL IMPLICATIONS OF MACRONUTRIENT SUBSTITUTES SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Nutritional Implications of Macronutrient Substitutes CY OCT 27-29, 1996 CL ARLINGTON, VA SP New York Acad Sci, Int Life Sci Inst, N Amer Tech Comm Macronutrient Substitut RP Rader, JI (reprint author), US FDA, CTR FOOD SAFETY & APPL NUTR, OFF FOOD LABELING, WASHINGTON, DC 20204 USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-084-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 819 BP 242 EP 246 DI 10.1111/j.1749-6632.1997.tb51814.x PG 5 WC Food Science & Technology; Multidisciplinary Sciences; Nutrition & Dietetics SC Food Science & Technology; Science & Technology - Other Topics; Nutrition & Dietetics GA BH98L UT WOS:A1997BH98L00022 PM 9186772 ER PT J AU Varricchio, F Husain, SR Leland, P Gill, P Puri, RK AF Varricchio, F Husain, SR Leland, P Gill, P Puri, RK TI Interleukin-4 receptor expression in vivo on human AIDS-related Kaposi's sarcoma SO ONCOLOGY RESEARCH LA English DT Article DE Kaposi's sarcoma; interleukin-1 receptors; immunohistochemistry; basic fibroblast growth factor; S-100 ID RENAL-CELL-CARCINOMA; IMMUNODEFICIENCY-VIRUS TYPE-1; FIBROBLAST GROWTH-FACTOR; ADHESION MOLECULE-1 ICAM-1; LONG-TERM CULTURE; TAT PROTEIN; DIFFERENTIAL EXPRESSION; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; GENE-EXPRESSION AB We have investigated the expression of interleukin-4 receptors (IL-4R) in acquired immunodeficiency syndrome (AIDS)-related Kaposi's Sarcoma (KS) in situ by immunohistochemistry. Frozen and fixed sections from five patch stage and two nodular stage KS lesions were stained with anti-IL-4R monoclonal antibody with similar results. Skin biopsies from the clinically apparent lesions and adjacent clinically uninvolved skin were also examined. We observed that individual KS cells lining the irregular vascular spaces were stained with anti-IL-4R antibody, although the degree of staining was variable. The epithelioid and oval cells appear to stain more than the spindle cells in plaque stages or nodular lesions. The sections from nonclinically involved skin also contained a few cells with features of KS, singly or in clusters that also stained for IL-4R. Skin sections from four normal donors did not stain with IL-4R antibody except for hair follicles, sweat glands, and faint staining of blood vessels. KS sections were also stained with antibodies to basic fibroblast growth factor (FGF), S100, fibronectin, and von Willebrand factor. KS lesions from clinically involved and uninvolved skin sections were positive for all four antibodies. Thus, the differences between KS lesion and clinically uninvolved skin adjacent to a KS lesion may be more quantitative than qualitative. The IL-4 receptors on KS cells were functional as IL-4 modulated intercellular adhesion molecule 1 (ICAM-1) on these cells. Taken together, our results suggest that AIDS-KS cells express eleveated levels of IL-4R compared to normal endothelial and skin cells and, thus, the receptors for IL-4 on KS may serve as an attractive target for anticancer therapy. C1 US FDA, Dept Biostat & Epidemiol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Univ So Calif, Sch Med, Dept Hematol, Los Angeles, CA USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, HFM-530,Bldg 29B,Room 2NN10,29 Lincoln Dr MSC 455, Bethesda, MD 20892 USA. EM PURI@A1.CBER.FDA.GOV NR 63 TC 9 Z9 9 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0965-0407 J9 ONCOL RES JI Oncol. Res. PY 1997 VL 9 IS 9 BP 495 EP 503 PG 9 WC Oncology SC Oncology GA YX637 UT WOS:000072061200006 PM 9495455 ER PT B AU Gannot, I Bonner, RF Gannot, G Fox, PC You, JS Waynant, RW Gandjbakhche, AH AF Gannot, I Bonner, RF Gannot, G Fox, PC You, JS Waynant, RW Gandjbakhche, AH BE Chance, B Alfano, RR TI Quantitative detection of multiple fluorophore sites as a tool for diagnosis and monitoring disease progression in salivary glands. SO OPTICAL TOMOGRAPHY AND SPECTROSCOPY OF TISSUE: THEORY, INSTRUMENTATION, MODEL, AND HUMAN STUDIES II, PROCEEDINGS OF SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Optical Tomography and Spectroscopy of Tissue - Theory, Instrumentation, Model, and Human Studies II CY FEB 09-12, 1997 CL SAN JOSE, CA SP Int Biomed Opt soc, Soc Photo Opt Instrumentat Engineers, Amer Soc Laser Med & Surg Inc AB A series of fluorescent surface images were obtained from physical models of localized fluorophores embedded al various depths and separations in tissue phantoms. Our random walk theory was applied to create an analytical model of multiple flurophores embedded in tissue-like phantom. Using this model, From accuired set of surface images, the location of the fluorophores was reconstructed and compared it to their known 3-D distributions. A good correlation was found, and the ability to resolve fluorophores as a function of depth and separation was determined. In paralel in in-vitro study, specific coloring of sections of minor salivary glands was also demonstrated. These results demonstrate the possibility of using inverse methods to reconstruct unknown locations and concentrations of optical probes specifically bound to infiltrating lymphocytes in minor salivary glands of patients with Sjorgen's syndrome. RP Gannot, I (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,ELECTROPT BRANCH,ROCKVILLE,MD 20857, USA. RI Bonner, Robert/C-6783-2015 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 0-8194-2390-4 J9 P SOC PHOTO-OPT INS PY 1997 VL 2979 BP 151 EP 156 DI 10.1117/12.280241 PG 6 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BJ71N UT WOS:A1997BJ71N00018 ER PT J AU Quakyi, EK Carter, PH Tsai, CM Marti, GE AF Quakyi, EK Carter, PH Tsai, CM Marti, GE TI Immunization with meningococcal membrane-bound lipooligosaccharide accelerates granulocyte recovery enhances lymphocyte proliferation in myelosuppressed mice SO PATHOBIOLOGY LA English DT Article DE septic shock; myelosuppression; granulocytes; lipooligosaccharide; meningococcus; cyclophosphamide; flow cytometry; interferon-gamma; interleukin-6; interleukin-1 beta; interleukin-3; white blood cell lysis ID COLONY-STIMULATING FACTOR; STEM-CELL FACTOR; MURINE HEMATOPOIETIC PROGENITORS; INTERFERON-GAMMA; BONE-MARROW; INTERLEUKIN-6; IL-6; CYCLOPHOSPHAMIDE; VACCINE; MECHANISMS AB Protective effects of detergent-treated outer membrane vesicles (D-OMVs) prepared from the parent group B M986 strain and the nonencapsulated M986-NCV mutant in myelosuppressed mice were investigated in models of experimental septic shock. The effects of D-OMVs on expansion of the myeloid compartment, on spleen cell proliferation to mitogen stimulation, and on cytokines induced during this period were investigated. On 3 consecutive days, mice were injected with 1 mu g/kg of lipooligosaccharide (LOS) or lipopolysaccharide, or 75 mu g/kg D-OMV followed by a single dose of cyclophosphamide (200 mg/kg) 24 h later, Eight weeks after the last injection, animals were challenged with a combination of galactosamine (400 mg/kg) and live Neisseria meningitidis. More than 90% of control mice died within 24 h when challenged with 10(5) CFU of bacteria. Mice immunized with LOS or D-OMV were rendered neutropenic but were protected against bacterial challenge of at least 10(7) CFU. At different time intervals, peripheral blood samples were obtained to characterize changes in circulating blood cells. The rise in absolute granulocyte numbers occurred 24 h earlier with peak cell counts about 3 times higher than those seen in the placebo groups, Peripheral blood cells from D-OMV-treated animals expressed about twofold more Gr-1 antigen (myeloid surface cell marker) than placebo-treated controls. The proliferative responses to both B and T cells were reduced in all treatment groups due to the effects of cyclophosphamide. D-OMV treatment afforded the greatest protection for mitogen-activated lymphocytes from the lethal effects of cyclophosphamide and also enhanced T and B cell proliferation. Low IL-1 beta levels and increases in serum IL-6 were detected in all treatment groups. In contrast, significant IFN-gamma and IL-3 levels were only detected in D-OMV-treated groups. These results indicate that D-OMVs, which have reduced toxicity, have prophylactic potential in inducing specific cytokines that accelerate granulocyte recovery following cytoreductive therapy by promoting both proliferation and maturation of myeloid precursors as well as augmenting the immune system. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CELL & GENE THERAPIES,FLOW & IMAGE CYTOMETRY SECT,NIH,BETHESDA,MD 20892. NR 49 TC 7 Z9 7 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-2008 J9 PATHOBIOLOGY JI Pathobiology PD JAN-FEB PY 1997 VL 65 IS 1 BP 26 EP 38 DI 10.1159/000164100 PG 13 WC Cell Biology; Pathology SC Cell Biology; Pathology GA XE702 UT WOS:A1997XE70200003 PM 9200187 ER PT J AU Berlin, CM McCarverMay, DG Notterman, DA Ward, RM Weismann, DN Wilson, GS Wilson, JT Weller, EB Bennett, DR Mulinare, J Kaufman, P Krough, C Rieder, MJ Troendle, G Yaffe, SJ Cote, CJ Szefler, SJ Blumer, JL Frader, JE Crain, LS Moseley, KL Nelson, RM Porter, IH Vizcarrondo, FE Bowes, WA Kazura, A Krug, EF Caniano, DA Dressser, R King, NMP AF Berlin, CM McCarverMay, DG Notterman, DA Ward, RM Weismann, DN Wilson, GS Wilson, JT Weller, EB Bennett, DR Mulinare, J Kaufman, P Krough, C Rieder, MJ Troendle, G Yaffe, SJ Cote, CJ Szefler, SJ Blumer, JL Frader, JE Crain, LS Moseley, KL Nelson, RM Porter, IH Vizcarrondo, FE Bowes, WA Kazura, A Krug, EF Caniano, DA Dressser, R King, NMP TI Considerations related to the use of recombinant human growth hormone in children SO PEDIATRICS LA English DT Article ID CONSTITUTIONAL SHORT STATURE; CREUTZFELDT-JAKOB DISEASE; CHRONIC-RENAL-FAILURE; DEFICIENT CHILDREN; TURNER SYNDROME; THERAPY; HYPOPITUITARISM; ADOLESCENTS; METABOLISM; SECRETION AB Since 1985 molecular biology techniques have made possible the synthetic synthesis of pure human growth hormone in potentially unlimited amounts. With this increased availability, its use in patients other than children with growth hormone deficiency has been associated with clinical and ethical questions. This statement presents an analysis of the current status of the use of human growth hormone in children. C1 AMER MED ASSOC,US PHARMACOPEIA,CHICAGO,IL. AMER COLL OBSTETRICIANS & GYNECOLOGISTS,WASHINGTON,DC. HLTH PROTECT BRANCH,OTTAWA,ON,CANADA. US FDA,ROCKVILLE,MD 20857. NIH,BETHESDA,MD. AMER BOARD PEDIAT INC,CHAPEL HILL,NC. RI Moseley, Kathryn/A-8859-2009; Frader, Joel/A-8610-2010 NR 71 TC 39 Z9 40 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 JAN PY 1997 VL 99 IS 1 BP 122 EP 129 PG 8 WC Pediatrics SC Pediatrics GA WB350 UT WOS:A1997WB35000020 ER PT J AU Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Gromisch, DS Kohl, S Marcy, SM Murray, DL Overturf, GD Whitley, RJ Yogev, R AF Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Gromisch, DS Kohl, S Marcy, SM Murray, DL Overturf, GD Whitley, RJ Yogev, R TI Recommended childhood immunization schedule - United States, January-December 1997 SO PEDIATRICS LA English DT Article C1 US FDA,ROCKVILLE,MD 20857. AMER THORAC SOC,NEW YORK,NY. NIAID,BETHESDA,MD. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30333. NR 1 TC 12 Z9 13 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 JAN PY 1997 VL 99 IS 1 BP 136 EP 138 PG 3 WC Pediatrics SC Pediatrics GA WB350 UT WOS:A1997WB35000023 ER PT J AU Field, RB Chirtel, SJ Redman, RS AF Field, RB Chirtel, SJ Redman, RS TI Effect of substance P and receptor antagonists on secretion of lingual lipase and amylase from rat von Ebner's gland SO PEPTIDES LA English DT Article DE substance P; substance P receptors; von Ebner's glands; lingual lipase; amylase; protein secretion; substance P analogs; substance P receptor antagonists; beta-adrenergic receptor antagonists; cholinergic receptor antagonist; CP-96,345; exocytosis; basal secretion; stimulated secretion ID PANCREATIC ACINAR-CELLS; PAROTID-GLAND; SALIVARY-GLANDS; FINE-STRUCTURE; SEROUS GLANDS; GUINEA-PIG; PROTEIN; STIMULATION; RELEASE; CALCIUM AB Substance P (SP, 1 mu M) when incubated with minced von Ebner's glands for 15, 30, and 60 min, stimulated secretion of lingual lipase (12.14%+/-0.90) and amylase (8.30%+/-0.42). Only 10 mu M of the SP receptor antagonist CP-96,345 significantly inhibited SP-evoked secretion. D-Pro(2).D-Phe(7)-D-Trp(9)-SP (Ia), D-Pro(2)-D-Trp(7,9)-SP (Ib), D-Arg(1)-D-Trp(7,9)-D-Leu(11)-SP (Ic), or 1 mu M CP-96,345 were not effective, suggesting that the SP receptor of von Ebner's gland might be an isoform. Propranolol and timolol, beta(1)/beta(2)-adrenergic receptor antagonists were not effective and the cholinergic receptor antagonist, atropine, was effective in only slightly reducing amylase secretion but not lingual lipase. Differential secretion of the two enzymes was observed for basal and stimulated secretion. Thus, exocytosis may not be the only pathway involved in SP-evoked protein secretion. Published by Elsevier Science Inc. C1 GEORGETOWN UNIV, MED CTR, DEPT PEDIAT, WASHINGTON, DC 20007 USA. US FDA, CTR FOOD SAFETY & APPL NUTR, DIV MATH, WASHINGTON, DC 20204 USA. RP Field, RB (reprint author), DEPT VET AFFAIRS MED CTR, ORAL PATHOL RES LAB 151I, 50 IRVING ST, NW, WASHINGTON, DC 20422 USA. FU NIDCR NIH HHS [DE 08699] NR 56 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 EI 1873-5169 J9 PEPTIDES JI Peptides PY 1997 VL 18 IS 2 BP 277 EP 285 DI 10.1016/S0196-9781(96)00286-0 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA WX954 UT WOS:A1997WX95400015 PM 9149301 ER PT S AU Lynn, F Reed, GF Meade, BD AF Lynn, F Reed, GF Meade, BD BE Brown, F Greco, D Mastrantonio, P Salmaso, S Wassilak, S TI A comparison of enzyme immunoassays used to measure serum antibodies to components of Bordetella pertussis SO PERTUSSIS VACCINE TRIALS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT International Symposium on Pertussis Vaccine Trials CY OCT 30, 1995-NOV 01, 1996 CL ROME, ITALY SP Ist Super Sanita, WHO, Childrens Vaccine Initiat, NiAID, Int Federat Pharm Manufacturers Assoc, European Commiss COST STD Initiat, European Vaccine Res, Int Assoc Biol Standardizat AB To evaluate the comparability of immunoassays, the Center for Biologics Evaluation and Research organized an international collaborative study in which 33 laboratories participated. For a coded panel of 21 samples, each laboratory measured IgG antibodies to specific proteins of Bordetella pertussis using assay systems currently in place. Analyses were performed to evaluate the assay precision and the quantitative agreement among laboratories. Data from a subset of 12 laboratories are used to illustrate points relevant to the use of immunoassays in seven vaccine efficacy studies. Differences among the laboratories in assay precision for samples with known twofold differences indicate that serological case definitions must take into consideration the characteristics of the assays and the concentration of antibody in the samples. Assays performed in different laboratories to assess vaccine immunogenicity may generate similar results but critical comparisons will probably require samples to be tested in the same laboratory at the same time. C1 CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD HFM490,ROCKVILLE,MD 20852. NR 6 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6481-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1997 VL 89 BP 197 EP 204 PG 8 WC Biology; Biotechnology & Applied Microbiology SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology GA BJ43T UT WOS:A1997BJ43T00022 PM 9272351 ER PT S AU Meade, B AF Meade, B BE Brown, F Greco, D Mastrantonio, P Salmaso, S Wassilak, S TI Rapporteur's summary SO PERTUSSIS VACCINE TRIALS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT International Symposium on Pertussis Vaccine Trials CY OCT 30, 1995-NOV 01, 1996 CL ROME, ITALY SP Ist Super Sanita, WHO, Childrens Vaccine Initiat, NiAID, Int Federat Pharm Manufacturers Assoc, European Commiss COST STD Initiat, European Vaccine Res, Int Assoc Biol Standardizat RP Meade, B (reprint author), CBER,DIV BACTERIAL PROD HFM490,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6481-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1997 VL 89 BP 333 EP 337 PG 5 WC Biology; Biotechnology & Applied Microbiology SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology GA BJ43T UT WOS:A1997BJ43T00040 ER PT S AU Burns, DL AF Burns, DL BE Brown, F Greco, D Mastrantonio, P Salmaso, S Wassilak, S TI Regulatory and standardization issues - Reporters summary SO PERTUSSIS VACCINE TRIALS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT International Symposium on Pertussis Vaccine Trials CY OCT 30, 1995-NOV 01, 1996 CL ROME, ITALY SP Ist Super Sanita, WHO, Childrens Vaccine Initiat, NiAID, Int Federat Pharm Manufacturers Assoc, European Commiss COST STD Initiat, European Vaccine Res, Int Assoc Biol Standardizat RP Burns, DL (reprint author), US FDA,CTR BIOL EVALUAT & RES,BLDG 29,ROOM 418,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6481-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1997 VL 89 BP 351 EP 352 PG 2 WC Biology; Biotechnology & Applied Microbiology SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology GA BJ43T UT WOS:A1997BJ43T00044 ER PT S AU Burns, DL AF Burns, DL BE Brown, F Greco, D Mastrantonio, P Salmaso, S Wassilak, S TI Public health implications: United kingdom - Reporters summary SO PERTUSSIS VACCINE TRIALS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT International Symposium on Pertussis Vaccine Trials CY OCT 30, 1995-NOV 01, 1996 CL ROME, ITALY SP Ist Super Sanita, WHO, Childrens Vaccine Initiat, NiAID, Int Federat Pharm Manufacturers Assoc, European Commiss COST STD Initiat, European Vaccine Res, Int Assoc Biol Standardizat RP Burns, DL (reprint author), US FDA,CTR BIOL EVALUAT & RES,BLDG 29,ROOM 418,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6481-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1997 VL 89 BP 369 EP 369 PG 1 WC Biology; Biotechnology & Applied Microbiology SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology GA BJ43T UT WOS:A1997BJ43T00048 ER PT S AU Burns, D AF Burns, D BE Brown, F Greco, D Mastrantonio, P Salmaso, S Wassilak, S TI Issues regarding future research on pertussis vaccines SO PERTUSSIS VACCINE TRIALS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT International Symposium on Pertussis Vaccine Trials CY OCT 30, 1995-NOV 01, 1996 CL ROME, ITALY SP Ist Super Sanita, WHO, Childrens Vaccine Initiat, NiAID, Int Federat Pharm Manufacturers Assoc, European Commiss COST STD Initiat, European Vaccine Res, Int Assoc Biol Standardizat RP Burns, D (reprint author), US FDA,CTR BIOL EVALUAT & RES,BLDG 29,ROOM 418,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6481-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1997 VL 89 BP 377 EP 377 PG 1 WC Biology; Biotechnology & Applied Microbiology SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology GA BJ43T UT WOS:A1997BJ43T00050 PM 9272375 ER PT S AU Burns, DL AF Burns, DL BE Brown, F Greco, D Mastrantonio, P Salmaso, S Wassilak, S TI Some thoughts for future pertussis research in Europe - Reporters summary SO PERTUSSIS VACCINE TRIALS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT International Symposium on Pertussis Vaccine Trials CY OCT 30, 1995-NOV 01, 1996 CL ROME, ITALY SP Ist Super Sanita, WHO, Childrens Vaccine Initiat, NiAID, Int Federat Pharm Manufacturers Assoc, European Commiss COST STD Initiat, European Vaccine Res, Int Assoc Biol Standardizat RP Burns, DL (reprint author), US FDA,CTR BIOL EVALUAT & RES,BLDG 29,ROOM 418,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6481-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1997 VL 89 BP 393 EP 394 PG 2 WC Biology; Biotechnology & Applied Microbiology SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology GA BJ43T UT WOS:A1997BJ43T00053 ER PT B AU Skopec, M AF Skopec, M BE Boom, H Robinson, C Rutten, W Neuman, M Wijkstra, H TI Hearing aid electromagnetic interference from digital cellular telephones SO PROCEEDINGS OF THE 18TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOL 18, PTS 1-5 SE PROCEEDINGS OF THE ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 18th Annual International Conference of IEEE Engineering-in-Medicine-amd-Biology-Society CY OCT 31-NOV 03, 1996 CL AMSTERDAM, NETHERLANDS SP IEEE Engn Med & Biol Soc DE hearing aid; electromagnetic interference; cellular telephones AB Several in-the-ear (ITE) and behind-the-car (BTE) hearing aids were tested for audible interference at various distances from five types of digital cellular telephones. The interference, which takes the form of a buzzing and a static sound, was quantified using a calibrated system including a frequency analyzer and a pressure field microphone. The output of the each hearing aid was coupled to the microphone via Tygon tubing and a standard 2 cc coupler. The highest interference induced sound pressure level (SPL), 122.5 dB, was measured from a BTE hearing aid placed within 2 cm of a transmitting GSM phone. In this case, interference was detected up to a separation distance of almost 3 meters. While all phones tested produced a similar interference level within 2 cm of this hearing aid, interference SPL from the CDMA based system decreased more rapidly with distance than the TDMA based phones tested. Subjective testing was also conducted using a listening stethoscope in order to further characterize the interference. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Skopec, M (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-3812-X J9 P IEEE EMBS PY 1997 VL 18 BP 409 EP 410 PG 2 WC Engineering, Biomedical SC Engineering GA BK41A UT WOS:000072079000200 ER PT B AU Lester, DS Kidder, LH Levin, IW Kalasinsky, VF Lewis, EN AF Lester, DS Kidder, LH Levin, IW Kalasinsky, VF Lewis, EN BE Boom, H Robinson, C Rutten, W Neuman, M Wijkstra, H TI Applications of Fourier transform infrared imaging microscopy in histopathology SO PROCEEDINGS OF THE 18TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOL 18, PTS 1-5 SE PROCEEDINGS OF THE ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 18th Annual International Conference of IEEE Engineering-in-Medicine-amd-Biology-Society CY OCT 31-NOV 03, 1996 CL AMSTERDAM, NETHERLANDS SP IEEE Engn Med & Biol Soc DE microspectroscopy; imaging; pathology; infrared; biopsy AB Infrared microspectroscopic imaging has the capabilities of generating spatial information as well as the standard spectroscopy. By taking advantage of the vibrational spectral signatures of biological components, such as lipids and proteins, we have the capability of obtaining images of the intrinsic distribution of these molecules. We have applied this approach to analyze tissue sections of biomedical relevance in order to determine the potential of this application as an alternate approach histopathology. The advantage of this technique is that tissue need not be fixed or stained, contrast obtained from the intrinsic distribution of the biomolecular components. This technique provides considerable application for many histopathological applications and could result in the significant increase in the speed and resolution of pathological analyses, such as biopsies. C1 US FDA, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. RP Lester, DS (reprint author), US FDA, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-3812-X J9 P IEEE EMBS PY 1997 VL 18 BP 2101 EP 2102 PG 2 WC Engineering, Biomedical SC Engineering GA BK41A UT WOS:000072079001016 ER PT B AU Bassen, HL AF Bassen, HL BE Boom, H Robinson, C Rutten, W Neuman, M Wijkstra, H TI Device specific standard test methods for electromagnetic interference of medical devices SO PROCEEDINGS OF THE 18TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOL 18, PTS 1-5 SE PROCEEDINGS OF THE ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 18th Annual International Conference of IEEE Engineering-in-Medicine-amd-Biology-Society CY OCT 31-NOV 03, 1996 CL AMSTERDAM, NETHERLANDS SP IEEE Engn Med & Biol Soc DE electromagnetic compatibility; radio frequency interference; medical devices AB Several device-specific, radiated electromagnetic interference test methods have been developed for particular combinations of medical devices and nearby sources of radio frequency interference (RFI). These tests are useful for supplementing the prevailing, generic standardized medical device RFI immunity test methods. Generic tests such as those specified IEC 601-1-2 and related standards underestimate the degree of RFI problems that can be encountered in the close proximity of handheld transmitters and cellular telephones. This occurs because the generic standards admittedly do not relate their test conditions to extreme exposure situations. Device-specific test methods have been developed by several organizations to evaluate the susceptibility to nearby transmitters of implantable cardiac pacemakers and defibrillators, as well as hearing aids. The U.S. Food and Drug Administration (FDA) developed and rested a "universal", simulated near-field RF source for this kind of test. It consists of a standard dipole antenna connected to an amplitude-modulated RF generator that can simulate a wide range of worst-case RF carrier frequencies and modulations. Another new device-specific test is the draft ASC 63 standardized test method for "ad-hoc" RFI testing. It is proposed to be used to evaluate the RFI susceptibility of a wide variety of specific medical devices. Individual KF sources will be used, such as handheld transmitters, placed one meter from the medical device under test in the actual clinical setting. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Bassen, HL (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12721 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-3812-X J9 P IEEE EMBS PY 1997 VL 18 BP 2198 EP 2200 PG 3 WC Engineering, Biomedical SC Engineering GA BK41A UT WOS:000072079001059 ER PT S AU Bassen, HI AF Bassen, HI GP IEEE IEEE TI Electric field probes for cellular phone dosimetry SO PROCEEDINGS OF THE 19TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOL 19, PTS 1-6: MAGNIFICENT MILESTONES AND EMERGING OPPORTUNITIES IN MEDICAL ENGINEERING SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society CY OCT 30-NOV 02, 1997 CL CHICAGO, IL SP IEEE Engn Med & Biol Soc, Natl Inst Hlth DE electromagnetic fields; cellular phones; electric field probe; dosimetry; radiation; microwave AB Miniature implantable electric field probes (E-field Probes) enable the measurements of microwave electric fields induced in biological subjects by relatively low level exposures. Using these instruments, the rate of energy deposition (Specific Absorption Rate or SAR) can be determined throughout models or actual bodies of laboratory animals and humans exposed to emissions from cellular phones and other radiators. E-field probes consist of an array of three electrically short dipole antennas. Each antenna has the following components: a diode detector, a dielectric coating and mechanical support, a highly resistive balanced transmission line, a differential amplifier, and a detected signal processor. Most modern microwave safety standards and several medical applications of microwave energy require SAR data to be measured. E-field probes are unique in that they are sensitive enough to measure the local SAR using actual low-power radiation sources such as a handheld cellular phone. A spatial map of the local SAR can be obtained by mechanically scanning a model of a biological subject filled with a lossy dielectric liquid that simulates body tissues. Sensitivities of one microwatt/ gram (one mW/kg) are practical in such systems. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Bassen, HI (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12721 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-4262-3 J9 P ANN INT IEEE EMBS PY 1997 VL 19 BP 2492 EP 2495 PN 1-6 PG 4 WC Engineering, Biomedical SC Engineering GA BM91F UT WOS:000080103400717 ER PT B AU Faustino, PJ Ellison, CD Flora, KP AF Faustino, PJ Ellison, CD Flora, KP GP 1996 INT SYMP LAB AUTOMAT & ROBOT TI Solid phase extraction of antidepressants from mouse, rat and human plasma utilizing robotic workstations SO PROCEEDINGS OF THE INTERNATIONAL SYMPOSIUM ON LABORATORY AUTOMATION AND ROBOTICS 1996 LA English DT Proceedings Paper CT International Symposium on Laboratory Automation and Robotics (ISLAR 96) CY OCT 20-23, 1996 CL BOSTON, MA AB We have developed and evaluated automated solid phase extraction methods for two antidepressant compounds and their pharmacologically active metabolites from plasma. A first generation tricyclic antidepressant, amitriptyline, and a second generation selective serotonin reuptake inhibitor, fluoxetine, were extracted from mouse, rat and human plasma using BenchMate(TM) robotic workstations. Here we overview a simple protocol to automate the development of bioanalytical extraction methods. Automated solid phase extraction (SPE) methods that are reproducible and accurate have been proven essential for the preparation of large numbers of pre-clinical samples. Robotic workstations can play an important role in the rapid development of methods for the preparation of bioanalytical samples. RP Faustino, PJ (reprint author), US FDA,CTR DRUG EVALUAT & RES,OFF TESTING & RES,LAUREL,MD 20708, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ZYMARK CORP PI HOPKINTON PA ZYMARK CTR, HOPKINTON, MA 01748 BN 0-931565-14-6 PY 1997 BP 431 EP 444 PG 14 WC Automation & Control Systems; Biotechnology & Applied Microbiology; Medical Laboratory Technology; Pharmacology & Pharmacy SC Automation & Control Systems; Biotechnology & Applied Microbiology; Medical Laboratory Technology; Pharmacology & Pharmacy GA BJ23J UT WOS:A1997BJ23J00049 ER PT B AU Faustino, PJ Layloff, TP AF Faustino, PJ Layloff, TP GP 1996 INT SYMP LAB AUTOMAT & ROBOT TI The research laboratory and the road to validation SO PROCEEDINGS OF THE INTERNATIONAL SYMPOSIUM ON LABORATORY AUTOMATION AND ROBOTICS 1996 LA English DT Proceedings Paper CT International Symposium on Laboratory Automation and Robotics (ISLAR 96) CY OCT 20-23, 1996 CL BOSTON, MA RP Faustino, PJ (reprint author), US FDA,CTR DRUG EVALUAT & RES,OFF TESTING & RES,DIV PROD QUAL RES,LAUREL,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ZYMARK CORP PI HOPKINTON PA ZYMARK CTR, HOPKINTON, MA 01748 BN 0-931565-14-6 PY 1997 BP 506 EP 511 PG 6 WC Automation & Control Systems; Biotechnology & Applied Microbiology; Medical Laboratory Technology; Pharmacology & Pharmacy SC Automation & Control Systems; Biotechnology & Applied Microbiology; Medical Laboratory Technology; Pharmacology & Pharmacy GA BJ23J UT WOS:A1997BJ23J00062 ER PT J AU Ellenberg, SS Chen, RT AF Ellenberg, SS Chen, RT TI The complicated task of monitoring vaccine safety SO PUBLIC HEALTH REPORTS LA English DT Article ID SUDDEN-INFANT-DEATH; PRONE SLEEPING POSITION; PERTUSSIS IMMUNIZATION; UNITED-STATES; RISK-FACTORS; DISEASE; SYSTEM AB VACCINATION IS AN ESSENTIAL component of modern public health programs and is among our most cost-effective medical interventions. Yet despite vaccines' clear effectiveness in reducing risks of diseases that previously attacked large proportions of the population, caused many deaths, and left many people with permanent disabilities, current vaccination policies are not without controversy. Vaccines, like all other pharmaceutical products, are not entirely risk-free; while most known side effects are minor and self-limited, some vaccines have been associated with very rare but serious adverse effects. Because such rare effects are often not evident until vaccines come into widespread use, the Federal government maintains ongoing surveillance programs to monitor vaccine safety. The interpretation of data from such programs is complex and is associated with substantial uncertainty. A continual effort to monitor these data effectively and to develop more precise ways of assessing risks of vaccines is necessary to ensure public confidence public confidence in immunization programs. C1 US FDA,DIV BIOSTAT & EPIDEMIOL,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20857. CDC,VACCINE SAFETY & DEV ACT EPIDEMIOL & SURVEILLANCE,NATL IMMUNIZATION PROGRAM,ATLANTA,GA 30333. NR 48 TC 80 Z9 82 U1 0 U2 4 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JAN-FEB PY 1997 VL 112 IS 1 BP 10 EP 20 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WD994 UT WOS:A1997WD99400018 PM 9018282 ER PT J AU Swann, JP AF Swann, JP TI Drug abuse control under FDA, 1938-1968 SO PUBLIC HEALTH REPORTS LA English DT Article RP Swann, JP (reprint author), US FDA,HIST OFF,HFC 24,ROOM 13-51,PARKLAWN BLDG,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JAN-FEB PY 1997 VL 112 IS 1 BP 83 EP 86 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WD994 UT WOS:A1997WD99400032 PM 9018295 ER PT J AU Rosenstein, M Thompson, DL AF Rosenstein, M Thompson, DL TI Comparison of derived intervention levels for accidental contamination of food using effective dose equivalent (H-E) and effective dose (E) SO RADIATION PROTECTION DOSIMETRY LA English DT Article AB Recommendations on accidental radioactive contamination of human food and animal feeds were issued in 1982 by the United Slates Food and Drug Administration (FDA) as guidance to State and local government officials. In a proposed update of the recommendations, FDA employed the quantity effective dose equivalent (H-E), which is the quantity currently used by all Federal agencies in the United States. In 1990, a modified version of H-E called effective dose (E) was introduced by ICRP. This paper compares the Derived Intervention Levels for radionuclides relevant to accidental contamination of food, employing H-E and E for the same intervention level of dose. For seven bone-seeking radionuclides, the Derived Intervention Levels for E, using the FDA approach, increase by factors of 3.4 to 8.8 compared to those using H-E. For three radioiodines, the Derived Intervention Levels for E increase by a factor of two compared to those using H-E. For the remaining radionuclides, the ratios of Derived Intervention Levels for E to H-E are in the range of 0.8 to 1.2. RP Rosenstein, M (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,HFZ-240,1350 PICCARD DR,ROCKVILLE,MD 20850, USA. NR 19 TC 1 Z9 1 U1 0 U2 0 PU NUCLEAR TECHNOLOGY PUBL PI ASHFORD PA PO BOX 7, ASHFORD, KENT, ENGLAND TN23 1YW SN 0144-8420 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PY 1997 VL 71 IS 1 BP 47 EP 51 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA WX787 UT WOS:A1997WX78700006 ER PT J AU Couch, LH Churchwell, MI Doerge, DR Tolleson, WH Howard, PC AF Couch, LH Churchwell, MI Doerge, DR Tolleson, WH Howard, PC TI Identification of ceramides in human cells using liquid chromatography with detection by atmospheric pressure chemical ionization mass spectrometry SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID SPHINGOLIPID BIOSYNTHESIS; FUSARIUM-MONILIFORME; 2ND MESSENGER; RAT; DIFFERENTIATION; SPHINGOSINE; DERIVATIVES; FUMONISINS; INHIBITION; MEDIATOR AB Ceramides are intermediates in the biosynthesis of membrane sphingolipids, These biomolecules are also important as second messengers in signal transduction pathways controlling cell growth. We have developed two reversed-phase high pressure liquid chromatography (RPHPLC) techniques for identification and quantification of ceramides from mammalian cells, One method was based on atmospheric pressure chemical ionization-mass spectrometry (APCI-MS) detection of ceramides and had the advantage of requiring minimal sample preparation, yielding significant structural information, and affording high sensitivity, The second method relied on perbenzoylation of the ceramides and detection at 230 mn, The predominant ceramides detected in the human leukemic HL-60 cell were N-(palmitoyl)-sphingosine, N-(nervonyl)-sphingosine, and N-(lignoceroyl)-sphingosine. When selected ion monitoring was used with RPHPLC/APCI-MS, approximately 2.2 pmol N-(palmitoyl)-sphingosine and 1.7 pmol N-(nervonyl)-sphingosine were observed in an extract from 40 000 HL-60 cells, Perbenzoylation with benzoyl chloride permitted RPHPLC separation and 230 nm UV absorbance detection of the trisbenzoyl derivatives of sphingosine, N-(palmitoyl)-sphingosine, N-(nervonyl)-sphingosine, and N-(lignoceroyl)-sphingosine in the HL-60 cells, These results demonstrate the utility of utilizing two different methods coupled with APCI-MS for the quantification and identification of ceramides in biological samples. (C) 1997 by John Wiley & Sons, Ltd. C1 US FDA,NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079. US FDA,NATL CTR TOXICOL RES,DIV CHEM,JEFFERSON,AR 72079. NR 29 TC 32 Z9 33 U1 1 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 1997 VL 11 IS 5 BP 504 EP 512 DI 10.1002/(SICI)1097-0231(199703)11:5<504::AID-RCM886>3.3.CO;2-X PG 9 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA WT708 UT WOS:A1997WT70800016 PM 9131820 ER PT J AU Holder, CL Preece, SW Conway, SC Pu, YM Doerge, DR AF Holder, CL Preece, SW Conway, SC Pu, YM Doerge, DR TI Quantification of heterocyclic amine carcinogens in cooked meats using isotope dilution liquid chromatography atmospheric pressure chemical ionization tandem mass spectrometry SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID CANCER; BEEF AB Heterocyclic aromatic amines (HAAs) are formed in cooked meats through pyrolysis reactions of different amino acids in the presence or absence of creatine/creatinine and sugars, HAAs are mutagens, colon/mammary gland carcinogens in rodents, and are suspected in the etiology of human cancers. In this study, cooked meats containing incurred HAAs as well as control (microwave) meat, were spiked with four labeled HAA internal standards (MeIQx, IQ, AAC and PhIP) and extracted using a liquid/liquid cleanup procedure, Isotope dilution measurements were made using on-line liquid chromatography atmosphere pressure chemical ionization tandem mass spectrometry with multiple reaction monitoring to provide the sensitivity and specificity needed for trace analysis in these complex matrices, The procedure was validated using control meat spiked with the four native HAAs at 0-50 ppb, The levels of HAAs found in cooked meats ranged from non-detectable (limit of detection 0.1-1.0 ppb) in microwave-cooked hamburger to 226 ppb PhIP and 104 ppb AAC in well-done grilled chicken, This methodology has the potential to provide accurate data on the consumption of HAAs in the diet for use in human cancer risk assessment. (C) 1997 by John Whey & Sons, Ltd. C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. MICROMASS INC,ALTRINCHAM WA14 5RZ,ENGLAND. BIONET CORP,JEFFERSON,AR 72079. NR 11 TC 48 Z9 49 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 1997 VL 11 IS 15 BP 1667 EP 1672 DI 10.1002/(SICI)1097-0231(19971015)11:15<1667::AID-RCM58>3.0.CO;2-N PG 6 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA YB074 UT WOS:A1997YB07400007 PM 9364795 ER PT J AU Duarte, CG Zhang, J Ellis, S AF Duarte, CG Zhang, J Ellis, S TI The SHR as a small animal model for radiocontrast renal failure. Relation of nephrotoxicity to animal's age, gender, strain, and dose of radiocontrast SO RENAL FAILURE LA English DT Article ID SPONTANEOUSLY HYPERTENSIVE RAT; CONTRAST-MEDIA; INJURY; PATHOPHYSIOLOGY; PROSTAGLANDINS; NEPHROPATHY; PROTEINURIA; ENDOTHELIN; MEDULLA; SYSTEM AB The male spontaneously hypertensive rat (SHR), as it ages, suffers many of the renal and cardiovascular complications that are recognized in humans as risk factors for radiocontrast (RC) agent induced renal failure (RF). Knowledge of this led us to test this strain of rats as a small animal model for RC-induced renal failure (RC-RF). Functional studies demonstrated a significant fall in GFR in the recovery period after Re administration. In addition, histopathologic evaluation of the kidneys was done in this study. Our results are based on assigning separate scale values to the histopathological evaluation of the (a) glomeruli, (b) tubules, (c) interstitium, and(d) arteries and arterioles of the kidneys. Saline (S) was administered to one group and the RC agent Hypaque-76 (diatrizoate meglumine sodium) to paired groups of 5-, 8-, 10-, 12-, and 14-month-old male SHR. The results indicated that younger animals (5 and 8 months old) were resistant to the nephrotoxic effects of the RC, but developed susceptibility at 10 months of age, when spontaneous renal pathology became manifest. Both spontaneous renal pathology and RC-induced renal damage (RC-RD) increased as the animals aged. In addition, when the administered dose of RC was repeated after a short interval of only 6 h, the degree of RC-RD increased greatly. In parallel control studies of the influence of gender and strain on the response to RC in 12-month-old rats, neither hypertensive female SHR nor male normotensive Wistar-Kyoto (WKY) rats demonstrated significant spontaneous renal pathology or the marked susceptibility to RC nephrotoxicity shown by their male SHR counterparts. This small animal model for RC-RD, similar to those characterized in humans for RC-RF, develop spontaneously without requiring any special treatment or surgical intervention. RP Duarte, CG (reprint author), US FDA,HFD110,DIV CARDIORENAL DRUG PROD,CTR DRUG EVALUAT & RES,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 50 TC 19 Z9 19 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0886-022X J9 RENAL FAILURE JI Ren. Fail. PY 1997 VL 19 IS 6 BP 723 EP 743 DI 10.3109/08860229709037213 PG 21 WC Urology & Nephrology SC Urology & Nephrology GA YL104 UT WOS:A1997YL10400002 PM 9415930 ER PT J AU DeLap, RJ AF DeLap, RJ TI Obstacles at the FDA? SO SCIENTIFIC AMERICAN LA English DT Letter RP DeLap, RJ (reprint author), US FDA,DIV ONCOL DRUG PROD,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 0036-8733 J9 SCI AM JI Sci.Am. PD JAN PY 1997 VL 276 IS 1 BP 8 EP 8 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VY022 UT WOS:A1997VY02200005 PM 8972611 ER PT J AU Tabor, E AF Tabor, E TI Liver tumors and host defense SO SEMINARS IN LIVER DISEASE LA English DT Review DE cytotoxic T lymphocytes; LAK cells; p53; thrombomodulin; transforming growth factor beta ID TRANSFORMING GROWTH-FACTOR; HEPATITIS-B-VIRUS; HUMAN HEPATOCELLULAR-CARCINOMA; HUMAN HEPATOMA-CELLS; WILD-TYPE; P53 GENE; FACTOR-BETA; SUPPRESSOR GENE; MESSENGER-RNA; BREAST-CANCER AB Complex molecular and cellular mechanisms exist to protect cells against tumor formation and to protect the entire organ ism against further development and spread of established tumors. The p53 tumor suppressor gene controls the cell cycle through at least two mechanisms, namely; mitotic arrest and apoptosis. Human hepatocellular carcinomas (HCCs) are often found to have mutant p53, or sometimes may have dysfunctional p53 as a result of its being bound by viral or cellular proteins. Another mechanism of host response is the production of transforming growth factor beta 1, which acts on receptors in normal hepatocytes to cause inhibition of DNA synthesist abnormalities of transforming growth factor beta 1 have been documented in HCCs, but their biologic significance is unclear. Other host defense mechanisms incline cellular responses to the tumor and the proliferation of substances with anticoagulant properties. C1 US FDA, Ctr Biol Evaluat & Res, Div Transfus Transmitted Dis, Bethesda, MD 20892 USA. RP Tabor, E (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Transfus Transmitted Dis, HFM-310,1401 Rockville Pike, Bethesda, MD 20892 USA. NR 51 TC 5 Z9 5 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PY 1997 VL 17 IS 4 BP 351 EP 355 DI 10.1055/s-2007-1007212 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 176BP UT WOS:000079130900010 PM 9408971 ER PT J AU Goldberger, MJ AF Goldberger, MJ TI Treatment of tuberculosis: Current status and future promise SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE tuberculosis; treatment; clinical trials ID IMMUNODEFICIENCY-VIRUS INFECTION; MULTIDRUG-RESISTANT TUBERCULOSIS; EARLY BACTERICIDAL ACTIVITY; SHORT-COURSE CHEMOTHERAPY; DIAGNOSED PULMONARY TUBERCULOSIS; SPUTUM VIABLE COUNTS; MYCOBACTERIUM-TUBERCULOSIS; CONTROLLED TRIAL; HIV-INFECTION; RIFAMPIN AB Treatment for drug-susceptible tuberculosis remains highly effective, but the need for prolonged therapy has led to problems in patient compliance that in turn promote an increase in drug-resistance, Improving compliance is being addressed by directly observed therapy and combination drug products and through the development of products that will simplify dosing, but the ultimate goal would be to shorten the overall duration of therapy, Therapy of MDR-TB is more difficult particularly in the HIV-positive patient, and new therapies are clearly needed, Methods exist to assess new drugs prior to their introduction into clinical trials, and this approach is clearly important given the economic considerations in developing new drugs for tuberculosis. RP Goldberger, MJ (reprint author), US FDA,HFD 590,DSPIDP,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 77 TC 1 Z9 1 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 SN 1069-3424 J9 SEM RESP CRIT CARE M JI Semin. Respir. Crit. Care Med. PY 1997 VL 18 IS 5 BP 439 EP 448 DI 10.1055/s-2007-1009359 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA YL159 UT WOS:A1997YL15900004 ER PT J AU Silverman, BG Gross, TP AF Silverman, BG Gross, TP TI Use and effectiveness of condoms during anal intercourse - A review SO SEXUALLY TRANSMITTED DISEASES LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; WOMAN SEXUAL TRANSMISSION; MALE-TO-FEMALE; HOMOSEXUAL MEN; BISEXUAL MEN; RISK-FACTORS; GAY MEN; HIV; BEHAVIOR; INFECTION AB Background and Objectives: Anal intercourse has been associated with a high risk of human immunodeficiency virus transmission, Survey data suggest that unprotected anal intercourse is practiced by a substantial proportion of the sexually active population, regardless of sexual orientation, Goal: To review the literature related to the use and effectiveness of condoms during anal intercourse, with emphasis on prevention of human immunodeficiency virus transmission, Study Design: Literature review, Results: Epidemiologic studies have shown that consistent, correct condom use reduces the overall risk of sexual transmission of human immunodeficiency virus, Evidence for the effectiveness of condoms used during anal intercourse is less definitive, Survey and clinical trials data indicate that condom breakage and slippage rates vary during anal intercourse and may be considerably higher than during vaginal intercourse, Although condoms designed for anal intercourse have been studied and marketed in Europe, data on their actual performance are scarce, In addition, no information exists on the effectiveness of polyurethane or other nonlatex condoms for use during anal intercourse. Conclusions: Development of newer and more effective condoms for use during anal intercourse requires consideration of the ethical issues involved in testing and marketing devices used during an activity that carries with it the potential for a substantial risk to health. RP US FDA, CTR DEVICES & RADIOL HLTH, OFF SURVEILLANCE & BIOMETR, 1350 PICCARD DR, ROOM 3080A HFZ-541, ROCKVILLE, MD 20850 USA. OI Silverman, Barbara/0000-0002-0337-4919 NR 36 TC 27 Z9 27 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0148-5717 EI 1537-4521 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD JAN PY 1997 VL 24 IS 1 BP 11 EP 17 DI 10.1097/00007435-199701000-00004 PG 7 WC Infectious Diseases SC Infectious Diseases GA WB805 UT WOS:A1997WB80500004 PM 9018778 ER PT B AU Katzper, M AF Katzper, M BE Anderson, JG Katzper, M TI Pain alleviation modeling by response levels SO SIMULATION IN THE MEDICAL SCIENCES LA English DT Proceedings Paper CT Simulation in the Medical Sciences Conference, at the 1997 Western MultiConference CY JAN 12-15, 1997 CL PHOENIX, AZ SP Soc Comp Simulat Int DE pain; NSAID; pharmacometric model AB Pain alleviation by nonsteroidal anti-inflammatory drugs (NSAIDs) is modeled by considering the count in each relief level as the entity to be tracked. Pharmacokinetic, placebo and physiologically oriented modules are combined to control a state transition module determining the reported pain level. Simulation results obtained were similar to representative data from NSAID trials. This approach provides another manner of characterizing the time course of expected degrees of pain alleviation. RP Katzper, M (reprint author), US FDA,CTR DRUG EVALUAT & RES,5600 FISHERS LANE,HFD 550,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC COMPUTER SIMULATION INT PI SAN DIEGO PA PO BOX 17900, SAN DIEGO, CA 92177 BN 1-56555-105-2 PY 1997 BP 101 EP 106 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA BH94Q UT WOS:A1997BH94Q00018 ER PT B AU DoLuu, HM Hutter, JC AF DoLuu, HM Hutter, JC BE Anderson, JG Katzper, M TI A PBPK model to investigate the fate of 2,4-toluenediamine SO SIMULATION IN THE MEDICAL SCIENCES LA English DT Proceedings Paper CT Simulation in the Medical Sciences Conference, at the 1997 Western MultiConference CY JAN 12-15, 1997 CL PHOENIX, AZ SP Soc Comp Simulat Int DE pharmacokinetic; polymer degradation; polyurethanes AB Physiologically-based pharmacokinetic modeling, also known as PBPK, has been widely used in the study of drugs. Little progress has been made in applying this approach to assess the hazard(s) of medical devices. 2,4-Toluenediamine (2,4-TDA), a known mutagen and rodent carcinogen, was found as a degration product of the polyesterurethane (PU) foam cover of Memen(TM) breast implants in vivo. The carcinogenicity of 2,4-TDA was studied in mice and rats and found both dose-dependent and to vary with the route and species tested. PBPK modeling is used to describe the fate of 2,4-TDA in the rat. The PBPK model was calibrated with data derived from studies of 2,4-TDA related to the biodegradation of the PU foam. This computer based PBPK model was used to predict chemical exposure from biomaterial degradation, and help assess the risk from the implant degradation products leached into the body. The model of ordinary differential equations was solved using Mathcad PLUS 6.0 (MathSoft, Cambridge MA). RP DoLuu, HM (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,12200 WILKINS AVE,ROCKVILLE,MD 20852, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC COMPUTER SIMULATION INT PI SAN DIEGO PA PO BOX 17900, SAN DIEGO, CA 92177 BN 1-56555-105-2 PY 1997 BP 113 EP 121 PG 9 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA BH94Q UT WOS:A1997BH94Q00020 ER PT S AU Calvey, EM Block, E AF Calvey, EM Block, E BE Risch, SJ Ho, CT TI Supercritical fluid extraction of Allium species SO SPICES: FLAVOR CHEMISTRY AND ANTIOXIDANT PROPERTIES SE ACS Symposium Series LA English DT Review CT Symposium on Spices - Flavor Chemistry and Antioxidant Properties, at the 211th National Meeting of the American-Chemical-Society CY MAR 24-28, 1996 CL NEW ORLEANS, LA SP Amer Chem Soc, Div Agr & Food Chem ID CHROMATOGRAPHY MASS-SPECTROMETRY; CARBON-DIOXIDE EXTRACTION; GAS-CHROMATOGRAPHY; ESSENTIAL OIL; OFF-LINE; CHEMISTRY; PRODUCTS; ONION; FOOD; SFE AB Supercritical fluid technologies are viable alternatives for the extraction and analysis of natural products because of the heightened awareness of the cost and safety hazards associated with the use and disposal of conventional organic solvents. Supercritical CO2 (SC-CO2) is of particular interest to the food industry. Because of its low critical temperature, SC-CO2 extraction can provide an accurate representation of the taste, color and odor of naturally occurring materials found in spices, flavors and foods. The application of supercritical fluid extraction technology to the analysis and/or production of spice and flavor extracts is discussed. The use of the technology in the extraction of organosulfur compounds found in Allium species is emphasized. C1 SUNY ALBANY, DEPT CHEM, ALBANY, NY 12222 USA. RP Calvey, EM (reprint author), US FDA, CTR FOOD SAFETY & APPL NUTR, 200 C ST SW, WASHINGTON, DC 20204 USA. RI Block, Eric/D-3989-2014 NR 59 TC 7 Z9 7 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 0-8412-3495-7 J9 ACS SYM SER JI ACS Symp. Ser. PY 1997 VL 660 BP 113 EP 124 PG 12 WC Biochemistry & Molecular Biology; Plant Sciences; Chemistry, Organic; Food Science & Technology SC Biochemistry & Molecular Biology; Plant Sciences; Chemistry; Food Science & Technology GA BH61W UT WOS:A1997BH61W00010 ER PT S AU Coelho, JAP Mendes, RL Provost, MC Cabral, JMS Novais, JM Palavra, AMF AF Coelho, JAP Mendes, RL Provost, MC Cabral, JMS Novais, JM Palavra, AMF BE Abraham, MA Sunol, AK TI Supercritical carbon dioxide extraction of volatile compounds from rosemary SO SUPERCRITICAL FLUIDS: EXTRACTION AND POLLUTION PREVENTION SE ACS Symposium Series LA English DT Review CT Symposium on Supercritical Fluids - Extraction and Pollution Prevention, at the 211th National Meeting of the American-Chemical-Society CY MAR 24-28, 1996 CL NEW ORLEANS, LA SP Amer Chem Soc, Div Ind & Engn Chem Inc ID FLUID EXTRACTION AB Supercritical CO2 extraction of oleoresin from portuguese rosemary (Rosmarinus Officinalis L.) was carried out with a now apparatus at temperatures of 35 and 40 degrees C and pressures of 100, 125 and 200 bar. The highest fraction of volatile compounds (oil) in the oleoresin was obtained at 100 bar and 40 degrees C. An unsteady mathematical model was able to give good representation of the supercritical extraction curves and a mass transfer coefficient was determined using the successive quadratic programming method. Values of this coefficient ranged between 4.49 and 15.07 kg/m(3)s and the shift to a diffusion-controlled regime occurred when 44% of the total oil was extracted. C1 Univ Tecn Lisboa, DEPT ENGN QUIM, INST SUPER TECN, P-1096 LISBON, PORTUGAL. INST NACL ENGN & TECNOL IND, DEPT ENERGIAS RENOVAVEIS, P-1699 LISBON, PORTUGAL. US FDA, CTR DEVICES & RADIOL HLTH, ROCKVILLE, MD 20850 USA. RI Cabral, Joaquim /G-2052-2010; Coelho, Jose/G-2626-2011; Palavra, Antonio/H-9235-2012 OI Cabral, Joaquim /0000-0002-2405-5845; Coelho, Jose/0000-0001-8118-0864; Palavra, Antonio/0000-0003-4838-1589 NR 15 TC 11 Z9 12 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 0-8412-3517-1 J9 ACS SYM SER JI ACS Symp. Ser. PY 1997 VL 670 BP 101 EP 109 PG 9 WC Chemistry, Applied; Chemistry, Multidisciplinary; Engineering, Chemical SC Chemistry; Engineering GA BJ86W UT WOS:A1997BJ86W00008 ER PT J AU Yang, DTC Zhang, CJ Fu, PP Kabalka, GW AF Yang, DTC Zhang, CJ Fu, PP Kabalka, GW TI Oxidation of alpha-substituted carbonyl compounds to carboxylic acids in aqueous media using ultrasound SO SYNTHETIC COMMUNICATIONS LA English DT Article ID SODIUM-HYPOCHLORITE; ORGANIC-SYNTHESIS; ALCOHOLS; DIOLS AB Carbonyl compounds containing electron-withdrawing substituents are efficiently oxidized by aqueous sodium hypochlorite in the absence of added organic solvents using ultrasound agitation. C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72079. UNIV TENNESSEE,DEPT CHEM,KNOXVILLE,TN 37996. RP Yang, DTC (reprint author), UNIV ARKANSAS,DEPT CHEM,LITTLE ROCK,AR 72204, USA. NR 28 TC 4 Z9 4 U1 1 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0039-7911 J9 SYNTHETIC COMMUN JI Synth. Commun. PY 1997 VL 27 IS 9 BP 1601 EP 1605 DI 10.1080/00397919708006098 PG 5 WC Chemistry, Organic SC Chemistry GA WR789 UT WOS:A1997WR78900018 ER PT J AU Yang, DTC Zhang, CJ Haynie, BC Fu, PP Kabalka, GW AF Yang, DTC Zhang, CJ Haynie, BC Fu, PP Kabalka, GW TI Microwave-assisted oxidation of alpha-substituted carbonyl compounds to carboxylic acids in aqueous media SO SYNTHETIC COMMUNICATIONS LA English DT Article ID SODIUM-HYPOCHLORITE; ORGANIC-SYNTHESIS; DIOLS AB Carbonyl compounds containing electron-withdrawing substituents are efficiently oxidized by aqueous sodium hypochlorite in the absence of added organic solvents using microwaves. C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72079. UNIV TENNESSEE,DEPT CHEM,KNOXVILLE,TN 37996. RP Yang, DTC (reprint author), UNIV ARKANSAS,DEPT CHEM,LITTLE ROCK,AR 72204, USA. NR 27 TC 3 Z9 3 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0039-7911 J9 SYNTHETIC COMMUN JI Synth. Commun. PY 1997 VL 27 IS 18 BP 3235 EP 3239 DI 10.1080/00397919708004184 PG 5 WC Chemistry, Organic SC Chemistry GA XN912 UT WOS:A1997XN91200016 ER PT B AU Furfine, CS AF Furfine, CS BE Waegemann, CP TI Medical device amendments to the federal food, drug and cosmetic act SO TOWARD AN ELECTRONIC PATIENT RECORD '97 - CONFERENCE AND EXPOSITION, PROCEEDINGS, VOLS 1-3 LA English DT Proceedings Paper CT Conference on Toward an Electronic Patient Record 97 CY APR 27-MAY 03, 1997 CL NASHVILLE, TN SP Med Records Inst RP Furfine, CS (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MEDICAL RECORDS INSTITUTE PI NEWTON PA 567 WALNUT ST, PO BOX 600770, NEWTON, MA 02160 BN 0-9640667-9-3 PY 1997 BP C297 EP C300 PG 4 WC Health Policy & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA BH83G UT WOS:A1997BH83G00159 ER PT J AU Friedman, L Gaines, DW Chi, RK Smith, MC Braunberg, RC Thorpe, CW AF Friedman, L Gaines, DW Chi, RK Smith, MC Braunberg, RC Thorpe, CW TI Interaction of aflatoxins as measured by their biochemical action on rat liver slices and hepatocytes SO TOXIC SUBSTANCE MECHANISMS LA English DT Article ID METABOLIC-ACTIVATION; DNA-BINDING; OCHRATOXIN; TOXICITY; B1; IDENTIFICATION; MUTAGENICITY; CARCINOGENS; ANALOGS; KUPFFER AB The possible interaction, between pairs of aflatoxins commonly occurring together in, foods was evaluated by determining their biochemical actions on, the liver and hepatocytes of young mature rats. RNA synthesis, a sensitive and early target of the effects of aflatoxin B-1, was measured with [C-14]orotic acid or [H-3]uridine used as substrates. In the first study (comprised of four replicate experiments), liver slices treated with aflatoxin B-1 at 0, 120, 240, and 480 ng/ml were incubated in the presence and absence of aflatoxin B-1 at 120 ng/ml. In the second study, liver slices were treated with the same concentrations of B-1 incubated in the presence and absence of aflatoxin G(1) at 120 ng/ml (comprised of four replicate experiments) or at 240 ng/ml (comprised of two replicate experiments). In the third study (single experiment), isolated hepatocytes were treated with aflatoxin B-1 at 0, 60, 120, 240, and 480 ng/ml in the presence and absence of aflatoxin G(1) at 120 ng/ml. Leakage of lactic acid dehydrogenase (LDH) into the medium was determined as a measure of cell membrane integrity. A 30-min preincubation of the slices with aflatoxin B-1 before the radiolabeled precursor was added greatly increased the sensitivity of liver slices to the inhibition of RNA synthesis by the toxin. Use of the precursor [C-14]orotic acid increased the degree of inhibition into RNA by B-1 more than did [H-3]uridine. Relationships were consistent between B-1 and inhibition of RNA synthesis. RNA synthesis was not inhibited by aflatoxin B-2; however, inhibition was approximately 15 and 26% in liver slices when G(1) was used at 120 and 240 ng/ml, respectively, and 21% for hepatocytes for G(1) used at 120 ng/ml. A two-way analysis of variance (ANOVA) showed virtually no interaction between aflatoxins B-1 and B-2; however, interaction between aflatoxins B-1 and G(1) was evident. With results expressed as percent inhibition and data pooled from the respective experiments, an interaction between aflatoxins B-1 and G(1) was seen only at the higher level of G(1) (240 ng/ml). With hepatocytes, aflatoxins B-1 and G(1) interacted in their inhibition of RNA synthesis and in B-1-induced leakage of LDH. For liver slices and hepatocytes at the aflatoxin concentrations used, weak evidence was found for an interaction between aflatoxins B-1 and G(1) as measured by inhibition of RNA synthesis. There was no evidence that this interaction was synergistic. C1 US FDA, DIV TOXICOL RES, BELTSVILLE, MD USA. NR 77 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1076-9188 J9 TOX SUBST MECH JI Tox. Subst. Mech. PD JAN-MAR PY 1997 VL 16 IS 1 BP 15 EP 41 DI 10.1080/107691897229775 PG 27 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA WE542 UT WOS:A1997WE54200003 ER PT J AU Moch, RW Dua, PN Hines, FA AF Moch, RW Dua, PN Hines, FA TI Food and drug administration risk assessment - Process and toxicologic pathology SO TOXICOLOGIC PATHOLOGY LA English DT Article DE safety evaluation; pathology evaluation; carcinogenic assessment; rodent studies; dog studies; brain hemorrhages AB A general outline of the risk assessment process at the Center for Food Safety and Applied Nutrition (CFSAN) of the Food and Drug Administration based on the toxicologic evaluation of data is described. Examples of recent pathology evaluations are presented to illustrate primarily the pathology review process at the CFSAN. These examples include the review of data from rodent studies from proposed indirect food additives and data from dog studies submitted in support of an investigational new drug, a shea-acting opioid, proposed as an anesthetic in humans. RP Moch, RW (reprint author), US FDA,PATHOL BRANCH,DIV GEN SCI SUPPORT,OFF SCI ANAL & SUPPORT,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204, USA. NR 12 TC 3 Z9 3 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 JAN-FEB PY 1997 VL 25 IS 1 BP 61 EP 67 PG 7 WC Pathology; Toxicology SC Pathology; Toxicology GA WK635 UT WOS:A1997WK63500012 PM 9061853 ER PT B AU Littlefield, NA Sheldon, WG Lyn-Cook, B Hass, BS AF Littlefield, NA Sheldon, WG Lyn-Cook, B Hass, BS BE Fischer, PWF Labbe, MR Cockell, KA Gibson, RS TI The effect of dietary magnesium on the transformation process in mice SO TRACE ELEMENTS IN MAN AND ANIMALS - 9 LA English DT Proceedings Paper CT 9th International Symposium on Trace Elements in Man and Animals (TEMA 9) CY MAY 19-24, 1996 CL BANFF, CANADA SP Int Lead Zinc Res Org Inc, Int Cooper Assoc Ltd, Kellogg Canada Inc, MRC Canada, Nestec SA, Procter & Gamble Co, Ross Labs, Div Abbott Labs Ltd, US Pharmocopeial Convent Inc, Wyeth Ayerst Res, Zinpro Corp DE magnesium; transformation; mice; tumorigenesis C1 Natl Ctr Toxicol Res, Div Nutr Toxicol, US FDA, Jefferson, AR 72079 USA. RP Littlefield, NA (reprint author), Natl Ctr Toxicol Res, Div Nutr Toxicol, US FDA, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA BUILDING M-55, OTTAWA, ON KIA OR6, CANADA BN 0-660-16404-3 PY 1997 BP 183 EP 185 PG 3 WC Agriculture, Dairy & Animal Science; Environmental Sciences; Food Science & Technology; Public, Environmental & Occupational Health; Nutrition & Dietetics; Zoology SC Agriculture; Environmental Sciences & Ecology; Food Science & Technology; Public, Environmental & Occupational Health; Nutrition & Dietetics; Zoology GA BK57Z UT WOS:000072613500071 ER PT J AU Klein, HG Dodd, RY Ness, PM Fratantoni, JA Nemo, GJ AF Klein, HG Dodd, RY Ness, PM Fratantoni, JA Nemo, GJ TI Current status of microbial contamination of blood components: Summary of a conference SO TRANSFUSION LA English DT Editorial Material ID RNA GENE PROBE; BACTERIAL-CONTAMINATION; YERSINIA-ENTEROCOLITICA; RED-CELLS; TRANSFUSION; IDENTIFICATION; PLATELETS; SURVEILLANCE; SEPTICEMIA; SEPSIS C1 AMER RED CROSS,JEROME H HOLLAND LAB,ROCKVILLE,MD. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,BETHESDA,MD 20892. NHLBI,DIV BLOOD DIS & RESOURCES,TRANSFUS MED SCI RES GRP,BETHESDA,MD 20892. JOHNS HOPKINS UNIV HOSP,BLOOD BANK,BALTIMORE,MD 21287. RP Klein, HG (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BLDG 10,ROOM 1C711,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 22 TC 58 Z9 64 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JAN PY 1997 VL 37 IS 1 BP 95 EP 101 DI 10.1046/j.1537-2995.1997.37197176958.x PG 7 WC Hematology SC Hematology GA WF548 UT WOS:A1997WF54800018 PM 9024497 ER PT J AU Epstein, JS AF Epstein, JS TI Detection of acquired B antigen by monoclonal anti-B blood grouping reagents - Response SO TRANSFUSION LA English DT Letter RP Epstein, JS (reprint author), US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20014, USA. NR 7 TC 1 Z9 2 U1 1 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JAN PY 1997 VL 37 IS 1 BP 103 EP 105 DI 10.1046/j.1537-2995.1997.37197186498.x PG 3 WC Hematology SC Hematology GA WF548 UT WOS:A1997WF54800021 PM 9036594 ER PT J AU Maxim, PE AF Maxim, PE GP AMER ASSOC CLIN CHEM TI FDA tumor marker reclassification SO TUMOR MARKERS: RECLASSIFICATION, REIMBURSEMENT & RECENT ADVANCES LA English DT Proceedings Paper CT AACC Regulatory-Affairs-Committee Tumor Marker Conference CY MAR 12, 1997 CL WASHINGTON, DC SP Amer Assoc Clin Chem, Regulatory Affairs Comm RP Maxim, PE (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,IMMUNOL BRANCH,DIV CLIN LAB DEVICES,OFF DEVICE EVALUAT,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2029 K STREET NW, SEVENTH FLOOR, WASHINGTON, DC 20006 PY 1997 BP 7 EP 21 PG 15 WC Oncology; Medical Laboratory Technology SC Oncology; Medical Laboratory Technology GA BJ75S UT WOS:A1997BJ75S00002 ER PT J AU Pabst, HF Spady, DW Carson, MM Stelfox, HT Beeler, JA Krezolek, MP AF Pabst, HF Spady, DW Carson, MM Stelfox, HT Beeler, JA Krezolek, MP TI Kinetics of immunologic responses after primary MMR vaccination SO VACCINE LA English DT Article DE immunologic responses; measles; vaccination; infants ID MEASLES-VIRUS VACCINATION; INFECTION; IMMUNITY; IMMUNODEFICIENCY; POPULATION; SENEGAL; INFANTS; CHILD AB To study the kinetics of humoral as well as cellular immunity to measles and to test for associated immunosuppression 124 12 month old children were studied twice, before routine MMR and either 14, 22, 30, or 38 days after vaccination. Plaque reduction neutralization (PRN) titres were determined at these time points and lymphocytes were evaluated to identify changes in proportions of phenotype, their capacity to generate cytokines and to respond to blast transformation (BT) to measles hemagglutinin (HA), tetanus toroid, and Candida antigen. The PRN titre and BT to HA plateaued at 30 days and CD8+ and NK cells increased after immunization. Interleukin 2, 4, and 10 showed no significant changes. There was mild suppression of BT at 14 and 22 days postimmunization. Interferon-gamma was the principal cytokine produced after primary measles immunization, suggesting primary measles immunization induces predominantly, a TH1 type response. Copyright (C) 1997 Published by Elsevier Science Ltd. C1 US FDA,DIV VIRAL PROD,BETHESDA,MD 20014. RP Pabst, HF (reprint author), UNIV ALBERTA,DEPT PEDIAT,WALTER MACKENZIE CTR 2C300,EDMONTON,AB T6G 2R7,CANADA. FU NIAID NIH HHS [RD1 AI33996-02] NR 24 TC 48 Z9 48 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD JAN PY 1997 VL 15 IS 1 BP 10 EP 14 DI 10.1016/S0264-410X(96)00124-7 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WF984 UT WOS:A1997WF98400004 PM 9041660 ER PT S AU Scott, DE Golding, B AF Scott, DE Golding, B BE Gregoriadis, G McCormack, B Allison, AC TI A single treatment with adjuvant stimulates Th1-like cytokines and downregulates Th2-mediated primary and secondary allergic responses SO VACCINE DESIGN: THE ROLE OF CYTOKINE NETWORKS SE NATO ADVANCED SCIENCE INSTITUTES SERIES, SERIES A, LIFE SCIENCES LA English DT Proceedings Paper CT 5th NATO Advanced Studies Institute Workshop on Vaccine Design - The Role of Cytokine Networks CY JUN 24-JUL 05, 1996 CL CAPE SOUNION BEACH, GREECE SP NATO, Sci Affairs Div, SmithKline Beecham Pharmaceut C1 US FDA, Ctr Biol Evaluat & Res, Lab Plasma Derivat, Div Hematol,Off Blood, Bethesda, MD 20892 USA. RP Scott, DE (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Plasma Derivat, Div Hematol,Off Blood, Bldg 29,Rm 232,8800 Rockville Pike, Bethesda, MD 20892 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 USA SN 0258-1213 BN 0-306-45818-7 J9 NATO ADV SCI I A-LIF PY 1997 VL 293 BP 67 EP 79 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA BK80U UT WOS:000073457700008 ER PT S AU Golding, H Zaitseva, MB Lapham, CK Golding, B AF Golding, H Zaitseva, MB Lapham, CK Golding, B BE Gregoriadis, G McCormack, B Allison, AC TI Induction of IL-12 secretion and enhanced surface expression of B7.1/B7.2 and icam-1 in human monocytes activated by the vaccine carrier Brucella abortus: Correlation with in vivo generation of cellular immune responses SO VACCINE DESIGN: THE ROLE OF CYTOKINE NETWORKS SE NATO ADVANCED SCIENCE INSTITUTES SERIES, SERIES A, LIFE SCIENCES LA English DT Proceedings Paper CT 5th NATO Advanced Studies Institute Workshop on Vaccine Design - The Role of Cytokine Networks CY JUN 24-JUL 05, 1996 CL CAPE SOUNION BEACH, GREECE SP NATO, Sci Affairs Div, SmithKline Beecham Pharmaceut C1 US FDA, Ctr Biol Evaluat & Res, Lab Retrovirus Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Golding, H (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Retrovirus Res, Div Viral Prod, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0258-1213 BN 0-306-45818-7 J9 NATO ADV SCI I A-LIF PY 1997 VL 293 BP 81 EP 97 PG 17 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA BK80U UT WOS:000073457700009 ER PT S AU Slikker, W Gaylor, DW AF Slikker, W Gaylor, DW BE Manzo, L Descotes, J Hoskins, J TI Developmental neurotoxicity of inhaled methanol: a quantitative, dose-response risk assessment model SO VOLATILE ORGANIC COMPOUNDS IN THE ENVIRONMENT - RISK ASSESSMET AND NEUROTOXICITY SE ADVANCES IN OCCUPATIONAL MEDICINE & REHABILITATION LA English DT Proceedings Paper CT International Conference on Volatile Organic Compounds CY OCT 05-07, 1997 CL SALVATORE MAUGERI FDN MED CTR, PAVIA, ITALY SP Univ Pavia, Salvatore Maugeri Fdn, Int Soc Built Environm, Natl Res Council, Rome, AgipPetroli, BASF, CON TEC Engn, DANI, Draeger Italiana, FIAT Auto, FKV, Instrumentat Lab, IPSOA Editore Indicitalia, Perkin Elmer, Pollut Srl Clean Air Syst, San Air Ambiente, Tecnol Ind & Ambientali, Unione Petrolifera, Zambelli HO SALVATORE MAUGERI FDN MED CTR AB Even though biologically-based risk assessment guidelines for non-cancer endpoints are gaining acceptance, quantitative and/or dose-response risk assessment models are not widely utilised. As new guidelines are implemented, dose-response data concerning critical, biologically based biomarkers will be available as a basis of quantitative risk assessment. Strategies demonstrating the application of quantitative approaches need to be elaborated in order to evaluate their usefulness. A quantitative, dose-response risk assessment of the VOC methanol (ME) was completed in pregnant rats. Foetal weight (continuous variable) and blain abnormalities (quantal variable) collected on gestation day 20 of darns exposed to ME by inhalation for 7 h.day(-1) on day 1-19 of gestation for 0, 5000, 10,000 ppm ME and day 7-15 for 20,000 ppm ME were evaluated (Nelson ct al., 1985). Foctal weights for the various, treatment groups (:N=15 litters) were evaluated: a) the average and standard deviation of foetal weight for the control animals were estimated, b) abnormal values were identified as the first percentile (2.33 standard deviations below the average) from the:statistical distribution of the normally distributed control values, c) a dose-response relationship was established to estimate average values as a function of dose, d) the probabilities of values in the abnormal foetal weight range were calculated from the estimated averages and their standard deviations. The foetal weight outcome indicates that an excess risk of 0.10, 0.01 and 0.001 would result from ME concentrations of 16,000, 5,400 and 980 ppm, respectively. For foetal brain abnormalities (i.e., hydrocephaly, exencephaly or encephalocele), an excess risk of 0.1, 0.01 and 0.001 would result from ME concentrations of 11,000. 3,400 and 1,100 ppm, respectively. The quantitative results were compared to the permissible exposure level (PEL) and outcome fr om the currently used no observed adverse effect level (NOAEL)/safety factor approach. Advantages of the quantita tive approach include the use of all the data defining the dose-response curve, the use of both continuous and quantal data, anti the calculation of the risk resulting from exposure to a given dose. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Slikker, W (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU FONDAZIONE SALVATORE MAUGERI EDIZIONI, PI-ME PRESS PI PAVIA 27100 PA VIALE SARDEGNA 64, PAVIA 27100, ITALY SN 1123-8364 BN 88-7963-085-7 J9 ADV OCCUP MED REHAB PY 1997 VL 3 IS 3 BP 191 EP 197 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Rehabilitation; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Rehabilitation; Toxicology GA BM07W UT WOS:000077556200021 ER PT J AU Fritsche, J Mossoba, MM Yurawecz, MP Roach, JAG Sehat, N Ku, Y Steinhart, H AF Fritsche, J Mossoba, MM Yurawecz, MP Roach, JAG Sehat, N Ku, Y Steinhart, H TI Conjugated linoleic acid (CLA) isomers in human adipose tissue SO ZEITSCHRIFT FUR LEBENSMITTEL-UNTERSUCHUNG UND-FORSCHUNG A-FOOD RESEARCH AND TECHNOLOGY LA English DT Article DE human adipose tissue; cancer; conjugated linoleic acid; CLA; gas chromatography; infrared spectroscopy; mass spectrometry ID MASS-SPECTROMETRY; SPECTROSCOPY; DERIVATIVES; LOCATION AB The methyl ester and 4,4-dimethyloxazoline (DMOX) derivatives of the geometric isomers cis9,trans11-and trans9,trans11-octadecadienoic acid and the two minor isomers trans9,cis11- and cis9,cis11-octadecadienoic acid were found in human adipose tissue, by using gas chromatography-direct deposition-Fourier transform infrared spectroscopy (GC-DD-FTIR) and gas chromatography-electron ionization mass spectrometry (GC-ELMS). C1 Univ Hamburg, Inst Biochem & Food Chem, D-20146 Hamburg, Germany. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Steinhart, H (reprint author), Univ Hamburg, Inst Biochem & Food Chem, Grindelallee 117, D-20146 Hamburg, Germany. NR 13 TC 23 Z9 24 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1431-4630 J9 Z LEBENSM UNTERS F A JI Z Lebensm. Unters. Forsch. A-Food Res. Technol. PY 1997 VL 205 IS 6 BP 415 EP 418 DI 10.1007/s002170050191 PG 4 WC Food Science & Technology SC Food Science & Technology GA YL955 UT WOS:000071012200004 ER PT J AU Park, YM Yoo, YD Paik, SY Kim, BS Tabor, E AF Park, YM Yoo, YD Paik, SY Kim, BS Tabor, E TI Mutation of tumor suppressor gene p53 in hepatocellular carcinomas from Korea SO EXPERIMENTAL AND MOLECULAR MEDICINE LA English DT Article DE reverse transcription polymerase chain reaction; polymerase chain reaction single strand conformation polymorphism; p53; tumor suppressor gene; hepatocellular carcinoma ID CHINA; HETEROGENEITY; ABERRATIONS; EXPRESSION; OCCUR AB Mutation of the p53 gene in hepatocellular carcinoma has been recognized as one of the most important genetic alterations to occur during hepatocarcinogenesis. This study was performed to analyze the frequency and nature of p53 mutations in advanced hepatocellular carcinomas from Korea. Tissue samples were obtained by laparoscopic biopsy from 35 patients; adjacent nontumorous liver tissue was also obtained from 24 of them. Mutations of the p53 gene were identified in 11/35 (31%) of hepatocellular carcinomas, These included 7 missense mutations and 4 deletion mutations. Only one mutation was detected at codon 249, a ''hot spot'' at which mutations have been found frequently in hepatocellular carcinomas from some geographic areas; however, this was an A-to-T transversion at the first nucleotide, thus differing from commonly reported G-to-T transversion at the third nucleotide of codon 249 in hepatocellular carcinomas, Patients whose serum alkaline phosphatase levels were higher than the mean Value were more likely to have p53 mutations, compared to patients whose alkaline phosphatase levels were lower than the mean value [55% (6/11) vs. 21% (5/24)] (p<0.05). Thus, p53 mutations are found in many hepatocellular carcinomas in Korea. However, mutations commonly thought to be due to aflatoxin B-1 (G-to-T transversion at codon 249) were not found, suggesting that aflatoxin-B-1 does not play an important role in the etiology of hepatocellular carcinoma in Korea. C1 NCI,NIH,BETHESDA,MD 20892. CATHOLIC UNIV,SCH MED,KANGNAM ST MARYS HOSP,DEPT INTERNAL MED,SEOUL,SOUTH KOREA. KOREAN CANC CTR HOSP,LAB EXPT THERAPEUT,SEOUL,SOUTH KOREA. CATHOLIC UNIV,SCH MED,DEPT MICROBIOL,SEOUL,SOUTH KOREA. US FDA,BETHESDA,MD 20014. NR 26 TC 6 Z9 6 U1 1 U2 2 PU KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY PI SEOUL PA #812 KOFST, 635-4 YOKSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1226-3613 J9 EXP MOL MED JI Exp. Mol. Med. PD DEC 31 PY 1996 VL 28 IS 4 BP 173 EP 179 PG 7 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA WC363 UT WOS:A1996WC36300004 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 (vol 79, pg 13, 1996) SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Correction, Addition RP Syin, C (reprint author), US FDA,LAB PARASIT BIOL & BIOCHEM,DIV ALLERGEN PROD & PARASITOL,OFF VACCINE REVIEW & RES,ROCKVILLE,MD 20852, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 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 DEC 20 PY 1996 VL 83 IS 2 BP 263 EP 263 DI 10.1016/S0166-6851(96)02758-2 PG 1 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA WF108 UT WOS:A1996WF10800016 ER PT J AU Kanegane, H Wang, F Tosato, G AF Kanegane, H Wang, F Tosato, G TI Virus-cell interactions in a natural killer-like cell line from a patient with lymphoblastic lymphoma SO BLOOD LA English DT Article ID EPSTEIN-BARR-VIRUS; LATENT MEMBRANE-PROTEIN; CD3-NEGATIVE LYMPHOPROLIFERATIVE DISEASE; POLYMERASE CHAIN-REACTION; VIRAL-DNA; MONOCLONAL-ANTIBODIES; BURKITT-LYMPHOMA; IL-2 RECEPTOR; B-CELLS; GRANULAR LYMPHOCYTES AB Lymphoproliferative disorders involving Epstein-Barr virus (EBV) infected natural killer (NK) cells are reported with increasing frequency, but the nature and role of EBV infection in these cells remains undefined. In this study, we have investigated virus-cell interactions in the EBV-positive YTN10 cell line, an NK-like cell line established from a patient with lymphoblastic lymphoma. Low level expression of the EBV receptor CD21 molecule was detected by FACS and reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Immunoblotting and RT-PCR analysis identified a latency II pattern of EBV gene expression, consisting of EBNA-1 transcription from the Qp promoter, in the absence of other EBNA gene expression, and accompanied by LMP-1 and LMP-ZA expression. The EBV genome was present in episomal form and there was evidence for lytic viral replication. This latency pattern is typical of EBV gene expression in nasopharyngeal carcinoma and Hodgkin's disease, and differs from the full spectrum of EBV latent gene expression in most posttransplant lymphoproliferative disorders and from the restricted EBNA-1 expression in Burkitt's lymphoma tissues. The interaction between EBV and NK cells described here has important implications for the pathogenesis and treatment of EBV-infected NK malignancies. This is a US government work. There are no restrictions on its use. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV INFECT DIS,BOSTON,MA 02115. RP Kanegane, H (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BLDG 29A,ROOM 2D06,HFM-535,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 49 TC 16 Z9 17 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 DEC 15 PY 1996 VL 88 IS 12 BP 4667 EP 4675 PG 9 WC Hematology SC Hematology GA VZ305 UT WOS:A1996VZ30500030 PM 8977260 ER PT J AU Roetzheim, R Fox, SA Leake, B Houn, F Zapka, J Costanza, ME Lane, DS Rimer, B Breen, N Haynes, SG Kessler, LG Feuer, E AF Roetzheim, R Fox, SA Leake, B Houn, F Zapka, J Costanza, ME Lane, DS Rimer, B Breen, N Haynes, SG Kessler, LG Feuer, E TI The influence of risk factors on breast carcinoma screening of Medicare-insured older women SO CANCER LA English DT Article DE mammography; screening; breast neoplasms; prevention; risk factors; older women; trends ID FAMILY HISTORY; MAMMOGRAPHY UTILIZATION; PSYCHOLOGICAL DISTRESS; CANCER RISK; HEALTH; AGE; INTERVENTION; IMPACT; PARTICIPATION; RELATIVES AB BACKGROUND. It is not certain whether older women with additional breast carcinoma risk factors are adequately screened or whether they are more likely to undergo screening than other older women. This study was conducted to determine whether selected risk factors influence the breast carcinoma screening rates of Medicare-insured older women (i.e., age 65 years or older). METHODS. Self-reported rates of screening mammography and clinical breast examination in the previous year were compared for women with benign breast disease, women with a family history of breast carcinoma, and women lacking these risks, using samples of non-Hispanic white, Medicare-insured women surveyed at the 5 National Cancer Institute Breast Cancer Screening Consortium sites in 1991 (n = 5376, mean age = 69.7 years) and 1994 (n = 5086, mean age = 69.7 years). RESULTS. In 1993, rates of screening mammography reported in the previous year at the 5 Consortium sites had a range of 46-61% for women with a family history of breast carcinoma, 49-66% for women with benign breast disease, and 31-43% for women lacking these risks. Women with a positive family history or a personal history of benign breast disease were also more likely to report having had a clinical breast examination in the previous year and having received a physician's mammography recommendation. A substantial proportion of older women with a positive family history remain inadequately screened, however. Between 25% and 35% of women in this group had not had a screening mammogram in the previous 2 years, while at some Consortium sites more than 20% reported never having had a mammogram in their lives. CONCLUSIONS. Older women with additional risk factors are more likely to undergo screening mammography. This is due partly to more frequent physician recommendations for screening and partly to more frequent provision of clinical breast examinations. However, a substantial proportion of high risk older women remain inadequately screened, despite widespread clinical consensus that these women should be regularly screened. Interventions that target older women with risk factors and their physicians appear warranted. Understanding the mechanisms by which risk factors influence screening is an important area for future research. (C) 1996 American Cancer Society. C1 RAND CORP, SANTA MONICA, CA USA. UNIV CALIF LOS ANGELES, DIV GEN INTERNAL MED, LOS ANGELES, CA USA. US FDA, RADIAT PROGRAM, ROCKVILLE, MD 20857 USA. US FDA, DIV MAMMOG, QUAL PROGRAM, ROCKVILLE, MD 20857 USA. RP Roetzheim, R (reprint author), UNIV S FLORIDA, DEPT FAMILY MED, 12901 BRUCE B DOWNS BLVD, MDC 13, TAMPA, FL 33612 USA. RI Roetzheim, Richard/J-4696-2012 FU BHP HRSA HHS [2T32PE19001-06]; NCI NIH HHS [NCI RO1CA45003] NR 41 TC 15 Z9 15 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD DEC 15 PY 1996 VL 78 IS 12 BP 2526 EP 2534 DI 10.1002/(SICI)1097-0142(19961215)78:12<2526::AID-CNCR12>3.0.CO;2-Y PG 9 WC Oncology SC Oncology GA VW714 UT WOS:A1996VW71400012 PM 8952561 ER PT J AU Puri, RK Hoon, DS Leland, P Snoy, P Rand, RW Pastan, I Kreitman, RJ AF Puri, RK Hoon, DS Leland, P Snoy, P Rand, RW Pastan, I Kreitman, RJ TI Preclinical development of a recombinant toxin containing circularly permuted interleukin 4 and truncated Pseudomonas exotoxin for therapy of malignant astrocytoma SO CANCER RESEARCH LA English DT Article ID RENAL-CELL-CARCINOMA; TUMOR-NECROSIS-FACTOR; RECEPTOR GAMMA-CHAIN; CHIMERIC PROTEIN; IL-4 RECEPTORS; HUMAN-MELANOMA; EXPRESSION; GROWTH; INHIBITION; INTERFERON AB Effective treatment is lacking for malignant glioblastoma/astrocytoma. We have identified interleukin-4 receptors (IL-4R) on human malignant astrocytoma. We demonstrate that 16 of 21 surgical samples of high-grade astrocytoma and glioblastoma but not normal brain tissues expressed IL-4R as assessed by reverse transcriptase PCR. We further demonstrate that human malignant astrocytoma cell lines express high-affinity IL-4R. Using a chimeric protein composed of circularly permuted IL-4 and a truncated form of Pseudomonas exotoxin A, we observed that this toxin (IL4(38-37)-PE38KDEL) is highly cytotoxic to IL-4R-bearing glioblastoma cells. Compared with a previously reported IL4-PE chimeric protein (IL-PE4E), IL4(38-37)-PE38KDEL bound with higher affinity and was 3-30-fold more cytotoxic to glioblastoma cell lines, Upon intrathecal administration in monkeys, high cerebrospinal fluid IL4(38-37)-PE38KDEL levels mere achieved using 2- and 6-mu g/kg doses without any central nervous system or other abnormalities. IL4(38-37)-PE38KDEL levels were not detectable in the serum of any monkey studied. When IL4(38-37)-PE38KDEL was injected into the right frontal cortex of rats, localized necrosis was observed at 1000-ng/ml doses but not at less than or equal to 100-ng/ml doses. We conclude that by localized administration, nontoxic levels of IL4(38-37)-PE38KDEL can be achieved, which may have significant cytotoxic activity against malignant astrocytoma. C1 NIH,LAB MOL TUMOR BIOL,DIV VET SERV,CTR BIOL EVALUAT & RES,FOOD & DRUG ADM,BETHESDA,MD 20892. ST JOHNS HOSP,JOHN WAYNE CANC INST,DIV MOL & CELLULAR IMMUNOL & NEUROONCOL,SANTA MONICA,CA 90404. NCI,MOL BIOL LAB,DIV CANC BIOL DIAGNOSIS & CTR,NIH,BETHESDA,MD 20892. RP Puri, RK (reprint author), NIH,LAB MOL TUMOR BIOL,DIV CELLULAR & GENE THERAPIES,CTR BIOL EVALUAT & RES,FOOD & DRUG ADM,BETHESDA,MD 20892, USA. OI Hoon, Dave/0000-0003-1915-3683 NR 32 TC 91 Z9 95 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 DEC 15 PY 1996 VL 56 IS 24 BP 5631 EP 5637 PG 7 WC Oncology SC Oncology GA VX880 UT WOS:A1996VX88000020 PM 8971168 ER PT J AU Zhang, MJ Dayton, AI AF Zhang, MJ Dayton, AI TI Two secondary structures for the RRE of HIV-1? SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE RRE; ReV protein; HIV-1 ID REV-RESPONSE ELEMENT; TARGET SEQUENCE; GENE-PRODUCT; VIRUS; PROTEIN; RNA; LOCALIZATION; RECOGNITION; EXPRESSION; BINDING AB The RRE, the target sequence for the Rev protein of HIV-1, is a highly structured RNA sequence characterized by multiple stem loops. Although agreement on the stem/loop organization outside the high-affinity site was reached some time ago by several laboratories, recent work has suggested an alternative structure in which sequences from two of the stem/loops (IV and V) pair to form one long stem/loop (IV/V) when enough HIV material is present to allow the formation of an extended central stem structure (I/I'). Here we address the contribution of the original and alternative structures to function in RRE constructs with short and extended I'I' regions. We confirm that extended I/I' structures improve RRE function and may stabilize the overall structure. However, we find no evidence that an extended I/I' structure preferentially stabilizes either alternative structure with respect to the other. The two alternative structures are approximately functionally equivalent, and both are probably present in an in vivo population of RREs. C1 US FDA,MOL VIROL LAB,DIV TRANSFUS TRANSMITTED DIS,OFF BLOOD RES & REVIEW,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20857. NR 21 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD DEC 15 PY 1996 VL 13 IS 5 BP 403 EP 407 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VY574 UT WOS:A1996VY57400001 PM 8970465 ER PT J AU Mor, G Yamshchikov, G Sedegah, M Takeno, M Wang, RB Houghten, RA Hoffman, S Klinman, DM AF Mor, G Yamshchikov, G Sedegah, M Takeno, M Wang, RB Houghten, RA Hoffman, S Klinman, DM TI Induction of neonatal tolerance by plasmid DNA vaccination of mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE DNA vaccine; tolerance; malaria; neonate; epitope ID CIRCUMSPOROZOITE PROTEIN; IMMUNE-RESPONSES; CELLS; GENE; IMMUNIZATION; PROTECTION; MATURATION; INJECTION; MALARIA; IL-6 AB Plasmid DNA vaccines capable of preventing viral, bacterial, and parasitic infections are currently under development, Our labs have shown that a plasmid DNA vaccine encoding the circumsporozoite protein of the malaria parasite elicits protective immunity against live sporozoite challenge in adult BALB/c mice. We now find that the same DNA vaccine induces tolerance rather than immunity when administered to 2-5 d-old mice, Neonatal, tolerized animals were unable to mount antibody, cytokine or cytotoxic responses when rechallenged a with DNA vaccine in vitro or in vivo. Tolerance was specific for immunogenic epitopes expressed by the vaccine-encoded, endogenously produced antigen. Mice challenged with exogenous circumsporozoite protein produced antibodies against a different set of epitopes, and were not tolerized, These findings demonstrate important differences in the nature and specificity of the immune response elicited by DNA vaccines versus conventional protein immunogens. C1 US FDA,CTR BIOL EVALUAT & RES,SECT RETROVIRAL IMMUNOL,BETHESDA,MD 20892. TORREY PINES INST MOL STUDIES,SAN DIEGO,CA 92121. USN,MED RES INST,MALARIA PROGRAM,BETHESDA,MD 20889. NR 35 TC 105 Z9 111 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC 15 PY 1996 VL 98 IS 12 BP 2700 EP 2705 DI 10.1172/JCI119094 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VZ318 UT WOS:A1996VZ31800008 PM 8981914 ER PT J AU Yi, AK Klinman, DM Martin, TL Matson, S Krieg, AM AF Yi, AK Klinman, DM Martin, TL Matson, S Krieg, AM TI Rapid immune activation by CpG motifs in bacterial DNA - Systemic induction of IL-6 transcription through an antioxidant-sensitive pathway SO JOURNAL OF IMMUNOLOGY LA English DT Article ID B-CELL DIFFERENTIATION; TUMOR-NECROSIS-FACTOR; GENE-EXPRESSION; INTERLEUKIN-6 PROMOTER; GROWTH; IDENTIFICATION; STIMULATION; FIBROBLASTS; MACROPHAGE; INFECTION AB Unmethylated CpG dinucleotides (CpG motif) in bacterial DNA or synthetic oligodeoxynucleotides (CpG DNA) rapidly activate murine B cells to secrete IL-6 and IgM, as well as to proliferate, Within 30 min after CpG DNA stimulation in vivo, IL-6 mRNA levels were increased in liver, spleen, and thymus cells, Serum IL-6 protein was markedly increased within 1 h of stimulation, Treatment of a B cell line with CpG DNA led to an increase in the transcriptional activity of the IL-6 promoter, This CpG DNA-induced IL-6 production was not mediated via either a protein kinase C (PKC)-, protein kinase A (PKA)-, or nitric oxide (NO)-dependent pathway but was inhibited by an antioxidant. In addition, the level of intracellular reactive oxygen species was increased within 20 min after CpG DNA, but not control non-CpG DNA, treatment, These results suggest that CpG DNA-induced IL-6 production is mediated through a reactive oxygen intermediate-dependent pathway. CpG DNA-mediated IL-6 production was enhanced by simultaneous signals delivered through the Ag receptor, The addition of neutralizing Abs against IL-6 to B cell cultures along with CpG oligodeoxynucleotides essentially abolished the CpG DNA-induced increased IgM secretion but had no significant effect on the B cell proliferation induced by the CpG motif, Our results suggest that the induction of IL-6 expression in response to CpG motifs in bacterial DNA may be an important immune defense mechanism that facilitates a rapid response to microbial infection. C1 UNIV IOWA, DEPT INTERNAL MED, COLL MED, IOWA CITY, IA 52242 USA. US FDA, CTR BIOL EVALUAT, RETROVIRAL IMMUNOL SECT, BETHESDA, MD 20892 USA. VET AFFAIRS MED CTR, IOWA CITY, IA 52246 USA. FU NIAMS NIH HHS [R20-AR42556-01] NR 43 TC 220 Z9 230 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1996 VL 157 IS 12 BP 5394 EP 5402 PG 9 WC Immunology SC Immunology GA VX026 UT WOS:A1996VX02600023 PM 8955187 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 Professional flexible labeling - Task force report .2. Response to comments on the proposed model of a professional 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 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 DEC 15 PY 1996 VL 209 IS 12 BP 2068 EP 2070 PG 3 WC Veterinary Sciences SC Veterinary Sciences GA VX283 UT WOS:A1996VX28300033 PM 8960188 ER PT J AU Luo, WH Yin, BZ Ang, CYW Rushing, L Thompson, HC AF Luo, WH Yin, BZ Ang, CYW Rushing, L Thompson, HC TI Determination of lincomycin residues in salmon tissues by gas chromatography with nitrogen-phosphorus detection SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE lincomycin ID RESISTANCE AB A sensitive method for the determination of lincomycin residues in fish tissues is described. Lincomycin was extracted from fish tissues with phosphate buffer (pH 4.5). The extract was concentrated with a C-18 solid-phase extraction cartridge and further cleaned up by solvent extraction. Lincomycin was derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide to form a trimethylsilyl derivative before being analyzed by gas chromatography with nitrogen-phosphorus detection. Coumaphos was used as the internal standard. Assays showed good linearity in the range 25-250 ppb (ng/g) (r=0.9994). Recoveries of fortified lincomycin at 50, 100 and 200 ppb were >80% with relative standard deviations <6%. The limit of detection of the method was 1.7 ppb and the limit of quantitation was 3.8 ppb. C1 US FDA,NATL CTR TOXICOL RES,DEPT HLTH & HUMAN SERV,PUBL HLTH SERV,JEFFERSON,AR 72079. NR 14 TC 24 Z9 32 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD DEC 13 PY 1996 VL 687 IS 2 BP 405 EP 411 DI 10.1016/S0378-4347(96)00238-1 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WD016 UT WOS:A1996WD01600011 PM 9017464 ER PT J AU Kessler, DA Hass, AE Feiden, KL Lumpkin, M Temple, R AF Kessler, DA Hass, AE Feiden, KL Lumpkin, M Temple, R TI Approval of new drugs in the United States - Comparison with the United Kingdom, Germany, and Japan SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article AB In a study reported herein, the marketing approval dates of 214 drugs newly introduced into the world market from January 1990 through December 1994 were compared in 4 countries. The analysis reveals that the United States and the United Kingdom have similar patterns of drug availability, although the United States has a number of therapies with significant public health benefits that are not yet available in the United Kingdom. The findings also show that the United States outpaces both Germany and Japan in approving important new drugs. Various strategies adopted by the Food and Drug Administration to expedite its pharmaceutical review process, including the use of industry user fees, are described. C1 US FDA, OFF PLANNING & EVALUAT, ROCKVILLE, MD 20857 USA. US FDA, CTR DRUG EVALUAT & RES, ROCKVILLE, MD 20857 USA. RP Kessler, DA (reprint author), US FDA, OFF COMMISSIONER, 5600 FISHERS LN, ROCKVILLE, MD 20857 USA. NR 7 TC 24 Z9 24 U1 0 U2 1 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 DEC 11 PY 1996 VL 276 IS 22 BP 1826 EP 1831 DI 10.1001/jama.276.22.1826 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA VV997 UT WOS:A1996VV99700033 PM 8946904 ER PT J AU Farizo, KM Cafarella, TG Burns, DL AF Farizo, KM Cafarella, TG Burns, DL TI Evidence for a ninth gene, ptlI in the locus encoding the pertussis toxin secretion system of Bordetella pertussis and formation of a PtlI-PtlF complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ISLET-ACTIVATING PROTEIN; ADENYLATE-CYCLASE; SUBCELLULAR-LOCALIZATION; NUCLEOTIDE-SEQUENCE; VIRB OPERON; PLASMID; MODEL AB The pertussis toxin secretion system of Bordetella pertussi initially was thought to comprise eight proteins, Pt1A-Pt1H. We have investigated the existence of another protein, PtlI, encoded by a putative gene located between ptlD and ptlE. A B. pertussis strain expressing a ptlI::phoA translational fusion possessed alkaline phosphatase activity, suggesting that ptlI encodes a protein. In B. pertussis, a protein with an apparent molecular weight of similar to 5,200 (similar to that predicted by the ptlI sequence) was immunoreactive with an antibody raised to a PtlI-maltose-binding protein fusion protein, PtlE expression in a mutant sustaining an in-frame deletion in ptlI indicated that ptlE starts further downstream than initially predicted. Pt1F, not detected in the ptlI deletion mutant, was restored partially by expressing ptlI in trans, A 36-kDa species, consistent with a Pt1I-Pt1F complex, was immunoreactive with antibodies to Pt1I and Pt1F in nonreduced cell extracts of a Bordetella bronchiseptica strain which overexpresses the Pt1 proteins. Upon dithiothreitol treatment, the 36-kDa species was diminished greatly or undetectable. In B. pertussis, Pt1I and Pt1F co-precipitated with antibody to Pt1F. These findings demonstrate the existence of Pt1I and a Pt1I-Pt1F complex, providing the first description of an interaction between Pt1 proteins. RP Farizo, KM (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,HFM-434,BLDG 29,RM 418,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 37 TC 36 Z9 41 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 DEC 6 PY 1996 VL 271 IS 49 BP 31643 EP 31649 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VW686 UT WOS:A1996VW68600095 PM 8940184 ER PT J AU Sandberg, JA Duhart, HM Lipe, G Binienda, Z Slikker, W Kim, CS AF Sandberg, JA Duhart, HM Lipe, G Binienda, Z Slikker, W Kim, CS TI Distribution of 2,4-dichlorophenoxyacetic acid (2,4-D) in maternal and fetal rabbits SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article ID TREATED EGGS; BUTYL ESTER; MALE-RATS; HERBICIDES; ABSORPTION; EXCRETION; ACCUMULATION; TRANSPORT; HALOTHANE; KETAMINE AB The distribution of 2,4-dichlorophenoxyacetic acid (2,4-D) was examined in maternal and fetal rabbits. Pregnant New Zealand rabbits (28-30 d gestational age) were anesthetized with ketamine/xylazine and the femoral vein and artery were catheterized for compound administration and sampling. Darns received iv [C-14]2,4-D (12.5 mu Ci/kg) with unlabeled sodium 2,4-D (1, 10, or 40 mg/kg) in saline. Blood and tissue were collected up to 2 h after dosing. Fetal to maternal plasma AUC ratios were 0.09, 0.07, and 0.16 after the 1, 10, or 40 mg/kg dose, respectively. Extraplasma AUCs were greatest in maternal kidney and uterus and lowest in maternal and fetal brain. A greater than fourfold elevation in fetal AUC was found when the dose was increased from 10 to 40 mg/kg, suggesting saturation of maternal plasma binding of 2,4-D. Although the in vitro fetal brain tissue to incubation media ratio was unity (1.03 +/- 0.1, mean +/- SD), fetal brain AUCs were 10% or less of the fetal plasma AUCs, indicating the brain barrier system to 2,4-D is functioning in the late-gestation fetal rabbit However, its development may not be complete due to the higher brain tissue to plasma ratios in the fetus compared to the dam. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,DIV TOXICOL RES,LAUREL,MD. RP Sandberg, JA (reprint author), US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,HFT-132,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 32 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 DEC 6 PY 1996 VL 49 IS 5 BP 497 EP 509 PG 13 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA VX941 UT WOS:A1996VX94100004 PM 8968410 ER PT J AU Nightingale, SL AF Nightingale, SL TI Breath test for Helicobacter pylori collection kit 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 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 DEC 4 PY 1996 VL 276 IS 21 BP 1710 EP 1710 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VV566 UT WOS:A1996VV56600009 PM 8940307 ER PT J AU Nightingale, SL AF Nightingale, SL TI Warning on severe renal impairment with use of cidofovir injection 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 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 DEC 4 PY 1996 VL 276 IS 21 BP 1710 EP 1710 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VV566 UT WOS:A1996VV56600010 PM 8940307 ER PT J AU Nightingale, SL AF Nightingale, SL TI Protease inhibitor charts available 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 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 DEC 4 PY 1996 VL 276 IS 21 BP 1710 EP 1710 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VV566 UT WOS:A1996VV56600008 PM 8940307 ER PT J AU Nightingale, SL AF Nightingale, SL TI New spinal fusion devices 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 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 DEC 4 PY 1996 VL 276 IS 21 BP 1710 EP 1710 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VV566 UT WOS:A1996VV56600007 PM 8940307 ER PT J AU Perrotta, DM Coody, G Culmo, C AF Perrotta, DM Coody, G Culmo, C TI Adverse events associated with ephedrine-containing products - Texas, December 1993 September 1995 (Reprinted from MMWR, vol 45, pg 689-693, 1996) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint ID DOUBLE-BLIND; CAFFEINE C1 TEXAS DEPT HLTH,BUR FOOD & DRUG SAFETY,AUSTIN,TX 78756. TEXAS DEPT HLTH,TEXAS POISON CTR NETWORK,AUSTIN,TX 78756. US FDA,CTR FOOD SAFETY & APPL NUTR,CLIN RES & REVIEW SATFF,ROCKVILLE,MD 20857. CTR DIS CONTROL,NATL CTR ENVIRONM HLTH,DIV ENVIRONM HAZARDS & HLTH EFFECTS,ATLANTA,GA 30333. RP Perrotta, DM (reprint author), TEXAS DEPT HLTH,BUR EPIDEMIOL,AUSTIN,TX 78756, USA. NR 9 TC 30 Z9 30 U1 0 U2 1 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 DEC 4 PY 1996 VL 276 IS 21 BP 1711 EP 1712 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VV566 UT WOS:A1996VV56600011 ER PT J AU Fields, BA Goldbaum, FA DallAcqua, W Malchiodi, EL Cauerhff, A Schwarz, FP Ysern, X Poljak, RJ Mariuzza, RA AF Fields, BA Goldbaum, FA DallAcqua, W Malchiodi, EL Cauerhff, A Schwarz, FP Ysern, X Poljak, RJ Mariuzza, RA TI Hydrogen bonding and solvent structure in an antigen-antibody interface. Crystal structures and thermodynamic characterization of three Fv mutants complexed with lysozyme SO BIOCHEMISTRY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; INFLUENZA-VIRUS NEURAMINIDASE; CROSS-REACTION COMPLEX; 3-DIMENSIONAL STRUCTURE; PROTEIN STABILITY; INHIBITOR COMPLEXES; BINDING; FAB; RESOLUTION; BARNASE AB Using site-directed mutagenesis, X-ray crystallography, and titration calorimetry, we have examined the structural and thermodynamic consequences of removing specific hydrogen bonds in an antigen-antibody interface. Crystal structures of three antibody FvD1.3 mutants, V(L)Tyr50Ser (V(L)Y50S), V(H)Tyr32Ala (V(H)Y32A), and V(H)Tyr101Phe (V(H)Y101F) bound to hen egg white lysozyme (HEL) have been determined at resolutions ranging from 1.85 to 2.10 Angstrom. In the wild-type (WT) FvD1.3-HEL complex, the hydroxyl groups of V(L)Tyr50, V(H)Tyr32, and V(H)Tyr101 each form at least one hydrogen bond with the lysozyme antigen. Thermodynamic parameters for antibody-antigen association have been measured using isothermal titration calorimetry, giving equilibrium binding constants K-b (M(-1)) of 2.6 x 10(7) (V(L)Y50S), 7.0 x 10(7) (V(H)Y32A), and 4.0 x 10(6) (V(H)Y101F). For the WT complex, K-b is 2.7 x 10(8) M(-1); thus, the affinities of the mutant Fv fragments for HEL are 10-, 4-, and 70-fold lower than that of the original antibody, respectively. In all three cases entropy compensation results in an affinity loss that would otherwise be larger. Comparison of the three mutant crystal structures with the WT structure demonstrates that the removal of direct antigen-antibody hydrogen bonds results in minimal shifts in the positions of the remaining protein atoms. These observations show that this complex is considerably tolerant, both structurally and thermodynamically, to the truncation of antibody side chains that form hydrogen bonds with the antigen. Alterations in interface solvent structure for two of the mutant complexes (V(L)Y50S and V(H)Y32A) appear to compensate for the unfavorable enthalpy changes when protein-protein interactions are removed. These changes in solvent structure, along with the increased mobility of side chains near the mutation site, probably contribute to the observed entropy compensation. For the V(H)Y101F complex, the nature of the large entropy compensation is not evident from a structural comparison of the WT and mutant complexes. Differences in the local structure and dynamics of the uncomplexed Fv molecules may account for the entropic discrepancy in this case. C1 UNIV MARYLAND,CTR ADV RES BIOTECHNOL,INST BIOTECHNOL,ROCKVILLE,MD 20850. NATL INST STAND & TECHNOL,ROCKVILLE,MD 20850. UNIV BUENOS AIRES,FAC FARM & BIOQUIM,CONICET,CATEDRA INMUNOL,RA-1113 BUENOS AIRES,DF,ARGENTINA. US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. OI Malchiodi, Emilio/0000-0001-7501-3330 FU NIGMS NIH HHS [GM52801] NR 53 TC 40 Z9 40 U1 3 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 3 PY 1996 VL 35 IS 48 BP 15494 EP 15503 DI 10.1021/bi961709e PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VW439 UT WOS:A1996VW43900045 PM 8952503 ER PT J AU Calvert, RJ Buzard, GS Anisimov, VN Rice, JM AF Calvert, RJ Buzard, GS Anisimov, VN Rice, JM TI K-ras codon 12 and 61 point mutations in bromodeoxyuridine- and N-nitrosomethylurea-induced rat renal mesenchymal tumors SO CANCER LETTERS LA English DT Article DE K-ras; bromodeoxyuridine; N-nitrosomethylurea; renal mesenchymal tumors; polymerase chain reaction ID MAMMARY-GLANDS; ONCOGENES; ACTIVATION; CELLS; GENE; CARCINOGENESIS; MUTAGENESIS; METHYLUREA AB The mutagenic thymidine analog bromodeoxyuridine (BrdUrd) may incorrectly incorporate opposite deoxyguanine in DNA, then pair with deoxyadenosine during subsequent replication. It appears to preferentially target the 3'-G of 5'-NGGN-3' sequences in mammalian cells in culture to induce G --> A transitions. Ras genes should therefore be vulnerable to activation by mutation at glycine codons 12 (GGT) and/or 13 (GGC) by misincorporation of BrdUrd. There is limited evidence that BrdUrd may be carcinogenic or co-carcinogenic in rats: three renal mesenchymal tumors, a tumor known to be associated with activating mutations in the c-K-ras-2 oncogene, were reported in 87 rats treated with BrdUrd alone, while N-nitrosomethylurea (NMU) alone or MMU + BrdUrd resulted in incidences of 12/52 and 26/76, respectively, against a zero incidence in untreated rats. We analyzed renal mesenchymal tumors from rats treated with BrdUrd for mutations in K-ras exons 1 and 2 and compared the prevalence and spectrum of mutations with those found in comparable tumors induced with NMU. DNAs from 22 paraffin-embedded renal mesenchymal tumors from rats treated 12-15 months earlier with BrdUrd (three specimens) or NMU (11 specimens) or both agents sequentially (eight specimens) were amplified by PCR. The base sequence of codons 12-13 and 59-63 of K-ras was determined by the dideoxynucleotide method. Sequencing results were confirmed by allele-specific oligonucleotide hybridization. Two of three tumors that appeared in rats given BrdUrd alone contained both a codon 12 GGT --> GAT transition and a codon 61 CAA --> CTA transversion. One tumor induced by NMU alone also showed a codon 12 GGT --> GAT mutation, while only wild type sequence could be demonstrated in the codon 12-13 region in the remaining ten such tumors. Three NMU-induced tumors also showed codon 61 CAA --> CTA mutations, while the remaining tumors had wild type sequence. While the GGT --> GAT transitions identified in tumors from BrdUrd-treated rats are consistent with BrdUrd mutagenesis by misincorporation, the co-occurrence of CAA --> CTA transversions, the overall low prevalence of mutations, and the lack of any difference in mutation spectrum between tumors induced by NMU and those that occurred in BrdUrd-treated rats suggests that in both groups the mutations that did occur did not result from a direct effect of either agent. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NN PETROV ONCOL RES INST,ST PETERSBURG,RUSSIA. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RP Calvert, RJ (reprint author), US FDA,OFF SPECIAL NUTRIT,MOD-1,HFS-452,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 22 TC 4 Z9 4 U1 2 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 DEC 3 PY 1996 VL 109 IS 1-2 BP 1 EP 7 DI 10.1016/S0304-3835(96)04350-9 PG 7 WC Oncology SC Oncology GA VZ698 UT WOS:A1996VZ69800001 PM 9020896 ER PT J AU Lauermann, V Peden, K Boeke, JD AF Lauermann, V Peden, K Boeke, JD TI Alternative tRNA primers for HIV SO AIDS LA English DT Letter ID IMMUNODEFICIENCY-VIRUS TYPE-1; TRANSFER-RNA; NUCLEOTIDE-SEQUENCE; RHESUS-MONKEYS; BINDING-SITE; AIDS VIRUS; RETROTRANSPOSITION; DEFECT; TY1 C1 US FDA,CTR BIOL EVALUAT & RES,LAB RETROVIRUS RES,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21205. RP Lauermann, V (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS BASIC RES PROGRAM,FREDERICK,MD 21702, USA. NR 19 TC 2 Z9 2 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD DEC PY 1996 VL 10 IS 14 BP 1738 EP 1740 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA VY172 UT WOS:A1996VY17200021 PM 8970697 ER PT J AU Soriano, V Mas, A Heredia, A Vallejo, A Hewlett, I Epstein, J GonzalezLahoz, J AF Soriano, V Mas, A Heredia, A Vallejo, A Hewlett, I Epstein, J GonzalezLahoz, J TI Long-term zidovudine responders: Is there still rationale for HIV monotherapy? SO AIDS LA English DT Letter C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20014. RP Soriano, V (reprint author), INST SALUD CARLOS III,INFECT DIS SERV,MADRID,SPAIN. RI Vallejo, Alejandro/I-5881-2015; Mas, Antonio/F-2505-2011 OI Vallejo, Alejandro/0000-0001-5360-878X; Mas, Antonio/0000-0003-2563-570X NR 4 TC 2 Z9 2 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD DEC PY 1996 VL 10 IS 14 BP 1741 EP 1741 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA VY172 UT WOS:A1996VY17200022 PM 8970698 ER PT J AU Levy, AS Teisl, MF Derby, BM AF Levy, AS Teisl, MF Derby, BM TI Health-chain information and consumer awareness of diet-disease relationships. SO AMERICAN JOURNAL OF AGRICULTURAL ECONOMICS LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER AGRICULTURAL ECONOMICS ASSOC PI AMES PA 1110 BUCKEYE AVE, AMES, IA 50010-8063 SN 0002-9092 J9 AM J AGR ECON JI Am. J. Agr. Econ. PD DEC PY 1996 VL 78 IS 5 BP 1391 EP 1391 PG 1 WC Agricultural Economics & Policy; Economics SC Agriculture; Business & Economics GA WZ984 UT WOS:A1996WZ98400139 ER PT J AU Teisl, MF Levy, AS AF Teisl, MF Levy, AS TI Valuing nutrition information results from a willingness-to-pay experiment. SO AMERICAN JOURNAL OF AGRICULTURAL ECONOMICS LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER AGRICULTURAL ECONOMICS ASSOC PI AMES PA 1110 BUCKEYE AVE, AMES, IA 50010-8063 SN 0002-9092 J9 AM J AGR ECON JI Am. J. Agr. Econ. PD DEC PY 1996 VL 78 IS 5 BP 1391 EP 1391 PG 1 WC Agricultural Economics & Policy; Economics SC Agriculture; Business & Economics GA WZ984 UT WOS:A1996WZ98400140 ER PT J AU Selvam, MP Buck, SM Blay, RA Mayner, RE Mied, PA Epstein, JS AF Selvam, MP Buck, SM Blay, RA Mayner, RE Mied, PA Epstein, JS TI Inhibition of HIV replication by immunoliposomal antisense oligonucleotide SO ANTIVIRAL RESEARCH LA English DT Article DE phosphorothioate; rev; immunoliposome; polymerase chain reaction; antisense; human immunodeficiency virus ID IMMUNODEFICIENCY-VIRUS TYPE-1; CELLS; OLIGODEOXYNUCLEOTIDE; LIPOSOMES; INFECTIVITY; MECHANISMS; RECEPTOR; ANALOGS; REV AB The sequence-specific suppression of HIV-1 replication using CD4 monoclonal-antibody-targeted liposomes, containing Rev antisense phosphorothioate oligonucleotides is described. Liposomes were prepared by encapsulating the 20-mer antisense DNA sequence of the rev HIV-I regulatory gene, in the form of a phosphorothioate oligonucleotide. Specific targeting was accomplished by conjugating anti-CD4 mouse monoclonal antibody to the surface of the liposomes. HIV-l-infected H9 cells as well as peripheral blood T-lymphocytes were incubated with the immunoliposomes of antisense found to have potential antiviral effect. HIV-1 replication was reduced by 85% in antisense immunoliposome-treated H9 cells and peripheral blood lymphocytes, whereas the inhibition of HIV-I replication was not observed using either empty immunoliposomes or immunoliposomes containing scrambled Rev phosphorothioate oligonucleotide sequences. The antiviral activity of both the free and the encapsulated oligonucleotides were assessed by p24, reverse transcriptase (RT) assays and polymerase chain reaction (PCR) analysis. Liposome preparations demonstrated minimal toxicity in H9 as well as in peripheral blood lymphocyte cell culture experiments. These in vitro culture results demonstrate the potential efficacy of immunoliposomes to inhibit HIV replication. RP Selvam, MP (reprint author), US FDA,CTR BIOL EVALUAT & RES,HFM-321,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 23 TC 22 Z9 22 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 DEC PY 1996 VL 33 IS 1 BP 11 EP 20 DI 10.1016/S0166-3542(96)00993-X PG 10 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA VV545 UT WOS:A1996VV54500002 PM 8955849 ER PT J AU Higley, JD Mehlman, PT Poland, RE Taub, DM Vickers, J Suomi, SJ Linnoila, M AF Higley, JD Mehlman, PT Poland, RE Taub, DM Vickers, J Suomi, SJ Linnoila, M TI CSF testosterone and 5-HIAA correlate with different types of aggressive behaviors SO BIOLOGICAL PSYCHIATRY LA English DT Article DE nonhuman primate; aggression; serotonin; impulsivity; cerebrospinal fluid testosterone ID CEREBROSPINAL-FLUID MONOAMINE; 5-HYDROXYINDOLEACETIC ACID; PERSONALITY DIMENSIONS; AMINE METABOLITES; PLASMA TESTOSTERONE; HOMOVANILLIC-ACID; VIOLENT OFFENDERS; IMPULSE CONTROL; FIRE SETTERS; NEUROENDOCRINE FINDINGS AB We studied the potential roles of testosterone and serotonin in various forms of aggressive and violent behaviors by measuring each biochemical and behavior in free-ranging adolescent male nonhuman primates. Our results showed that (1) CSF free testosterone concentrations were positively correlated with overall aggressiveness, but not with measures of impulsivity. (2) CSF 5-HIAA concentrations were negatively correlated with impulsive behavior, and severe, unrestrained aggression, but not with overall rates of aggression, High rates of impulsive behavior were positively correlated with severe, unrestrained aggression, but not overall rates of aggression. (3) Dimensional analyses showed that while subjects with low CSF 5-HIAA exhibited high rates of aggression, high CSF testosterone further augmented rates and intensity of aggression in subjects with low CSF 5-HIAA. We conclude that high CSF free testosterone concentrations are associated with competitive aggression, while low CSF 5-HIAA concentrations are associated with severe aggression which results from impaired impulse control, and perseverance. (C) 1996 Society of Biological Psychiatry C1 NIAAA, CLIN STUDIES LAB, DICBR, BETHESDA, MD 20892 USA. LAB ANIM BREEDERS & SERV, YEMASSEE, SC USA. HARBOR UCLA MED CTR, DIV BIOL PSYCHIAT, TORRANCE, CA 90509 USA. US FDA, WASHINGTON, DC 20204 USA. RP Higley, JD (reprint author), NICHHD, COMPARAT ETHOL LAB,NIH,ANIM CTR,BLDG 112, POB 529, POOLESVILLE, MD 20837 USA. NR 67 TC 219 Z9 221 U1 1 U2 25 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 1 PY 1996 VL 40 IS 11 BP 1067 EP 1082 DI 10.1016/S0006-3223(95)00675-3 PG 16 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VT527 UT WOS:A1996VT52700001 PM 8931909 ER PT J AU Nissen, E Konig, P Feinstone, SM Pauli, G AF Nissen, E Konig, P Feinstone, SM Pauli, G TI Inactivation of hepatitis A and other enteroviruses during heat treatment (pasteurization) SO BIOLOGICALS LA English DT Article C1 US FDA,PUBL HLTH SERV,ROCKVILLE,MD 20857. RP Nissen, E (reprint author), ROBERT KOCH INST,NORDUFER 20,D-13353 BERLIN,GERMANY. NR 5 TC 17 Z9 19 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD DEC PY 1996 VL 24 IS 4 BP 339 EP 341 DI 10.1006/biol.1996.0048 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA WM837 UT WOS:A1996WM83700011 PM 9088550 ER PT J AU MireSluis, AR Gerrard, T Das, RG Padilla, A Thorpe, R AF MireSluis, AR Gerrard, T Das, RG Padilla, A Thorpe, R TI Biological assays: Their role in the development and quality control of recombinant biological medicinal products SO BIOLOGICALS LA English DT Article ID INTERNATIONAL STANDARD; GROWTH-FACTOR; MONOCLONAL-ANTIBODIES; CLINICAL-APPLICATIONS; THERAPY; CYTOKINES; INTERLEUKIN-6; REPLACEMENT; RECEPTOR; CANCERS C1 NATL INST BIOL STAND & CONTROLS, DIV INFORMAT, POTTERS BAR EN6 3QG, HERTS, ENGLAND. US FDA, CTR BIOL EVALUAT & RES, DIV CYTOKINE BIOL, BETHESDA, MD 20892 USA. WHO, BIOL UNIT, CH-1211 GENEVA 27, SWITZERLAND. RP MireSluis, AR (reprint author), NATL INST BIOL STAND & CONTROLS, DIV IMMUNOBIOL, BLANCHE LANE S MIMMS, POTTERS BAR EN6 3QG, HERTS, ENGLAND. RI Thorpe, Robin/E-6853-2013 NR 75 TC 14 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD DEC PY 1996 VL 24 IS 4 BP 351 EP 362 DI 10.1006/biol.1996.0050 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA WM837 UT WOS:A1996WM83700013 PM 9088552 ER PT J AU Jansen, DL Meade, BD AF Jansen, DL Meade, BD TI Preparation and standardization of US standard pertussis vaccine, lot no 11 SO BIOLOGICALS LA English DT Article AB The Center for Biologics Evaluation and Research within the U.S. Food and Drug Administration has prepared a new U.S. Standard Pertussis Vaccine. Whole cell pertussis vaccine concentrate was diluted in 5% (w/v) lactose and lyophilized. The preparation was tested for toxicity, sterility, heterogeneity and residual moisture. Based on data from an international collaborative study involving 11 laboratories, the potency was estimated in relation to the U.S. Master Standard Pertussis Vaccine, Lot 4 and the international Standard for Pertussis Vaccine, Lot 2. The potency of the preparation was defined to be 90 units per ampoule. When reconstituted and stored according to instructions, no significant change in potency was observed in the 14 days following reconstitution. This material was shown to be suitable for a pertussis vaccine standard and accordingly it was designated as U.S. Standad Pertussis Vaccine, Lot 11 on March 22, 1994. (C) 1996 The International Association of Biological Standardization. RP Jansen, DL (reprint author), US FDA,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 12 TC 5 Z9 5 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 DEC PY 1996 VL 24 IS 4 BP 363 EP 370 DI 10.1006/biol.1996.0051 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA WM837 UT WOS:A1996WM83700014 PM 9088553 ER PT J AU Fishman, RB Branham, WS Streck, RD Sheehan, DM AF Fishman, RB Branham, WS Streck, RD Sheehan, DM TI Ontogeny of estrogen receptor messenger ribonucleic acid expression in the postnatal rat uterus SO BIOLOGY OF REPRODUCTION LA English DT Article ID GROWTH-FACTOR; REPRODUCTIVE TRACTS; UTERINE; MOUSE; DIETHYLSTILBESTROL; FETAL; RNAS; SENSITIVITY; EPITHELIUM; ESTRADIOL AB During the first 2 wk of postnatal life, the rodent uterus undergoes a period of marked growth and differentiation. To further examine the role of the estrogen receptor (ER) in the mediation of uterine development, we analyzed the ontogeny of ER mRNA expression in the postnatal rat uterus using in situ hybridization. ER mRNA was present in the uterine stroma on the day of birth and progressively increased in abundance during the first 2 wk of postnatal life. In contrast, ER mRNA was not detectable in the luminal epithelium at birth and did not become abundant in this region until postnatal day (P) 7. ER mRNA abundance increased in the luminal epithelium and in the invaginating and fully formed glandular epithelium during the second week of life. At P21 ER mRNA was more abundant in the glandular epithelium than in any other uterine cell type. These results are consistent with, and extend the findings of, previous studies using uterine homogenate binding assays and immunohistochemistry to define ER ontogeny in rodents. Delineation of the temporal and cell-type specific pattern of ER mRNA ontogeny in the postnatal rat uterus furthers our understanding of the molecular basis of both endogenous and exogenous estrogen effects on uterine growth and development. C1 UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM,LITTLE ROCK,AR 72205. RP Fishman, RB (reprint author), US FDA,NATL CTR TOXICOL RES,DEPT HLTH & HUMAN SERV,DIV REPROD & DEV TOXICOL,HFT-130,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 39 TC 20 Z9 20 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD DEC PY 1996 VL 55 IS 6 BP 1221 EP 1230 DI 10.1095/biolreprod55.6.1221 PG 10 WC Reproductive Biology SC Reproductive Biology GA VU778 UT WOS:A1996VU77800005 PM 8949877 ER PT J AU Alarcon, GS Tilley, B Cooper, S Clegg, DO Trentham, DE Pillemer, SR Neuner, R Fowler, S AF Alarcon, GS Tilley, B Cooper, S Clegg, DO Trentham, DE Pillemer, SR Neuner, R Fowler, S TI Another look at minocycline SO BULLETIN ON THE RHEUMATIC DISEASES LA English DT Letter ID PLACEBO-CONTROLLED TRIAL; RHEUMATOID-ARTHRITIS; DOUBLE-BLIND; THERAPY C1 UNIV VERMONT,COLL MED,BURLINGTON,VT. UNIV UTAH,MED CTR,SALT LAKE CITY,UT. BETH ISRAEL HOSP,BOSTON,MA 02215. NIH,BETHESDA,MD 20892. US FDA,ROCKVILLE,MD 20857. HENRY FORD HLTH CTR,MIRA,INVESTIGATORS GRP,DETROIT,MI. RP Alarcon, GS (reprint author), UNIV ALABAMA,BIRMINGHAM,AL, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU ARTHRITIS FOUNDATION PI ATLANTA PA 1314 SPRING STREET NW, ATLANTA, GA 30309 SN 0007-5248 J9 B RHEUM DIS JI Bull. Rheum. Dis. PD DEC PY 1996 VL 45 IS 8 BP 6 EP 7 PG 2 WC Rheumatology SC Rheumatology GA WC708 UT WOS:A1996WC70800002 PM 8997812 ER PT J AU Munoz, EF Diwan, BA Calvert, RJ Weghorst, CM Anderson, J Rice, JM Buzard, GS AF Munoz, EF Diwan, BA Calvert, RJ Weghorst, CM Anderson, J Rice, JM Buzard, GS TI Transplacental mutagenicity of cisplatin: H-ras codon 12 and 13 mutations in skin tumors of SENCAR mice SO CARCINOGENESIS LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; MAJOR DNA ADDUCT; DRUG CISPLATIN; COLD SSCP; GENE; CARCINOGENESIS; AMPLIFICATION; CHEMOTHERAPY; MUTAGENESIS; PCR AB Cisplatin is an anticancer agent sometimes used in pregnant women, It is also a potent initiator of skin tumors in mice when administered transplacentally, For characterization of the transplacental mutagenicity of cisplatin, tumors initiated in fetal skin by cisplatin or 7,12-dimethylbenz-[n]anthracene (DMBA) and promoted by postnatal 12-O-tetradecanoyl-phorbol-13-acetate (TPA) were analyzed for H-ms mutations by 'cold' single-strand conformation polymorphism analysis and direct sequencing, The expected high incidence of exon II codon 61 mutations (20/20) was found in transplacental DMBA-initiated tumors, with no exon I change, By contrast, 6/10 cisplatin tumors had seven mutations in codons 12 or 13 of exon I, all at GpG dinucleotides, Four of these were unique codon 13 GGC --> GTC changes, significantly different from the DMBA group and from historical TPA-only controls, The activation of codons 12 and 13 by cisplatin is in accord with the known in vitro preference of cisplatin for GpG sites for intrastrand cross-linking adduct formation, These results provide the first evidence that cisplatin can act transplacentally to cause specific mutations in fetal skin that are not seen in skin tumors caused by treatment of adult skin with this agent, This is evidence for unique molecular fetal carcinogenic pathways and underscores concern about human fetal risk due to maternal cisplatin treatment. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. US FDA,OFF SPECIAL NUTRIT,MOD LAB 1,CLIN RES & REVIEW STAFF,LAUREL,MD 20708. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 32 TC 15 Z9 15 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 1996 VL 17 IS 12 BP 2741 EP 2745 DI 10.1093/carcin/17.12.2741 PG 5 WC Oncology SC Oncology GA WC820 UT WOS:A1996WC82000029 PM 9006114 ER PT J AU Berkower, I AF Berkower, I TI The promise and pitfalls of monoclonal antibody therapeutics SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Article ID CARDIAC ALLOGRAFT SURVIVAL; GRAM-NEGATIVE SEPSIS; T-CELL LEUKEMIA; INTERLEUKIN-2 RECEPTOR; COLORECTAL-CANCER; ACUTE REJECTION; CLINICAL-TRIAL; LUNG-CARCINOMA; DOUBLE-BLIND; INVIVO AB Recent experience has helped io clarify the best ways to use monoclonal antibodies to solve clinical problems. For example, imaging based on tumor antigens, rather than tumor size, will permit early detection of cancer and accurate staging. Blocking receptor-ligand interactions may permit therapeutic intervention in cell growth or function but activity may depend on the choice of an antiligand or antireceptor strategy. Humanized antibodies will achieve greater intensity and duration of therapy, while allowing repeat administration in chronic diseases. (C) Current Biology Ltd ISSN 0958-1669.. RP Berkower, I (reprint author), US FDA,CTR BIOL,OFF VACCINE RES,DIV ALLERGEN PROD & PARASITOL,LAB IMMUNOREGULAT,BLDG 29,BETHESDA,MD 20892, USA. NR 50 TC 22 Z9 23 U1 0 U2 0 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 DEC PY 1996 VL 7 IS 6 BP 622 EP 628 DI 10.1016/S0958-1669(96)80073-5 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA VU443 UT WOS:A1996VU44300007 PM 8939645 ER PT J AU Schwan, WR Kopecko, DJ AF Schwan, WR Kopecko, DJ TI Transcriptional downregulation of a mouse Golgi mannosidase gene following Salmonella typhimurium uptake into murine macrophages SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE differential PCR; Salmonella typhimurium; alpha-mannosidase; differential transcription ID SIGNAL-TRANSDUCTION; DIFFERENTIAL TRANSCRIPTION; INHIBITORS; CELL; RNA AB Uptake of Salmonella typhimurium into murine macrophage cells caused transcriptional downregulation of a mRNA population in eukaryotic cells after 2 h of infection. The cloned cDNA that was identified showed extensive homology with a murine alpha 1,2-mannosidase gene involved in N-oligosaccharide processing. These findings suggest a disruption of eukaryotic protein processing after phagocytosis of S. typhimurium by the murine macrophage cells. RP Schwan, WR (reprint author), US FDA,CTR BIOL EVALUAT & RES,LAB ENTER & SEXUALLY TRANSMITTED DIS,BETHESDA,MD 20892, USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD DEC 1 PY 1996 VL 145 IS 2 BP 215 EP 219 PG 5 WC Microbiology SC Microbiology GA VV670 UT WOS:A1996VV67000012 PM 8961559 ER PT J AU Zhang, DL Yang, YF Castlebury, LA Cerniglia, CE AF Zhang, DL Yang, YF Castlebury, LA Cerniglia, CE TI A method for the large scale isolation of high transformation efficiency fungal genomic DNA SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE Cunninghamella elegans; drug metabolism; fungal DNA isolation; genomic DNA library ID METABOLISM AB A procedure for isolation of genomic DNA from the zygomycete Cunninghamella elegans and other filamentous fungi and yeasts is reported. This procedure involves disruption of cells by grinding using dry ice, removal of polysaccharides using cetyltrimethylammonium bromide and by phenol extractions, and precipitation of DNA with isopropanol at room temperature. The isolation method produced large scare (approximate 1 mg DNA/5 g wet cells) and highly purified high molecular mass DNA. Sau3AI partially digested DNA showed high transformation efficiency (> 10(6)/100 ng DNA) when ligated to ZAP-express lambda vector. C1 US FDA, NATL CTR TOXICOL RES, DIV MICROBIOL, JEFFERSON, AR 72079 USA. NR 15 TC 46 Z9 51 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0378-1097 EI 1574-6968 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD DEC 1 PY 1996 VL 145 IS 2 BP 261 EP 265 DI 10.1111/j.1574-6968.1996.tb08587.x PG 5 WC Microbiology SC Microbiology GA VV670 UT WOS:A1996VV67000019 PM 8961565 ER PT J AU Lewis, CJ Randell, A Scarbrough, FE AF Lewis, CJ Randell, A Scarbrough, FE TI Nutrition labelling of foods: Comparisons between US regulations and Codex guidelines SO FOOD CONTROL LA English DT Article DE food labelling; harmonization; Codex Alimentarius AB Nutrition labelling of food impacts not only on consumers and the food industry, but on international trade as as well. When requirements for food label information are similar among countries, trade is facilitated Comparisons between recent nutrition labelling regulations issued by the USA and the international guidelines formulated by Codex Alimentarius identify not only challenges to international harmonization that require focused efforts, bur also opportunities for increasing international agreement on nutrition labelling. Factors to be considered are the continued benefits of a generalized Coder guideline as well as technical issues including analytical methods, nutrients to be declared, bases for declaration, and reference values. Published by Elsevier Science Ltd. C1 FAO,DIV FOODS & NUTR,FOOD QUAL & STANDARDS SERV,ROME,ITALY. RP Lewis, CJ (reprint author), US FDA,OFF FOOD LABELING,WASHINGTON,DC 20204, USA. NR 21 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0956-7135 J9 FOOD CONTROL JI Food Control PD DEC PY 1996 VL 7 IS 6 BP 285 EP 293 DI 10.1016/S0956-7135(96)00027-8 PG 9 WC Food Science & Technology SC Food Science & Technology GA WC723 UT WOS:A1996WC72300003 ER PT J AU Prival, MJ Cebula, TA AF Prival, MJ Cebula, TA TI Adaptive mutation and slow-growing revertants of an Escherichia coli lacZ amber mutant SO GENETICS LA English DT Article ID EPISOMAL FRAMESHIFT MUTATION; SALMONELLA-TYPHIMURIUM; REVERSION; CONJUGATION; DELETIONS; SELECTION; ORIGIN; OCCUR AB We have studied revertants, selected on lactose minimal agar medium, of the Escherichia coli lacZ(am) strain that was first used by Cairns and his colleagues to demonstrate the phenomenon of ''adaptive mutation.'' We have found, by performing appropriate reconstruction studies, that most of the late-arising Lac(+) revertants of this lac amber strain (appearing as colonies in 3-5 days) are slow-growing ochre suppressor mutants that probably existed in the culture prior to plating and cannot, therefore, be classified as ''adaptive.'' The appearance of a small number of fast-growing, late-arising Lac(+) revertants may result from residual cell growth and turnover or from phenomena related to the fact that the lacZ(am) mutation in strain SM195 is carried on an F' plasmid. Thus, the appearance of late-arising revertants in this lacZ(am) system does not provide convincing evidence that selective conditions specifically increase the rate of occurrence of favorable mutations. C1 US FDA,MOL BIOL BRANCH,WASHINGTON,DC 20204. RP Prival, MJ (reprint author), US FDA,GENET TOXICOL BRANCH HFS236,200 C ST SW,WASHINGTON,DC 20204, USA. NR 31 TC 20 Z9 21 U1 1 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD DEC PY 1996 VL 144 IS 4 BP 1337 EP 1341 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA VY931 UT WOS:A1996VY93100002 PM 8978023 ER PT J AU Wynant, R AF Wynant, R TI Introduction to the issue on lasers in medicine SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Editorial Material RP Wynant, R (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,ELECTROOPT BRANCH,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 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD DEC PY 1996 VL 2 IS 4 BP 789 EP 789 PG 1 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA XD616 UT WOS:A1996XD61600001 ER PT J AU Gannot, I Inberg, A Oksman, M Waynant, R Croitoru, N AF Gannot, I Inberg, A Oksman, M Waynant, R Croitoru, N TI Current status of flexible waveguides for IR laser radiation transmission SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article ID GLASS WAVE-GUIDES; OPTICAL FIBERS; ER-YAG; HOLLOW; DELIVERY; BAND AB Minimal invasive surgery (MIS) is the preferred method for performing medical operations today due it's lower cost, fastest healing, and minimal post-operative pain and discomfort to the treated patients, It is rapidly expanding with the development and miniaturization of two-dimensional (2-D) and three-dimensional (3-D) endoscopic imaging systems. Laser surgery has also proved itself to be a preferred tool of operation over standard tools in a lot of the cases, Development of a reliable flexible fiber or waveguide will enable surgeons to brine the laser beam transendoscopically within body cavities. It will combine the endoscopy technique with the advantageous laser interaction with tissue to create a powerful surgical tool which will be the ultimate choice of operating procedure, A number of research groups have suggested flexible waveguides for the mid-IR region between 2.5 and 11 mu m, which contains very important and useful laser wavelengths and it is not covered by the silica fibers, The gold goals for the development of such delivery devices are summarized. The different suggested solutions are broadly described and thoroughly analyzed for their performances and prospective. C1 TEL AVIV UNIV,FAC ENGN,DEPT PHYS ELECT,IL-69978 TEL AVIV,ISRAEL. RP Gannot, I (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,ELECTROOPT BRANCH,ROCKVILLE,MD 20852, USA. NR 24 TC 13 Z9 13 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 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD DEC PY 1996 VL 2 IS 4 BP 880 EP 889 DI 10.1109/2944.577310 PG 10 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA XD616 UT WOS:A1996XD61600011 ER PT J AU Gandjbakhche, AH Gannot, I AF Gandjbakhche, AH Gannot, I TI Quantitative fluorescent imaging of specific markers of diseased tissue SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article ID OPTICAL-PROPERTIES; TURBID MEDIA; MODEL AB We have developed a random walk theory to relate observable fluorescent intensities on tissue surfaces to the presence of several embedded fluorescent masses. This work is an extension of analysis previously carried out for an isolated fluorescent site, Results depend on the optical properties of tissue at the excitation and emission wavelengths, as well as on the location of fluorescent targets and positions of source and detector. Measurements on tissue-like phantoms were performed to test the theory, Analysis of fluorescent signals, performed in accordance with the theory, yields accurate information about the location of the targets. Prospects of a noninvasive quantitative fluorescent imaging system, to diagnose and monitor salivary glands disease, is presented. C1 US FDA, CTR DEVICES & RADIOL HLTH, ELECTROOPT BRANCH, ROCKVILLE, MD 20857 USA. RP Gandjbakhche, AH (reprint author), NICHHD, PHYS SCI LAB, DIV COMP RES & TECHNOL, NIH, BETHESDA, MD 20892 USA. NR 27 TC 11 Z9 11 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD DEC PY 1996 VL 2 IS 4 BP 914 EP 921 DI 10.1109/2944.577316 PG 8 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA XD616 UT WOS:A1996XD61600016 ER PT J AU vandeVerg, LL Hartman, AB Bhattacharjee, AK Tall, BD Yuan, L Sasala, K Hadfield, TL Zollinger, WD Hoover, DL Warren, RL AF vandeVerg, LL Hartman, AB Bhattacharjee, AK Tall, BD Yuan, L Sasala, K Hadfield, TL Zollinger, WD Hoover, DL Warren, RL TI Outer membrane protein of Neisseria meningitidis as a mucosal adjuvant for lipopolysaccharide of Brucella melitensis in mouse and guinea pig intranasal immunization models SO INFECTION AND IMMUNITY LA English DT Article ID ABORTUS INFECTION; IMMUNE-RESPONSES; MICE; PROTECTION; VACCINE; COMPLEX; IMMUNOGENICITY; ANTIBODY; POLYSACCHARIDE; LYMPHOCYTES AB A mucosal vaccine against brucellosis consisting of the Iipopolysaccharide (LPS) of Brucella melitensis complexed with the outer membrane protein (GBOMP) of group B Neisseria meningitidis was tested in small-animal models of intranasal immunization, Mice given two doses of the vaccine developed high levels of immunoglobulin G (IgG) and IgA antibodies specific for B. melitensis LPS in lung lavages and specific IgG and IgA antibody-secreting cells in the lungs and spleen, Similarly, in guinea pigs immunized twice intranasally, IgG and IgA LPS-specific antibodies were detected in lung lavages, and specific antibody-secreting cells were isolated from the spleen and cervical nodes, In mice immunized with LPS only, pulmonary responses consisted mostly of IgM antibodies, while guinea pigs given LPS alone developed local antibody of all three isotypes, but at lower levels compared to animals given the complex vaccine, Both mice and guinea pigs also developed high levels of serum IgG and moderate levels of IgA as a result of intranasal immunization with the complex vaccine, The serum antibodies in both cases were found to cross-react with the LPS of B. abortus, which shares an immunogenic epitope with B. melitensis LPS. In mice given the complex vaccine, there was a prominent serum IgG1 response that was absent in the mice given LPS alone, In conclusion, the N. meningitidis GBOMP was an effective mucosal adjuvant for secretory IgA and IgG responses in the lungs of both mice and guinea pigs, The IgG1 subclass response in mice suggests that GBOMP may have favored a Th-5 type of response to the LPS. A vaccine capable of stimulating high levels of antibody at local sites has the potential to protect against brucellae, since these pathogens gain entry to the host via mucosal routes. C1 WALTER REED ARMY INST RES,DEPT ENTER INFECT,WASHINGTON,DC 20307. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. ARMED FORCES INST PATHOL,DEPT INFECT & PARASIT DIS,WASHINGTON,DC 20306. RP vandeVerg, LL (reprint author), WALTER REED ARMY INST RES,DEPT BACTERIAL DIS,WASHINGTON,DC 20307, USA. OI Tall, Ben/0000-0003-0399-3629 NR 28 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1996 VL 64 IS 12 BP 5263 EP 5268 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VU635 UT WOS:A1996VU63500054 PM 8945575 ER PT J AU Hauck, WW Chen, ML Hyslop, T Patnaik, R Schuirmann, D Williams, R AF Hauck, WW Chen, ML Hyslop, T Patnaik, R Schuirmann, D Williams, R TI Mean difference vs variability reduction: Tradeoffs in aggregate measures for individual bioequivalence SO INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE individual bioequivalence; intra-subject variability; subject-by-formulation interaction ID POPULATION AB Aggregate criteria for individual bioequivalence allow a tradeoff between difference in average bioavailability and reduction in within-subject variability. That is, a large difference in the average bioavailability between a test and reference formulation can be offset by a sufficient reduction in variability of the test formulation. This offset could allow the test formulation to pass many individual bioequivalence criteria. We have identified 4 possible approaches for dealing with this tradeoff issue: say ''No problem,'' since a reduction in variability is desirable; use disaggregate criteria; use general weighted forms of the individual bioequivalence criteria that weight the variance terms; and change the acceptable upper limits to reduce the impact of scaling to the reference formulation's within-subject variability. A dataset with a 14% increase in average bioavailability and a 48% reduction in within-subject standard deviation is used as an example of these issues. C1 US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. RP Hauck, WW (reprint author), THOMAS JEFFERSON UNIV,DIV CLIN PHARMACOL,BIOSTAT SECT,SHERIDAN BLDG 403,135 S 9TH ST,PHILADELPHIA,PA 19107, USA. FU PHS HHS [223-94-3001] NR 10 TC 28 Z9 31 U1 1 U2 1 PU DUSTRI-VERLAG DR KARL FEISTLE PI MUNCHEN-DEISENHOFEN PA BAHNHOFSTRABE 9 POSTFACH 49, W-8024 MUNCHEN-DEISENHOFEN, GERMANY SN 0946-1965 J9 INT J CLIN PHARM TH JI Int. J. Clin. Pharmacol. Ther. PD DEC PY 1996 VL 34 IS 12 BP 535 EP 541 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VX988 UT WOS:A1996VX98800003 PM 8996848 ER PT J AU Budillon, A Clair, T Hartman, N Strong, J Sobukawa, Y Miki, K Worby, A Murray, KJ ChoChung, YS AF Budillon, A Clair, T Hartman, N Strong, J Sobukawa, Y Miki, K Worby, A Murray, KJ ChoChung, YS TI Novel growth inhibitory effect of 8-Cl-cAMP is dependent on serum factors that modulate protein kinase A expression but not the hydrolysis of 8-Cl-cAMP SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE cAMP; protein kinase A; serum factors; phosphodiesterase ID HL-60 LEUKEMIA-CELLS; SELECTIVE CAMP ANALOGS; CHINESE-HAMSTER OVARY; CYCLIC-AMP ANALOGS; 8-CHLOROADENOSINE 3',5'-MONOPHOSPHATE; ADENOSINE METABOLITE; 8-CHLORO-CYCLIC AMP; DOWN-REGULATION; MOLT-4 CELLS; CANCER AB 8-Chloro-cyclic AMP (8-Cl-cAMP) exhibits growth inhibition in vitro and in vivo in a broad spectrum of cancer cell lines. We examined whether the hydrolyzed metabolite is involved in the effect of 8-Cl-cAMP. 8-Cl-cAMP (5 mu M, 3 days) exerted varying degrees (0-51%) of growth inhibition on the same cell line cultured in the medium containing different heat-inactivated serum. HPLC analysis neither detected 8-Cl-adenosine in the medium nor demonstrated any correlation between the decrease in 8-Cl-cAMP concentration in the medium and the degree of growth inhibition. The low K-m phosphodiesterase activity in the sera did not correlate with the varying degrees of growth inhibition. The cAMP-dependent protein kinase RI(alpha) subunit expression in the same cell line varied widely with the different serum supplements. 8-Cl-CAMP-, but not 8-Cl-adenosine-induced, growth inhibition correlated with the basal levels of RI(alpha) and specific downregulation of RI(alpha). 8-Cl-cAMP, but not 8-Cl-phenyl-thio-cAMP or N-6-benzyl-cAMP, inhibited cell growth in serum-free medium. These results show that 8-Cl-cAMP induces growth inhibition through down-regulation of protein kinase A type I in the absence of its hydrolysis. C1 NCI,CELLULAR BIOCHEM SECT,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. US FDA,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. TERUMO CO LTD,KANAGAWA,JAPAN. SMITH KLINE BEECHAM PHARMACEUT,WELWYN GARDEN CIT,HERTS,ENGLAND. OI Budillon, Alfredo/0000-0002-6330-6053 NR 26 TC 1 Z9 1 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD DEC PY 1996 VL 9 IS 6 BP 1113 EP 1120 PG 8 WC Oncology SC Oncology GA VU549 UT WOS:A1996VU54900004 PM 21541619 ER PT J AU Vallejo, A Ferrante, P Soriano, V Calabro, ML Mancuso, R Heredia, A Mannella, E Favero, A GarciaSaiz, A ChiecoBianchi, L GonzalezLahoz, J Hewlett, IK AF Vallejo, A Ferrante, P Soriano, V Calabro, ML Mancuso, R Heredia, A Mannella, E Favero, A GarciaSaiz, A ChiecoBianchi, L GonzalezLahoz, J Hewlett, IK TI Nucleotide sequence and restriction fragment-length polymorphism analysis of human T-Cell lymphotropic virus type II (HTLV-II) in southern Europe: Evidence for the HTLV-IIa and HTLV-IIb subtypes SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HTLV-II; sequencing; restriction fragment length polymorphism; subtyping; Spain; Italy; injecting drug users; blood donors ID DRUG-USERS; INDIAN POPULATIONS; CENTRAL-AFRICA; UNITED-STATES; INFECTION; IDENTIFICATION; CAMEROON; ISOLATE; COLOMBIA; VARIANT AB Human T-cell lymphotropic virus type II (HTLV-II) has been subtyped into two major groups, IIa and IIb, according to molecular studies involving env gene sequencing, Subsequently, this retrovirus was further subclassified by examining the long terminal repeat (LTR). the most divergent genomic region. Sequence analysis and restriction fragment-length polymorphism (RFLP) applied to the LTR region identified either four or five groups within the IIa subtype (depending on the restriction enzyme sets used) and six within the IIb subtype, In this study, we analyzed the LTR sequences of 29 samples obtained from HTLV-II-infected individuals living in Spain and Italy, which included 24 injecting drug users (IDUs), three blood donors, and two subjects at risk for HIV/HTLV infection. Sequence analysis and phylogenetic analysis of 720 base pairs of the LTR performed in 10 Spanish samples showed that all of these samples belonged to IIb subtype, with a divergence of 7.5% and 1.66% compared with MoT (IIa) and NRA/G12 (IIb) isolates, respectively, RFLP analysis demonstrated the presence of the IIb 4-subtype restriction pattern in 26 samples, a Ilb5-subtype pattern in one Italian IDU, and a IIa0-subtype pattern in two Italian samples (blood donors), according to W.M. Switzer's nomenclature, This is the first report of the presence of IIb5 in Southern Europe and IIa0 among Italian blood donors, RFLP correlated with nucleotide sequence and phylogenetic data obtained in this study, demonstrating the ability of the RFLP method to predict the phylogroup of HTLV-II-infected samples. C1 FDA,CBER,MOL VIROL LAB,ROCKVILLE,MD 20852. INST HLTH CARLOS III,MADRID,SPAIN. UNIV MILAN,INST MED MICROBIOL,MILAN,ITALY. UNIV PADUA,INST ONCOL,INTERUNIV CTR CANC RES,PADUA,ITALY. ITALIAN RED CROSS,CNTS,ROME,ITALY. DON C GNOCCHI FDN,IRCCS,MILAN,ITALY. RI Mancuso, Roberta/H-8986-2012; Vallejo, Alejandro/I-5881-2015; OI Mancuso, Roberta/0000-0002-4449-3623; Vallejo, Alejandro/0000-0001-5360-878X; Ferrante, Pasquale/0000-0001-7040-7293 NR 41 TC 20 Z9 20 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD DEC 1 PY 1996 VL 13 IS 4 BP 384 EP 391 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VV504 UT WOS:A1996VV50400013 PM 8948378 ER PT J AU MartinezLacaci, I Johnson, GR Salomon, DS Dickson, RB AF MartinezLacaci, I Johnson, GR Salomon, DS Dickson, RB TI Characterization of a novel amphiregulin-related molecule in 12-O-tetradecanoylphorbol-13-acetate-treated breast cancer cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; MAMMARY EPITHELIAL-CELLS; HEPARIN-BINDING DOMAIN; PROTEIN-KINASE-C; FACTOR-ALPHA; PHORBOL ESTER; HUMAN COLON; SURFACE; EXPRESSION; PRECURSOR AB Amphiregulin (AR) can be induced at the mRNA level by 17-beta-estradiol (E(2)) or the phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). This study compares the effects of TPA and E(2) on the regulation of processing of AR isoforms and on subcellular localization in human MCF-7 breast cancer cells. AR was localized in the nucleus of MCF-7 cells after E(2) treatment, whereas it was predominantly secreted after TPA treatment. AR isoforms of 28, 18, and 10 kDa and an additional species of approximately 55-60 kDa were detected in the cellular conditioned media after TPA stimulation. Expression of this unusual AR isoform was inhibited by protein kinase C (PKC) inhibitors such as bryostatin or H-7. The biochemical properties of this isoform are consistent with it being an N-linked glycosylated form of the AR precursor that contains unprocessed mannose residues. The size of this large isoform is reduced to approximately 40 kDa after treating the TPA-induced MCF-7 cells with tunicamycin or treating the conditioned media of such cells with N-glycosidase F or with endoglycosidase H. Moreover, this isoform is able to bind several lectins with specificity for mannose residues. The 55-60 kDa glycosylated AR isoform, like lower Mr AR isoforms, is able to bind to heparin and to stimulate the growth of MCF-10A cells by interacting with the EGF receptor. These data suggest that TPA activation of PKC may be involved in post-translational modifications of AR, such as glycosylation, and in alteration of its subcellular routing to predominantly a secretory pathway. (C) 1996 Wiley-Liss, Inc. C1 GEORGETOWN UNIV,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. GEORGETOWN UNIV,DEPT CELL BIOL,WASHINGTON,DC 20007. US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20892. NCI,TUMOR GROWTH FACTOR SECT,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892. NR 47 TC 11 Z9 11 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD DEC PY 1996 VL 169 IS 3 BP 497 EP 508 DI 10.1002/(SICI)1097-4652(199612)169:3<497::AID-JCP10>3.0.CO;2-3 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA VW030 UT WOS:A1996VW03000010 PM 8952699 ER PT J AU Sechler, JMG Lawler, A Hartley, JW Morse, HC McCarty, TC Swofford, R Rosenberg, AS AF Sechler, JMG Lawler, A Hartley, JW Morse, HC McCarty, TC Swofford, R Rosenberg, AS TI Induction of murine acquired immunodeficiency syndrome (MAIDS) in allophenic mice generated from strains susceptible and resistant to disease SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; CD4+ T-CELLS; LEUKEMIA VIRUSES; DEFECTIVE VIRUS; EXPRESSION; INFECTION; AIDS; IMMUNIZATION; ANTIBODY; SUBSET AB To examine whether a retroviral disease can be controlled in animals in which cells from a resistant strain coexist in a state of immunological tolerance with cells from a susceptible strain, allophenic mice were constructed and infected with LP-BM5 murine leukemia viruses which induce a fatal disorder, termed murine acquired immunodeficiency syndrome (MAIDS), characterized by lymphoproliferation and immunodeficiency in susceptible inbred strains of mice. We found that in two different strain combinations, resistance to MAIDS was contingent on the presence in individual animals of >50% of lymphocytes of resistant strain origin and correlated with reduction or elimination of retrovirus. In contrast, animals harboring substantial, but less than predominant, numbers of genetically resistant lymphocytes developed disease and died within the same time frame as susceptible control mice with uncontained proliferation of retrovirus. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT OBSTET & GYNECOL,BALTIMORE,MD 21287. NIAID,IMMUNOPATHOL LAB,NIH,BETHESDA,MD 20892. NIAID,MOL STRUCT LAB,FLOW CYMETRY SECT,NIH,BETHESDA,MD 20892. OI Morse, Herbert/0000-0002-9331-3705 NR 32 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1996 VL 184 IS 6 BP 2101 EP 2108 DI 10.1084/jem.184.6.2101 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VZ413 UT WOS:A1996VZ41300004 PM 9005249 ER PT J AU Shiu, GK AF Shiu, GK TI Pharmaceutical product quality research: An overview for solid oral dosage forms SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Review DE product quality; solid oral dosage forms; in vitro in vivo relationship ID INVITRO; RELEASE; BIOAVAILABILITY; DISSOLUTION AB Product quality, like safety and efficacy, is a prerequisite for manufacturing approval of all pharmaceutical products, This requirement must not be compromised even after the product has been approved for marketing, Development of in vitro testing methods that are predictive for product in vivo performance is the most challenging goal in product quality research, In recent years, our Laboratory has been involved in this area of research for a variety of pharmaceutical products including oral solid dosage forms, metered dose inhalers, suspension products, transdermal patches and topical products including creams, ointments, and suppositories, The author intends to share some of his research experience in addressing product quality issues for the above mentioned dosage forms in a series of review and research articles, As the first in this series, an overview of the quality issue for oral solid dosage forms is presented. C1 US FDA,PROD QUAL RES LABS,OFF PHARMACEUT SCI,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20850. NR 17 TC 1 Z9 1 U1 0 U2 3 PU NATL LABORATORIES FOODS DRUGS PI NANKANG, TAIPEI PA DEPT HEALTH, EXECUTIVE YUAN, 161-2 KUEN YANG ST DR. ERICK T. SUEN, DEPUTY DIR., NANKANG, TAIPEI, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD DEC PY 1996 VL 4 IS 4 BP 293 EP 299 PG 7 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA WF084 UT WOS:A1996WF08400002 ER PT J AU Cho, SS Bacon, CM Sudarshan, C Rees, RC Finbloom, D Pine, R OShea, JJ AF Cho, SS Bacon, CM Sudarshan, C Rees, RC Finbloom, D Pine, R OShea, JJ TI Activation of STAT4 by IL-12 and IFN-alpha - Evidence for the involvement of ligand-induced tyrosine and serine phosphorylation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID STIMULATED-GENE FACTOR-3; SIGNAL-TRANSDUCTION; GAMMA-INTERFERON; PROTEIN-KINASE; TRANSCRIPTION FACTORS; BINDING PROTEIN; RESPONSE FACTOR; KILLER CELLS; INTERLEUKIN-12; RECEPTOR AB The immunoregulatory cytokine IL-12 plays a central role in cell-mediated immune responses through its effects on NK cells and T lymphocytes. While IL-12 is known to share some functions with other cytokines, such as IFN-LU, it also maintains distinct roles, such as its ability to induce Th1 differentiation, The molecular basis for these unique and overlapping functions is not well understood, IL-12 has previously been shown to induce tyrosine phosphorylation and DNA-binding of STAT3 and STAT4, members of the signal transducers and activators of transcription (STAT) family, Because STAT4 has only been shown to be activated in response to IL-12, this specificity has been suggested to be a basis for the unique actions of IL-12, In this study, we demonstrated that STAT4 activation by IL-12 is not unique; IL-12 and IFN-alpha, but not IFN-gamma, induced tyrosine phosphorylation and DNA binding of STAT4, Since tyrosine and serine phosphorylation of STAT1 have previously been shown to be important in IFN-alpha-mediated signaling, we also investigated IL-12- and IFN-alpha-induced serine phosphorylation of STAT4, We demonstrated that both cytokines induced serine phosphorylation, This modification was not required for DNA binding, but may be important in STAT-mediated transcription, Thus, STAT4 activation was not IL-12 specific, and IL-12 and IFN-alpha activated STAT4 through both tyrosine and serine phosphorylation. These findings have significant implications for understanding the role of STAT4 in mediating biologic functions; specifically, the data argue that the unique effects of IL-12 cannot be solely explained by STAT4 activation. C1 NIAMSD,ARTHRIT & RHEUMATISM BRANCH,NIH,LYMPHOCYTE CELL BIOL SECT,BETHESDA,MD 20892. UNIV SHEFFIELD,SCH MED,INST CANC STUDIES,SHEFFIELD,S YORKSHIRE,ENGLAND. US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. PUBL HLTH RES INST,NEW YORK,NY 10016. NR 61 TC 205 Z9 210 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 DEC 1 PY 1996 VL 157 IS 11 BP 4781 EP 4789 PG 9 WC Immunology SC Immunology GA VU501 UT WOS:A1996VU50100006 PM 8943379 ER PT J AU Yee, D RhinehartJones, TR Elkins, KL AF Yee, D RhinehartJones, TR Elkins, KL TI Loss of either CD4(+) or CD8(+) T cells does not affect the magnitude of protective immunity to an intracellular pathogen, Francisella tularensis strain LVS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LISTERIA-MONOCYTOGENES INFECTION; BACILLUS-CALMETTE-GUERIN; KNOCK-OUT MICE; GAMMA-INTERFERON; ACQUIRED-RESISTANCE; SECONDARY INFECTION; BACTERIAL PATHOGEN; MURINE LISTERIOSIS; LEISHMANIA-MAJOR; DEFICIENT MICE AB Normal mice readily survive a sublethal intradermal (i.d.) infection with Francisella tularensis live vaccine strain (LVS), a model Intracellular bacterium, and are strongly protected against subsequent lethal challenge. However, athymic nu/nu mice, which lack mature alpha beta TCR(+) T lymphocytes, succumb to i.d. infection within 30 days. Here we characterize the alpha beta T cell subpopulations necessary for both resolution sf i.d. infection and generation of optimal protective Immunity to LVS. BALB/cByJ mice treated with anti-CD4 or anti-CD8 Abs before i.d. infection survived and cleared bacteria, and anti-CD4- or anti-CD8-treated immune mice survived a very strong i.p. challenge of 10,000 LD(50)s. Among mutant mice with targeted gene disruptions (knockouts), CD4(-), beta(2)-microglobulin-deficient (which are also CD8(-)), and gamma delta TCR(-) mice all resolved a large sublethal i.d. infection. All CD4(-) and beta(2)-microglobulin-deficient mice readily survived subsequent lethal i.p. challenge of 10,000 LD(50)s, even in the absence of specific Ige Abs, as did most (86%) gamma delta TCR(-) mice. In contrast, alpha beta TCR(-) mice or alpha beta + gamma delta TCR(-) mice died about 35 days after i.d. infection. Depletion of gamma delta(+) T cells from alpha beta TCR(-) mice had no effect on mean time to death from i.d. LVS infection. Therefore alpha beta TCR(+) cell are required for protection, but either CD4(+) or CD8(+) T cell are individually sufficient to resolve a large sublethal i.d. LVS infection and to protect against a maximal secondary lethal challenge, These results emphasize the remarkable plasticity of the alpha beta T cell response in protective immunity to intracellular bacteria. C1 US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,LAB ENTER & SEXUALLY TRANSMITTED DIS,BETHESDA,MD 20852. NR 46 TC 79 Z9 79 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 DEC 1 PY 1996 VL 157 IS 11 BP 5042 EP 5048 PG 7 WC Immunology SC Immunology GA VU501 UT WOS:A1996VU50100040 PM 8943413 ER PT J AU Putnak, R Barvir, DA Burrous, JM Dubois, DR DAndrea, VM Hoke, CH Sadoff, JC Eckels, KH AF Putnak, R Barvir, DA Burrous, JM Dubois, DR DAndrea, VM Hoke, CH Sadoff, JC Eckels, KH TI Development of a purified, inactivated, dengue-2 virus vaccine prototype in vero cells: Immunogenicity and protection in mice and rhesus monkeys SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TICK-BORNE ENCEPHALITIS; PRIMARY KIDNEY-CELLS; MONOCLONAL-ANTIBODIES; JAPANESE ENCEPHALITIS; ANTIGENIC DETERMINANTS; VIRAL-PROTEINS; SERIAL PASSAGE; LUNG-CELLS; CANDIDATE; IMMUNIZATION AB The feasibility of a purified, inactivated dengue (DEN) vaccine made in Vero cells was explored, A DEN-2 virus candidate was chosen for production of a monotypic, purified, inactivated vaccine (PIV), Virus was harvested from roller bottle culture supernatants, concentrated, and purified on sucrose gradients. The purified virus was inactivated with 0.05% formalin at 22 degrees C. After inactivation, the virus retained its antigenicity and was immunogenic in mice and rhesus monkeys, in which it elicited high titers of DEN-2 virus-neutralizing antibody. Mice were completely protected against challenge with live, virulent virus after receiving two 0.15-mu g doses of PIV. Monkeys vaccinated with three doses ranging as low as 0.25 mu g demonstrated complete absence or a significant reduction in the number of days of viremia after challenge with homologous virus. These results warrant further testing and development of PIVs for other DEN virus serotypes. C1 WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,DEPT BIOL RES,WASHINGTON,DC 20307. US FDA,DIV CLIN LAB DEVICES,ROCKVILLE,MD 20857. MERCK RES LABS,BLUE BELL,PA. NR 49 TC 98 Z9 105 U1 0 U2 5 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 DEC PY 1996 VL 174 IS 6 BP 1176 EP 1184 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VV272 UT WOS:A1996VV27200005 PM 8940206 ER PT J AU Khan, AS Shahabuddin, M Bryan, T Joshi, BH Lee, S Hewlett, IK AF Khan, AS Shahabuddin, M Bryan, T Joshi, BH Lee, S Hewlett, IK TI Analysis of live, oral poliovirus vaccine monopools for human immunodeficiency virus type 1 and simian immunodeficiency virus SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ORIGIN; AIDS; INFECTION; RETROVIRUSES; HIV-1; PCR AB Although there is no evidence for transmission of mammalian retroviruses to humans via vaccine immunization, the allegations of contamination of oral poliovirus vaccines with human immunodeficiency virus (HIV) type 1 or a hypothetical progenitor virus from monkeys has created controversy and dispute regarding the origin of AIDS in humans. Twelve monovalent lots of live, attenuated oral poliovirus vaccine types 1, 2, and 3, which were released for use by a North American manufacturer between 1976-1989, were tested for the presence of HIV-1 and simian immunodeficiency virus (SIV), HIV/SIV were not detected in these monovalent poliovirus vaccine lots with the reverse transcriptase assay, a general detection assay, and highly sensitive and specific polymerase chain reaction assays. C1 US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,MOL VIROL LAB,ROCKVILLE,MD 20852. RP Khan, AS (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,LAB RETROVIRUS RES,1401 ROCKVILLE PIKE,HFM-454,ROCKVILLE,MD 20852, USA. NR 29 TC 5 Z9 6 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 DEC PY 1996 VL 174 IS 6 BP 1185 EP 1190 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VV272 UT WOS:A1996VV27200006 PM 8940207 ER PT J AU Sun, H Ette, EI Ludden, TM AF Sun, H Ette, EI Ludden, TM TI On the recording of sample times and parameter estimation from repeated measures pharmacokinetic data SO JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS LA English DT Article DE sampling time error; repeated measures data; population pharmacokinetics; parameter estimation ID POPULATION PHARMACOKINETICS; EXPERIMENTAL-DESIGN AB A pharmacokinetic screen has been advocated for the characterization of the population pharmacokinetics of drugs during Phase 3 clinical trials. A common perception encountered in the collection of such data is that the accuracy of sampling times relative to dose is inadequate. A prospective simulation study was carried out to evaluate the effect of error in the recording of sampling times on the accuracy and precision of population parameter estimates from repeated measures pharmacokinetic data. A two-compartment model with intravenous bolus input(s) (single and multiple doses) was assumed Random and systematic error in sampling times ranging from 5-50% using profile (block) randomized design were introduced. Sampling times were simulated in EXCEL while concentration data simulation and analysis were done in NONMEM. The effect of error in sampling times was studied at levels of variability ranging from 15-45% for a drug assumed to be dosed at its elimination half-life. One hundred replicate data sets of 100 subjects each were simulated for each case. Although estimates of clearance (CL) and variability in clearance were robust for most of the sampling time errors, there teas an increase in bias and imprecision in overall parameter estimation as intersubject variability was increased. If there is interest in parameters other than CL, then rite design of prospective population studies should include procedures for minimizing the error in the recording of sample times relative to dosing history. C1 US FDA,OFF CLIN PHARMACOL & BIOPHARMACEUT,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. UNIV NEBRASKA,MED CTR,COLL PHARM,OMAHA,NE 68198. NR 17 TC 13 Z9 14 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0090-466X J9 J PHARMACOKINET BIOP JI J. Pharmacokinet. Biopharm. PD DEC PY 1996 VL 24 IS 6 BP 637 EP 650 DI 10.1007/BF02353484 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XV716 UT WOS:A1996XV71600006 PM 9300354 ER PT J AU Mahmood, I AF Mahmood, I TI Pharmacokinetic analysis of the absorption characteristics of diclofenac sodium in man by use of a multi-segment absorption model SO JOURNAL OF PHARMACY AND PHARMACOLOGY LA English DT Article ID PROFILES; PLASMA AB The pharmacokinetic analysis of an oral sustained-release preparation of diclofenac sodium has been investigated using multi-segment absorption models in which it has been assumed that the gastrointestinal tract can be divided into several segments in each of which the drug has its own lag-time and absorption rate constants. Plasma concentration-time data for sustained release diclofenac sodium in man were fitted both by a conventional pharmacokinetic method assuming first-order absorption and by a multi-segment absorption model. The plasma concentration of diclofenac sodium calculated on the basis of the multi-segment absorption model was found to correlate with the observed plasma concentration. It was concluded that diclofenac sodium data can be better described by a multi-segment absorption model than by a conventional pharmacokinetic model. The results also show that multi-segment absorption models are suitable for pharmacokinetic analysis of plasma drug-concentration data with irregular or multiple peaks in the absorption profiles, and also for the pharmacokinetic analysis of sustained-release preparations. RP Mahmood, I (reprint author), US FDA,DIV PHARMACEUT EVALUAT 1,OFF CLIN PHARMACOL & BIOPHARMACEUT,1451 ROCKVILLE PIKE,HFD-860,ROCKVILLE,MD 20852, USA. NR 12 TC 8 Z9 8 U1 0 U2 2 PU ROYAL PHARMACEUTICAL SOC GREAT BRITAIN PI LONDON PA 1 LAMBETH HIGH ST, LONDON, ENGLAND SE1 7JN SN 0022-3573 J9 J PHARM PHARMACOL JI J. Pharm. Pharmacol. PD DEC PY 1996 VL 48 IS 12 BP 1260 EP 1263 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WB699 UT WOS:A1996WB69900008 PM 9004188 ER PT J AU Ali, LH Angyal, G Weaver, CM Rader, JI Mossoba, MM AF Ali, LH Angyal, G Weaver, CM Rader, JI Mossoba, MM TI Determination of total trans fatty acids in foods: Comparison of capillary-column gas chromatography and single-bounce horizontal attenuated total reflection infrared spectroscopy SO JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY LA English DT Article DE attenuated total reflection infrared spectroscopy; capillary-column gas chromatography; trans fatty acids ID LIQUID-CHROMATOGRAPHY; OCTADECENOIC ACIDS; SPECTROPHOTOMETRY; MARGARINES; DISEASE; WOMEN; CIS AB The total trans fatty acid content of 18 food products was determined, after acid hydrolysis, extraction and methylation of fatty acids, by gas chromatography with a polar 100% cyanopropylsiloxane capillary column and by single-bounce horizontal attenuated total reflection spectroscopy (SB-HATR). The trans fatty acid methyl esters (FAME) of 9-hexadecenoate (9t-16:1), 9-octadecenoate (9t-18:1), and 9,12-octadecadienoate (9t, 12t-18:2) were identified by comparison of their retention times with those of known standards and quantitated. The isomers c,t- and t,c-18:2 were identified from their published retention times and included in the quantitation of trans FAME. Neat 50-mu L portions of the FAME that were used for gas-chromatographic analysis also were analyzed by SB-HATR. This technique requires neither weighing nor quantitative dilution of test portions prior to spectroscopic quantitation of isolated double bonds of trans configuration. A symmetric 966-cm(-1) absorption band on a horizontal background was obtained from unhydrogenated soybean oil FAME as the reference material. For 9 of 11 products with trans fat content >5% of total fat, results obtained by SB-HATR were higher than those obtained by gas chromatography. Results obtained by the gas-chromatographic procedure were slightly to significantly higher than those obtained by SB-HATR for the six foods in which trans fat content was <5% of total fat. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,OFF ANAL & SUPPORT,WASHINGTON,DC 20204. RP Ali, LH (reprint author), US FDA,OFF FOOD LABELING,HFS-175,200 C ST,SW,WASHINGTON,DC 20204, USA. NR 18 TC 24 Z9 25 U1 0 U2 5 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0003-021X J9 J AM OIL CHEM SOC JI J. Am. Oil Chem. Soc. PD DEC PY 1996 VL 73 IS 12 BP 1699 EP 1705 DI 10.1007/BF02517975 PG 7 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA VY896 UT WOS:A1996VY89600014 ER PT J AU George, EO Kodell, RL AF George, EO Kodell, RL TI Tests of independence, treatment heterogeneity, and dose-related trend with exchangeable binary data SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE adjusted Cochran-Armitage test; beta-binomial models; developmental toxicity data; effective sample size; generalized score test; likelihood ratio tests; variance inflation factor ID TERATOLOGICAL EXPERIMENTS; TOXICOLOGICAL EXPERIMENTS; DEVELOPMENTAL TOXICITY; ESTIMATING EQUATIONS; RESPONSES; MODEL; PROPORTIONS; OUTCOMES AB Existing methods of testing for treatment effects for clustered binary data include the beta-binomial, quasilikelihood, and GEE procedures. All of these methods revolve around the mean response and the second-order correlation. However, these two parameters alone do not fully determine the effect of treatment. This article develops nonparametric likelihood ratio procedures to test for independence, heterogeneity, and dose-related trend in dose-response studies involving exchangeable binary data. The hypotheses of independence, heterogeneity, and trend are expressed in terms of joint probabilities of similar responses among cluster mates. Constrained maximum likelihood estimates of these probabilities are computed and used to construct test statistics. Unlike the test statistics for independence and heterogeneity, the asymptotic distribution of the likelihood ratio test for trend is not exactly a chi-square. However, an upper bound of its p value is obtained by using a chi-squared distribution. A set of clustered binary data from the Shell Toxicology Laboratory, on the developmental effect of a chemical agent on banded Dutch rabbits, is used to illustrate the various test procedures. The same dataset is used to compare the proposed trend test with some existing trend tests, such as those based on a beta-binomial model, generalized estimating equations, and survey sampling methods. C1 US FDA, NATL CTR TOXICOL RES, DIV BIOMETRY & RISK ASSESSMENT, JEFFERSON, AR 72079 USA. RP George, EO (reprint author), UNIV MEMPHIS, DEPT MATH SCI, MEMPHIS, TN 38152 USA. NR 25 TC 21 Z9 21 U1 0 U2 2 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0162-1459 EI 1537-274X J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 1996 VL 91 IS 436 BP 1602 EP 1610 DI 10.2307/2291586 PG 9 WC Statistics & Probability SC Mathematics GA VX913 UT WOS:A1996VX91300023 ER PT J AU Romanova, L Alexandrov, I Nguyen, P Szallazi, Z Nordan, R Blumberg, P Trepel, J Mushinski, JF AF Romanova, L Alexandrov, I Nguyen, P Szallazi, Z Nordan, R Blumberg, P Trepel, J Mushinski, JF TI Crosstalk between PKC-delta and IL-3 pathways: Antagonizing effects on cell shape-controlling actin structures and additive effects on paxillin phosphorylation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2218 EP 2218 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802214 ER PT J AU Fishman, RB Branham, WS Streck, RD Sheehan, DM AF Fishman, RB Branham, WS Streck, RD Sheehan, DM TI Ontogeny of estrogen receptor mrna expression in the postnatal rat uterus. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2761 EP 2761 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802754 ER PT J AU Rajaratnam, VS Webb, PJ Streck, RD AF Rajaratnam, VS Webb, PJ Streck, RD TI IGFBP-1 mRNA expression within the urogenital region of the rat fetus is localized to the mesonephros. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2765 EP 2765 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802756 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 Hall, CB 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 Hall, CB Berkelman, RL Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR TI Prevention of hepatitis A infections: Guidelines for use of hepatitis A vaccine and immune globulin SO PEDIATRICS LA English DT Article ID INTENSIVE-CARE UNIT; A VACCINE; HEALTHY-CHILDREN; IMMUNOGENICITY; TRANSMISSION; OUTBREAK; SAFETY; TRAVELERS; EPIDEMIOLOGY; TOLERABILITY AB The licensing of two inactivated hepatitis A vaccines for persons 2 years or older necessitates development of recommendations for pediatric use, as well as a review of the current indications for immune globulin (IG) in hepatitis A prophylaxis.(1-4) Both vaccines are immunogenic and protective in children and adults. A single dose of vaccine induced antibody in 88% to 96% of subjects by 2 weeks and 97% to 100% by 1 month, and protected against subsequent hepatitis A virus (HAV) disease occurring 21 days after receipt of the dose in a community with endemic hepatitis A infection. However, completion of the full vaccine schedule is recommended to assure high antibody titers and likely long-term protection. The major pediatric indications for vaccine are: (1) travelers to areas with intermediate to high rates of endemic hepatitis A, (2) children living in defined and circumscribed communities with high endemic rates or periodic outbreaks of HAV infection, and (3) patients with chronic liver disease. Immune globulin is recommended for postexposure prophylaxis, as vaccine has not yet been demonstrated to be protective for this purpose. Except for travelers, recommendations for IG use are not changed from those in the current edition of the Red Book, and include contacts of cases in the home, child care centers, and other selected sites. C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30333. US FDA,ROCKVILLE,MD 20857. NR 50 TC 26 Z9 30 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 DEC PY 1996 VL 98 IS 6 BP 1207 EP 1215 PG 9 WC Pediatrics SC Pediatrics GA VW531 UT WOS:A1996VW53100039 ER PT J AU Sathe, PM Tsong, Y Shah, VP AF Sathe, PM Tsong, Y Shah, VP TI In-vitro dissolution profile comparison: Statistics and analysis, model dependent approach SO PHARMACEUTICAL RESEARCH LA English DT Article DE dissolution profile comparison; statistics; model dependent analysis AB Purpose. To develop and propose a 'model dependent' approach for the in-vitro dissolution profiles comparison. Methods. Diltiazem hydrochloride tablet dissolution profiles were compared using a statistical approach based on a mathematical model. A similarity region (SR) was defined based on the intra- and inter-lot parameter variances of the final production size standard lots. Statistical distances between the test and reference lot parameter means were computed and normalized. A 90% confidence region (CR) was developed around the statistical distance. The confidence region was compared with the similarity region to assess the similarity or dis-similarity of the test and reference (REF) lot dissolution profiles. Two test lots, one with a 'minor' modification(mm) the other with a 'major' modification (MM), were evaluated. Results. 'Weibull' was selected as the 'model' function. A comparison of the confidence regions around the statistical distance of 'mm-REF' and 'MM-REF' with the similarity region, suggested that the dissolution profiles of the 'mirror' modification lot were similar and that of 'major' modification lot were dis-similar to the reference lot. Conclusions,. A 'model dependent' approach was shown to be useful for the inter-lot in-vitro dissolution profiles comparison. RP Sathe, PM (reprint author), US FDA,CTR DRUG EVALUAT & RES,OFF PHARMACEUT SCI,7500 STANDISH PL,ROCKVILLE,MD 20855, USA. NR 8 TC 72 Z9 76 U1 1 U2 13 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 DEC PY 1996 VL 13 IS 12 BP 1799 EP 1803 DI 10.1023/A:1016020822093 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA WA895 UT WOS:A1996WA89500008 PM 8987074 ER PT J AU Ferguson, SA AF Ferguson, SA TI Neuroanatomical and functional alterations resulting from early postnatal cerebellar insults in rodents SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Review DE cerebellum; development; irradiation; methylazoxymethanol; hypothyroidism; hyperthyroidism; borna disease virus ID DEVELOPING RAT CEREBELLUM; EXTERNAL GERMINAL LAYER; BORNA-DISEASE VIRUS; IODINE DEFICIENCY DISORDERS; NEONATAL HYPO-THYROIDISM; X-IRRADIATION SCHEDULES; GRANULE CELL-MIGRATION; PURKINJE-CELLS; CLIMBING FIBERS; EARLY HYPOTHYROIDISM AB This review examines neuroanatomical and functional alterations in rodents resulting from postnatal insults during cerebellar development. Treatments such as irradiation and methylazoxy-methanol (MAM) administration produced near birth (< postnatal day 8 for irradiation treatment and < postnatal day 4 for MAM administration) result in more severe cerebellar damage than do similar treatments administered several days after birth. Prominent among the more severe alterations are foliation abnormalities, misalignment of Purkinje cells and continued multiple innervation of climbing fibers; few or none of these occur as a result of later treatments (> postnatal day 8 for irradiation treatment and > postnatal day 4 for MAM treatment). The functional alterations also differ: insults produced near birth result in hypoactivity, ataxia, tremor and accompanying learning deficits, whereas those produced later result in hyperactivity and few learning deficits. This hyperactivity may have relevance to human disorders. Brief discussions of cerebellar and functional alterations (e.g., hyperactivity) resulting from neonatal infection with the Borna disease virus and induction of hypo- and hyperthyroidism during the preweaning period are also presented. Copyright (C) 1996 Elsevier Science Inc. RP Ferguson, SA (reprint author), NATL CTR TOXICOL RES, DIV REPROD & DEV TOXICOL, 3900 NCTR RD, JEFFERSON, AR 72079 USA. NR 120 TC 46 Z9 46 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD DEC PY 1996 VL 55 IS 4 BP 663 EP 671 DI 10.1016/S0091-3057(96)00253-5 PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA VZ814 UT WOS:A1996VZ81400025 PM 8981598 ER PT J AU Shank, FR Bailey, CJ AF Shank, FR Bailey, CJ TI Trends of FDA resource allocations over the past 20 years: Expected future resources and workload SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT Workshop on Chronic Inhalation Toxicity and Carcinogenicity Testing of Respirable Fibrous Particles CY MAY 08-10, 1995 CL CHAPEL HILL, NC SP US EPA, Off Pollut Prevent & Toxics, NIEHS, NIOSH, Occupat Soc & Hlth Adm RP Shank, FR (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,200 C ST SW,ROOM 6815 HSF 1,WASHINGTON,DC 20204, USA. NR 2 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 DEC PY 1996 VL 24 IS 3 BP 218 EP 223 DI 10.1006/rtph.1996.0131 PG 6 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA WA825 UT WOS:A1996WA82500006 PM 8975748 ER PT J AU Rulis, AM Tarantino, LM AF Rulis, AM Tarantino, LM TI Food ingredient review at FDA: Recent data and initiatives to improve the process SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT Workshop on Chronic Inhalation Toxicity and Carcinogenicity Testing of Respirable Fibrous Particles CY MAY 08-10, 1995 CL CHAPEL HILL, NC SP US EPA, Off Pollut Prevent & Toxics, NIEHS, NIOSH, Occupat Soc & Hlth Adm RP Rulis, AM (reprint author), US FDA,200 C ST SW,HFS 200,WASHINGTON,DC 20204, USA. NR 0 TC 0 Z9 1 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 DEC PY 1996 VL 24 IS 3 BP 224 EP 231 DI 10.1006/rtph.1996.0132 PG 8 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA WA825 UT WOS:A1996WA82500007 PM 8975749 ER PT J AU Hattan, D AF Hattan, D TI The logistical requirements of current FDA review: Format of documentation requested SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT Workshop on Chronic Inhalation Toxicity and Carcinogenicity Testing of Respirable Fibrous Particles CY MAY 08-10, 1995 CL CHAPEL HILL, NC SP US EPA, Off Pollut Prevent & Toxics, NIEHS, NIOSH, Occupat Soc & Hlth Adm RP Hattan, D (reprint author), US FDA,200 C ST SW,HFS 225,WASHINGTON,DC 20204, 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 DEC PY 1996 VL 24 IS 3 BP 232 EP 235 DI 10.1006/rtph.1996.0133 PG 4 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA WA825 UT WOS:A1996WA82500008 PM 8975750 ER PT J AU Gaylor, DW AF Gaylor, DW TI Quantalization of continuous data for benchmark dose estimation SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID RISK ASSESSMENT AB Benchmark doses corresponding to low levels of noncancer disease risk have been proposed to replace the no-observed-adverse effect level for establishing allowable daily intakes or reference doses. For quantal data each animal is classified with or without a disease. The proportion of animals with an adverse effect (risk) is observed as a function of dose of a toxic substance. The calculation of a benchmark dose is relatively straightforward. For continuous data a somewhat more complicated designation of risk is required. Because of the more direct procedures with quantal data, consideration could be given to converting continuous data to quantal data before estimating benchmark doses. The purpose of this paper is to compare the precision of the two approaches (use of continuous or quantalized data) for a number of sublinear dose-response curves ranging from low to high probabilities of risk at the highest dose. In these studies, five animals per dose were generally satisfactory to estimate the benchmark dose for continuous data, whereas the corresponding quantalized data generally do not perform as well even with 10 to 20 animals per dose. For quantalized data, the lower 95% confidence limits on the estimates of the benchmark dose were generally a factor of 3 to 4 below the true benchmark dose, whereas the confidence limits using the continuous data were generally within a factor of 2 of the true benchmark dose. Although the use of quantalized data for the estimation of risk is more direct, estimates of benchmark doses using the continuous data were more precise. Based on this study, converting continuous data to quantal data is not recommended. (C) 1996 Academic Press, Inc. RP Gaylor, DW (reprint author), US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 11 TC 17 Z9 17 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 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD DEC PY 1996 VL 24 IS 3 BP 246 EP 250 DI 10.1006/rtph.1996.0137 PG 5 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA WA825 UT WOS:A1996WA82500012 PM 8975754 ER PT J AU Craun, G Dufour, A Eisenberg, J Foran, J Gauntt, C Gerba, C Haas, C Highsmith, A Irbe, R Julkunen, P Juranek, D LeChevallier, M Levine, M Macler, B Murphy, P Payment, P Pfaender, F Regli, S Roberson, A Rose, J Schaub, S Schiff, G Seed, J Smith, C Sobsey, M Spear, R Walls, I AF Craun, G Dufour, A Eisenberg, J Foran, J Gauntt, C Gerba, C Haas, C Highsmith, A Irbe, R Julkunen, P Juranek, D LeChevallier, M Levine, M Macler, B Murphy, P Payment, P Pfaender, F Regli, S Roberson, A Rose, J Schaub, S Schiff, G Seed, J Smith, C Sobsey, M Spear, R Walls, I TI A conceptual framework to assess the risks of human disease following exposure to pathogens SO RISK ANALYSIS LA English DT Article DE pathogen risk assessment; microbial; framework ID DRINKING-WATER AB Currently, risk assessments of the potential human health effects associated with exposure to pathogens are utilizing the conceptual framework that was developed to assess risks associated with chemical exposures. However, the applicability of the chemical framework is problematic due to many issues that art: unique to assessing risks associated with pathogens. These include, but are not limited to, an assessment of pathogen/host interactions, consideration of secondary spread, consideration of short- and long-term immunity, and an assessment of conditions that allow the microorganism to propagate. To address this concern, a working group was convened to develop a conceptual framework to assess the risks of human disease associated with exposure to pathogenic microorganisms. The framework that was developed consists of three phases: problem formulation, analysis (which includes characterization of exposure and human health effects), and risk characterization. The framework emphasizes the dynamic and iterative nature of the risk assessment process, and allows wide latitude for planning and conducting risk assessments in diverse situations, each based on the common principles discussed in the framework. C1 ILSI,RISK SCI INST,WASHINGTON,DC 20036. US FDA,ROCKVILLE,MD 20857. GLOBAL CONSULTING ENVIRONM HLTH,RADFORD,VA. US EPA,CINCINNATI,OH 45268. UNIV CALIF BERKELEY,BERKELEY,CA 94720. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. UNIV ARIZONA,TUCSON,AZ 85721. DREXEL UNIV,PHILADELPHIA,PA 19104. CTR DIS CONTROL & PREVENT,ATLANTA,GA. NUTRASWEET CO,MT PROSPECT,IL 60056. COCA COLA CO,ATLANTA,GA. AMER WATER WORKS ASSOC SERV CO,VOORHEES,NJ. UNIV MARYLAND,BALTIMORE,MD 21201. US EPA,SAN FRANCISCO,CA. UNIV QUEBEC,ST FOY,PQ G1V 2M3,CANADA. UNIV N CAROLINA,CHAPEL HILL,NC. AMER WATER WORKS ASSOC,WASHINGTON,DC. UNIV FLORIDA,ST PETERSBURG,FL. JAMES N GAMBLE INST MED RES,CINCINNATI,OH. CHARLOTTE SMITH & ASSOCIATES,VENICE,FL. NATL FOOD PROCESSORS ASSOC,WASHINGTON,DC 20005. NR 13 TC 52 Z9 54 U1 0 U2 4 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 DEC PY 1996 VL 16 IS 6 BP 841 EP 848 PG 8 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA VY703 UT WOS:A1996VY70300013 ER PT J AU Sotomayor, RE Jackson, R Nourbakhsh, A AF Sotomayor, RE Jackson, R Nourbakhsh, A TI A procedure to study unscheduled DNA synthesis in rat spermatogenic cells in vivo: Strain differences between Fisher-344 and Sprague-Dawley rats SO TOXICOLOGY LETTERS LA English DT Article DE UDS assay; spermatogenic cells; Fisher-344 rats; Sprague-Dawley rats; strain differences ID GERM-CELLS; MALE-MICE; METHYL METHANESULFONATE; ETHYL METHANESULFONATE; X-RAYS; INVIVO; SPERMATOCYTES; FISCHER-344; INDUCTION; REPAIR AB A liquid scintillation counting (LSC) procedure was used to study unscheduled DNA synthesis (UDS) in pachytene spermatocytes and spermatids from Fisher-344 (F344) and Sprague-Dawley (SPD) rats treated with methyl methanesulfonate (MMS). MMS induced a large, dose-dependent, UDS response in pachytene spermatocytes from both rat strains. On average, F344 pachytene spermatocytes showed a larger UDS response than those of SPD rats. The lowest dose of MMS that elicited a significant UDS response was 1 mg/kg in F344 rats but 5 mg/kg in SPD rats. Early spermatid stages from F344 rats also showed a larger UDS response than those from SPD rats. The time interval at which spermatid stages showed the maximum UDS response was between 20 and 24 days after MMS treatment. It is concluded that UDS can be measured quantitatively in rat spermatogenic cells in vivo by using the LSC procedure. C1 CORNING HAZLETON,GENET TOXICOL,VIENNA,VA 22182. RP Sotomayor, RE (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,HFS-509,LAUREL,MD 20708, USA. NR 18 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC PY 1996 VL 89 IS 1 BP 77 EP 81 DI 10.1016/S0378-4274(96)03792-7 PG 5 WC Toxicology SC Toxicology GA VV103 UT WOS:A1996VV10300012 PM 8952715 ER PT J AU Warden, MP Weir, JP AF Warden, MP Weir, JP TI Inducible gene expression of the human immunodeficiency virus LTR in a replication-incompetent herpes simplex virus vector SO VIROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; GLYCOPROTEIN-C GENE; BETA-GALACTOSIDASE; DELETION MUTANTS; TYPE-1 VECTORS; EARLY PROMOTER; INFECTION; SEQUENCES; LATENCY; DELIVERY AB Although replication-incompetent herpes simplex virus (HSV) Vectors have the capability to express foreign genes, successful development of these vectors for gene delivery would require that expression of the foreign gene be regulated. To investigate the feasibility of obtaining inducible expression of a foreign gene in such a vector, a replication-incompetent HSV vector, vd120/LTR beta, was developed that used the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) to express the Escherichia coli lacZ gene. Examination of lacZ expression from the HIV-1 LTR in vd120/LTR beta-infected cells indicated that the LTR was active as a promoter under both replicating and nonreplicating conditions, although expression of lacZ under nonreplicating conditions was approximately 4-fold lower. In addition, the LTR expressed lacZ in a manner distinct from that of well-characterized HSV-1 promoters of each temporal class. The effect of the HIV-1 regulatory protein Tat on expression from the LTR in vd120/LTR beta was examined by infection of two different HeLa-derived cell lines that constitutively expressed Tat, HL2/3, and HLtat. Compared to infection of HeLa cells, lacZ expression from vd120/LTR beta-infected HL2/3 and HLtat cells increased from 4- to 24-fold, depending on the multiplicity of vector infection. Sustained expression of lacZ from the LTR in vd120/LTR beta-infected cells was not observed even in the continuous presence of Tat, although vector could be recovered for up to 5 days after infection. However, the amount of recoverable vector decreased during this time, suggesting that cellular cytotoxicity may account for some of the decrease in Tat-mediated expression from the LTR. (C) 1996 Academic Press, Inc. C1 US FDA,CTR BIOL EVALUAT & RES,LAB DNA VIRUSES,BETHESDA,MD 20892. NR 36 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 0042-6822 J9 VIROLOGY JI Virology PD DEC 1 PY 1996 VL 226 IS 1 BP 127 EP 131 DI 10.1006/viro.1996.0635 PG 5 WC Virology SC Virology GA VV435 UT WOS:A1996VV43500014 PM 8941330 ER PT J AU Boal, JH Wilk, A Scremin, CL Gray, GN Phillips, LR Beaucage, SL AF Boal, JH Wilk, A Scremin, CL Gray, GN Phillips, LR Beaucage, SL TI Synthesis of (2-deoxy-alpha- and -beta-D-erythro-pentofuranosyl)(thymin-1-yl)alkanes and their incorporation into oligodeoxyribonucleotides. Effect of nucleobase-sugar linker flexibility on the formation of DNA-DNA and DNA-RNA hybrids SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID (5'->5')-INTERNUCLEOTIDIC PHOSPHODIESTER LINKAGES; OLIGONUCLEOTIDES; CONFORMATION; NUCLEOSIDES AB On the basis of modeling studies, the (2-deoxy-alpha- and beta-D-erythro-pentofuranosyl) (thymin-1-yl) alkanes 1a,b and 2a,b were selected as potential conformational probes for altDNA oligonucleotides. A straightforward approach to the synthesis of 1a,b and 2a,b from commercial 2-deoxy-D-ribose (3) and 1-O-methyl-2-deoxy-3,5-di-O-p-toluoyl-D-erythro-pentofuranose (13), respectively, was developed. These nucleoside analogues were converted to the phosphoramidite derivatives 27a,b-30a,b and incorporated into oligonucleotide 31 at predetermined sites and defined internucleotidic motifs. The insertion of 1a,b according to either a (3' --> 5')- or a (3' --> 3')-internucleotidic polarity produced oligonucleotides exhibiting a slightly higher affinity for their complementary unmodified DNA sequence than for the corresponding RNA sequence (Table 3). Conversely, the incorporation of 2a into 31 according to a (3' --> 3')-orientation generated, for the first time, an altDNA oligonucleotide displaying a greater affinity for its complementary unmodified RNA sequence (Delta T-m = 6 degrees C) than for the corresponding DNA sequence (Delta T-m = 10 degrees C). thermodynamically less stable than the duplex having unmodified alpha-2'-deoxythymidine similarly incorporated into 31 (Delta Delta T-m = 3 degrees C). C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. NATL CANC INST,DEV THERAPEUT PROGRAM,LAB DRUG DISCOVERY RES & DEV,FREDERICK,MD 21701. NR 33 TC 22 Z9 22 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD NOV 29 PY 1996 VL 61 IS 24 BP 8617 EP 8626 DI 10.1021/jo961548k PG 10 WC Chemistry, Organic SC Chemistry GA VV609 UT WOS:A1996VV60900046 ER PT J AU Sgadari, C Angiolillo, AL Cherney, BW Pike, SE Farber, JM Koniaris, LG Vanguri, P Burd, PR Sheikh, N Gupta, G TeruyaFeldstein, J Tosato, G AF Sgadari, C Angiolillo, AL Cherney, BW Pike, SE Farber, JM Koniaris, LG Vanguri, P Burd, PR Sheikh, N Gupta, G TeruyaFeldstein, J Tosato, G TI Interferon-inducible protein-10 identified as a mediator of tumor necrosis in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EPSTEIN-BARR-VIRUS; PLATELET FACTOR-IV; X-C CHEMOKINE; BURKITTS-LYMPHOMA; SOLID TUMORS; B-CELLS; IN-VIVO; ANGIOGENESIS; IP-10; INHIBITION AB Human Burkitt lymphoma cell lines give rise to progressively growing subcutaneous tumors in athymic mice. These tumors are induced to regress by inoculation of Epstein-Barr virus-immortalized normal human lymphocytes. In the present study, analysis of profiles of murine cytokine/chemokine gene expression in Burkitt tumor tissues excised from the nude mice showed that expression of the murine alpha-chemokine interferon-inducible protein-10 (IP-10) was higher in the regressing than in the progressive Burkitt tumors, We tested the effects of IP-10 on Burkitt tumor growth in nude mice. Inoculation of established Burkitt tumors either with crude preparations of murine IP-10 or with purified human IP-10 caused visible tumor necrosis in a proportion of the animals, although no complete tumor regressions were observed, Constitutive expression of murine IP-10 in Burkitt cells reduced their ability to grow as subcutaneous tumors, and caused visible tumor necrosis in a proportion of the animals, Histologically, IP-10-treated and IP-10-expressing Burkitt tumors had widespread evidence of tumor tissue necrosis and of capillary damage, including intimal thickening and vascular thrombosis. Thus, IP-10 is an antitumor agent that promotes damage in established tumor vasculature and causes tissue necrosis in human Burkitt lymphomas established subcutaneously in athymic mice. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,DEPT HEMATOL ONCOL,WASHINGTON,DC 20010. NIAID,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT SURG,BALTIMORE,MD 21205. UNIV MARYLAND,SCH MED,DEPT NEUROL,BALTIMORE,MD 21201. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20010. NCI,PATHOL LAB,HEMATOPATHOL SECT,NIH,BETHESDA,MD 20892. RI Sgadari, Cecilia/H-4302-2016 OI Sgadari, Cecilia/0000-0003-0364-4912 NR 33 TC 186 Z9 194 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 NOV 26 PY 1996 VL 93 IS 24 BP 13791 EP 13796 DI 10.1073/pnas.93.24.13791 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VV467 UT WOS:A1996VV46700062 PM 8943014 ER PT J AU Louie, AT Wahl, LM Hewlett, IK Epstein, JS Dhawan, S AF Louie, AT Wahl, LM Hewlett, IK Epstein, JS Dhawan, S TI Impaired antigen presentation to CD4+ T-cells by HIV-infected monocytes is related to down-modulation of CD4 expression on helper T-cells: Possible involvement of HIV-induced cellular factors SO FEBS LETTERS LA English DT Article DE HIV; AIDS; monocyte; T-cell; antigen presentation ID HUMAN-IMMUNODEFICIENCY-VIRUS; INVITRO; DYSFUNCTION; ACTIVATION; MEMBRANE; SYSTEM AB Defective antigen presentation by HIV-infected monocytes is related to severe immune dysfunction in patients with AIDS, although the mechanism by which this process occurs is not well defined, Here we report that reduced capacity by HIV-infected monocytes to stimulate or present antigen to CD4+ T-cells was mediated by cellular factors associated with the plasma membranes of HIV-infected monocytes, In contrast, soluble factors secreted by HIV-infected monocytes had little or no effect on T-cell stimulation, Reduced T-cell stimulation by HIV-infected monocytes was related to down-modulation of CD4 expression on helper T-cells and was not affected by the inclusion of anti-HIV-gp120 Ab, indicating the involvement of soluble or cell-associated viral envelope protein to be less likely, Exposure of CD4+ T-cells, that had been in co-culture with HIV-infected monocytes, to uninfected monocytes partially restored impaired T-cell stimulation, Thus, for the first time we report that altered capacity of HIV-infected monocytes to stimulate and present antigen to CD4+ T-cells is related to down-modulation of CD4 expression on T-cells, and appears to occur via membrane-associated cellular factors on HIV-infected monocytes. C1 DIV TRANSFUS TRANSMITTED DIS,IMMUNOCHEM LAB,ROCKVILLE,MD 20852. US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,MOL VIROL LAB,IMMUNOPATHOGENESIS SECT,BETHESDA,MD. NIDR,IMMUNOL LAB,BETHESDA,MD 20892. NR 24 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 25 PY 1996 VL 398 IS 1 BP 1 EP 6 DI 10.1016/S0014-5793(96)01164-7 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VV878 UT WOS:A1996VV87800001 PM 8946943 ER PT J AU Braden, BC Fields, BA Ysern, X DallAcqua, W Goldbaum, FA Poljak, RJ Mariuzza, RA AF Braden, BC Fields, BA Ysern, X DallAcqua, W Goldbaum, FA Poljak, RJ Mariuzza, RA TI Crystal structure of an Fv-Fv idiotope - Anti-idiotope complex at 1.9 angstrom resolution SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE antibody; anti-idiotypic antibody; protein structure; protein crystallography; molecular mimicry ID 3-DIMENSIONAL STRUCTURE; FAB COMPLEX; ANTIIDIOTYPIC ANTIBODIES; MOLECULAR REPLACEMENT; IDIOTYPIC ANTIBODIES; PROTEIN; MIMICRY; REFINEMENT; BINDING; CRYSTALLIZATION AB Anti-idiotopic antibodies react with unique antigenic features, usually associated with the combining sites, of other antibodies. They may thus mimic specific antigens that react with the same antibodies. The structural basis of this mimicry is analyzed here in detail for an anti-idiotopic antibody that mimics the antigen, hen egg-white lysozyme. The crystal structure of an anti-hen-egg-white lysozyme antibody (D1.3) complexed with an anti-idiotopic antibody (E5.2) has been determined at a nominal resolution of 1.9 Angstrom. E5.2 contacts substantially the same residues of D1.3 as lysozyme, thus mimicking its binding to D1.3. The mimicry embodies conservation of hydrogen bonding: six of the 14 protein-protein hydrogen bonds bridging D1.3-E5.2 are structurally equivalent to hydrogen bonds bridging D1.3-lysozyme. The mimicry includes a similar number of van der Waals interactions. The mimicry of E5.2 for lysozyme, however, does not extend to the topology of the non-polar surfaces of E5.2 and lysozyme, which are in contact with D1.3 as revealed by a quantitative analysis of the contacting surface similarities between E5.2 and lysozyme. The structure discussed herein shows that an anti-idiotopic antibody can provide an approximate topological and binding-group mimicry of an external antigen, especially in the case of the hydrophilic surfaces, even though there is no sequence homology between the anti-idiotope and the antigen. (C) 1996 Academic Press Limited C1 UNIV MARYLAND,INST BIOTECHNOL,CTR ADV RES BIOTECHNOL,ROCKVILLE,MD 20850. US FDA,CDER,ROCKVILLE,MD 20857. NR 44 TC 49 Z9 50 U1 0 U2 1 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 NOV 22 PY 1996 VL 264 IS 1 BP 137 EP 151 DI 10.1006/jmbi.1996.0629 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VU380 UT WOS:A1996VU38000012 PM 8950273 ER PT J AU Zhan, QM Alamo, I Yu, K Boise, LH Cherney, B Tosato, G OConnor, PM Fornace, AJ AF Zhan, QM Alamo, I Yu, K Boise, LH Cherney, B Tosato, G OConnor, PM Fornace, AJ TI The apoptosis-associated gamma-ray response of BCL-X(L) depends on normal p53 function SO ONCOGENE LA English DT Article DE BCL-X(L); p53; apoptosis; ionizing radiation ID TUMOR-SUPPRESSOR P53; CELL-CYCLE; BCL-X; ATAXIA-TELANGIECTASIA; CANCER-CELLS; DNA-DAMAGE; BAX GENE; IN-VIVO; C-MYC; EXPRESSION AB We have investigated the effect of DNA damage on the expression of BCL-X, a member of the BCL-2 family. BCL-X mRNA levels were found to increase upon exposure human cells to ionizing radiation (IR). The Bcl-X(L) protein, but not Bcl-X(S), was identified to be induced by IR. Like BAX, another member of the BCL-2 family and a p53-regulated gene, the induction of BCL-X(L) was dependent on normal p53 function and required that cells have an apoptosis-susceptible phenotype. The induction of BCL-X(L) was rapid, transient and dose-dependent. The mRNA level peaked at 4 h and returned to baseline by 24 h post-irradiation. In agreement with the increased transcript level, Bcl-X(L) protein level was also observed to increase in cells with wild-type p53 where IR triggered apoptosis. In addition, a survey of the BCL-X(L) mRNA basal levels in human cells with known apoptotic responses showed that low basal levels of BCL-X(L) mRNA in cells were highly correlated with a strong ability of cells to undergo IR-induced apoptosis. On the other hand, high levels of basal BCL-X(L) were correlated,vith the resistance of cells to IR-induced apoptosis regardless of p53 status. These results indicate that BCL-2 and BCL-X(L) behave differently in response to DNA damage treatment even though they both are able to protect cells from p53-mediated apoptosis; along with down-regulation of BCL-2, BCL-X(L) was up-regulated by IR in human cells with wild-type p53 and susceptibility to IR-induced apoptosis. We speculate that the physiological function of increased BCL-X(L) protein would be expected to probably limit the severity and length of BAX effect in order to maintain a proper threshold for apoptosis and to complete cell cycle arrest activated by p53. C1 UNIV CHICAGO,GWEN KNAPP CTR LUPUS & IMMUNOL,CHICAGO,IL 60637. US FDA,CTR BIOL,BETHESDA,MD 20892. RP Zhan, QM (reprint author), NCI,MOL PHARMACOL LAB,DIV BASIC SCI,ROOM 5C09,BLDG 37,BETHESDA,MD 20892, USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 35 TC 68 Z9 74 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 21 PY 1996 VL 13 IS 10 BP 2287 EP 2293 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VV145 UT WOS:A1996VV14500027 PM 8950997 ER PT J AU Bresee, JS Mast, EE Coleman, FJ Baron, MJ Schonberger, LB Alter, MJ Jonas, MM Yu, MYW Renzi, PM Schneider, LC AF Bresee, JS Mast, EE Coleman, FJ Baron, MJ Schonberger, LB Alter, MJ Jonas, MM Yu, MYW Renzi, PM Schneider, LC TI Hepatitis C virus infection associated with administration of intravenous immune globulin - A cohort study SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID NON-B-HEPATITIS; NON-A-HEPATITIS; POSTTRANSFUSION HEPATITIS; IMMUNOGLOBULIN; PLASMA; FRACTIONATION; TRANSMISSION; ANTIBODY; ASSAY AB Objective.-To determine the risk of and risk factors for hepatitis C virus (HCV) infection among persons with immune deficiencies who had received intravenous immune globulin (IGIV) between March 1993 and February 1994. Design.-Retrospective cohort study. Setting.-An immunology program in a tertiary care hospital. Patients.-Of 341 persons who had received IGIV between March 1, 1993, and February 22, 1994, 278 (82%) were enrolled. The mean age for the enrolled persons was 9 years, and 99% had primary immune deficiencies. Main Outcome Measures.-Evidence of HCV infection by detection in sera of antibody to HCV and/or HCV RNA by reverse transcriptase polymerase chain reaction. Results.-Twenty-three (11%) of 210 persons who received the IGIV Gammagard (Baxter Healthcare Corporation, Deerfield, Ill) became infected compared with none of 52 persons who received exclusively other IGIV products (P=.01). In a multivariate analysis, HCV infection was associated only with Gammagard produced from plasma screened by second-generation (multiantigen) anti-HCV tests (P=.03). Hepatitis C virus RNA was detected in Gammagard, and the risk of transmission to recipients increased with increasing quantity of HCV RNA infused, from 0 for those who received no HCV RNA-positive lots to 29% for the quartile of patients receiving the greatest amount (P<.001). At least 9 different lots of Gammagard were required to account for all cases. Conclusion.-Gammagard was the only IGIV product implicated in the transmission of HCV. Infection was associated with higher quantities of HCV RNA in Gammagard produced from second-generation anti-HCV-screened plasma. Further studies are needed to determine reasons for the infectivity of Gammagard, and viral inactivation and removal steps are needed to ensure the safety of IGIV products. C1 CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,HEPATITIS BRANCH,ATLANTA,GA 30333. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. CHILDRENS HOSP,DIV GASTROENTEROL,BOSTON,MA. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,BETHESDA,MD 20892. CHILDRENS HOSP,DIV IMMUNOL,BOSTON,MA. FU NCRR NIH HHS [M01 RR 2172] NR 20 TC 77 Z9 78 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 NOV 20 PY 1996 VL 276 IS 19 BP 1563 EP 1567 DI 10.1001/jama.276.19.1563 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA VT025 UT WOS:A1996VT02500028 PM 8918853 ER PT J AU Vostal, JG Mondoro, TH Shafer, B AF Vostal, JG Mondoro, TH Shafer, B TI Erbstatin analog selectively increases tyrosine phosphorylation of a 95 kDa protein in thrombin-activated platelets. SO BLOOD LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 118 EP 118 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300118 ER PT J AU Chang, AC Koo, EL Wood, LL Weinstein, MJ AF Chang, AC Koo, EL Wood, LL Weinstein, MJ TI The activation of coagulation factor VIII by thrombin requires a novel secondary recognition site in addition to the catalytic site of the enzyme. SO BLOOD LA English DT Meeting Abstract C1 US FDA,LAB HEMOSTASIS,DIV HEMATOL,OFF BLOOD RES & REVIEW,CTR BIOL EVALUAT & RES,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 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 NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1277 EP 1277 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301277 ER PT J AU Cheung, SC Lebel, D Wood, L Weinstein, M AF Cheung, SC Lebel, D Wood, L Weinstein, M TI The interaction of recombinant: Factor VIII with von Willebrand factor is modulated by the B domain of factor VIII. SO BLOOD LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,HEMOSTASIS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1289 EP 1289 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301289 ER PT J AU Murata, T Puri, RK AF Murata, T Puri, RK TI IL-13 augments Tyk2 phosphorylation in EBV-immortalized human B cells. SO BLOOD LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPY,LAB MOL TUMOR BIOL,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2143 EP 2143 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302143 ER PT J AU TeruyaFeldstein, J Jaffe, ES Burd, PR Kanegane, H Kingma, DW Wilson, WH Longo, DL Tosato, G AF TeruyaFeldstein, J Jaffe, ES Burd, PR Kanegane, H Kingma, DW Wilson, WH Longo, DL Tosato, G TI Expression of interferon-gamma inducible protein (IP-10) and the macrophage interferon-gamma induced gene (MIG) in lymphomatoid granulomatosis and nasal T/NK cell lymphoma with necrosis and vascular damage. SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20014. NIA,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2669 EP 2669 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302669 ER PT J AU Mondoro, TH Vostal, JG AF Mondoro, TH Vostal, JG TI GPIIb-IIIa dynamics in cold-treated platelets. SO BLOOD 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 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 NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2939 EP 2939 PN 2 PG 1 WC Hematology SC Hematology GA VT986 UT WOS:A1996VT98600200 ER PT J AU Mondoro, TH Wall, CD White, MM Jennings, LK AF Mondoro, TH Wall, CD White, MM Jennings, LK TI Selective induction of a glycoprotein IIIa ligand-induced binding site by fibrinogen and von Willebrand factor SO BLOOD LA English DT Article ID MONOCLONAL-ANTIBODY; PLATELET-AGGREGATION; VONWILLEBRAND-FACTOR; IIB/IIIA COMPLEX; CELL-ADHESION; GPIIB-IIIA; RECEPTOR; EXPOSURE; IIB; INTEGRIN AB Ligand-induced binding sites (LIBS) are neoantigenic regions of glycoprotein (GP)IIb-IIIa that are exposed upon interaction of the receptor with the ligand fibrinogen or the ligand recognition sequence (RGDS). LIBS have been suggested to contribute to postreceptor occupancy events such as full-scale platelet aggregation, adhesion to collagen, and clot retraction. This study examined the induction requirements of a GPIIIa LIBS with regard to ligand specificity. Through the use of the anti-LIBS D3, we report that this complex-activating antibody induces fibrinogen- and von Willebrand factor-binding to GPIIb-IIIa on intact platelets. Bound ligand was detected by flow cytometric analysis and platelet aggregation assays. These bound ligands increased the number of D3-binding sites and altered the affinity of D3 for GPIIb-IIIa on platelets. In contrast, activation of platelet GPIIb-IIIa by D3 did not increase the binding of another RGD-containing ligand, vitronectin. Furthermore, bound vitronectin on thrombin-stimulated platelets did not cause the expression of the D3 LIBS epitope. We conclude direct activation of GPIIb-IIIa in the absence of platelet activation results in selective ligand interaction and that D3 LIBS induction requires the binding of the multivalent ligands, fibrinogen or von Willebrand factor. Thus, the region of GPIIIa recognized by D3 may be an important regulatory domain in ligand-receptor interactions that directly mediate platelet aggregation, (C) 1996 by The American Society of Hematology. C1 UNIV TENNESSEE, DEPT MED, MEMPHIS, TN 38163 USA. UNIV TENNESSEE, DEPT BIOCHEM, MEMPHIS, TN 38163 USA. US FDA, CTR BIOL EVALUAT & RES, BETHESDA, MD USA. NR 27 TC 24 Z9 28 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 NOV 15 PY 1996 VL 88 IS 10 BP 3824 EP 3830 PG 7 WC Hematology SC Hematology GA VU984 UT WOS:A1996VU98400016 PM 8916946 ER PT J AU Aman, MJ Tayebi, N Obiri, NI Puri, RK Modi, WS Leonard, WJ AF Aman, MJ Tayebi, N Obiri, NI Puri, RK Modi, WS Leonard, WJ TI cDNA cloning and characterization of the human interleukin 13 receptor alpha chain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SEQUENCE CLEAVAGE SITES; LIGAND-BINDING; GAMMA-CHAIN; B-CELLS; CYTOKINE; EXPRESSION; MONOCYTES; SUBUNITS; IL-4 AB We have cloned cDNAs corresponding to the human interleukin 13 receptor alpha chain (IL-13R alpha). The protein has 76% homology to murine IL-13R alpha, with 95% amino acid identity in the cytoplasmic domain. Only weak IL-13 binding activity was found in cells transfected with only IL-13R alpha; however, the combination of both IL-13R alpha and IL-4R alpha resulted in substantial binding activity, with a K-d of approximately 400 pM, indicating that both chains are essential components of the IL-13 receptor. Whereas IL-13R alpha serves as an alternative accessory protein to the common cytokine receptor gamma chain (gamma(c)) for IL-4 signaling, it could not replace the function of gamma(c) in allowing enhanced IL-2 binding activity. Nevertheless, the overall size and length of the cytoplasmic domain of IL-13R alpha and gamma(c) are similar, and like gamma(c), IL-13R alpha is located on chromosome X. C1 NHLBI,LAB MOL IMMUNOL,NIH,BETHESDA,MD 20892. NIMH,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,FREDERICK,MD 21702. NR 28 TC 243 Z9 251 U1 2 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 NOV 15 PY 1996 VL 271 IS 46 BP 29265 EP 29270 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VT052 UT WOS:A1996VT05200078 PM 8910586 ER PT J AU LeClerc, JE Li, BG Payne, WL Cebula, TA AF LeClerc, JE Li, BG Payne, WL Cebula, TA TI High mutation frequencies among Escherichia coli and Salmonella pathogens SO SCIENCE LA English DT Article ID MISMATCH-REPAIR; HEMORRHAGIC COLITIS; SINGLE ORGANISM; STRAINS; TYPHIMURIUM; GENE; DNA; IDENTIFICATION; RECOMBINATION; AMPLIFICATION AB Here it is reported that the incidence of mutators among isolates of pathogenic Escherichia coli and Salmonella enterica is high (over 1 percent). These findings counter the theory, founded on studies with laboratory-attenuated strains, that suggests mutators are rare among bacterial populations. Defects in methyl-directed mismatch repair underlie all mutator phenotypes described here. Of nine independently derived hypermutable strains, seven contained a defective mutS allele. Because these mutant alleles increase the mutation rate and enhance recombination among diverse species, these studies may help explain both the rapid emergence of antibiotic resistance and the penetrance of virulence genes within the prokaryotic community. C1 US FDA,MOL BIOL BRANCH,CTR FOOD SAFETY & APPL NUTR HFS235,WASHINGTON,DC 20204. NR 33 TC 575 Z9 590 U1 4 U2 46 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 15 PY 1996 VL 274 IS 5290 BP 1208 EP 1211 DI 10.1126/science.274.5290.1208 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VT335 UT WOS:A1996VT33500059 PM 8895473 ER PT J AU Elashoff, M Lagakos, S AF Elashoff, M Lagakos, S TI HIV treatment strategies utilizing virologic and immunologic markers as criteria for changing treatments SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Symposium on Statistical Issues in HIV/AIDS Research CY JUN 12-13, 1995 CL NIH, BETHESDA, MD HO NIH ID ZIDOVUDINE; THERAPY; RESISTANCE; DISEASE; VIRUS; AIDS AB Currently available antiviral drugs used in the treatment of AIDS patients are effective for a limited time. Therapy consisting of different drugs given in sequence thus has the potential to yield the greatest possible benefit to patients, yet it is not known in what order the drugs should be administered, or for how long. Can patient-specific information, such as viral load or determination of mutation status, be used to make these decisions on a patient by patient basis? We propose a general model for the relationship between treatment, virologic or immunologic markers, and clinical disease progression that can provide answers to these questions. We develop guidelines for optimizing progression under several settings. Optimal survival is derived for full, partial, or no interim information. C1 HSPH,DEPT BIOSTAT,BOSTON,MA 02115. RP Elashoff, M (reprint author), US FDA,9201 CORP BLVD,GAITHERSBURG,MD 20878, USA. FU NIAID NIH HHS [AI24643] NR 14 TC 6 Z9 7 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 NOV 15 PY 1996 VL 15 IS 21-22 BP 2425 EP 2443 DI 10.1002/(SICI)1097-0258(19961130)15:22<2425::AID-SIM461>3.0.CO;2-D PG 19 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 VQ193 UT WOS:A1996VQ19300016 PM 8931211 ER PT J AU Fields, BA Malchiodi, EL Li, HM Ysern, X Stauffacher, CV Schlievert, PM Karjalainen, K Mariuzza, RA AF Fields, BA Malchiodi, EL Li, HM Ysern, X Stauffacher, CV Schlievert, PM Karjalainen, K Mariuzza, RA TI Crystal structure of a T-cell receptor beta-chain complexed with a superantigen SO NATURE LA English DT Article ID 3-DIMENSIONAL STRUCTURE; ANTIGEN RECEPTOR; BINDING; MHC AB SUPERANTIGENS (SAgs) are viral or bacterial proteins that act as potent T-cell stimulants and have been implicated in a number of human diseases, including toxic shock syndrome(1,2), diabetes mellitus(3) and multiple sclerosis(4). The interaction of SAgs with the T-cell receptor (TCR) and major histocompatibility complex (MHC) proteins results in the stimulation of a disproportionately large fraction of the T-cell population(2). We report here the crystal structures of the beta-chain of a TCR complexed with the Staphylococcus aureus enterotoxins C2 and C3 (SEC2, SEC3). These enterotoxins, which cause both toxic shock and food poisoning, bind in an identical way to the TCR beta-chain. The complementarity-determining region 2 (CDR2) of the beta-chain and, to lesser extents, CDR1 and hypervariable region 4 (HV4), bind in a cleft between the two domains of the SAgs. Thus, there is considerable overlap between the SAg-binding site and the peptide/MHC-binding sites of the TCR. A model of a TCR-SAg-MHC complex constructed from the crystal structures of (1) the beta-chain-SEC3 complex, (2) a complex between staphylococcal enterotoxin B (SEB) and an MHC molecule(5), and (3) a TCR V alpha domain(6), reveals that the SAg acts as a wedge between the TCR and MHC to displace the antigenic peptide away from the TCR combining site. In this way, the SAg is able to circumvent the normal mechanism for T-cell activation by specific peptide/MHC complexes. C1 UNIV MARYLAND,MARYLAND BIOTECHNOL INST,CTR ADV RES BIOTECHNOL,ROCKVILLE,MD 20850. UNIV BUENOS AIRES,FAC FARM & BIOQUIM,CATEDRA IMMUNOL,CONICET,INST ESTUDIOS INMUNIDAD HUMORAL,RA-1113 BUENOS AIRES,DF,ARGENTINA. US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. PURDUE UNIV,DEPT BIOL SCI,W LAFAYETTE,IN 47907. UNIV MINNESOTA,SCH MED,DEPT MICROBIOL,MINNEAPOLIS,MN 55455. BASEL INST IMMUNOL,CH-4005 BASEL,SWITZERLAND. RI Karjalainen, Klaus/A-2206-2011; OI Li, Hongmin/0000-0002-8684-5308 NR 31 TC 234 Z9 241 U1 2 U2 6 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD NOV 14 PY 1996 VL 384 IS 6605 BP 188 EP 192 DI 10.1038/384188a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VT336 UT WOS:A1996VT33600071 PM 8906797 ER PT J AU Ambrosone, CB Freudenheim, JL Graham, S Marshall, JR Vena, JE Brasure, JR Michalek, AM Laughlin, R Nemoto, T Gillenwater, KA Harrington, AM Shields, PG AF Ambrosone, CB Freudenheim, JL Graham, S Marshall, JR Vena, JE Brasure, JR Michalek, AM Laughlin, R Nemoto, T Gillenwater, KA Harrington, AM Shields, PG TI Cigarette smoking, N-acetyltransferase 2 genetic polymorphisms, and breast cancer risk SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RAT MAMMARY-GLAND; METABOLIC-ACTIVATION; ALCOHOL-CONSUMPTION; COLORECTAL-CANCER; BLADDER-CANCER; ACETYLATOR POLYMORPHISM; EPITHELIAL-CELLS; DNA ADDUCTS; PHENOTYPE; WOMEN AB Objective.-To determine if N-acetyltransferase 2 (NAT2) polymorphisms result in decreased capacity to detoxify carcinogenic aromatic amines in cigarette smoke, thus making some women who smoke more susceptible to breast cancer. Design.-Case-control study with genetic analyses, DNA analyses were performed for 3 polymorphisms accounting for 90% to 95% of the slow acetylation phenotype among whites. Setting and Participants.-White women with incident primary breast cancer (n=304) and community controls (n=327). Results.-Neither smoking nor NAT2 status was independently associated with breast cancer risk. There were no clear patterns of increased risk associated with smoking by NAT2 status among premenopausal women. In postmenopausal women, NAT2 strongly modified the association of smoking with risk. For slow acetylators, current smoking and smoking in the distant past increased breast cancer risk in a dose-dependent manner (odds ratios [95% confidence intervals] for the highest quartile of cigarettes smoked 2 and 20 years previously, 4.4 [1.3-14.8] and 3.9 [1.4-10.8], respectively). Among rapid acetylators, smoking was not associated with increased breast cancer risk. Conclusions.-Our results suggest that smoking may be an important risk factor for breast cancer among postmenopausal women who are slow acetylators, demonstrate heterogeneity in response to carcinogenic exposures, and may explain previous inconsistent findings for cigarette smoking as a breast cancer risk factor. C1 SUNY BUFFALO,DEPT SOCIAL & PREVENT MED,BUFFALO,NY 14260. SUNY BUFFALO,DEPT SURG,BUFFALO,NY 14260. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. RP Ambrosone, CB (reprint author), NATL CTR TOXICOL RES,DIV MOL EPIDEMIOL,3900 NCTR RD,JEFFERSON,AR 72079, USA. RI Shields, Peter/I-1644-2012 FU NCI NIH HHS [CA-62995, CA-01633, CA-11535] NR 77 TC 279 Z9 282 U1 0 U2 3 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 NOV 13 PY 1996 VL 276 IS 18 BP 1494 EP 1501 DI 10.1001/jama.276.18.1494 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA VQ774 UT WOS:A1996VQ77400032 PM 8903261 ER PT J AU Holson, RR Bowyer, JF Clausing, P Gough, B AF Holson, RR Bowyer, JF Clausing, P Gough, B TI Methamphetamine-stimulated striatal dopamine release declines rapidly over time following microdialysis probe insertion SO BRAIN RESEARCH LA English DT Article DE amphetamine; microdialysis; striatum; dopamine; DOPAC; time course; rat ID INDUCED NEUROTOXICITY; GLUTAMATE RELEASE; CAUDATE-PUTAMEN; TERMINAL INJURY; RAT STRIATUM; DIALYSIS; OVERFLOW; METABOLISM AB To investigate changes in striatal dopamine release over a series of brief methamphetamine (METH) exposures, METH was pulsed three times at 2-h intervals, with the first exposure occurring 2 h after microdialysis probe insertion. Whether METH was administered directly into the striatum via the microdialysate (20 mu M Of METH for 10 min), or via peripheral intraperitoneal (i.p.) injection (1 mg/kg METH, i.p.), the dopamine (DA) peak elicited by the third METH exposure was only 50% as large as that elicited by the first exposure, 4 h earlier. This decline in the magnitude of METH-induced DA release probably continued over at least 24 h, since the magnitude of a single peak 26 h after probe implantation was only one-seventh of that at 2 h. This reduction in the response to METH was a function of time post-probe insertion, and not of prior METH exposure. Thus, peak size was the same at 6 h post-implantation in animals which received two prior METH pulses or no prior METH pulses, and in both cases this 6-h peak was substantially lower than that at 2 h post-implantation. Circadian influences were also excluded as a factor, because size of the initial METH-induced DA peak did not vary as a function of time of probe implantation. It is concluded that METH-stimulated striatal DA release declines rapidly over time post-probe insertion. When METH exposures occur repeatedly at short intervals, this decline can mimic, but is not caused by, desensitization or depletion in response to prior METH exposure. C1 NATL CTR TOXICOL RES,DIV NEUROTOXICOL,JEFFERSON,AR 72079. RP Holson, RR (reprint author), NATL CTR TOXICOL RES,DIV DEV TOXICOL,JEFFERSON,AR 72079, USA. NR 26 TC 22 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 11 PY 1996 VL 739 IS 1-2 BP 301 EP 307 DI 10.1016/S0006-8993(96)00837-2 PG 7 WC Neurosciences SC Neurosciences & Neurology GA VV253 UT WOS:A1996VV25300034 PM 8955951 ER PT J AU Manjanatha, MG Chen, JB Shaddock, JG Harris, AJ Shelton, SD Casciano, DA AF Manjanatha, MG Chen, JB Shaddock, JG Harris, AJ Shelton, SD Casciano, DA TI Molecular analysis of lacI mutations in Rat2(TM) cells exposed to 7,12-dimethylbenz[a]anthracene: Evidence for DNA sequence and DNA strand biases for mutation SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE lacI; Rat2(TM) cell; mutant frequency; strand bias ID HAMSTER OVARY CELLS; UV-INDUCED MUTATIONS; TRANSGENIC MICE; EXCISION-REPAIR; HPRT GENE; HA-RAS; MAMMARY CARCINOGENESIS; TRANSCRIBED STRAND; HUMAN FIBROBLASTS; SHUTTLE VECTOR AB The Rat2(TM) cell line carries 50-70 stably integrated copies per cell of a lambda/lacl shuttle vector asa target for mutagenicity testing. Rat2(TM) cells were exposed to 1 and 10 mu g/ml of 7,12-dimethylbenz[a]anthracene (DMBA) for 24 h at 37 degrees C in the presence of primary rat hepatocytes, and grown to confluence. The shuttle vector was rescued from untreated and mutagen-treated cells and mutant frequencies were determined. The low and high doses of DMBA induced mutant frequencies that were 7-fold (25 +/- 4.9 x 10(-5)) and 33-fold (127 +/- 19.9 x 10(-5)) higher, respectively, than the spontaneous mutant frequency (3.8 +/- 0.7 x 10(-5)). DNA sequence analysis of the DMBA-induced lacl(-) mutants indicated that they contained mainly basepair substitution mutations at A:T and G:C, and that A:T --> T:A and G:C --> T:A transversions were the predominant types. In addition, 23 of 28 (82%) A:T basepair substitution mutations occurred with the mutated dA, the putatively adducted base, on the coding strand. Furthermore, 20 of the 28 (71%) A:T mutations had the mutated dA flanked 5' by a dC, and 17 of these were A:T --> T:A transversions, suggesting a sequence preference for this mutation. Except for a higher proportion of G:C --> A:T transitions in the low dose data, the mutational profiles from low and high doses of DMBA were similar. These results indicate that DMBA mutagenesis in the lacl gene of Rat2(TM) cells displays distinct DNA sequence and DNA strand preferences. RP Manjanatha, MG (reprint author), NATL CTR TOXICOL RES,DIV GENET TOXICOL,FOOD & DRUG ADM,DEPT HLTH & HUMAN SERV,JEFFERSON,AR 72079, USA. NR 54 TC 27 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD NOV 11 PY 1996 VL 372 IS 1 BP 53 EP 64 DI 10.1016/S0027-5107(96)00162-5 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA WE201 UT WOS:A1996WE20100007 PM 9003531 ER PT J AU Vostal, JG Shafer, B Mondoro, TH Fratantoni, JC AF Vostal, JG Shafer, B Mondoro, TH Fratantoni, JC TI Endogenous ADP prevents PGE(1)-induced tyrosine dephosphorylation of focal adhesion kinase in thrombin-activated platelets SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE platelet; tyrosine phosphorylation; prostaglandin E(1); thrombin; ADT; focal adhesion kinase ID GLYCOPROTEIN-IIB-IIIA; DEPENDENT PHOSPHORYLATION; PROTEIN-PHOSPHORYLATION; CAMP; FIBRINOGEN; MEMBRANE; INTEGRIN; BINDING; CA-2+; TRANSLOCATION AB Prostaglandin E(1)(PCE(1)) inhibits tyrosine phosphorylation induced by low thrombin concentration (0.05 U/ml), but this is overcome by a high thrombin (2.0 U/ml) concentration. Thromboxane A(2) and ADP are endogenous platelet agonists released during platelet activation which potentiate platelet responses, We investigated how these endogenous agonists influenced the effects of PGE(1) on thrombin (2.0 U/ml)-induced tyrosine phosphorylation by removing released ADP with apyrase (2.0 U/ml) and by inhibiting thromboxane A(2) synthesis with indomethacin(1 mu M). Adding PGE(1) (1 mu M) before thrombin in apyrase/indomethacin(A/I)-treated platelets selectively prevented thrombin-induced tyrosine phosphorylation of a 117 kDa protein while other substrates were not affected. This selective effect was evident only in the presence of apyrase and was not dependent on indomethacin. Addition of PGE(1) to A/I-treated platelets after thrombin also caused selective tyrosine dephosphorylation of the 117 kDa protein. Conditions which prevented thrombin-induced 117 kDa protein tyrosine phosphorylation also decreased fibrinogen binding to platelets. The 117 kDa protein was identified as the focal adhesion kinase (FAK) by immunoprecipitation with a monoclonal antibody to FAK and by absence of its tyrosine phosphorylation in the presence of RGDS peptide which inhibits fibrinogen binding and platelet aggregation. Thus, released endogenous ADP selectively prevents PGE(1)-mediated tyrosine dephosphorylation of platelet FAK most likely by stabilizing fibrinogen binding to platelets. RP Vostal, JG (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,LAB CELLULAR HEMATOL,BLDG 29,RM 323,HFM-335,BETHESDA,MD 20892, USA. NR 40 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD NOV 8 PY 1996 VL 1314 IS 1-2 BP 1 EP 12 DI 10.1016/S0167-4889(96)00066-3 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VW035 UT WOS:A1996VW03500002 PM 8972712 ER PT J AU Mulligan, KJ Brueggemeyer, TW Crockett, DF Schepman, JB AF Mulligan, KJ Brueggemeyer, TW Crockett, DF Schepman, JB TI Analysis of organic volatile impurities as a forensic tool for the examination of bulk pharmaceuticals SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS LA English DT Review DE reviews; headspace analysis; forensic analysis; statistical techniques; residual solvents; volatile organic compounds ID AUTOMATED HEADSPACE METHOD; CAPILLARY GAS-CHROMATOGRAPHY; RESIDUAL SOLVENTS; METHOD-I; SUBSTANCES; PRODUCTS; HEROIN; DRUGS AB This discussion offers an overview of some formally accepted methodology in the USA for the determination of organic volatile impurities in pharmaceuticals. Particular advantages of equilibrium headspace sampling with capillary gas chromatography for this task are outlined and some important considerations are expressed. Specific adaptations which we have made for forensic applications are described along with mention of select applications within the context of the detection of the counterfeiting of bulk pharmaceuticals. Finally, a brief description is provided of statistical techniques which can be used to effectively manipulate multivariate data sets for purposes of distinguishing between the manufacturers of a product based upon impurity profiles. RP Mulligan, KJ (reprint author), US FDA,FORENS CHEM CTR,1141 CENTRAL PKWY,CINCINNATI,OH 45202, USA. NR 46 TC 18 Z9 19 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B-Biomed. Appl. PD NOV 8 PY 1996 VL 686 IS 1 BP 85 EP 95 DI 10.1016/S0378-4347(96)00109-0 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA VV051 UT WOS:A1996VV05100011 PM 8953195 ER PT J AU Muskhelishvili, L Turturro, A Hart, RW James, SJ AF Muskhelishvili, L Turturro, A Hart, RW James, SJ TI pi-class glutathione-S-transferase-positive hepatocytes in aging B6C3F1 mice undergo apoptosis induced by dietary restriction SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ANDROGEN RECEPTOR GENE; PROGRAMMED CELL-DEATH; CALORIC RESTRICTION; RAT-LIVER; C-JUN; DEPENDENT EXPRESSION; PRENEOPLASTIC FOCI; FOOD RESTRICTION; CARCINOGENESIS; PROLIFERATION AB Liver sections front aging ad libitum-fed and diet-restricted B6C3F1 male mice were evaluated immunohistochemically pi-class glutathione S-transferase (GST-II). GST-II immunostaining of hepatocytes was diffuse and occurred in periportal regions of hepatic acinus, whereas perivenous areas were weakly stained or were stain-free. Expression of GST-II was significantly diminished in diet-restricted mice in all age groups and was associated with a marked decrease in liver tumor development. As most spontaneous liver tumors were GST-II positive, it can be speculated that they developed from GST-II-positive initiated hepatocytes, To determine whether dietary restriction induces apoptosis ill GST-II-positive hepatocytes, 24-month-old ad libitum-fed mice were introduced to 40% diet restriction. After 1 week of diet restriction, a decrease in GST-II expression tons associated with a threefold increase its the frequency of apoptotic bodies as detected by terminal deoxynucleotidyl transferase-mediated d-UTP nick end labeling of DNA fragments. A two-step immunohistochemical procedure revealed that approximately 70% of apoptotic bodies were GST-II positive, These results suggest that spontaneous, potentially preneoplastic hepatocytes in tumor-prone B6C3F1 mice are eliminated by apoptosis with dietary restriction. C1 US FDA,NATL CTR TOXICOL RES,DIV NUTR TOXICOL,JEFFERSON,AR 72079. US FDA,NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,JEFFERSON,AR 72079. NR 43 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1996 VL 149 IS 5 BP 1585 EP 1591 PG 7 WC Pathology SC Pathology GA VQ237 UT WOS:A1996VQ23700019 PM 8909248 ER PT J AU Putnak, R Cassidy, K Conforti, N Lee, R Sollazzo, D Truong, T Ing, E Dubois, D Sparkuhl, J Gastle, W Hoke, C AF Putnak, R Cassidy, K Conforti, N Lee, R Sollazzo, D Truong, T Ing, E Dubois, D Sparkuhl, J Gastle, W Hoke, C TI Immunogenic and protective response in mice immunized with a purified, inactivated, dengue-2 virus vaccine prototype made in fetal rhesus lung cells SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID TICK-BORNE ENCEPHALITIS; PRIMARY KIDNEY-CELLS; MONOCLONAL-ANTIBODIES; ANTIGENIC DETERMINANTS; JAPANESE ENCEPHALITIS; SERIAL PASSAGE; CANDIDATE; NEUTRALIZATION; IDENTIFICATION; REACTOGENICITY AB The feasibility of a purified, inactivated vaccine (PIV) against dengue type 2 (DEN-2) virus was explored. Dengue-2 virus strain 16681 was used for producing a monotypic PIV. Virus adapted to fetal. rhesus lung (FRhL-2) cells was harvested from roller bottle culture supernatant fluids, concentrated, and purified on sucrose gradients. Analysis of purified virus preparations by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting showed primarily envelope (E) and premembrane (prM) antigens. These preparations had a purity, estimated from silver-stained gels, of approximately 70%, and a yield, based on recovery of virus and viral antigen, of 10-20%. The purified virus was inactivated with 0.05% formalin at 22 degrees C, or alternatively, with 7 mRads from a Co-60 source. Vaccinated mice developed high titers of anti-DEN-2 virus neutralizing antibody and were partially protected from virus challenge. These results warrant further testing and development of PIVs for the other DEN virus serotypes. C1 MICROBIX BIOSYST INC,TORONTO,ON,CANADA. US FDA,OFF DEVICE EVALUAT,ROCKVILLE,MD 20857. RP Putnak, R (reprint author), WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,DEPT VIRUS DIS,WASHINGTON,DC 20307, USA. NR 31 TC 30 Z9 31 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 1996 VL 55 IS 5 BP 504 EP 510 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA VU702 UT WOS:A1996VU70200009 PM 8940981 ER PT J AU Yin, JJ Smith, MJ Eppley, RM Troy, AL Page, SW Sphon, JA AF Yin, JJ Smith, MJ Eppley, RM Troy, AL Page, SW Sphon, JA TI Effects of fumonisin B-1 and (hydrolyzed) fumonisin backbone AP(1) on membranes: A spin-label study SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE fumonisin; membrane; ESR ID ALTERS SPHINGOLIPID METABOLISM; ELECTRON DOUBLE-RESONANCE; VERTICAL FLUCTUATIONS; FUSARIUM-MONILIFORME; LATERAL DIFFUSION; CHAIN; BILAYER; PHOSPHOLIPIDS; CHOLESTEROL; TOXICITY AB Electron spin resonance (ESR) spectroscopy and spin label techniques have been used to study the effects of fumonisin B-1 (FB1) and hydrolyzed fumonisin backbone (AP(1)) on the structural and dynamic properties of phosphatidylcholine membranes at the molecular level. Multilamellar liposomes consisting of dimyristoylphosphatidylcholine (DMPC) and egg yolk phosphatidylcholine (EYPC) were used. Six different nitroxide spin labels were used to determine what effects FB1 may impart on the ordering and mobility of lipids in membranes. The experimental results disclose the following: (1) In the fluid phase membrane, FB1 significantly increases the fluidities of n-doxylstearic acid (SA) spin labels (SL) attached to carbons 5 and 7, which disorders the alkyl chains and perturbs the surface region of the bilayer; by comparison, minimal effects were detected near the center of the bilayer. (2) In the gel phase, FB1 and AP(1) imparts marked rigidifying effects on membrane fluidity, which enlarges the change in ordering on the phase transition even further. (3) FB1 also restricts the mobility of the (rigid) cholestane spin label. (4) A reduction in mobility of the tempo-stearate spin label suggests that the tricarballylic acid (TCA) moieties of FB1 might mimic the structure of polar headgroups in phospholipids. The present results may provide additional mechanisms to elucidate the toxicological activities of the fumonisins. (C) 1996 Academic Press, Inc. RP Yin, JJ (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,200 C ST SW,WASHINGTON,DC 20204, USA. RI Yin, Jun Jie /E-5619-2014 NR 36 TC 24 Z9 24 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD NOV 1 PY 1996 VL 335 IS 1 BP 13 EP 22 DI 10.1006/abbi.1996.0477 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VT732 UT WOS:A1996VT73200003 PM 8914830 ER PT J AU Seng, JE Gandy, J Turturro, A Lipman, R Bronson, RT Parkinson, A Johnson, W Hart, RW Leakey, JEA AF Seng, JE Gandy, J Turturro, A Lipman, R Bronson, RT Parkinson, A Johnson, W Hart, RW Leakey, JEA TI Effects of caloric restriction on expression of testicular cytochrome P450 enzymes associated with the metabolic activation of carcinogens SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE dietary restriction; testes; cytochrome P450 monooxygenase; testosterone 7 alpha-hydroxylase; CYP2A1; dealkylase; Leydig cell hyperplasia ID RAT-LIVER MICROSOMES; SPRAGUE-DAWLEY RATS; FISCHER-344 RATS; LEYDIG-CELLS; TESTOSTERONE 7-ALPHA-HYDROXYLASE; CHOLESTEROL 7-ALPHA-HYDROXYLASE; REPRODUCTIVE FUNCTION; PROSTATE MICROSOMES; SPECIES-DIFFERENCES; FOOD RESTRICTION AB Previous work demonstrated that microsomal cytochrome P4502A1 (CYP2A1) is expressed in rat testicular Leydig cells. The present study investigates the effects of diet, age, and strain on rat testicular CYP2A1 expression and assesses the potential role of testicular CYP2A1 in the metabolic activation of carcinogens. In ad libitum-fed 18-week-old Fischer 344 rats, testicular CYP2A1 immunoreactive protein and testosterone 7 alpha-hydroxylase activity (7 alpha-TOHase) exhibited a circadian variation with a daytime maximum and a night-time minimum (82.2 +/- 42.0 and 21.9 +/- 4.5 pmol 7 alpha-hydroxytestosterone/min/mg protein, respectively). Caloric restriction (to 60% of ad libitum consumption), which reduces the severity of Leydig cell tumors in rats, decreased expression of both CYP2A1 and testicular 7 alpha-TOHase >80% and eliminated their circadian variation. Conversely, caloric restriction induced a circadian rhythm in testicular 7-benzyloxyresorufin-O-dealkylase activity. Testicular microsomes from ad libitum-fed rats having peak diurnal 7 alpha-TOHase activity had significantly greater (30%) microsome-mediated aflatoxin B-1-DNA binding activity compared to microsomes prepared from nocturnal phase ad libitum-fed or calorically restricted rats which expressed low 7 alpha-TOHase activity. In 12-month-old Fischer 344 rats, high CYP2A1 expression was correlated with severe Leydig cell hyperplasia (r = 0.80), whereas CYP2A immunoreactive protein and 7 alpha-TOHase were expressed at lower levels in Sprague-Dawley than in Fischer 344 rats and were undetectable in pig, monkey, and human testes. These are strains/species that do not exhibit significant Leydig cell hyperplasia. This suggests that caloric intake, strain, and circadian factors may all mediate testicular CYP2A1 expression in the rat and that CYP2A1 may in turn influence carcinogen activation and pathological status in the testis. C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72079. UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL TOXICOL,LITTLE ROCK,AR 72205. UNIV KANSAS,MED CTR,CTR ENVIRONM & OCCUPAT HLTH,DEPT PHARMACOL TOXICOL & THERAPEUT,KANSAS CITY,KS 66160. TUFTS UNIV,USDA,HUMAN NUTR RES CTR AGING,BOSTON,MA 02111. US FDA,CTR FOOD SAFETY & APPL NUTR,LAUREL,MD 20708. FU NIEHS NIH HHS [ES05318]; PHS HHS [E503765, NIA 224-86-0001] NR 59 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD NOV 1 PY 1996 VL 335 IS 1 BP 42 EP 52 DI 10.1006/abbi.1996.0480 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VT732 UT WOS:A1996VT73200006 PM 8914833 ER PT J AU Kuipers, JG Raybourne, RB Williams, KM Zeidler, H Yu, DTY AF Kuipers, JG Raybourne, RB Williams, KM Zeidler, H Yu, DTY TI Specificities of human TAP alleles for HLA-B27 binding peptides SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ANKYLOSING-SPONDYLITIS; TRANSPORTERS; POLYMORPHISM; ASSOCIATION; VARIANTS AB Objective. Allelic TAP polymorphism has been linked to susceptibility to Reiter's syndrome and was suggested to influence disease phenotype in HLA-B27 positive patients with ankylosing spondylitis. In the present study, we examined whether the human TAP alleles functionally differ in their translocation specificity for HLA-B27-binding nonamers. Methods. TAP translocation of a panel of HLA-B27-binding peptides was measured with a labeled reporter peptide containing an N-linked glycosylation acceptor site in streptolysin O-permeabilized cells with different TAP alleles. Results. The different human TAP alleles tested did not measurably differ in their peptide specificity. Conclusion. The polymorphism of human TAP does not affect the translocated repertoire of HLA-B27 ligands and is therefore unlikely to play a decisive role in the development of HLA-B27-associated disease. C1 US FDA,LAUREL,MD. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. RP Kuipers, JG (reprint author), HANNOVER MED SCH,DIV RHEUMATOL,D-30623 HANNOVER,GERMANY. NR 12 TC 3 Z9 3 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 NOV PY 1996 VL 39 IS 11 BP 1892 EP 1895 DI 10.1002/art.1780391116 PG 4 WC Rheumatology SC Rheumatology GA VR600 UT WOS:A1996VR60000015 PM 8912512 ER PT J AU Volpe, DA Tomaszewski, JE Parchment, RE Garg, A Flora, KP Murphy, MJ Grieshaber, CK AF Volpe, DA Tomaszewski, JE Parchment, RE Garg, A Flora, KP Murphy, MJ Grieshaber, CK TI Myelotoxic effects of the bifunctional alkylating agent bizelesin on human, canine and murine myeloid progenitor cells SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE comparative; CFU-gm; in vitro; bizelesin; clonal assays ID INTERSTRAND CROSS-LINKING; ANTI-TUMOR AGENT; PHASE-I; DNA; CC-1065; U-73,975; U-77,779; FCE-24517; BINDING; ANALOG AB Bizelesin is a potent synthetic derivative of the anticancer agent CC-1065 that preferentially alkylates and binds the minor grove of DNA. Preclinical animal studies have found bizelesin to be more toxic to beagle dogs than to rodents and that myelosuppression was the dose-limiting toxicity. This toxicity was dose- and time-dependent in all species. Due to the significant difference in the in vivo myelotoxicity between species, it was important to determine which one most closely resembles humans on a pharmacodynamic basis. Therefore, hematopoietic clonal assays were utilized to evaluate the effects of bizelesin on granulocyte-macrophage (CFU-gm) colony formation. Marrow cells were exposed in vitro to bizelesin (0.001-1000 nM) for 1 or sh and then assayed for colony formation. There was a 3-log difference in drug concentration at which 100% colony inhibition occurred (1 or 8 h) for murine CFU-gm versus human or canine CFU-gm. The IC70 value after an 8-h bizelesin exposure for human CFU-gm (0.006 +/- 0.002 nM) was 2220-times lower than for murine CFU-gm (13.32 +/- 8.31 nM). At any given concentration, an 8 h drug exposure resulted in greater colony inhibition than a 1 h exposure for all species (P < 0.05). Increasing exposure time from 1 to 8 h increased toxicity to human and canine CFU-gm much more than to murine CFU-gm. The clinically formulated drug solution was a more potent inhibitor of human colony formation than drug dissolved in DMSO. The IC70 value after a 1-h exposure was 1.7 times lower for human CFU-gm with formulated bizelesin (0.106 +/- 0.105 nM) than bulk drug in DMSO (0.184 +/- 0.044 nM). The results of these in vitro clonal assays were qualitatively consistent with those seen in whole animal studies, suggesting that bizelesin will be a potent myelosuppressive agent in the clinic. Since the dose-limiting toxicity in preclinical models is myelosuppression and the in vitro sensitivity of human and canine CFU-gm is similar, the canine maximum tolerated dose (MTD) is better than the murine MTD to determine a safe starting dose for phase I clinical trials. C1 NCI,TOXICOL & PHARMACOL BRANCH,BETHESDA,MD 20892. HIPPLE CANC RES CTR,DAYTON,OH. RP Volpe, DA (reprint author), US FDA,DIV RES & TESTING,MOD-1 BLDG,ROOM 2009,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. FU NCI NIH HHS [N01-CM-37834] NR 24 TC 43 Z9 43 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 NOV-DEC PY 1996 VL 39 IS 1-2 BP 143 EP 149 DI 10.1007/s002800050550 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA VW720 UT WOS:A1996VW72000020 PM 8995512 ER PT J AU Ritter, CL Bennett, KK Fullerton, NF Beland, FA MalejkaGiganti, D AF Ritter, CL Bennett, KK Fullerton, NF Beland, FA MalejkaGiganti, D TI Effect of ovariectomy on the in vitro and in vivo activation of carcinogenic N-2-fluorenylhydroxamic acids by rat mammary gland and liver SO CARCINOGENESIS LA English DT Article ID N-HYDROXY ARYLAMINES; METABOLIC-ACTIVATION; ARYLHYDROXAMIC ACIDS; N-HYDROXY-2-ACETYLAMINOFLUORENE SULFOTRANSFERASE; PERITONEAL SEROSA; DNA ADDUCTS; FEMALE RATS; ACETYLTRANSFERASE; N-HYDROXY-N-2-FLUORENYLACETAMIDE; ACYLTRANSFERASE AB N-Hydroxy-N-2-fluorenylacetamide (N-OH-2-FAA) and its benzamide analogue N-OH-2-FBA are mammary gland carcinogens in the female Sprague-Dawley rat. Ovariectomy inhibits tumorigenicity of topically applied N-OH-2-FAA suggesting modulation of carcinogen-activating enzymes in the gland. This study concerned the activation of N-OH-2-FAA and N-OH-2-FBA by the mammary gland and liver, a chief site of metabolism, from 50-day-old female rats and effects on the activation of ovariectomy performed at 22 days of age. The levels of N-debenzolyation of N-OH-2-FBA to N-hydroxy-N-2-fluorenamine (N-OH-2-FA), catalyzed by microsomal carboxyl-esterases in mammary gland and liver were similar and increased 1.5- and 1.7-fold, respectively, by ovariectomy. N-Debenzoylating activity in cytosols of both tissues appeared to be partially of microsomal origin, Mammary gland cytosol contained N-, O- and N,O-acyltransferase activities at levels 40-50% those of liver, N-Acyltransferase activity was determined via acetyl coenzyme A (AcCoA)-dependent acetylation of 2-FA and a new assay, N-OH-2-FAA-dependent acetylation of 9-oxo-2-FA. The latter activity was decreased in mammary gland by ovariectomy, Microsomal N-acyltransferase activities were <36% those of cytosols, AcCoA-dependent binding of N-OH-2-[ring-H-3]FBA to DNA, catalyzed by cytosol, was consistent with a two-step activation of N-OH-2-FBA involving esterase-catalyzed N-debenzoylation to N-OH-2-FA and its O-acyltransferase-catalyzed acetylation to the electrophilic N-acetoxy-2-FA. O-Acetyltransfer by mammary gland appeared to be rate-limiting since ovariectomy-dependent increases in N-debenzoylation did not increase binding with S9 fraction. Little or no sulfotransferase-catalyzed binding of N-OH-2-[ring-H-3]FBA-derived N-OH-2-[ring-H-3]FA was detected in the liver or mammary gland cytosol, respectively. The level of binding of N-OH-2-[ring-H-3]FAA to DNA catalyzed by cytosolic N,O-acyltransferase was decreased similar to 23% in mammary gland and increased 1.2-fold in liver by ovariectomy, P-32-Postlabeling analyses indicated a single adduct N-(deoxyguanosin-8-yl)-2-fluorenamine in DNA of both tissues 24 h after one intraperitoneal injection of N-OH-2-FBA or N-OH-2-FAA. Respective levels were 3.6- and 5.5-fold greater in liver than mammary gland, After ovariectomy, the adduct levels from N-OH-2-FBA increased 1.8-fold in mammary gland and from N-OH-2-FAA decreased similar to 50% in both tissues, Thus, the ovariectomy-dependent changes in levels of enzymes activating N-OH-2-FBA and N-OH-2-FAA were consistent with in vivo DNA adduct levels in the target mammary gland, but not in the liver. C1 VET AFFAIRS MED CTR,RES SERV 151,MINNEAPOLIS,MN 55417. NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079. UNIV MINNESOTA,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455. FU NCI NIH HHS [CA-28000] NR 56 TC 4 Z9 4 U1 0 U2 0 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 NOV PY 1996 VL 17 IS 11 BP 2411 EP 2418 DI 10.1093/carcin/17.11.2411 PG 8 WC Oncology SC Oncology GA VW458 UT WOS:A1996VW45800019 PM 8968056 ER PT J AU Tamano, S Ward, JM Diwan, BA Keefer, LK Weghorst, CM Calvert, RJ Henneman, JR Ramljak, D Rice, JM AF Tamano, S Ward, JM Diwan, BA Keefer, LK Weghorst, CM Calvert, RJ Henneman, JR Ramljak, D Rice, JM TI Histogenesis and the role of p53 and K-ras mutations in hepatocarcinogenesis by glyceryl trinitrate (nitroglycerin) in male F344 rats SO CARCINOGENESIS LA English DT Article ID NITRIC-OXIDE SYNTHASE; IN-VITRO; NITRATE TOLERANCE; ORGANIC NITRATES; LIVER-TUMORS; H-RAS; MECHANISMS; APOPTOSIS; ACTIVATION; CARCINOGENICITY AB Glyceryl trinitrate (GTN) was previously reported to induce hepatocellular carcinoma (HCC) in rats after prolonged feeding, The present experiments were undertaken to evaluate the histogenesis and molecular biology of these tumors and the possible role of nitric oxide (NO), a GTN metabolite, in their development, Male F344 rats received a single i.g. intubation of GTN (1.2 g/kg) at 6 weeks of age and/or a diet containing 1% GTN from 8 weeks of age until necropsy, i.e. for up to 78 weeks, Some animals were subjected to 2/3 partial hepatectomy (PH) at 9 weeks of age, Five sequential sacrifices (14, 32, 52, 78 and 84 weeks of age) were performed, No liver tumors developed in control rats or in rats that received GTN only by a single i.g. intubation, even when intubation was followed by PH, Preneoplastic foci, mainly of clear cell and mixed cell type (identified as positive for glutathione S-transferase placental form) were found from 14 weeks of age in rats receiving GTN in the diet, Focal eosinophilic areas (atypical foci) composed of atypical hepatocytes that often extended into the veins were observed beginning at 52 weeks of age, Some mixed hepatocholangiocellular adenomas and carcinomas arose in eosinophilic lesions, HCCs were seen beginning at 78 weeks of age, but only in rats receiving dietary GTN, Incidence of HCC in the latter animals was 50-75%, Most HCCs were well differentiated, The carcinogenic effect of GTN given in the diet was not affected by prior intubation of a large single dose followed by PH, No p53 mutations were found in 18 tumors but K-ras point mutations, all within codon 12, were found in 8/18 tumors, mostly those with cholangiocellular elements, These were first or second position G-->T transversions or second position G-->A transitions, While these mutation types have also been commonly seen in bacteria after NO-related DNA damage, the fact that tumors arose only on prolonged feeding of this potently bioactive agent at massive doses seems consistent with a more complex mechanism involving multiple (i.e. genetic and/or epigenetic) factors in carcinogenesis by GTN. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,FREDERICK,MD 21702. SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. US FDA,CTR FOOD SAFETY & APPL NUTR,OFF SPECIAL NUTR,CLIN RES & REVIEW STAFF,LAUREL,MD 20708. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NCI NIH HHS [N01-CO-56000] NR 50 TC 17 Z9 17 U1 0 U2 0 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 NOV PY 1996 VL 17 IS 11 BP 2477 EP 2486 DI 10.1093/carcin/17.11.2477 PG 10 WC Oncology SC Oncology GA VW458 UT WOS:A1996VW45800029 PM 8968066 ER PT J AU Lynn, F Reed, GF Meade, BD AF Lynn, F Reed, GF Meade, BD TI Collaborative study for the evaluation of enzyme-linked immunosorbent assays used to measure human antibodies to Bordetella pertussis antigens SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID INFECTION; SEROLOGY; VACCINE; TRIAL AB Acellular pertussis vaccines are being evaluated in multiple clinical studies, and human immunogenicity data will likely be pivotal in the appraisal of vaccine responses between populations and the responses to different vaccine combinations. Antibody response to pertussis antigens is also used in the diagnosis of pertussis. An international study was designed to assess the comparability of data generated in different laboratories by enzyme-linked immunosorbent assays (ELISAs). Thirty-three participating laboratories were asked to quantitate specific antibody to pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), or fimbrial proteins (FIM) in 21 samples. Samples were to be assayed in triplicate in five independent assays by each ELISA routinely performed in the laboratory to assess intra-assay, interassay, and population variability. The mean sample values were used to compare quantitative results among the laboratories. Thirteen of the 32 laboratories which submitted evaluable data for an assay to measure antibodies to PT, 12 of 30 laboratories with assays for FHA, 10 of 17 laboratories with assays for PRN, and 6 of 13 laboratories with assays for FIM maintained a coefficient of variation below 20% for 75% of the samples tested. Assays that measure antibodies to FIM appear to be less precise than the other assays. Precision varied among laboratories that used similar methods. The relative values of intra- and interassay variabilities were not consistent for a given assay within a laboratory, indicating that the sources of these variability components may be unrelated. Precision and agreement appeared less reliable for samples with low antibody levels. Ranking and regression analyses suggest that some laboratories generated comparable quantitative results, although direct comparison or combination of results from different laboratories remains difficult to support. Calibration to the U.S. Reference Pertussis Antisera appears to have been successful at standardizing the results in some laboratories, Statistical analyses are affected by assay precision and are not necessarily reliable sole predictors of biologically relevant differences in quantitative results. If results from different laboratories must be compared, appropriate studies of precision and quantitative agreement should be conducted to support the specific comparisons. C1 NIAID,BIOMETRY BRANCH,BETHESDA,MD 20892. NIAID,DIV MICROBIOL & INFECT DIS,BETHESDA,MD 20892. RP Lynn, F (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,LAB PERTUSSIS,HFM-490,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 22 TC 48 Z9 49 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD NOV PY 1996 VL 3 IS 6 BP 689 EP 700 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VQ351 UT WOS:A1996VQ35100012 PM 8914760 ER PT J AU Heredia, A Soriano, V Weiss, SH Bravo, R Vallejo, A Denny, TN Epstein, JS Hewlett, IK AF Heredia, A Soriano, V Weiss, SH Bravo, R Vallejo, A Denny, TN Epstein, JS Hewlett, IK TI Development of a multiplex PCR assay for the simultaneous detection and discrimination of HIV-1, HIV-2, HTLV-I and HTLV-II SO CLINICAL AND DIAGNOSTIC VIROLOGY LA English DT Article DE human retroviruses; mixed infections; multiplex PCR ID POLYMERASE CHAIN-REACTION; T-CELL LEUKEMIA; VIRUS TYPE-I; RETROVIRAL INFECTIONS; WEST-AFRICA; DNA; PREVALENCE; SEQUENCE; I/II AB Background: Multiplex polymerase chain reaction (PCR) has been established as a general technique for the simultaneous amplification of different target sequences. Uses of multiplex include pathogens identification, linkage analysis and genetic disease diagnosis. The high sensitivity of PCR may produce false-positive results due to contamination with previously amplified material. Objectives: To develop a multiplex PCR technique that can simultaneously detect and discriminate human immunodeficiency virus types 1 and 2 (HIV-1/2) and human T-lymphotropic virus types 1 and 2 (HTLV-I/II) proviral sequences. Such a method should incorporate a system that prevents the occurrence of false-positive results. Study design: Combinations of four primer pairs, one for each retrovirus, were assayed in order to determine the combination of oligonucleotides as well as the PCR conditions that yield the most specific and sensitive coamplification of proviral sequences. To prevent contamination with DNA from previous PCR amplifications, the uracil N-glycosylase (UNG) system was incorporated into the coamplification format. Results. A combination of primer pairs from the gag region of HIV-1, env of HIV-2, pol of HTLV-I and tax of HTLV-II yielded specific and sensitive coamplification of proviral sequences. The UNG system was incorporated and shown to be efficient in the degradation of contaminating DNA. In the evaluation of a serologically well established panel of singly and dually infected individuals, the assay detected 20/22 HIV-1, 8/10 HIV-2, 8/8 HTLV-I and 8/8 HTLV-II infections. Conclusions: A multiplex PCR method for the detection and discrimination of HIV-1/2 and HTLV-I/II has been developed. Under standardized conditions, all four proviral sequences were detected in a specific and sensitive manner. The evaluation of a panel of clinical specimens from infected individuals by one or more retroviruses showed that the technique detected most of the infected individuals. A low viral load may explain cases where multiplex PCR failed to detect target sequences. (C) 1996 Elsevier Science B.V. C1 US FDA,MOL VIROL LAB,DIV TRANSFUS & TRANSMITTED DIS,CTR BIOL EVALUAT & RES,HFM315,ROCKVILLE,MD 20852. INST SALUD CARLOS III,SERV INFECT DIS MICROBIOL & IMMUNOL,MADRID 28010,SPAIN. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,DEPT PREVENT MED & COMMUNITY HLTH,NEWARK,NJ 07107. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,DEPT PEDIAT,NEWARK,NJ 07103. RI Vallejo, Alejandro/I-5881-2015; OI Vallejo, Alejandro/0000-0001-5360-878X; Denny, Thomas/0000-0002-7364-8276 NR 25 TC 19 Z9 23 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0197 J9 CLIN DIAGN VIROL JI Clin. Diagn. Virol. PD NOV PY 1996 VL 7 IS 2 BP 85 EP 92 DI 10.1016/S0928-0197(96)00255-3 PG 8 WC Virology SC Virology GA WH084 UT WOS:A1996WH08400003 PM 9137864 ER PT J AU Nishimura, T Newkirk, K Sessions, RB Andrews, PA Trock, BJ Rasmussen, AA Montgomery, EA Bischoff, EK Cullen, KJ AF Nishimura, T Newkirk, K Sessions, RB Andrews, PA Trock, BJ Rasmussen, AA Montgomery, EA Bischoff, EK Cullen, KJ TI Immunohistochemical staining for glutathione S-transferase predicts response to platinum-based chemotherapy in head and neck cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; INDUCTION CHEMOTHERAPY; DRUG-RESISTANCE; CISPLATIN; AMPLIFICATION; INFUSION; PRESERVATION; LOCALIZATION; EXPRESSION; ENZYMES AB The glutathione S-transferases (GSTs) play an important role in the cell's defense against toxic substances, The GSTs are a family of enzymes produced by several genes that interact with distinct but overlapping substrates and that may play a role in resistance of tumor cells to several chemotherapeutic agents, We examined the correlation between expression of GSTs determined by immunohistochemistry and clinical response to platinum-based chemotherapy in 51 patients with head and neck cancer, who received a total of 56 courses of chemotherapy, The overall response rate for the 56 chemotherapy treatment courses was 48%, The overall response rate (complete response + partial response) for patients with low GST scores was 88% (21 of 24), whereas among the patients with high GST scores, the overall response rate was 19% (6 of 32; P = 0.001), Patients with a low GST score were 4.7 times more likely to respond to chemotherapy than patients with high GST scores, GST scores corresponded to response in 84% of cases, Among 23 patients treated with neoadjuvant chemotherapy, the overall response rate for patients with low GST scores was 100% (14 of 14), whereas among the patients with high GST scores, the overall response rate was 44% (4 of 9; P = 0.002), Among 33 patients treated with chemotherapy for relapsed disease, the overall response rate for patients with low GST scores was 70% (7 of 10), whereas among the patients with high GST scores, the overall response rate was 8.6% (2 of 23; P < 0.001), We conclude that GST expression correlates well with response to platinum-based chemotherapy in head and neck cancer. C1 GEORGETOWN UNIV,LOMBARDI CANC CTR,WASHINGTON,DC 20007. GEORGETOWN UNIV,DEPT OTOLARYNGOL HEAD & NECK SURG,WASHINGTON,DC 20007. GEORGETOWN UNIV,DEPT PATHOL,WASHINGTON,DC 20007. KANAZAWA UNIV,DEPT OTOLARYNGOL,KANAZAWA,ISHIKAWA 920,JAPAN. US FDA,ROCKVILLE,MD 20857. NR 39 TC 62 Z9 65 U1 0 U2 1 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 NOV PY 1996 VL 2 IS 11 BP 1859 EP 1865 PG 7 WC Oncology SC Oncology GA VQ901 UT WOS:A1996VQ90100008 PM 9816141 ER PT J AU Ette, EI AF Ette, EI TI Comparing non-hierarchical models: Application to non-linear mixed effects modeling SO COMPUTERS IN BIOLOGY AND MEDICINE LA English DT Article DE bootstrap; non-hierarchical models; log-likelihood difference; goodness-of-fit; longitudinal pharmacokinetic data; non-linear mixed effects model ID BOOTSTRAP AB There is no method available to compare the fit of two non-hierarchical non-linear mixed effects models, although the common practice is to select the model with the lower objective function. Bootstrapping the log-likelihood differences (LLDs) of non-hierarchical models and constructing a bootstrap confidence interval on the LLDs is proposed for comparing the goodness-of-fit of such models. This is illustrated with different parameterizations of clearance models for an anti-infective agent in a longitudinal pharmacokinetic study which are compared. Additive and exponential models of creatinine clearance as a predictor of clearance are used as examples. Copyright (C) 1996 Elsevier Science Ltd. RP Ette, EI (reprint author), US FDA,PHARMACOMETR STAFF,OFF CLIN PHARMACOL & BIOPHARMACEUT,CTR DRUG EVALUAT & RES,HFD-855,ROCKVILLE,MD 20857, USA. NR 21 TC 10 Z9 10 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0010-4825 J9 COMPUT BIOL MED JI Comput. Biol. Med. PD NOV PY 1996 VL 26 IS 6 BP 505 EP 512 DI 10.1016/S0010-4825(96)00031-5 PG 8 WC Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Computer Science; Engineering; Mathematical & Computational Biology GA WB950 UT WOS:A1996WB95000006 PM 8997544 ER PT J AU Parker, RJ Collins, JM Strong, JM AF Parker, RJ Collins, JM Strong, JM TI Identification of 2,6-xylidine as a major lidocaine metabolite in human liver slices SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID PERFUSED RAT-LIVER; CHROMATOGRAPHY-MASS-SPECTROMETRY; INVIVO METABOLISM; COVALENT BINDING; MECHANISMS; KINETICS; QUANTIFICATION; DERIVATIVES AB Human liver slices, in vitro, were used to establish whether lidocaine (LIDO) can be converted by human liver tissue to 2,6-xylidine (XYL), a compound shown to be carcinogenic in rodents. XYL was identified by GC/MS as a major metabolite in human liver slices from five individual donors after incubation with either LIDO (100 mu M) or its deethylated metabolite, monoethylglycinexylidide (MEGX; 100 mu M). Similar media XYL concentrations (9.8 mu M+/-2.1 SD and 7.9 mu M+/-2.1 SD) were achieved after either LIDO or MEGX incubation for 4 hr, respectively. With LIDO, the mean media XYL to MEGX ratios were 1.1 at 1-hr and 1.0 at 4-hr incubation times. In contrast, when LIDO (>500 mu M) was incubated with human liver microsomes for 1 hr, the XYL to MEGX ratio was similar to 0.01. No XYL was detected when LIDO (100 mu M) was incubated with either human liver S9 fractions or whole liver homogenates. These results suggest that the enzyme primarily responsible for hydrolysis of LIDO may be labile in subcellular fractions. Kinetic analysis of the data suggests that XYL can be produced from either LIDO directly, or sequentially through MEGX. Although these metabolic data are helpful in addressing issues of LIDO toxicity, the overall risk assessment for LIDO is determined in large part by other factors, including the relative rates of activation to other potentially toxic species such as 4-HO-2,6-XYL as well as inactivation by detoxification pathways. The results presented emphasize the important role human liver slices can play in drug metabolism studies. C1 US FDA,DIV CLIN PHARMACOL RES,CTR,CDER,LAUREL,MD 20708. NR 26 TC 40 Z9 40 U1 1 U2 2 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 NOV PY 1996 VL 24 IS 11 BP 1167 EP 1173 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VT357 UT WOS:A1996VT35700001 PM 8937848 ER PT J AU Matthews, AM Roberts, DW Hinson, JA Pumford, NR AF Matthews, AM Roberts, DW Hinson, JA Pumford, NR TI Acetaminophen-induced hepatotoxicity - Analysis of total covalent binding vs specific binding to cysteine SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID SUBCELLULAR LIVER FRACTIONS; ADDUCT FORMED INVITRO; REACTIVE METABOLITES; PROTEIN ADDUCTS; 3'-HYDROXYACETANILIDE; REGIOISOMER; MOUSE; ARYLATION; INVIVO; SERUM AB Acetaminophen-induced hepatotoxicity is believed to be mediated by covalent binding of the reactive metabolite N-acetyl-p-benzoquinone imine to essential proteins in liver, it has been shown that the primary reaction of this metabolite with hepatic proteins is the formation of 3-(cysteine-S-yl)-acetaminophen adducts. The importance of covalent binding to other amino acids that may be formed by reaction of N-acetyl-p-benzoquinone imine with protein is unclear. previously we developed immunochemical assays for the acetaminophen cysteine adducts by immunizing animals with the conjugate 3-(N-acetylcystein-S-yl)acetaminophen-keyhole limpet hemocyanin, wherein the carboxyl group of the N-acetyl-cysteine moiety was coupled to amino groups on the protein. A very sensitive and specific immunochemical assay was developed for acetaminophen specifically bound to cysteine groups on protein [3-(cystein-S-yl)acetaminophen protein adducts]. Analysis of protein adducts indicated that after toxic doses, acetaminophen covalently bound at high levels to cysteine residues on a relatively small number of hepatic proteins. In the present work, a new antiacetaminophen antiserum was prepared by immunizing mice with 4-acetamidobenzoic acid coupled to keyhole limpet hemocyanin. Competitive ELISA data indicate that the resulting antiserum has excellent recognition of acetaminophen and related arylacetamide derivatives. Using this new antiserum. Western blot analyses of liver proteins from acetaminophen-intoxicated mouse livers were performed and compared with similar assays using the anti-3-(cystein-S-yl)acetaminophen antiserum. Visual and densitometric analyses of the Western blots indicate that the two antisera detect the same primary acetaminophen protein adducts; however, minor differences in the intensity of certain bands were observed. These differences may represent either differences in antibody accessibility to 3-(cystein-S-yl)acetaminophen adducts or differences in the proportion of acetaminophen bound to cysteine vs. binding to other amino acids. C1 UNIV ARKANSAS MED SCI HOSP,DIV TOXICOL,LITTLE ROCK,AR 72205. NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079. FU NIGMS NIH HHS [GM48749] NR 22 TC 46 Z9 46 U1 0 U2 2 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 NOV PY 1996 VL 24 IS 11 BP 1192 EP 1196 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VT357 UT WOS:A1996VT35700005 PM 8937852 ER PT J AU Vawter, MP BasaricKeys, J Li, YH Lester, DS Lebovics, RS Lesch, KP Kulaga, H Freed, WJ Sunderland, T Wolozin, B AF Vawter, MP BasaricKeys, J Li, YH Lester, DS Lebovics, RS Lesch, KP Kulaga, H Freed, WJ Sunderland, T Wolozin, B TI Human olfactory neuroepithelial cells: Tyrosine phosphorylation and process extension are increased by the combination of IL-1 beta, IL-6, NGF, and bFGF SO EXPERIMENTAL NEUROLOGY LA English DT Article ID NERVE GROWTH-FACTOR; SIGNAL-TRANSDUCING RECEPTOR; TUMOR-NECROSIS-FACTOR; ALZHEIMERS-DISEASE; PC12 CELLS; NEUROTROPHIC FACTOR; AMINOPEPTIDASE-N; KINASE-ACTIVITY; IN-VITRO; SYMPATHOADRENAL PROGENITOR AB Olfactory neuroepithelial cells (ONC) grown from biopsies of human donors are a novel cell culture system that may facilitate studies into normal and disease-related human neurobiology. We further characterized the expression of cell surface markers and intermediate filaments, and responses to neurotrophic factors by ONC. ONC are positive for cell surface markers N-CAM, PSA-N-CAM, neutral endopeptidase, N-aminopeptidase, NGF low-affinity receptor homologue (CD40), and transferrin receptor by flow cytometry for the intermediate filament proteins peripherin, vimentin, and NF-H by immunocytochemistry. Responses to neurotrophic factors measured were process outgrowth, cytoskeletal protein expression, and protein phosphorylation. Process outgrowth was increased by interleukin-1 beta(164-171) (IL-1 beta) or by the combination of IL-1 beta, interleukin-6 (IL-6), nerve growth factor (NGF), and basic fibroblast growth factor (bFGF). This combination of IL-1 beta, IL-6, NGF, and bFGF (16NF) increased expression of two cytoskeletal proteins, NF-H protein and microtubule-associated protein tau. Application of the individual neurotrophic factors IL-1 beta, IL-6, NGF, and bFGF increased protein phosphorylation, while 16NF produced an immediate increase in tyrosine phosphorylation of several proteins (MW of 40-80, 120, 150, and 190 kDa). The 16NF combination appears to act through a tyrosine-kinase-mediated pathway to induce process extension and increase NF-H expression. The ONC culture has the potential to be further explored to examine the relationship among process outgrowth, protein phosphorylation, and synergy between neurotrophin and cytokine receptor systems. (C) 1996 Academic Press, Inc. C1 NIMH, SECT GERIATR PSYCHIAT, WASHINGTON, DC 20032 USA. NIMH, NEUROPSYCHIAT BRANCH, WASHINGTON, DC 20032 USA. UNIV WURZBURG, DEPT PSYCHIAT, D-8700 WURZBURG, GERMANY. US FDA, CDER, DIV RES & TESTING, LAUREL, MD 20708 USA. NIDCD, BETHESDA, MD 20892 USA. RP Vawter, MP (reprint author), NIMH, SECT PRECLIN NEUROSCI, WASHINGTON, DC 20032 USA. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 77 TC 26 Z9 28 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD NOV PY 1996 VL 142 IS 1 BP 179 EP 194 DI 10.1006/exnr.1996.0189 PG 16 WC Neurosciences SC Neurosciences & Neurology GA VT664 UT WOS:A1996VT66400017 PM 8912909 ER PT J AU Thangaraj, HS Bull, TJ DeSmet, KAL Hill, MK Rouse, DA Moreno, C Ivanyi, J AF Thangaraj, HS Bull, TJ DeSmet, KAL Hill, MK Rouse, DA Moreno, C Ivanyi, J TI Duplication of genes encoding the immunodominant 38 kDa antigen in Mycobacterium intracellulare SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE Mycobacterium intracellulare; pst operon; miPstS2; miPstS1a; miPstS1b; miPstB; miPstC; 38 kDa ID NUCLEOTIDE-SEQUENCE ANALYSIS; ESCHERICHIA-COLI; SEROLOGIC CHARACTERIZATION; AVIUM COMPLEX; AIDS PATIENTS; PROTEIN; TUBERCULOSIS; IDENTIFICATION; EXPRESSION AB Mycobacterium avium is a causative agent of mycobacterioses in systemically immunocompromised individuals, whereas Mycobacterium intracellulare is responsible for causing infections in relatively immunocompetent hosts. In an attempt to identify components that could be involved in virulence, we characterised the 38 kDa-encoding gene of M. intracellulare that is absent in M. avium. This antigen cross-reacts immunologically with a major 38 kDa antigen of M. tuberculosis, and both antigens are homologues of the phosphate transport subunit S (PstS) of the pst complex of Escherichia coli. Unlike the M. tuberculosis complex the M. intracellulare coding gene was found to be duplicated. We also identified and characterised other pst genes that may constitute an operon. Considering that multiple isoforms of PstS are present in mycobacteria the possible role of pstS1 genes for pathogenesis is discussed. C1 CHARING CROSS HOSP,DEPT MED MICROBIOL,LONDON,ENGLAND. US FDA,CTR BIOL EVALUAT & RES,LAB MYCOBACTERIA,BETHESDA,MD. RP Thangaraj, HS (reprint author), HAMMERSMITH HOSP,MRC,CTR CLIN SCI,TB & RELATED INFECT UNIT,DU CANE RD,LONDON W12 0NN,ENGLAND. NR 20 TC 13 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD NOV 1 PY 1996 VL 144 IS 2-3 BP 235 EP 240 DI 10.1111/j.1574-6968.1996.tb08536.x PG 6 WC Microbiology SC Microbiology GA VP815 UT WOS:A1996VP81500020 PM 8900068 ER PT J AU Limm, W Hollifield, HC AF Limm, W Hollifield, HC TI Modelling of additive diffusion in polyolefins SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE antioxidant; diffusion coefficient; food additive petition; migration; polyolefin ID STATISTICAL MECHANICAL MODEL; FOOD CONTACT MATERIALS; SIMPLE PENETRANTS; DENSITY POLYETHYLENE; ALTERNATIVE METHODS; COMPLEX PENETRANTS; SMALL MOLECULES; IRGANOX 1010; POLYMERS; MIGRATION AB A semi-empirical model has been developed for additive diffusion in polymers. The model estimates apparent diffusion coefficients of an additive migrating through polyolefin polymers into a fatty food simulant for a range of temperatures between the glass transition and melting temperatures of the polymer. This diffusion model has been applied to several additive/polyolefin systems to determine its validity and limitations. RP Limm, W (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,200 C ST SW,WASHINGTON,DC 20204, USA. NR 25 TC 77 Z9 87 U1 2 U2 21 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD NOV-DEC PY 1996 VL 13 IS 8 BP 949 EP 967 PG 19 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA VU461 UT WOS:A1996VU46100008 PM 8950115 ER PT J AU Waynant, RW AF Waynant, RW TI Nickels and dimes 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 NOV PY 1996 VL 12 IS 6 BP 2 EP 2 PG 1 WC Engineering, Electrical & Electronic; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA VT489 UT WOS:A1996VT48900001 ER PT J AU Mukherjee, A Hale, VG Borga, O Stein, R AF Mukherjee, A Hale, VG Borga, O Stein, R TI Predictability of the clinical potency of NSAIDs from the preclinical pharmacodynamics in rats SO INFLAMMATION RESEARCH LA English DT Article DE antiinflammatory; analgesic; antipyretic; pK(a); octanol-water partition coefficient; NSAIDs animal models; carrageenin ED(50) ID ANTI-INFLAMMATORY DRUGS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ASPIRIN-LIKE DRUGS; PROSTAGLANDIN SYNTHESIS; ACID; PHARMACOKINETICS; INHIBITION; PIROXICAM; AGENT; FLURBIPROFEN AB Objective and Design. Relevance of the preclinical pharmacodynamic, toxicity and pharmacokinetic parameters predicting the clinical potency of nonsteroidal antiinflammatory drugs (NSAIDs) was evaluated. Material: Data for oral potencies of 24 NSAIDs in rats were collected from the literature and from New Drug Applications with respect to the following parameters: antiinflammatory, analgesic, antipyretic, acute ulcerogenic activities, acute toxicity, in vitro inhibition of prostaglandin synthesis, acid dissociation constant (pK(a)), octanol-water partition coefficient and elimination half-life. Treatment. Data for most of the in vivo parameters in rats were collected following single dose administration with the exception of adjuvant arthritis. Single and daily clinical doses were considered. All of these NSAIDs have been approved for marketing although not all have been sold in the USA. Methods: The preclinical data were compared to human dose (unit or daily doses) using single and multiple stepwise regression analyses. Results: Analyses suggest that NSAIDs are effective in all models of preclinical tests for fever, pain and inflammation, however, carrageenin-induced rat paw edema model is clearly the best predictor of human dose. Rank order of preclinical models for predicting human dose is carrageenin > yeast induced fever > pressure induced pain = adjuvant arthritis in rats. The analysis suggested that the pain and adjuvant arthritis models in rats may also involve a prostaglandin independent mechanism. Of the two physicochemical factors tested, pK(a) contributed best to the carrageenin model towards predicting the clinical potency of NSAIDs. Mathematical relationships between human dose, carrageenin ED(50) and pK(a) were established that may assist in the future clinical development of NSAIDs. Conclusions: Carrageenin-induced paw edema model in rats is the most robust predictor of the clinical potency of NSAIDs. Acid dissociation constant (pK(a)) appears to be a secondary contributor to the potency of NSAIDs. The relevance of the data analyses for developing cyclooxygenase-2 (COX-2) selective NSAIDs is discussed. C1 US FDA,CTR DRUG EVALUAT & RES,OFF CLIN PHARMACOL & BIOPHARMACEUT,ROCKVILLE,MD 20857. RP Mukherjee, A (reprint author), US FDA,DIV ANTIINFLAMMATORY ANALGES & OPHTHALMOL DRUG PR,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 89 TC 38 Z9 39 U1 0 U2 6 PU BIRKHAUSER VERLAG AG PI BASEL PA PO BOX 133 KLOSTERBERG 23, CH-4010 BASEL, SWITZERLAND SN 1023-3830 J9 INFLAMM RES JI Inflamm. Res. PD NOV PY 1996 VL 45 IS 11 BP 531 EP 540 DI 10.1007/BF02342223 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA VV222 UT WOS:A1996VV22200001 PM 8951503 ER PT J AU Black, PL McKinnon, KM Wooden, SL Ussery, MA AF Black, PL McKinnon, KM Wooden, SL Ussery, MA TI Antiviral activity of biological response modifiers in a murine model of AIDS. Requirement for augmentation of natural killer cell activity and synergy with oral AZT SO INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY LA English DT Article DE AIDS; animal model; Rauscher murine leukemia virus; biological response modifier(s); interferon inducer(s) ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY SYNDROME; TRIHYDROCHLORIDE CL 246,738; INTERFERON-ALPHA; NK-CELLS; HIV-INFECTION; KAPOSIS-SARCOMA; SELECTIVE DEPLETION; HOMOSEXUAL MEN; LEUKEMIA-VIRUS AB We employed the Rauscher murine leukemia virus (RMuLV) as a murine retrovirus model of AIDS, to test biological response modifiers (BRM) and antiviral agents for potential therapeutic activity against the human immunodeficiency virus (HIV). We examined the relationship between the augmentation of natural killer (NK) cell activity and antiviral efficacy of a series of BRM, most of which are known inducers of interferon, in this model. Poly [I,C]-LC, MVE-2, and CL 246,738, but not Ampligen, soluble glucan, or 7-thia-8-oxoguanosine, consistently produced antiviral activity. In addition, the combination of suboptimal doses of oral 3'-azido-3'-deoxythymidine (AZT) (in drinking water) and poly [I,C]-LC produced a synergistic antiviral effect. With all the BRM tested, a consistent pattern emerged, namely that antiviral activity always correlated with the augmentation of splenic NK cell activity in infected animals. For instance, poly [I,C]-LC boosted NK activity much more in infected mice treated therapeutically (treatment initiated after infection) than prophylactically (treatment initiated before infection), and it had greater antiviral activity therapeutically than prophylactically. For the BRM tested, antiviral activity did not occur without augmentation of NK activity in infected mice. In contrast, augmentation of NK activity in uninfected mice bore no relationship to antiviral activity. Furthermore, elimination of NK cells by treating mice with anti-asialo GM(1) abolished the antiviral activity of poly [I,C]-LC. Although splenic NK activity was ablated by anti-asialo GM(1), serum interferon levels were not affected by this treatment. These results point to a causal connection between the augmentation of NK cell activity and the antiviral efficacy of these BRM in this murine AIDS model. NK cells thus appear to play a key role in resistance to this retrovirus, as has been suggested for HIV. (C) 1997 International Society for Immunopharmacology. C1 US FDA,CTR DRUG EVALUAT & RES,DIV ANTIVIRAL DRUG PROD,ROCKVILLE,MD 20857. RP Black, PL (reprint author), SO RES INST,FREDERICK CANC RES CTR,FREDERICK,MD, USA. FU NIAID NIH HHS [1U01AI25617] NR 64 TC 8 Z9 9 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0192-0561 J9 INT J IMMUNOPHARMACO JI Int. J. Immunopharmacol. PD NOV PY 1996 VL 18 IS 11 BP 633 EP 650 DI 10.1016/S0192-0561(96)00064-1 PG 18 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA WP701 UT WOS:A1996WP70100003 PM 9089007 ER PT J AU Ryan, TA AF Ryan, TA TI Endovascular brachytherapy: The FDA's perspective SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Letter RP Ryan, TA (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,INTERVENT CARDIOL DEVICES GRP,ROCKVILLE,MD 20850, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 1996 VL 36 IS 4 BP 992 EP 993 DI 10.1016/S0360-3016(97)89881-1 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA VX992 UT WOS:A1996VX99200045 PM 8960543 ER PT J AU Lehr, GJ AF Lehr, GJ TI Determination of diphenoxylate hydrochloride and atropine sulfate in combination drug formulations by liquid chromatography SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB An isocratic, reversed-phase liquid chromatographic (LC) method was developed for simultaneous determination of diphenoxylate hydrochloride (I) and atropine sulfate (II) in pharmaceutical products, Analysis is conducted on a Spherisorb CN column (5 mu m), with a mobile phase consisting of 47% 0.001M pentanesulfonic acid sodium salt monohydrate, 53% acetonitrile, and 0.1% phosphoric acid, The detection wavelength is 220 nm, Tablets are extracted with acetonitrile-water (50 + 50), Oral solutions are determined directly after dilution, The method is validated for linearity, precision, system reproducibility, and accuracy, Recoveries at 80-120% of label claim ranged from 98.7 to 101.0% and from 99.5 to 102.5% for I and II, respectively, Results were linear fr > 0.9999) in the ranges 125-375 mu g/mL and 1.25-3.75 mu g/mL for I and ll, respectively, Assay and content uniformity results for each ingredient, in both innovator products and generic formulations, are reported, Diphenoxylic acid, the principal degradation product and major metabolite of I, is separated and can be determined in tablets and oral solutions. RP Lehr, GJ (reprint author), US FDA,NE REG LAB,850 3RD AVE,BROOKLYN,NY 11232, USA. NR 6 TC 5 Z9 5 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 NOV-DEC PY 1996 VL 79 IS 6 BP 1288 EP 1293 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA VU050 UT WOS:A1996VU05000008 PM 8946706 ER PT J AU June, GA Sherrod, PS Hammack, TS Amaguana, RM Andrews, WH AF June, GA Sherrod, PS Hammack, TS Amaguana, RM Andrews, WH TI Relative effectiveness of selenite cystine broth, tetrathionate broth, and rappaport-vassiliadis medium for recovery of Salmonella spp from raw flesh, highly contaminated foods, and poultry feed: Collaborative study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ENRICHMENT MEDIUM; GREEN BROTH AB A collaborative study was performed in 18 laboratories to validate use of Rappaport-Vassiliadis (RV) medium in the standard culture method for recovery of Salmonella spp, from raw, highly contaminated foods and poultry feed, RV medium made from its individual ingredients and incubated at 42 degrees C was compared with selenite cystine (SC) broth incubated at 35 degrees C and tetrathionate (TT) broth incubated at 35 degrees and 43 degrees C for effectiveness in recovery of Salmonella spp, Four artificially contaminated foods (oysters, frog legs, mushrooms, and shrimp) and poultry feed and one naturally contaminated food (chicken) were analyzed, The artificially contaminated foods were inoculated with single serovars of Salmonella at target levels of 0.04 colony-forming units (CFU)/g for the low level and 0.4 CFU/g for the high level, For analysis of 1125 test portions, RV medium (42 degrees C) recovered Salmonella from 409 test portions; TT (43 degrees C), from 368 test portions; TT (35 degrees C), from 310 test portions; and SC (35 degrees C), from 334 test portions, Overall, RV medium was comparable with or better than other selective enrichments for recovery of Salmonella from the foods in this study, except mushrooms, From mushrooms, SC broth (35 degrees C) recovered more positive test portions than did RV medium (42 degrees C) and TT broth (43 degrees C), The method for detection of Salmonella in raw, highly contaminated foods and poultry feed using RV medium has been adopted by AOAC INTERNATIONAL, AOAC Official Method 967.25, Salmonella in Foods, Preparation of Culture Media and Reagents, has been revised to include RV medium, and the applicability of AOAC Official Method 967.26, Salmonella in Foods, Detection, has been restricted to processed foods. RP June, GA (reprint author), US FDA,DIV MICROBIOL STUDIES,WASHINGTON,DC 20204, USA. NR 15 TC 30 Z9 32 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 NOV-DEC PY 1996 VL 79 IS 6 BP 1307 EP 1323 PG 17 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA VU050 UT WOS:A1996VU05000012 PM 8946709 ER PT J AU DiProssimo, VP Malek, EG AF DiProssimo, VP Malek, EG TI Comparison of three methods for determining aflatoxins in melon seeds SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB The suitability of 3 methods for determining aflatoxins in melon seeds was examined, The first 2 are the Contaminants Branch (CB) method and the Best Foods (BF) method, both official methods for determining aflatoxins in peanuts and peanut products. The third method, the modified CB method-Rapid Modification of the Cottonseed (CB-RCS-Mod) method, devised in this work, was derived by combining steps from the CS method and the Rapid Modification of the Cottonseed method, The CB method was superior to the other 2 methods for quantitation of aflatoxins, It gave better recoveries and cleaner extracts that exhibit less fluorescent interference for thin-layer chromatography (TLC) than the BF method, Also, its solvent efficiency was better than that of the CB-RCS-Mod method, With the CB method, recoveries from spiked samples were 85.0% for aflatoxin B-1 and 90.0% for aflatoxin B-2. Recoveries of G aflatoxins were more variable, averaging 90.0% for aflatoxin G(1) and 72.5% for aflatoxin G(2). Total aflatoxin recovery was 86.5% for the CB method, At a low aflatoxin contamination level (8 mu g B-1/kg sample), aflatoxin B-1 was detectable by the CB method but not by the BF method, Detection of aflatoxins in BF method sample extracts by TLC was not improved by the use of chloroform-acetone-water (88 + 12 + 1), benzene-ethanol-water, or ether-methanol-water (96 + 3 + 1) in place of the standard chloroform-acetone (88 + 12) developer, Use of ether-methanol-water (96 + 3 + 1) for detecting aflatoxins by TLC in the CB method extracts increased interference compared with the standard chloroform-acetone (88 + 12) developer. RP DiProssimo, VP (reprint author), US FDA,NE REG LAB,850 3RD AVE,BROOKLYN,NY 11232, USA. NR 9 TC 8 Z9 8 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 NOV-DEC PY 1996 VL 79 IS 6 BP 1330 EP 1335 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA VU050 UT WOS:A1996VU05000014 PM 8946711 ER PT J AU Honkanen, RE Mowdy, DE Dickey, RW AF Honkanen, RE Mowdy, DE Dickey, RW TI Detection of DSP-toxins, okadaic acid, and dinophysis toxin-1 in shellfish by serine/threonine protein phosphatase assay SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID TUMOR PROMOTER; INHIBITORY ACTIVITY; POTENT INHIBITOR; CAUSATIVE TOXIN; MOUSE SKIN; IDENTIFICATION; DERIVATIVES; TYPE-2A; PHYTOPLANKTON; PURIFICATION AB A relatively rapid protein phosphatase-based assay was developed for detecting okadaic acid in extracts of shellfish, using oysters (Crassostrea virginica) as a model, The assay has good sensitivity detecting okadaic acid in crude methanolic extracts of oysters at greater than or equal to 4 ng/ml (greater than or equal to 0.1 ng/assay). Assay accuracy for detecting toxic shellfish was validated through a series of spike recovery experiments, In more than 320 assessments, all oysters containing toxic amounts of okadaic acid (greater than or equal to 0.2 mu g/g) were detected, Results of analysis of the same extract by phosphatase assay and liquid chromatography gave very high correlation. C1 US FDA, OFF SEAFOOD, DAUPHIN ISL, AL 36528 USA. RP Honkanen, RE (reprint author), UNIV S ALABAMA, COLL MED, DEPT BIOCHEM & MOL BIOL, MOBILE, AL 36688 USA. NR 51 TC 20 Z9 22 U1 0 U2 6 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 1996 VL 79 IS 6 BP 1336 EP 1343 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA VU050 UT WOS:A1996VU05000015 PM 8946712 ER PT J AU Schenck, FJ Calderon, L Saudarg, DE AF Schenck, FJ Calderon, L Saudarg, DE TI Florisil solid-phase extraction cartridges for cleanup of organochlorine pesticide residues in foods SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID POLYCHLORINATED BIPHENYL RESIDUES; SCREENING-PROCEDURE; FAT AB Florisil solid-phase extraction cartridges were evaluated for cleanup of organochlorine pesticide residues in food extracts, Elution patterns and recoveries were determined for 24 organochlorine pesticides, A range of elution solvents was evaluated, A 2% ethyl ether-petroleum ether eluant optimized overall recoveries while minimizing interferences from coextractants. RP Schenck, FJ (reprint author), US FDA,BALTIMORE DIST LAB,900 MADISON AVE,BALTIMORE,MD 21201, USA. NR 14 TC 21 Z9 21 U1 1 U2 6 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 NOV-DEC PY 1996 VL 79 IS 6 BP 1454 EP 1458 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA VU050 UT WOS:A1996VU05000029 PM 8946723 ER PT J AU Vick, JA VonBredow, JD AF Vick, JA VonBredow, JD TI Effectiveness of intramuscularly administered cyanide antidotes on methemoglobin formation and survival SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article ID BLOOD AB Successful first aid therapy for cyanide intoxication is dependent upon immediate administration of antidotes which directly or indirectly interact with the cyanide ion to remove it from circulation. Owing to the severe respiratory, cardiovascular and convulsive episodes following acute cyanide intoxication, the most practical approach is to administer antidotes by intramuscular injection, Exceptionally rapid methemoglobin formers-hydroxylamine hydrochloride (HH) and dimethylaminophenol (DMAP)-are usually able to prevent the lethal effect of cyanide following intramuscular injections in doses sufficient to induce 20% methemoglobin (HH = 20 mg kg(-1) and DMAP = 2 mg kg(-1)). Sodium nitrite, the methemoglobin inducer approved for military use, must be administered by intravenous infusion because it is not an effective cyanide antidote by the intramuscular route, In the normal unintoxicated animal an intramuscular injection of 20 mg kg(-1) sodium nitrite will form 20% methemoglobin; however, in acute cyanide intoxication the associated severe bradycardia appears to limit the rate of absorption and thus the rapid formation of methemoglobin, If the bradycardia is prevented or reversed by atropine, the rate of absorption of sodium nitrite and the formation of methemoglobin is able to reverse the otherwise lethal effects of cyanide, Thus, an intramuscularly administered combination of 20 mg kg(-1) sodium nitrite and 1 mg kg(-1) atropine sulfate, rapidly absorbed from the intramuscular site, appears to achieve the same degree of effectiveness against acute cyanide intoxication as intramuscularly administered HH or DMAP, It would appear from these studies that HH, DMAP and sodium nitrite with atropine are all potentially effective intramuscular antidotes for acute cyanide poisoning. C1 WALTER REED ARMY INST RES,DIV EXPT THERAPEUT,WASHINGTON,DC 20307. RP Vick, JA (reprint author), US FDA,DIV RES & TESTING,WASHINGTON,DC 20204, USA. NR 30 TC 9 Z9 9 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD NOV-DEC PY 1996 VL 16 IS 6 BP 509 EP 516 DI 10.1002/(SICI)1099-1263(199611)16:6<509::AID-JAT382>3.0.CO;2-V PG 8 WC Toxicology SC Toxicology GA VW443 UT WOS:A1996VW44300007 PM 8956097 ER PT J AU Flahiff, CM Blackwell, AS Hollis, JM Feldman, DS AF Flahiff, CM Blackwell, AS Hollis, JM Feldman, DS TI Analysis of a biodegradable composite for bone healing SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article ID INTERNAL-FIXATION; FRACTURE FIXATION; STRENGTH; INVITRO; RODS AB A degradable L-PLA/calcium carbonate composite made of interconnecting phases was examined. This structure was used both to slow the degradation rate and to reduce the brittleness of the ceramic. Both in vitro and in vivo degradation studies were performed. Samples were incubated in buffered saline or placed in the dorsum of rats for 0, 1, or 4 weeks. Mechanical testing was performed on both groups, volume fraction of each component was determined for in vitro samples, and histology was performed on in vivo samples. Failure load, tensile strength, and elastic modulus significantly decreased during the Ist week for both groups. Continued decreases were seen at 4 weeks for in vitro samples but not for in vivo. Failure strain and tensile strength decreased only for in vitro specimens. PLA fraction significantly decreased during the Ist week and then stabilized. Histology showed that tissue ingrowth occurred at 4 weeks. The decrease in mechanical properties was probably a result of the decreased PLA fraction. The stabilization and even a slight increase in tensile strength and failure strain in the in vivo samples was probably due to the tissue ingrowth forming an implant-tissue composite. (C) 1996 John Wiley & Sons, inc. C1 UNIV ALABAMA,DEPT BIOMED ENGN,BIRMINGHAM,AL 35294. UNIV ARKANSAS MED SCI HOSP,DEPT ORTHOPAED,LITTLE ROCK,AR 72205. US FDA,ODE,ROCKVILLE,MD 20850. UNIV S ALABAMA,DEPT ORTHOPAED,MOBILE,AL 36617. NR 13 TC 34 Z9 36 U1 0 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 NOV PY 1996 VL 32 IS 3 BP 419 EP 424 PG 6 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA VM553 UT WOS:A1996VM55300015 PM 8897147 ER PT J AU Tang, YB Reepmeyer, JC Revelle, LK Wilson, JA AF Tang, YB Reepmeyer, JC Revelle, LK Wilson, JA TI Enantioseparation of 3-phenylacetylamino-2,6-piperidinedione and related chiral compounds SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE enantiomer separation; mobile phase composition; phenylacetylaminopiperidinedione; glutamines; glutamic acids ID STATIONARY PHASE; CELLULOSE; ANTINEOPLASTON-A10; RESOLUTION; HPLC AB This paper reports HPLC methodology for the first successful enantiomeric separations of 3-phenylacetylamino-2,6-piperidinedione (PAP), a naturally occurring peptide derivative used for inhibiting the growth of cancer tissues. The chiral separation of four related hydrolysates is also described. A commercially available tris-4-methylbenzoate cellulose (Chiralcel OJ) column was used as the chiral stationary phase, operated in the normal-phase mode. The results demonstrated that hydrolyzed products of PAP, each of which has a carboxylic acid functionality present in its structure, eluted in a reasonable time and are enantiomerically resolved only when a trace amount of organic acid is present in the mobile phase. Different alcohols (ethanol and isopropanol) and acid additives (trifluoroacetic acid, trichloroacetic acid and acetic acid) were evaluated. In general, for the separation of the acidic enantiomers, ethanol is superior to isopropanol and stronger acids enhance the resolution more effectively. However, chiral separation of PAP could only be accomplished with isopropanol in the mobile phase and no acidic additive was needed. RP Tang, YB (reprint author), US FDA,DIV DRUG ANAL,ST LOUIS,MO, USA. NR 22 TC 14 Z9 15 U1 0 U2 1 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 NOV 1 PY 1996 VL 752 IS 1-2 BP 93 EP 99 DI 10.1016/S0021-9673(96)00463-3 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA VW224 UT WOS:A1996VW22400009 PM 8962498 ER PT J AU Feng, P Fields, PI Swaminathan, B Whittam, TS AF Feng, P Fields, PI Swaminathan, B Whittam, TS TI Characterization of nonmotile variants of Escherichia coli O157 and other serotypes by using an antiflagellin monoclonal antibody SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; FLAGELLIN GENES; IDENTIFICATION; STRAINS; INFECTIONS AB An antiflagellin monoclonal antibody (15D8) was used to detect the presence of flagella in nonmotile variants of several pathogenic Escherichia coli serotypes. Of the 48 isolates examined, 15 reacted with monoclonal antibody 15D8 and were culturally confirmed to be motile. Of the 38 clinical strains designated O157:NM or O157:H-, 7 were antibody reactive and motile and agglutinated with anti-H7 sera. C1 CTR DIS CONTROL & PREVENT,FOODBORNE DIARRHEAL DIS BRANCH,ATLANTA,GA 30333. PENN STATE UNIV,DEPT BIOL,UNIVERSITY PK,PA 16802. RP Feng, P (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV MICROBIOL STUDIES,HFS-516,200 C ST SW,WASHINGTON,DC 20204, USA. NR 19 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 1996 VL 34 IS 11 BP 2856 EP 2859 PG 4 WC Microbiology SC Microbiology GA VM556 UT WOS:A1996VM55600046 PM 8897201 ER PT J AU Flamand, V Shores, EW Tran, T Huang, K Lee, E Grinberg, A Kinet, JP Love, PE AF Flamand, V Shores, EW Tran, T Huang, K Lee, E Grinberg, A Kinet, JP Love, PE TI Delayed maturation of CD4(-)CD8(-) Fc gamma RII/III+ T and natural killer cell precursors in Fc epsilon RI gamma transgenic mice SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ANTIGEN RECEPTOR COMPLEX; HIGH-AFFINITY RECEPTOR; LYMPHOCYTES-T; IGE RECEPTOR; ZETA-CHAIN; SUBUNIT; EXPRESSION; GENE; THYMOCYTES; ASSOCIATION AB Fc epsilon RI gamma (gamma) is a member of a group of related proteins (the zeta-family dimers) that function as signal-transducing components of both Fc receptors and the T cell antigen receptor (TCR). Analysis of gamma expression during fetal thymus ontogeny revealed that it is expressed in early thymocytes, before the initiation of clonotypic TCR-alpha and TCR-beta gene rearrangement but is down-regulated in most adult thymocytes. To explore a possible role for gamma in thymocyte development, we generated transgenic mice in which this protein was overexpressed at all stages of ontogeny. Overexpression of gamma inhibited the maturation of T cells as well as natural killer (NK) cells. The developmental effects were transgene dose related and correlated with markedly delayed maturation of fetal CD4(-)CD8(-) FcRII/III+ thymocytes, cells thought to include the progenitors of both T and NK cells. These results suggest that the zeta and gamma chains serve distinctive functions in thymocyte development and indicate that Fc receptor(s) may play an important role in regulating the differentiation of early progenitor cells within the thymus. C1 NICHHD,LAB MAMMALIAN GENES & DEV,NIH,BETHESDA,MD 20892. NIAID,LAB MOL ALLERGY & IMMUNOL,NIH,ROCKVILLE,MD 20852. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. NR 35 TC 20 Z9 20 U1 0 U2 1 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 NOV 1 PY 1996 VL 184 IS 5 BP 1725 EP 1735 DI 10.1084/jem.184.5.1725 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VT694 UT WOS:A1996VT69400013 PM 8920861 ER PT J AU Noah, CW Poteet, SS Lister, MM Roderick, CN Smith, DB Colvert, RM Holland, MA Cerniglia, CE AF Noah, CW Poteet, SS Lister, MM Roderick, CN Smith, DB Colvert, RM Holland, MA Cerniglia, CE TI Production and characterization of monoclonal antibodies to detect Vibrio cholerae serogroup O1 in a rapid enzyme-linked immunosorbent assay SO JOURNAL OF FOOD PROTECTION LA English DT Article DE Vibrio cholerae O1; ELISA; monoclonal antibodies ID EPIDEMIC AB Monoclonal antibodies (MAbs) were developed for a rapid and efficient screening procedure to detect cultures of Vibrio cholerae serogroup O1. Spleen cells of BALB/c mice previously immunized with an attenuated control strain of V. cholerae were fused with mouse myeloma cell line SP2/0. An enzyme-linked immunosorbent assay (ELISA) was used to test cultural hybridoma secretions of two MAbs against 120 strains of V. cholerae O1, 38 strains of V. cholerae non-O1, 15 strains of other Vibrio spp., and 20 strains of other bacterial species. Results of tests using both MAbs were identical. The MAbs successfully detected all of the confirmed serotype O1 strains. Three additional V. cholerae strains that agglutinated antisera and the saline control were considered serologically inconclusive. Of these, one was detected as positive for V. cholerae by both MAbs. The MAbs gave no false-positive reactions when tested against the confirmed non-Ol strains, other Vibrio spp., and other bacterial species. Use of this ELISA will enhance the speed and accuracy needed for detecting V. cholerae O1 cultures. C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RP Noah, CW (reprint author), US FDA,DALLAS DIST OFF,3032 BRYAN ST,DALLAS,TX 75204, USA. NR 14 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 NOV PY 1996 VL 59 IS 11 BP 1153 EP 1157 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA VW029 UT WOS:A1996VW02900001 ER PT J AU Mitchell, GV Grundel, E Jenkins, MY AF Mitchell, GV Grundel, E Jenkins, MY TI Bioavailability for rats of vitamin E from fortified breakfast cereals SO JOURNAL OF FOOD SCIENCE LA English DT Article DE breakfast cereal; vitamin E; rat bioassay; bioavailability ID ALPHA-TOCOPHERYL ACETATE; ANTIOXIDANT ACTIVITY; PLASMA; HUMANS; CELLS AB Bioavailability of vitamin E in three fortified breakfast cereals and dose-response relationships among dietary vitamin E and selected biochemical indices were investigated using a rat depletion-repletion model. Response criteria included concentrations of oc-tocopherol in plasma, red blood cells, liver, heart, and adipose tissue, and plasma pyruvate kinase activity. Bioavailability of vitamin E in whole grain cereal and corn flakes was generally comparable to that of the tocopheryl acetate standard. Bioavailability of vitamin E in bran flakes was lower than that of the standard based on four of the criteria. A food matrix effect in bran flakes resulted in the lower bioavailability. RP Mitchell, GV (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,OFF FOOD LABELING,HFS-175,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 33 TC 9 Z9 9 U1 0 U2 1 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 NOV-DEC PY 1996 VL 61 IS 6 BP 1257 EP 1260 DI 10.1111/j.1365-2621.1996.tb10974.x PG 4 WC Food Science & Technology SC Food Science & Technology GA VZ334 UT WOS:A1996VZ33400035 ER PT J AU Barry, TL Petzinger, G Zito, SW AF Barry, TL Petzinger, G Zito, SW TI GC/MS comparison of the west Indian aphrodisiac ''Love Stone'' to the Chinese medication ''Chan Su'': Bufotenine and related bufadienolides SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; Love Stone; Chan Su; GC/MS; bufotenine; bufadienolides; resibufogenin; bufalin; cinobufagin; street drugs; chemistry AB The death of a 23-year-old man resulting from digoxin-like toxicity and heart failure was attributed to ingestion of a West Indian aphrodisiac known as ''Love Stone.'' GC/MS analyses identified bufotenine, a controlled substance under both US and New York State statutes. In addition, a series of bufadienolides, namely resibufogenin, bufalin, and cinobufagin, were also identified. Bufadienolides, which are derived from toad venom or secretions, are cardiotonic steroids that cause symptoms similar to digoxin. GC/MS analyses of the Chinese medication ''Chan Su,'' a product derived from toads, produced a highly similar elution profile and contained the same compounds as ''Love Stone.'' The data demonstrate that the aphrodisiac was also derived from toads. C1 ST JOHNS UNIV,COLL PHARM & ALLIED HLTH PROFESS,DEPT PHARMACEUT SCI,JAMAICA,NY 11439. RP Barry, TL (reprint author), US FDA,NE REG LAB,MASS SPECTROMETRY SERV CTR,850 3RD AVE,BROOKLYN,NY 11232, USA. NR 16 TC 23 Z9 25 U1 0 U2 0 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD NOV PY 1996 VL 41 IS 6 BP 1068 EP 1073 PG 6 WC Medicine, Legal SC Legal Medicine GA VQ772 UT WOS:A1996VQ77200029 PM 8914298 ER PT J AU Li, MF Muller, J Rao, V Hearing, V Lueders, K Gorelik, E AF Li, MF Muller, J Rao, V Hearing, V Lueders, K Gorelik, E TI Loss of intracisternal A-type retroviral particles in BL6 melanoma cells transfected with MHC class I genes SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID TNF-MEDIATED CYTOTOXICITY; INCREASED SENSITIVITY; PROVIRAL ELEMENTS; BINDING SITES; H-2K(B) GENE; H-2 GENES; EXPRESSION; MOUSE; ANTIGEN; LYMPHOCYTES AB Electron microscopy of B16 melanoma and its sublines revealed that these cells produce numerous intracisternal A-type retroviral particles (IAPs). To identify and sequence the melanoma-associated IAPs of C57BL/6 mice, a cDNA library was constructed from IAP-producing BL6-8 cell RNA and screened using MIA14 IAP DNA as a probe. A 6 . 8 kb mRNA was identified that represents the full-length message for a new subfamily of IAP, termed MeIAP. The melanoma-derived IAP cDNA showed high similarity to MIA14 with major differences in the LTR. A nine base motif of the R region showed that this IAP differs from other previously sequenced IAPs. Analysis of the individual clones from BL6 melanoma revealed that IAPs were produced only in the clones that failed to express H-2K(b) molecules. No IAPs were found in the melanoma clones that expressed endogenous H-2K(b). To analyse further the association between MHC class I genes and IAP production, the H-2K(b)-negative clones of BL6 melanoma were transfected with various H-2 genes. Transfection of the H-2K(b) or H-2K(d), but not H-2D(d) or H-2L(d) genes resulted in the elimination of IAPs. Northern blot analysis revealed that loss of IAPs in the H-2K gene-transfected BL6 melanoma cells was due to lack of IAP transcripts. Elimination of IAPs in the H-2K(b)-positive BL6 melanoma cells was also accompanied by alterations in expression of various cellular genes and changes of their phenotypic properties. C1 UNIV PITTSBURGH,PITTSBURGH CANC INST,PITTSBURGH,PA 15213. UNIV PITTSBURGH,DEPT PATHOL,PITTSBURGH,PA 15213. US FDA,DIV VIRAL PROD,BETHESDA,MD 20892. NCI,NIH,CELL BIOL LAB,BETHESDA,MD 20892. NCI,NIH,BIOCHEM LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA-59903] NR 37 TC 10 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 NOV PY 1996 VL 77 BP 2757 EP 2765 DI 10.1099/0022-1317-77-11-2757 PN 11 PG 9 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA VT286 UT WOS:A1996VT28600010 PM 8922469 ER PT J AU SchartonKersten, TM Wynn, TA Denkers, EY Bala, S Grunvald, E Hieny, S Gazzinelli, RT Sher, A AF SchartonKersten, TM Wynn, TA Denkers, EY Bala, S Grunvald, E Hieny, S Gazzinelli, RT Sher, A TI In the absence of endogenous IFN-gamma, mice develop unimpaired IL-12 responses to Toxoplasma gondii while failing to control acute infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; NECROSIS-FACTOR-ALPHA; INTERFERON-GAMMA; LEISHMANIA-MAJOR; INTERLEUKIN-12 PRODUCTION; LISTERIA-MONOCYTOGENES; NITRIC-OXIDE; IN-VIVO; RESISTANCE; INDUCTION AB The relationship between IFN-gamma and IL-12 in generating innate immune responses and resistance to acute Toxoplasma gondii infection was assessed in T. gondii-exposed lFN-gamma knockout (gko) mice. Gko mice, in contrast to wild-type (wt) animals, rapidly succumbed to infection with either the avirulent ME49 strain or, surprisingly, an attenuated temperature-sensitive mutant strain, ts4. Microscopic examination of peritoneal exudates from infected gko mice demonstrated that mortality is associated with unchecked tachyzoite replication. Nevertheless, both wt and gko animals developed a peritoneal inflammatory response that in gko animals was greater due to a 5- to 10-fold increase in the number of granulocytes recruited to the site of infection. In addition, IL-12 production in gko mice was both unimpaired and functional since a significant, albeit lower than wt, IL-12-dependent NK cell response developed in these animals. Regardless, no evidence for an IFN-gamma-independent protective function for IL-12 or NK cells was apparent since in vivo treatment of gko mice with an IL-12-neutralizing mAb ablated the NK cell response, but did not decrease survival. Together, these data identify distinct functions for IL-12 and IFN-gamma in host resistance to T. gondii: IL-12 precedes and initiates synthesis of IFN-gamma, while the latter lymphokine directly controls parasite growth and diminishes the contribution of IL-4- and IL-5-producing T cell subsets. C1 US FDA, DIV ANTIVIRAL DRUG PROD, ROCKVILLE, MD 20857 USA. UNIV FED MINAS GERAIS, DEPT BIOCHEM & IMMUNOL, BELO HORIZONTE, MG, BRAZIL. RP SchartonKersten, TM (reprint author), NIAID, PARASIT DIS LAB,IMMUNOBIOL SECT,NIH,BLDG 4, ROOM 132, BETHESDA, MD 20892 USA. RI Wynn, Thomas/C-2797-2011 NR 56 TC 199 Z9 201 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1996 VL 157 IS 9 BP 4045 EP 4054 PG 10 WC Immunology SC Immunology GA VP227 UT WOS:A1996VP22700035 PM 8892638 ER PT J AU Mdluli, K Sherman, DR Hickey, MJ Kreiswirth, BN Morris, S Stover, CK Barry, CE AF Mdluli, K Sherman, DR Hickey, MJ Kreiswirth, BN Morris, S Stover, CK Barry, CE TI Biochemical and genetic data suggest that InhA is not the primary target for activated isoniazid in Mycobacterium tuberculosis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MOLECULAR MECHANISMS; CATALASE PEROXIDASE; RESISTANCE; DRUG; CHEMOTHERAPY; ETHIONAMIDE; ACIDS; KATG AB An examination of the pattern of lipid biosynthetic responses to isoniazid (INH) treatment of Mycobacterium tuberculosis and Mycobacterium smegmatis suggests that the mode of action of activated INH differs between these 2 organisms, Transformation of M. smegmatis with inhA on a plasmid construct conferred high-level resistance to INH, while the same construct failed to confer resistance upon M. tuberculosis, The inhA region from 2 clinical isolates whose resistance has been attributed to changes in the upstream promoter region has been cloned and was not sufficient to impart INH resistance to the level of the parent strain on sensitive M. tuberculosis, These putative mutant promoter elements appear to elevate expression levels of gene fusion reporter constructs, suggesting some noncausal connection between the observed mutations and the lipid metabolism of drug-resistant organisms, These results suggest that InhA is not the major target for activated INH in M. tuberculosis. C1 ROCKY MT LABS,NIAID,TB RES UNIT,HAMILTON,MT 59840. PATHOGENESIS CORP,LAB TB & MOL MICROBIOL,SEATTLE,WA. PUBL HLTH RES INST,TB CTR,NEW YORK,NY. US FDA,CTR BIOL EVALUAT & RES,LAB MYCOBACTERIA,BETHESDA,MD. RI Barry, III, Clifton/H-3839-2012; OI Stover, Charles/0000-0002-7406-1696 FU Intramural NIH HHS [Z01 AI000783-11] NR 25 TC 85 Z9 89 U1 0 U2 1 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 NOV PY 1996 VL 174 IS 5 BP 1085 EP 1090 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VN181 UT WOS:A1996VN18100026 PM 8896513 ER PT J AU Didolkar, MS Jackson, AJ Lesko, LJ Fitzpatrick, JL Buda, BS Johnston, GS Zech, LA AF Didolkar, MS Jackson, AJ Lesko, LJ Fitzpatrick, JL Buda, BS Johnston, GS Zech, LA TI Pharmacokinetics of dacarbazine in the regional perfusion of extremities with melanoma SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article ID IMIDAZOLE CARBOXAMIDE; NSC-45388; MELPHALAN; THERAPY AB Background: The pharmacokinetics of dacarbazine (DTIC), which has been shown to be an effective therapeutic agent against metastatic melanoma, has not been extensively studied. However, to improve the clinical use of the drug, more information on the kinetics is required. Methods: A pharmacokinetic study was undertaken in six patients with melanoma of an extremity who were undergoing hyperthermic isolation perfusion with DTIC in order to understand better its clinical pharmacokinetics. Plasma was sampled from the arterial and venous lines of an extracorporeal pump during the perfusion with the systemic vein and urine sampled postperfusion. Samples were analyzed for DTIC, 2-azahypoxanthine (2-AZA), and aminoimidazole carboxamide (AIC). Tc-99m (Technetium) human serum albumin (HSA) was used in the perfusion circuit to monitor the crossover of the perfusate into the systemic circulation during the procedure. The data were analyzed using a compartmental model of sampled body compartments incorporating the isolated extremity. Results: High tissue DTIC levels were maintained throughout the perfusion, whereas in the systemic circulation, plasma DTIC concentrations, when observed, were 40-100-fold less than those in the perfusate. Almost 70% of the DTIC administered was not recovered in the perfusate after the washout of the extremity. Conclusions: High levels of DTIC can be maintained in an extremity (i.e., arm or leg) during perfusion. (C) 1996 Wiley-Liss, Inc. C1 UNIV MARYLAND,BALTIMORE,MD 21201. US FDA,ROCKVILLE,MD 20857. NIH,BETHESDA,MD 20892. RP Didolkar, MS (reprint author), SINAI HOSP,DEPT SURG,2435 W BELVEDERE AVE,BALTIMORE,MD 21215, USA. NR 19 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD NOV PY 1996 VL 63 IS 3 BP 148 EP 158 DI 10.1002/(SICI)1096-9098(199611)63:3<148::AID-JSO4>3.0.CO;2-D PG 11 WC Oncology; Surgery SC Oncology; Surgery GA VW032 UT WOS:A1996VW03200004 PM 8944058 ER PT J AU Harris, GR Myers, MR Gammell, PM AF Harris, GR Myers, MR Gammell, PM TI The response of transiently excited thick transducers at low frequencies SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID RECEIVERS AB The generation of acoustic transients via short-pulse excitation of thick piezoelectric disks has proven to be useful in a number of applications, including broadband measurements of attenuation, directivity, and frequency response. However, one aspect of this technique that has received little attention is the lower-frequency limit. In the present study the frequency response was analyzed theoretically using the Mason/Redwood model for a thickness-expansion drive transducer. Two factors were found that Limit the useful range of the technique at low frequencies. The first is related to the negative capacitance that appears in the equivalent circuit of a thickness expander. This element can be ignored in some transducer applications, but its presence must be accounted for in the low-frequency case. The second factor is due to the finite measurement time available, which for small transmitter/receiver separation distances is equal to the acoustic transit time through the piezoelectric disk. For an air-backed transducer radiating into water, the two limitations restrict the usable bandwidth to frequencies above approximately (10h(2) epsilon(s)/pi z(T)x(T))exp(2h(2) epsilon(S)/pi c(T)z(T)) and c(T)/x(T), respectively, where h is a piezoelectric constant, epsilon(S) is the clamped dielectric permittivity, and z(T), x(T), and c(T) are the transducer characteristic impedance, thickness, and speed of sound. For a 2.5-cm-thick lead zirconate titanate transducer (Navy Type I), the lower limit considering both factors is approximately 200 kHz. This limit is acceptable for determining the frequency response of hydrophones used in diagnostic ultrasound field measurements, but it is insufficient for characterizing hydrophones used to measure extracorporeal shock-wave lithotripsy pressure pulses. RP Harris, GR (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20852, USA. NR 24 TC 3 Z9 3 U1 0 U2 2 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD NOV PY 1996 VL 100 IS 5 BP 3115 EP 3120 DI 10.1121/1.417199 PG 6 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA VT753 UT WOS:A1996VT75300023 ER PT J AU Keller, WC AF Keller, WC TI Progress in FDA pharmacosurveillance SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Letter RP Keller, WC (reprint author), US FDA,CTR VET MED,DIV SURVEILLANCE,ROCKVILLE,MD 20857, USA. NR 1 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 NOV 1 PY 1996 VL 209 IS 9 BP 1546 EP 1547 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA VN997 UT WOS:A1996VN99700005 PM 8899014 ER PT J AU Young, JF Schwetz, BA Willhite, CC Kacew, S AF Young, JF Schwetz, BA Willhite, CC Kacew, S TI Symposium on pharmacokinetics pharmacodynamics in the developing system and impact on risk assessment: Executive summary SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Editorial Material C1 DEPT TOX SUBSTANCE CONTROL,BERKELEY,CA. UNIV OTTAWA,DEPT PHARMACOL,OTTAWA,ON,CANADA. RP Young, JF (reprint author), NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,3900 NCTR DR,HFT 130,JEFFERSON,AR 72079, USA. NR 0 TC 5 Z9 5 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 NOV PY 1996 VL 49 IS 4 BP 339 EP 341 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA VU212 UT WOS:A1996VU21200001 ER PT J AU Banks, MA Berlin, E Johnson, WA Peters, RC AF Banks, MA Berlin, E Johnson, WA Peters, RC TI Vitamin E levels and susceptibility to lipid peroxidation increase with aging in heart plasma membrane from miniature swine SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID FATTY-ACID COMPOSITION; SUPEROXIDE RADICAL FORMATION; DELTA-6 DESATURASE ACTIVITY; AGE-RELATED-CHANGES; FOOD RESTRICTION; FLUORESCENCE POLARIZATION; LIQUID-CHROMATOGRAPHY; INSULIN BINDING; FLUIDITY; LIVER AB Age-related changes in heart plasma membrane fatty acid composition, vitamin E content, membrane fluidify, susceptibility to lipid peroxidation, and the subcellular distribution of vitamin E: were observed in merle and female Hormel-Hanford miniswine over a wide range of ages: prepubertal, <0.5 years; young, 0.5-2.5 years; middle-aged, 5.9-10 years; and old, 11.5-13.9 years. Pigs were continuously fed the same low-fat, cholesterol-free, vitamin E-adequate stock diet at restricted maintenance levels. Membrane lipid peroxidation tended to increase in middle-aged and elderly pigs, but not significantly, perhaps being somewhat ameliorated by the significantly increased membrane vitamin E in middle-aged and old pigs. Mid-bilayer membrane fluidity was significantly increased in old pigs, but fluidity of the polar headgroup domains decreased with age. Thus, lipid peroxidation tended to increase over the long life span of miniswine even when they are food restricted. C1 USDA ARS,MNIL,BHNRC,BELTSVILLE,MD 20705. US FDA,CTR FOOD SAFETY & APPL NUTR,LAUREL,MD. NR 52 TC 3 Z9 3 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 1996 VL 51 IS 6 BP B409 EP B416 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA WD352 UT WOS:A1996WD35200005 PM 8914490 ER PT J AU Rouse, DA DeVito, JA Li, ZM Byer, H Morris, SL AF Rouse, DA DeVito, JA Li, ZM Byer, H Morris, SL TI Site-directed mutagenesis of the katG gene of Mycobacterium tuberculosis: Effects on catalase-peroxidase activities and isoniazid resistance SO MOLECULAR MICROBIOLOGY LA English DT Article ID MOLECULAR MECHANISMS; ESCHERICHIA-COLI; TARGET; INHA; ETHIONAMIDE; SENSITIVITY; BOVIS AB Recent studies examining the molecular mechanisms of isoniazid (INH) resistance in Mycobacterium tuberculosis have demonstrated that a significant percentage of drug-resistant strains are mutated in the katG gene which encodes a catalase-peroxidase, and the majority of these alterations are missense mutations which result in the substitution of a single amino acid. In previous reports, residues which may be critical for enzymatic activity and the drug-resistant phenotype have been identified by evaluating INH-resistant clinical isolates and in vitro mutants. In this study, site-directed mutagenesis techniques were utilized to alter the wild-type katG gene from M. tuberculosis at 13 of these codons. The effects of these mutations were determined using complementation assays in katG-defective, INH-resistant strains of Mycobacterium smegmatis and Mycobacterium bovis BCG. This mutational analysis revealed that point mutations in the katG gene at nine of the 13 codons can cause drug resistance, and that enzymatic activity and resistance to INH are inversely related. In addition, mutations in the mycobacterial catalase-peroxidase which reduce catalase activity also decrease peroxidase activity. RP Rouse, DA (reprint author), US FDA,CTR BIOL EVALUAT & RES,LAB MYCOBACTERIA,BLDG 29,ROOM 406,HFM-431,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 34 TC 126 Z9 141 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 1996 VL 22 IS 3 BP 583 EP 592 DI 10.1046/j.1365-2958.1996.00133.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA VT204 UT WOS:A1996VT20400017 PM 8939440 ER PT J AU Sobotka, TJ Brown, R Quander, DY Jackson, R Smith, M Long, SA Barton, CN Rountree, RL Hall, S Eilers, P Johannessen, JN Scallet, AC AF Sobotka, TJ Brown, R Quander, DY Jackson, R Smith, M Long, SA Barton, CN Rountree, RL Hall, S Eilers, P Johannessen, JN Scallet, AC TI Domoic acid: Neurobehavioral and neurohistological effects of low-dose exposure in adult rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE domoic acid; behavior; neuropathology; adult rat; scopolamine pretreatment ID MONKEYS MACACA-FASCICULARIS; KAINATE RECEPTOR ACTIVATION; LONG-TERM POTENTIATION; D-ASPARTATE RECEPTOR; ENHANCES PERFORMANCE; DORSAL HIPPOCAMPUS; LEARNING-TASKS; KAINIC ACID; MICE; NEUROTOXICITY AB Adult rats treated IP with domoic acid at 0, 0.22, 0.65, or 1.32 mg/kg were tested for passive avoidance (PA), auditory startle (AS), or conditioned avoidance (CAR) behaviors. Clinical signs were observed only at the 1.32 mg/kg dose level. Within 24 h of dosing, rats surviving a dose of 1.32 mg/kg exhibited transient decreased body weight and exaggerated AS responding. Startle latency and habituation, PA, and CAR were not affected. Examination of brains from six rats per group revealed a subset (2/6) of animals receiving 1.32 mg/kg domoic acid with degenerating neurons in the hippocampal CA1/CA3 subregions and gliosis. The decreased body weight and increased startle suggest a hyperreactivity syndrome possibly related to neuronal degeneration in the hippocampus. In a separate experiment, domoic acid at an IP dose of 0.93 mg/kg was found to produce hypomotility in addition to a decrease in body weight. Both effects were reduced by pretreatment with scopolamine (2 mg/kg), but not with caffeine (30 mg/kg), indicating a possible cholinergic involvement in domoate's toxicity. Copyright (C) 1996 Elsevier Science Inc. C1 US FDA, CTR FOOD SAFETY & APPL NUTR, WASHINGTON, DC 20204 USA. US FDA, NATL CTR TOXICOL RES, JEFFERSON, AR 72079 USA. NR 60 TC 34 Z9 38 U1 3 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD NOV-DEC PY 1996 VL 18 IS 6 BP 659 EP 670 DI 10.1016/S0892-0362(96)00120-1 PG 12 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA VV686 UT WOS:A1996VV68600007 PM 8947943 ER PT J AU Englund, JA Baker, CJ Raskino, C McKinney, RE Lifschitz, MH Petrie, B Fowler, MG Connor, JD Mendez, H ODonnell, K Wara, DW Shliozberg, J Shearer, WT Stechenberg, B Borkowsky, W Bonaforte, RJ Cooper, ER Wiznia, A Toltzis, P Israele, V VanDyke, RB Yogev, R Starr, S Oleske, F Frenkel, L McIntosh, K Montgomery, M Petru, A Squires, JE Wade, N Moore, EC Rakusan, TA Baker, RC Brady, MT Pildes, RS Cervia, JS Wilfert, C Nesheim, S Bellanti, JA Keller, M Abrams, EJ Dossett, JH Rana, SR Tishler, DM Nicholas, SW Lambert, JS Wong, V Gupta, A Deveikis, A Kovacs, A Johnson, G Bamji, M Sacks, HS Pahwa, S GarciaRias, D Flynn, C Philipp, CS Jimenez, E Bonagura, VR Shenap, JL Grieco, MH Lischner, H Minnefor, AB Maldonado, Y Nachman, SA Fikrig, S Weiner, LB Levin, M Gershon, AA Bryson, Y Spector, S Diaz, C Reichman, RR Robinson, J Luzuriaga, K Crain, MJ Lim, W Rich, K Vink, PE Doyle, MG Scott, GB Munoz, J Andiman, WA Behrman, R Hetherington, S McLaren, C Millison, K Moye, J Nozyce, M Pearson, DA Purdue, L Schoenfeld, D Scott, G Spector, SA AF Englund, JA Baker, CJ Raskino, C McKinney, RE Lifschitz, MH Petrie, B Fowler, MG Connor, JD Mendez, H ODonnell, K Wara, DW Shliozberg, J Shearer, WT Stechenberg, B Borkowsky, W Bonaforte, RJ Cooper, ER Wiznia, A Toltzis, P Israele, V VanDyke, RB Yogev, R Starr, S Oleske, F Frenkel, L McIntosh, K Montgomery, M Petru, A Squires, JE Wade, N Moore, EC Rakusan, TA Baker, RC Brady, MT Pildes, RS Cervia, JS Wilfert, C Nesheim, S Bellanti, JA Keller, M Abrams, EJ Dossett, JH Rana, SR Tishler, DM Nicholas, SW Lambert, JS Wong, V Gupta, A Deveikis, A Kovacs, A Johnson, G Bamji, M Sacks, HS Pahwa, S GarciaRias, D Flynn, C Philipp, CS Jimenez, E Bonagura, VR Shenap, JL Grieco, MH Lischner, H Minnefor, AB Maldonado, Y Nachman, SA Fikrig, S Weiner, LB Levin, M Gershon, AA Bryson, Y Spector, S Diaz, C Reichman, RR Robinson, J Luzuriaga, K Crain, MJ Lim, W Rich, K Vink, PE Doyle, MG Scott, GB Munoz, J Andiman, WA Behrman, R Hetherington, S McLaren, C Millison, K Moye, J Nozyce, M Pearson, DA Purdue, L Schoenfeld, D Scott, G Spector, SA TI Clinical and laboratory characteristics of a large cohort of symptomatic, human immunodeficiency virus-infected infants and children SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE acquired immunodeficiency syndrome; human immunodeficiency virus; children; infection; antiretroviral therapy; zidovudine; didanosine; development; cortical atrophy; growth failure ID ZIDOVUDINE; TYPE-1; GROWTH AB Background. A large cohort of antiretroviral therapy-naive, symptomatic, HIV-infected children were enrolled into a controlled therapeutic trial (AIDS Clinical Trials Group Protocol 152), providing an opportunity to describe their clinical and laboratory characteristics and determine age-related distinctions. Methods. Study entry evaluations for 838 of 839 enrolled children were analyzed. Weight, head circumference (if <30 months of age), neuroradiologic imaging of the head, developmental or cognitive status and neurologic examination were assessed. Laboratory studies included hemoglobin, absolute neutrophil count, CD4 cell count, serum amylase, alanine aminotransaminase, p24 antigen and HIV blood culture. Data were categorized by age (3 to <12 months, 12 to <30 months, 30 months to 6 years and greater than or equal to 6 years). Results. Younger children had significantly higher rates of abnormalities before antiretroviral therapy, especially factors relating to growth and neurologic or cognitive function. Lower CD4+ cell counts and percentages as well as a positive serum p24 antigen correlated with lower weight-for-age Z scores and developmental indices. Conclusions. These data provide a description of the clinical characteristics of HIV-infected US children at the time antiretroviral therapy is initiated for HIV-related symptoms. The high rate of abnormalities of growth, development and cognitive ability that were observed in children <30 months of age demonstrates that treatment strategies should be developed for earlier intervention. C1 BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. DUKE UNIV,SCH MED,DEPT PEDIAT,DURHAM,NC. NIAID,BETHESDA,MD 20892. UNIV CALIF SAN DIEGO,DEPT PEDIAT & PHARMACOL,SAN DIEGO,CA 92103. SUNY HLTH SCI CTR,DEPT PEDIAT,BROOKLYN,NY 11203. UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94143. US FDA,KENSINGTON,MD. GLAXO WELLCOME INC,RES TRIANGLE PK,NC 27709. BRISTOL MYERS SQUIBB CO,WALLINGFORD,CT 06492. ACTG OPERAT OFF,BETHESDA,MD. NICHHD,PEDIAT & ADOLESCENT BRANCH,BETHESDA,MD. BRONX LEBANON HOSP CTR,NEW YORK,NY. UNIV TEXAS,SCH MED,HOUSTON,TX. UNIV MIAMI,SCH MED,MIAMI,FL. RP Englund, JA (reprint author), BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030, USA. OI moye, john/0000-0001-9976-8586 NR 27 TC 52 Z9 55 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD NOV PY 1996 VL 15 IS 11 BP 1025 EP 1036 DI 10.1097/00006454-199611000-00018 PG 12 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA VT450 UT WOS:A1996VT45000010 PM 8933553 ER PT J AU Shah, VP Yacobi, A Barr, WH Benet, LZ Breimer, D Dobrinska, MR Endrenyi, L Fairweather, W Gillespie, W Gonzalez, MA Hooper, J Jackson, A Lesko, LJ Midha, KK Noonan, PK Patnaik, R Williams, RL AF Shah, VP Yacobi, A Barr, WH Benet, LZ Breimer, D Dobrinska, MR Endrenyi, L Fairweather, W Gillespie, W Gonzalez, MA Hooper, J Jackson, A Lesko, LJ Midha, KK Noonan, PK Patnaik, R Williams, RL TI Evaluation of orally administered highly variable drugs and drug formulations SO PHARMACEUTICAL RESEARCH LA English DT Editorial Material RP Shah, VP (reprint author), US FDA,CTR DRUG EVALUAT & RES,OFF PHARMACEUT SCI,7500 STANDISH PL,ROCKVILLE,MD 20855, USA. RI Benet, Leslie/K-8286-2016 NR 0 TC 71 Z9 75 U1 0 U2 3 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 NOV PY 1996 VL 13 IS 11 BP 1590 EP 1594 DI 10.1023/A:1016468018478 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA VW974 UT WOS:A1996VW97400002 PM 8956322 ER PT J AU Rosenzweig, BA Hoskins, A Sistare, FD AF Rosenzweig, BA Hoskins, A Sistare, FD TI A proposed in vitro cellular insulin assay to replace the USP bioidentity test SO PHARMACOPEIAL FORUM LA English DT Article ID GLUCOSE CONSUMPTION; 3T3-L1 ADIPOCYTES; HUMAN PROINSULIN; INVITRO; GROWTH; PROLIFERATION; TRANSPORT; RECEPTORS; INVIVO; CELLS AB The goal of our investigation was to develop and assess a nonradioactive in vitro assay for insulin that could replace the in vivo USP Bioidentity Test(2). We have developed and tested a cell culture bioassay for insulin that is based on this hormone's primary biological effect, the stimulation of glucose uptake and metabolism, We have compared the precision and accuracy of an in vitro cellular bioactivity assay with the USP Bioidentity Test, total nitrogen measurement, and high-performance liquid chromatography (HPLC) assay of particular components. We propose that this cellular assay can be used to confirm that the hormone complex is in a biologically active conformation that can interact productively with relevant membrane receptors, Therefore, it could usefully replace the USP Bioidentity Test. [NOTE- It might be clearer if the names of these tests be changed, The USP Bioidentity Test might better be entitled the ''Biological Activity Test,'' and the HPLC test be entitled the ''Test for Insulin Content,'' The HPLC procedures furnish the amount of insulin, and related analogs (e.g., proinsulin) in the test material, It is possible to assign a theoretical potency which may be used for labeling, by adding the amounts of the components, adjusted where appropriate with a factor. The biological test would be an assay to confirm overall biological potency. There must be a reasonable relationship of results from the two test, within specified limits, the validity of which would be confirmed by the statistical calculations from the cell culture test data.] This cell culture bioassay uses 3T3-L1 preadipocytes that have been differentiated to adipocytes. Following differentiation of these cells, glucose transport and metabolism become robust and highly sensitive to insulin. The insulin-dependent disappearance of glucose from the media can be measured spectrophotometrically with a 96-well microplate reader, The assay shows a high level of ao curacy, and by virtue of its almost 3-fold lower index of precision and its narrow 95% confidence limits, this assay has also been found to be more precise when compared to the USP Bioidentity Test as currently formulated. Since rabbit blood sugar measurement has evolved over time into a bioidentity test rather than a true assay for determining precise potency, we have exceeded the rigors of required testing by showing the reproducible Precision and accuracy of this cell culture assay. The index of precision for the rabbit test averaged -0.41 +/- 0.56 (mean +/- standard deviation (SD), n=18), while for the cellular assay the index of precision was -0.15 +/- 0.07, (n - 60). The 95% confidence interval for eight rabbit tests averaged +/- 39%, while for the cellular glucose metabolism assays the 95% confidence interval averaged +/- 19%, We have also used human proinsulin; [des-64, 65] human proinsulin; [Asp(B10) des-(B28-30]) human insulin; [Lys(B28), Pro(B29]) human insulin; and human insulin dimers to test the specificity and flexibility of the assay. Potencies relative to human insulin in this cellular assay generally agreed with previously determined in vivo relative potencies for all analogs except the human insulin dimers (87% in this cellular assay versus 15% from previously published in vivo data) and [Lys(B28), Pra(B29]) human insulin (74% in this cellular assay versus 100% in vivo). A real virtue of the biological assay lies in its use of a sigmoidal dose-response relationship, where 6 doses of insulin bracket the calculated insulin concentration at the middle of the dose-response curve (EC(50)) and yield the expected receptor-mediated biological effect. The: USP Bioidentity Test measures a small difference in rabbit blood glucose at two selected doses of insulin, but does not provide the same information as a test that uses a wide range of biological activity. RP Rosenzweig, BA (reprint author), US FDA,CDER,DIV RES & TESTING,MOD 1,RM 2007,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 18 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 NOV-DEC PY 1996 VL 22 IS 6 BP 3270 EP 3287 PG 18 WC Medicine, Legal; Pharmacology & Pharmacy SC Legal Medicine; Pharmacology & Pharmacy GA VT671 UT WOS:A1996VT67100003 ER PT J AU Black, JC Layloff, T AF Black, JC Layloff, T TI Summer of 1995 - Mailbox temperature excursions in St Louis SO PHARMACOPEIAL FORUM LA English DT Article RP Black, JC (reprint author), US FDA,DIV DRUG ANAL,ST LOUIS,MO 63101, USA. NR 0 TC 5 Z9 5 U1 0 U2 1 PU US PHARMACOPEIAL CONVENTION PI ROCKVILLE PA 12601 TWINBROOK PKWY, ROCKVILLE, MD 20852 SN 0363-4655 J9 PHARMACOPEIAL FORUM JI Pharmacop. Forum PD NOV-DEC PY 1996 VL 22 IS 6 BP 3305 EP 3305 PG 1 WC Medicine, Legal; Pharmacology & Pharmacy SC Legal Medicine; Pharmacology & Pharmacy GA VT671 UT WOS:A1996VT67100005 ER PT J AU Callahan, TJ Spyker, D Sapirstein, W AF Callahan, TJ Spyker, D Sapirstein, W TI Concern about safety of carotid angioplasty SO STROKE LA English DT Letter RP Callahan, TJ (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,OFF DEVICE EVALUAT,DIV CARDIOVASC RESP & NEUROL DEVICES,ROCKVILLE,MD 20857, USA. NR 1 TC 6 Z9 6 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 1996 VL 27 IS 11 BP 2144 EP 2145 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA VQ163 UT WOS:A1996VQ16300045 PM 8898831 ER PT J AU Turturro, A Duffy, P Hart, R Allaben, WT AF Turturro, A Duffy, P Hart, R Allaben, WT TI Rationale for the use of dietary control in toxicity studies - B6C3F1 mouse SO TOXICOLOGIC PATHOLOGY LA English DT Article; Proceedings Paper CT XV International Symposium of the Society-of-Toxicologic-Pathologists CY JUN 09-13, 1996 CL ST LOUIS, MO SP Soc Toxicol Pathologists DE dietary restriction; nutrition; body weight; tumor incidence variability; spontaneous tumorigenesis; test variability; NTP bioassays ID BODY-WEIGHT; CALORIC RESTRICTION; FISCHER-344 RATS; TUMOR-INCIDENCE; MICE; SURVIVAL; CARCINOGENICITY; VARIABILITY; MECHANISMS; GROWTH AB Significant variability in critical study parameters such as tumor incidences and survival, increasing tumor incidence and decreasing survival in common toxicity test models, and agent-induced changes in body weight(BW) and BW distribution all generate concern about the reproducibility, consistency, and equity of chronic toxicity tests used in regulation. These concerns have led to suggestions to control BW in chronic tests by the modulation of dietary intake without inducing malnutrition [dietary control (DC)] thereby minimizing tumor and survival variability both between and within studies. Evaluating the reports of the best controlled set of chronic experiments, the National Toxicology Program bioassay series, from studies initiated from 1981 to 1990, there is an increase in tumor incidence, especially liver tumors, with a consistent increase in BW. The studies are classified as to whether normal or aberrant BW growth curves occur. When the studies with normal growth curves are considered, the variance in the BW at 12 mo on test (BW12) can account for over 50% of the variance in liver tumor incidence. Additional stratification by study type, which alter tumor prevalences, as well as appreciation of housing effects [group housing decreases survival (in male mice) and induces tumors in males and females when compared to individual housing], further increase the strength of the correlations, accounting for up to 90% of the variance seen in tumor incidences. These updated analyses further support the hypothesis that it is the BW variation that is resulting in much of the variability seen in tumor incidences and refine the suggestions for the BW curves used as the desired targets for DC. RP Turturro, A (reprint author), NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,HFT-020,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 26 TC 42 Z9 42 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 NOV-DEC PY 1996 VL 24 IS 6 BP 769 EP 775 PG 7 WC Pathology; Toxicology SC Pathology; Toxicology GA WB824 UT WOS:A1996WB82400019 PM 8994308 ER PT J AU Allaben, WT Turturro, A Leakey, JEA Seng, JE Hart, RW AF Allaben, WT Turturro, A Leakey, JEA Seng, JE Hart, RW TI FDA points-to-consider documents: The need for dietary control for the reduction of experimental variability within animal assays and the use of dietary restriction to achieve dietary control SO TOXICOLOGIC PATHOLOGY LA English DT Article; Proceedings Paper CT XV International Symposium of the Society-of-Toxicologic-Pathologists CY JUN 09-13, 1996 CL ST LOUIS, MO SP Soc Toxicol Pathologists DE caloric restriction, bioassay variability; cancer bioassay; rodent survival; rodent body weight ID B6C3F1 MICE; BODY-WEIGHT; CALORIC RESTRICTION; TUMOR-INCIDENCE; F344/N RATS; SURVIVAL; CARCINOGENICITY; TOXICITY; GROWTH; TRENDS AB Standard protocols for conducting chronic toxicity and carcinogenicity studies have been refined over the years to carefully control for many variables. Nevertheless, over the last 2 decades, there has been a steady increase in variability, a decrease in survival, an increase in tumor incidence rates, and an increase in the average body weight of control animals among the various rodent species and strains used for toxicity testing. These observations have prompted an evaluation of chronic study designs to determine what factor(s) may be responsible for such confounding changes. Ad libitum feeding and the selection of successful breeders with rapid offspring growth is believed to be at least partially responsible for the heavier, obese rodents with which many laboratories are coping today. As a result of these changes, some studies used for the evaluation of safety have been deemed inconclusive or inadequate for regulatory purposes and either additional supportive studies have been requested and/or studies per se have been repeated. Research on the molecular mechanisms of caloric restriction and agent-induced toxicity at the Food and Drug Administration (FDA) National Center for Toxicological Research stimulated the first international conference on the biological effects of dietary restriction in 1989; this was followed in 1993 by an FDA workshop exploring the utility of dietary restriction in controlling reduced survival in chronic tests and an international conference in 1994 exploring the implications for the regulatory community of using dietary restriction in toxicity and carcinogenicity studies used in support of a sponsor's submission or in risk assessments. The outcome of that conference was the FDA's commitment to develop Points-to-Consider documents that address the issue of dietary control in chronic toxicity and carcinogenicity studies. RP Allaben, WT (reprint author), US FDA,NATL CTR TOXICOL RES,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 31 TC 29 Z9 29 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 NOV-DEC PY 1996 VL 24 IS 6 BP 776 EP 781 PG 6 WC Pathology; Toxicology SC Pathology; Toxicology GA WB824 UT WOS:A1996WB82400020 PM 8994309 ER PT J AU Temple, R AF Temple, R TI The architecture of government regulation of medical products - Commentary SO VIRGINIA LAW REVIEW LA English DT Editorial Material ID UNITED-STATES; MORTALITY C1 US FDA,OFF DRUG EVALUAT 1,ROCKVILLE,MD 20857. RP Temple, R (reprint author), US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857, USA. NR 32 TC 3 Z9 3 U1 0 U2 0 PU UNIV VIRGINIA PI CHARLOTTESVILLE PA SCHOOL LAW, CHARLOTTESVILLE, VA 22901 SN 0042-6601 J9 VA LAW REV JI VA. Law Rev. PD NOV PY 1996 VL 82 IS 8 BP 1877 EP 1906 DI 10.2307/1073691 PG 30 WC Law SC Government & Law GA WY452 UT WOS:A1996WY45200013 ER PT J AU Pahor, M Ferrucci, L Corti, MC Salive, ME Cerhan, JR AF Pahor, M Ferrucci, L Corti, MC Salive, ME Cerhan, JR TI Calcium-channel blockers and cancer - Reply SO LANCET LA English DT Letter C1 IST NAZL RIEEREA & CURA ANZIANI,DEPT GERIATR,I FRATICINI,FLORENCE,ITALY. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20857. UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. RP Pahor, M (reprint author), UNIV TENNESSEE,DEPT PREVENT MED,MEMPHIS,TN 38105, 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 OCT 26 PY 1996 VL 348 IS 9035 BP 1167 EP 1167 DI 10.1016/S0140-6736(05)65298-1 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VP106 UT WOS:A1996VP10600042 ER PT J AU Hass, BS Lewis, SM Duffy, PH Ershler, W Feuers, RJ Good, RA Ingram, DK Lane, MA Leakey, JEA Lipschitz, D Poehlman, ET Roth, GS Sprott, RL Sullivan, DH Turturro, A Verdery, RB Walford, RL Weindruch, R Yu, BP Hart, RW AF Hass, BS Lewis, SM Duffy, PH Ershler, W Feuers, RJ Good, RA Ingram, DK Lane, MA Leakey, JEA Lipschitz, D Poehlman, ET Roth, GS Sprott, RL Sullivan, DH Turturro, A Verdery, RB Walford, RL Weindruch, R Yu, BP Hart, RW TI Dietary restriction in humans: Report on the Little Rock Conference on the value, feasibility, and parameters of a proposed study SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article ID CHRONIC CALORIC RESTRICTION; LOWERS BLOOD-GLUCOSE; MALE FISCHER-344 RAT; BODY-COMPOSITION; ANTIOXIDANT ENZYMES; RHESUS-MONKEYS; METABOLIC-RATE; EXPRESSION; CANCER; VARIABLES RP Hass, BS (reprint author), NATL CTR TOXICOL RES,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 49 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing. Dev. PD OCT 25 PY 1996 VL 91 IS 2 BP 79 EP 94 DI 10.1016/0047-6374(96)01775-7 PG 16 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA VM783 UT WOS:A1996VM78300001 PM 8905607 ER PT J AU Manjanatha, MG LynCook, LE Culp, SJ Beland, FA Heflich, RH Aidoo, A AF Manjanatha, MG LynCook, LE Culp, SJ Beland, FA Heflich, RH Aidoo, A TI Lymphocyte mutant frequency in relation to DNA adduct formation in rats treated with tumorigenic doses of the mammary gland carcinogen 7,12-dimethylbenz[a]anthracene SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE hprt; 6-thioguanine-resistant; Sprague-Dawley rat; N-ethyl-N-nitrosourea; P-32-postlabeling ID ETHYL-N-NITROSOUREA; 6-THIOGUANINE-RESISTANT LYMPHOCYTES; PERIPHERAL-BLOOD; FISCHER-344 RATS; FEMALE RAT; F344 RATS; INVIVO; INDUCTION; 7,12-DIMETHYLBENZ(A)ANTHRACENE; 1,6-DINITROPYRENE AB The ability of the rat lymphocyte hprt assay to detect tissue-specific carcinogens was evaluated using 7,12-dimethylbenz[a]anthracene (DMBA) administered under conditions that result in mammary gland tumors. Fifty-day-old female Sprague-Dawley rats were given single doses of 5 and 20 mg/kg DMBA by gavage, and the frequency of 6-thioguanine-resistant (TG(r)) T-lymphocytes was measured over a period of 21 weeks. A time- and dose-dependent increase in mutant frequency was found, with a maximum frequency found 9-15 weeks after treatment with 20 mg/kg of DMBA, Rats were also dosed with 1, 2.5, 5, 10, 15 and 20 mg/kg of DMSA and assayed for TG(r) mutant frequency 10 weeks after treatment. A significant linear dose-response was found, with all the DMBA doses resulting in significant increases in mutant frequency. To determine whether or not DMBA-induced mutants in rat lymphocytes reflected the DNA damage in the target tissue, rats were treated with 5 and 20 mg/kg of DMBA and spleen lymphocytes and mammary gland tissue were assayed for DNA adduct formation 1, 3 and 7 days later. A similar pattern of P-32-postlabeled adducts, involving both dG and dA nucleotides, was found in DNA from both the target tissue and the surrogate lymphocytes, Adduct formation was dose responsive in both tissues, with a 2.3- to 4-fold higher concentration in mammary gland as compared with lymphocytes, These results indicate that the rat lymphocyte hprt assay is sensitive to a mammary gland carcinogen and that similar types of DNA adducts are associated with both the lymphocyte mutants and the mammary gland tumors induced by DMBA. 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,JEFFERSON,AR 72079, USA. NR 29 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD OCT 25 PY 1996 VL 357 IS 1-2 BP 89 EP 96 DI 10.1016/0027-5107(96)00086-3 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA VM364 UT WOS:A1996VM36400011 PM 8876684 ER PT J AU Morris, SM Domon, OE McGarrity, LJ Chen, JJ Manjanatha, MG Andrews, AM Aidoo, A Casciano, DA AF Morris, SM Domon, OE McGarrity, LJ Chen, JJ Manjanatha, MG Andrews, AM Aidoo, A Casciano, DA TI A role for apoptosis in the toxicity and mutagenicity of bleomycin in AHH-1 tk(+/-) human lymphoblastoid cells SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE bleomycin; apoptosis; cytotoxicity; tk mutation; hprt mutation; human lymphoblastoid cell ID CHEMOTHERAPY-INDUCED APOPTOSIS; RADIATION-INDUCED APOPTOSIS; DOUBLE-STRAND CLEAVAGE; ASCITES TUMOR-CELLS; BCL-2 GENE FAMILY; P53 STATUS; 6-THIOGUANINE-RESISTANT MUTANTS; SUPEROXIDE-DISMUTASE; MUTATION-INDUCTION; ANTICANCER AGENTS AB The chromosomal mutagen, bleomycin, is also noted for its toxic properties, although the mechanism of cell death is not fully understood. In order to determine if cell death occurred by apoptosis or necrosis, AHH-1 tk(+/-) cells were exposed to bleomycin and the percentage of viable, apoptotic and necrotic cells quantified by flow cytometry. Logistic regression analysis indicated that the primary manner of cell death was through the apoptosis pathways, that apoptosis was delayed, and that apoptosis was accompanied by an arrest in the G(2) phase of the cell cycle, Once apoptosis was established as a mechanism for cell death, the efficiency with which these pathways removed damaged cells from the population was evaluated with the use of specific-locus mutation assays (tk and hprt) as indicators of cells with DNA damage that maintained viability and clonogenicity. Linear regression analysis detected a significant, concentration-dependent increase in the numbers of TFTr clones with the slow-growth phenotype. This suggests that a proportion of cells with bleomycin-induced DNA damage did not undergo cell death by apoptosis and that apoptosis, a mechanism for the destruction of damaged cells, is not fully efficient in the AHH-1 tk(+/-) cell line. C1 US FDA,NATL CTR TOXICOL RES,DIV GENET TOXICOL,DEPT HLTH & HUMAN SERV,JEFFERSON,AR 72079. US FDA,NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,DEPT HLTH & HUMAN SERV,JEFFERSON,AR 72079. PATHOL ASSOC INT,JEFFERSON,AR 72079. NR 76 TC 15 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD OCT 25 PY 1996 VL 357 IS 1-2 BP 143 EP 165 DI 10.1016/0027-5107(96)00095-4 PG 23 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA VM364 UT WOS:A1996VM36400017 PM 8876690 ER PT J AU Lapham, CK Ouyang, J Chandrasekhar, B Nguyen, NY Dimitrov, DS Golding, H AF Lapham, CK Ouyang, J Chandrasekhar, B Nguyen, NY Dimitrov, DS Golding, H TI Evidence for cell-surface association between fusin and the CD4-gp120 complex in human cell lines SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN; T-CELL; CD4; COMPONENT(S); MACROPHAGES; MODULATION; TROPISM AB Accessory cell-surface molecules involved in the entry of human immunodeficiency virus-type 1 into cells have recently been identified and shown to belong to the family of chemokine receptors, Treatment of human cell lines with soluble monomeric gp120 at 37 degrees C induced an association between the surface CD4-gp120 complex and a 45-kilodalton protein, which can be down-modulated by the phorbol ester phorbol 12-myristate 13-acetate. The three proteins were coprecipitated from the cell membranes with antibodies to CD4 or to gp120, The 45-kilodalton protein comigrated with fusin on sodium dodecyl sulfate gels and reacted with rabbit antisera to fusin in protein immunoblots, No 45-kilodalton protein could be coprecipitated from similarly treated nonhuman cells, However, infection of 3T3.CD4.401 cells with vaccinia-fusin recombinant virus (vCBYF1), followed by gp120 treatment, resulted in coprecipitation of fusin and CD4.401 molecules from their membranes. Together these data provide evidence for physical association between fusin and the CD4-gp120 complex on cell membranes. C1 NCI, MEMBRANE STRUCT & FUNCT SECT, BETHESDA, MD 20892 USA. US FDA, CTR BIOL EVALUAT & RES, FACIL BIOTECHNOL RESOURCES, BETHESDA, MD 20892 USA. RP Lapham, CK (reprint author), US FDA, CTR BIOL EVALUAT & RES,DIV VIRAL PROD,BLDG 29B, ROOM 3G21,HFM 454, 8800 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 17 TC 331 Z9 336 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 25 PY 1996 VL 274 IS 5287 BP 602 EP 605 DI 10.1126/science.274.5287.602 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VN919 UT WOS:A1996VN91900048 PM 8849450 ER PT J AU Schachter, JB Lester, DS Alkon, DL AF Schachter, JB Lester, DS Alkon, DL TI Synergistic activation of protein kinase C by arachidonic acid and diacylglycerols in vitro: Generation of a stable membrane-bound, cofactor-independent state of protein kinase C activity SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE kinase C; diacylglycerol; arachidonic acid; calcium; lipid; vesicle ID UNSATURATED FATTY-ACIDS; LONG-TERM POTENTIATION; PHORBOL ESTERS; RAT-BRAIN; PHOSPHOLIPID-VESICLES; CELLS; EXPRESSION; INVITRO; DELTA; AUTOPHOSPHORYLATION AB The present study examines the synergistic activation of PKC by arachidonic acid and diacylglycerols in phospholipid vesicles and demonstrates that this combination of activators leads to the formation of a constitutively active, phospholipid-bound form of the enzyme. Activation of PKC was almost entirely calcium-dependent with vesicles containing dioleoylglycerol alone. In contrast, considerable calcium-independent activity was observed when vesicles contained both a diacylglycerol and free arachidonic acid. High-affinity association of enzyme activity with diacylglycerol-containing vesicles was calcium dependent and reversible. However, addition of arachidonic acid to diacylglycerol-containing vesicles resulted in irreversible PKC binding in the absence of calcium. Immunoblot analysis indicated that the calcium-independent binding was not isozyme-specific. The activity of the vesicle-associated PKC, bound to vesicles in the absence of calcium, was predominantly calcium-dependent. On the other hand, when the binding and isolation of vesicle-bound enzyme was conducted in the presence of calcium, the subsequent activity was almost entirely resistant to calcium chelation. This vesicle-associated form of the enzyme, when detergent extracted and recombined with phospholipid vesicles, maintained significant 'constitutive' activity (activity in the absence of both diacylglycerol and calcium). The data from this in vitro system provide the basis for a model of the physiological regulation of PKC in which the combined actions of arachidonate and diacylglycerol facilitate the stable formation of a tightly membrane-associated, intrinsically active form of PKC. C1 NINCDS, LAB ADAPT SYST, BETHESDA, MD 20892 USA. US FDA, CDER, DIV RES & TESTING, LAUREL, MD 20708 USA. NR 60 TC 34 Z9 34 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 EI 1872-8006 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD OCT 24 PY 1996 VL 1291 IS 2 BP 167 EP 176 DI 10.1016/0304-4165(96)00063-3 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VN766 UT WOS:A1996VN76600011 PM 8898879 ER PT J AU Ali, SF Newport, GD Slikker, W Rothman, RB Baumann, MH AF Ali, SF Newport, GD Slikker, W Rothman, RB Baumann, MH TI Neuroendocrine and neurochemical effects of acute ibogaine administration: A time course evaluation SO BRAIN RESEARCH LA English DT Article DE ibogaine; prolactin; corticosterone; dopamine; serotonin ID NMDA RECEPTOR COMPLEX; ANTI-ADDICTIVE DRUG; PARASAGITTAL ZONES; GROWTH-HORMONE; MK-801 BINDING; RATS; MORPHINE; DOPAMINE; PHENCYCLIDINE; PROLACTIN AB Ibogaine (IBO) is an indole alkaloid that is reported to facilitate drug abstinence in substance abusers. Despite considerable investigation, the mechanism of IBO action in vivo and its suitability as a treatment for drug addiction remains unclear. The present study was designed to evaluate the time-course effects of acute IBO on neuroendocrine and neurochemical indices. Adult male rats were treated with i.p. saline or 50 mg/kg IBO and sacrificed 15: 30, 60, 120 min and 24 h later. Trunk blood was collected for hormone measures and brains were dissected for neurochemical analyses. IBO produced a rapid elevation in plasma prolactin that declined to control levels by 60 min. Corticosterone levels increased 15 min after drug administration, continued to increase for 120 min, but returned to control levels 24 h after dosing. IBO decreased dopamine (DA) concentrations in the striatum and frontal cortex at 30, 60 and 120 min after injection while DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were elevated over the same time period. 24 h after IBO, DOPAC concentrations in striatum and HVA levels in the frontal cortex were below control values. Serotonin (5-HT) and its metabolite 5-hydroxyindole acetic acid (5-HIAA) were decreased at 60 min after IBO administration only in the striatum. These data indicate that a single injection of IBO produces a spectrum of effects that includes: (I) elevation of plasma prolactin and corticosterone, (2) short- and long-term effects on DA neurotransmission, and (3) modest, transient effects of 5-HT neurotransmission. The effects of IBO reported herein may have relevance to the anti-addictive properties of this drug, and this proposal warrants further investigation. C1 NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,NIH,IRP,BALTIMORE,MD 21224. US FDA,NATL CTR TOXICOL RES,NEUROCHEM LAB,DIV NEUROTOXICOL,JEFFERSON,AR 72079. NR 36 TC 17 Z9 18 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 OCT 21 PY 1996 VL 737 IS 1-2 BP 215 EP 220 DI 10.1016/0006-8993(96)00734-2 PG 6 WC Neurosciences SC Neurosciences & Neurology GA VR614 UT WOS:A1996VR61400025 PM 8930368 ER PT J AU Zhang, DL Evans, FE Freeman, JP Yang, YF Deck, J Cerniglia, CE AF Zhang, DL Evans, FE Freeman, JP Yang, YF Deck, J Cerniglia, CE TI Formation of mammalian metabolites of cyclobenzaprine by the fungus, Cunninghamella elegans SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE cyclobenzaprine; Cunninghamella elegans; cytochrome P-450; drug metabolism; hydroxylation; microbial biotransformation; N-demethylation; N-oxidation ID POLYCYCLIC AROMATIC-HYDROCARBONS; CELL-EXTRACTS; BENZANTHRACENE; BIODEGRADATION AB The fungus, Cunninghamella elegans, was used as a microbial model of mammalian drug metabolism to biotransform a tricyclic antidepressant, cyclobenzaprine. Seventy-Eve percent of this drug at a concentration of 1 mM was metabolized within 72 h by C. elegans grown on Sabouraud dextrose broth. Milligram amounts of fungal metabolites were isolated by reversed-phase high performance liquid chromatography (HPLC) and their structures were characterized by H-1 NMR spectroscopy, mass spectrometry, and UV spectroscopy analyses. The major fungal metabolites of cyclobenzaprine were 2-hydroxycyclobenzaprine (59%), N-desmethylcyclobenzaprine (21%), cyclobenzaprine trans-10,11-dihydrodiol (5%), N-desmethyl-2-hydroxy-cyclobenzaprine (3%), 3-hydroxycyclobenzaprine (3%), and cyclobenzaprine N-oxide (1%). These fungal metabolites were used as standards to investigate the metabolism of cyclobenzaprine by rat liver microsomes. Rat liver microsomes also biotransformed cyclobenzaprine to produce similar metabolites as the fungus. The isotope labeling of 2-hydroxycyclobenzaprine by O-18(2), and the trans-configuration of the dihydrodiol suggested that these reactions were catalyzed by cytochrome P-450 monooxygenases in C. elegans. These results also demonstrated that the fungal biotransformation system could be used to predict and synthesize the mammalian drug metabolites. C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 24 TC 23 Z9 23 U1 1 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD OCT 21 PY 1996 VL 102 IS 2 BP 79 EP 92 DI 10.1016/S0009-2797(96)03736-2 PG 14 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA VU542 UT WOS:A1996VU54200002 PM 8950223 ER PT J AU Hoang, B Moos, M Vukicevic, S Luyten, FP AF Hoang, B Moos, M Vukicevic, S Luyten, FP TI Primary structure and tissue distribution of FRZB, a novel protein related to Drosophila frizzled, suggest a role in skeletal morphogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMINO-ACID SEQUENCE; POLARITY GENE; EXPRESSION; OSTEOGENIN; CLEAVAGE; SITES AB Articular cartilage extracts were prepared to characterize protein fractions with in vivo chondrogenic activity (Chang, S., Hoang, B., Thomas, J. T., Vukicevic, S., Luyten, F. P., Ryba, N. J. P., Kozak, C. A., Reddi, A. H., and Woos, M. (1994) J. Biol. Chem. 269, 28227-28234). Trypsin digestion of highly purified chondrogenic protein fractions allowed the identification of several unique peptides by amino acid sequencing. We discovered a novel cDNA encoding a deduced 36-kDa protein by using degenerate oligonucleotide primers derived from a 30-residue peptide in reverse transcription polymerase chain reactions. Its N-terminal domain showed similar to 50%, amino acid identity to the corresponding region of the Drosophila gene frizzled, which has been implicated in the specification of hair polarity during development. Hydropathy and structural analyses of the open reading frame revealed the presence of a signal peptide and a hydrophobic domain followed by multiple potential serine/threonine phosphorylation sites and a serine-rich C terminus. Cell fractionation studies of primary bovine articular chondrocytes and transfected COS cells suggested that the protein is membrane-associated. In situ hybridization and immunostaining of human embryonic sections demonstrated predominant expression surrounding the chondrifying bone primordia and subsequently in the chondrocytes of the epiphyses in a graded distribution that decreased toward the primary ossification center. Transcripts were present in the craniofacial structures but not in the vertebral bodies. Because it is expressed primarily in the cartilaginous cores of developing long bones during embryonic and fetal development (6-13 weeks) and is homologous to the polarity-determining gene frizzled, we believe that this gene, which we named frzb, is involved in morphogenesis of the mammalian skeleton. C1 NIDR,BONE RES BRANCH,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DEV BIOL LAB,BETHESDA,MD 20892. MED SCH ZAGREB,DEPT ANAT,ZAGREB 41000,CROATIA. RI Moos, Malcolm/F-3673-2011 OI Moos, Malcolm/0000-0002-9575-9938 NR 29 TC 181 Z9 188 U1 0 U2 5 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 OCT 18 PY 1996 VL 271 IS 42 BP 26131 EP 26137 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VN180 UT WOS:A1996VN18000063 PM 8824257 ER PT J AU Pogue, GP Joshi, M Lee, NS Dwyer, DM Kenney, RT Gam, AA Nakhasi, HL AF Pogue, GP Joshi, M Lee, NS Dwyer, DM Kenney, RT Gam, AA Nakhasi, HL TI Conservation of low-copy gene loci in Old World leishmanias identifies mechanisms of parasite evolution and diagnostic markers SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE restriction-fragment length polymorphism(s); pulsed-field gel electrophoresis; chromosome structure; differential gene expression; evolution ID POLYMERASE CHAIN-REACTIONS; MOLECULAR KARYOTYPE; NUCLEAR-DNA; DONOVANI; STRAINS; CLASSIFICATION; POLYMORPHISMS; SEQUENCE; TUBULIN; COMPLEX AB Genome plasticity. has been hypothesized to be a driving force behind parasite speciation. We have evaluated divergence in single and low-copy genes in terms of locus organization, chromosomal localization and gene expression in Leishmania infantum, L. major, L. tropica and three widely divergent geographic isolates of L. donovani. Seventeen genes of low to moderate copy number (1-4 copies/haploid genome) were analyzed to identify restriction fragment length polymorphisms (RFLPs) providing heritable markers distinguishing Old World (OW) leishmanias. These RFLP markers were conserved in parasite isolates from primary infections demonstrating their utility as diagnostic tools. The species designations established by RFLP analysis of field isolates was confirmed by use of monoclonal antibodies. All 17 genes were present in each OW leishmania analyzed except LSIP (A45), which was absent from L. infantum. The 17 genes were found to be distributed among 9 distinct chromosomes. However, in spite of variations in chromosome karyotypes among the various OW leishmanias, individual gene probes localized to a similar sized chromosome from each isolate. These observations coupled with a molecular tree derived from RFLP data suggest that the OW leishmanias comprise a monophyletic lineage, with species associated with cutaneous disease exhibiting the greatest level of divergence. Data from this study supports previous observations that species causing cutaneous and visceral disease have diverged primarily by nucleotide substitutions. Such nucleotide divergence may not only lead to changes in protein function and antigenicity, but may also alter gene regulation programs as exemplified by the finding that the LdI-9-5 and LdE-6-1 genes were expressed only in visceralizing leishmanias. C1 US FDA,VPAR,DVP,OVRR,CBER,LAB MOL PHARMACOL,DIV HEMATOL PROD,OTRR,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. US FDA,LAB PARASIT BIOL & BIOCHEM,DIV ALLERGEN & PARASIT PROD,OVRR,CBER,BETHESDA,MD 20892. NR 39 TC 16 Z9 16 U1 0 U2 3 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 OCT 18 PY 1996 VL 81 IS 1 BP 27 EP 40 DI 10.1016/0166-6851(96)02697-7 PG 14 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA VL193 UT WOS:A1996VL19300003 PM 8892303 ER PT J AU Joshi, M Pogue, GP Duncan, RC Lee, NS Singh, NK Atreya, CD Dwyer, DM Nakhasi, HL AF Joshi, M Pogue, GP Duncan, RC Lee, NS Singh, NK Atreya, CD Dwyer, DM Nakhasi, HL TI Isolation and characterization of Leishmania donovani calreticulin gene and its conservation of the RNA binding activity SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE calreticulin; RNA binding protein; phosphorylation; glycosylation; trypanosomatid; functional conservation ID SARCOPLASMIC-RETICULUM; ENDOPLASMIC-RETICULUM; MOLECULAR-CLONING; PROTEIN; IDENTIFICATION; GLYCOPROTEINS; EXPRESSION; MEMBRANE; INVITRO AB Calreticulin has been implicated in multiple cell functions. Recently, we have shown that both human and simian calreticulin are RNA binding proteins and that their binding activity is due to phosphorylation. To demonstrate that the RNA binding property of calreticulin is an intrinsic part of this multi-functional molecule and is evolutionarily conserved, we isolated and characterized the calreticulin gene from the unicellular parasite, Leishmania donovani. Amino acid sequence homology between human and Leishmania calreticulin (L. d. cal) is limited, but like the human homologue, L. d. cal binds Ca++, can be phosphorylated in vitro and binds certain RNA sequences in a phosphorylation-dependent manner. Unlike human calreticulin, L. d. cal is glycosylated and its binding to endogenous Leishmania RNA is phosphorylation-independent. The binding of L. d. cal to Leishmania RNA suggests that the RNA binding activity of calreticulin has remained evolutionarily conserved. C1 US FDA,MOL PHARMACOL LAB,DHP,OTRR,CBER,BETHESDA,MD 20892. NIAID,CELL BIOL SECT,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 NR 39 TC 35 Z9 35 U1 0 U2 0 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 OCT 18 PY 1996 VL 81 IS 1 BP 53 EP 64 DI 10.1016/0166-6851(96)02676-X PG 12 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA VL193 UT WOS:A1996VL19300005 PM 8892305 ER PT J AU Feller, SE Pastor, RW Rojnuckarin, A Bogusz, S Brooks, BR AF Feller, SE Pastor, RW Rojnuckarin, A Bogusz, S Brooks, BR TI Effect of electrostatic force truncation on interfacial and transport properties of water SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID MOLECULAR-DYNAMICS SIMULATION; LONG-RANGE INTERACTIONS; PARTICLE MESH EWALD; COMPUTER-SIMULATION; BOUNDARY-CONDITIONS; LIQUID/LIQUID INTERFACES; PHOSPHOLIPID-BILAYERS; SURFACE-TENSION; LIPID BILAYERS; MONTE-CARLO AB The importance of accurately accounting for all Coulombic forces in molecular dynamics simulations of water at interfaces is demonstrated by comparing the Ewald summation technique with various spherical truncation methods, The increased structure induced by truncation methods at 12 Angstrom leads to water/vapor surface tensions and surface potentials that are respectively 50% and 100% greater than obtained with Ewald. The orientational polarization of water at the lipid/water interface is analyzed within the Marcelja-Radic theory of the hydration force, yielding decay parameters of 2.6 and 1.8 Angstrom for spherical truncation and Ewald, respectively, as compared with 1.7-2.1 Angstrom obtained from experiment. Bulk water transport properties such as the viscosity and diffusion constants differ by as much as 100% between simulations carried out with and without truncation; this may be related to ordering in the neighborhood of the cutoff radius. The diffusion constant calculated from the Ewald simulation is significantly further from experiment than the cutoff result, pointing out the need to reparametrize the TIP3P water model for use with Ewald summation. Appendices describe a method for carrying out the Ewald summation on a distributed memory parallel computer and other computational details relevant when simulating large systems. C1 US FDA,CTR BIOL EVALUAT & RES,BIOL LAB,ROCKVILLE,MD 20852. UNIV WISCONSIN,DEPT CHEM ENGN,MADISON,WI 53706. WALTER REED ARMY INST RES,DEPT GASTROENTEROL,WASHINGTON,DC 20307. NIH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,BETHESDA,MD 20892. NR 52 TC 265 Z9 268 U1 1 U2 29 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 OCT 17 PY 1996 VL 100 IS 42 BP 17011 EP 17020 DI 10.1021/jp9614658 PG 10 WC Chemistry, Physical SC Chemistry GA VN802 UT WOS:A1996VN80200034 ER PT J AU Wachsman, M BarditchCrovo, P Lietman, PS Trapnell, CB AF Wachsman, M BarditchCrovo, P Lietman, PS Trapnell, CB TI Lack of beta-oxidation defects in human immunodeficiency virus-positive subjects with and without chronic zidovudine exposure SO BLOOD LA English DT Letter ID TUMOR-NECROSIS-FACTOR; MITOCHONDRIAL; AIDS C1 US FDA,CTR DRUG EVALUAT & RES,BETHESDA,MD. RP Wachsman, M (reprint author), JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21287, USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 1996 VL 88 IS 8 BP 3243 EP 3244 PG 2 WC Hematology SC Hematology GA VN595 UT WOS:A1996VN59500053 PM 8874227 ER PT J AU Herman, EH Lipshultz, SE Rifai, N Zhang, J Papoian, T Yu, ZX Ferrans, VJ AF Herman, EH Lipshultz, SE Rifai, N Zhang, J Papoian, T Yu, ZX Ferrans, VJ TI Cardiac troponin T: Elevated serum levels and loss from cardiac myocytes in doxorubicin toxicity. SO CIRCULATION LA English DT Meeting Abstract C1 US FDA,LAUREL,MD. BOSTON UNIV,CHILDRENS HOSP,BOSTON,MA. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 486 EP 486 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900485 ER PT J AU Benton, RE Sale, M Chen, YW Trapnell, CB Flockhart, DA Woosley, RL AF Benton, RE Sale, M Chen, YW Trapnell, CB Flockhart, DA Woosley, RL TI Women have greater QTc prolongation with quinidine than men SO CIRCULATION LA English DT Meeting Abstract C1 GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20057. US FDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 4314 EP 4314 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11904305 ER PT J AU Ramachandra, S Metcalf, RA Fredrickson, T Marti, GE Raveche, E AF Ramachandra, S Metcalf, RA Fredrickson, T Marti, GE Raveche, E TI Requirement for increased IL-10 in the development of B-1 lymphoproliferative disease in a murine model of CLL SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE IL-10; B-1 cell; CD5+B cell; B-CLL; lymphoproliferation ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; ANTISENSE IL-10; B-LYMPHOCYTES; CELL LYMPHOMA; SERUM LEVELS; NZB MICE; INTERLEUKIN-10; EXPRESSION; GROWTH AB Malignant B-l cells derived from NZB mice, a murine model of spontaneous autoimmunity and B cell lymphoproliferative disease, produce significantly higher levels of IL-10 mRNA than normal B-l or B cells, IL-10 may act as an autocrine growth factor for the expansion of malignant B-l cells. In order to determine if elevated endogenous production of IL-10 was a required element for the malignant transformation of B-l cells in NZB mice, backcross animals were studied for the linkage between elevated IL-10 expression and the presence of lymphoid malignancy. The phenotypes of aged (NZB x DBA/2)F-1 x NZB animals were determined and a strong correlation was found between the elevated levels of IL-10 mRNA and the development of B-l malignant clones, In contrast, an increased level of IL-10 message was not associated with elevated serum IgM or the presence of anemia or reticulocytosis which is mainly seen in response to autoantibody production. These results indicate that, at least in NZB, the autoimmunity and lymphoproliferation phenotypes are not linked genetically, IL-10 may enhance proliferation and the development of B-l cell malignancy rather than antibody production by the B-l cell subpopulation, Thus, IL-10 plays an important role in B-l malignancies, and downregulation of IL-10 could be a likely site for intervention in B cell malignancies. C1 UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,DEPT PATHOL,NEWARK,NJ 07103. US FDA,CTR BIOL EVALUAT & RES,NIH,BETHESDA,MD 20812. FU NCI NIH HHS [CA-71478] NR 34 TC 35 Z9 36 U1 1 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT 15 PY 1996 VL 98 IS 8 BP 1788 EP 1793 DI 10.1172/JCI118978 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VN973 UT WOS:A1996VN97300014 PM 8878429 ER PT J AU Greenhouse, JB Silliman, NP AF Greenhouse, JB Silliman, NP TI Applications of a mixture survival model with covariates to the analysis of a depression prevention trial SO STATISTICS IN MEDICINE LA English DT Article ID CLINICAL-TRIALS; BAYES FACTORS; THERAPY; DISORDERS AB This paper presents a case study of model selection for survival analysis data. We use an approximate Bayesian method for model selection based on assessing the posterior probability of competing models given the data. We introduce the Schwarz criteria, an approximation to the logarithm of the Bayes factor, to provide an indication of evidence in favour of one model compared to another. Specifically,in the context of a depression prevention clinical trial we evaluate the efficacy of treatment in preventing or delaying the time to recurrence of depression, and evaluate how differences in the survival distributions between the two treatment groups depend on explanatory variables of interest. This investigation is based on a mixture survival model that explicitly incorporates the possibility of a surviving fraction. C1 US FDA,DIV BIOMETR,ROCKVILLE,MD 20857. RP Greenhouse, JB (reprint author), CARNEGIE MELLON UNIV,DEPT STAT,PITTSBURGH,PA 15213, USA. FU NCI NIH HHS [CA54852]; NIMH NIH HHS [MHCRC30915] NR 32 TC 7 Z9 7 U1 1 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 OCT 15 PY 1996 VL 15 IS 19 BP 2077 EP 2094 DI 10.1002/(SICI)1097-0258(19961015)15:19<2077::AID-SIM348>3.0.CO;2-X PG 18 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 VK325 UT WOS:A1996VK32500008 PM 8896141 ER PT J AU Soh, Y Rhee, HM Sohn, DH Song, BJ AF Soh, Y Rhee, HM Sohn, DH Song, BJ TI Immunological detection of CYP2E1 in fresh rat lymphocytes and its pretranslational induction by fasting SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID LIPID-PEROXIDATION; ETHANOL; EXPRESSION; PROTEIN; CYTOCHROME-P450IIE1; STABILIZATION; DEHYDROGENASE; CHLORZOXAZONE; GLUTATHIONE; KIDNEY AB The level of ethanol-inducible cytochrome P450 2E1 (CYP2E1) in fresh lymphocytes compared with cultured cells and its induction mechanism by fasting were studied. CYP2E1 in the homogenate and 8-9 fraction of fresh lymphocytes was elevated about 5-fold by fasting, comparable to the induction observed in cultured lymphocytes. This induction was accompanied by increased level of CYP2E1 mRNA, confirmed by nested RT-PCRs, Southern blot, and DNA sequence analysis. Our data thus demonstrated that CYP2E1 in fresh lymphocytes is pretranslationally induced by fasting, in parallel to the hepatic enzyme, and that measurement of CYP2E1 in the lymphocyte homogenate can be useful to estimate the hepatic CYP2E1 level in a relatively noninvasive manner. (C) 1996 Academic Press, Inc. C1 NIAAA,NEUROGENET LAB,NIH,ROCKVILLE,MD 20852. WONKWANG UNIV,COLL PHARM,IKSAN,SOUTH KOREA. US FDA,DIV METAB & ENDOCRINE DRUG PROD,ROCKVILLE,MD 20857. NR 26 TC 34 Z9 34 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 14 PY 1996 VL 227 IS 2 BP 541 EP 546 DI 10.1006/bbrc.1996.1542 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VP321 UT WOS:A1996VP32100037 PM 8878549 ER PT J AU Akasawa, A Hsieh, LS Martin, BM Liu, T Lin, Y AF Akasawa, A Hsieh, LS Martin, BM Liu, T Lin, Y TI A novel acidic allergen, Hev b 5, in latex - Purification, cloning and characterization SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CONTACT URTICARIA; CROSS-REACTIVITY; GLOVES; RUBBER; BRASILIENSIS; PROTEINS AB Latex allergy is recognized as a serious health problem among health care workers and children with spina bifida, A number of IgE-reactive proteins have been identified in natural and processed latex products. One of the most acidic proteins in the cytoplasm of lacticifer cells of rubber trees (Hevea brasiliensis) is demonstrated to be a potent allergen in eliciting allergic reactions in humans, This protein, with pI = 3.5, has a molecular mass of 16 kDa with a blocked N terminus and an unusual amino acid composition, This acidic protein was found in extracts prepared from latex gloves, which were shown to be allergenic, The purified protein elicits histamine release from human basophils passively sensitized with serum from latex-allergic individuals in a dose dependent manner. From a latex cDNA library, the cDNA coding for this protein was isolated and sequenced. The deduced amino acid sequence shows a high degree of homology to another acidic protein identified in kiwifruit (Actinidia deliciosa var. deliciosa). The sequence homology (47% sequence identity) between these two acidic proteins suggests a molecular explanation for the high frequency of fruit hypersensitivity in latex-allergic patients. C1 US FDA,DIV ALLERGEN PROD & PARASITOL,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852. NIMH,CLIN NEUROSCI BRANCH,UNIT MOL STRUCT,BETHESDA,MD 20892. RI Moussa, Luciana /M-2257-2013 NR 23 TC 73 Z9 76 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 OCT 11 PY 1996 VL 271 IS 41 BP 25389 EP 25393 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VL693 UT WOS:A1996VL69300049 PM 8810305 ER PT J AU Nightingale, SL AF Nightingale, SL TI Symposium on deadly diseases and people of color: Are clinical trials an option? 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 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 OCT 9 PY 1996 VL 276 IS 14 BP 1128 EP 1128 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VL332 UT WOS:A1996VL33200005 PM 8827954 ER PT J AU Nightingale, SL AF Nightingale, SL TI Plan for distribution of prescription drug information for patients 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 3 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 OCT 9 PY 1996 VL 276 IS 14 BP 1128 EP 1128 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VL332 UT WOS:A1996VL33200004 PM 8827954 ER PT J AU Nightingale, SL AF Nightingale, SL TI Treatment to protect against poison ivy 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 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 OCT 9 PY 1996 VL 276 IS 14 BP 1128 EP 1128 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VL332 UT WOS:A1996VL33200006 PM 8827954 ER PT J AU Nightingale, SL AF Nightingale, SL TI Final regulations to reduce children's use of tobacco issued 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 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 OCT 9 PY 1996 VL 276 IS 14 BP 1128 EP 1128 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VL332 UT WOS:A1996VL33200007 PM 8827954 ER PT J AU Miller, L Mangione, E Beebe, J Hoffman, RE Levy, P Huitt, G Miller, GL AF Miller, L Mangione, E Beebe, J Hoffman, RE Levy, P Huitt, G Miller, GL TI Infection with Mycobacterium abscessus associated with intramuscular injection of adrenal cortex extract - Colorado and Wyoming, 1995-1996 (Reprinted from MMWR, vol 45, pg 713, 1996) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 NATL JEWISH CTR IMMUNOL & RESP MED,DENVER,CO 80206. WYOMING DEPT HLTH,CHEYENNE,WY 82006. US FDA,ROCKVILLE,MD 20857. CTR DIS CONTROL,NATL CTR INFECT DIS,DIV BACTERIAL & MYCOT DIS,CHILDHOOD & RESP DIS BRANCH,ATLANTA,GA 30333. CTR DIS CONTROL,NATL CTR INFECT DIS,DIV AIDS STD & TB LAB RES,TB MYCOBACTERIOL BRANCH,ATLANTA,GA 30333. RP Miller, L (reprint author), COLORADO DEPT PUBL HLTH & ENVIRONM,DENVER,CO 80222, USA. NR 1 TC 4 Z9 4 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 OCT 9 PY 1996 VL 276 IS 14 BP 1130 EP 1130 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VL332 UT WOS:A1996VL33200008 ER PT J AU Freyaldenhoven, TE Cadet, JL Ali, SF AF Freyaldenhoven, TE Cadet, JL Ali, SF TI The dopamine-depleting effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in CD-1 mice are gender-dependent SO BRAIN RESEARCH LA English DT Article DE MPTP; MPP(+); striatal dopamine; gender; CD-I mouse; neurotoxicity ID STRIATAL DOPAMINE; SUBSTANTIA-NIGRA; NEUROTOXIN 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; 1-METHYL-4-PHENYLPYRIDINIUM ION; CHRONIC PARKINSONISM; SPECIES SENSITIVITY; TRANSGENIC MICE; MOUSE-BRAIN; OXIDASE-B; MPTP AB 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyrine (MPTP) is a selective dopaminergic neurotoxin affecting the nigrostriatal system in a variety of species including, rodents, nonhuman primates and humans. There exists, however, a great deal of variability in the sensitivity of different species to the effects of MPTP. The present study was designed to determine whether a significant difference in gender susceptibility to the toxin in CD-I mice might also exist. A dosing regiment of 30 mg/kg MPTP once a day for 3 days (90 mg/kg total dose) in 4-month-old male and female CD-I mice led to a significant depletion of striatal dopamine in both sexes. Two way ANOVA analysis of a time-course generated by measuring striatal dopamine at 4, 12 and 24 h after each dose of MPTP revealed that the initial dopamine reduction is significantly greater in male CD-1 mice (P < 0.001). Further, dopamine levels were reduced to a greater extent in male mice 5 days after the last dose (31% vs. 59% of control; P < 0.02). HPLC analysis using fluorescence detection revealed no difference in the striatal nor the cerebellar levels of MPP(+) between the two sexes, however, accumulation of larger amounts of MPP(+) was observed in the livers of the female mice. These findings suggest that, while female CD-1 mice are more resistant to the dopamine-depleting effects of MPTP, this gender difference is not due to decreased production or accumulation of striatal MPP(+). C1 NATL CTR TOXICOL RES,DIV NEUROTOXICOL,NEUROCHEM LAB,JEFFERSON,AR 72079. UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM & MOL BIOL,LITTLE ROCK,AR 72205. NIDA,MOL NEUROPSYCHIAT SECT,NIH,ADDICT RES CTR,BALTIMORE,MD 21224. NR 44 TC 50 Z9 50 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 OCT 7 PY 1996 VL 735 IS 2 BP 232 EP 238 DI 10.1016/0006-8993(96)00598-7 PG 7 WC Neurosciences SC Neurosciences & Neurology GA VP317 UT WOS:A1996VP31700006 PM 8911661 ER PT J AU Levy, M Fletcher, M Moody, M Cory, D Corbitt, W Borowiecki, C Gries, D Heidingsfelder, J Oglesby, A Butwin, J Ewert, D Bixler, D Barrett, B Laurie, K Muniz, E Steele, G Baldonti, A Williamson, B Layton, M Kornstein, L Griffin, E Cambridge, M Fogg, N Guzewich, J Root, T Morse, D Wagoner, J Deasey, M Miller, K AF Levy, M Fletcher, M Moody, M Cory, D Corbitt, W Borowiecki, C Gries, D Heidingsfelder, J Oglesby, A Butwin, J Ewert, D Bixler, D Barrett, B Laurie, K Muniz, E Steele, G Baldonti, A Williamson, B Layton, M Kornstein, L Griffin, E Cambridge, M Fogg, N Guzewich, J Root, T Morse, D Wagoner, J Deasey, M Miller, K TI Outbreaks of Salmonella serotype enteritidis infection associated with consumption of raw shell eggs - United States, 1994-1995 (Reprinted from MMWR, vol 45, pg 735-742, 1996) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 VANDERBURGH CTY HLTH DEPT,EVANSVILLE,IN. INDIANA STATE DEPT HLTH,INDIANAPOLIS,IN 46202. ALBERT EINSTEIN COLL MED,NEW YORK,NY. SUFFOLK CTY HLTH DEPT,HAUPPAUGE,NY. NEW YORK CITY DEPT HLTH,BUR COMMUNICABLE DIS CONTROL,NEW YORK,NY 10013. NEW YORK CITY DEPT HLTH,BUR LABS,NEW YORK,NY 10013. NEW YORK CITY DEPT HLTH,BUR ENVIRONM INVEST,NEW YORK,NY 10013. NEW YORK CITY DEPT HLTH,BUR COMMUNITY SANITAT & FOOD PROTECT,NEW YORK,NY 10013. NEW YORK CITY DEPT HLTH,WADSWORTH CTR LABS & RES,NEW YORK,NY 10013. NEW YORK STATE DEPT AGR & MARKETS,ALBANY,NY 12235. PENN DEPT HLTH,DIV EPIDEMIOL,HARRISBURG,PA 17108. US FOOD SAFETY & INSPECT SERV,USDA,WASHINGTON,DC 20250. ANIM & PLANT HLTH INSPECT SERV,FOOD SAFETY & INSPECT SERV,USDA,WASHINGTON,DC. US FDA,ROCKVILLE,MD 20857. CDC,FOODBORNE & DIARRHEAL DIS BRANCH,DIV BACTERIAL & MYCOT DIS,NATL CTR INFECT DIS,ATLANTA,GA 30333. PENN DEPT AGR,HARRISBURG,PA 17110. RP Levy, M (reprint author), DIST COLUMBIA COMMISS PUBL HLTH,BUR EPIDEMIOL & DIS CONTROL,WASHINGTON,DC, USA. NR 6 TC 4 Z9 4 U1 0 U2 3 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 OCT 2 PY 1996 VL 276 IS 13 BP 1017 EP & PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VK035 UT WOS:A1996VK03500004 ER PT J AU Kumar, GS Musser, SM Cummings, J Tomasz, M AF Kumar, GS Musser, SM Cummings, J Tomasz, M TI 2,7-diaminomitosene, a monofunctional mitomycin C derivative, alkylates DNA in the major groove. Structure and base-sequence specificity of the DNA adduct and mechanism of the alkylation SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID CROSS-LINK ADDUCT; REDUCTIVE ACTIVATION; DT-DIAPHORASE; NUCLEIC-ACIDS; TUMOR-TISSUE; METABOLISM; BINDING; RAT; SELECTIVITY; CARCINOGEN AB Reductive activation of the bifunctional alkylator and DNA cross-linking agent mitomycin C (MC) yields 2,7-diaminomitosene (2,7-DAM) as the major product of its activation both in cell-free systems and in vivo. 2,7-DAM lacks one of the alkylating functions of MC, the aziridine. We show that 2,7-DAM itself alkylates DNA monofunctionally upon reductive activation, to form a heat-labile adduct. A guanine-N7-2,7-DAM adduct was isolated from the drug-DNA complex upon heating. Nuclease digestion yielded this adduct both in the nucleoside (dG-2,7-DAM) and dinucleoside phosphate [d(GpG)-2,7-DAM] forms. The structures of all three forms were determined by LC-ESIMS and differential UV spectroscopy. The adduct is sequence-specific to guanines in (G)(n) tracts of DNA. A guanine-N7-2,7-DAM adduct in DNA was indirectly observed previously by Prakash et al. (Prakash, A. S.; Beall, H.; Ross, D.; Gibson, N. W. Biochemistry 1993, 32, 5518-5525). The results indicate that selective removal of the aziridine function of MC results in a switch from minor to major groove alkylation of DNA, and a switch of sequence specificity from guanines in CpG to guanines in (G)(n) tracts, They also show that the mitosene C-10 carbamate intrinsically reacts as an S(N)2 alkylating agent, specific to guanine-N7. C1 CUNY HUNTER COLL,DEPT CHEM,NEW YORK,NY 10021. US FDA,INSTRUMENTAT & BIOPHYS BRANCH,WASHINGTON,DC 20204. WESTERN GEN HOSP,IMPERIAL CANC RES FUND,EDINBURGH,MIDLOTHIAN,SCOTLAND. NR 55 TC 44 Z9 44 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD OCT 2 PY 1996 VL 118 IS 39 BP 9209 EP 9217 PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA VK780 UT WOS:A1996VK78000001 ER PT J AU Pipkin, JL Hinson, WG LynCook, LE Duffy, PH Feuers, RJ Leakey, JEA Aly, KB Hart, RW Casciano, DA AF Pipkin, JL Hinson, WG LynCook, LE Duffy, PH Feuers, RJ Leakey, JEA Aly, KB Hart, RW Casciano, DA TI P48: A novel nuclear protein possibly associated with aging and mortality SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE aging; mortality; p48 ID CALORIC RESTRICTED RATS; HEAT-SHOCK PROTEINS; STRESS PROTEINS; CELL-CYCLE; POLYACRYLAMIDE GELS; SODIUM ARSENITE; HYPOTHALAMUS; MOUSE; ELECTROPHORESIS; BIOMARKERS AB The synthesis ([S-35]-incorporation) of stress proteins (sps, i.e., 24, 25, 70, 90 Mr) and of nuclear protein 48 (p48) was investigated in the heart and bone marrow cells of three groups of male Fischer 344 mts following administration of isoproterenol (IPR). Two groups of rats, young ad libitum (Y/AL-3(1/2) months) and old/AL (O/AL-28 months), had full access to rat chow; a third group of old diet restricted (O/DR-28 months) rats was maintained on a diet restricted intake of 40% of the Y/AL animals. Sp synthesis in the bone marrow (25, 70, 90 Mr) and heart (24, 70, 90 Mr) nuclei of O/AL was significantly reduced, as compared with Y/AL and O/DR rats, following their induction with IPR. A unique sp24 was expressed in heart following IPR dosing. A 1 mg/kg dose of IPR was lethal for O/AL, but not for Y/AL or O/DR animals. This lethal dose induced synthesis of p48 in heart and bone marrow nuclei of O/AL rats only. P48 existed in isoform states in bone marrow and when a lethal dose of IPR was administered in this tissue, it was expressed in O/AL rats in a cell-cycle regulated pattern. Stress proteins and other non-sps were seen as cell cycle regulated following IPR administration. P48 in bone marrow and heart nuclei from O/AL rats showed an antigenic response identical to that of p48 in HL60 nuclei. The presence of p48 is correlated with mortality and with an ad libitum diet in old rats, since it is absent in old diet restricted animals; therefore, DR may impede the expression of p48 through a mechanism(s) that is undisclosed at this time. (C) 1996, Editrice Kurtis C1 NATL CTR TOXICOL RES, OFF RES SUPPORT, JEFFERSON, AR 72079 USA. UNIV ARKANSAS MED SCI HOSP, LITTLE ROCK, AR 72205 USA. CAIRO UNIV, FAC MED, CAIRO, EGYPT. RP Pipkin, JL (reprint author), NATL CTR TOXICOL RES, DIV GENET TOXICOL, HFT-120, 3900 NC-TR RD, JEFFERSON, AR 72079 USA. NR 37 TC 4 Z9 4 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1594-0667 J9 AGING CLIN EXP RES JI Aging Clin. Exp. Res. PD OCT PY 1996 VL 8 IS 5 BP 311 EP 319 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA VW760 UT WOS:A1996VW76000003 PM 8959232 ER PT J AU Fenichel, RR Lipicky, RJ AF Fenichel, RR Lipicky, RJ TI On the trough-to-peak ratio of drug effect in antihypertensive trials SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE trough-to-peak effect; Food and Drug Administration; time course of drug effect; drug effectiveness; antihypertensive drug trials AB Blood pressure in hypertensives (treated or untreated) varies over the course of the day, and, although animal models and human intervention studies have demonstrated that the ill effects of hypertension are mediated by the pressure itself, and not by some confounder, it remains unknown what time-related function of pressure (simple mean, root-mean-square, duration of pressure above some threshold, and so on) might be the best predictor of hypertension-related morbidity. There is no accepted means of describing the time course of blood pressure, let alone a difference between two such descriptions, which might then be a description of the time course of a drug effect. In a document dated 1988, the US Food and Drug Administration (FDA) defined the trough-to-peak drug-effect ratio and indicated that drug approval would be granted only when values of this statistic were satisfactory. The FDA's belief in the importance of the timecourse of drug effect has grown stronger over time, but the idea that only drugs with certain trough-to-peak ratios could be approved was discarded by the FDA within months of its appearance. In recent years, more promising means of assessing the time-course of drug effect have begun to take shape. RP Fenichel, RR (reprint author), US FDA, DIV CARDIORENAL DRUG PROD, CTR DRUG EVALUAT & RES, DCRDP HFD-110, ROCKVILLE, MD 20857 USA. NR 2 TC 11 Z9 11 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD OCT PY 1996 VL 9 IS 10 SU S BP S105 EP S107 PN 2 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VM464 UT WOS:A1996VM46400015 PM 8896672 ER PT J AU Myers, MG Lipicky, RJ Uscinowicz, T Carruthers, SG White, WB AF Myers, MG Lipicky, RJ Uscinowicz, T Carruthers, SG White, WB TI Panel discussion #2 SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Editorial Material C1 US FDA,DIV CARDIORENAL DRUG PROD,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. FED BUR PRESCRIPT DRUGS,OTTAWA,ON,CANADA. UNIV WESTERN ONTARIO,LONDON,ON,CANADA. UNIV CONNECTICUT,HLTH SCI CTR,SECT HYPERTENS & VASC MED,FARMINGTON,CT. RP Myers, MG (reprint author), SUNNYBROOK HLTH SCI CTR,DIV CARDIOL,2075 BAYVIEW AVE,SUITE A-222,TORONTO,ON M4N 3M5,CANADA. NR 3 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 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD OCT PY 1996 VL 9 IS 10 SU S BP S108 EP S109 PN 2 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VM464 UT WOS:A1996VM46400016 ER PT J AU Myers, MG Meredith, PA Stewart, WH Lipicky, RJ Elliott, HL White, WB Feldman, R Carruthers, SG AF Myers, MG Meredith, PA Stewart, WH Lipicky, RJ Elliott, HL White, WB Feldman, R Carruthers, SG TI Panel Discussion #1 SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Editorial Material C1 UNIV GLASGOW,WESTERN INFIRM,DEPT MED & THERAPEUT,GLASGOW G11 6NT,LANARK,SCOTLAND. HOECHST MARION ROUSSEL INC,US STAT,KANSAS CITY,MO. US FDA,DIV CARDIORENAL DRUG PROD,CTR DRUG EVALUAT & RES,ROCKVILLE,MD. UNIV CONNECTICUT,HLTH SCI CTR,SECT HYPERTENS & VASC MED,FARMINGTON,CT. UNIV WESTERN ONTARIO,LONDON,ON,CANADA. RP Myers, MG (reprint author), SUNNYBROOK HLTH SCI CTR,DIV CARDIOL,2075 BAYVIEW AVE,SUITE A-222,TORONTO,ON M4N 3M5,CANADA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD OCT PY 1996 VL 9 IS 10 SU S BP S87 EP S90 PN 2 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VM464 UT WOS:A1996VM46400010 ER PT J AU Sagripanti, JL Bonifacino, A AF Sagripanti, JL Bonifacino, A TI Comparative sporicidal effect of liquid chemical germicides on three medical devices contaminated with spores of Bacillus subtilis SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article AB Background: The relatively limited variety of sur faces and geometries challenged in current sporicidal resting reduces the predictive value of these analyses when extrapolated to the wide variety of medical devices. The unknown spore load being challenged and the qualitative nature (growth/no growth) of those tests further prevent precise comparison among liquid chemical disinfectants. Hence, the relative activity of different chemical substances has not been clearly established, hindering selection of the best agent for each clinical situation. Methods: A micromethod was developed io assess sporicidal activity against Bacillus subtilis spores deposited on three different medical devices: carbon-steel dental burs, silicone-rubber medical catheters, and titanium-alloy dental abutmeat screws. The spore load on each device and the recovery after three analytical steps were quantitatively assessed with spores radiolabeled with carbon 14 methionine. Results: The killing of 2 to 7 x 10(6) spores loaded on three different devices and exposed to glutaraldehyde, formaldehyde, copper ascorbate, hydrogen peroxide, peracetic acid, sodium hypochlorite, or phenol for 30 minutes at 20 degrees C ranged from a 10(3)-fold decrease For 10% hydrogen peroxide to zero decrease for 5% phenol. Our results suggest that the nature of the surface being challenged may affect the sporicidal activity of some chemical agents. Conclusion: The quantitative data presented allow comparison of the sporicidal effect of different liquid chemical agents. These findings may help prevent an overestimation of sporicidal activity and possible transmission of pathogens from the surface of improperly decontaminated medical devices. RP Sagripanti, JL (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,MOL BIOL BRANCH,HFZ-113,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 24 TC 24 Z9 25 U1 1 U2 7 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD OCT PY 1996 VL 24 IS 5 BP 364 EP 371 DI 10.1016/S0196-6553(96)90024-3 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA VM664 UT WOS:A1996VM66400005 PM 8902111 ER PT J AU Kim, YI Pogribny, IP Salomon, RN Choi, SW Smith, DE James, SJ Mason, JB AF Kim, YI Pogribny, IP Salomon, RN Choi, SW Smith, DE James, SJ Mason, JB TI Exon-specific DNA hypomethylation of the p53 gene of rat colon induced by dimethyl hydrazine - Modulation by dietary folate SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID COLORECTAL-CANCER; 5-METHYLCYTOSINE CONTENT; ULCERATIVE-COLITIS; METHYLATION; DYSPLASIA; RISK; DEFICIENCY; CARCINOMA; CELLS; ALCOHOL AB Folate deficiency enhances colorectal carcinogenesis in dimethylhydrazine-treated rats. Folate is an important mediator of DNA methylation, an epigenetic modification of DNA that is known to be dysregulated in the early stages of colorectal cancer, This study investigated the effect of dimethylhydrazine on DNA methylation of the colonic p53 gene and the modulation of this effect by dietary folate, Sprague-Dawley rats were fed diets containing 0, 2, 8, or 40 mg of folate/kg of diet, Five weeks after diet initiation, dimethylhydrazine was injected weekly for fifteen weeks. Folate-depleted and folate-replete control animals did not receive dimethylhydrazine and were fed the 0- and 8 mg folate diets, respectively, The extent of p53 methylation was determined by a quantitative HpaII-polymerase chain reaction, In exons 6 and 7, significant p53 hypomethylation was observed in all dimethylhydrazine-treated rats relative to controls (P < 0.01), independent of dietary folate, In exon 8, significant p53 hypomethylation was observed only in the dimethylhydrazine-treated folate-depleted rats compared with controls (P = 0.038) and was effectively overcome by increasing levels of dietary folate (P = 0.008). In this model, dimethylhydrazine induces exon-specific p53 hypomethylation, In some exons, this occurs independent of dietary folate, and in others, increasing levels of dietary folate effectively override the induction of hypomethylation in a dose-responsive manner. This may be a mechanism by which increasing levels of dietary folate inhibit colorectal carcinogenesis. C1 TUFTS UNIV,USDA,VITAMIN BIOAVAILABIL LAB,JEAN MAYER HUMAN NUTR RES CTR AGING,BOSTON,MA 02111. TUFTS UNIV NEW ENGLAND MED CTR,DEPT INTERNAL MED,DIV GASTROENTEROL,BOSTON,MA 02111. TUFTS UNIV NEW ENGLAND MED CTR,DEPT INTERNAL MED,DIV CLIN NUTR,BOSTON,MA 02111. US FDA,DIV NUTR TOXICOL,NATL CTR TOXICOL RES,JEFFERSON,AR. TUFTS UNIV NEW ENGLAND MED CTR,DEPT PATHOL,BOSTON,MA 02111. FU NCI NIH HHS [1UO1 CA63812-01] NR 61 TC 82 Z9 85 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 1996 VL 149 IS 4 BP 1129 EP 1137 PG 9 WC Pathology SC Pathology GA VM314 UT WOS:A1996VM31400007 PM 8863662 ER PT J AU Brennan, MJ Shahin, RD AF Brennan, MJ Shahin, RD TI Pertussis antigens that abrogate bacterial adherence and elicit immunity SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT 11th Transatlantic Airway Conference on Interactions of Bacteria with Airway Cells and Secretions CY JAN 11-12, 1996 CL LUZERN, SWITZERLAND SP Boehringer Ingelheim ID ARG-GLY-ASP; BORDETELLA-PERTUSSIS; FILAMENTOUS HEMAGGLUTININ; RESPIRATORY-INFECTION; OUTER-MEMBRANE; CELLS; PROTEIN; ADHESIN; HEPARIN; SEQUENCE AB Infectious disease processes follow the initial steps of adherence of the organism to host tissues and subsequent colonization of the target tissues that can occur through specific adhesion-receptor systems. Bordetella pertussis, the human pathogen that causes whooping cough, has evolved a genetically controlled system whereby adhesins are expressed when they enter the human host. Two adhesins, filamentous hemagglutinin (FHA) and pertactin, mediate the adherence of the bacterium to eukaryotic cells through varied attachment mechanisms, including lectin-like binding sites that interact with sulfated sugars on cell surface glycoconjugates and the ARG-GLY-ASP binding sequence, which recognizes a family of integrins found on the cell surface. The differential expression of relevant receptors by various eukaryotic cells likely plays a role in the pathogenesis and immune response to the bacterium by the host, directing the organism to specific cell types and to specific tissue sites. Substantial evidence exists that the B. pertussis adhesins, FHA and pertactin, elicit immune responses that are protective in animal models for the disease, including serum antibody production and local immune responses in the respiratory tract following nasal administration of encapsulated antigens. Both of these adhesins are components of new acellular pertussis vaccines that have proven safe and highly effective for prevention of serious disease in infants. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. NR 34 TC 14 Z9 14 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT PY 1996 VL 154 IS 4 SU S BP S145 EP S149 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA VN550 UT WOS:A1996VN55000005 PM 8876533 ER PT J AU Welsh, WJ Lin, WK Tersigni, SH Collantes, E Duta, R Carey, MS Zielinski, WL Brower, J Spencer, JA Layloff, TP AF Welsh, WJ Lin, WK Tersigni, SH Collantes, E Duta, R Carey, MS Zielinski, WL Brower, J Spencer, JA Layloff, TP TI Pharmaceutical fingerprinting: Evaluation of neural networks and chemometric techniques for distinguishing among same product manufacturers SO ANALYTICAL CHEMISTRY LA English DT Article ID EOSINOPHILIA-MYALGIA-SYNDROME; PATTERN-RECOGNITION; MASS-SPECTRA; TRYPTOPHAN; CHEMISTRY; 1,1'-ETHYLIDENEBIS(L-TRYPTOPHAN); CLASSIFICATION AB The present study was undertaken to evaluate several computer-based classifiers as potential tools for pharmaceutical fingerprinting by utilizing normalized data obtained from HPLC trace organic impurity patterns, To assess the utility of this approach, samples of L-tryptophan (LT) drug substance were analyzed from commercial production lots of six different manufacturers, The performance of several artificial neural network (ANN) architectures was compared with that of two standard chemometric methods, K-nearest neighbors (KNN) and soft independent modeling of class analogy (SIMCA), as well as with a panel of human experts, The architecture of all three computer-based classifiers was varied with respect to the number of input variables, The ANNs were also optimized with respect to the number of nodes per hidden layer and to the number of hidden layers, A novel preprocessing scheme known as the Window method was devised for converting the output of 899 data entries extracted from each chromatogram into an appropriate input file for the classifiers, Analysis of the test set data revealed that an ANN with 46 inputs (i.e., ANN-46) was superior to all other classifiers evaluated, with 93% of the chromatograms correctly classified. Among the classifiers studied in detail, the order of performance was ANN-46 (93%) > SIMCA-46 (87%) > KNN-46 (85%) = ANN-899 (85%) > ''human experts'' (83%) > SIMCA-899 (78%) greater than or equal to ANN-22 (77%)= KNN-22 (77%) greater than or equal to KNN-899 (76%) > SIMCA-22 (73%), These results confirm that ANNs, particularly when used in conjunction with the Window preprocessing scheme, can provide a fast, accurate, and consistent methodology applicable to pharmaceutical fingerprinting. Particular attention was paid to variations in the HPLC patterns of same-manufacturer samples due to differences in LT production lots, HPLC columns, and even run-days to quantify how these factors might hinder correct classifications. The results from these classification studies indicate that the chromatograms evidenced variations across LT manufacturers, across the three HPLC columns and, for one manufacturer, across lots, The extent of column-to-column variations is particularly noteworthy in that all three columns had identical specifications with respect to their stationary-phase characteristics and two of the three columns were from the same vendor. C1 US FDA,DIV DRUG ANAL,ST LOUIS,MO 63101. RP Welsh, WJ (reprint author), UNIV MISSOURI,DEPT CHEM,ST LOUIS,MO 63121, USA. NR 34 TC 64 Z9 69 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD OCT 1 PY 1996 VL 68 IS 19 BP 3473 EP 3482 DI 10.1021/ac951164e PG 10 WC Chemistry, Analytical SC Chemistry GA VK590 UT WOS:A1996VK59000033 PM 8843143 ER PT J AU Townes, JM Cieslak, PR Hatheway, CL Solomon, HM Holloway, JT Baker, MP Keller, CF McCroskey, LM Griffin, PM AF Townes, JM Cieslak, PR Hatheway, CL Solomon, HM Holloway, JT Baker, MP Keller, CF McCroskey, LM Griffin, PM TI An outbreak of type a botulism associated with a commercial cheese sauce SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE botulism; botulinum toxins; Clostridium botulinum; cheese; diagnosis, differential ID UNITED-STATES; TOXIN AB Background: Although botulism is rare, recognition of a possible case of this illness represents a public health emergency. To prevent more cases, prompt investigation must be done to determine whether illness is linked to a commercial product or restaurant, Botulism can masquerade as other illnesses, and seemingly unlikely foods can harbor botulinum toxin. Objective: To confirm the diagnosis and determine the cause and extent of an outbreak of botulism associated with food served at a delicatessen. Design: Retrospective cohort study of patrons of the delicatessen; laboratory analysis of food, serum samples, and stool samples; and traceback of implicated food. Setting: Community in Georgia. Participants: Patrons of the delicatessen. Main Outcome Measures: Botulinum toxin in food, serum, or stool and Clostridium botulinum in food and stools. Results: 8 of 52 patrons (15%) met the case definition for botulism. In 4 of the 8 patrons, an illness other than botulism was initially diagnosed. Five of the 8 were hospitalized, and 1 died. Stool cultures from 4 patrons yielded type A C. botulinum, and two serum samples contained botulinum toxin. All ill persons ate food from the delicatessen on 1 October 1993. Of the 22 persons who ate at the delicatessen that day, all 8 ill persons but none of the 14 well persons ate a potato stuffed with meat and cheese sauce. An open can of cheese sauce contained type A botulinum toxin and yielded C. botulinum on culture. Cheese sauce experimentally inoculated with C. botulinum spores became toxic after 8 days at a temperature of 22 degrees C (room temperature). Conclusions: A commercial, canned cheese caused a botulism outbreak. This product readily becomes toxic when contaminated by C. botulinum spores and left at room temperature. Mild botulism caused by unusual vehicles may be misdiagnosed. Botulism should be included in the differential diagnosis of persons with signs or symptoms of acute cranial nerve dysfunction. C1 GEORGIA DEPT HUMAN RESOURCES,ATLANTA,GA. SE HLTH UNIT,WAYCROSS,GA 31501. US FDA,WASHINGTON,DC 20204. RP Townes, JM (reprint author), CTR DIS CONTROL & PREVENT,FOODBORNE & DIARRHEAL DIS BRANCH,MAILSTOP A-38,ATLANTA,GA 30333, USA. NR 20 TC 49 Z9 49 U1 0 U2 4 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 OCT 1 PY 1996 VL 125 IS 7 BP 558 EP & PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA VJ653 UT WOS:A1996VJ65300004 PM 8815754 ER PT J AU Motes, ML DePaola, A AF Motes, ML DePaola, A TI Offshore suspension relaying to reduce levels of Vibrio vulnificus in oysters (Crassostrea virginica) SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID GULF-COAST; SEAWATER; TEMPERATURE; ENVIRONMENT; IMMUNOASSAY; SALINITY; SEDIMENT AB Oysters naturally contaminated with 10(3) to 10(4) most probable numbers (MPN) of Vibrio vulnificus per g were relayed to offshore waters (salinity, 30 to 34 ppt), where they were suspended in racks at a depth of 7.6 m, V. vulnificus counts in oysters were reduced to <10 MPN/g within 7 to 17 days in five of the six studies, At the end of the studies (17 to 49 days), V. vulnificus levels were reduced further and ranged from a mean of 0.23 to 2.6 MPN/g, Oyster mortalities during relaying were <6%, The reduction of V. vulnificus in relayed oysters is associated with exposure to high-salinity environments essentially devoid of V. vulnificus. Offshore suspension relaying may be a method that industry can employ to reduce V., vulnificus levels in raw Gulf Coast oysters. RP Motes, ML (reprint author), US FDA,GULF COAST SEAFOOD LAB,1 IBERVILLE DR,POB 158,DAUPHIN ISL,AL 36528, USA. NR 17 TC 51 Z9 54 U1 0 U2 5 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 OCT PY 1996 VL 62 IS 10 BP 3875 EP 3877 PG 3 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA VK372 UT WOS:A1996VK37200052 PM 8837445 ER PT J AU DeanRoss, D Cerniglia, CE AF DeanRoss, D Cerniglia, CE TI Degradation of pyrene by Mycobacterium flavescens SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; CONTAMINATED SOIL; BIODEGRADATION; PHENANTHRENE; FLUORANTHENE; FLUORENE AB A strain of Mycobacterium flavescens was isolated from polluted sediments. It was capable of utilizing pyrene as a sole source of carbon and energy. When pyrene was supplied as a suspension at 50 mu g/ml, the generation time was 9.6 h and the rate of pyrene utilization was 0.56 mu g ml(-1) day(-1). In addition to pyrene, the strain could mineralize phenanthrene (17.7%) and fluoranthene (17.9%), but failed to mineralize naphthalene, chrysene, anthracene, fluorene, acenaphthene and benzo[a]pyrene, as determined by recovery of radio-labeled CO2 in incubations conducted for 2 weeks under growth conditions. Metabolites produced during growth on pyrene were detected and characterized by HPLC and GC-MS. The product of initial ring oxidation, 4,5-dihydroxy-4,5-dihydropyrene was identified, as well as ring-fission products including 4-phenanthroic acid, phthalic acid, and 4,5-phenanthrenedioic acid. C1 NATL CTR TOXICOL RES, DIV MICROBIOL, JEFFERSON, AR 72079 USA. RP DeanRoss, D (reprint author), INDIANA UNIV PURDUE UNIV, DEPT BIOL, FT WAYNE, IN 46805 USA. NR 22 TC 133 Z9 140 U1 0 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD OCT PY 1996 VL 46 IS 3 BP 307 EP 312 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA VQ226 UT WOS:A1996VQ22600017 PM 8933844 ER PT J AU Kanegane, H Wado, T Nunogami, K Seki, H Taniguchi, N Tosato, G AF Kanegane, H Wado, T Nunogami, K Seki, H Taniguchi, N Tosato, G TI Chronic persistent Epstein-Barr virus infection of natural killer cells and B cells associated with granular lymphocytes expansion SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Epstein-Barr virus; natural killer cells; granular lymphocyte proliferative disorder; polymerase chain reaction; in situ hybridization ID CD3-NEGATIVE LYMPHOPROLIFERATIVE DISEASE; VIRAL-DNA; HODGKINS-DISEASE; DISORDERS; TRANSPLANTATION; MONONUCLEOSIS; ANTIBODIES; GENOME; LINE AB B lymphocytes and epithelial cells are the only cell types known to be infected with Epstein-Barr virus (EBV) in normal individuals. Rarely, EBV also infects other cells, including natural killer (NK) cells, almost always in the contest of fatal leukaemias or lymphoproliferative disorders, We report on a 6-year-old previously healthy girl who developed fevers and liver function abnormalities for 3 months. The peripheral blood revealed an abnormal expansion of large granular lymphocytes, comprising 24% of the white blood cells. Flow cytometric analysis of the peripheral blood mononuclear cells showed an abnormal increase of CD16-positive NK cells, 62% of which were EBV-infected by in situ EBER-1 hybridization. The circulating B cells were normal in number, but 18% were infected with EBV by in situ EBER-1 hybridization. Approximately 2 years after resolution of all symptoms and continued good health, 35% of the circulating mononuclear cells were EBV-infected, indicative of persistent expansion of EBV-infected cells. We conclude that abnormal expansions of EBV-infected NK and B cells can be associated with a chronic benign course. C1 KANAZAWA UNIV,SCH MED,DEPT PAEDIAT,KANAZAWA,ISHIKAWA 920,JAPAN. RP Kanegane, H (reprint author), US FDA,CBER,DHP,BLDG 29A,ROOM 2D06,HFM-535,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 30 TC 29 Z9 30 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 1996 VL 95 IS 1 BP 116 EP 122 DI 10.1046/j.1365-2141.1996.7532375.x PG 7 WC Hematology SC Hematology GA VM980 UT WOS:A1996VM98000018 PM 8857947 ER PT J AU Li, MF Muller, J Xu, F Hearing, VJ Gorelik, E AF Li, MF Muller, J Xu, F Hearing, VJ Gorelik, E TI Inhibition of melanoma-associated antigen expression and ecotropic retrovirus production in B16BL6 melanoma cells transfected with major histocompatibility complex class I genes SO CANCER RESEARCH LA English DT Article ID MURINE LEUKEMIA-VIRUS; TNF-MEDIATED CYTOTOXICITY; B-16 MELANOMA; MONOCLONAL-ANTIBODIES; INCREASED SENSITIVITY; H-2K(B) GENE; H-2 GENES; DNA; ORGANIZATION; METASTASES AB We have previously reported that expression of the melanoma-associated antigen (MAA) recognized by MM2-9B6 monoclonal antibody in B16 melanoma was closely associated with C-type ecotropic retroviral particle production. Our present data show that this MAA is encoded by the env gene of an ecotropic retrovirus produced by B16 melanoma cells. Transfection of H-2K(b) or H-2K(d) genes into two individual clones isolated from B16BL6 melanoma, BL6-8 (H-2K(b)-, H-2D(b)+) and BL6-2- (H-2K(b)-, H-2D(b)-), resulted in a loss of MAA expression. Electron immunohistochemical analysis of melanoma cells and reverse transcriptase assay revealed that the loss of MAA expression in the H-2K gene-transfected cells paralleled the elimination of retroviral particles. In contrast, expression of the endogenous H-2D(b) gene or transfection with the H-2D(d) or H-2L(d) gene had no effect on MAA expression or retrovirus production. Northern blot analysis showed equivalent retroviral messages in retrovirus-producing and -nonproducing BL6 melanoma clones. Southern blot analysis revealed that H-2K(b)-negative BL6 melanoma cells contain at least four different ecotropic retroviruses with different insertion sites that somatically emerged during malignant transformation or progression. Restriction enzyme analysis showed various changes in proviral DNAs from the H-2K(b)- and H-2K(d)-transfected cells that failed to produce retroviral particles. The observed alterations in the patterns of PstI- and HindIII-digested proviral DNA mere found to be due to the appearance of PstI and loss of HindIII restriction sites in the pol region as a result of several nucleotide substitutions. Thus, BL6 melanoma cells produce melanoma-specific ecotropic murine leukemia viruses that encode serologically detectable cell surface MAA. The transfection of BL6 melanoma cells with H-2K(b) or H-2K(d) genes but not H-2D(d) or H-2L(d) genes resulted in a loss of MAA expression that was attributed to the changes in proviral DNA and loss of melanoma-specific ecotropic retrovirus particle production. C1 UNIV PITTSBURGH,INST CANC,PITTSBURGH,PA 15213. UNIV PITTSBURGH,DEPT PATHOL,PITTSBURGH,PA 15213. US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,BETHESDA,MD 20892. NCI,NIH,CELL BIOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA59903] NR 37 TC 16 Z9 16 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 OCT 1 PY 1996 VL 56 IS 19 BP 4464 EP 4474 PG 11 WC Oncology SC Oncology GA VK307 UT WOS:A1996VK30700034 PM 8813142 ER PT J AU Kazachkov, Y Khaoustov, V Yoffe, B Solomon, H Klintmalm, GBG Tabor, E AF Kazachkov, Y Khaoustov, V Yoffe, B Solomon, H Klintmalm, GBG Tabor, E TI P53 Abnormalities in hepatocellular carcinoma from United States patients: Analysis of all 11 exons SO CARCINOGENESIS LA English DT Article ID HEPATITIS-B VIRUS; NITRIC-OXIDE; CODON 249; GENE; MUTATION; DNA; ONCOGENES; CELLS AB Mutations of the tumor suppressor gene p53 have been found in hepatocellular carcinomas (HCCs) from many countries where HCC is common, but p53 mutations detected by direct sequencing in HCCs from the United States (where HCC is uncommon) have been reported only rarely. p53 Exons 1 to 11 were analyzed by polymerase chain reaction, single-strand conformation polymorphism analysis, and direct sequencing in HCCs from 12 patients from the United States and in adjacent non-tumorous liver from 10 of them, Abnormalities of the p53 gene were found in five of the 12 tumors, including mutations in exon 4 (one patient), exon 5 (one patient) and exon 8 (three patients). In all 12 tumors, a normal conformation of exon 7 was found; in five of these HCCs the absence of mutations was confirmed by direct sequencing, Thus, the mutations of p53 codon 249 that have frequently been found in HCCs from endemic areas apparently do not play a role in most HCCs in the United States, Since the mutations in codon 249 are thought to be due to aflatoxin ingestion, the data suggest that factors other than aflatoxin may be responsible for the p53 abnormalities in the patients from the USA. C1 US FDA,CTR BIOL EVALUAT & RES HFM310,ROCKVILLE,MD 20852. BAYLOR COLL MED,VA MED CTR,HOUSTON,TX 77030. BAYLOR UNIV,MED CTR,DALLAS,TX. NR 28 TC 25 Z9 26 U1 0 U2 0 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 OCT PY 1996 VL 17 IS 10 BP 2207 EP 2212 DI 10.1093/carcin/17.10.2207 PG 6 WC Oncology SC Oncology GA VM805 UT WOS:A1996VM80500016 PM 8895490 ER PT J AU Obiri, NI Husain, SR Debinski, W Puri, RK AF Obiri, NI Husain, SR Debinski, W Puri, RK TI Interleukin 13 inhibits growth of human renal cell carcinoma cells independently of the p140 interleukin 4 receptor chain SO CLINICAL CANCER RESEARCH LA English DT Article ID B-CELLS; SIGNAL-TRANSDUCTION; HUMAN KERATINOCYTES; IL-13 RECEPTORS; HUMAN-MELANOMA; IGE SYNTHESIS; T-CELLS; EXPRESSION; CYTOKINE; GAMMA AB Interleukin-13 (TL-13) is a cytokine produced primarily by activated T lymphocytes. It exerts a variety of effects on different cell types, including monocytes, B lymphocytes, mast cells, and keratinocytes. The effects of IL-13 on target cells are often similar to the effects of IL-4, which is another cytokine product of activated T lymphocytes. We recently described the expression of intermediate- to high-affinity receptors for IL-13 (IL-13R) on renal cell carcinoma (RCC) cells. In the present study, we examined the effect of IL-13 on the growth of RCC cells as measured by [H-3]thymidine uptake and a clonogenic assay. In addition, we used an IL-4R-specific antibody to examine the specificity of IL-4R and IL-13R binding and function, We observed that IL-13 inhibited RCC cell proliferation by up to 50% and colony formation by up to 32% when compared with cells cultured in medium alone. A combination of IL-4 and IL-13 did not have an additive or synergistic effect on the growth of RCC cells, These cells expressed mRNA for IL-13 and secreted immunoreactive IL-13 protein in culture, The growth-inhibitory effects of IL-13 were specific, because they were not affected by antibodies to 1L-4 or to the 140-kilodalton subunit of IL-4R. Furthermore, polyclonal antibodies to LL-4R failed to inhibit the binding of I-125-IL-13 to RCC cells, These results indicate that IL-13 has significant antiproliferative effects on human RCC cells, and the inhibition of IL-13 effects by anti-IL-4R antibody previously reported in lymphoid cells does not occur in RCC cells. C1 US FDA,LAB MOL TUMOR BIOL,DIV CELLULAR & GENE THERAPIES,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. PENN STATE UNIV,COLL MED,MILTON S HERSHEY MED CTR,DEPT MED,DIV NEUROSURG,HERSHEY,PA 17033. NR 32 TC 53 Z9 53 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 OCT PY 1996 VL 2 IS 10 BP 1743 EP 1749 PG 7 WC Oncology SC Oncology GA VL234 UT WOS:A1996VL23400015 PM 9816125 ER PT J AU Kenney, R Sacks, D Gam, A AF Kenney, R Sacks, D Gam, A TI Interleukin-12 as an adjuvant for a vaccine against Leishmania amazonensis SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. NIAID,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT PY 1996 VL 23 IS 4 BP 64 EP 64 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VN246 UT WOS:A1996VN24600112 ER PT J AU Lee, SJ Goldstein, H Fox, C Baseler, M Adelsberger, J Golding, H AF Lee, SJ Goldstein, H Fox, C Baseler, M Adelsberger, J Golding, H TI HIV-1 infection of the CD8+ thymocyte in the SCID-hu mouse SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,LRR,BETHESDA,MD. PRI DYNCORP,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT PY 1996 VL 23 IS 4 BP 124 EP 124 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VN246 UT WOS:A1996VN24600171 ER PT J AU Bash, MC Barroso, DE Frasch, CE AF Bash, MC Barroso, DE Frasch, CE TI Identification and typing of Neisseria meningitidis porB from cerebrospinal fluid using nested PCR and biotin labeled probe hybridization SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. FUNDACAO OSWALDO CRUZ,INST OSWALDO CRUZ,RIO JANEIRO,BRAZIL. NR 0 TC 1 Z9 1 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT PY 1996 VL 23 IS 4 BP 337 EP 337 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VN246 UT WOS:A1996VN24600383 ER PT J AU Hight, SC AF Hight, SC TI Lead migration from lead crystal wine glasses SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE lead; migration; glass; lead crystal; food ID DECANTERS AB Lead release from lead crystal wine glasses was measured at 15 contact times from 1 min to 24 h (1440 min) in 4% acetic acid and wine at room temperature. Lead release at 1 min was equal to approximately 50 and 30% of cumulative lead release measured at 30 and 1440 min, respectively, in both extractants. Lead release at 1440 min was 467 ng/ml in acetic acid and 358 ng/ml in wine. Lead release was less in wine (pH 3.14) than in acetic acid (pH 2.39) because of the increased pH and ethanol content of wine. Lead release was also measured under conditions that simulated consumer use. In experiments with chilled and room temperature wine that was steadily removed from vessels during 1-30 min of contact, results were not significantly less than results of experiments in which wine temperature was 20.0 +/- 2.5 degrees C and contact area was constant. In repeated-leaching experiments, the total mu g of lead released in 30 min decreased and was a function of 1/L(2), where L was leach number. Wine results fit a linear regression model of lead release vs square root of time which was previously proposed to describe corrosion of lead silicate glass by acetic acid. Slopes and intercepts of the square-root-of-time model were used to explain results of repeated-leaching experiments. RP Hight, SC (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,ELEMENTAL RES BRANCH,WASHINGTON,DC 20204, USA. NR 26 TC 9 Z9 11 U1 0 U2 8 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD OCT PY 1996 VL 13 IS 7 BP 747 EP 765 PG 19 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA VH923 UT WOS:A1996VH92300002 PM 8885316 ER PT J AU Kauppi, KL Tatini, SR Harrell, F Feng, P AF Kauppi, KL Tatini, SR Harrell, F Feng, P TI Influence of substrate and low temperature on growth and survival of verotoxigenic Escherichia coli SO FOOD MICROBIOLOGY LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; HEMORRHAGIC COLITIS; APPLE CIDER; O157-H7; OUTBREAK; DIARRHEA; 0157-H7; FATE AB Growth and survival of verotoxigenic Escherichia coli (VTEC) were studied in tryptic soy broth (TSB), brain-heart infusion (BHI), and whole milk at 12, 9.5, 8.5, 7.5, 6.5, and 5.5 degrees C (+/-0.2 degrees C). Colony forming units (cfu) were enumerated by surface plating on eosin methylene blue (EMB) agar plates and incubating at 37 degrees C for 24 h. Growth curves were plotted and lag and generation times were determined. Results indicated that the average generation times for each strain was similar in each medium (4.6+/-0.9 h) at 12 degrees C. However, at 9.5 degrees C the average generation time differed significantly among the media (P<0.05). The average generation time was longer in BHI compared to TSB and whole milk at 9.5 degrees C (14 h in BHI vs 11 h in milk and TSB). Also, the generation time of individual strains in BHI varied from 9.5-22 h at 9.5 degrees C. Decrease of temperature to 8.5 degrees C resulted in lack of growth of two strains in BHI. At 7.5 degrees C none of the strains grew in BHI, one grew in TSB, whereas all grew in milk. A further decrease of temperature to 6.5 degrees C did not allow growth of any of the strains in TSB or BHI whereas all grew in milk. Addition of 5% lactose to TSB and BHI enabled survival and growth of all strains at 6.5 degrees C. The results of this study demonstrate the influence of growth medium composition on the minimum growth temperature of verotoxigenic E. coli. (C) 1996 Academic Press Limited C1 UNIV MINNESOTA,DEPT FOOD SCI & NUTR,ST PAUL,MN 55108. US FDA,MLMI,MINNEAPOLIS,MN. US FDA,WASHINGTON,DC 20204. NR 35 TC 28 Z9 29 U1 6 U2 14 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 OCT PY 1996 VL 13 IS 5 BP 397 EP 405 DI 10.1006/fmic.1996.0046 PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA VM607 UT WOS:A1996VM60700007 ER PT J AU Farshid, M Mitchell, F Biswas, R Nidimbie, O Ding, M AF Farshid, M Mitchell, F Biswas, R Nidimbie, O Ding, M TI Prevalence of hepatitis C virus in HCV infected patients and in HCV contaminated intravenous immunoglobulin products SO HEPATOLOGY LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,HEPATATIS LAB,BETHESDA,MD 20892. UNIV PITTSBURGH,MED CTR,PITTSBURGH,PA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 413 EP 413 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28500413 ER PT J AU Kazachkov, Y Khaoustov, VI Yoffe, B Solomon, H Klintmalm, GBG Tabor, E AF Kazachkov, Y Khaoustov, VI Yoffe, B Solomon, H Klintmalm, GBG Tabor, E TI Microsatellite instability in human hepatocellular carcinoma. SO HEPATOLOGY LA English DT Meeting Abstract C1 US FDA,BETHESDA,MD 20014. BAYLOR COLL MED,VAMC,HOUSTON,TX 77030. BAYLOR UNIV,MED CTR,DALLAS,TX. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 863 EP 863 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28500861 ER PT J AU Nakashima, Y Nakashima, O Hsia, CC Kojiro, M Tabor, E AF Nakashima, Y Nakashima, O Hsia, CC Kojiro, M Tabor, E TI Vascularization in small hepatocellular carcinomas: Correlation with differentiation. SO HEPATOLOGY LA English DT Meeting Abstract C1 US FDA,BETHESDA,MD 20014. KURUME UNIV,DEPT PATHOL 1,FUKUOKA,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 875 EP 875 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28500873 ER PT J AU Nakashima, Y Yuwen, H Hsia, CC Nakashima, O Kojiro, M Tabor, E AF Nakashima, Y Yuwen, H Hsia, CC Nakashima, O Kojiro, M Tabor, E TI Overexpression of topoisomerase II and p53 in hepatocellular carcinoma. SO HEPATOLOGY LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. KURUME UNIV,DEPT PATHOL 1,FUKUOKA,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 1701 EP 1701 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28501696 ER PT J AU Park, YM Choi, JY Byun, BH Kim, BS Tabor, E AF Park, YM Choi, JY Byun, BH Kim, BS Tabor, E TI Differential RNA expression of NM23-H1, NM23-H2, and GAPDH genes in advanced hepatocellular carcinoma. SO HEPATOLOGY LA English DT Meeting Abstract C1 CATHOLIC UNIV,COLL MED,KANGNAM ST MARYS HOSP,DEPT INTERNAL MED,HEPATOGASTROENTEROL DIV,SEOUL,SOUTH KOREA. US FDA,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 1733 EP 1733 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28501728 ER PT J AU Yuwen, H Hsia, CC Nakashima, Y Evangelista, A Tabor, E AF Yuwen, H Hsia, CC Nakashima, Y Evangelista, A Tabor, E TI Overexpression of topoisomerase II in human hepatocellular carcinomas and binding of wild-type p53 by topoisomerase II. SO HEPATOLOGY LA English DT Meeting Abstract C1 US FDA,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 1 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 OCT PY 1996 VL 24 IS 4 SU S BP 1897 EP 1897 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28501892 ER PT J AU Talbot, NC Worku, M Paape, MJ Grier, P Rexroad, CE Pursel, VG AF Talbot, NC Worku, M Paape, MJ Grier, P Rexroad, CE Pursel, VG TI Continuous cultures of macrophages derived from the 8-day epiblast of the pig SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE culture; differentiation; epiblast; macrophage; pig ID EMBRYONIC STEM-CELLS; NAPHTHYL ACETATE ESTERASE; IN-VITRO; ALVEOLAR MACROPHAGE; GROWTH-FACTOR; DEVELOPING MOUSE; BOVINE; INVITRO; MONOCYTES; RECEPTOR AB Secondary macrophage cell cultures were generated from the primary culture of epiblasts of 8-d-old pig blastocysts. The epiblast-derived macrophagelike (EDM) cells have a morphology and ameboid behavior that is typical of tissue histocytes. The cells reacted positively with monoclonal antibodies specific for pig granulocyte-macrophage lineage cells, and were not reactive with monoclonal antibodies specific for pig B and T lymphocytes. Marked phagocytic behavior and the formation of phagosomes were demonstrated following incubation with FITC-labeled bacteria. The EDM cells stained positively for nonspecific acid esterase that was not inhibited by sodium fluoride. Dil-acetylated-LDL was rapidly taken up by the cells. Transmission electron microscopy of the EDM cells showed phagolysosomes, numerous cytoplasmic vacuoles, large, lobed nuclei, and numerous pseudopods or filopodia at the cell surface. Strong reactivity of the cells with anti-CD14 monoclonal antibody was observed. Further, cytotoxic activity was produced from the EDM cells after exposure to lipopolysaccharide in a concentration and time-dependent manner. The cultures could be maintained and expanded for several months on STO co-culture. Their derivation from the epiblast of the pig demonstrates the possibility of obtaining hemopoietic cell cultures from the preimplantation blastocysts of all mammals. C1 USDA ARS,BELTSVILLE AGR RES CTR,LPSI,MILK SECRET & MASTITIS LAB,BELTSVILLE,MD 20705. USDA ARS,BELTSVILLE AGR RES CTR,LPSI,GROWTH BIOL LAB,BELTSVILLE,MD 20705. US FDA,CTR BIOL EVALUAT & RES,DIV HAEMATOL,LAB CELLULAR HAEMATOL,BETHESDA,MD 20892. RP Talbot, NC (reprint author), USDA ARS,BELTSVILLE AGR RES CTR,LPSI,GENE EXALUAT & MAPPING LAB,BLDG 200,ROOM 13,BELTSVILLE,MD 20705, USA. NR 51 TC 11 Z9 11 U1 0 U2 0 PU SOC IN VITRO BIOLOGY PI COLUMBIA PA 8815 CENTRE PARK DRIVE SUITE 210, COLUMBIA, MD 21045 SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD OCT PY 1996 VL 32 IS 9 BP 541 EP 549 PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA VU884 UT WOS:A1996VU88400007 PM 8946226 ER PT J AU Hausman, SZ Cherry, JD Heininger, U vonKonig, CHW Burns, DL AF Hausman, SZ Cherry, JD Heininger, U vonKonig, CHW Burns, DL TI Analysis of proteins encoded by the ptx and ptl genes of Bordetella bronchiseptica and Bordetella parapertussis SO INFECTION AND IMMUNITY LA English DT Article ID PERTUSSIS TOXIN GENES; MONOCLONAL-ANTIBODIES; ADENYLATE-CYCLASE; SP-NOV; EXPRESSION; SECRETION; OPERON; MODEL; LOCALIZATION; SUBUNITS AB Bordetella pertussis is the only bacterial species which is known to produce pertussis toxin (PT); however, both Bordetella bronchiseptica and Bordetella parapertussis contain regions homologous to the ptx genes of B. pertussis that encode the toxin subunits. After finding that several children with B. parapertussis infections exhibited modest antibody titers to PT, we examined the ptx genes of both B. parapertussis and B. bronchiseptica to determine whether they would encode stable, functional proteins even though their promoters are thought to be inactive under the conditions that have been examined. We inserted a functional promoter directly upstream of the ptx-ptl region of both species and examined culture supernatants of the resulting strains for PT activity. Biologically active PT was found in the culture supernatants of both engineered species. The toxin encoded by the B. parapertussis ptx genes appeared more labile in culture supernatants than did toxin produced by either B. pertussis or the engineered strain of B. bronchiseptica. This lability might be due to the lack of a full-length S2 subunit. We also investigated the ptl genes of these species, which are necessary for the secretion of this toxin, and found that both B. bronchiseptica and B. parapertussis contain at least certain of these genes, including ptlE and ptlF. Moreover, B. bronchiseptica appeared to contain all essential ptl genes since the introduction of a functional promoter directly upstream of the ptx-ptl region resulted in both production and efficient secretion of toxin. These results indicate that despite a number of amino acid changes in the sequences of the toxins, the toxins encoded by B. bronchiseptica and B. parapertussis are active. C1 US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,LOS ANGELES,CA 90024. UNIV ERLANGEN NURNBERG,KLIN KINDER & JUGENDLICHE,ERLANGEN,GERMANY. KLINIKUM KREFELD,INST HYG & LAB MED,KREFELD,GERMANY. NR 31 TC 20 Z9 41 U1 0 U2 0 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 OCT PY 1996 VL 64 IS 10 BP 4020 EP 4026 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VJ794 UT WOS:A1996VJ79400010 PM 8926063 ER PT J AU Gu, XX Tsai, CM Ueyama, T Barenkamp, SJ Robbins, JB Lim, DJ AF Gu, XX Tsai, CM Ueyama, T Barenkamp, SJ Robbins, JB Lim, DJ TI Synthesis, characterization, and immunologic properties of detoxified lipooligosaccharide from nontypeable Haemophilus influenzae conjugated to proteins SO INFECTION AND IMMUNITY LA English DT Article ID NONTYPABLE HEMOPHILUS-INFLUENZAE; OUTER-MEMBRANE PROTEIN; ACUTE OTITIS-MEDIA; BACTERICIDAL ANTIBODY; BIOLOGIC ACTIVITY; SERUM; LIPOPOLYSACCHARIDES; PROTECTION; CHILDREN; IMMUNIZATION AB Nontypeable Haemophilus influenzae (NTHi) is an important cause of otitis media in children and of pneumonitis in adults with depressed resistance. Lipooligosaccharide (LOS) is a major surface antigen of NTHi and elicits bactericidal and opsonic antibodies, We prepared detoxified LOS (dLOS) protein conjugates from NTHi for use as experimental vaccines. LOS from NTHi 9274 was treated with anhydrous hydrazine and had its toxicity reduced to clinically acceptable levels, dLOS was bound to tetanus toroid (TT) or high-molecular-weight proteins (HMPs) from NTHi through a linker of adipic acid dihydrazide to form dLOS-TT or dLOS-HMP. The molar ratio of the dLOS to protein carriers ranged from 26:1 to 50:1. The antigenicity of the conjugates was similar to that of the LOS alone as determined by double immunodiffusion. Subcutaneous or intramuscular injection of the conjugates elicited a 28- to 486-fold rise in the level of immunoglobulin G antibodies in mice to the homologous LOS after two or three injections and a 169- to 243-fold rise in the level of immunoglobulin G antibodies in rabbits after two injections. The immunogenicity of the conjugates in mice and rabbits was enhanced by formulation with monophosphoryl lipid A plus trehalose dimycolate. In rabbits, conjugate-induced LOS antibodies induced complement-mediated bactericidal activity against the homologous strain 9274 and prototype strain 3189, These results indicate that a detoxified LOS-protein conjugate is a candidate vaccine for otitis media and pneumonitis caused by NTHi. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NICHHD,BETHESDA,MD 20892. ST LOUIS UNIV,SCH MED,DEPT PEDIAT,ST LOUIS,MO 63104. ST LOUIS UNIV,CARDINAL GLENNON CHILDRENS HOSP,PEDIAT RES INST,ST LOUIS,MO 63104. RP Gu, XX (reprint author), NIDOCD,NIH,VACCINE DEV UNIT,LAB CELLULAR BIOL,5 RES CT,RM 2A31,ROCKVILLE,MD 20850, USA. OI Barenkamp, Stephen/0000-0002-3054-8910 NR 54 TC 43 Z9 44 U1 0 U2 0 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 OCT PY 1996 VL 64 IS 10 BP 4047 EP 4053 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VJ794 UT WOS:A1996VJ79400014 PM 8926067 ER PT J AU Butterton, JR Ryan, ET Shahin, RA Calderwood, SB AF Butterton, JR Ryan, ET Shahin, RA Calderwood, SB TI Development of a germfree mouse model of Vibrio cholerae infection SO INFECTION AND IMMUNITY LA English DT Article ID VIRULENCE DETERMINANTS; VACCINE PROTOTYPE; O139; EXPRESSION; STRAINS AB A mouse model of Vibrio cholerae infection was successfully developed with germfree mice. Three- to four-week-old germfree mice were orally inoculated with strains of V. cholerae to be tested and then moved to normal housing after inoculation, Stool culture, measurement of serum vibriocidal antibody titers, and determination of immune responses to the cholera toxin B subunit demonstrated that germfree mice are readily colonized by V. cholerae and develop systemic and mucosal immune responses to antigens expressed by these organisms, Immune responses to the B subunit of Shiga toxin 1, which was expressed from a V. cholerae vaccine vector, were less pronounced, This model should be valuable for studying immune responses to V. cholerae infection and immunization, including responses to heterologous antigens expressed by cholera vector strains. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. US FDA,CTR BIOL EVALUAT & RES,LAB PERTUSSIS,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. FU NIAID NIH HHS [T32 AI007061, T32AI07061-18, AI34968] NR 18 TC 34 Z9 35 U1 0 U2 0 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 OCT PY 1996 VL 64 IS 10 BP 4373 EP 4377 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VJ794 UT WOS:A1996VJ79400062 PM 8926115 ER PT J AU Lindler, LE Hadfield, TL Tall, BD Snellings, NJ Rubin, FA Vandeverg, LL Hoover, D Warren, RL AF Lindler, LE Hadfield, TL Tall, BD Snellings, NJ Rubin, FA Vandeverg, LL Hoover, D Warren, RL TI Cloning of a Brucella melitensis group 3 antigen gene encoding Omp28, a protein recognized by the humoral immune response during human brucellosis (vol 64, pg 2498, 1996) SO INFECTION AND IMMUNITY LA English DT Correction, Addition C1 ARMED FORCES INST PATHOL,DEPT INFECT & PARASIT DIS,WASHINGTON,DC 20306. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. RP Lindler, LE (reprint author), WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,DEPT BACTERIAL DIS,WASHINGTON,DC 20307, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1996 VL 64 IS 10 BP 4414 EP 4414 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VJ794 UT WOS:A1996VJ79400072 ER PT J AU Gehring, TA Rushing, LG Churchwell, MI Doerge, DR McErlane, KM Thompson, HC AF Gehring, TA Rushing, LG Churchwell, MI Doerge, DR McErlane, KM Thompson, HC TI HPLC determination of sulfadiazine residues in coho salmon (Oncorhynchus kisutch) with confirmation by liquid chromatography with atmospheric pressure chemical ionization mass spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE sulfadiazine; salmon; Oncorhynchus kisutch; liquid chromatography; mass spectrometry ID TRIMETHOPRIM; PLASMA AB High-performance liquid chromatography and postcolumn derivatization with fluorescamine were used to determine sulfadiazine (SDZ) residues in muscle and skin from salmon dosed with Tribrissen. Determinations in the fish ranged from 0.2 to 21600 ng of SDZ/g; in each fish tested, the concentration of SDZ in the skin was at least twice that in the muscle. Liquid chromatography with atmospheric pressure chemical ionization mass spectrometry (LC-APCI/MS) was used to confirm SDZ residues. In-source collision induced dissociation was optimized to produce a mass spectrum containing the protonated molecule and four fragment ions. Sulfadiazine was confirmed in muscle fortified with 10 ng of SDZ/g and in muscle from fish dosed with SDZ by the accurate agreement of ion intensity ratios generated from muscle compared with those generated from SDZ standard injections. C1 UNIV BRITISH COLUMBIA,FAC PHARMACEUT SCI,VANCOUVER,BC V6T 1Z3,CANADA. RP Gehring, TA (reprint author), US FDA,NATL CTR TOXICOL RES,DIV CHEM,JEFFERSON,AR 72079, USA. NR 10 TC 21 Z9 23 U1 1 U2 5 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 OCT PY 1996 VL 44 IS 10 BP 3164 EP 3169 DI 10.1021/jf9601877 PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA VN644 UT WOS:A1996VN64400046 ER PT J AU Mossoba, MM Yurawecz, MP Roach, JAG McDonald, RE Flickinger, BD Perkins, EG AF Mossoba, MM Yurawecz, MP Roach, JAG McDonald, RE Flickinger, BD Perkins, EG TI Analysis of cyclic fatty acid monomer 2-alkenyl-4,4-dimethyloxazoline derivatives by gas chromatography matrix isolation Fourier transform infrared spectroscopy SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE cyclic fatty acid monomers; infrared ID MASS-SPECTROMETRY; HEAT-TREATMENT; FRYING OILS; CONFIGURATION; POSITION AB Recently, cyclic fatty acid monomers (CFAMs) were isolated from heated flaxseed (linseed) oil and analyzed as methyl ester (ME) derivatives by capillary gas chromatography-matrix isolation-Fourier transform infrared spectroscopy (GC-MI-FTIR) and as 2-alkenyl-4,4-dimethyloxazoline (DMOX) derivatives by GC-electron ionization mass spectrometry (EIMS). The latter produced fragmentation patterns that were used to determine ring and double-bond positions along the hydrocarbon chain. However, for four CFAM ME derivatives, the FTIR spectra were consistent with CFAM structures having either a cyclohexenyl or a cyclohexadienyl ring, whereas those found by EIMS for the corresponding CFAM DMOX derivatives were consistent with both ring structures. In the present study, the FTIR spectra observed for the DMOX derivatives of this CFAM mixture were consistent with the earlier FTIR results obtained for the corresponding ME derivatives. Mass spectral data observed for deuterated analogues are also reported. C1 UNIV ILLINOIS,URBANA,IL 61801. USDA,NATL CTR FOOD SAFETY & TECHNOL,SUMMIT ARGO,IL 60501. RP Mossoba, MM (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,MAIL STOP HFS-717,WASHINGTON,DC 20204, USA. NR 17 TC 16 Z9 16 U1 0 U2 2 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 OCT PY 1996 VL 44 IS 10 BP 3193 EP 3196 DI 10.1021/jf960002w PG 4 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA VN644 UT WOS:A1996VN64400051 ER PT J AU Gogolewski, S MainilVarlet, P Dillon, JG AF Gogolewski, S MainilVarlet, P Dillon, JG TI Sterility, mechanical properties, and molecular stability of polylactide internal-fixation devices treated with low-temperature plasmas SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article ID POLYMER SURFACES; GAS PLASMAS; STERILIZATION; DEGRADATION; SUTURES AB The effect of low-temperature plasma on sterility, molecular, mechanical, and crystalline properties of poly(L-lactide), poly (L/D-lactide) and poly(L/DL-lactide) was investigated. Polymers were treated for 15 and 30 min at 100 W with nitrogen, argon, oxygen, and carbon dioxide plasma. All polymers treated with oxygen or carbon dioxide plasma were rendered sterile after 15 min of treatment. Only 70% of the samples treated under similar conditions with nitrogen or argon plasma were sterile. Extension of the exposure time to 30 min and increasing power to 200 W did not improve sterilization efficiency. Plasma sterilization, under the conditions used, caused no significant decrease or increase in overall molecular weight or polydispersity of the polylactides used. In most instances the effect of plasma sterilization was to slightly increase the overall molecular weight of the polymers studied. Treatment with argon plasma led to a more consistent increase in molecular weight than did treatment with nitrogen, oxygen, or carbon dioxide. Analysis of the surface (skin) of a poly(L-lactide) injection-molded rod following plasma sterilization indicated an increase in molecular weight as related to the interior (core) of the rod. Comparison of Mark-Houwink plots for the surface and interior of poly(L-lactide) injection-molded rods following plasma sterilization indicated an increase in chain branching for the surface relative to the interior of the rod. Generally the highly crystalline poly(L-lactide) was less susceptible to change upon plasma treatment than was the less crystalline poly(L/D-lactide) and poly(L/DL-lactide). The mechanical properties (shear strength, bending strength, and moduli) of the polylactides were not affected by plasma treatment. The overall melting temperature and the heat of melting of polylactides studied were not affected by plasma treatment. The melting temperature of the skin of the samples was about 1 degrees C higher than the melting temperature of the core due to the chain orientation upon injection-molding. Plasma treatment of the polylactides reduced the melting temperature of the skin by 3 degrees C to 5 degrees C due to the crosslinking or branching at the surface layer. (C) 1996 John Wiley & Sons, Inc. C1 US FDA,DIV MECH & MAT SCI,ROCKVILLE,MD 20852. RP Gogolewski, S (reprint author), AO ASIF RES INST,CLAVADELERSTR,CH-7270 DAVOS,SWITZERLAND. NR 29 TC 41 Z9 43 U1 1 U2 6 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 OCT PY 1996 VL 32 IS 2 BP 227 EP 235 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA VG920 UT WOS:A1996VG92000013 PM 8884500 ER PT J AU Pastakia, KB Brownson, NE Terle, DA Poindexter, BJ AF Pastakia, KB Brownson, NE Terle, DA Poindexter, BJ TI Amphotericin B induced abnormalities in human platelets SO JOURNAL OF CLINICAL PATHOLOGY-CLINICAL MOLECULAR PATHOLOGY EDITION LA English DT Article DE amphotericin B; platelets; surface membrane glycoprotein; flow cytometry ID MEMBRANE-GLYCOPROTEINS; ACTIVATED PLATELETS; P-SELECTIN; TRANSFUSION; NEUTROPHILS; EXPRESSION; MONOCYTES; ADHESION; PROTEIN AB Aims-To investigate in vitro the effect of amphotericin B on platelets in order to understand poor platelet recovery in patients receiving platelet transfusions and amphotericin B simultaneously. Methods-Washed platelets were isolated from platelet concentrates and exposed to amphotericin B (4 mu g/ml) for one hour. Platelet function was assessed by aggregation response to thrombin (0-0.6 U/ml), serotonin release, response to hypotonic stress, and mean platelet volume. The expression of surface membrane glycoprotein (GP) Ib-IX complex, GPIIb-IIIa complex and CD62P (P-selectin) was examined by flow cytometry using fluorescence labelled monoclonal antibodies. Heterotypic cell adhesion was measured in amphotericin B treated platelets coincubated with isolated, autologous polymorphonuclear leucocytes (PMN) by flow cytometric analysis. Results-Amphotericin B induced platelet dysfunction. The rate of aggregation by thrombin, serotonin uptake and thrombin induced release of serotonin, and the response of platelets to hypotonic stress were inhibited. There was up to a two-fold increase in the mean platelet volume. The expression of platelet surface GPIb-IX and GPIIb-IIIa was not affected. P-selectin, normally expressed only on the surface of activated platelets, was also expressed on unactivated platelets. Amphotericin B increased platelet adherence to PMN and the number of platelets bound per PMN. Conclusions-In vitro, amphotericin B induces P-selectin expression on the surface of unactivated platelets and increases platelet adhesion to PMN, which is exacerbated by storage. Platelet dysfunction resulting from exposure to amphotericin B may contribute to poor platelet recovery in vivo when amphotericin B is administered concomitantly with platelet transfusion. 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 27 TC 0 Z9 0 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 OCT PY 1996 VL 49 IS 5 BP M301 EP M307 PG 7 WC Pathology SC Pathology GA VL974 UT WOS:A1996VL97400010 ER PT J AU Goldman, SA AF Goldman, SA TI Lithium and neuroleptics in combination: Is there enhancement of neurotoxicity leading to permanent sequelae? SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; PERSISTING NEUROLOGIC SEQUELAE; AFFECTIVE-DISORDERS; MALIGNANT SYNDROME; BIPOLAR DISORDER; HEAT-STROKE; CEREBELLAR DEGENERATION; PSYCHOTROPIC-DRUGS; UNITED-STATES; SERUM LEVELS AB Neurotoxicity in relation to concomitant administration of lithium and neuroleptic drugs, particularly haloperidol, has been an ongoing issue. This study examined whether use of lithium with neuroleptic drugs enhances neurotoxicity leading to permanent sequelae, The Spontaneous Reporting System database of the United States Food and Drug Administration and extant literature were reviewed for spectrum cases of lithium/neuroleptic neurotoxicity. Groups taking lithium alone (Li), lithium/haloperidol (LiHal) and lithium/nonhaloperidol neuroleptics (LiNeuro), each paired for recovery and sequelae, were established for 237 cases. Statistical analyses included pairwise comparisons of lithium levels using the Wilcoxon Rank Sum procedure and logistic regression to analyze the relationship between independent variables and development of sequelae. The Li and LiNeuro groups showed significant statistical differences in median lithium levels between recovery and sequelae pairs, whereas the LiHal pair did not differ significantly. Lithium level was associated with sequelae development overall and within the Li and LiNeuro groups; no such association was evident in the LiHal group. On multivariable logistic regression analysis, lithium level and taking lithium/haloperidol were significant factors in the development of sequelae, with multiple possibly confounding factors (e.g., age, sex) not statistically significant. Multivariable logistic regression analyses with neuroleptic dose as five discrete dose ranges or actual dose did not show an association between development of sequelae and dose. Database limitations notwithstanding, the lack of apparent impact of serum lithium level on the development of sequelae in patients treated with haloperidol contrasts notably with results in the Li and LiNeuro groups. These findings may suggest a possible effect of pharmacodynamic factors in lithium/neuroleptic combination therapy. RP Goldman, SA (reprint author), US FDA,OFF OPERAT,HF-2,5600 FISHERS LANE,ROOM 9-57,ROCKVILLE,MD 20857, USA. NR 82 TC 19 Z9 19 U1 2 U2 4 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 OCT PY 1996 VL 36 IS 10 BP 951 EP 962 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VR622 UT WOS:A1996VR62200012 PM 8930783 ER PT J AU Murakami, EG Sweat, VE Sastry, SK Kolbe, E AF Murakami, EG Sweat, VE Sastry, SK Kolbe, E TI Analysis of various design and operating parameters of the thermal conductivity probe SO JOURNAL OF FOOD ENGINEERING LA English DT Article AB The thermal conductivity (k) probe is derived from an idealized transient heat transfer model; therefore, there are inevitable differences between the real probe and the theoretical model. However the k probe is still an accurate and practical measurement device with wide-ranging applications if designed and used properly. Users of a thermal conductivity probe must be aware of its limitations and the possible errors that can develop in its application. This paper includes a theoretical derivation of the k probe equation and some experimental and theoretical simulations of parameters that can cause errors in the application of the k probe. An explanation is given of the significance of certain design and operating parameters. Some of the findings in the study are that the time-correction factor is not required and contact resistance does not affect accuracy. The calibration factor is necessary since it compensates for the difference in the thermal masses of the probe and the sample. Errors due to edge effects and convection can be avoided by limiting data analysis to the linear section of the time-temperature plot. The truncation error is minimized by making beta as small as possible. Copyright (C) 1996 Elsevier Science Limited C1 TEXAS A&M UNIV,DEPT AGR ENGN,COLLEGE STN,TX 77843. OHIO STATE UNIV,DEPT AGR ENGN,COLUMBUS,OH 43210. OREGON STATE UNIV,DEPT BIORESOURCE ENGN,CORVALLIS,OR 97331. OREGON STATE UNIV,DEPT FOOD SCI & TECHNOL,CORVALLIS,OR 97331. RP Murakami, EG (reprint author), US FDA,NATL CTR FOOD SAFETY & TECHNOL,6502 S ARCHER AVE,SUMMIT ARGO,IL 60501, USA. NR 26 TC 24 Z9 24 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0260-8774 J9 J FOOD ENG JI J. Food Eng. PD OCT-NOV PY 1996 VL 30 IS 1-2 BP 209 EP 225 DI 10.1016/S0260-8774(96)00010-6 PG 17 WC Engineering, Chemical; Food Science & Technology SC Engineering; Food Science & Technology GA WD989 UT WOS:A1996WD98900015 ER PT J AU Restaino, L Castillo, HJ Stewart, D Tortorello, ML AF Restaino, L Castillo, HJ Stewart, D Tortorello, ML TI Antibody-direct epifluorescent filter technique and immunomagnetic separation for 10-h screening and 24-h confirmation of Escherichia coli O157:H7 in beef SO JOURNAL OF FOOD PROTECTION LA English DT Article DE E-coli O157:H7; beef; epifluorescence; immunomagnetic separation; rapid screening ID FOOD AB Rapid screening of beef for the presence of Escherichia coli O157:H7 was shown to be feasible using a 10-h enrichment in modified buffered peptone water and the antibody-direct epifluorescent filter technique (Ab-DEFT). The Ab-DEFT involved membrane filtration, fluorescent antibody staining and epifluorescence microscopy and was accomplished in less than 1 h. The procedure allowed detection of the pathogen artificially inoculated into beef patties at 0.1 CFU/g, The 10-h nonselective enrichment broth supported rapid growth, which provided sufficient numbers of cells for a positive determination by the Ab-DEFT after fewer than 10 microscope fields were scanned using a 40x objective lens. Immunomagnetic separation using anti-E. coli O157 Dynabeads(R) was used to confirm presumptively positive cultures within 24 h. The ease and rapidity of the Ab-DEFT may provide a substantial time and cost savings to the beef industry for screening beef for the presence of E. coli O157:H7. C1 US FDA,NATL CTR FOOD SAFETY & TECHNOL,SUMMIT ARGO,IL 60501. R&F LABS,BRIDGEVIEW,IL 60455. NR 10 TC 22 Z9 22 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 OCT PY 1996 VL 59 IS 10 BP 1072 EP 1075 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA VQ542 UT WOS:A1996VQ54200009 ER PT J AU Bennett, RW AF Bennett, RW TI Atypical toxigenic Staphylococcus and non-Staphylococcus aureus species on the horizon? An update SO JOURNAL OF FOOD PROTECTION LA English DT Article; Proceedings Paper CT Symposium Series on Issues and Answers in Food Microbiology and Safety - Today, Tomorrow, and Beyond, at the IAMFES Annual Meeting CY JUL 30-AUG 02, 1995 CL PITTSBURGH, PA SP Int Assoc Milk Food & Environm Sanitarians Inc DE enterotoxigenic staphylococci; non-S-aureus pathogenic staphylococci; Staphylococcus intermedius ID ENTEROTOXIN PRODUCTION; INTERMEDIUS; FOODS; STRAINS AB Staphylococcal food poisoning is a commonly reported illness caused by the ingestion of preformed staphylococcal enterotoxin in foods, With some exceptions, enterotoxin production is associated with coagulase-positive rather than coagulase-negative staphylococci. Of the coagulase-positive staphylococcal species, S. aureus was historically thought to be exclusively implicated in human foodborne illness, More recently, however, other coagulase-positive and some coagulase-negative staphylococcal species have been associated with foodborne intoxication. Coagulase activity has been used to indicate pathogenicity of a foodborne isolate, and thermostable nuclease is being suggested as a more reliable indictor of enterotoxigenicity. Evidence suggests that the metabolic expressions that are the bases of the tests may not be reliable indicators of pathogenicity. A more useful approach to determine the pathogenicity of a Staphylococcus species is to test directly for enterotoxigenicity with one of the new rapid methods. None of the conventional ancillary identification tests has been conclusively associated with enterotoxin synthesis, Furthermore, evidence exists that enterotoxin production is a characteristic of several species in the genus Staphylococcus. RP Bennett, RW (reprint author), US FDA,DIV MICROBIOL STUDIES,200 C ST SW,WASHINGTON,DC 20204, USA. NR 30 TC 22 Z9 23 U1 0 U2 2 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2838 SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD OCT PY 1996 VL 59 IS 10 BP 1123 EP 1126 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA VQ542 UT WOS:A1996VQ54200017 ER PT J AU Temple, R OBrien, P AF Temple, R OBrien, P TI Why would anyone have expected anything else? Characteristics of materials distributed by drug companies: Four points of view SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material RP Temple, R (reprint author), US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857, USA. NR 1 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 1996 VL 11 IS 10 BP 640 EP 641 DI 10.1007/BF02599034 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA WA569 UT WOS:A1996WA56900011 PM 8945698 ER PT J AU Nguyen, NY Sackett, D Hirata, RDC Levy, DE Enterline, JC Bekisz, JB Hirata, MH AF Nguyen, NY Sackett, D Hirata, RDC Levy, DE Enterline, JC Bekisz, JB Hirata, MH TI Isolation of a biologically active soluble human interferon-alpha receptor-GST fusion protein expressed in Escherichia coli SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID HUMAN LYMPHOBLASTOID INTERFERON; IFN-ALPHA; COMMON RECEPTORS; BINDING-SITES; BETA RECEPTOR; HUMAN-CELLS; SUBUNIT; ANTIBODIES; COMPONENTS; CLONING AB The cDNA encoding the extracellular domain of the human interferon-alpha (IFN-alpha) receptor (Uze, G., Lutfalla, G., and Gresser, I. Cell 1990;60:225-234) lacking the signal peptide has been expressed in Escherichia coli as a fusion protein with glutathione S-transferase, The fusion protein represented 12% of total bacterial proteins and was found exclusively within cytoplasmic inclusion bodies, Inclusion body material was completely solubilized by 8 M urea; 20% solubilization was achieved by cell lysis in the presence of 0.45% cholamidopropyl dimethylammoniol-propane sulfonate and 1% Triton X-100, The soluble fusion protein was purified by gel filtration and affinity chromatography, Overall recovery of affinity purified fusion protein was approximately 100-200 mu g/liter of cell culture, The affinity purified and refolded fusion protein exhibited the expected amino terminal sequence and M(r) of 68,000 on reduced sodium dodecylsulfate gel electrophoresis, The protein reacted with antibodies specific for the cloned IFN-alpha receptor and inhibited the antiviral and antiproliferative activities of recombinant IFN-alpha B. We have demonstrated that the fusion protein binds to IFN-alpha B and competes with the cell surface receptor for binding to this IFN-alpha species. C1 US FDA, CTR BIOL EVALUAT & RES, OFF THERAPEUT RES & REVIEW, DIV CYTOKINE BIOL, BETHESDA, MD 20892 USA. RI Hirata, Rosario/A-7284-2011; Hirata, Mario/C-9718-2013 NR 49 TC 17 Z9 20 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD OCT PY 1996 VL 16 IS 10 BP 835 EP 844 DI 10.1089/jir.1996.16.835 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA VP290 UT WOS:A1996VP29000011 PM 8910769 ER PT J AU Hirata, MH Sackett, D Hirata, RDC Nguyen, NY AF Hirata, MH Sackett, D Hirata, RDC Nguyen, NY TI Human interferon-alpha receptor: Identification of the region involved in binding to interferon-alpha B SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID HUMAN LYMPHOBLASTOID INTERFERON; I IFN RECEPTOR; COMMON RECEPTORS; ESCHERICHIA-COLI; RNA-POLYMERASE; BETA RECEPTOR; HUMAN-CELLS; EXPRESSION; SUBUNIT; GENES AB Three polypeptides comprising amino acids 1-102, 93-260, and 261-410 of the extracellular domain of the human interferon-alpha receptor HuIFN-alpha R (Uze, G., Lutfalla, G., and Gresser, I. Cell 1990; 60:225-234) have been expressed in Escherichia coli, The polypeptides were sequestered within bacterial inclusion bodies, Inclusion body material was solubilized by 8 M urea, and the polypeptides were purified by gel filtration or histidine tag-based affinity chromatography, Overall recovery of each purified and refolded polypeptide was approximately 0.5-0.8 mg/liter of cell culture, The polypeptides migrated as homogeneous monomers of 12 kDa, 22 kDa, and 17 kDa, respectively on reduced sodium dodecylsulfate polyacrylamide gel electrophoresis, The polypeptide fragments corresponding to amino acids 1-102, and 93-260 of the extracellular domain of HuIFN-alpha R lacked the ability to bind to IFN-alpha B and to inhibit its biologic activities, The polypeptide fragment corresponding to amino acids 261-410 of the receptor molecule inhibited the antiproliferative activity of IFN-alpha B and competed with the Daudi cell surface receptor for binding to this IFN-alpha species. C1 US FDA,CTR BIOL EVALUAT & RES,OFF THERAPEUT RES & REVIEW,DIV CYTOKINE BIOL,BETHESDA,MD 20892. RI Hirata, Rosario/A-7284-2011; Hirata, Mario/C-9718-2013 NR 42 TC 4 Z9 4 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD OCT PY 1996 VL 16 IS 10 BP 845 EP 852 DI 10.1089/jir.1996.16.845 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA VP290 UT WOS:A1996VP29000012 PM 8910770 ER PT J AU Musser, SM Gay, ML Mazzola, EP Plattner, RD AF Musser, SM Gay, ML Mazzola, EP Plattner, RD TI Identification of a new series of fumonisins containing 3-hydroxypyridine SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID FUSARIUM-MONILIFORME; CORN; MYCOTOXINS; CULTURES; AREAS; B-1 AB A new series of fumonisins, designated FP1-3, were isolated from a culture of Fusarium monoiliforme (M-2285) grown on solid corn. The new compounds contain a 3-hydroxypyridinium moiety at the C-2 position of the eicosane backbone instead of the amine found in the B series of fumonisins. The new fumonisins were characterized by UV, LC-MS-MS, H-1 NMR, and C-13 NMR. LC-MS analysis of culture extracts indicates that the new fumonisins can occur at levels up to approximately one-third the amount of their amine-containing analogues (FB1, FB2, and FB3). C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. USDA ARS,BIOACT CONSTITUENTS RES,NATL CTR AGR UTILIZAT RES,PEORIA,IL 61604. NR 20 TC 46 Z9 46 U1 1 U2 3 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD OCT PY 1996 VL 59 IS 10 BP 970 EP 972 DI 10.1021/np960349t PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA VQ084 UT WOS:A1996VQ08400014 PM 8904846 ER PT J AU Itzhak, Y Ali, SF AF Itzhak, Y Ali, SF TI The neuronal nitric oxide synthase inhibitor, 7-nitroindazole, protects against methamphetamine-induced neurotoxicity in vivo SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE methamphetamine; dopamine; neurotoxicity; nitric oxide synthase; 7-nitroindazole ID STRIATAL DOPAMINE; 7-NITRO INDAZOLE; IN-VIVO; RELEASE; MICE; TEMPERATURE; AMPHETAMINE; GLUTAMATE; SLICES; MOUSE AB The present study was undertaken to investigate whether the relatively selective neuronal nitric oxide synthase (NOS) inhibitor, 7-nitroindazole (7-NI), protects against methamphetamine (METH)-induced neurotoxicity. Male Swiss Webster mice received the following treatments (i.p.; q 3 h X 3): (a) vehicle/saline, (b) 7-NI (25 mg/kg)/saline, (c) vehicle/METH (5 mg/kg), and (d) 7-NI (25 mg/kg)/METH (5 mg/kg). On the second day, groups (a) and (b) received two vehicle injections, and groups (c) and (d) received two 7-NI injections (25 mg/kg, each). Administration of vehicle/METH resulted in 68, 44, and 55% decreases in the concentration of dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid, respectively, and a 48% decrease in the number of [H-3]mazindol binding sites in the striatum compared with control values. Treatment with 7-NI (group d) provided full protection against the depletion of dopamine and its metabolites and the loss of dopamine transporter binding sites. Administration of 7-NI/saline (group b) affected neither the tissue concentration of dopamine and its metabolites nor the binding parameters of [H-3]mazindol compared with control values. 7-NI had no significant effect on animals' body temperature, and it did not affect METH-induced hyperthermia. These findings indicate a role for nitric oxide in methamphetamine-induced neurotoxicity and also suggest that blockade of NOS may be beneficial for the management of Parkinson's disease. C1 US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,NEUROCHEM LAB,JEFFERSON,AR 72079. RP Itzhak, Y (reprint author), UNIV MIAMI,SCH MED,DEPT BIOCHEM & MOL BIOL R629,POB 016129,MIAMI,FL 33101, USA. FU NIDA NIH HHS [R55DA08584] NR 27 TC 147 Z9 150 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 1996 VL 67 IS 4 BP 1770 EP 1773 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA VH578 UT WOS:A1996VH57800053 PM 8858965 ER PT J AU Revelle, LK DAvignon, DA Wilson, JA AF Revelle, LK DAvignon, DA Wilson, JA TI 3-[(phenylacetyl)amino]-2,6-piperidinedione hydrolysis studies with improved synthesis and characterization of hydrolysates SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID ORAL FORMULATION; ANTINEOPLASTON-A10; TOXICOLOGY; DNA AB In an attempt to clarify ambiguities in earlier reports on the preclinical chemistry of Antineoplaston A10 (3-[(phenylacetyl)amino]-2,6-piperidinedione; PAP), we detail herein hydrolysis studies with improved synthesis and characterization of PAP hydrolysis products, (phenylacetyl)glutamine (PAG), (phenylacetyl)isoglutamine (PAIG), and (phenylacetyl)glutamic acid (PAGA). Flash chromatography proved superior to extraction in the isolation of synthetic standards and hydrolysates. Synthesis of PAIG directly from commercial isoglutamine showed consistently better yields than the previously reported method. The H-1 and C-13 NMR and HPLC-MS data from the synthesized standards matched the data from the isolated PAP hydrolysates formed under acid and alkaline degradation conditions. Multiple quantum coherence NMR methods (HMQC and HMBC) and HPLC-MS-MS methods were applied to provide unambiguous structural assignments for key isomers PAG and PAIG. Previous PAP hydrolysis studies are shown to be reproducible, and the structures of hydrolysis products are elucidated in detail. C1 WASHINGTON UNIV,DEPT CHEM,ST LOUIS,MO 63130. RP Revelle, LK (reprint author), US FDA,DIV DRUG ANAL,ROOM 1002,1114 MARKET ST,ST LOUIS,MO 63101, USA. NR 14 TC 3 Z9 3 U1 1 U2 2 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 OCT PY 1996 VL 85 IS 10 BP 1049 EP 1052 DI 10.1021/js960120y PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA VL690 UT WOS:A1996VL69000005 PM 8897269 ER PT J AU Laughren, TP AF Laughren, TP TI Regulatory issues in pediatric psychopharmacology SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE regulatory; pediatric; psychopharmacology; labeling AB Labeling claims for the effectiveness of drugs in the treatment of psychiatric illnesses in children and adolescents must be based on data from adequate and well-controlled investigations. The preferred design for demonstrating the effectiveness of a drug in pediatric psychopharmacology is generally a placebo-controlled trial. Safety information in labeling may be derived from more diverse sources. The Food and Drug Administration (FDA) has taken several steps to encourage more informative labeling of drugs for pediatric use, including a recent labeling initiative that emphasizes the possibility of extrapolating effectiveness data from adult studies to pediatric populations under appropriate circumstances. This recently finalized regulation requires pharmaceutical sponsors to reexamine existing data for their drugs to determine whether there is a sufficient basis for modifying labeling for pediatric use. Included in this new rule is a reminder that in certain situations the FDA may require new pediatric studies, thereby signaling the FDA's determination to improve labeling for the pediatric use of drugs. Improved preclinical models for predicting drug effects on growth and development, as well as improved clinical methods for detecting such changes, need to keep pace with the expansion of research in pediatric psychopharmacology. RP Laughren, TP (reprint author), US FDA,HFD-120,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 14 TC 5 Z9 5 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD OCT PY 1996 VL 35 IS 10 BP 1276 EP 1282 DI 10.1097/00004583-199610000-00014 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA VK055 UT WOS:A1996VK05500014 PM 8885581 ER PT J AU Brynes, SD Teske, RH AF Brynes, SD Teske, RH TI A case study: Harmonization of veterinary drug maximum residue levels between the US and Canada SO JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY LA English DT Article DE trade; harmonization; veterinary drugs AB The Free Trade Agreement between the United States and Canada (FTA) went into effect January 1, 1989. To implement certain provisions of the agreement on technical regulations and standards, the United States Center for Veterinary Medicine, the Canadian Bureau of Veterinary Drugs, and Agriculture Canada established the Working Group on Veterinary Drug Tolerances. The primary charges to the Working Group on Veterinary Drug Tolerances were (1) to harmonize the procedures used for evaluating new animal drugs, performing risk assessments and calculating tolerances, and (2) to harmonize the tolerances (or maximum residue levels, MRLs) for approved drugs, with the goal of having the same tolerances in each country. The first of these charges was met early in the negotiations. Both the US and Canada will use a 6-step evaluation procedure for the human food safety evaluation of new animal drugs. On September 29, 1990, Canada published a list of MRLs for 38 drugs that had been harmonized through the FTA. The progress of the working group and its continuing efforts to harmonize tolerances for approximately 15 other veterinary drugs will be discussed. This paper proposes use of the toxicologically determined acceptable daily intake (ADI) for the drug as the safety standard for reaching conclusions on the acceptability of residues in meat for human consumption. Specifically, the 'equivalence' of different MRLs for the same veterinary drug would be determined by considering whether they are likely to result in dietary residues that exceed the other country's ADI for the drug. Estimates are made for the veterinary drugs lasalocid and halofuginone hydrobromide. Based on these estimates, the US and Canadian MRLs for each drug would be considered 'equivalent' for trade purposes. RP Brynes, SD (reprint author), US FDA,CTR VET MED HFV144,7500 STANDISH PL,ROCKVILLE,MD 20855, USA. NR 4 TC 1 Z9 1 U1 0 U2 0 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 OCT PY 1996 VL 15 IS 5 BP 436 EP 444 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA VQ532 UT WOS:A1996VQ53200010 ER PT J AU Mossoba, MM Yurawecz, PM Roach, JAC McDonald, RE Perkins, EG AF Mossoba, MM Yurawecz, PM Roach, JAC McDonald, RE Perkins, EG TI Confirmatory mass-spectral data for cyclic fatty acid monomers SO JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY LA English DT Article DE 2-alkyl-4,4-dimethyloxazoline; cyclic fatty acid monomers; gas chromatography; electron ionization mass spectrometry ID METHYL LINOLENATE; HEAT-TREATMENT; SPECTROMETRY; CHROMATOGRAPHY; CONFIGURATION; DERIVATIVES; POSITION; LOCATION; CHAIN; OILS AB Cyclic fatty acid monomers (CFAM) are degradation products found in heat-abused edible oils. This study confirms previously published data and reports the structural elucidation of hydrogenated and deuterated monocyclic and bicyclic CFAM prepared from the corresponding unsaturated species that were previously isolated from healed flaxseed (linseed) oil. CFAM structures were determined as 2-alkyl-4,4-dimethyloxazoline derivatives by using gas chromatography-electron ionization mass spectrometry. The observed retention times for the deuterated CFAM were about 0.1 min shorter than those of the corresponding hydrogenated species. For two minor six-membered ring CFAM components, an increase in the mass of the unsaturated ring by eight mass units upon deuteration indicated the addition of four deuterium atoms to two double bonds in that ring. These data unequivocally confirmed the identity of cyclohexadienyl CFAM species in the original CFAM mixture that was isolated from heated linseed oil. The observed electron ionization mass spectrometic data for minor hydrogenated and deuterated CFAM species, which correspond to the last two eluting monounsaturated species, were consistent with CFAM having bicyclic (fused 5- and 6-membered rings) structures. The location of the ring along the fatty acid chain was also confirmed for all saturated CFAM mixture components. The presence of a pair of deuterium atoms on two adjacent carbon atoms further confirmed the previously determined double-bond position along the fatty acid chain of the corresponding parent (unsaturated) compound. C1 US FDA,NATL CTR FOOD SAFETY & TECHNOL,SUMMIT ARGO,IL 60501. UNIV ILLINOIS,URBANA,IL 61801. RP Mossoba, MM (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204, USA. NR 16 TC 10 Z9 10 U1 0 U2 2 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0003-021X J9 J AM OIL CHEM SOC JI J. Am. Oil Chem. Soc. PD OCT PY 1996 VL 73 IS 10 BP 1317 EP 1321 DI 10.1007/BF02525462 PG 5 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA VM301 UT WOS:A1996VM30100015 ER PT J AU Schneiderman, RD Farrell, KB Wilson, CA Eiden, MV AF Schneiderman, RD Farrell, KB Wilson, CA Eiden, MV TI The Japanese feral mouse Pit1 and Pit2 homologs lack an acidic residue at position 550 but still function as gibbon ape leukemia virus receptors: Implications for virus binding motif SO JOURNAL OF VIROLOGY LA English DT Article ID CELLULAR RECEPTOR; HAMSTER-CELLS; MURINE; RETROVIRUS; INFECTION; GLVR1 AB Murine cells are typically resistant to gibbon ape leukemia virus (GALV). MMMol, a Japanese feral mouse cell line, is an exception in that these cells are susceptible to infection by GALV. We show here that MMMol cells are further distinguished by their unusual receptor properties. MMMol cells infected by GALV are resistant to subsequent infection not only by GALV but also by amphotropic murine leukemia virus. This suggests that GALV can enter MMMol via not only the GALV receptor (MolPit1) but also the amphotropic murine leukemia virus receptor (MolPit2). Therefore, MolPit2 was cloned, sequenced, and compared with the previously reported sequence of MolPit1. Earlier studies have shown that a stretch of nine residues (position 550 to 558) in the fourth extracellular domain of Pit1 is crucial for GALV entry acid that an acidic residue at position 550 is indispensable. However, MolPit1 has isoleucine at this position and MolPit2 has glutamine at the corresponding position (position 522), thus breaking this consensus. To determine what effect these specific changes in the fourth extracellular domain of MolPit1 and MolPit2 have on GALV receptor function, chimeric receptors were made by substituting the fourth extracellular domain of either MolPit1 or MolPit2 for the same region of Pit2, a nonfunctional receptor for GALV. These chimeras were then tested in MDTF, a cell line that lacks functional GALV receptors and is resistant to GALV. Results show that MDTF expressing these chimeras became susceptible to GALV, whereas cells expressing wild-type Pit2 remained resistant. Further, the MolPit1 chimera was identical to Pit1 in efficiency, but the MolPit2 chimera proved substantially less efficient. C1 NIMH,UNIT MOL VIROL,CELL BIOL LAB,BETHESDA,MD 20892. US FDA,DIV CELLULAR & GENE THERAPIES,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20892. NR 20 TC 15 Z9 15 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 OCT PY 1996 VL 70 IS 10 BP 6982 EP 6986 PG 5 WC Virology SC Virology GA VG127 UT WOS:A1996VG12700056 PM 8794342 ER PT J AU Chumakov, KM AF Chumakov, KM TI PCR engineering of viral quasispecies: A new method to preserve and manipulate genetic diversity of RNA virus populations SO JOURNAL OF VIROLOGY LA English DT Article ID ORAL POLIOVIRUS VACCINE; POLYMERASE ERROR FREQUENCY; MULLER RATCHET; SABIN STRAIN; IN-VITRO; FITNESS; DNA; AMPLIFICATION; MICROEVOLUTION; SELECTION AB A PCR-based method for the controlled manipulation of individual genomic sites of poliovirus with concomitant preservation of the sequence heterogeneity of the rest of the genome is proposed. The new approach can be used for the creation of stable DNA repositories of populations of extremely heterogenous RNA viruses and may have implications for live vaccine technology. RP Chumakov, KM (reprint author), US FDA,CTR BIOL EVALUAT & RES,HFM-255,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 29 TC 20 Z9 20 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 OCT PY 1996 VL 70 IS 10 BP 7331 EP 7334 PG 4 WC Virology SC Virology GA VG127 UT WOS:A1996VG12700107 PM 8794393 ER PT J AU Jackson, CD Weis, C Poirier, LA Bechtel, DH AF Jackson, CD Weis, C Poirier, LA Bechtel, DH TI Interactions of varying levels of dietary fat, carbohydrate, and fiber on food consumption and utilization, weight gain and fecal fat contents in female Sprague-Dawley rats SO NUTRITION RESEARCH LA English DT Article DE dietary fat; dietary carbohydrate; dietary fiber; fecal fat ID MAMMARY TUMORIGENESIS; BODY-WEIGHT; CELL-PROLIFERATION; WHEAT BRAN; CARCINOGENESIS; CANCER; RESTRICTION; CALORIES; ENERGY; COLON AB The purpose of this study was to better define a nutritional regime for the DMBA-induced rat mammary tumor model for studying the interdependent effects of fats, carbohydrates, and fiber on mammary tumor development. Female Sprague-Dawley rats were administered (ad libitum) a modified AIN-76A diet containing different ratios of dietary fat, carbohydrate, and fiber for 6 weeks. Food consumption was decreased in the higher fat groups, but the decrease did not compensate completely for the higher caloric density of the diets. Calorie consumption and body weight gain were greater in both the mid and high than in the low fat groups. Dietary fiber had only a marginally significant effect on food consumption but did decrease both calorie consumption and body weight gain in the high fat groups. There was no significant interaction between fat and fiber with respect to food or calorie consumption, but there was a marginally significant interaction between these two dietary components on body weight gain. Food utilization, with respect to weight gain, was increased by fat and decreased by fiber, with a significant antagonistic interaction between the two. Calorie utilization (g weight gain/100 kcal) was increased by increased fat but the effect of fiber was not significant. Dry fecal weight was increased by dietary fiber and decreased by dietary fat. The amount of fecal fat excreted was increased by dietary fiber but the effects of dietary fat on fecal fat excretion were inconsistent. The results indicate a complex interaction of dietary fat and fiber. Animals administered the low fat/high fiber diet consumed the least number of calories and thus would be the control group in a pair fed, isocaloric study. C1 BEST FOODS, SOMERSET, NJ 08873 USA. RP Jackson, CD (reprint author), NATL CTR TOXICOL RES, 3900 NCTR DR, JEFFERSON, AR 72079 USA. NR 34 TC 5 Z9 5 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 OCT PY 1996 VL 16 IS 10 BP 1735 EP 1747 DI 10.1016/0271-5317(96)00193-5 PG 13 WC Nutrition & Dietetics SC Nutrition & Dietetics GA VK313 UT WOS:A1996VK31300012 ER PT J AU Mordenti, J Cavagnaro, JA Green, JD AF Mordenti, J Cavagnaro, JA Green, JD TI Design of biological equivalence programs for therapeutic biotechnology products in clinical development: A perspective SO PHARMACEUTICAL RESEARCH LA English DT Editorial Material DE bioequivalence; biotechnology products; recombinant proteins; pharmacokinetics; pharmacodynamics; efficacy; immunogenicity; safety ID NERVE GROWTH-FACTOR; N-ACETYLNEURAMINIC ACID; PROTEIN PHARMACEUTICALS; INJECTION TECHNIQUE; BINDING-PROTEINS; BIOEQUIVALENCE; RECOMBINANT; PHARMACOKINETICS; HORMONE; INSULIN AB The determination of biological equivalence requires that studies are conducted to establish that two molecules, two formulations, or two dosing regimens, for example, are indistinguishable with respect to safety and efficacy profiles that have been previously established. The criteria that are used to establish biological equivalence will depend on the nature of the change (e.g., molecular, process, formulation), the stage of the development program, the duration of treatment, and the intended clinical indications. Key components of an equivalence program include chemical characterization, in vitro and in vivo bioactivity against reference material, pharmacokinetics, and safety. Special considerations for patient populations, endogenous concentrations, environmental factors, immunogenicity, assay methodology, biochemical identity, pharmacodynamic equivalence, and statistical methodology are discussed. in addition, the role of preclinical in vivo assessments is addressed. Specific case studies provide insight into the varied nature of approaches that are currently employed. C1 US FDA, CTR BIOL EVALUAT & RES, ROCKVILLE, MD 20857 USA. RP Mordenti, J (reprint author), GENENTECH INC, 460 POINT SAN BRUNO BLVD, S SAN FRANCISCO, CA 94080 USA. NR 57 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORDR JI Pharm. Res. PD OCT PY 1996 VL 13 IS 10 BP 1427 EP 1437 DI 10.1023/A:1016002823485 PG 11 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA VN257 UT WOS:A1996VN25700002 PM 8899831 ER PT J AU Clausing, P Bloom, D Newport, GD Holson, RR Slikker, W Bowyer, JF AF Clausing, P Bloom, D Newport, GD Holson, RR Slikker, W Bowyer, JF TI Individual differences in dopamine release but not rotational behavior correlate with extracellular amphetamine levels in caudate putamen in unlesioned rats SO PSYCHOPHARMACOLOGY LA English DT Article DE amphetamine; pharmacokinetics; microdialysis; dopamine; rotational behavior; hyperthermia; brain temperature; unlesioned rats; individual differences ID LEFT-RIGHT DISCRIMINATION; RECEPTOR SUBTYPES; THERMOREGULATION; TEMPERATURE; ASYMMETRY; COCAINE AB It has been postulated that differences in pharmacokinetics do not contribute to the well-known individual variability in response to amphetamine (AMPH), but this is yet to be investigated thoroughly. Therefore, rotational behavior of outbred rats (Sprague-Dawley, 4 months old) was recorded during microdialysis sessions and striatal microdialysate was analyzed concomitantly for AMPH and dopamine concentrations after a single injection of 2.5 mg/kg AMPH SC. Three hours later these rats received three doses of 5 mg/kg AMPH SC (spaced 2 h apart) and their brain temperature was recorded every 20 min. The most important findings were: 1) the increase in extracellular dopamine was highly correlated with the corresponding peak AMPH levels in the microdialysate; 2) the peak dopamine level in response to 2.5 mg/kg AMPH was predictive of the hyperthermic response observed during 3 x 5 mg/kg AMPH and 3) high versus low rotators differed neither in their AMPH nor in their dopamine extracellular striatal concentrations. C1 NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079. RP Clausing, P (reprint author), NATL CTR TOXICOL RES,DIV NEUROTOXICOL,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 44 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD OCT PY 1996 VL 127 IS 3 BP 187 EP 194 DI 10.1007/BF02805993 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA VN803 UT WOS:A1996VN80300002 PM 8912396 ER PT J AU Fitzpatrick, SC Vilim, A Lambert, G Yong, MS Brynes, SD AF Fitzpatrick, SC Vilim, A Lambert, G Yong, MS Brynes, SD TI Dietary intake estimates as a means to the harmonization of maximum residue levels for veterinary drugs .2. Proposed application to the Free Trade Agreement between the United States and Canada SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article AB The Free Trade Agreement between the United States and Canada (FTA) went into effect January 1, 1989. To implement certain provisions of the agreement on technical regulations and standards, the United States Food and Drug Administration's Center for Veterinary Medicine, Health and Welfare Canada's Bureau of Veterinary Drugs, and Agriculture Canada established the Working Group on Veterinary Drug Tolerances, The progress of the working group and its continuing efforts to harmonize tolerances for approximately 15 veterinary drugs are discussed. This paper proposes use of the toxicologically determined acceptable daily intake (ADI) for the drug as the safety standard for reaching conclusions on the acceptability of residues in meat for human consumption. Specifically, the ''equivalence'' of different MRLs for the same veterinary drug would be determined by considering whether they are likely to result in dietary residues that exceed the other country's ADI for the drug. Estimates are made for the veterinary drugs lasalocid, fenbendazole, morantel tartrate, halofuginone, and tilmicosin. Based on these estimates, the U.S. and Canadian MRLs for each drug would be considered equivalent for trade purposes. (C) 1996 Academic Press, Inc. C1 VET DRUG CONSULTANT,ROCKVILLE,MD 20853. HLTH & WELF CANADA,BUR VET DRUGS,OTTAWA,ON K1A 1B7,CANADA. US FDA,CTR VET MED,ROCKVILLE,MD 20855. NR 7 TC 7 Z9 8 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 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD OCT PY 1996 VL 24 IS 2 BP 177 EP 183 DI 10.1006/rtph.1996.0123 PN 1 PG 7 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA VU990 UT WOS:A1996VU99000011 PM 8933631 ER PT J AU Feng, CD Ming, YD Hesketh, PJ Gendel, SM Stetter, JR AF Feng, CD Ming, YD Hesketh, PJ Gendel, SM Stetter, JR TI Confirmation of immobilizing IgG on different surfaces with AFM and impedance investigations of a Pt electrode during the immobilization SO SENSORS AND ACTUATORS B-CHEMICAL LA English DT Article; Proceedings Paper CT Proceedings of the 6th International Meeting on Chemical Sensors CY JUL 22-25, 1996 CL GAITHERSBURG, MD DE immobilizing IgG; atom force microscope; impedance; Pt electrode ID PLATINUM FILM AB Immobilization of anti-SEB on SiO2, Pt and Au thin films have been carried out by using a conventional covalent bonding technique. AFM investigation showed that after the immobilization, a monolayer of the antibody molecules was formed on the SiO2 film, By reacting the immobilized anti-SEB with gold colloid conjugated anti-IgG, gold particles were observed on the antibody immobilized film surface by AFM. Pt films showed the highest coverage of anti-SEB after immobilization. Impedance change of a Pt electrode in PBS solution was also investigated before and after the immobilization of anti-SEB. C1 UNIV ILLINOIS,DEPT ELECT ENGN & COMP SCI,CHICAGO,IL 60617. US FDA,NATL CTR FOOD SAFETY & TECHNOL,SUMMIT ARGO,IL 60501. RP Feng, CD (reprint author), IIT,DEPT CHEM & BIOL SCI,CHICAGO,IL 60616, USA. NR 3 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0925-4005 J9 SENSOR ACTUAT B-CHEM JI Sens. Actuator B-Chem. PD OCT PY 1996 VL 36 IS 1-3 BP 431 EP 434 DI 10.1016/S0925-4005(97)80110-4 PG 4 WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation SC Chemistry; Electrochemistry; Instruments & Instrumentation GA WJ775 UT WOS:A1996WJ77500032 ER PT J AU Oravecz, T Pall, M Norcross, MA AF Oravecz, T Pall, M Norcross, MA TI Effect of the N-L, T-cell and myeloid section antibodies on homotypic cell adhesion and HIV-1 induced syncytium formation. SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 NIH,FDA,CBER,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD OCT PY 1996 VL 48 IS 4-II BP NL406 EP NL406 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA VR930 UT WOS:A1996VR93000364 ER PT J AU Macpherson, SE Barton, CN Bronaugh, RL AF Macpherson, SE Barton, CN Bronaugh, RL TI Use of in vitro skin penetration data and a physiologically based model to predict in vivo blood levels of benzoic acid SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID INVITRO PERCUTANEOUS-ABSORPTION; GLYCINE CONJUGATION; DERMAL ABSORPTION; DRUG-METABOLISM; ENZYME-ACTIVITY; GUINEA-PIG; RATS; XENOBIOTICS; DEPENDENCE; VIABILITY AB A physiologically based pharmacokinetic (PB PK) model was developed to predict plasma levels of benzoic acid (BA) in the hairless guinea pig after topical exposure at three finite dose levels, The PB PK model consisted of four compartments: (1) rapidly perfused tissues; (2) slowly perfused tissues; (3) liver, representing the route of elimination of BA from the plasma after biotransformation to hippuric acid; and (4) plasma, The predictive capacity of the PB PK model was assessed by comparing plasma BA levels measured experimentally with those predicted by the model, The percutaneous absorption of finite doses of BA in the model was described by a transdermal input function, which was derived from in vitro percutaneous absorption studies in which viable hairless guinea pig skin in flow-through diffusion cells was exposed to BA, Physiological parameters used in the model were calculated from previously published values, Biochemical parameters, including partition coefficients and metabolic constants, were measured experimentally in vitro, The PB PK model predictions were generally in good agreement with measured plasma levels for each of the dose levels studied, The predicted plasma BA levels and the measured values were closer for the highest dose (120 mu g/cm(2)) than for either of the other two doses used (12 and 40 mu g/cm(2)), The effects of optimizing the metabolic constants and the transdermal input function parameters on the predicted curve shape and fit to that of the measured plasma BA levels were assessed, Varying the transdermal input parameters produced closer agreement between predicted and measured values. (C) 1996 Academic Press, Inc. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,COSMET TOXICOL BRANCH,LAUREL,MD 20708. US FDA,CTR FOOD SAFETY & APPL NUTR,DIV MATH,WASHINGTON,DC 20204. NR 29 TC 6 Z9 6 U1 1 U2 5 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 OCT PY 1996 VL 140 IS 2 BP 436 EP 443 DI 10.1006/taap.1996.0240 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA VN707 UT WOS:A1996VN70700027 PM 8887461 ER PT J AU Freyaldenhoven, TE Ali, SF AF Freyaldenhoven, TE Ali, SF TI Heat shock proteins protect cultured fibroblasts from the cytotoxic effects of MPP(+) SO BRAIN RESEARCH LA English DT Article DE MPTP; MPP(+); heat shock protein; cytotoxicity; fibroblast ID 1-METHYL-4-PHENYLPYRIDINIUM ION MPP+; STRIATAL DOPAMINE; SUBSTANTIA-NIGRA; MOUSE-BRAIN; CHRONIC PARKINSONISM; ALZHEIMERS-DISEASE; MONOAMINE-OXIDASE; THERMAL-STRESS; ATP LOSS; MPTP AB 1-Methyl-4-phenylpyridinium (MPP(+)), the cytotoxic metabolite of 1-methyl-3-phenyl-1,2,3,6-tetrahydropyridine (MPTP), has been shown to be toxic to a variety of cell types in culture. The addition of media containing 1 mM MPP(+) to cultures of Chinese hamster ovary (CHO) fibroblasts led to the gradual depletion of cellular ATP stores and subsequent cell death. A 12-min heat shock of the cells at 45 degrees C, 3 h prior to the addition of MPP(+)-containing media, significantly attenuated cell death. Heat shock pretreatment led to an increased synthesis of all the major heat shock proteins (HSPs) in CHO cells. Further, the addition of the protein synthesis inhibitor, cycloheximide, prevented the protective effect of heat shock pretreatment, indicating that this protection was dependent upon new protein synthesis. In additional experiments, a rat fibroblast cell line which has been stably transfected with, and constitutively expresses a cloned human HSP-70 gene, was found to be more resistant to the cytotoxic effects of MPP(+) than the parental fibroblast cell line. These results indicate that HSPs are protective toward the deleterious effects of MPP(+) and that their synthesis represents an important parameter in the neurotoxicity of MPTP. C1 NATL CTR TOXICOL RES,DIV NEUROTOXICOL,NEUROCHEM LAB,JEFFERSON,AR 72079. UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM & MOL BIOL,LITTLE ROCK,AR 72205. NR 55 TC 17 Z9 19 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 SEP 30 PY 1996 VL 735 IS 1 BP 42 EP 49 PG 8 WC Neurosciences SC Neurosciences & Neurology GA VM547 UT WOS:A1996VM54700006 PM 8905168 ER PT J AU Kessler, DA Witt, AM Barnett, PS Zeller, MR Natanblut, SL Wilkenfeld, JP Lorraine, CC Thompson, LJ Schultz, WB AF Kessler, DA Witt, AM Barnett, PS Zeller, MR Natanblut, SL Wilkenfeld, JP Lorraine, CC Thompson, LJ Schultz, WB TI The Food and Drug Administration's regulation of tobacco products SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DEPENDENCE; CHILDREN RP Kessler, DA (reprint author), US FDA,OFF COMMISSIONER,5600 FISHERS LN,HF-1,ROCKVILLE,MD 20857, USA. NR 63 TC 86 Z9 87 U1 0 U2 1 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 SEP 26 PY 1996 VL 335 IS 13 BP 988 EP 994 DI 10.1056/NEJM199609263351321 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA VK148 UT WOS:A1996VK14800035 PM 8782508 ER PT J AU Wysowksi, DK Bacsanyi, J AF Wysowksi, DK Bacsanyi, J TI Blood dycrasias and hematologic reactions in ticlopidine users SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP Wysowksi, DK (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 5 TC 29 Z9 29 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 SEP 25 PY 1996 VL 276 IS 12 BP 952 EP 952 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VH990 UT WOS:A1996VH99000027 PM 8805723 ER PT J AU Morris, SM Manjanatha, MG Shelton, SD Domon, OE McGarrity, LJ Casciano, DA AF Morris, SM Manjanatha, MG Shelton, SD Domon, OE McGarrity, LJ Casciano, DA TI A mutation in the p53 tumor suppressor gene of AHH-1 tk(+/-) human lymphoblastoid cells SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE AHH-1 tk(+/-) human lymphoblastoid cell; MCL-5 human lymphoblastoid cell; p53 mutation; CpG mutation ID WILD-TYPE P53; MUTANT P53; HUMAN CANCERS; APOPTOSIS; INDUCTION; PROTEIN; LINE; SENSITIVITY; COMPETENT; MUTAGEN AB Loss-of-function mutations in the p53 tumor suppressor gene result in an altered response to DNA-damaging agents. Included in the mutant p53 phenotype are the loss of the G(1) checkpoint and delayed apoptotic cell death, characteristics we have consistently observed in the the AHH-1 tk(+/-) cell line following exposure to DNA-damaging agents. In order to determine the functional status of p53 in the AHH-1 tk(+/-) cell line, molecular analysis (single-strand conformational polymorphism [SSCP] and sequence analysis) was performed on exons 5-9 of the p53 gene. In addition, the status of the p53 gene in the closely related lymphoblast line, MCL-5, which, in our hands, has a much higher spontaneous rate of apoptosis than AHH-1 tk(+/-), was also determined by molecular analysis. Initial SSCP analysis of AHH-1 tk(+/-) revealed an abnormal migration pattern of exon 8 when compared to a wild-type control. Subsequent sequence analysis indicated that a base-pair substitution ((C) under bar GG --> (T) under bar GG) mutation had occurred at codon 282, a reported 'hot spot' for 5-methylcytosine mutations in the human p53 gene. Neither SSCP nor sequence analysis of exons 5-9 of MCL-5 indicated any differences from wild-type DNA. These results suggest that the lack of a G(1) arrest and the delayed entrance into apoptosis observed in chemically-exposed AHH-1 tk(+/-) cells are, at least partially, accounted for by a loss-of-function mutation in the p53 gene. RP Morris, SM (reprint author), US FDA,DIV GENET TOXICOL,NATL CTR TOXICOL RES,DEPT HLTH & HUMAN SERV,HFT 120,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 33 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD SEP 23 PY 1996 VL 356 IS 2 BP 129 EP 134 DI 10.1016/0027-5107(96)00133-9 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA VJ559 UT WOS:A1996VJ55900001 PM 8841477 ER PT J AU Husain, SR Leland, P Aggarwal, BB Puri, RK AF Husain, SR Leland, P Aggarwal, BB Puri, RK TI Transcriptional up-regulation of interleukin 4 receptors by human immunodeficiency virus type 1 tat gene SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HIV-1 TAT; CELL-LINE; BINDING-PROTEIN; IL-4 RECEPTOR; HIGH-AFFINITY; GAMMA-CHAIN; EXPRESSION; INFECTION; IDENTIFICATION; MACROPHAGES AB The human immunodeficiency virus type 1 (HIV-1) regulatory gene, tat, encodes an early transactivator protein (Tat) necessary for virus replication, We have reported that the HIV-1 tat gene can up-regulate interleukin 4 receptors (IL-4R) however, the mechanism of this up-regulation is not understood, We now show that in Raji cells, I-125-labeled IL-4 cross-linked to three proteins of 140, 70, and 63 kDa, which were immunoprecipitated with an antibody to the human IL-4R. Although this level of all three IL-4 binding proteins increased in tat-transfected cells, the binding characteristics of the IL-4R on control or mock transfected control and tat-transfected cells remained similar, The exogenous recombinant Tat protein or supernatant of tat transfected Raji cells also up-regulated the expression of the IL-4R on two renal cell carcinoma cell lines in a concentration-dependent manner. The actinomycin D chase experiments revealed that the half-lives of the IL-4R protein (t(1/2) 3.5 hr) and the mRNA transcripts (t(1/2) 2.5 hr) were similar in both control and tat-transfected cells, In contrast, nuclear run-on experiments revealed that the rate of the IL-4R mRNA transcription increased 3- to 5-fold in Raji-tat compared to Raji cells, These data indicate that the HIV-1 tat gene up-regulates IL-4R expression by increasing the transcription rate rather than posttranscriptional stabilization of either the mRNA or the protein, HIV-tat inducible exogenous tumor necrosis factor (TNF-alpha) did not up-regulate IL-4R and IL-4 inducible activation of signal transducers and activators of transcription (STAT-6) was not observed by Tat even though IL-4R were up-regulated, These results allow us to speculate that HIV-1 tat may interact directly with the IL-4R gene and up-regulate IL-4R transcription. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,LAB MOL TUMOR BIOL,BETHESDA,MD 20892. UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT MOL ONCOL,CYTOKINE RES SECT,HOUSTON,TX 77030. RI Aggarwal, Bharat/G-3388-2013 NR 64 TC 22 Z9 22 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 SEP 20 PY 1996 VL 12 IS 14 BP 1349 EP 1359 DI 10.1089/aid.1996.12.1349 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA VJ248 UT WOS:A1996VJ24800007 PM 8891114 ER PT J AU Hunyady, L Zhang, M Jagadeesh, G Bor, M Balla, T Catt, KJ AF Hunyady, L Zhang, M Jagadeesh, G Bor, M Balla, T Catt, KJ TI Dependence of agonist activation on a conserved apolar residue in the third intracellular loop of the AT(1) angiotensin receptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE G protein-coupled receptors; inositol phosphate signaling; receptor internalization; site-directed mutagenesis ID BETA-ADRENERGIC-RECEPTOR; ADRENAL GLOMERULOSA CELLS; PROTEIN-COUPLED RECEPTORS; SMOOTH-MUSCLE CELLS; II RECEPTOR; INDUCED INTERNALIZATION; SIGNAL-TRANSDUCTION; ALDOSTERONE SECRETION; POTENTIAL MECHANISM; TYROSINE RESIDUE AB The coupling of agonist-activated seven transmembrane domain receptors to G proteins is known to involve the amino-terminal region of their third cytoplasmic loop. Analysis of the amino acids in this region of the rat type 1a angiotensin (AT(1a)) receptor identified Leu-222 as an essential residue in receptor activation by the physiological agonist, angiotensin II (Ang II). Nonpolar replacements for Leu-222 yielded functionally intact AT(1) receptors, while polar or charged residues caused progressive impairment of Ang II-induced inositol phosphate generation. The decrease in agonist-induced signal generation was associated with a parallel reduction of receptor internalization, and was most pronounced for the Lys-222 mutant receptor. Although this mutant showed normal binding of the peptide antagonist, [Sar(1),Ile(8)]Ang II, its affinity for Ang II was markedly reduced, consistent with its inability to adopt the high-affinity conformation. A search revealed that many G(q)-coupled receptors contain an apolar amino acid (frequently leucine) in the position corresponding to Leu-222 of the AT(1) receptor. These findings suggest that such a conserved apolar residue in the third intracellular loop is a crucial element in the agonist-induced activation of the AT(1) and possibly many other G protein-coupled receptors. C1 NIH,ENDOCRINOL & REPROD RES BRANCH,NICHHD,BETHESDA,MD 20892. US FDA,DIV CARDIO RENAL DRUG PROD,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. OI Balla, Tamas/0000-0002-9077-3335 NR 54 TC 33 Z9 34 U1 1 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 SEP 17 PY 1996 VL 93 IS 19 BP 10040 EP 10045 DI 10.1073/pnas.93.19.10040 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VJ203 UT WOS:A1996VJ20300011 PM 8816747 ER PT J AU Rheinstein, PH AF Rheinstein, PH TI Seven tips for sun sense SO AMERICAN FAMILY PHYSICIAN LA English DT Article RP Rheinstein, PH (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD SEP 15 PY 1996 VL 54 IS 4 BP 1385 EP 1388 PG 4 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA VJ808 UT WOS:A1996VJ80800017 PM 8816578 ER PT J AU Khattri, R Sperling, AI Qian, DP Fitch, FW Shores, EW Love, PE Bluestone, JA AF Khattri, R Sperling, AI Qian, DP Fitch, FW Shores, EW Love, PE Bluestone, JA TI TCR-gamma delta cells in CD3 zeta-deficient mice contain Fc epsilon RI gamma in the receptor complex but are specifically unresponsive to antigen SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; ZETA-CHAIN; LYMPHOCYTES-T; INTRAEPITHELIAL LYMPHOCYTES; SIGNAL-TRANSDUCTION; MONOCLONAL-ANTIBODY; ACTIVATION; IDENTIFICATION; AFFINITY; CD3-ZETA AB Unlike TCR-alpha beta cells, TCR-gamma delta cells express a distinct member of the zeta family, the gamma-chain of Fc epsilon RI (Fc epsilon RI gamma) within the TCR complex. To study the role of the Fc epsilon RI gamma-chain in TCR-gamma delta cells, a TCR-gamma delta transgenic mouse (G8) has been crossed with CD3 zeta-chain-deficient mice (G8.zeta(-/-)). Thy-1(+) spleen and lymph node cells of these animals expressed low levels of CD3/TCR, These results suggested that the zeta-chain is required for effective TCR transport to the cell surface. In contrast, intraepithelial TCR-gamma delta cells of G8.zeta(-/-) mice expressed high levels of TCR. Immunoprecipitation with anti-CDS showed that Fc epsilon RI gamma-chains were associated with the TCR complex in T cells isolated from zeta-deficient mice, Although the Fc epsilon RI gamma-expressing T cells proliferated in response to stimulation by TCR-specific Abs including anti-CD3 epsilon, anti-pan gamma delta, and anti-V gamma 2 mAb, the G8.zeta(-/-) T cells did not respond to the G8-specific Ag(T10(b)), anti-Thy-1 mAb, or Con A, The unresponsiveness to the Ag was not due to the reduced TCR expression, because intraepithelial TCR-gamma delta cells from the zeta-deficient mice did not respond to Ag. The inability of the G8.zeta(-/-) T cells to respond to Ag could not be overcome by providing an anti-CD28 costimulatory signal or by adding exogenous rIL-2, Taken together, our data suggest that the Fc epsilon RI gamma-chain associates with the TCR-gamma delta complex in the absence of the zeta-chain, but it is not able to substitute for the zeta-chain for effective transport of TCR to the cell surface or functional responses to Ag. C1 UNIV CHICAGO,BEN MAY INST CANC RES,DEPT PATHOL,COMM IMMUNOL,CHICAGO,IL 60637. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. NICHHD,LAB MAMMALIAN GENES & DEV,NIH,BETHESDA,MD 20892. FU NHLBI NIH HHS [T32 HL 07605-11]; NIAID NIH HHS [R01 AI26847] NR 41 TC 8 Z9 11 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 SEP 15 PY 1996 VL 157 IS 6 BP 2320 EP 2327 PG 8 WC Immunology SC Immunology GA VL103 UT WOS:A1996VL10300013 PM 8805629 ER PT J AU Chen, SY Takeoka, Y Ansari, AA Boyd, R Klinman, DM Gershwin, ME AF Chen, SY Takeoka, Y Ansari, AA Boyd, R Klinman, DM Gershwin, ME TI The natural history of disease expression in CD4 and CD8 gene-deleted New Zealand black (NZB) mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; B-CELL ACTIVATION; T-CELLS; THYMIC MICROENVIRONMENT; AUTOIMMUNE-DISEASE; MURINE LUPUS; AUTOANTIBODIES; ANTIBODIES; ABNORMALITIES; DEFICIENT AB CD4 and CD8 gene-deleted New Zealand black (NZB) mice and, as controls, B6.CD4 -/-, B6.CD8 -/-, NZB, and B6 wild-type (wt) mice were studied for phenotypic and immunologic parameters to determine the contribution of CD4 and CD8 cell lineages in NZB mice, These studies suggest surprisingly that a number of abnormalities are not due to either CD4(+) or CD8(+) cell lineages but rather are most likely due to non-CD4(+) and -CD8(+) cell lineages and/or background genes. Such abnormalities include altered thymic architecture, decreased staining of MTS 33(+) medullary thymocytes, and an increased frequency of splenic IgM secretory cells, In contrast, deletion of either CD4(+) or CD8(+) cells appears to differentially influence immunologic function, Deletion of CD8(+) cells did not influence titers of spontaneously occurring anti-erythrocyte or anti-DNA autoantibodies. interestingly, 50% of NZ8.CD4 -/- mice contained levels of anti-erythrocyte IgG and anti-ssDNA IgM autoantibodies even without detectable CD4(+) cells, Such deletion of CD4(+) cells, while leading to marked decreases in the prototype cytokines that characterize Th1 and Th2 subsets in B6 mice, led to a marked increase in IFN-gamma and a moderate increase in IL-4 mRNA levels in NZB.CD4 -/- mice, These data suggest that whereas non-CD4(+) and -CD8(+) cell lineages and NZB background genes have a marked influence in the development of autoimmune abnormalities, CD4(+) cells appear to play a major role in influencing the cytokine environment, whereas CD8(+) cells appear to play a minor role. C1 UNIV CALIF DAVIS,SCH MED,DIV RHEUMATOL ALLERGY & CLIN IMMUNOL,DAVIS,CA 95616. EMORY UNIV,SCH MED,DEPT PATHOL,ATLANTA,GA 30322. MONASH UNIV,DEPT PATHOL & IMMUNOL,PRAHRAN,VIC 3181,AUSTRALIA. US FDA,DEPT HLTH & HUMAN SERV,PUBL HLTH SERV,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NIPPON ZOKI PHARMACEUT CO LTD,INST BIOACT SCI,YASHIRO,HYOGO,JAPAN. FU NIAMS NIH HHS [AR20816] NR 46 TC 29 Z9 31 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 SEP 15 PY 1996 VL 157 IS 6 BP 2676 EP 2684 PG 9 WC Immunology SC Immunology GA VL103 UT WOS:A1996VL10300057 PM 8805673 ER PT J AU Szekely, Z Konya, Z Becskei, A Goldring, WPD Perczel, A Penke, B Molnar, J Michejda, CF Aszalos, A Csizmadia, IG AF Szekely, Z Konya, Z Becskei, A Goldring, WPD Perczel, A Penke, B Molnar, J Michejda, CF Aszalos, A Csizmadia, IG TI Suggested binding mechanism of the HIV-gp120 to its CD4 receptor SO JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM LA English DT Article DE ab initio calculation; anti-HIV drug; CD4; gp120; docking; MM and MD simulations ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN GP120; MOLECULAR-ORBITAL METHODS; VALENCE BASIS-SETS; CRYSTAL-STRUCTURE; ATOMIC-STRUCTURE; PEPTIDE MODELS; SOLUBLE CD4; RAT CD4; HIV AB The molecular recognition and attachment of the CD4 molecule and the HIV envelope glycoprotein (gp120) might be described as a consecutive three-step molecular recognition process. (a) Long range interaction: electrostatic pre-orientation, (b) short range interaction: electronic attachment followed by a 'Locking-in' (via aromatic ring orientation) and (c) internal interaction (induced fit): conformational readjustment of the protein molecules. On the basis of the preliminary investigations (X-ray structures of CD4 and biological studies of CD4 and gp120 point mutants) we described a computational model. This approach consists of empirical calculations as well as ab initio level of quantum chemistry. The conformational analysis of the wild type and mutant CD4 molecules was supported by molecular mechanics and dynamics (Amber force field). The latter analysis involves the application of a novel method, the Amino Acid Conformation Assignment of Proteins (ACAP) software, developed for the notation of secondary protein structures. According to the cardinal role of the electrostatic factors during this interaction, several ab initio investigations were performed for better understanding of the recognition process on submolecular level. Using the above mentioned computational model, we could interpret the basic behaviours and predict some additional features of CD4-gp120 interaction, in spite of the missing gp120 X-ray structure. C1 UNIV TORONTO, DEPT CHEM, TORONTO, ON M5S 1A1, CANADA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM,MSL, MOL ASPECTS DRUG DESIGN SECT, FREDERICK, MD 21702 USA. ATTILA JOZSEF UNIV, DEPT APPL CHEM, H-6720 SZEGED, HUNGARY. EOTVOS LORAND UNIV, DEPT ORGAN CHEM, H-1518 BUDAPEST, HUNGARY. UNIV OXFORD, DEPT BIOCHEM, OXFORD OX1 3QU, ENGLAND. ALBERT SZENT GYORGYI MED UNIV, DEPT MICROBIOL, H-6720 SZEGED, HUNGARY. US FDA, CELL BIOL LABS, WASHINGTON, DC 20204 USA. RP Szekely, Z (reprint author), ALBERT SZENT GYORGYI MED UNIV, DEPT MED CHEM, DOM TER 8, H-6720 SZEGED, HUNGARY. RI Konya, Zoltan/C-2492-2009; OI Konya, Zoltan/0000-0002-9406-8596; Becskei, Attila/0000-0002-9462-0934 NR 41 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-1280 J9 J MOL STRUC-THEOCHEM JI Theochem-J. Mol. Struct. PD SEP 15 PY 1996 VL 367 BP 159 EP 186 DI 10.1016/S0166-1280(96)04501-0 PG 28 WC Chemistry, Physical SC Chemistry GA VV061 UT WOS:A1996VV06100019 ER PT J AU Brown, SL AF Brown, SL TI Lowered serum cholesterol and low mood - The link remains unproved SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID ASSOCIATION; TRIALS RP Brown, SL (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,1350 PICCARD DR,HFZ-541,ROCKVILLE,MD 20850, USA. NR 10 TC 18 Z9 19 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD SEP 14 PY 1996 VL 313 IS 7058 BP 637 EP 638 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VH165 UT WOS:A1996VH16500001 PM 8811745 ER PT J AU Debinski, W Miner, R Leland, P Obiri, NI Puri, RK AF Debinski, W Miner, R Leland, P Obiri, NI Puri, RK TI Receptor for interleukin (IL) 13 does not interact with IL4 but receptor for IL4 interacts with IL13 on human glioma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PSEUDOMONAS EXOTOXIN-A; SIGNAL-TRANSDUCTION; PROTEIN; AERUGINOSA; TOXIN; IMMUNOTOXIN; EXPRESSION; COMPONENT; THERAPY; MICE AB Recently, we have demonstrated that human (h) glioma cell Lines express large number of receptors (R) for interleukin 13 (IL13) (Debinski, W., Obiri, N. I., Powers, S. K., Pastan, L., and Purl, R. K. (1995) Clin. Cancer Res. 1, 1253-1258). These cells are extremely sensitive to a chimeric protein composed of hIL13 and a derivative of Pseudomonas exotoxin (PE), PE38QQR. We have found that the cytotoxicity of hIL13-PE38QQR was blocked by hIL13 but not by hIL4 on the U-251 MG and U-373 MG cells, contrary to what was observed on several adenocarcinoma cell lines. In the present study, we further explored interactions between receptor for IL13 and IL4 on glioma cells. Established human glioma cell lines, such as DBTRG MG, Hs 683, U-87 MG, SNB-19, and A-172, are very susceptible to hIL13-PE38QQR, and the action of the chimeric toxin is not blocked by hIL4 on all these cells either. Also, hIL4 is not a competitor for I-125-hIL13 binding sites on glioma cells. Of interest, a corresponding hIL4-based chimeric toxin, hIL4-PE38QQR, is poorly active or not active on all the tested glioma cell lines. When active, however, hIL4 toxin action was blocked by hIL13. hIL13 is a competitor for I-125-hIL14 binding in a competitive binding assay on glioma cells. hIL13 and hIL4 did not affect the growth of the tested glioma cell lines. Human glioblastoma multiforme explant cells exhibited similar responses to the chimeric toxins and interleukins when compared with that found in established glioma cultures. Our results suggest that the hIL13R on glioma cells is expressed in one predominant form, the form that does not interact with IL4. Thus, this type of hIL13R is apparently different from the one demonstrated previously on several adenocarcinoma cell lines. C1 US FDA,LAB MOL TUMOR BIOL,DIV CELLULAR & GENE THERAPIES,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. RP Debinski, W (reprint author), PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT SURG,DIV NEUROSURG,500 UNIV DR,HERSHEY,PA 17033, USA. NR 28 TC 83 Z9 84 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 SEP 13 PY 1996 VL 271 IS 37 BP 22428 EP 22433 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VG672 UT WOS:A1996VG67200025 PM 8798406 ER PT J AU Green, L Wysowski, DK Fourcroy, JL AF Green, L Wysowski, DK Fourcroy, JL TI Gynecomastia and breast cancer during finasteride therapy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Green, L (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 4 TC 33 Z9 33 U1 0 U2 1 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 SEP 12 PY 1996 VL 335 IS 11 BP 823 EP 823 DI 10.1056/NEJM199609123351116 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VF786 UT WOS:A1996VF78600025 PM 8778596 ER PT J AU Nightingale, SL AF Nightingale, SL TI Public meeting about medical product promotion on the Internet SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP Nightingale, SL (reprint author), US FDA,OFF HLTH AFFAIRS,FDA PARKLAWN BLDG,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 0 TC 3 Z9 3 U1 1 U2 1 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 SEP 11 PY 1996 VL 276 IS 10 BP 774 EP 774 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VF219 UT WOS:A1996VF21900006 ER PT J AU Nightingale, SL AF Nightingale, SL TI New fluoroquinolone warning label SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP Nightingale, SL (reprint author), US FDA, OFF HLTH AFFAIRS, FDA 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 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 11 PY 1996 VL 276 IS 10 BP 774 EP 774 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VF219 UT WOS:A1996VF21900007 ER PT J AU Nightingale, SL AF Nightingale, SL TI Urine-based HIV 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, FDA 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 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 11 PY 1996 VL 276 IS 10 BP 774 EP 774 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VF219 UT WOS:A1996VF21900008 ER PT J AU Razzaque, A Francillon, Y Jilly, PN Varricchio, F AF Razzaque, A Francillon, Y Jilly, PN Varricchio, F TI Detection of human herpesvirus 6 sequences in lymphoma tissues by immunohistochemistry and polymerase chain reactions SO CANCER LETTERS LA English DT Article DE human herpesvirus-6; transformation; lymphomas ID EPSTEIN-BARR-VIRUS; NON-HODGKINS-LYMPHOMA; LYMPHOPROLIFERATIVE DISORDERS; HHV-6; IDENTIFICATION; DNA; INFECTION; TRANSFORMATION; EXPRESSION; SALIVARY AB We have analyzed one Hodgkin's and six non-Hodgkin's lymphomas for the presence of human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) DNA by polymerase chain reaction (PCR) and antigens by immunohistochemistry. A large cell B-cell lymphoma and a T-cell lymphoma were positive for HHV-6 antigens by immunohistochemistry. Using PCR primers from the HHV-6 ZVH14 transforming DNA segment, all seven tumors were positive. EBV DNA was not detected by PCR using sequences from EBV internal repeat-3 region as primers. The data suggest an etiologic involvement of HHV-6 in some human lymphomas. Although all seven of the lymphoma tissues examined contained HHV-6 DNA, expression of HHV-B antigens was observed in only two cases, suggesting that expression of proteins was not required for transformation. C1 HOWARD UNIV,DEPT PATHOL,WASHINGTON,DC 20060. US FDA,CTR BIOL EVALUAT & RES,DIV BIOSTAT & EPIDEMIOL,ROCKVILLE,MD 20852. RP Razzaque, A (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 24 TC 3 Z9 3 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 SEP 10 PY 1996 VL 106 IS 2 BP 221 EP 226 DI 10.1016/0304-3835(96)04329-7 PG 6 WC Oncology SC Oncology GA VJ545 UT WOS:A1996VJ54500011 PM 8844976 ER PT J AU Leber, P AF Leber, P TI Observations and suggestions on antidementia drug development SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article; Proceedings Paper CT Fisher Symposium on Strategies for the Prevention of Alzheimer Disease, at Alzheimers Disease Research Planning Meeting III CY NOV 30-DEC 02, 1994 CL BETHESDA, MD DE drug product development; clinical trials; re-randomized design; randomized start design AB Recent advances in the theoretical neurosciences have suggested a number of novel strategies that might be applied to prevent and/or retard the progression of Alzheimer disease. Whether or not these interventions will succeed cannot be determined on theoretical grounds, however; the value of each new stratagem must be evaluated in patients with Alzheimer disease. How best to conduct clinical studies of disease-modifying treatments remains a controversial subject. The author reviews and compares two clinical trial designs that may prove useful in assessing whether or not a putative treatment actually modifies the course of dementia. RP Leber, P (reprint author), US FDA,CTR DRUG EVALUAT & RES,OFF NEW DRUG EVALUAT 1,DIV NEUROPHARMACOL DRUG PROD,ROCKVILLE,MD 20850, USA. NR 0 TC 46 Z9 47 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD FAL PY 1996 VL 10 SU 1 BP 31 EP 35 DI 10.1097/00002093-199601031-00009 PG 5 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA VF274 UT WOS:A1996VF27400009 PM 8876787 ER PT J AU Palmisano, B Bedford, RF AF Palmisano, B Bedford, RF TI Oralet (oral transmucosal fentanyl lozenges) SO ANESTHESIOLOGY LA English DT Editorial Material RP Palmisano, B (reprint author), US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3 BP A31 EP A31 PG 1 WC Anesthesiology SC Anesthesiology GA VK280 UT WOS:A1996VK28000002 ER PT J AU Fujito, BT Lytle, CD AF Fujito, BT Lytle, CD TI Elution of viruses by ionic and nonionic surfactants SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID MEMBRANE FILTERS; SURROGATE VIRUSES; BARRIER MATERIALS; POLIOVIRUS AB The ionic and nonionic surfactants sodium dodecyl sulfate and Triton X-100, respectively, eluted two viruses, phi X174 and PRD1, which were adsorbed to the ionic and nonionic binding membranes cationic polysulfone and nitrocellulose, respectively. Results indicated that complete elution was readily achieved only when combinations of surfactants and binding membranes were matched (i,e,, ionic-ionic or nonionic-nonionic). C1 US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857. THOMAS JEFFERSON HIGH SCH SCI & TECHNOL,ALEXANDRIA,VA 22312. NR 17 TC 16 Z9 17 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 SEP PY 1996 VL 62 IS 9 BP 3470 EP 3473 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA VF616 UT WOS:A1996VF61600063 PM 8795240 ER PT J AU Zhang, DL Hansen, EB Deck, J Heinze, TM Sutherland, JB Cerniglia, CE AF Zhang, DL Hansen, EB Deck, J Heinze, TM Sutherland, JB Cerniglia, CE TI Fungal biotransformation of the antihistamine azatadine by Cunninghamella elegans SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID MICROBIAL TRANSFORMATION; N-OXIDE; METABOLITES; URINE; DRUG AB The metabolism of the antihistamine azatadine by the zygomycete fungus Cunninghamella elegans ATCC 9245 was investigated. Within 72 h from the addition of the drug to 48-h-old cultures grown in Sabouraud dextrose broth, 95% of azatadine was biotransformed. Two major metabolites, 7-hydroxyazatadine (25%) and 8-hydroxyazatadine (50%), and two minor metabolites, N-desmethylazatadine and 9-hydroxyazatadine, were isolated by high-performance liquid chromatography and characterized by mass spectrometric and proton nuclear magnetic resonance spectroscopic analyses. C1 US FDA,NATL CTR TOXICOL RES,DIV MICROBIOL,JEFFERSON,AR 72079. US FDA,NATL CTR TOXICOL RES,DIV CHEM,JEFFERSON,AR 72079. US FDA,NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079. NR 14 TC 16 Z9 17 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 SEP PY 1996 VL 62 IS 9 BP 3477 EP 3479 PG 3 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA VF616 UT WOS:A1996VF61600065 PM 8795241 ER PT J AU Desai, VG Weindruch, R Hart, RW Feuers, RJ AF Desai, VG Weindruch, R Hart, RW Feuers, RJ TI Influences of age and dietary restriction on gastrocnemius electron transport system activities in mice SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE electron transport system; mitochondria; aging; dietary restriction; muscle; mouse ID RESPIRATORY-CHAIN FUNCTION; SKELETAL-MUSCLE; CALORIC RESTRICTION; FOOD RESTRICTION; MITOCHONDRIAL; METABOLISM; MUTATIONS; OXIDASE; RAT AB Alterations in the mitochondrial electron transport system (ETS) may contribute to aging, Dietary restriction (DR) provides a model to investigate retarded aging, ETS activities were measured in gastrocnemius from 10- and 20-month-old B6C3F(1) female mice fed either ad libitum (AL) or DR diets (40% < AL), Older (26 month old) AL mice were studied for complex IV, Activities of complexes I, III, and IV decreased 54-74% from PO to 20 months of age in AL mice. At 10 months, activities of complexes I, III, and IV were 33-64% lower in DR compared to AL mice, The K-m for ubiquinol-2 of complex III increased 29% by 20 months of age in AL mice while no change occurred in DR mice, The V-max of complex IV declined by 90% from 10 to 26 months of age in AL mice and this change was opposed by DR, Complex IV contains high- and low-affinity binding sites, The K-m for high-affinity sites was not influenced by age or diet through 20 months; however, the K-m was approximately twofold higher at 26 months in AL mice, The percentage of total binding sites which were of high affinity fell from 68% at 10 months in AL mice to 46% at 20 months and was even lower (33%) at 26 months, This value was 80% for DR mice at 10 and 20 months, These alterations with aging in mitochondrial ETS capacities may contribute to decreases in skeletal muscle function. (C) 1996 Academic Press, Inc. C1 NATL CTR TOXICOL RES,DIV GENET TOXICOL,JEFFERSON,AR 72079. UNIV WISCONSIN,DEPT MED,MADISON,WI 53706. UNIV WISCONSIN,VA GERIATR RES EDUC & CLIN CTR,MADISON,WI 53706. NR 29 TC 82 Z9 84 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP 1 PY 1996 VL 333 IS 1 BP 145 EP 151 DI 10.1006/abbi.1996.0375 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VD629 UT WOS:A1996VD62900019 PM 8806765 ER PT J AU Okada, S Rohan, PJ Miller, FW Love, LA AF Okada, S Rohan, PJ Miller, FW Love, LA TI Myopathies following ingestion of special nutritional products. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 US FDA,CBER,WASHINGTON,DC 20204. US FDA,CFSAN,WASHINGTON,DC 20204. 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 SEP PY 1996 VL 39 IS 9 SU S BP 136 EP 136 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300136 ER PT J AU Shamim, EA Rider, LG Okada, S Love, LA Targoff, IN Pandey, JP Song, YW Miller, FW AF Shamim, EA Rider, LG Okada, S Love, LA Targoff, IN Pandey, JP Song, YW Miller, FW TI Genetic risk factors for idiopathic inflammatory myopathy (IIM) differ between Caucasians and Koreans. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 FDA,CBER,BETHESDA,MD. OI Miller, Frederick/0000-0003-2831-9593 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 SEP PY 1996 VL 39 IS 9 SU S BP 425 EP 425 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300425 ER PT J AU Donnelly, RP Freeman, S Dickensheets, HL AF Donnelly, RP Freeman, S Dickensheets, HL TI Interleukin-10 up-regulates and interferon-gamma down-regulates production of soluble type-II tumor necrosis factor receptors by human monocytes. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1996 VL 39 IS 9 SU S BP 604 EP 604 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300606 ER PT J AU Katzper, M Katz, L Neuner, R AF Katzper, M Katz, L Neuner, R TI Analysis of individuals data using full and reduced joint counts. 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 SEP PY 1996 VL 39 IS 9 SU S BP 785 EP 785 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300786 ER PT J AU Ackermann, B Gohlke, F Herr, W Yu, DTY Raybourne, R zumBuschenfelde, KHM MarkerHermann, E AF Ackermann, B Gohlke, F Herr, W Yu, DTY Raybourne, R zumBuschenfelde, KHM MarkerHermann, E TI Quantification of TNF-alpha and IFN-gamma producing Yersinia urease beta-subunit specific CD8+ and CD4+ T cells using an elispot assay - A study in reactive arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV MAINZ,DEPT MED 1,D-6500 MAINZ,GERMANY. UNIV CALIF LOS ANGELES,DEPT RHEUMATOL,LOS ANGELES,CA 90095. US FDA,LAUREL,MD 20708. 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 SEP PY 1996 VL 39 IS 9 SU S BP 816 EP 816 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300817 ER PT J AU Gilkeson, G Pisetsky, D Klinman, D AF Gilkeson, G Pisetsky, D Klinman, D TI Bacterial DNA immunization of NZB/NZW F1 mice modulates systemic cytokine production. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 DUKE UNIV,MED CTR,DURHAM VAMC,MED RES SERV,DURHAM,NC 27710. US FDA,CTR BIOL,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 SEP PY 1996 VL 39 IS 9 SU S BP 911 EP 911 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300912 ER PT J AU Klinman, D Gilkeson, G Conover, J AF Klinman, D Gilkeson, G Conover, J TI Bacterial DNA induces cytokine and anti-DNA autoantibody production. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. DUKE UNIV,DURHAM,NC 27705. 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 SEP PY 1996 VL 39 IS 9 SU S BP 913 EP 913 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300914 ER PT J AU Gilkeson, G Cannon, C Goldman, D Petri, M AF Gilkeson, G Cannon, C Goldman, D Petri, M TI Correlation of a serum measure of nitric oxide production with lupus disease activity measures. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 DUKE UNIV,VAMC,MED RES SERV,DURHAM,NC 27710. JOHNS HOPKINS UNIV,BALTIMORE,MD 21205. US FDA,CTR BIOL,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 SEP PY 1996 VL 39 IS 9 SU S BP 1343 EP 1343 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301344 ER PT J AU Hagiwara, E Pando, J Ishigatsubo, Y Klinman, D AF Hagiwara, E Pando, J Ishigatsubo, Y Klinman, D TI Abnormal ratio of type 1: Type 2 cytokine secreting cells in patients with primary Sjogren's syndrome. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 YOKOHAMA CITY MED SCH,YOKOHAMA,KANAGAWA,JAPAN. NIH,CTR BIOL,FDA,BETHESDA,MD 20892. NIAMS,NIH,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 SEP PY 1996 VL 39 IS 9 SU S BP 1561 EP 1561 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301561 ER PT J AU Brown, K Petri, M Goldman, D AF Brown, K Petri, M Goldman, D TI Cutaneous manifestations of SLE: Associations with other manifestations of SLE and with smoking. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. US FDA,ROCKVILLE,MD 20852. 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 SEP PY 1996 VL 39 IS 9 SU S BP 1583 EP 1583 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301583 ER PT J AU Klinman, D Elias, K Shak, S Verthelyi, D AF Klinman, D Elias, K Shak, S Verthelyi, D TI DNAse treatment of DNA - Anti-DNA immune complexes in SLE. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 US FDA,CTR BIOL,BETHESDA,MD 20892. GENENTECH INC,S SAN FRANCISCO,CA 94080. 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 SEP PY 1996 VL 39 IS 9 SU S BP 1676 EP 1676 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301676 ER PT J AU Maximova, O Dragunsky, E Taffs, R Snoy, P Cogan, J Marsden, S Levenbook, I AF Maximova, O Dragunsky, E Taffs, R Snoy, P Cogan, J Marsden, S Levenbook, I TI Monkey neurovirulence test for live mumps vaccine SO BIOLOGICALS LA English DT Article C1 US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852. LA TARASSEVICH STANDARDIZAT & CONTROL MED PREPARA,MOSCOW 121002,RUSSIA. NATL INST BIOL STAND & CONTROLS,POTTERS BAR EN6 3QG,HERTS,ENGLAND. NR 2 TC 15 Z9 16 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 SEP PY 1996 VL 24 IS 3 BP 223 EP 224 DI 10.1006/biol.1996.0030 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA VZ364 UT WOS:A1996VZ36400029 PM 8978921 ER PT J AU Roscioli, NA Renshaw, CA Gilbert, AA Kerry, CF Probst, PG AF Roscioli, NA Renshaw, CA Gilbert, AA Kerry, CF Probst, PG TI Environmental monitoring considerations for biological manufacturing SO BIOPHARM-THE TECHNOLOGY & BUSINESS OF BIOPHARMACEUTICALS LA English DT Article AB Each manufacturing system requires a unique set of environmental parameters. This article provides guidance toward designing an environmental monitoring program for viable and nonviable particulate contaminants for all stages of biological product manufacturing. C1 US FDA,CTR BIOL EVALUAT & RES,OFF ESTAB LICENSING & PROD SURVEILLANCE,DIV ESTAB LICENSING,ROCKVILLE,MD 20852. NR 5 TC 1 Z9 1 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 SN 1040-8304 J9 BIOPHARM-TECHNOL BUS JI Biopharm-Technol. Bus. Biopharm. PD SEP PY 1996 VL 9 IS 8 BP 32 EP & PG 7 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA VX512 UT WOS:A1996VX51200006 ER PT J AU Feller, SE Pastor, RW AF Feller, SE Pastor, RW TI On simulating lipid bilayers with an applied surface tension: Periodic boundary conditions and undulations SO BIOPHYSICAL JOURNAL LA English DT Article ID MOLECULAR-DYNAMICS SIMULATION; ENTROPY-DRIVEN TENSION; LIQUID/LIQUID INTERFACES; COMPUTER-SIMULATION; BENDING ELASTICITY; FLUID MEMBRANES; VESICLES RP Feller, SE (reprint author), US FDA,BIOPHYS LAB,CBER,1041 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 32 TC 145 Z9 148 U1 0 U2 9 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 1996 VL 71 IS 3 BP 1350 EP 1355 PG 6 WC Biophysics SC Biophysics GA VF097 UT WOS:A1996VF09700022 PM 8874010 ER PT J AU Landi, MT Zocchetti, C Bernucci, I Kadlubar, FF Tannenbaum, S Skipper, P Bartsch, H Malaveille, C Shields, P Caporaso, NE Vineis, P AF Landi, MT Zocchetti, C Bernucci, I Kadlubar, FF Tannenbaum, S Skipper, P Bartsch, H Malaveille, C Shields, P Caporaso, NE Vineis, P TI Cytochrome P4501A2: Enzyme induction and genetic control in determining 4-aminobiphenyl-hemoglobin adduct levels SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; CAFFEINE URINARY METABOLITES; BLADDER-CANCER; JAPANESE POPULATION; HEMOGLOBIN ADDUCTS; CIGARETTE-SMOKING; DRUG-METABOLISM; ODDS RATIO; HUMAN LUNG; SMOKERS AB Cytochrome P4501A2 (CYP1A2) activity may be related to bladder cancer risk through metabolic activation of aromatic amines, such as 4-aminobiphenyl (ABP), to reactive intermediates that can form DNA and hemoglobin (Hb) adducts, In the context of a study on smoking and bladder cancer risk, 97 healthy male volunteers were investigated, CYP1A2-dependent N-oxidation activity was measured using a molar ratio of urinary caffeine metabolites [(paraxanthine + 1,7-dimethyluric acid)/caffeine] obtained between the fourth and fifth h after drinking a standardized cup of coffee, N-Oxidation activity was induced by blond tobacco smoke, meat consumption the dinner before the test, or more than four cups of coffee a day, The regular use of medication appeared associated with a decrease in N-oxidation levels. Age and alcohol consumption were not related with CYP1A2 activity, A polymorphic distribution of the CYP1A2 and N-acetyltransferase-2 (determined by the caffeine metabolite ratio 5-acetylamino-6-formylamino-3-methyluracil:1-methylxanthine) phenotypes was examined in relation to susceptibility to ABP-Hb adduct formation, Rapid oxidizers and subjects with the combined slow acetylator-rapid oxidizer phenotype showed the highest ABP-Hb adduct levels at a low smoking dose, Blond tobacco smokers exhibited higher adduct levels compared with black tobacco smokers, after adjustment for the quantity of cigarettes smoked. At the highest levels of smoking exposure, no major difference in ABP-Hb adduct levels was found among the different combinations of CYP1A2 and N-acetyltransferase-2 phenotypes, In a subset of only 45 available samples, no association was seen between the ABP-Hb adduct levels and the glutathione S-transferase M1 genotype. C1 IST CLIN PERFEZIONAMENTO, I-20122 MILAN, ITALY. UNIV TURIN, DIPARTIMENTO SCI BIOMED & ONCOL UMANA, I-10126 TURIN, ITALY. NATL CTR TOXICOL RES, JEFFERSON, AR 72079 USA. MIT, CAMBRIDGE, MA 02139 USA. GERMAN CANC RES CTR, D-69120 HEIDELBERG, GERMANY. INT AGCY RES CANC, F-69372 LYON, FRANCE. NIH, NATL CANC INST, HUMAN CARCINOGENESIS LAB, BETHESDA, MD 20892 USA. NIH, NATL CANC INST, GENET EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA. RP Landi, MT (reprint author), UNIV MILAN, EPIDEMIOL RES CTR, EPOCA, VIA S BARNABA 8, I-20122 MILAN, ITALY. RI Shields, Peter/I-1644-2012 NR 47 TC 58 Z9 59 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 1996 VL 5 IS 9 BP 693 EP 698 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VF687 UT WOS:A1996VF68700005 PM 8877060 ER PT J AU Kadlubar, FF Young, JF Lang, NP Caporaso, NE Sinha, R Landi, MT AF Kadlubar, FF Young, JF Lang, NP Caporaso, NE Sinha, R Landi, MT TI Correspondence re: Letter to the editor by B.K. Wang and W. Kalow on CYP1A2 phenotyping using caffeine. Cancer Epidemiol Biomarkers & Prev, vol 5, pg 231, 1996 SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Letter ID URINARY METABOLITES C1 ARKANSAS CANC RES CTR,LITTLE ROCK,AR 72205. NCI,BETHESDA,MD 20892. UNIV MILAN,EPIDEMIOL RES CTR,EPOCA,I-20122 MILAN,ITALY. RP Kadlubar, FF (reprint author), NATL CTR TOXICOL RES,DIV MOL EPIDEMIOL,3900 NCTR RD HFT-100,JEFFERSON,AR 72079, USA. NR 11 TC 7 Z9 7 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 1996 VL 5 IS 9 BP 757 EP 758 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VF687 UT WOS:A1996VF68700014 PM 8877069 ER PT J AU Moore, SK Zambrano, N Lynch, HT Lipkin, M Kopelovich, L AF Moore, SK Zambrano, N Lynch, HT Lipkin, M Kopelovich, L TI Absence of germline mutations in exons 5-9 of the p53 gene in patients with Li-Fraumeni-like (SBLA) and familial adenomatous polyposis heritable cancer syndromes SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID TUMOR-SUPPRESSOR GENE; CULTURED SKIN FIBROBLASTS; BREAST-CANCER; EXPRESSION; CHILDREN; CELLS; DNA; PREVALENCE; NEOPLASMS; SPECTRUM AB Although acquired mutations in the human p53 gene occur in many tumor types, germline mutations are rare. An exception is the occurrence of germline p53 mutations in a fraction of families afflicted with the Li-Fraumeni syndrome (LFS). Previous studies from our laboratory demonstrated increased levels of wild type p53 protein in skin fibroblasts (SF) of patients from heritable cancer syndrome, including familial adenomatous polyposis (FAP), neurofibromatosis type 1 (NF1), and bilateral retinoblastoma (bRB) (Kopelovich and DeLeo, 1984,1986). Here, we further address the association between germline p53 alterations and genetic predisposition to cancer in the SBLA syndrome and in FAP. DNA sequencing and single-stranded conformational polymorphism analysis (SSCP) were utilized to screen for the presence of mutations within exons 5-9 of the p53 gene in SF and in benign tumors. Thus we observed no germline mutations in exons 5-9 of the p53 gene in SF from SBLA or FAP patients, including the Gardner variant. In addition, we observed no acquired mutations in exons 5-9 of the p53 gene in benign tumors from FAP patients. In conclusion, we found no association between germline p53 mutations and SBLA or FAP. How mechanisms that involve nonmutational activation of the p53 protein might affect genetic predisposition to cancer remains to be established. C1 VET ADM MED CTR,BAY PINES,FL 33504. US FDA,CTR DRUG EVALUAT & RES,DIV METAB & ENDOCRINE DRUG PROD,ROCKVILLE,MD 20857. NATL CANC INST,NATL INST HLTH,CELL BIOL LABS,BETHESDA,MD. CREIGHTON CANC CTR,OMAHA,NE. CREIGHTON UNIV,SCH MED,DEPT PREVENT MED,OMAHA,NE 68178. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. UNIV S FLORIDA,COLL MED,DEPT BIOL MOL,TAMPA,FL. UNIV S FLORIDA,DEPT PATHOL,TAMPA,FL. RI Zambrano, Nicola/B-9352-2014 OI Zambrano, Nicola/0000-0001-9395-3481 NR 44 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 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD SEP PY 1996 VL 90 IS 2 BP 125 EP 129 DI 10.1016/S0165-4608(96)00072-6 PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA VJ108 UT WOS:A1996VJ10800006 PM 8830720 ER PT J AU Alexandrov, K Rojas, M Kadlubar, FF Lang, NP Bartsch, H AF Alexandrov, K Rojas, M Kadlubar, FF Lang, NP Bartsch, H TI Evidence of anti-benzo[a]pyrene diolepoxide-DNA adduct formation in human colon mucosa SO CARCINOGENESIS LA English DT Article ID COLORECTAL-CANCER; BENZO(A)PYRENE; SMOKING; VALIDATION; ACTIVATION; GENOTYPE; MOUSE; CELLS; RISK; FOOD AB As risk factors for colorectal cancer include consumption of foods potentially contaminated with polycyclic aromatic hydrocarbons (PAHs), the level of (+)-r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE] bound to DNA of human colon mucosa samples was quantified by a sensitive and specific HPLC/fluorescence method (Alexandrov et al., Cancer Res, 51, 6248-6253, 1992), (+)-anti-BPDE-DNA adducts were detected in four out of seven colon mucosa samples but not in any of 11 human pancreas samples from smokers and non-smokers. Adduct levels in human colon varied between 0.2 and 1.0 (+)-anti-BPDE-DNA adducts/10(8) nucleotides, Our results provide evidence that: (i) the DNA in human colon cells can be damaged by benzo[a]pyrene, possibly derived from diet and/or tobacco smoke; (ii) DNA adduct formation in human colon epithelium proceeds via the diol epoxide pathway; (iii) benzo[a]pyrene and other PAHs could play a role in the etiology of human colorectal cancer. C1 DEUTSCH KREBSFORSCHUNGSZENTRUM,DIV TOXICOL & CANC RISK FACTORS,D-69120 HEIDELBERG,GERMANY. NATL CTR TOXICOL RES,DIV MOL EPIDEMIOL,JEFFERSON,AR 72079. ARKANSAS CANC RES CTR,LITTLE ROCK,AR 72205. NR 26 TC 67 Z9 68 U1 0 U2 2 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 SEP PY 1996 VL 17 IS 9 BP 2081 EP 2083 DI 10.1093/carcin/17.9.2081 PG 3 WC Oncology SC Oncology GA VH728 UT WOS:A1996VH72800044 PM 8824539 ER PT J AU Hartman, AB VanDeVerg, LL Mainhart, CR Tall, BD SmithGill, SJ AF Hartman, AB VanDeVerg, LL Mainhart, CR Tall, BD SmithGill, SJ TI Specificity of monoclonal antibodies elicited by mucosal infection of BALB/c mice with virulent Shigella flexneri 2a SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID EVOKE KERATOCONJUNCTIVITIS; ESCHERICHIA-COLI; CLONES BINDING; GUINEA-PIGS; ANTIGENS; VACCINE; PROTECTION; EPITOPE; SONNEI; LIPOPOLYSACCHARIDES AB Protective immunity against shigellosis is thought to be determined by the O-antigen side chains of the lipopolysaccharide (LPS) molecule, To study possible common protective epitopes, monoclonal antibodies reacting with Shigella flexneri 2a LPS were generated from BALB/c mice infected ocularly with the virulent serotype 2a strain S. flexneri 2457T and tested against a panel of S. flexneri LPSs by enzyme-linked immunosorbent and immunoblot assays, Four monoclonal antibodies were identified, all of which showed restricted specificity patterns. Three different patterns of reactivity to LPS possessing the 3,4 group antigen were seen: (i) 2a only, (ii) 2a and 5a, and (iii) 2a, 4a, 5a, and Y. These results have implications for designing a Shigella vaccine that will be protective against related serotypes. Electron microscopy studies showed that the monoclonal antibodies bind to the bacterial surface in a patchy pattern, suggesting their potential use for examining the LPS distribution on the sun-face of the bacteria. C1 NIH,GENET LAB,BETHESDA,MD 20892. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. RP Hartman, AB (reprint author), WALTER REED ARMY INST RES,DEPT ENTER INFECT,WASHINGTON,DC 20307, USA. OI Tall, Ben/0000-0003-0399-3629 NR 34 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD SEP PY 1996 VL 3 IS 5 BP 584 EP 589 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VG961 UT WOS:A1996VG96100018 PM 8877140 ER PT J AU Hagiwara, E Adams, EM Plotz, PH Klinman, DM AF Hagiwara, E Adams, EM Plotz, PH Klinman, DM TI Abnormal numbers of cytokine producing cells in patients with polymyositis and dermatomyositis SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE polymyositis; dermatomyositis; cytokines ID SYSTEMIC LUPUS-ERYTHEMATOSUS; IDIOPATHIC INFLAMMATORY MYOPATHIES; RHEUMATOID-ARTHRITIS; IL-6; INTERLEUKIN-6; MUSCLE; BLOOD; QUANTITATION; LYMPHOCYTES; EXPRESSION AB Objective: To examine the constitutive pattern of cytokine production inpatients with polymyositis (PM) and dermatomyositis (DM). Methods. PBMC secreting the type 1 cytokines IL-2 and IFN gamma and the type 2 cytokines IL-6 and IL-10 were monitored by ELlspot assay. Results: The frequency of IFN gamma-secreting PBMC was reduced 2 - 20 fold in patients with PM and DM when compared to normal controls (p < 0.01). This change correlated inversely with disease activity (p < 0.01). PM and DM were also characterized by increased numbers of cells secreting IL-10. Patients with DM had fewer IL-2 (p < 0.03) and more IL-6 (p < 0.006) secreting cells than normal controls or patients with other myopathies. Conclusions: Abnormal patterns of cytokine production characterize patients with PM and DM. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,SECT RETROVIRAL IMMUNOL,BETHESDA,MD 20892. NIAMDSD,ARTHRITIS & RHEUMATISM BRANCH,NIH,BETHESDA,MD. NR 41 TC 16 Z9 18 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD SEP-OCT PY 1996 VL 14 IS 5 BP 485 EP 491 PG 7 WC Rheumatology SC Rheumatology GA VL365 UT WOS:A1996VL36500003 PM 8913649 ER PT J AU Kuipers, JG Raybourne, R Williams, KM Zeidler, H Yu, DTY AF Kuipers, JG Raybourne, R Williams, KM Zeidler, H Yu, DTY TI Requirements for HLA-B*2705-binding peptides with special regard to the transporter associated with antigen processing (TAP) SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE HLA-B27; TAP; spondarthritis; ankylosing spondylitis; reactive arthritis ID ANKYLOSING-SPONDYLITIS; HLA-B27; TRANSLOCATION; RECOGNITION; SPECIFICITY; MOLECULES; SELECTION; BINDING; MOUSE; RAT AB Objective. To refine the algorithms governing peptide presentation by HLA-B*2705 by analyzing: (i) the specificity of the human transporter associated with antigen processing (TAP) for HLA-B27 binding peptides; and (ii) the peptide binding affinity to HLA-B*2705. Methods. TAP-translocation was measured with a labeled reporter peptide containing an N-linked glycosylation acceptor site in Streptolysin O-permeabilized cells for a panel of HLA-B27 binding peptides. Peptide binding affinity was determined by peptide-induced stabilization of empty HLA-B*2705 expressed by the TAP-deficient cell line T2-B27. Results. Human TAP preferentiallu translocated analogues with residues leucine, isoleucine, methionine and arginine as the carboxy-terminal amino acids, whereas analogues with aspartic acid and serine were translocated poorly. The binding affinity to HLA-B*2705 of the poorly translocated aspartic acid and serine analogues was about 100-fold less compared to the parent HLA-B27 binding peptide. Conclusions. Human TAP shows considerable specificity for the C-terminus of potential HLA-B27 ligands. Nonamer peptides with aspartic acid and serine at the C-terminus are poorly translocated by the TAP and have low binding affinity for HLA-B*2705, and are therefore unlikely to become presented by HLA-B*2705. C1 US FDA,IMMUNOBIOL BRANCH,LAUREL,MD. UNIV CALIF LOS ANGELES,SCH MED,DIV RHEUMATOL,LOS ANGELES,CA. RP Kuipers, JG (reprint author), HANNOVER MED SCH,DIV RHEUMATOL,ABT RHEUMATOL,D-30623 HANNOVER,GERMANY. NR 21 TC 1 Z9 1 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD SEP-OCT PY 1996 VL 14 IS 5 BP 523 EP 529 PG 7 WC Rheumatology SC Rheumatology GA VL365 UT WOS:A1996VL36500008 PM 8913654 ER PT J AU Marshall, JL Richmond, E DeLap, RJ AF Marshall, JL Richmond, E DeLap, RJ TI Biochemical modulation in the treatment of advanced cancer: A study of combined leucovorin, fluorouracil, and iododeoxyuridine SO CLINICAL CANCER RESEARCH LA English DT Article ID ADVANCED COLORECTAL-CANCER; COLONY-STIMULATING FACTOR; PHASE-I; 5-FLUOROURACIL; 5-IODO-2'-DEOXYURIDINE; MYELOSUPPRESSION; RADIOTHERAPY; PHARMACOLOGY; CHEMOTHERAPY; COMBINATION AB Multiple studies have shown that leucovorin-fluorouracil regimens are modestly superior to fluorouracil alone in the treatment of advanced colorectal cancer. Laboratory data suggest that iododeoxyuridine could further enhance the efficacy of leucovorin-fluorouracil regimens. This report describes the Phase I clinical evaluation of a leucovorin-fluorouracil-iododeoxyuridine chemotherapy regimen. Twenty-four patients received treatment with leucovorin (500 mg/m(2)), fluorouracil (500 mg/m(2)), and iododeoxyuridine (escalating doses) on days 1 and 8 of a 21-day cycle. The maximum tolerated dose of iododeoxyuridine was 1200 mg/m(2), with a recommended Phase II dose of 1000 mg/m(2). Myelosuppression (leukopenia) was dose limiting; other commonly observed treatment toxicities were nausea/vomiting, mucositis, and hyperlacrimation. Although the 1200 mg/m(2) dose was tolerated during the initial few cycles of therapy, chronic administration could not be maintained secondary to dose-limiting neutropenia. Since neutropenia was dose limiting, in a follow-up study, 10 patients received a modified regimen (treatment on days 1 and 6 instead of days 1 and 8) with the addition of granulocyte colony-stimulating factor (days 8-19). The addition of granulocyte colony-stimulating factor, however, did not permit further escalation of the iododeoxyuridine dose. Three partial responses and six minor responses were observed. Phase II studies of this regimen are ongoing in advanced colorectal and advanced pancreatic cancer to determine response rates in these diseases. C1 US FDA,DIV ONCOL DRUG PROD,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20854. RP Marshall, JL (reprint author), GEORGETOWN UNIV HOSP,VINCENT T LOMBARDI CANC RES CTR,DEPT MED,DIV HEMATOL ONCOL,PODIUM LEVEL,WASHINGTON,DC 20007, USA. NR 29 TC 2 Z9 2 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 SEP PY 1996 VL 2 IS 9 BP 1475 EP 1480 PG 6 WC Oncology SC Oncology GA VH107 UT WOS:A1996VH10700006 PM 9816323 ER PT J AU Anderson, LW Chen, TL Colvin, OM Grochow, LB Collins, JM Kennedy, MJ Strong, JM AF Anderson, LW Chen, TL Colvin, OM Grochow, LB Collins, JM Kennedy, MJ Strong, JM TI Cyclophosphamide and 4-hydroxycyclophosphamide/aldophosphamide kinetics in patients receiving high-dose cyclophosphamide chemotherapy SO CLINICAL CANCER RESEARCH LA English DT Article ID BONE-MARROW TRANSPLANTATION; METASTATIC BREAST-CANCER; PLASMA HALF-LIFE; PHASE-I TRIAL; PHARMACOKINETICS; METABOLITES; IFOSFAMIDE; ETOPOSIDE; BLOOD AB Using a recently developed gas chromatography and mass spectrometry method to determine whole-blood cyclophosphamide (CP) and 4-hydroxycyclophosphamide/aldophosphamide (4-HO-CP/AP) concentrations, we investigated their pharmacokinetics in women receiving CP therapy. Patients (n = 18) received one or two courses of CP: (a) a 90-min i.v. infusion (4 g/m(2)) followed by a 96-h i.v. infusion (6 g/m(2)) in combination with high-dose thiotepa; or (b) a 96-h i.v. infusion (6 g/m(2)) in combination with high-dose thiotepa. Whole-blood exposures to CP [area under the whole blood concentration versus time curve (AUC(CP))] and 4-HO-CP/AP (AUC(4HOCP)) between courses 1 and 2 were compared after normalization to dose (g/m(2)). A nonproportional increase was observed for the AUC(CP) between the first course [1112 mu M . h/g/m(2) +/- 14% coefficient of variation (CV)] and the second course (1579 mu M . h/g/m(2) +/- 25% CV) (P < 0.001). In contrast, the AUC(4HOCP) (27 mu M . h/g/m(2) +/- 25% CV) determined for the first course was 29% higher than the AUC(4HOCP) (21 mu M h/g/m(2) +/- 26% CV) for the second course (P < 0.01). The interpatient whole-blood exposures to both CP and 4-HO-CP/AP were remarkably consistent in this patient population with percent CVs ranging from 14 to 28%. Because thiotepa (800 mg/m(2)) was administered simultaneously with CP during the second course of treatment, possible inhibition of CP metabolism by thiotepa was investigated using human liver microsomes in vitro. IC50 values determined for inhibition of CP metabolism in three individual liver donors ranged from 1.0 to 40 mu M. However, the clinical relevance of this observation has not been established. C1 US FDA,DIV CLIN PHARMACOL RES,CTR DRUG EVALUAT & RES,OTR,LAUREL,MD 20708. JOHNS HOPKINS UNIV,CTR ONCOL,SCH MED,BALTIMORE,MD 21287. FU NCI NIH HHS [CA63437, CA15396] NR 30 TC 34 Z9 34 U1 0 U2 6 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 SEP PY 1996 VL 2 IS 9 BP 1481 EP 1487 PG 7 WC Oncology SC Oncology GA VH107 UT WOS:A1996VH10700007 PM 9816324 ER PT J AU Torchin, CD McNeilly, PJ Kapetanovic, IM Strong, JM Kupferberg, HJ AF Torchin, CD McNeilly, PJ Kapetanovic, IM Strong, JM Kupferberg, HJ TI Stereoselective metabolism of a new anticonvulsant drug candidate, losigamone, by human liver microsomes SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID ENANTIOMER-ENANTIOMER INTERACTION; RAT; (S)-PROPAFENONE; (R)-PROPAFENONE; PHARMACOLOGY; MECHANISM; ISOMERS AB Losigamone (LSG) is a new candidate anticonvulsant drug undergoing preclinical and clinical development. Metabolism of racemic (+/-)-LSG and its two enantiomers, AO-242 [(+)-LSG] and AO-294 [(-)-LSG], was studied using human liver microsomes and recombinant cytochrome P450 isozymes. HPLC with both UV and electrochemical detection was used for analysis of the incubation media. Five metabolites (M1, M2, M3, M4, and M5) were generated from racemic (+/-)-LSG by both human liver microsomes and recombinant enzymes. Stereoselective metabolism was observed when each enantiomer was incubated separately with human liver microsomes. M1 was the major metabolite produced from (+)-LSG, whereas M3, M4, and M5 were primarily produced from (-)-LSG. The production of M1 from (+)-LSG was markedly inhibited by (-)-LSG, indicating a metabolic enantiomer/enantiomer interaction. (+/-)-LSG enantiomers were selectively metabolized by recombinant cytochrome P450 2A6, and the metabolism of (+)-LSG and (-)-LSG by human liver microsomes was preferentially inhibited by coumarin, a cytochrome P450 2A6-selective compound. C1 NINCDS,EPILEPSY BRANCH,NIH,BETHESDA,MD 20892. US FDA,CTR DRUG EVALUAT & RES,OFF PHARMACEUT SCI,DIV CLIN PHARMACOL RES,ROCKVILLE,MD 20857. NR 23 TC 29 Z9 29 U1 0 U2 0 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 SEP PY 1996 VL 24 IS 9 BP 1002 EP 1008 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VH337 UT WOS:A1996VH33700012 PM 8886611 ER PT J AU Chen, JJ Lensing, S AF Chen, JJ Lensing, S TI Causal modelling of multivariate outcomes from developmental toxicity experiments SO ENVIRONMENTAL AND ECOLOGICAL STATISTICS LA English DT Article DE correlation; path analysis; structural equation modelling; 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) ID QUANTITATIVE RISK ASSESSMENT; DOSE-RESPONSE MODEL; FETAL WEIGHT; MALFORMATION; TERATOLOGY; DISCRETE; MICE AB Exposure to developmental toxicants may cause foetal malformations, increase foetal death or resorption and reduce foetal weight. The correlations among these developmental endpoints have been reported, but their causal relationships have not been investigated. Structural equation models (path models) were applied to study the patterns of causation among the four developmental outcomes, number of viable foetuses, number of malformations, number of deaths/resorptions, and average foetal weight; these outcomes were modelled as response variables with the dose level and number of implants (litter size) modelled as independent variables. Three hypothesized path models were fitted to developmental toxicity data from a study of the herbicide 2,4,5-T exposure in mice. One model, which hypothesized that foetal weight, implicitly a mechanism such as cellular growth, affects both malformations and death/resorption (equivalently, viability) with no causation relationship between malformation and death/resorption, described data consistently well for three strains of mice. The most consistent relationship found was a strong direct effect of foetal weight on malformations, and the correlation between malformations and death/resorption (or reduced viability) was likely spurious. C1 US FDA,NATL CTR TOXICOL RES,COMP SCI CORP,JEFFERSON,AR 72079. RP Chen, JJ (reprint author), US FDA,NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,JEFFERSON,AR 72079, USA. NR 22 TC 5 Z9 5 U1 0 U2 1 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 1352-8505 J9 ENVIRON ECOL STAT JI Environ. Ecol. Stat. PD SEP PY 1996 VL 3 IS 3 BP 207 EP 218 DI 10.1007/BF00453010 PG 12 WC Environmental Sciences; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Environmental Sciences & Ecology; Mathematics GA VM417 UT WOS:A1996VM41700004 ER PT J AU Chen, JJ Li, LA Jackson, CD AF Chen, JJ Li, LA Jackson, CD TI Analysis of quantal response data from mixture experiments SO ENVIRONMETRICS LA English DT Article DE Becker model; Cox polynomial; dose addition; Scheffe polynomial; slack model ID MODELS AB This paper presents a logistic regression procedure for the analysis of mixture data. The design of the mixture experiment is based on the simplex-lattice designs where the components represent the proportions of a mixture, i.e. each component is expressed as a fraction of the mixture with the sum equal to one. The Scheffe (1958) and Cox (1971) polynomial and Becker (1968) non-polynomial forms are used to model relationships between the expected response and individual components of the mixture. In a three components mixture it was shown that if one component is completely linear with the remaining two components, then the proper representation of such a system is the Becker non-polynomial model. An experimental data set designed to study the interrelating effects of calories from dietary fat, carbohydrate and fibre on tumour incidence is used to illustrate the analysis and the additive effect of the fibre component. Each mixture (diet) of fat, carbohydrate and fibre was administered to provide the same total caloric consumption. C1 ACAD SINICA,INST STAT SCI,TAIPEI 11529,TAIWAN. US FDA,NATL CTR TOXICOL RES,DIV NUTR TOXICOL,JEFFERSON,AR 72079. RP Chen, JJ (reprint author), US FDA,NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,JEFFERSON,AR 72079, USA. NR 13 TC 11 Z9 11 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 SEP-OCT PY 1996 VL 7 IS 5 BP 503 EP 512 PG 10 WC Environmental Sciences; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Environmental Sciences & Ecology; Mathematics GA VJ626 UT WOS:A1996VJ62600004 ER PT J AU Danelli, MGM Alves, CMA Bastos, RC Batoreu, NM Barroso, DE Peralta, JM Frasch, CE AF Danelli, MGM Alves, CMA Bastos, RC Batoreu, NM Barroso, DE Peralta, JM Frasch, CE TI Human immune response to epitopes on the meningococcal outer membrane class 5 protein following natural infection SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE monoclonal antibody; Neisseria meningitidis; class 5 protein ID GROUP-B POLYSACCHARIDE; NEISSERIA-MENINGITIDIS; GEL-ELECTROPHORESIS; ANTIBODY-RESPONSE; ANTIGENS; VACCINE; CARRIERS; COMPLEX; GROWTH; CLONE AB Two monoclonal antibodies (mAbs) were produced against a serogroup B Neisseria meningitidis strain. These mAbs recognized two epitopes in the class 5 outer membrane proteins (OMP), designated P5.7 and P5.Bm, and were able to kill the homologous strain through complement activation. Both epitopes were surface exposed and 68% of group B meningococcal clinical isolates had one or both epitopes present in their class 5 OMP. Antibodies to one or both epitopes were demonstrated in 17 patients with meningococcal meningitis using an ELISA inhibition assay. Of the 17 paired sera, 41% and 29% of the acute-phase sera had antibodies to the P5.7 and P5.Bm epitopes, respectively. Immunoglobulin G to P5.Bm were found in all 17 convalescent-phase sera while specific antibodies against P5.7 were only found in 6 of these sera. These results demonstrate the potential importance of the P5.Bm and P5.7 epitopes on the class 5 OMP as candidates for vaccine composition. C1 UNIV FED RIO DE JANEIRO,INST MICROBIOL,BR-21941 RIO JANEIRO,BRAZIL. UNIV FED RIO DE JANEIRO,FDN OSWALDO CRUZ,INST TECNOL IMUNOBIOL BIOMANGUINHOS,RIO JANEIRO,BRAZIL. UNIV FED RURAL RIO DE JANEIRO,INST VET,DEPT EPIDEMIOL & SAUDE PUBL,RIO JANEIRO,BRAZIL. FDN OSWALDO CRUZ,INST OSWALDO CRUZ,DEPT TROP MED,RIO JANEIRO,BRAZIL. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. NR 32 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD SEP PY 1996 VL 15 IS 2-3 BP 159 EP 168 DI 10.1016/0928-8244(96)00058-2 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VG614 UT WOS:A1996VG61400013 PM 8880142 ER PT J AU Pennington, JAT AF Pennington, JAT TI Issues of food description SO FOOD CHEMISTRY LA English DT Article; Proceedings Paper CT 2nd International Food Data Base Conference on Food Composition Research - The Broader Context CY AUG 28-30, 1995 CL LAHTI, FINLAND ID INTERNATIONAL INTERFACE STANDARD; DATABASES AB Food names and descriptions identify and distinguish among foods listed in databases. Descriptive terms may be captured in free form with the food name and in faceted systems. The INFOODS Food Description System is faceted with free text. The International Interface (which includes LANGUAL) is a faceted system with standardized vocabulary. Faceted systems provide a checklist to fully describe foods, and they allow for retrievals and matching of foods among databases. On-line dictionaries can be used to clarify implicit and complex food names. Relevant descriptive information varies among foods and food types. Information about cooking methods, ingredients, recipes, cuisine and preparation location is important to fully define some foods. Sample descriptions (as opposed to food descriptions) identify the products analysed in the laboratory. Market share and default entries should be clearly identified. Pictures of foods (hard-copy or computerized) are useful for product identification. A universal system to describe foods will enhance the sharing and exchange of food composition data. Published by Elsevier Science Ltd C1 US FDA,WASHINGTON,DC 20204. RP Pennington, JAT (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 8 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0308-8146 J9 FOOD CHEM JI Food Chem. PD SEP PY 1996 VL 57 IS 1 BP 145 EP 148 DI 10.1016/0308-8146(96)00152-5 PG 4 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA VR298 UT WOS:A1996VR29800023 ER PT J AU Gaylor, DW AF Gaylor, DW TI Comments on the EPA uncertainty factor workshop SO HUMAN AND ECOLOGICAL RISK ASSESSMENT LA English DT Letter RP Gaylor, DW (reprint author), US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 3 TC 0 Z9 2 U1 0 U2 0 PU CRC PRESS INC PI BOCA RATON PA 2000 CORPORATE BLVD NW, JOURNALS CUSTOMER SERVICE, BOCA RATON, FL 33431 SN 1080-7039 J9 HUM ECOL RISK ASSESS JI Hum. Ecol. Risk Assess. PD SEP PY 1996 VL 2 IS 3 BP 405 EP 406 PG 2 WC Biodiversity Conservation; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA WT986 UT WOS:A1996WT98600002 ER PT J AU Ngoh, MA Cullison, R AF Ngoh, MA Cullison, R TI Determination of trichlorfon and dichlorvos residues in shrimp using gas chromatography with nitrogen-phosphorus detection SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Trichlorfon; dichlorvos; shrimp; gas chromatography; nitrogen-phosphorus detector ID ATLANTIC SALMON; LICE AB A method capable of quantifying trichlorfon and dichlorvos in shrimp at concentrations of 20-80 ng/g has been developed. Ground shrimp is homogenized in ethyl acetate and centrifuged. The supernatant is dried completely on a rotatory evaporator. The extract is dissolved in petroleum ether, concentrated on a solid phase extraction column, and analyzed by gas chromatography using a cool on-column inlet and a nitrogen-phosphorus detector. The analytes are separated from matrix components using a thermal gradient on a (cyanopropyl)phenyl-methylpolysiloxane column. The method was validated with control shrimp fortified at 20, 40, and 80 ng/g trichlorfon and dichlorvos. The average recoveries and intralaboratory coefficients of variations were 50-83% and 15-21% respectively. RP Ngoh, MA (reprint author), US FDA,CTR VET MED,BELTSVILLE,MD 20705, USA. NR 21 TC 7 Z9 7 U1 1 U2 6 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 SEP PY 1996 VL 44 IS 9 BP 2686 EP 2689 DI 10.1021/jf960194v PG 4 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA VH807 UT WOS:A1996VH80700039 ER PT J AU DeVeau, EJI AF DeVeau, EJI TI Determination of phenylbutazone residues in bovine milk by liquid chromatography with UV detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PHARMACOKINETICS; METABOLISM; EXCRETION; HORSE AB A published liquid chromatographic (LC) method was modified for quantitation of phenylbutazone (PBZ) residues in the range of 25-300 ng/mL in bovine milk. Milk samples (1 mL) were diluted with absolute ethanol and 25% NH4OH. Diethyl ether and petroleum ether were added sequentially to the milk extract and the mixture was agitated on a Vortex mixer to partition out milk fat. The organic phase was removed and discarded. Tetrahydro-furan-hexane (1 + 4) was added to the aqueous phase and the extract was acidified with 3M HCl. The samples were mixed on a Vortex mixer for 30 min, and centrifuged. The organic layer, containing PBZ, was transferred to a clean test tube. The organic solvents were evaporated to dryness under a stream of N-2 at room temperature. The resulting extract was dissolved in 1 mL mobile phase and filtered before injection. The chromatographic system was a C-18 reversed-phase column connected to a UV detector set at 264 nm, Recoveries of PBZ from raw bovine milk fortified at 25-300 ng/mL ranged from 79 to 84%; relative standard deviations (RSDs) ranged from 6 to 7%. The RSDs for incurred PBZ quantitated from 34 to 229 ng/mL ranged from 1 to 4%. RP DeVeau, EJI (reprint author), US FDA,CTR VET MED,BARC E,BLDG 328A,BELTSVILLE,MD 20705, USA. NR 8 TC 15 Z9 16 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 SEP-OCT PY 1996 VL 79 IS 5 BP 1050 EP 1053 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA VJ030 UT WOS:A1996VJ03000005 PM 8823913 ER PT J AU Heller, DN AF Heller, DN TI Determination and confirmation of pirlimycin residue in bovine milk and liver by liquid chromatography thermospray mass spectrometry: Interlaboratory study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Three laboratories participated in trials of methods to determine and confirm pirlimycin residue in bovine milk and liver The methods used liquid chromatography/thermospray mass spectrometry (LC/MS) with an internal standard to measure residue concentration. The internal standard was isopirlimycin, a stereoisomer of pirlimycin, which was resolved chromatographically. Determinative procedures were validated by replicate analyses of negative control, fortified control, and residue-incurred milk. For the milk method, average corrected recoveries (and coefficients of variation, CVs) were 83-113% (CV, 7.5-15.4%) at 0.2 ppm, 91-98% (CV, 3.4-18.5%) at 0.4 ppm, and 89-102% (CV, 8.8-22.9%) at 0.8 ppm. For the liver method, average corrected recoveries were 94-103% (CV, 2.2-7.1%) at 0.25 ppm, 87-94% (CV, 4.8-10.3%) at 0.5 ppm, and 96-101% (CV, 5.5-6.9%) at 1.0 ppm. There were no interferences in control samples of either matrix. Pirlimycin was confirmed by matching the retention time and relative abundances of 4 ions from sample extracts to corresponding values obtained for pirlimycin standard. Pirlimycin was confirmed in ail residue-incurred samples and all samples fortified at regulatory tolerances (0.4 ppm in milk and 0.5 ppm in liver) by 2 of the 3 laboratories and in most samples by the third laboratory. RP Heller, DN (reprint author), US FDA,CTR VET MED,BARC E,BLDG 328A,BELTSVILLE,MD 20705, USA. NR 6 TC 4 Z9 5 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 SEP-OCT PY 1996 VL 79 IS 5 BP 1054 EP 1061 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA VJ030 UT WOS:A1996VJ03000006 PM 8823914 ER PT J AU Mossoba, MM Adams, S Roach, JAG Trucksess, MW AF Mossoba, MM Adams, S Roach, JAG Trucksess, MW TI Analysis of trichothecene mycotoxins in contaminated grains by gas chromatography matrix isolation Fourier transform infrared spectroscopy and gas chromatography mass spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID DEOXYNIVALENOL; QUANTITATION; WHEAT; NIVALENOL; BARLEY; FOODS; CORN AB Gas chromatography/matrix isolation/fourier transform infrared (GC/MI/FTIR) spectroscopy and GC/mass spectrometry (MS) were used to confirm the identities of trimethylsilyl (TMS) derivatives of trichothecene mycotoxins in naturally contaminated grains. infrared spectral bands observed in the fingerprint region were unique for 10 trichothecene standards. Characteristic absorption bands were observed for the ester (near 1750 cm(-1)) and ketone (near 1700 cm(-1)) carbonyl stretching vibrations, the acetate CH3 symmetric bend (1370 cm(-1)), the epoxide ring (1262 cm(-1)), the trimethylsilyl CH3 in-plane deformation (1253 cm(-1)), the ester (O)C-O asymmetric stretching vibration (near 1244 cm(-1)), and several other bands including intense features due to the TMS function. Infrared bands observed under cryogenic matrix isolation conditions were compared with those found at room temperature in a potassium bromide matrix for 5 of these standards. Identities of deoxynivalenol (DON) from barley and mixed feed, nivalenol from wheat and barley, and DON and fusarenon-x from sweet corn were confirmed by comparison of their infrared spectral bands with those of standards. The identity of DON in the same test samples of sweet corn was confirmed further by GC/MS. GC/MS was also used to quantitate the levels of DON (67-455 ppm) in sweet corn test samples. C1 US FDA,DIV NAT PROD,WASHINGTON,DC 20204. RP Mossoba, MM (reprint author), US FDA,DIV GEN SCI SUPPORT,WASHINGTON,DC 20204, USA. NR 20 TC 22 Z9 22 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 SEP-OCT PY 1996 VL 79 IS 5 BP 1116 EP 1123 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA VJ030 UT WOS:A1996VJ03000014 PM 8823920 ER PT J AU Anderson, DL Cunningham, WC AF Anderson, DL Cunningham, WC TI Nondestructive determination of lead, cadmium, tin, antimony, and barium in ceramic glazes by radioisotope X-ray fluorescence spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ELEMENTS AB Quantitation capabilities of radioisotope X-ray fluorescence spectrometry (RXRFS) for determining lead, cadmium, tin, antimony, and barium in ceramic glazes were investigated. Twenty-one air-dried glazes and 85 fired glazes on test tiles were analyzed by using Cd-109 and Co-57 excitation sources. Accurate Pb determinations, with limits of detection (LODs) of about 0.3 mg/cm(2) for 5 min counting times, were achieved by using the 75 keV K-alpha 1 X-ray photopeak and a Pb foil calibration proce dure. Cd, Sn, Sb, and Ba concentrations were determined with LODs from about 0.5 to 1.5 mg/cm(2), For Pb and Ba, results obtained by using absorption corrections based only on element concentrations determined by RXRFS and an iterative approach led to analytical biases of less than or equal to 4% relative to results obtained by using corrections based on known total element compositions. Biases were more severe for Cd, Sn, and Sb because lower X-ray energies were involved and sensitivities varied as a function of matrix Pb content. Pb concentrations were above LODs (1.3-40 mg/cm(2)) in 39 of 47 fired ''food-safe'' glazes and in 33 of the other 38 fired glazes (0.4-39 mg/cm(2)). RP Anderson, DL (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,ELEMENTAL RES BRANCH,WASHINGTON,DC 20204, USA. NR 17 TC 11 Z9 11 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 SEP-OCT PY 1996 VL 79 IS 5 BP 1141 EP 1157 PG 17 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA VJ030 UT WOS:A1996VJ03000018 PM 8823923 ER PT J AU Cook, KK AF Cook, KK TI Determination of selenium in infant formula and enteral formula by dry ash graphite furnace atomic absorption spectrometry with deuterium background correction SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID SOLVENT-EXTRACTION; ANIMAL-TISSUES; WET DIGESTION; PALLADIUM; MODIFIER; FOODS; MILK; ACID AB A method was developed to determine selenium in infant formula using a graphite furnace equipped with deuterium background correction after dry ashing. The method circumvents the use of perchloric acid, 2,3-diaminonapthalene (DAN) and hydride generation without the use of Zeeman background correction, Twelve commercial infant and enteral formulas and corresponding spiked products (30-500 ng) were analyzed in triplicate for Se to evaluate this method. All test portions were digested on a hot plate after addition of magnesium nitrate-nitric acid. Following heating, digests were evaporated to dryness and placed in a 500 degrees C muffle furnace for 30 min to complete ashing. All Se was converted to Se+4 by dissolving the ash in HCl (5 + 1) and holding the solution for 20 min in a 60 degrees C water bath. Se+4 was subsequently reduced to Se-0 with ascorbic acid and collected on a membrane filter. The membrane filters were digested in a small volume of nitric acid in a microwave oven. Following digestion, contents of the vessels were diluted and analyzed for Se by graphite furnace atomic absorption spectrometry. Selenium standards in starch or in unfortified formula containing trace levels of Se were carried through the entire process. The recovery range for Se was 85-127%, and analyzed reference materials fell within their certified range for Se. This method is as sensitive (detection limit 0.44 ng Se/g) as methods reported in the literature and may be applicable to other foods. RP Cook, KK (reprint author), US FDA,DIV SCI & APPL TECHNOL,OFF FOOD LABELING,200 C ST SW,WASHINGTON,DC 20204, USA. NR 29 TC 5 Z9 5 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 SEP-OCT PY 1996 VL 79 IS 5 BP 1162 EP 1166 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA VJ030 UT WOS:A1996VJ03000020 PM 8823924 ER PT J AU Firestone, D Fehringer, NV Walters, SM Kozara, RJ Ayres, RJ Ogger, JD Schneider, LF Glidden, RM Ahlrep, JR Brown, PJ Ford, SE Davy, RA Gulick, DJ McCullough, BH Sittig, RA Smith, PV Syvertson, CN Barber, MR AF Firestone, D Fehringer, NV Walters, SM Kozara, RJ Ayres, RJ Ogger, JD Schneider, LF Glidden, RM Ahlrep, JR Brown, PJ Ford, SE Davy, RA Gulick, DJ McCullough, BH Sittig, RA Smith, PV Syvertson, CN Barber, MR TI TCDD residues in fish and shellfish from US waterways SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID CAPILLARY GAS-CHROMATOGRAPHY; DIBENZO-PARA-DIOXINS; GREAT-LAKES; BACKGROUND LEVELS; PAPER-MILLS; PCDDS; PCDFS; CONTAMINATION; PULP; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN AB TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) in the edible portion of fish and shellfish from various U.S. waterways has been monitored since 1979. Analytical results for the period 1979-1994 are reported. Extracts obtained after column chromatographic and liquid chromatographic cleanup were examined by electron capture detection-gas chromatography (GC), and final quantitation and confirmation were performed by GC/mass spectrometry with multiple ion detection. Analyses of 1623 test samples indicated that TCDD residues in fish and shellfish were not widespread but rather were localized in areas near waste sites, chlorophenol manufacturers, and pulp and paper mills. Analytical results indicated that levels in aquatic species from these sites have been declining steadily. No TCDD (limit of detection and confirmation, 1-2 ppt) has been found in recent years in aquatic species from most Atlantic, Pacific, and Gulf of Mexico sites and Great Lakes other than Lake Ontario and Saginaw Bay (Lake Huron). C1 US FDA,PESTICIDES & IND CHEM RES CTR,DETROIT,MI 48207. US FDA,SCI BRANCH,CHICAGO,IL 60616. RP Firestone, D (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204, USA. NR 34 TC 9 Z9 9 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 SEP-OCT PY 1996 VL 79 IS 5 BP 1174 EP 1183 PG 10 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA VJ030 UT WOS:A1996VJ03000022 PM 8823925 ER PT J AU Hepp, NM AF Hepp, NM TI Spectrometric determination of chromium in FD&C Blue No 1 by X-ray fluorescence SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB An X-ray fluorescence spectrometry (XRF) method was developed and validated for determination of chromium in FD&C Blue No. 1. Results of this analysis were compared with those obtained with an atomic absorption spectroscopy (AAS) method currently used by the U.S. Food and Drug Administration. Levels of Cr, as determined by the XRF and AAS methods, were comparable. The limit of quantitation for the XRF method is 4 mu g Cr/g. The predicted 95% confidence interval at the specification level is 50 +/- 5 mu g/g. RP Hepp, NM (reprint author), US FDA,OFF COSMET & COLORS,200 C ST SW,WASHINGTON,DC 20204, USA. NR 1 TC 7 Z9 7 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 SEP-OCT PY 1996 VL 79 IS 5 BP 1189 EP 1190 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA VJ030 UT WOS:A1996VJ03000024 PM 8823926 ER PT J AU Schenck, FJ Calderon, L Podhorniak, LV AF Schenck, FJ Calderon, L Podhorniak, LV TI Determination of organochlorine pesticide and polychlorinated biphenyl residues in fatty fish by tandem solid-phase extraction cleanup SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A rapid, multiresidue solid-phase extraction (SPE) technique for determination of organochlorine pesticide and polychlorinated biphenyl (PCB) residues in nonfatty fish was modified for use with fatty fish, In the modified procedures, samples are extracted with acetonitrile, and the extract is cleaned up with both C-18 and Florisil SPE columns, Residues are determined by gas chromatography with electron capture detection. The original method was modified for use with fatty fish by reducing the amount of tissue extracted and by using an improved Florisil SPE cleanup, Recovery data are presented for 24 fortified organochlorine pesticide residues (0.12 ppm) and 3 fortified PCB residues (0.80 ppm) from flounder, bluefish, and shad samples, which contained 0.8, 5.4, and 22.6% fat, respectively. for the 3 types of fish, recoveries of 23 of 24 fortified organochlorine pesticide residues ranged from 55 to 129%, and recoveries of 3 fortified PCB residues ranged from 55 to 104%, There were no significant differences in recovery based on fish species and/or fat content for the majority of residues studied, This SPE method and the official AOAC method yielded comparable results for fish containing incurred organochlorine residues. RP Schenck, FJ (reprint author), US FDA,BALTIMORE DIST LAB,900 MADISON AVE,BALTIMORE,MD 21201, USA. NR 9 TC 18 Z9 21 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 SEP-OCT PY 1996 VL 79 IS 5 BP 1209 EP 1214 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA VJ030 UT WOS:A1996VJ03000028 PM 8823927 ER PT J AU Schenck, FJ AF Schenck, FJ TI Screening of nonfatty fish for organochlorine pesticide residues by solid-phase extraction cleanup: Interlaboratory study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Six U.S. Food and Drug Administration laboratories participated in an interlaboratory trial of a solid-phase extraction cleanup method for determination of pesticides in nonfatty seafood products. The participants analyzed control and fortified (about 0.050 ppm lindane, heptachlor epoxide, p,p'-DDE, and endrin) croaker and flounder samples and a sea trout sample containing incurred p,p'-DDE residues. Mean recoveries of the fortified residues from the fish ranged from 89.1 to 107.8%. The within-laboratory coefficients of variation (CVs) ranged from 4.2 to 8.5%, and the among-laboratory CVs ranged from 10.9 to 26.5%. The 6 laboratories reported a mean value of 0.040 ppm p,p'-DDE in a fish sample which contained incurred residues. The same value (0.040 ppm) was obtained by using official methodology. The within-laboratory CVs ranged from 3.5 to 18.3%, and the among-laboratory CV was 17.3%. RP Schenck, FJ (reprint author), US FDA,BALTIMORE DIST LAB,900 MADISON AVE,BALTIMORE,MD 21201, USA. NR 6 TC 8 Z9 8 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 SEP-OCT PY 1996 VL 79 IS 5 BP 1215 EP 1219 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA VJ030 UT WOS:A1996VJ03000029 PM 8823928 ER PT J AU Pfenning, AP Munns, RK Turnipseed, SB Roybal, JE Holland, DC Long, AR Plakas, SM AF Pfenning, AP Munns, RK Turnipseed, SB Roybal, JE Holland, DC Long, AR Plakas, SM TI Determination and confirmation of identities of flumequine and nalidixic, oxolinic, and piromidic acids in salmon and shrimp SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LIQUID-CHROMATOGRAPHY; UV DETECTION; FLUORESCENCE; FISH AB A previously published liquid chromatographic (LC) method for determining residues of flumequine (FLU) and nalidixic (NAL), oxolinic (OXO), and piromidic (PIR) acids in catfish tissue was applied to salmon and shrimp muscle. Identities of all 4 residues in salmon and shrimp were confirmed by gas chromatography/mass spectrometry (GC/MS). The tissue is homogenized with acetone, the acetone extract is defatted with hexane, and the quinolones are extracted into chloroform, The extract is further purified by first partitioning into base and then back-extracting from a solution acidified to pH 6.0. Analytes are determined by LC with simultaneous UV and fluorescence detection. Muscle tissue was fortified with each quinolone at 5, 10, 20, 40, and 80 ng/g. Average recoveries and relative standard deviations (RSDs) for salmon, which represent an average of the 5 levels for each analyte, ranged from 75.9 to 90.8% and from 2.25 to 6.40%, respectively, Average recoveries and RSDs for shrimp ranged from 81.3 to 91.2% and from 7.34 to 10.7%, respectively, Identities of OXO, FLU, NAL, and PIR were confirmed in extracts of salmon and shrimp tissue fortified at 10 ng/g by determination of decarboxylated quinolones by GC/MS, Four diagnostic ions were monitored for OXO, FLU, and PIR, and 5 ions were monitored for NAL, All ion relative abundances were within 10% of those calculated for standard decarboxylated quinolones, Optimum conditions for decarboxylation and GC/MS confirmation are given. C1 US FDA,GEN CHEM SECT,DENVER FED CTR,DENVER,CO 80225. US FDA,DIV SEAFOOD RES,DAUPHIN ISL,AL 36528. RP Pfenning, AP (reprint author), US FDA,ANIM DRUGS RES CTR,DENVER,CO 80225, USA. NR 3 TC 23 Z9 23 U1 2 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 SEP-OCT PY 1996 VL 79 IS 5 BP 1227 EP 1235 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA VJ030 UT WOS:A1996VJ03000031 PM 8823929 ER PT J AU Chapekar, MS AF Chapekar, MS TI Regulatory concerns in the development of biologic-biomaterial combinations SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article ID PROTEINS AB Several biologic-biomaterial combinations are currently under development in an attempt to modulate tissue or organ function in patients, The FDA regulations on combination products and the intercenter agreements among the Center for Biologics Evaluation and Research (CBER), the Center for Devices and Radiological Health (CDRH), and the Center for Drugs Evaluation and Research (CDER) provide further guidance on center jurisdiction of combination products and other products where there are jurisdictional concerns. The biological component of biologic-biomaterial combinations raises a number of issues that relate to the safety and bioactivity of the final product, For example, transmission of adventitious agents to patients via somatic cells, tissue, or cell-derived products is a major safety concern as are in vivo inflammatory responses elicited by the biomaterial component, CBER has drafted a number of ''Points to Consider'' documents to provide further guidance in the development of biological products, The intent of this article is to provide the highlights of the FDA regulations for combination products and the intercenter agreement between CBER and CDRH delineating the responsibilities of each center for medical device activities. In addition, the article focuses on the CBER's concerns related to the development of somatic cell-biomaterial combinations for therapeutic use. (C) 1996 John Wiley & Sons, Inc. RP Chapekar, MS (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV APPLICAT REVIEW & POLICY,OFF THERAPEUT RES & REVIEW,HFM 591,ROCKVILLE,MD 20852, USA. NR 13 TC 14 Z9 14 U1 0 U2 1 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 FAL PY 1996 VL 33 IS 3 BP 199 EP 203 DI 10.1002/(SICI)1097-4636(199623)33:3<199::AID-JBM10>3.0.CO;2-C PG 5 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA VC840 UT WOS:A1996VC84000010 PM 8864892 ER PT J AU Kapur, R Lilien, J Picciolo, GL Black, J AF Kapur, R Lilien, J Picciolo, GL Black, J TI Human monocyte morphology is affected by local substrate charge heterogeneity SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article ID MEMBRANE; ELECTROPHORESIS; OSTEOBLASTS; ADHESION; SURFACES; CELLS; NERVE; SHAPE; ACTIN AB Cells are sensitive to topological, chemical, and electrical properties of substrates on which they are grown. However, most studies of cell-surface interactions have neglected electrical effects or confounded them with other substrate properties. The use of nanofabrication technology has made it possible to fabricate optically transparent surfaces with controlled chemistry and topology, and with active, controllable surface charge density in domains as small as 1-4 mu m. Human monocytes incubated on polystyrene with 3.3 mu m-wide strip domains, alternately charged so as to maintain overall charge neutrality, show significant charge density and time-dependent increases (greater than twofold) in cell area and cell perimeter after challenge with a phagocytic trigger (human IgG opsonized zymosan particles). Additional ultra-structural studies on silicon dioxide substrates show charge-density-dependent qualitative morphological differences. These studies clearly demonstrate that human monocytes respond in vitro to local surface-charge heterogeneity in the absence of substrate topology and compositional variation. (C) 1996 John Wiley & Sons, Inc. C1 CLEMSON UNIV,DEPT BIOENGN,CLEMSON,SC 29634. US FDA,DIV MECH & MAT SCI,ROCKVILLE,MD 20852. WAYNE STATE UNIV,DEPT BIOL SCI,DETROIT,MI 48202. IMN BIOMAT,KING OF PRUSSIA,PA 19406. NR 28 TC 10 Z9 10 U1 0 U2 0 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 SEP PY 1996 VL 32 IS 1 BP 133 EP 142 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA VC839 UT WOS:A1996VC83900017 PM 8864882 ER PT J AU Pastor, RW Zwanzig, R Szabo, A AF Pastor, RW Zwanzig, R Szabo, A TI Diffusion limited first contact of the ends of a polymer: Comparison of theory with simulation SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID CONTROLLED INTRACHAIN REACTIONS AB The mean first passage time for the close approach of the ends of a polymer is investigated by computer simulation of the Brownian dynamics of a Rouse model. There are N bonds, of length b, and the contact distance is a. The results for N=50, 75, and 100 are compared with theoretical predictions by Wilemski and Fixman (WF), and by Szabo, Schulten, and Schulten (SSS). Theory differs from simulation by a factor of 1.3 to 3 when a is comparable to b but improves considerably when a is reduced. Closest agreement is obtained at a/b = 0.1 for WF with a delta function sink, where theory is within the statistical error (approximate to 5%) of the simulation for each case. C1 NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. RP Pastor, RW (reprint author), US FDA,CTR BIOL EVALUAT & RES,BIOPHYS LAB,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. RI Szabo, Attila/H-3867-2012 NR 12 TC 108 Z9 108 U1 1 U2 16 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 SEP 1 PY 1996 VL 105 IS 9 BP 3878 EP 3882 DI 10.1063/1.472208 PG 5 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA VD768 UT WOS:A1996VD76800056 ER PT J AU Menozzi, FD Rouse, JH Alavi, M LaudeSharp, M Muller, J Bischoff, R Brennan, MJ Locht, C AF Menozzi, FD Rouse, JH Alavi, M LaudeSharp, M Muller, J Bischoff, R Brennan, MJ Locht, C TI Identification of a heparin-binding hemagglutinin present in mycobacteria SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID FILAMENTOUS HEMAGGLUTININ; CELL-SURFACE; BORDETELLA-PERTUSSIS; EPITHELIAL-CELLS; COMPLEMENT COMPONENT-C3; YERSINIA-ENTEROCOLITICA; SULFATE PROTEOGLYCANS; AVIUM COMPLEX; TUBERCULOSIS; RECEPTORS AB Adherence to mammalian host tissues is an important virulence trait in microbial pathogenesis, yet little is known about the adherence mechanisms of mycobacteria. Here, we show that binding of mycobacteria to epithelial cells but not to macrophages can be specifically inhibited by sulfated carbohydrates. Using heparin-Sepharose chromatography, a 28-kD heparin-binding protein was purified from culture supernatants and cell extracts of Mycobacterium bovis and Mycobacterium tuberculosis. This protein, designated heparin-binding hemagglutinin (HBHA), promotes the agglutination of rabbit erythrocytes, which is specifically inhibited by sulfated carbohydrates. HBHA also induces mycobacterial aggregation, suggesting that it can mediate bacteria-bacteria interactions as well. Hemagglutination, mycobacterial aggregation, as well as attachment to epithelial cells are specifically inhibited in the presence of anti-HBHA antibodies. Immunoelectron microscopy using anti-HBHA monoclonal antibodies revealed that the protein is surface exposed, consistent with a role in adherence. Immunoblot analyses using antigen-specific antibodies indicated that HBHA is different from the fibronectin-binding proteins of the antigen 85 complex and p55, and comparison of the NH2-terminal amino acid sequence of purified HBHA with the protein sequence data bases did not reveal any significant similarity with other known proteins. Sera from tuberculosis patients but not from healthy individuals were found to recognize HBHA, indicating its immunogenicity in humans during mycobacterial infections. Identification of putative mycobacterial adhesins, such as the one described in this report, may provide the basis for the development of new therapeutic and prophylactic strategies against mycobacterial diseases. C1 US FDA,CBER,LAB MYCOBACTERIA,ROCKVILLE,MD 20852. INST PASTEUR,LAB MICROBIOL GENET & MOL,INST NATL SANTE & RECH MED,U447,F-59019 LILLE,FRANCE. TRANSGENE SA,F-67082 STRASBOURG,FRANCE. RI Bischoff, Rainer/H-5404-2011 NR 47 TC 176 Z9 186 U1 1 U2 4 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 SEP 1 PY 1996 VL 184 IS 3 BP 993 EP 1001 DI 10.1084/jem.184.3.993 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VG868 UT WOS:A1996VG86800021 PM 9064359 ER PT J AU Murakami, EG Okos, MR AF Murakami, EG Okos, MR TI Calculation of initial freezing point, effective molecular weight and unfreezable water of food materials from composition and thermal conductivity data SO JOURNAL OF FOOD PROCESS ENGINEERING LA English DT Article AB A procedure was developed for simultaneous determination of the effective molecular weight, unfreezable water, and initial freezing point of foods based on composition and thermal conductivity data. Freezing properties were determined by trial and error and optimized by minimizing the difference between calculated and reported values of thermal conductivity. The procedure involved determination of the ice fraction at several temperature levels. Corresponding thermal conductivity values at each temperature level were then calculated. Results showed that calculated values of effective molecular weight, unfreezable water, and initial freezing point for various types of meat and fish are comparable to those published. The parallel-perpendicular model was found an excellent predictor of thermal conductivity of frozen meat and fish with muscle fibers oriented toward the direction of the heat flow. C1 PURDUE UNIV,DEPT AGR ENGN,W LAFAYETTE,IN 47907. RP Murakami, EG (reprint author), US FDA,NATL CTR FOOD SAFETY & TECHNOL,6502 S ARCHER AVE,SUMMIT ARGO,IL 60501, USA. NR 20 TC 6 Z9 6 U1 1 U2 3 PU FOOD NUTRITION PRESS INC PI TRUMBULL PA 6527 MAIN ST, P O BOX 374, TRUMBULL, CT 06611 SN 0145-8876 J9 J FOOD PROCESS ENG JI J. Food Process Eng. PD SEP PY 1996 VL 19 IS 3 BP 301 EP 320 DI 10.1111/j.1745-4530.1996.tb00395.x PG 20 WC Engineering, Chemical; Food Science & Technology SC Engineering; Food Science & Technology GA VJ212 UT WOS:A1996VJ21200004 ER PT J AU Tran, TT Hitchins, AD AF Tran, TT Hitchins, AD TI Evaluation of a selective enrichment most probable number enumeration method for viable Listeria spp in dairy products SO JOURNAL OF FOOD PROTECTION LA English DT Article DE Listeria; foodborne; MPN enumeration; selective enrichment ID MONOCYTOGENES; FOODS; MEDIA AB A most probable number (MPN) method for enumerating low numbers of Listeria spp. in dairy foods was developed by adapting the U.S. Food and Drug Administration (FDA) Listeria isolation methodology. Milk, cheese, and other milk products were diluted and homogenized in enrichment broth (1 g/10 mi). Homogenates were inoculated with L. monocytogenes Lm82, a streptomycin-resistant variant of strain Scott A, at < 1 to 320 CFU/g and further diluted in FDA enrichment broth to give 0.1, 0.01, and 0.001 g of food sample per 10 mi. Dilution aliquots (10 mi) in triplicate or quintuplicate were incubated at 30 degrees C for 48 h before being subcultured on Oxford agar at 35 degrees C. Esculin-hydrolyzing colonies on Oxford agar were confirmed as the inoculum strain by their ability to grow on Trypticase soy agar containing streptomycin. Differences between inoculum and MPN values were evaluated by using tabulated 95% confidence limits. The calculated MPNs agreed with the inoculum levels in 91% (58 of 64) of noncheese dairy foods and in 49% (56 of 112) of 15 varieties of ripened cheeses. Competitive microflora affected by cheese age and the kind of milk used may account for the suboptimal performance of the MPN method with the cheeses. C1 US FDA,DIV MICROBIOL STUDIES,WASHINGTON,DC 20204. NR 13 TC 12 Z9 13 U1 1 U2 5 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2838 SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD SEP PY 1996 VL 59 IS 9 BP 928 EP 931 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA VK557 UT WOS:A1996VK55700004 ER PT J AU Dallas, HL Sathyamoorthy, V Hitchins, AD AF Dallas, HL Sathyamoorthy, V Hitchins, AD TI Purification of the anti-listerial bacteriocin-like inhibitory substance produced by Enterococcus faecium 108 SO JOURNAL OF FOOD SAFETY LA English DT Article ID GRAM-POSITIVE BACTERIA; MONOCYTOGENES AB Extracellular antimicrobial substances produced by certain enterococci inhibit Listeria monocytogenes. Enterococcus faecium 108, a competitive food isolate, produced a heat-stable and protease-sensitive anti-L. monocytogenes bacteriocin-like substance (Ef108) in Listeria selective enrichment broth and other media. Ef108 activity was purified to homogeneity by a four-step procedure including (NH4)(2)SO4 fractionation, chromatography on anion exchange Q-Sepharose column, and two Superose 12 gel filtration columns. In activities represented by two peaks (Ef108A and Ef108B), 90% of the crude activity was due to peak B. Ef108A is believed to be a variable aggregate of the active moiety in Ef108B. All Listeria spp. and five L. monocytogenes serotypes were inhibited by Ef108B in several media including Listeria enrichment medium. The Ef108 activity may be due to a bacteriocin-like inhibitory substance produced by E. faecium 108 that may suppress the growth and predominance of Listeria monocytogenes during selective enrichment. C1 US FDA,DIV VIRULENCE ASSESSMENT,WASHINGTON,DC 20204. RP Dallas, HL (reprint author), US FDA,DIV MICROBIOL STUDIES HFS516,200 C ST SW,WASHINGTON,DC 20204, USA. NR 26 TC 4 Z9 4 U1 0 U2 0 PU FOOD NUTRITION PRESS INC PI TRUMBULL PA 6527 MAIN ST, P O BOX 374, TRUMBULL, CT 06611 SN 0149-6085 J9 J FOOD SAFETY JI J. Food Saf. PD SEP PY 1996 VL 16 IS 3 BP 183 EP 199 DI 10.1111/j.1745-4565.1996.tb00159.x PG 17 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA VN782 UT WOS:A1996VN78200002 ER PT J AU McCarthy, SA AF McCarthy, SA TI Effect of sanitizers on Listeria monocytogenes attached to latex gloves SO JOURNAL OF FOOD SAFETY LA English DT Article AB Contamination of ready-to-eat seafoods with Listeria monocytogenes is a major concern of the seafood industry. One means of control is the use of hand sanitizers, Five sanitizers (chlorine bleach, Zep-i-dine(TM), Zepamine A(TM) Zep(TM) Instant Hand Sanitizer, and Ultra-Kleen(TM)) were evaluated for effectiveness against L. monocytogenes attached to latex gloves in the presence of phosphate buffered saline or crab cooking water, Cooking water had been used to boil the crabs and was heavily laden with organic nutrients. Chlorine, Zepamine A(TM), and Ultra-Kleen(TM) reduced numbers of attached L. monocytogenes to nondetectable levels in the presence of phosphate buffered saline; Zep-i-dine(TM) and Zep(TM) Instant Hand Sanitizer were less effective. In the presence of crab cooking water, only Ultra-Kleen(TM) reduced cell numbers to nondetectable levels; the effectiveness of the remaining sanitizers was reduced. Extreme care must be taken when choosing hand sanitizers as their efficacy may be affected by organic residues on the gloves of food handlers. RP McCarthy, SA (reprint author), US FDA, GULF COAST SEAFOOD LAB, POB 158, DAUPHIN ISL, AL 36528 USA. NR 19 TC 6 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0149-6085 J9 J FOOD SAFETY JI J. Food Saf. PD SEP PY 1996 VL 16 IS 3 BP 231 EP 237 DI 10.1111/j.1745-4565.1996.tb00163.x PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA VN782 UT WOS:A1996VN78200006 ER PT J AU Boswell, CM Stein, KE AF Boswell, CM Stein, KE TI Avidity maturation, repertoire shift, and strain differences in antibodies to bacterial levan, a type 2 thymus-independent polysaccharide antigen? SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFLUENZA-VIRUS HEMAGGLUTININ; BINDING MYELOMA PROTEINS; AMINO-ACID-SEQUENCES; BALB-C MICE; IMMUNE-RESPONSE; MONOCLONAL-ANTIBODIES; GERMINAL-CENTERS; B POLYSACCHARIDE; CLONAL CHARACTERIZATION; SUBCLASS RESTRICTION AB Our previous studies of 102 mAb from mice injected with bacterial levan (BL), a beta(2-->6) linked polyfructosan with beta(2-->1) branch points (inulin determinant, In) showed that BALB/c and CBA/Ca mAb differed in V-H and V-L gene family usage and fine specificity. We now show that BALB/c and CBA/Ca mAb used different V(H)J606 germ-line genes in response to BL: V14A in BALB/c and a previously unidentified gene in CBA/Ca. CBA/Ca mice were found to lack the BALB/c V14A gene. Also, we have compared the responses to one (primary, 1 degrees) or two (secondary, 2 degrees) injections of polysaccharide. The secondary BALB/c anti-BL panel has been expanded to a total of 22 mAb, and we report here the isotype, fine specificity, and V-H/V-L usage of the new mAb. Eight of nine primary BALB/c In-binding mAb were germ-line, whereas both secondary BALB/c In-binding mAb that were sequenced differed from the BALB/c germ-line gene V14A. Germ-line primary mAb were low avidity whereas all five secondary mAb and the one non-germ-line primary were high avidity. There was also a repertoire shift from approximately 90% V(H)J606/V kappa 11 in primary mAb to only 50% in secondary mAb (p = 0.002). The data presented provide evidence that avidity maturation and repertoire shifts, features usually associated with a memory response to thymus-dependent Ags, also can occur in response to a second immunization with a thymus-independent type 2 polysaccharide Ag. C1 US FDA,DIV MONOCLONAL ANTIBODIES,OFF THERAPEUT RES & REVIEW,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 70 TC 17 Z9 17 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 SEP 1 PY 1996 VL 157 IS 5 BP 1996 EP 2005 PG 10 WC Immunology SC Immunology GA VF753 UT WOS:A1996VF75300025 PM 8757320 ER PT J AU Henchal, LS Midthun, K Goldenthal, KL AF Henchal, LS Midthun, K Goldenthal, KL TI Selected regulatory and scientific topics for candidate rotavirus vaccine development SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 5th Rotavirus Vaccine Workshop CY OCT 16-17, 1995 CL CTR DIS CONTROL & PREVENT, BETHESDA, MD SP Ctr Dis Control & Prevent, NIAIS, NIH, Emory Univ Sch Med HO CTR DIS CONTROL & PREVENT ID INFLUENZAE TYPE-B; ACELLULAR PERTUSSIS VACCINES; ORAL POLIOVIRUS VACCINE; RHESUS-ROTAVIRUS; CAPSULAR POLYSACCHARIDE; REASSORTANT VACCINE; VENEZUELAN INFANTS; RURAL BANGLADESH; VIRAL GASTROENTERITIS; IMMUNOLOGICAL MEMORY AB Various aspects of the development of rotavirus vaccine candidates are discussed. As is true with other vaccines, comprehensive testing must be done to detect the possible presence of adventitious agents in the vaccine and seed preparations. Consideration must also be given to other biologic materials that come in contact with the vaccine preparation during production to prevent the introduction of contaminants. The clinical testing of rotavirus vaccines from early safety and immunogenicity studies through final efficacy studies is also discussed. Issues surrounding coadministration of investigational rotavirus vaccines with US-licensed vaccines are ideally addressed before initiation of efficacy trials. Other subjects discussed are identification of correlates of protection, multivalent vaccines, foreign efficacy trials, safety data, and statistical considerations. Sponsors of investigational vaccines are urged to contact the Food and Drug Administration for guidance during the development process, especially before the investigational new drug application and pivotal efficacy trial stages. RP Henchal, LS (reprint author), US FDA,CTR BIOL RES & REVIEW,OFF VACCINES RES & REVIEW,ROCKVILLE,MD 20852, USA. NR 92 TC 2 Z9 2 U1 1 U2 1 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 SEP PY 1996 VL 174 SU 1 BP S112 EP S117 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VE910 UT WOS:A1996VE91000019 PM 8752300 ER PT J AU Zhang, J Clark, JR Herman, EH Ferrans, VJ AF Zhang, J Clark, JR Herman, EH Ferrans, VJ TI Doxorubicin induced apoptosis in spontaneously hypertensive rats: Differential effects in heart, kidney and intestine, and inhibition by ICRF-187 SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE doxorubicin toxicity; ICRF-187; apoptosis; cardiomyopathy; nephropathy ID PROGRAMMED CELL-DEATH; TOPOISOMERASE-II; DNA-DAMAGE; BIS(2,6-DIOXOPIPERAZINE) DERIVATIVES; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; TUMOR-CELLS; ADRIAMYCIN; INDUCTION; GROWTH AB The occurrence of apoptosis in heart, kidney and small intestine was investigated in spontaneously hypertensive rats (SHR) treated with doxorubicin (1 mg/kg/week for 6, 9 and 12 weeks) with and without pretreatment with the iron chelator ICRF-187 [(+)1,2-bis(3.5-dioxopiperazinyl-1-yl)propane] (25 mg/kg, i.p., given 30 min before doxorubicin). Animals receiving either ICRF-187 alone or saline were used as controls, Cells undergoing apoptosis were identified ultrastructurally and by staining using the nick-end labeling method, The results obtained by counting cells with positive nick-end labeling showed that, when given in cumulative doses of 9 and 12 (but not 6) mg/kg, doxorubicin induced significant toxicity in the heart, kidneys and intestine in association with apoptosis in epithelial cells of the intestinal mucosa and renal tubules but not in cardiac myocytes. At these doses, nick end labeling in the heart was confined to occasional endothelial cells, interstitial dendritic cells and macrophages. The frequency of doxorubicin-induced apoptosis in renal and intestinal epithelial cells was decreased by pretreatment of the SHR with ICRF-187. Our data support the concept that the chronic cardiomyopathy induced by doxorubicin is not mediated by apoptosis of the cardiac myocytes. (C) 1996 Academic Press Limited C1 NHLBI, PATHOL SECT, NIH, BETHESDA, MD 20892 USA. US FDA, DIV RES & TESTING, LAUREL, MD 20708 USA. NR 47 TC 96 Z9 97 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD SEP PY 1996 VL 28 IS 9 BP 1931 EP 1943 DI 10.1006/jmcc.1996.0186 PG 13 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA VK818 UT WOS:A1996VK81800011 PM 8899552 ER PT J AU Crison, JR Shah, VP Skelly, JP Amidon, GL AF Crison, JR Shah, VP Skelly, JP Amidon, GL TI Drug dissolution into micellar solutions: Development of a convective diffusion model and comparison to the film equilibrium model with application to surfactant-facilitated dissolution of carbamazepine SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID PHYSICAL-CHEMICAL BEHAVIOR; ADULT HUMAN-BEINGS; INTESTINAL DIGESTION; AGGREGATION STATES; BILIARY LIPIDS; PHASE; ABSORPTION; DIETARY; FORMS AB The intrinsic dissolution rate of carbamazepine in solutions of sodium lauryl sulfate was measured to study the convective diffusion transport of drug-loaded micelles from a rotating disk. Alternative definitions for effective diffusivity and reaction factor are presented and compared with those commonly used for this type of transport problem. The conventional and alternative approaches are based on the same fundamental assumptions differing only in their interpretation of the diffusional boundary layer. For example, in this study it was observed that, above the cmc, a 2% w/v solution of sodium lauryl sulfate increased the dissolution rate approximately 6-fold and the solubility approximately 20-fold. This difference between the solubility and dissolution enhancement was attributed to the contribution to the total transport of both the enhanced solubility, a 20-fold increase, and the effective diffusivity of the drug-micelle complex, a 3-fold decrease, hence a net 6-fold increase in dissolution. The diffusivity of the drug-loaded micelle estimated from the dissolution data using the new definitions compared well with values determined by other methods (D-sm = 8.4 x 10(-7) cm(2)/s). On the basis of these results, the new definitions for the effective diffusivity and reaction factor offer a practical method for estimating micellar diffusion coefficients and predicting drug dissolution under the well-defined hydrodynamics of the rotating disk. It may also be possible to extend the application of these definitions to study the dissolution of water-insoluble drugs in other media, such as emulsions, to better understand drug dissolution under fed conditions in vivo. C1 US FDA,ROCKVILLE,MD 20855. COPLEY PHARMACEUT INC,CANTON,MA 02121. UNIV MICHIGAN,COLL PHARM,ANN ARBOR,MI 48109. RP Crison, JR (reprint author), TSRL INC,540 AVIS DR,SUITE A,ANN ARBOR,MI 48108, USA. FU FDA HHS [FD01462] NR 32 TC 36 Z9 36 U1 0 U2 7 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 SEP PY 1996 VL 85 IS 9 BP 1005 EP 1011 DI 10.1021/js930336p PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA VF662 UT WOS:A1996VF66200019 PM 8877894 ER PT J AU Lytle, CD Routson, LB Thoms, DP Regnault, WF Cyr, WH AF Lytle, CD Routson, LB Thoms, DP Regnault, WF Cyr, WH TI Two parameters limiting the sensitivity of laboratory tests of condoms as viral barriers SO JOURNAL OF TESTING AND EVALUATION LA English DT Article DE condom test; punctured condom; latex condom; viruses; virus barrier; protective clothing ID SURROGATE VIRUSES AB The practical limits of a laboratory test for evaluating condoms as virus barriers were characterized by determining virus penetration through small punctures in latex condoms. The test quantifies virus penetration through a pressurized, restrained condom filled with challenge virus. Estimation of the minimum-detectable hole (narrow slit) dimensions indicated that a limiting factor in virus transmission through such a puncture is fluid flow. The virus penetration rates decreased with time, apparently caused by the hole closing or being blocked, indicating that extending the test duration to allow more virus penetration was of limited value. Further, it was found that adsorption of virus particles during passage through a hole may limit the useful sensitivity of the test. With bacteriophage phi X174 as the challenge virus, the practical limit for detecting virus penetration may be approximately 2 x 10(-6) mL; with more adsorptive viruses, the test would be less sensitive. C1 US FDA,DIV MECH & MAT SCI,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857. BIOCON INC,ROCKVILLE,MD 20857. RP Lytle, CD (reprint author), US FDA,DIV LIFE SCI,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857, USA. NR 14 TC 6 Z9 6 U1 0 U2 1 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 SEP PY 1996 VL 24 IS 5 BP 279 EP 286 PG 8 WC Materials Science, Characterization & Testing SC Materials Science GA VK271 UT WOS:A1996VK27100002 ER PT J AU Yasaei, PM Yang, GC Warner, CR Daniels, DH Ku, Y AF Yasaei, PM Yang, GC Warner, CR Daniels, DH Ku, Y TI Singlet oxygen oxidation of lipids resulting from photochemical sensitizers in the presence of antioxidants SO JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY LA English DT Article DE antioxidants; chemiluminescence; conjugated dienes; fatty acids; lipid hydroperoxides; photosensitizers ID PHOTOOXIDATION; PRODUCTS AB Singlet oxygen produced by photochemical sensitizers may play an important role in the oxidation of lipids in foods. Therefore, we studied the singlet oxygen oxidation of lipids and the scavenging ability of antioxidants. Singlet oxygen was generated using the photosensitizer rose bengal. The oxidation products of lipids and antioxidants were separated by high-performance liquid chromatography and monitored using post-column chemiluminescence and/or iodometric detection. The competitive reaction rates of various antioxidants and lipids were studied to elucidate the roles played by antioxidants in the prevention of food oxidation by singlet oxygen. RP Yasaei, PM (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,BIOANALYT CHEM BRANCH HFS346,200 C ST SW,WASHINGTON,DC 20204, USA. NR 10 TC 20 Z9 20 U1 1 U2 7 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0003-021X J9 J AM OIL CHEM SOC JI J. Am. Oil Chem. Soc. PD SEP PY 1996 VL 73 IS 9 BP 1177 EP 1181 DI 10.1007/BF02523381 PG 5 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA VJ032 UT WOS:A1996VJ03200015 ER PT J AU Acchiardo, SR Moore, LW Feuers, R Dulaney, J Burk, L Smith, S Cardoso, S AF Acchiardo, SR Moore, LW Feuers, R Dulaney, J Burk, L Smith, S Cardoso, S TI Activity of antioxidant enzymes in red blood cells (RBC) of hemodialysis (HD) patients (pts) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV TENNESSEE,MEMPHIS,TN. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A1105 EP A1105 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07401101 ER PT J AU Pogue, GP Hofmann, J Duncan, R Best, JM Etherington, J Sontheimer, RD Nakhasi, HL AF Pogue, GP Hofmann, J Duncan, R Best, JM Etherington, J Sontheimer, RD Nakhasi, HL TI Autoantigens interact with cis-acting elements of rubella virus RNA SO JOURNAL OF VIROLOGY LA English DT Article ID LUPUS ANTIGEN-LA; POLYMERASE-III; TRANSCRIPTION TERMINATION; CHRONIC ARTHRITIS; BINDING PROTEIN; LEADER RNA; CALRETICULIN; INFECTION; IMMUNIZATION; VACCINATION AB Rubella virus (RV) infections in adult women can be associated with acute and chronic arthritic symptoms. In many autoimmune individuals, antibodies are found targeting endogenous proteins, called autoantigens, contained in ribonucleoprotein complexes (RNPs). In order to understand the molecular mechanisms involved in the RV-associated pathology, we investigated the nature of cellular factors binding RV RNA and whether such RNPs were recognized by antibodies in infected individuals. Previously, we noted that cellular proteins associated with the RV 5'(+) stem-loop (SL) RNA are recognized by serum with Ro reactivity. To better understand the nature of the autoantigens binding RV cis-acting elements, serum samples from individuals with various autoimmune diseases were tested for their ability to immunoprecipitate RNPs containing labeled RV RNAs. A subset of serum samples recognizing autoantigen La, or Ro and La, immunoprecipitated both the RV 5'(+)SL and 3'(+)SL RNA-protein complexes. Autoantigens binding the RV 5'(+)SL and 3'(+)SL RNAs differed in molecular mass, specificities for respective RNA binding substrates, and sensitivity to alkaline phosphatase treatment. The La autoantigen was found to interact with the RV 5'(+)SL RNA as determined by immunological techniques and binding reactions with mixtures containing recombinant La protein. To test whether there is a correlation between La binding to an RV RNA element and the appearance of an anti-La response, we measured anti-La titers in RV-infected individuals. Significant anti-La activity was detected in approximately one-third of RV-infected individuals 2 years postinfection. C1 US FDA,CTR BIOL EVALUAT & RES,OFF THERAPEUT RES & REV,DIV HEMATOL PROD,LAB MOL PHARMACOL,BETHESDA,MD 20892. UNIV LEIPZIG,INST VIROL,D-7010 LEIPZIG,GERMANY. ST THOMAS HOSP,DEPT VIROL,LONDON SE1 7EH,ENGLAND. ST THOMAS HOSP,DEPT RHEUMATOL,LONDON SE1 7EH,ENGLAND. UNIV TEXAS,SW MED CTR,DEPT DERMATOL,DALLAS,TX 75235. RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 NR 49 TC 26 Z9 26 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 SEP PY 1996 VL 70 IS 9 BP 6269 EP 6277 PG 9 WC Virology SC Virology GA VB415 UT WOS:A1996VB41500066 PM 8709254 ER PT J AU Elespuru, RK AF Elespuru, RK TI Future approaches to genetic toxicology risk assessment SO MUTATION RESEARCH-REVIEWS IN GENETIC TOXICOLOGY LA English DT Article DE genetic toxicology; short-term test; DNA damage; risk assessment ID MOUSE LYMPHOMA-CELLS; FLUORESCENCE INSITU HYBRIDIZATION; THYMIDINE KINASE LOCUS; CARCINOGEN-DNA ADDUCTS; CHINESE-HAMSTER CELLS; HUMAN CANCER RISK; GENOMIC INSTABILITY; ESCHERICHIA-COLI; STRESS-RESPONSE; TESTER STRAINS AB Short-term genetic toxicology tests were developed for the purpose of identifying chemical carcinogens in the environment. After two decades of development and validation, the tests are well-established in routine testing schemes, but our views of their utility for safety evaluation have undergone re-assessment. The correlation between identified mutagens and identified carcinogens has turned out to be significantly less than one, Processes or mechanisms that are not directly genotoxic appear to play a role in carcinogenesis. While short term test data are still components of the assessment of carcinogenic risk, genetic damage also has been recognized as important in its own right, in relation to heritable genetic risk and other health-related effects, such as aging, reproductive failure and developmental toxicity. The revolution in molecular biology and genetic analysis occurring over the past 20 years has contributed to the wealth of new information on the complexities of cell regulation, differentiation, and the carcinogenic process. These technologies have provided new experimental approaches to genetic toxicology assessments, including transgenic cell and animal models, human monitoring, and analysis of macromolecular interactions at environmentally relevant exposures. The potential exists for the development of more efficient and more relevant genetic toxicology testing schemes for use assessing human safety. A delineation of contemporary needs, a modem view of the elements of cancer induction, and an examination of new assays and technologies may provide a framework for integrating new approaches into current schemes for evaluating the potential genetic and carcinogenic risk of environmental chemicals. RP Elespuru, RK (reprint author), US FDA, CTR DEVICES & RADIOL HLTH, HFZ-113, 12709 TWINBROOK PKWY, ROCKVILLE, MD 20852 USA. NR 93 TC 8 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1110 J9 MUTAT RES-REV GENET JI Mutat. Res.-Rev. Genet. Toxicol. PD SEP PY 1996 VL 365 IS 1-3 SI SI BP 191 EP 204 DI 10.1016/S0165-1110(96)90021-4 PG 14 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA VP854 UT WOS:A1996VP85400014 PM 8898998 ER PT J AU Sobotka, TJ Ekelman, KB Slikker, W Raffaele, K Hattan, DG AF Sobotka, TJ Ekelman, KB Slikker, W Raffaele, K Hattan, DG TI Food and drug administration proposed guidelines for neurotoxicological testing of food chemicals SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 5th Meeting of the International-Neurotoxicology-Association CY JUN 25-30, 1995 CL PORT LUDLOW, WA DE neurotoxicity; test guidelines; food chemicals; Food and Drug Administration; ''Revised Redbook'' ID DEVELOPMENTAL NEUROTOXICITY; BEHAVIORAL INDEXES; RISK ASSESSMENT; TEST BATTERY; TOXICOLOGY; SCREEN; RATS; NEUROPATHOLOGY; TOXICITY AB The fact that some chemicals may adversely affect the nervous system is certainly not a new concept in regulatory toxicology. In 1982, the FDA issued testing guidelines for the safety evaluation of proposed direct food and color additives wh ich included the assessment of nervous system toxicity as part of the genera ! toxicological profile. However, these guidelines provide only broad and nonspecific recommendations as to how this assessment may best be carried out. The information derived from toxicity screening studies conducted according to these guidelines enable little more than the detection of clearly evident adult nervous system toxicity associated with general neuropathology and overt neurological dysfunction. Little consistent or systematically documented information is typically developed about other equally important types of neurotoxic effects including, for example, behavioral dysfunction and developmental neurotoxicity. Concerns about these more subtle types of neurotoxic effects have become a prominent public health issue and have resulted in demands for an increasing level of assurance that efforts are being made to minimize even further the risks of neurotoxicity from human exposure to chemical substances. In an effort to address these concerns, the FDA is including specific attention to neurotoxicity in a proposed revision of its toxicity testing guidelines for food additives. These proposed guidelines focus on a more careful evaluation of structural and functional measures of neurotoxicity as a routine component of safety assessment. This focus will enable the development of the type of information needed for a more effective assessment of the full spectrum of neurotoxic hazards. The revised guidelines for neurotoxicity testing will be discussed in terms of the FDA's overall approach to safety assessment. (C) 1996 Intox Press, Inc. C1 US FDA, NATL CTR TOXICOL RES, JEFFERSON, AR 72079 USA. RP US FDA, CTR FOOD SAFETY & APPL NUTR, HFS-507, 8301 MUIRKIRK RD, LAUREL, MD 20708 USA. NR 52 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X EI 1872-9711 J9 NEUROTOXICOLOGY JI Neurotoxicology PD FAL-WIN PY 1996 VL 17 IS 3-4 BP 825 EP 836 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA WP102 UT WOS:A1996WP10200031 PM 9086506 ER PT J AU Ferguson, SA Paule, MG Holson, RR AF Ferguson, SA Paule, MG Holson, RR TI Functional effects of methylazoxymethanol-induced cerebellar hypoplasia in rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE cerebellum; granule cells; activity; methylazoxymethanol acetate ID WEAVER MUTANT MICE; TEMPORAL RESPONSE DIFFERENTIATION; EXTERNAL GRANULAR LAYER; BRAIN-DEVELOPMENT; MOUSE CEREBELLUM; MOTOR ABNORMALITIES; RETARDATION; PERFORMANCE; ACETATE; MODEL AB The behavioral effects of a series of methylazoxymethanol acetate (MAM) injections in neonatal rats were investigated. Pups were injected twice daily on days 5-8 after birth with 4 mg/kg MAM or saline. Similar treatment paradigms cause cerebellar hypoplasia, which is a result of a depletion of granule cells. MAM treatment reduced adult cerebellar weight to 92% that of control and was without effect on weight of other brain regions examined. Postweaning body weight gain in males was reduced. Nest odor preference and emergence (light/dark box) assessments indicated no significant effects. Complex maze assessments and performance in an operant test battery demonstrated no cognitive deficits. Indeed, MAM-treated females performed better in a complex maze under lighted conditions than same-sex controls. Open field and running wheel activity levels in females were unaffected. Though not statistically significant, males exhibited a mild hyperactivity syndrome characterized by an increase in running wheel and open field activity, as well as a depressed startle response. Both sexes were hypersensitive to the locomotor-increasing effects of methamphetamine. These results suggest that the functional effects resulting from cerebellar hypoplasia produced by MAM treatment on PNDs 5-8 are milder than those resulting from MAM treatment beginning on the day of birth, The results are compared with other forms of cerebellar lesions and provide support for the hypothesis that early insult (day of birth or shortly after) produces hypoactivity whereas a later insult (day 4 or later after birth) produces a syndrome of hyperactivity. C1 NCTR, HFT 130, DIV NEUROTOXICOL, JEFFERSON, AR 72079 USA. RP Ferguson, SA (reprint author), NCTR, HFT 130, DIV REPROD & DEV TOXICOL, 3900 NCTR RD, JEFFERSON, AR 72079 USA. NR 39 TC 31 Z9 31 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 EI 1872-9738 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD SEP-OCT PY 1996 VL 18 IS 5 BP 529 EP 537 DI 10.1016/0892-0362(96)00083-9 PG 9 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA VK098 UT WOS:A1996VK09800002 PM 8888017 ER PT J AU Schmued, LC Albertson, CM Andrews, A Sandberg, JA Nickols, J Slikker, W AF Schmued, LC Albertson, CM Andrews, A Sandberg, JA Nickols, J Slikker, W TI Evaluation of brain and nerve pathology in rats chronically dosed with ddI or isoniazid SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE AIDS drugs; tuberculosis drugs; isoniazid; ddI; neuropathology; rat ID IMMUNODEFICIENCY-VIRUS INFECTION; AIDS-RELATED COMPLEX; PERIPHERAL NEUROPATHY; TUBERCULOSIS; DIDEOXYINOSINE; TOXICITY; THERAPY AB The antiviral adenosine analog, 2',3'-dideoxyinosine (ddI), and the antitubercular nicotinic acid analogue, isoniazid, have recently received widespread clinical application in the treatment of acquired immunodeficiency syndrome (AIDS). Clinical studies indicate that the primary dose limiting side effect of both drugs is neurological in nature. Most clinical studies are confounded by the fact that the observed neuropathy must be evaluated in the presence of the ongoing disease process associated with human immunodeficiency virus (HIV) infection. The purpose of this study was to develop and validate a rat model of ddI- and isoniazid-induced neuropathy in the absence of any disease-induced pathology. Myelin splitting and intramyelin edema were the most frequent abnormalities observed in the sciatic nerves of ddI-dosed animals, whereas whorls, extracellular debris, macrophages, and reduced myelinated axon number were seen following chronic isoniazid administration. Isoniazid also resulted in myelinopathy of the CNS. Thus, contrary to previous reports, the rodent is a suitable model for ddI- and isoniazid-induced neuropathies. C1 NATL CTR TOXICOL RES, DIV PATHOL, JEFFERSON, AR 72079 USA. UNIV ARKANSAS MED SCI HOSP, COLL MED, LITTLE ROCK, AR 72205 USA. JOHN L MCCLELLAN MEM VET ADM MED CTR, DEPT NEUROL, LITTLE ROCK, AR 72205 USA. RP Schmued, LC (reprint author), NATL CTR TOXICOL RES, DIV NEUROTOXICOL, HFT-132, 3900 NCTR RD, JEFFERSON, AR 72079 USA. FU NIEHS NIH HHS [Y01-ES-10187]; PHS HHS [334-91-0001] NR 36 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 EI 1872-9738 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD SEP-OCT PY 1996 VL 18 IS 5 BP 555 EP 563 DI 10.1016/0892-0362(96)00088-8 PG 9 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA VK098 UT WOS:A1996VK09800005 PM 8888020 ER PT J AU Niu, MT Davis, DM Ellenberg, S AF Niu, MT Davis, DM Ellenberg, S TI Recombinant hepatitis B vaccination of neonates and infants: Emerging safety data from the vaccine adverse Event Reporting System SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE hepatitis B vaccine; infants; adverse events; Vaccine Adverse Event Reporting System (VAERS) ID CLINICAL-EXPERIENCE; PROTECTIVE EFFICACY; POSITIVE MOTHERS; VIRUS-VACCINE; UNITED-STATES; NEAR-SIDS; IMMUNOGENICITY; DNA AB Objectives, To evaluate the postmarketing safety of recombinant hepatitis B (HE) vaccine given to neonates and infants in the US, Methods. US reports associated with HE vaccination and received between January 1, 1991, and May 31, 1995, by the national Vaccine Adverse Events Reporting System (VAERS) were reviewed as a case series, Results, During 1991 through 1994, 12 520 (32%) VAERS reports were received for events temporally associated with administration of HE vaccine, of which 14% were received for neonates and infants, More reports described serious outcomes for neonates (< 0.1 year old) than for other age groups (40% vs, 6 to 15%), HE alone was administered to 58 (97%) neonates; review of these reports did not reveal unexpected serious events, Among infants (0.1 to 0.9 years old) 192 (9%) received HE vaccine alone and 1469 (66%) received HE in combination with diphtheria-tetanus-pertussis (DTP) vaccine, Similar serious adverse events reported in neonates and infants included fever, agitation and apnea. Events reported for infants receiving HB/DTP and DTP alone were similar and differed from reports filed for infants receiving HE vaccine alone, suggesting that these events may be associated with use of DTP vaccine. Conclusions. This review shows no unexpected adverse events in neonates and infants given HE vaccine despite use of at least 12 million doses of vaccine given in these age groups, Although VAERS lacks the ability to distinguish coincidental events from true vaccine reactions, this database represents the largest case series of events temporally associated with HE vaccination of neonates and infants. RP Niu, MT (reprint author), US FDA,CBER,OELPS,DBE,1401 ROCKVILLE PIKE,HFM-220,ROCKVILLE,MD 20852, USA. NR 45 TC 30 Z9 32 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD SEP PY 1996 VL 15 IS 9 BP 771 EP 776 DI 10.1097/00006454-199609000-00007 PG 6 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA VG538 UT WOS:A1996VG53800006 PM 8878219 ER PT J AU Beer, JZ Zmudzka, BZ AF Beer, JZ Zmudzka, BZ TI Effects of UV on HIV and other infections (vol 64, pg 231, 1996) SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Correction, Addition ID HUMAN-IMMUNODEFICIENCY-VIRUS; ULTRAVIOLET; PSORIASIS; RADIATION; DISEASE; CELLS RP Beer, JZ (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,RADIOL BRANCH,HFZ-114,ROCKVILLE,MD 20857, USA. NR 15 TC 10 Z9 10 U1 0 U2 2 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 SEP PY 1996 VL 64 IS 3 BP 231 EP 233 DI 10.1111/j.1751-1097.1996.tb02449.x PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VG533 UT WOS:A1996VG53300001 PM 8760559 ER PT J AU Malek, A Miller, RK Mattison, DR Kennedy, S Panigel, M diSantAgnese, PA Jessee, L AF Malek, A Miller, RK Mattison, DR Kennedy, S Panigel, M diSantAgnese, PA Jessee, L TI Energy charge monitoring via magnetic resonance spectroscopy P-31 in the perfused human placenta: Effects of cadmium, dinitrophenol and iodoacetate SO PLACENTA LA English DT Article ID RAT; ISCHEMIA; TOXICITY; FETAL; METALLOTHIONEIN; ACCUMULATION; INJECTIONS; INVITRO; ATP AB Phosphorus 31 nuclear magnetic resonance spectroscopy as a non-invasive technique was applied to monitor the metabolic activity of the human placenta during perfusion in vitro. During control perfusions (n=3) there was an initial increase in adenosine triphosphate (ATP) and a fall in inorganic phosphate (Pi). Thereafter, however, the level of both ATP and Pi remained constant throughout the perfusion period (11 h). Additional biochemical parameters such as glucose consumption, lactate production and the release of hormones, human chorionic gonadotrophin (hGC), measured in the perfusate samples, vc ere also used to assess the viability of the placental tissue. As with ATP, all these biochemical parameters under the control conditions showed a stable rate of metabolic activity throughout the length of the experiments. In additional experiments, the effect of the metabolic inhibitor dinitrophenol (n=2) and dinitrophenol (DNP) together with iodoacetic acid (IOA, n=2) were studied, DNP (0.1 mM) alone showed a slight decrease of all parameters. In contrast, the addition of IOA (0.1 mM) with DNP (0.1 mM) not only blocked the production of ATP but also produced a substantial impact on placental metabolic activity. The effect of a toxic dose of cadmium (20 nmol/ml) was studied also (n=3). This dose of cadmium demonstrated no effect on phosphorus metabolism. However, the rate of glucose consumption and the release of hCG were significantly reduced. (C) 1996 W. B. Saunders Company Ltd C1 UNIV ROCHESTER,MED CTR,DEPT OBSTET GYNECOL,ROCHESTER,NY 14642. UNIV ROCHESTER,MED CTR,DEPT ENVIRONM MED,ROCHESTER,NY 14642. UNIV ARKANSAS MED SCI HOSP,DEPT OBSTET & GYNECOL,LITTLE ROCK,AR. NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079. UNIV ROCHESTER,MED CTR,DEPT BIOPHYS,ROCHESTER,NY 14642. UNIV PARIS 06,PARIS,FRANCE. UNIV ROCHESTER,MED CTR,DEPT PATHOL & LAB MED,ROCHESTER,NY 14642. RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 FU NIEHS NIH HHS [ES01247, ES02774] NR 52 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0143-4004 J9 PLACENTA JI Placenta PD SEP PY 1996 VL 17 IS 7 BP 495 EP 506 DI 10.1016/S0143-4004(96)90032-6 PG 12 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA VL495 UT WOS:A1996VL49500014 PM 8899879 ER PT J AU Boring, DL Berglund, BA Howlett, AC AF Boring, DL Berglund, BA Howlett, AC TI Cerebrodiene, arachidonyl-ethanolamide, and hybrid structures: Potential for interaction with brain cannabinoid receptors SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID PHARMACOLOGICAL ACTIVITY; ANANDAMIDE; AGONIST; SLEEP AB Cerebrodiene (cis-9, 10-octadecanoamide) was recently isolated from cerebral fluid of sleep-deprived cats and shown to induce sleep in rats. Because this lipid amide is related to arachidonylethanolamide (AEA), and because AEA binds to the cannabinoid receptor with high affinity, we investigated the binding affinity of cerebrodiene and some analogs to the cannabinoid receptor. In addition, we tested the ability of these compounds to act as cannabinoid receptor agonists by determining GTP gamma S binding. Each of the analogs competed for [H-3] CP55940 binding, but with relatively low affinity (K-i = 26-44 mu M). These analogs were not able to stimulate binding of GTP gamma S at concentrations of 100 mu M or 1 mM. We conclude that the sleep-inducing actions of cerebrodiene are not mediated via activation of the cannabinoid receptor. C1 ST LOUIS UNIV,SCH MED,DEPT PHARMACOL & PHYSIOL SCI,ST LOUIS,MO 63104. US FDA,CTR DRUG EVALUAT & RES,DIV ANTIVIRAL DRUG PROD,ROCKVILLE,MD 20857. OI Howlett, Allyn/0000-0002-2810-0164 FU NIDA NIH HHS [R01-DA03690, R01-DA06312]; PHS HHS [K05-00182] NR 18 TC 44 Z9 44 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 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD SEP PY 1996 VL 55 IS 3 BP 207 EP 210 DI 10.1016/S0952-3278(96)90100-3 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA VR542 UT WOS:A1996VR54200014 PM 8931121 ER PT J AU Shope, TB AF Shope, TB TI Radiation-induced skin injuries from fluoroscopy SO RADIOGRAPHICS LA English DT Article; Proceedings Paper CT 1995 Meeting of the Radiological-Society-of-North-America CY NOV 26-DEC 01, 1995 CL CHICAGO, IL SP Radiol Soc N Amer DE fluoroscopy; interventional procedures, complications,; radiations, injurious effects, skin, effects of irradiation on AB Since 1992, the U.S. Food and Drug Administration (FDA) has received reports of radiation-induced injuries to the skin in patients who had undergone fluoroscopically guided interventional procedures. The reports were investigated to determine the procedure- or equipment-related factors that may have contributed to the injury. The injuries ranged in severity from erythema to moist desquamation to tissue necrosis that required skin grafting, They occurred after a variety of interventional procedures that required extended periods of fluoroscopy compared with those of typical diagnostic procedures. Medical facilities and physicians should be aware of the magnitude of radiation doses to the skin that can result from the long exposure times required by complex interventional procedures, The FDA recommends several steps for reducing these injuries, including establishing protocols for each procedure, determining radiation dose rates for specific fluoroscopy systems and operating modes, and monitoring cumulative absorbed doses to areas of the skin. RP Shope, TB (reprint author), US FDA,CTR DEVICES & RADIOL HLTH HFZ140,OFF SCI & TECHNOL,12720 TWINBROOK PKWY,ROCKVILLE,MD 20857, USA. NR 6 TC 185 Z9 190 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP PY 1996 VL 16 IS 5 BP 1195 EP 1199 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VK251 UT WOS:A1996VK25100018 PM 8888398 ER PT J AU Fujimura, RK Bockstahler, LE Goodkin, K Werner, T BrackWerner, R Shapshak, P AF Fujimura, RK Bockstahler, LE Goodkin, K Werner, T BrackWerner, R Shapshak, P TI Neuropathology and virology of HIV associated dementia SO REVIEWS IN MEDICAL VIROLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; CENTRAL-NERVOUS-SYSTEM; NECROSIS-FACTOR-ALPHA; BLOOD-BRAIN-BARRIER; HUMAN CHOROID-PLEXUS; HTLV-III INFECTION; SEROPOSITIVE INDIVIDUALS; CEREBROSPINAL-FLUID; PROVIRAL DNA C1 US FDA, CTR DEVICES & RADIOL HLTH, ROCKVILLE, MD 20857 USA. GSF, INST SAUGETIERGENET, D-85764 OBERSCHLEISSHEIM, GERMANY. GSF, INST MOL VIROL, D-85764 OBERSCHLEISSHEIM, GERMANY. UNIV MIAMI, SCH MED, DEPT PSYCHIAT, MIAMI, FL 33136 USA. UNIV MIAMI, SCH MED, DEPT NEUROL, MIAMI, FL 33136 USA. UNIV MIAMI, SCH MED, DEPT PATHOL, MIAMI, FL 33136 USA. UNIV MIAMI, SCH MED, COMPREHENS DRUG RES CTR, MIAMI, FL 33136 USA. RP Fujimura, RK (reprint author), UNIV MIAMI, SCH MED, DEPT PSYCHIAT, MIAMI, FL 33136 USA. RI Brack-Werner, Ruth/M-4615-2014 OI Brack-Werner, Ruth/0000-0002-8651-9318 NR 109 TC 16 Z9 16 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1052-9276 J9 REV MED VIROL JI Rev. Med. Virol. PD SEP PY 1996 VL 6 IS 3 BP 141 EP 150 DI 10.1002/(SICI)1099-1654(199609)6:3<141::AID-RMV141>3.0.CO;2-1 PG 10 WC Virology SC Virology GA VH295 UT WOS:A1996VH29500002 ER PT J AU Ashwell, JD King, LB Vacchio, MS AF Ashwell, JD King, LB Vacchio, MS TI Cross-talk between the T cell antigen receptor and the glucocorticoid receptor regulates thymocyte development SO STEM CELLS LA English DT Review DE steroids; thymocyte development; thymocyte selection; T cell receptor; glucocorticoids; glucocorticoid receptor; apoptosis ID POSITIVE SELECTION; TRANSGENIC MICE; NEGATIVE SELECTION; INDUCED APOPTOSIS; FREE CORTICOSTERONE; FAS-LIGAND; ACTIVATION; DEATH; THYMUS; BCL-2 AB The fate of an immature thymocyte, life or death, is largely determined by the ligand-specificity of its T cell antigen receptor (TCR), The default pathway for thymocytes bearing TCRs with subthreshold avidity for self-antigens is death (death by neglect), Thymocytes bearing TCRs with high avidity for self also undergo apoptosis (negative selection), Those thymocytes with intermediate avidities, or that perhaps recognize self-peptides that have partial agonist or antagonist properties, survive and differentiate into mature immunocompetent T cells (positive selection), How TCR avidity is interpreted as a ''rescue'' signal or a death signal is unknown, Based upon a T cell hybridoma model, our laboratory proposed that glucocorticoids, which themselves are potent inducers of thymocyte apoptosis, antagonize TCR-mediated thymocyte deletion and allow positive selection to occur, In fact, epithelial cells in the thymus proved to be a source of steroid production, and interference with steroid synthesis in fetal thymic organ culture resulted in a greatly enhanced sensitivity of thymocytes to TCR-mediated apoptosis, Transgenic mice with reduced glucocorticoid receptor (GR) levels were produced by tissue-specific expression of GR antisense, Thymocytes in these mice had high levels of spontaneous apoptosis, and were exquisitely sensitive to deletion induced by cross-linking the TCR, Moreover, there was a very large (greater than or equal to 90%) loss of CD4(+)CD8(+) thymocytes, signifying a block at the CD4(-)CD8(-) to CD4(+)CD8(+) transition, perhaps due to apoptosis of cells upon engagement of the pre-TCR in the absence of an antagonizing glucocorticoid stimulus, The molecular mechanism of the antagonism is currently being investigated, These data indicate that there is cross-talk in thymocytes between the TCR and glucocorticoid signaling pathways resulting in apoptosis, and that locally produced steroids, in a paracrine fashion, participate in setting the TCR avidity thresholds that determine whether developing thymocytes survive or die, and therefore help to mold the antigen-specific T cell repertoire. C1 US FDA, CTR BIOL EVALUAT & RES, DIV HEMATOL PROD, IMMUNOL LAB, BETHESDA, MD USA. RP Ashwell, JD (reprint author), NIH, NCI, LAB IMMUNE CELL BIOL, ROOM 1B-40, BLDG 10, BETHESDA, MD 20852 USA. NR 58 TC 53 Z9 53 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD SEP PY 1996 VL 14 IS 5 BP 490 EP 500 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA VJ494 UT WOS:A1996VJ49400002 PM 8888490 ER PT J AU Whittaker, P Hines, FA Robl, MG Dunkel, VC AF Whittaker, P Hines, FA Robl, MG Dunkel, VC TI Histopathological evaluation of liver, pancreas, spleen, and heart from iron-overloaded Sprague-Dawley rats SO TOXICOLOGIC PATHOLOGY LA English DT Article DE iron toxicity; hepatocellular hemosiderosis; pancreatic atrophy; cardiotoxicity; splenic atrophy; apoptosis ID LIPID-PEROXIDATION; IDIOPATHIC HEMOCHROMATOSIS; PATHOLOGY; LESIONS; DISEASE; STORES; RISK AB The effects of increasing dietary levels of Fe on the histopathology of liver, pancreas, spleen, and heart were examined in a rat model for iron overload. Sprague-Dawley rats were fed diets containing 35, 350, 3,500, or 20,000 mu g Fe/g, and, after 12 wk, there was a direct correlation between increased liver nonheme Fe and lipid peroxidation measured by the lipid-conjugated diene assay. Histopathological examination of tissues revealed the following: (a) hepatocellular hemosiderosis in all groups of rats, with a dose-related accumulation of cytoplasmic Fe-positive material predominantly in hepatocytes located in the periportal region (Zone 1), (b) myocardial degeneration and necrosis (cardiomyopathy) with hemosiderin in interstitial macrophages or in myocardial fibers of animals with heart damage, (c) splenic lymphoid atrophy affecting the marginal zone of the white pulp and hemosiderin deposition in the sinusoidal macrophages, and (d) pancreatic atrophy with loss of both the endocrine and exocrine pancreatic tissue in those animals receiving 3,500 and 20,000 mu g Fe/g of diet. The toxic effects of Fe overload in this rat model include cellular apoptosis or necrosis in heart, spleen, and pancreas and, when coupled with the findings on lipid peroxidation, suggests that oxidative stress is involved in the pathogenesis of the lesions. RP Whittaker, P (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,200 C ST SW,WASHINGTON,DC 20204, USA. NR 29 TC 34 Z9 34 U1 0 U2 1 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 SEP-OCT PY 1996 VL 24 IS 5 BP 558 EP 563 PG 6 WC Pathology; Toxicology SC Pathology; Toxicology GA VR345 UT WOS:A1996VR34500004 PM 8923676 ER PT J AU Poirier, LA AF Poirier, LA TI Food and drug administration workshop on indirect mechanisms of carcinogenesis SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material DE biological and biochemical endpoints; indirect-acting compound; secondary agents AB A workshop sponsored by the Food and Drug Administration (FDA) was held on March 4-5, 1996, at the Lister Hill Auditorium of the National Institutes of Health (NIH) Campus in Bethesda, Maryland. The workshop considered both the scientific aspects and the regulatory implications of indirect-acting carcinogens. A wide variety of agents and of prospective mechanisms was discussed. The organizing committee for the workshop consisted of Drs. James Farrelly and Joseph DeGeorge of the Center for Drug Evaluation and Research (CDER), Ronald J. Lorentzen and Sidney Green of the Center for Food Safety and Applied Nutrition (CFSAN), Martin D. Green of the Center for Biologics, Evaluation and Research (CBER), C. Darnell Jackson and Lionel A. Poirier of the National Center for Toxicological Research (NCTR), Rosalie K. Elespuru of the Center for Devices and Radiological Health (CDRH), and David G. Longfellow of the National Cancer Institute (NCI). Following an introduction by Dr. Poirier, who provided a description of indirect carcinogens, the major talks were grouped into three formal sessions: indirect-acting compounds and agents of FDA interest, biological and biochemical endpoints commonly seen with indirect agents, and specific problems associated with the indirect-acting compounds. A panel discussion followed and the concluding remarks were made by Dr. Bernard A. Schwetz, Associate Commissioner for Science, FDA. RP Poirier, LA (reprint author), US FDA,NATL CTR TOXICOL RES,DIV NUTR TOXICOL,JEFFERSON,AR 72079, USA. NR 0 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 SEP-OCT PY 1996 VL 24 IS 5 BP 659 EP 661 PG 3 WC Pathology; Toxicology SC Pathology; Toxicology GA VR345 UT WOS:A1996VR34500026 PM 8923694 ER PT J AU Lynch, TJ Weinstein, MJ Tankersley, DL Fratantoni, JC Finlayson, JS AF Lynch, TJ Weinstein, MJ Tankersley, DL Fratantoni, JC Finlayson, JS TI Considerations of pool size in the manufacture of plasma derivatives SO TRANSFUSION LA English DT Article ID ACUTE HEPATITIS-A; PARVOVIRUS B19; HEMOPHILIA-A; PREVALENCE; ANTIBODIES; NORWEGIANS; INFECTION; PRODUCTS; VIRUS AB Background: The pooling of human plasma from many donors for the purpose of manufacturing therapeutic proteins increases the risk of exposing recipients of these proteins to pathogens that may contaminate 1 or a few units included in the pool. Study Design and Methods: This risk is estimated for a range of manufacturing scales that would derive material from a varied number of donors and for a number of hypothetical infectious agents that may exist in the donor population over a wide range of prevalence. Risk is also calculated both for recipients of single doses of a plasma protein and for those who depend on long-term treatment with plasma derivatives. Results: Risk of exposure increases with pool size and the prevalence of the agent in question and accumulates with repeated treatments with material manufactured from different pools. Conclusion: Reducing pool size would at best decrease this risk in proportion to the reduction in manufacturing scale. However, for individuals requiring repeated or continuous treatments, the risk of exposure to all but the rarest infectious agents would be only minimally affected, even by large reductions in manufacturing scale. C1 US FDA,DIV HEMATOL,OFF BLOOD RES & REVIEW,CTR BIOL EVALUAT & RES,LAB PLASMA DERIVAT,ROCKVILLE,MD 20852. RP Lynch, TJ (reprint author), US FDA,DIV HEMATOL,OFF BLOOD RES & REVIEW,CTR BIOL EVALUAT & RES,LAB HEMOSTASIS,ROCKVILLE,MD 20852, USA. NR 23 TC 15 Z9 15 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1996 VL 36 IS 9 BP 770 EP 775 DI 10.1046/j.1537-2995.1996.36996420751.x PG 6 WC Hematology SC Hematology GA VJ087 UT WOS:A1996VJ08700003 PM 8823448 ER PT J AU Alving, BM Weinstein, MJ Finlayson, JS Fratantoni, JC AF Alving, BM Weinstein, MJ Finlayson, JS Fratantoni, JC TI Further information on the fibrin sealant conference SO TRANSFUSION LA English DT Letter C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. RP Alving, BM (reprint author), WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,WASHINGTON,DC 20307, USA. NR 1 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1996 VL 36 IS 9 BP 845 EP 846 PG 2 WC Hematology SC Hematology GA VJ087 UT WOS:A1996VJ08700019 ER PT J AU Gross, PA Denning, CR Gaerlan, PF Bonelli, J Bernius, M Dran, S Monk, G Vassallo, M Quinnan, GV Levandowski, R Cataruozolo, PE Wallenstein, S AF Gross, PA Denning, CR Gaerlan, PF Bonelli, J Bernius, M Dran, S Monk, G Vassallo, M Quinnan, GV Levandowski, R Cataruozolo, PE Wallenstein, S TI Annual influenza vaccination: Immune response in patients over 10 years SO VACCINE LA English DT Article ID RESPIRATORY VIRAL-INFECTIONS; CYSTIC-FIBROSIS; YOUNG-ADULTS; EFFICACY AB Objective: To determine the effect of repeated annual influenza immunization on the host's serum antibody. Design: Ten year observational study with cohort design. Setting: Cystic Fibrosis Center at St. Vincent's Hospital and Medical Center, New York City, NY. Patients: thirty-eight children and young adults with cystic fibrosis (CF). Measurements: Serum hemagglutination inhibition (HI) antibody titers were determined at the time of vaccination and 4 weeks later each year in the fall before the influenza epidemic. Shwachman scores were determined each year. Results: While the pre-vaccination and post-vaccination geometric mean serum HI antibody titers varied from year to year, no upward or downward trend was evident over the 10 year period. The reciprocal of the post-vaccination geometric mean HI titers ranged annually from 32 to 74 for the influenza A (H3N2) vaccine strains, from 53 to 133 for the influenza A (H1N1) strains, and from 18 to 174 for influenza B strains. In addition, the majority of vaccinees had a presumably protective post-vaccination serum HI titer greater than or equal to 1:40 each year for all three vaccine strains. The initial mean Shwachman score of the group was 77. The final score of 76 after 10 years was not significantly different. Conclusions: Annual influenza vaccination appears to regularly induce presumably protective serum antibody levels in most CF children and young adults studied over a 10 year period. Copyright (C) 1996 Elsevier Science Ltd. C1 UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,NEWARK,NJ 07103. ST VINCENTS HOSP & MED CTR,DEPT PEDIAT,NEW YORK,NY 10011. NEW YORK MED COLL,VALHALLA,NY. UNIFORMED SERV UNIV HLTH SCI,DEPT PREVENT MED & BIOMETR,BETHESDA,MD 20814. US PHS,CTR BIOL EVALUAT & RES,US FDA,BETHESDA,MD. MT SINAI SCH MED,DEPT BIOMATH SCI,NEW YORK,NY. RP Gross, PA (reprint author), HACKENSACK UNIV,MED CTR,DEPT INTERNAL MED,30 PROSPECT AVE,HACKENSACK,NJ 07601, USA. FU PHS HHS [233-90-1102] NR 27 TC 24 Z9 24 U1 0 U2 2 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD SEP PY 1996 VL 14 IS 13 BP 1280 EP 1284 DI 10.1016/S0264-410X(96)00004-7 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VV440 UT WOS:A1996VV44000016 PM 8961518 ER PT J AU Tischler, AS Sheldon, W Gray, R AF Tischler, AS Sheldon, W Gray, R TI Immunohistochemical and morphological characterization of spontaneously occurring pheochromocytomas in the aging mouse SO VETERINARY PATHOLOGY LA English DT Article DE adrenal medulla; catecholamines; chromogranin A; epinephrine; mice; phenylethanolamine-N-methyltransferase; pheochromocytoma; tyrosine hydroxylase ID CATECHOLAMINE-SYNTHESIZING ENZYMES; RAT ADRENAL-MEDULLA; TRANSGENIC MICE; CHROMAFFIN CELLS; B6C3F1 MICE; PROLIFERATIVE LESIONS; ANTIGEN RETRIEVAL; TISSUE-SECTIONS; CHROMOGRANIN-A; TUMORS AB Pheochromocytomas in mice are rare tumors, and their expression of functional markers has not previously been assessed. In this study, 29 spontaneously occurring mouse pheochromocytomas were characterized morphologically and immunohistochemically to determine whether there are functional correlates to previously described morphological features and to provide a database for comparison with tumors that arise in genetically engineered animals. The tumors were derived from 28 mice 828-1,489 days old, of three genotypes. Considerable cytological and architectural polymorphism was observed both within and between tumors. Most of the tumor cells were comparable in size to normal chromaffin cells or were larger. Small basophilic cells, which are the predominant cell type in rat pheochromocytomas, were usually in the minority. All of the tumors and most of the cells within individual tumors expressed immunoreactive tyrosine hydroxylase (TH). The tumors were variably positive for phenylethanolamine-N-methyltransferase (PNMT) and chromogranin A (CGA). There did not appear to be a global association of specific cytological features with expression of TH, PNMT, or CGA, although cells of similar appearance often shared similar immunoreactivities within individual tumors. Small basophilic cells could be either PNMT-positive or PNMT-negative. The frequency, morphology, and immunophenotype of mouse pheochromocytomas suggest that the mouse may be more appropriate than the rat as a model for human adrenal medullary pathology. In addition, the expression of immunoreactive PNMT by mouse pheochromocytomas suggests that these tumors are a potential source of epinephrine-producing cell lines, for which adequate models currently do not exist. C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RP Tischler, AS (reprint author), TUFTS UNIV,SCH MED,DEPT PATHOL,750 WASHINGTON ST,BOX 802,BOSTON,MA 02111, USA. FU NCI NIH HHS [CA27808, CA48017] NR 43 TC 19 Z9 19 U1 0 U2 0 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD SEP PY 1996 VL 33 IS 5 BP 512 EP 520 PG 9 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA VJ271 UT WOS:A1996VJ27100005 PM 8885177 ER PT J AU Conte, ED Conway, SC Miller, DW Perschbacher, PW AF Conte, ED Conway, SC Miller, DW Perschbacher, PW TI Determination of methylisoborneol in channel catfish pond water by solid phase extraction followed by gas chromatography mass spectrometry SO WATER RESEARCH LA English DT Article DE methylisoborneol; off-flavor ID 2-METHYLISOBORNEOL AB Several compounds exist which are responsible for unwanted taste and odor characteristics that have been found in the edible tissue of the channel catfish (Ictalurus punctatus). Methylisoborneol (MIB), one compound responsible for these off-flavors, is produced through the metabolism of cyanobacteria in aqueous systems such as reservoirs and ponds. The channel catfish accumulates MIB in its tissues from the intake of its culture-pond water. Current methods of analysis for MIB, such as closed- and open-loop stripping, and liquid-liquid extraction, are time-consuming and labor-intensive. A method for the analysis of MIB in catfish culture-pond water is described which, unlike other methods, is rapid, inexpensive, and does not require specialized sample preparation equipment. This method utilizes C-18 solid-phase extraction followed by capillary gas chromatography with detection by mass spectrometry. Standard MIB and the internal standard, butylisoborneol (BIB), were prepared from the reaction of D-camphor with methylmagnesium chloride and n-butyllithium, respectively. Extraction efficiencies for MIB in channel catfish pond water averaged 89% at 101 parts per trillion (ppt) and 84% at 202 parts per billion (ppb). The detection limit of the method was calculated to be 11.5 ppt. Copyright (C) 1996 Elsevier Science Ltd C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72079. UNIV ARKANSAS,PINE BLUFF,AR 71601. NR 9 TC 15 Z9 21 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0043-1354 J9 WATER RES JI Water Res. PD SEP PY 1996 VL 30 IS 9 BP 2125 EP 2127 DI 10.1016/0043-1354(96)00030-9 PG 3 WC Engineering, Environmental; Environmental Sciences; Water Resources SC Engineering; Environmental Sciences & Ecology; Water Resources GA VM119 UT WOS:A1996VM11900024 ER PT J AU Mahmood, I Balian, JD AF Mahmood, I Balian, JD TI Interspecies scaling: Predicting clearance of drugs in humans. Three different approaches SO XENOBIOTICA LA English DT Article ID ANTIPYRINE INTRINSIC CLEARANCE; PLASMA BINDING; ANIMAL DATA; PHARMACOKINETICS; DOG; RAT; MOUSE AB 1. The interspecies scaling approach to predict clearance in humans from animal data was tested for a wide variety of drugs. 2. Three different methods were utilized to generate plots to scale-up the clearance values: (i) method I, clearance versus body weight (simple allometric equation); (ii) method II, product of clearance and maximum life-span potential; (iii) method III, product of clearance and brain weight versus body weight. 3. The circumstances under which the three methods can be applied to predict clearance in humans were evaluated. 4. If the exponent lies between 0.55 to 0.7 then method I predicts clearance reasonably well. 5. If the exponent lies between 0.71 to 1.0 clearance can be predicted reasonably well by method II. 6. If the exponent is > 1.0 clearance can be predicted using method III. RP Mahmood, I (reprint author), US FDA,DIV PHARMACEUT EVALUAT 1,OFF CLIN PHARMACOL & BIOPHARMACEUT,WOODMONT OFF CTR 2,ROCKVILLE,MD 20852, USA. NR 41 TC 151 Z9 154 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD SEP PY 1996 VL 26 IS 9 BP 887 EP 895 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA VK226 UT WOS:A1996VK22600001 PM 8893036 ER PT J AU Chu, CHC Hao, YW Tabor, E AF Chu, CHC Hao, YW Tabor, E TI Hot-spot mutations in hepatitis B virus X gene in hepatocellular carcinoma SO LANCET LA English DT Letter C1 US FDA,DIV TRANSFUS TRANSMITTED DIS,BETHESDA,MD 20852. NR 3 TC 3 Z9 6 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 AUG 31 PY 1996 VL 348 IS 9027 BP 625 EP 626 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VF186 UT WOS:A1996VF18600071 ER PT J AU Wong, L Johnson, GR AF Wong, L Johnson, GR TI Epidermal growth factor induces coupling of protein-tyrosine phosphatase 1D to GRB2 via the COOH-terminal SH3 domain of GRB2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SH2-CONTAINING PHOSPHOTYROSINE PHOSPHATASE; SRC HOMOLOGY-2 DOMAINS; FACTOR RECEPTOR; RAS; INSULIN; KINASE; CORKSCREW; SH-PTP2; SYP; PHOSPHORYLATION AB The Src homology 2 (SH2) and SH3 domain-containing adaptor protein GRB2 and the SH2 domain-containing protein-tyrosine phosphatase 1D (PTP1D, also called SHPTP2, PTP2C, SHPTP3, Syp, or SHP-2) function as positive mediators of growth factor-induced mitogenesis, Epidermal growth factor (EGF) is a potent mitogen for MCF-10A human mammary epithelial cells and EGF receptor-expressing mouse NR6 fibroblasts, Western blot analysis of anti-PTP1D immune complexes derived from EGF-treated cells demonstrated a ligand-dependent coupling between the phosphatase and GRB2 in vivo. Probing of lysates from these cells with glutathione S-transferase (GST) fusion proteins corresponding to the individual domains of GRB2 revealed that this interaction was mediated exclusively by the COOH-terminal SH3 domain of GRB2. Importantly, a GST fusion protein containing the PTP1D SH2 domains was not capable of generating the EGF-induced linkage to GRB2. Additional experiments indicated that neither the binding of the nucleotide exchange factor Sos to GRB2 nor tyrosine phosphorylation of PTP1D was required for EGF-stimulated coupling of PTP1D to GRB2. This is the first demonstration of a growth factor- or cytokine-induced coupling of a protein through an SH3 domain and suggests that GRB2 functions to target PTP1D, in addition to Sos, to the plasma membrane in response to EGF. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. NR 28 TC 32 Z9 32 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 AUG 30 PY 1996 VL 271 IS 35 BP 20981 EP 20984 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VE477 UT WOS:A1996VE47700003 PM 8702859 ER PT J AU Christenson, JC Pavia, AT Woods, ML Carroll, K Nichols, C AF Christenson, JC Pavia, AT Woods, ML Carroll, K Nichols, C TI Ochrobactrum anthropi meningitis associated with cadaveric pericardial tissue processed with a contaminated solution - Utah, 1994 (Reprinted from MMWR, vol 45, pg 671-673, 1996) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 UTAH DEPT HLTH,SALT LAKE CITY,UT 84116. CDC,NATL CTR INFECT DIS,HOSP INFECT PROGRAM,ATLANTA,GA 30333. US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857. RP Christenson, JC (reprint author), UNIV UTAH,SCH MED,SALT LAKE CITY,UT 84112, USA. RI Woods, Marion/G-3126-2013 OI Woods, Marion/0000-0001-7712-4819 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 AUG 28 PY 1996 VL 276 IS 8 BP 596 EP 596 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VC853 UT WOS:A1996VC85300013 ER PT J AU Page, SW Stutsman, MJ AF Page, SW Stutsman, MJ TI US FDA perspectives on economic adulteration. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,CTR FOOD SAFETY,OFF PLANT & DAIRY FOODS & BEVERAGES,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 AUG 25 PY 1996 VL 212 BP 2 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91500002 ER PT J AU Ziobro, GC AF Ziobro, GC TI Current research efforts at FDA on the problem of food adulteration. 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 AUG 25 PY 1996 VL 212 BP 3 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91500003 ER PT J AU Vanderveen, JE AF Vanderveen, JE TI Regulation of fat substitutes. 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 AUG 25 PY 1996 VL 212 BP 25 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91500025 ER PT J AU Chen, JS You, JL Brown, D Woodward, BB AF Chen, JS You, JL Brown, D Woodward, BB TI Detection of meat adulteration using enzyme-linked immunosorbent assay. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 FDACS,DIV FOOD SAFETY,FOOD LAB,TALLAHASSEE,FL 32399. 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 AUG 25 PY 1996 VL 212 BP 33 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91500033 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 ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & 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 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 AUG 25 PY 1996 VL 212 BP 42 EP TOXI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91501078 ER PT J AU Wiese, FW Chang, HC Lloyd, RV Freeman, JP Samokyszyn, VM AF Wiese, FW Chang, HC Lloyd, RV Freeman, JP Samokyszyn, VM TI Peroxidase-catalyzed oxidation of 2,4,6-trichlorophenol. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV ARKANSAS MED SCI HOSP,DIV TOXICOL,LITTLE ROCK,AR 72205. MEMPHIS UNIV,DEPT CHEM,MEMPHIS,TN 38152. US FDA,NATL CTR TOXICOL RES,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 AUG 25 PY 1996 VL 212 BP 43 EP TOXI PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91501079 ER PT J AU Chang, HC Freyaldenhoven, MA Compadre, RL Evans, FE Freeman, JP Samokyszyn, VM AF Chang, HC Freyaldenhoven, MA Compadre, RL Evans, FE Freeman, JP Samokyszyn, VM TI Regiospecificity of peroxyl radical addition to (E)-retinoic acid SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & TOXICOL,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT BIOPHARMACEUT SCI,LITTLE ROCK,AR 72205. NATL CTR TOXICOL RES,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 AUG 25 PY 1996 VL 212 BP 50 EP TOXI PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91501086 ER PT J AU Doerge, DR Divi, RL AF Doerge, DR Divi, RL TI Inhibition of thyroid peroxidase-catalyzed iodination and coupling by minocycline concomitant with conversion to a reactive species. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NATL CTR TOXICOL RES,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 AUG 25 PY 1996 VL 212 BP 61 EP TOXI PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91501097 ER PT J AU Trucksess, MW AF Trucksess, MW TI The use of immunoaffinity columns for mycotoxin analysis. 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. HLTH CANADA,HLTH PROTECT BRANCH,OTTAWA,ON K1A 0L2,CANADA. 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 AUG 25 PY 1996 VL 212 BP 71 EP AGRO PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91500206 ER PT J AU Chen, ET Schroeder, LW AF Chen, ET Schroeder, LW TI A HPL: Method for simultaneous quantitative resolution of mixtures of three types of leachable latex accelerators by using PDA and EC detectors in series. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,CTR DEVICES & RADIOL HLTH,DIV MECH & MAT SCI,ROCKVILLE,MD 20857. 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 AUG 25 PY 1996 VL 212 BP 72 EP ANYL PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91500317 ER PT J AU Sheehan, DM Branham, WS Baker, ME Medlock, KL AF Sheehan, DM Branham, WS Baker, ME Medlock, KL TI Reproductive and developmental toxicity of estrogenic isoflavonoids. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,DHHS,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 AUG 25 PY 1996 VL 212 BP 128 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91500128 ER PT J AU Pahor, M Guralnik, JM Salive, ME Corti, MC Havlik, RJ AF Pahor, M Guralnik, JM Salive, ME Corti, MC Havlik, RJ TI Do calcium antagonists cause cancer? Reply SO LANCET LA English DT Letter C1 US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20857. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. RP Pahor, M (reprint author), UNIV TENNESSEE,DEPT PREVENT MED,MEMPHIS,TN 38105, USA. NR 2 TC 1 Z9 1 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 AUG 24 PY 1996 VL 348 IS 9026 BP 541 EP 542 DI 10.1016/S0140-6736(05)64694-6 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VD427 UT WOS:A1996VD42700039 ER PT J AU Britvan, L Gould, K Dryjanski, J Kerndt, P Mascola, L Sun, R Waterman, S AF Britvan, L Gould, K Dryjanski, J Kerndt, P Mascola, L Sun, R Waterman, S TI Identification of HIV-1 group O infection - 1996 (Reprinted from MMWR, vol 45, pg 561-565, 1996) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 LOS ANGELES CTY DEPT HLTH SERV,LOS ANGELES,CA. CALIF DEPT HLTH SERV,SACRAMENTO,CA 95814. US FDA,OFF BLOOD RES & REVIEW,ROCKVILLE,MD 20857. CDC,NATL CTR INFECT DIS,DIV AIDS STD & TB LAB RES,ATLANTA,GA 30333. CDC,NATL CTR HIV STD & TB PREVENT,DIV HIV AIDS PREVENT,ATLANTA,GA 30333. RP Britvan, L (reprint author), KAISER PERMANENTE MED GRP,SAN DIEGO,CA 92103, 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 AUG 21 PY 1996 VL 276 IS 7 BP 521 EP 522 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VC101 UT WOS:A1996VC10100010 ER PT J AU Schreurs, BG Lester, DS AF Schreurs, BG Lester, DS TI High-resolution fluorescent labeling of living cerebellar slices SO BRAIN RESEARCH LA English DT Article DE cerebellum; slice; fluorescence; microscopy; phospholipid ID PROTEIN-KINASE-C; PURKINJE-CELL DENDRITES; ACID; PROJECTIONS AB In the present study, we extend previous research on staining of living brain slices with fluorescent phospholipids. This new procedure allows high-resolution staining of specific cell types, in particular, Purkinje cells, in the cerebellar slice while not affecting the intrinsic electrical activity of the tissue. Four different nitrobenzoxadiole (NBD)-phospholipids were incorporated into living cerebellar slices via loading from small unilamellar vesicles (SUVs), composed of a carrier and the fluorescent lipid. The labeled acidic phospholipid, NBD-phosphatidic acid (NBD-PA), produced the highest resolution images with exquisite labeling of the dendritic fields. The label was incorporated predominantly into the Purkinje cell body (excluding the nucleus), with more diffuse staining in other cell types, including stellate, basket and granule cells. The labeled lipid concentration and composition of the carrier Lipid were significant in determining the specificity of labeling. Labeling, which was optimal after a 1 h incubation, was present throughout the depth of the slice. This procedure provides a promising approach to fluorescent labeling that will allow simultaneous monitoring of changes in cellular morphology and electrophysiology of living brain slices. C1 US FDA,CDER,DIV RES TESTING,LAUREL,MD 20708. NINCDS,NIH,LAB ADAPT SYST,BETHESDA,MD 20892. OI Schreurs, Bernard/0000-0002-5776-0807 NR 22 TC 0 Z9 0 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 AUG 19 PY 1996 VL 730 IS 1-2 BP 125 EP 132 PG 8 WC Neurosciences SC Neurosciences & Neurology GA VH291 UT WOS:A1996VH29100014 PM 8883896 ER PT J AU French, ED Dillon, K Ali, SF AF French, ED Dillon, K Ali, SF TI Effects of ibogaine, and cocaine and morphine after ibogaine, on ventral tegmental dopamine neurons SO LIFE SCIENCES LA English DT Letter DE ibogaine; cocaine; morphine; ventral tegmental dopamine neurons ID INDUCED LOCOMOTOR STIMULATION; NMDA RECEPTOR COMPLEX; INVIVO MICRODIALYSIS; MK-801 BINDING; RATS; AMPHETAMINE; MICE AB Ibogaine, an indole containing alkaloid, has been shown to reduce the rate of injection of morphine and cocaine in self-administration protocols. Since morphine- and cocaine-induced modulation of dopamine release is impulse dependent and essential for their reinforcing effects, disruption of dopamine neuronal activity by ibogaine could explain its purported 'antiaddictive' properties. Therefore, the present study was designed to determine. (1) the acute effects of ibogaine on the activity of VTA dopamine neurons, and (2) whether ibogaine pretreatment causes a persistent modification of the dopamine neuronal response to morphine and cocaine. Extracellular recordings in anesthetized animals found that intravenous ibogaine markedly excited VTA dopamine neuronal firing. However, ibogaine pretreatment (6-8 hr and 19 hr before) failed to alter either the spontaneous activity of VTA neurons, or the response of these dopamine neurons to morphine or cocaine. Thus, ibogaine's excitatory effect on VTA neurons is not longlasting nor does it persistently alter cocaine- or morphine-induced changes in dopamine neuron impulse activity. Therefore, other mechanisms must be explored to account for the proposed antiaddictive properties of ibogaine. C1 NATL CTR TOXICOL RES,DIV NEUROTOXICOL,NEUROCHEM LAB,JEFFERSON,AR 72079. RP French, ED (reprint author), UNIV ARIZONA,COLL MED,DEPT PHARMACOL,TUCSON,AZ 85724, USA. NR 17 TC 2 Z9 2 U1 0 U2 0 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 AUG 16 PY 1996 VL 59 IS 12 BP PL199 EP PL205 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA VC753 UT WOS:A1996VC75300012 ER PT J AU Rosen, RL Winestock, KD Chen, G Liu, XW Hennighausen, L Finbloom, DS AF Rosen, RL Winestock, KD Chen, G Liu, XW Hennighausen, L Finbloom, DS TI Granulocyte-macrophage colony-stimulating factor preferentially activates the 94-kD STAT5A and an 80-kD STAT5A isoform in human peripheral blood monocytes SO BLOOD LA English DT Article ID TYROSINE PHOSPHORYLATION; TRANSCRIPTION FACTORS; GAMMA-INTERFERON; GENE FAMILY; T-CELLS; CYTOKINE; SIGNALS; EXPRESSION; PROTEINS; RECEPTOR AB Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces immediate effects in monocytes by activation of the Janus kinase (JAK2) and STAT transcription factor (STAT5) pathway. Recent studies have identified homo logues of STAT5, STAT5A, and STAT5B, as well as lower molecular weight variants of STAT5. To define the activation of the STAT5 homologues and lower molecular weight variant in human monocytes and monocytes differentiated into macrophages by culture in macrophage-CSF (M-CSF), we measured the GM-CSF induced tyrosine phosphorylation of STAT5A, STAT5B, and any lower molecular weight STAT5 isoforms. Freshly isolated monocytes expressed 94-kD STAT5A, 92-kD STAT5B, and an 80-kD STAT5A molecule. Whereas 94-kD STAT5A was clearly tyrosine phosphorylated and bound to the enhancer element, the gamma response region (GRR), of the Fc gamma RI gene, substantially less tyrosine phosphorylated STAT5B bound to the immobilized GRR element. Macrophages lost their ability to express the 80-kD STAT5A protein, but retained their ability to activate STAT5A. STAT5A-STAT5A homodimers and STAT5A-STAT5B heterodimers formed in response to GM-CSF. Therefore, activation of STAT5A predominates compared to STAT5B when assayed by direct immunoprecipitation and by evaluation of bound STATs to immobilized GRR. Selective activation of STAT5 homologues in addition to generation of lower molecular isoforms may provide specificity and control to genes expressed in response to cytokines such as GM-CSF. C1 US FDA,DIV CYTOKINE BIOL,CTR BIOL RES & EVALUAT,BETHESDA,MD 20892. NIDDKD,BIOCHEM LAB,BETHESDA,MD. NR 27 TC 80 Z9 80 U1 1 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 AUG 15 PY 1996 VL 88 IS 4 BP 1206 EP 1214 PG 9 WC Hematology SC Hematology GA VC854 UT WOS:A1996VC85400009 PM 8695838 ER PT J AU Kaplan, G Totsuka, A Thompson, P Akatsuka, T Moritsugu, Y Feinstone, SM AF Kaplan, G Totsuka, A Thompson, P Akatsuka, T Moritsugu, Y Feinstone, SM TI Identification of a surface glycoprotein on African green monkey kidney cells as a receptor for hepatitis A virus SO EMBO JOURNAL LA English DT Article DE HAV; integral membrane glycoprotein; mucin; picornavirus; virus receptor ID A-VIRUS; MOLECULAR-CLONING; MONOCLONAL-ANTIBODY; IMMUNE-COMPLEXES; XENOPUS-LAEVIS; GENE; CULTURE; PROTEIN; LINES; CDNA AB Very little is known about the mechanism of cell entry of hepatitis A virus (HAV), and the identification of cellular receptors for this picornavirus has been elusive. Here we describe the molecular cloning of a cellular receptor for HAV using protective monoclonal antibodies raised against susceptible African green monkey kidney (AGMK) cells as probes, Monoclonal antibodies 190/4, 235/4 and 263/6, which reacted against similar epitopes, specifically protected AGMK cells against HAV infection by blocking the binding of HAV, Expression; cloning and nucleotide sequence analysis of the cDNA coding for epitope 190/4 revealed a novel mucin-like class I integral membrane glycoprotein of 451 amino acids, the HAV cellular receptor 1 (HAV cr-1). Immunofluorescence anal;sis indicated that mouse Ltk(-) cells transfected with HAV cr-1 cDNA gained Limited susceptibility to HAV infection, which was blocked by treatment with monoclonal antibody 190/4, Our results demonstrate that the HAV cr-1 polypeptide is an attachment receptor for HAV and strongly suggest that it is also a functional receptor which mediates HAV infection, This report constitutes the first identification of a cellular receptor for HAV. C1 NATL INST HLTH,DEPT VIRAL DIS & VACCINE CONTROL,TOKYO 208,JAPAN. RP Kaplan, G (reprint author), NIH,US FDA,CTR BIOL EVALUAT & RES,LAB HEPATITIS RES,OFF VACCINE REVIEW & RES,DIV VIRAL PROD,BETHESDA,MD 20892, USA. NR 57 TC 152 Z9 163 U1 0 U2 8 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD AUG 15 PY 1996 VL 15 IS 16 BP 4282 EP 4296 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VE353 UT WOS:A1996VE35300021 PM 8861957 ER PT J AU Oravecz, T Pall, M Norcross, MA AF Oravecz, T Pall, M Norcross, MA TI beta-chemokine inhibition of monocytotropic HIV-1 infection - Interference with a postbinding fusion step SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; LEUKOCYTE CHEMOATTRACTANT RECEPTORS; T-CELL ACTIVATION; HEPARAN-SULFATE; REPLICATION; BINDING; MIP-1-BETA; RANTES; CD26 AB The beta-chemokines RANTES, MIP-1 alpha, and MIP-1 beta have potent suppressive effects on HIV-1 infection resulting from an early postbinding block in virus fusion and entry, inhibition was observed only with monocytotropic isolates and mapped to the V3 region of the HIV-1 envelope. RANTES did not inhibit virus expression in chronically infected cells or reduce initial virus attachment to the cell membrane. Inhibitory activity required RANTES binding to the target cell but not G protein-mediated signaling or protein tyrosine kinase activity. The results are consistent with a reversible competitive mechanism of virus inhibition that prevents a V3-associated postbinding step in membrane fusion. The data support a role for a RANTES chemokine receptor as a coreceptor for monocytotropic HIV-1. C1 NIH,DIV HEMATOL PROD,CTR BIOL EVALUAT & RES,US FDA,BETHESDA,MD 20892. NR 29 TC 129 Z9 130 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 AUG 15 PY 1996 VL 157 IS 4 BP 1329 EP 1332 PG 4 WC Immunology SC Immunology GA VH124 UT WOS:A1996VH12400001 PM 8759710 ER PT J AU Nightingale, SL AF Nightingale, SL TI FDA conference on human subject protection 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 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 AUG 14 PY 1996 VL 276 IS 6 BP 443 EP 443 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VA863 UT WOS:A1996VA86300005 PM 8691538 ER PT J AU Nightingale, SL AF Nightingale, SL TI One-day course on clinical trials 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 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 AUG 14 PY 1996 VL 276 IS 6 BP 443 EP 443 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VA863 UT WOS:A1996VA86300008 PM 8691538 ER PT J AU Nightingale, SL AF Nightingale, SL TI Quality of mammography facilities improved 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 2 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 AUG 14 PY 1996 VL 276 IS 6 BP 443 EP 443 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VA863 UT WOS:A1996VA86300007 PM 8691538 ER PT J AU Nightingale, SL AF Nightingale, SL TI T-PA approved for acute ischemic stroke 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 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 AUG 14 PY 1996 VL 276 IS 6 BP 443 EP 443 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VA863 UT WOS:A1996VA86300006 PM 8691538 ER PT J AU Pravdenkova, SV Basnakian, AG James, SJ Andersen, BJ AF Pravdenkova, SV Basnakian, AG James, SJ Andersen, BJ TI DNA fragmentation and nuclear endonuclease activity in rat brain after severe closed head injury SO BRAIN RESEARCH LA English DT Article DE closed head injury; head trauma; apoptosis; cell death; Ca/Mg-dependent endonuclease; nucleus; DNA fragmentation ID PROGRAMMED CELL-DEATH; APOPTOSIS; MECHANISMS; ACTIVATION; CALCIUM; CYCLE; MODEL AB Previous studies have suggested that brain cells undergo apoptotic cell death during several neurodegenerative disorders such as Alzheimer's disease, Parkinsonism and ischemic stroke. In the present study, apoptotic DNA fragmentation and activation of nuclear endonuclease were evaluated in rat brain cells after head trauma. Severe closed head injury was induced in rats by the impact of a 450-g weight dropped from a height of 2 m. A 12% mortality was experienced after head trauma. Brain cell nuclei and DNA were isolated at intervals of 3, 10, 24 h, 3 and 10 days after head trauma. DNA fragmentation was measured by the random oligonucleotide-primed synthesis (ROPS) assay and was significantly increased with the maximum level of DNA fragmentation occurring at 10 h after trauma. The DNA and nuclei yields decreased 10 h after injury and remained at a reduced level at all subsequent sampling intervals. The DNA fragmentation induced after severe head trauma was accompanied by an increase in the activity of the Ca/Mg-dependent endonuclease associated with apoptosis. These data indicate that severe head injury is associated with significant brain cell death by apoptosis. C1 UNIV ARKANSAS MED SCI HOSP,LITTLE ROCK,AR 72205. NATL CTR TOXICOL RES,DIV NUTR TOXICOL,US FDA,JEFFERSON,AR 72079. NYU MED CTR,NEW YORK,NY 10016. NR 33 TC 54 Z9 58 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 12 PY 1996 VL 729 IS 2 BP 151 EP 155 DI 10.1016/0006-8993(96)00222-3 PG 5 WC Neurosciences SC Neurosciences & Neurology GA VE644 UT WOS:A1996VE64400002 PM 8876983 ER PT J AU Ahn, CH Kong, JY Choi, WC Hwang, MS AF Ahn, CH Kong, JY Choi, WC Hwang, MS TI Selective inhibition of the effects of phorbol ester on doxorubicin resistance and P-glycoprotein by the protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7) in multidrug-resistant MCF-7/Dox human breast carcinoma cells SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE multidrug resistance; protein kinase C; P-glycoprotein; phorbol ester; breast cancer ID TUMOR-CELLS; DRUG-RESISTANCE; CYCLOSPORINE-A; CANCER-CELLS; BETA-II; VERAPAMIL; REVERSAL; IDENTIFICATION; ACCUMULATION; EXPRESSION AB The possible regulation of the multidrug-resistant (MDR) phenotype and P-glycoprotein by protein kinase C (PKC) was investigated in the doxorubicin (Dox)-resistant MCF-7 cell line (MCF-7/Dox). In a clonogenic assay, cells exposed to 100 nM phorbol 12-myristate 13-acetate (PMA) for 1 hr were about 3-fold more resistant to Dox than were cells exposed to Dox alone. The PKC inhibitor 1-(5-isoquinolinesulionyl)-2-methylpiperazine (H7, 30 mu M) completely blocked the PMA-induced effect, but did nut reverse the MDR phenotype. Complete down-regulation of PKC from MCF-7/Dox cells by 24-hr preincubation with PMA did not alter the degree of Dox resistance. Intracellular accumulation of [C-14]Dox decreased from a baseline of 28 pmol/10(6) cells to 15 pmol/10(6) cells in the presence of 100 nM PMA. The reduced Dox accumulation in the presence of PMA was not blocked by pretreatment of cells with H7. Following a 24-hr pretreatment with PMA, the cells accumulated almost equal amounts of [C-14]Dox in the absence or presence of PMA. Cells from PMA-treated colonies showed significantly higher levels of expression of P-glycoprotein when compared with those from control colonies. H7 did not affect the basal level of P-glycoprotein in cells from control colonies or PMA induced overexpression of P-glycoprotein in cells from PMA-treated colonies. Upon stimulation with PMA (100 nM), PKC alpha and beta translocated to the cell membrane and nucleus and PKC delta and epsilon to the perinuclear membrane and the nucleus, respectively. H7 (30 mu M) completely inhibited PMA-induced translocations of PKC delta and epsilon, whereas it only partially blocked the translocations of PKC alpha and beta. These results suggest that PMA appears to alter Dox resistance and intracellular Dox accumulation in a PKC-dependent manner and to induce increased expression of P-glycoprotein in MCF-7/Dox cells. Differential effects of H7 on the PMA-induced changes suggest that different isoforms of PKC may be involved in cell growth and drug accumulation processes as well as P-glycoprotein expression. C1 US FDA,CTR DRUG EVALUAT & RES,DIV RES & TESTING,ROCKVILLE,MD 20857. RP Ahn, CH (reprint author), US FDA,CDER,DIV ONCOL,HFD 150,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 45 TC 6 Z9 7 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD AUG 9 PY 1996 VL 52 IS 3 BP 393 EP 399 DI 10.1016/0006-2952(96)00240-7 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UU196 UT WOS:A1996UU19600002 PM 8687492 ER PT J AU Vostal, JG Shafer, B AF Vostal, JG Shafer, B TI Thapsigargin-induced calcium influx in the absence of detectable tyrosine phosphorylation in human platelets SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTRACELLULAR CA2+ STORES; PROTEIN-KINASE-C; PLASMA-MEMBRANE; CA-2+ ENTRY; GENISTEIN; ACTIVATION; INHIBITORS; RECEPTOR; MOBILIZATION; MECHANISMS AB Tyrosine phosphorylation is a potential mechanism for mediating store-operated calcium (SOC) influx in platelets and other nonexcitable cells. Thapsigargin induces calcium-dependent tyrosine phosphorylation and SOC influx in platelets. We prevented thapsigargin-induced tyrosine phosphorylation by buffering cytosolic calcium rise with the calcium chelator 1,2-bis-(o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid-acetomethoxyester (BAPTA-AM). Calcium influx, induced by thapsigargin and measured by Ca-45(2+) accumulation, persisted in BAPTA-loaded platelets in the absence of tyrosine phosphorylation. This calcium influx was blocked by the SOC influx inhibitor SKF-96365. Tyrosine kinase inhibitors have been used to demonstrate a role for tyrosine phosphorylation in SOC influx. We compared the effects of four tyrosine kinase inhibitors genistein, methyl-2,5-dihydroxycinnamate (erbstatin analog), tyrphostin A47, and lavendustin A, on thapsigargin-induced tyrosine phosphorylation in control platelets and on thapsigargin-induced SOC influx into BAPTA-loaded platelets in absence of tyrosine phosphorylation, Tyrphostin A47 prevented all measurable tyrosine phosphorylation in control platelets, but did not decrease calcium influx into BAPTA-loaded platelets. Genistein and the erbstatin analog were poor inhibitors of tyrosine phosphorylation but decreased SOC influx into BAPTA-loaded platelets to 55.8 +/- 3% and 51.9 +/- 7.5% of control, respectively. Lavendustin A did not decrease tyrosine phosphorylation or calcium influx. Thus, thapsigargin-induced SOC influx can occur without detectable tyrosine phosphorylation and the inhibition of SOC influx by tyrosine kinase inhibitors does not correlate with their ability to prevent tyrosine phosphorylation. RP Vostal, JG (reprint author), US FDA,CBER,DIV HEMATOL,LAB CELLULAR HEMATOL,BLDG 29,RM 323,HFM 335,BETHESDA,MD 20892, USA. NR 36 TC 25 Z9 25 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 AUG 9 PY 1996 VL 271 IS 32 BP 19524 EP 19529 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB684 UT WOS:A1996VB68400079 PM 8702645 ER PT J AU Lin, ST Jih, YF Fu, PP AF Lin, ST Jih, YF Fu, PP TI Mass spectral analysis of nitropolycyclic aromatic hydrocarbons with torsion angle obtained from semiempirical calculations SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID MECHANICAL MOLECULAR-MODELS; DIRECT-ACTING MUTAGENICITY; NITRO-GROUP ORIENTATION; 6-NITROBENZOPYRENE; DERIVATIVES; SUBSTITUENT AB The mass spectra of nitroarenes were studied under EI conditions. The spectra consist of the signals from loss of 30 and 46 mass units along with molecular ions and doubly charged ions of [M - 47](+). The ratios between [M - 30](+) and ([M - 46](+) + [M - 47](+)) are well correlated with the torsion angles of O-N-C-C obtained from calculation using the PM3 method except that the nitro group is between two peri positions. C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72709. RP Lin, ST (reprint author), PROVIDENCE UNIV,DEPT APPL CHEM,SHA LU,TAICHUNG 433,TAIWAN. NR 24 TC 22 Z9 22 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD AUG 9 PY 1996 VL 61 IS 16 BP 5271 EP 5273 DI 10.1021/jo9602276 PG 3 WC Chemistry, Organic SC Chemistry GA VD350 UT WOS:A1996VD35000018 ER PT J AU Yin, JJ Smith, MJ Eppley, RM Page, SW Sphon, JA AF Yin, JJ Smith, MJ Eppley, RM Page, SW Sphon, JA TI Effects of fumonisin B-1 on oxygen transport in membranes SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID NITROXIDE SPIN-LABEL; FUSARIUM-MONILIFORME; BACTERIORHODOPSIN MUTANTS; LIPID BILAYERS; DIFFUSION; RESONANCE; PARAMETER; TOXICITY; DISEASES; BARRIER AB Electron spin resonance (ESR) spin-label oximetry has been used to study the effects of fumonisin B-1 (FB1), a sphingoid-like mycotoxin, on oxygen transport in phosphatidylcholine (PC) bilayers. Moreover, the use of spin labels attached to different carbons of fatty acids makes it possible to do structural and oximetric determinations with the same test sample. Specifically, the incorporation of 10 mol% FB1 increased the oxygen transport properties of both saturated and unsaturated membranes at 37 degrees C by ca. 30% and decreased the ordering of the hydrocarbon chains near the surface of the membranes; concomitantly, oxygen transport near the center of bilayers was diminished slightly, and the relative oxygen diffusion-concentration product profile curves were markedly flattened. (C) 1996 Academic Press, Inc. RP Yin, JJ (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204, USA. RI Yin, Jun Jie /E-5619-2014 NR 33 TC 13 Z9 13 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 AUG 5 PY 1996 VL 225 IS 1 BP 250 EP 255 DI 10.1006/bbrc.1996.1162 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VE983 UT WOS:A1996VE98300042 PM 8769126 ER PT J AU Pipkin, JL Hinson, W LynCook, LE Duffy, PH Feuers, RJ Leakey, JEA Aly, KB Hart, RW Casciano, DA AF Pipkin, JL Hinson, W LynCook, LE Duffy, PH Feuers, RJ Leakey, JEA Aly, KB Hart, RW Casciano, DA TI The effect of aging and dietary restriction on the retinoylation of nuclear matrix proteins in rats SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE aging; diet restriction; nuclear matrix proteins; retinoylation ID RETINOIC ACID; CALORIC RESTRICTION; STRESS PROTEINS; POLYACRYLAMIDE GELS; CELL; LEUKEMIA; PHOSPHORYLATION; INDUCTION; HL-60 AB The labeling in vivo of young ad libitum (Y/AL) and old diet restricted (O/DR) rats with [H-3]retinoic acid (RA) for 6 hours, and the exposure of electrophoretically separated nuclear matrix proteins from bone marrow tissue on film for 48 days revealed the presence of eleven retinoylated proteins. Dosing with RA (100 mg/kg body weight;) for 96 hours and exposure to [H-3]RA enhanced the levels of radioactive incorporation of several nuclear matrix proteins, including p51, and p55, similarly in Y/AL and O/DR rats. Dosing of old ad libitum (O/AL) rats with [H-3]RA for 6 hours showed the incorporation of six proteins following 48 days of exposure on film. Long-term dosing of RA (96 hours) did not increase [H-3]RA incorporation in these proteins, including p51 and p55, in O/AL rats. Increasing the level of RA by two-fold (200 mg/kg body weight;) in Y/AL and O/DR rats elicited an increase in the incorporation levels of [H-3]R4 in five proteins. This dose response following increased levels of RA was not seen in the retinoylated proteins of O/AL animals. Analysis by the Western blotting technique showed p51 and p55 from rat bone marrow cells to have the same immunochemical determinates with proteins of identical molecular masses in HL60 cells. The levels of retinoylation of nuclear matrix proteins in O/DR animals, altered by age- and diet-dependent factors, suggests a condition that is more reminiscent of Y/AL than of O/AL animals. (C)1994, Editrice Kurtis RP Pipkin, JL (reprint author), NATL CTR TOXICOL RES,DIV GENET TOXICOL,HFT-120,3900 NC-TR RD,JEFFERSON,AR 72079, USA. NR 30 TC 5 Z9 5 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0394-9532 J9 AGING-CLIN EXP RES JI Aging-Clin. Exp. Res. PD AUG PY 1996 VL 8 IS 4 BP 263 EP 270 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA VK199 UT WOS:A1996VK19900007 PM 8904956 ER PT J AU Conte, ED Shen, CY Miller, DW Perschbacher, PW AF Conte, ED Shen, CY Miller, DW Perschbacher, PW TI Microwave distillation-solid phase adsorbent trapping device for the determination of off-flavors, geosmin and methylisoborneol, in catfish tissue below their rejection levels SO ANALYTICAL CHEMISTRY LA English DT Article ID CHANNEL CATFISH; PONDS AB Described is a rapid microwave-mediated steam distillation device for determining two predominant off-flavor compounds, geosmin and methylisoborneol, in catfish tissue. A microwave on-time of 10 min is needed to efficiently remove these off-flavor compounds from the sample matrix and trap them on a solid phase adsorbent, A minimal amount of organic solvent is used to elute the trapped compounds. The extract is then analyzed by gas chromatography with ion trap detection in the selective ion storage mode. Detection limits in the sub-parts-per-billion range are obtained with this method. C1 UNIV ARKANSAS,AGR EXPT STN,PINE BLUFF,AR 71601. RP Conte, ED (reprint author), NATL CTR TOXICOL RES,DIV CHEM,JEFFERSON,AR 72079, USA. NR 11 TC 26 Z9 28 U1 0 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD AUG 1 PY 1996 VL 68 IS 15 BP 2713 EP 2716 DI 10.1021/ac960296k PG 4 WC Chemistry, Analytical SC Chemistry GA VA003 UT WOS:A1996VA00300048 PM 8694266 ER PT J AU Harp, JA Fayer, R Pesch, BA Jackson, GJ AF Harp, JA Fayer, R Pesch, BA Jackson, GJ TI Effect of pasteurization on infectivity of Cryptosporidium parvum oocysts in water and milk SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID OUTBREAK AB Cryptosporidium parvum is a major cause of diarrheal disease in humans and has been identified in 78 other species of mammals, The oocyst stage, excreted in feces of infected humans and animals, has been responsible for recent waterborne outbreaks of human cryptosporidiosis. High temperature and long exposure time have been shown to render oocysts (suspended in water) noninfectious, but for practical purposes, it is important to know if high-temperature-short-time conditions (71.7 degrees C for 15 s) used in commercial pasteurization are sufficient to destroy infectivity of oocysts, In this study, oocysts were suspended in either water or whole milk and heated to 71.7 degrees C for 15, 10, or 5 s in a laboratory-scale pasteurizer. Pasteurized and nonpasteurized (control) oocysts were then tested for the ability to infect infant mice, No mice (0 of 177) given 10(5) oocysts pasteurized for 15, 10, or 5 s in either water or milk were found to be infected with C. parvum on the basis of histologic examination of the terminal ileum. In contrast, all (80 of 80) control mice given nonpasteurized oocysts were heavily infected. These data indicate that high-temperature-short-time pasteurization is sufficient to destroy the infectivity of C. parvum oocysts in water and milk. C1 BELTSVILLE AGR RES CTR E,IMMUN & DIS RESISTANCE LAB,BELTSVILLE,MD 20705. US FDA,WASHINGTON,DC 20204. RP Harp, JA (reprint author), USDA ARS,NATL ANIM DIS CTR,METAB DIS & IMMUNOL RES UNIT,POB 70,AMES,IA 50010, USA. NR 13 TC 53 Z9 58 U1 0 U2 7 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 AUG PY 1996 VL 62 IS 8 BP 2866 EP 2868 PG 3 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA UZ996 UT WOS:A1996UZ99600029 PM 8702279 ER PT J AU Reimer, L Brokopp, C Mottice, S Den, R Nichols, C AF Reimer, L Brokopp, C Mottice, S Den, R Nichols, C TI Persistent lack of detectable HIV-1 antibody in a person with HIV infection - Utah, 1995 SO ARCHIVES OF DERMATOLOGY LA English DT Article C1 UNIV UTAH,SALT LAKE CITY,UT 84112. UTAH DEPT HLTH,SALT LAKE CITY,UT 84116. US FDA,OFF BLOOD RES & REV,ROCKVILLE,MD 20857. CDC,NATL CTR INFECT DIS,DIV AIDS STD & TB LAB RES,ATLANTA,GA. CDC,NATL CTR PREVENT SERV,DIV HIV AIDS PREVENT,ATLANTA,GA. RP Reimer, L (reprint author), VET AFFAIRS MED CTR,SALT LAKE CITY,UT 84148, USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD AUG PY 1996 VL 132 IS 8 BP 873 EP 874 PG 2 WC Dermatology SC Dermatology GA VB378 UT WOS:A1996VB37800001 ER PT J AU Merritt, K Brown, SA AF Merritt, K Brown, SA TI Distribution of cobalt chromium wear and corrosion products and biologic reactions SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TOTAL HIP-REPLACEMENT; TOTAL JOINT REPLACEMENTS; METAL SENSITIVITY; OCCUPATIONAL ASTHMA; STAINLESS-STEEL; NICKEL; ARTHROPLASTY; RELEASE; SERUM; ANTIBODIES AB Replacement hip arthroplasty with the use of ultrahigh molecular weight polyethylene for the cup articulating with a metal head has provided a low friction arthroplasty with years of success. However, the search for improved materials and designs for articulating surfaces continues. The use of metallic heads articulating with metallic cups is now being reconsidered for total hip replacements. Success will be enhanced if wear and corrosion of the articulating surfaces can be kept below that of the metal on ultrahigh molecular weight polyethylene couple. Concern has been raised about the release, and biologic fate, of metal species from corrosion and wear. Titanium alloys have been shown to have limitations as an articulating surface showing significant wear, and the alloy per se should not be considered for wear couples in total hip replacements. The cobalt chromium alloys are known to have reasonable wear and corrosion properties and continue to be evaluated. The issue of cobalt chromium wear and corrosion products and how this relates to the biologic performance of total hip replacement devices is reviewed. Under the condition of wear as currently experienced at the articulating surfaces of cobalt chromium alloys and ultrahigh molecular weight polyethylene, the amount of metallic products transferred to the tissues is sufficiently low to be well tolerated by the biologic system. Nickel and cobalt ions are rapidly transported from the implant site and eliminated in the urine, Chromium is stored in the tissue and eliminated more slowly. The issue of host hypersensitivity to these elements remains of concern. All 3 elements, in ionic form, are known to cause contact dermatitis. Untoward biologic reactions, including hypersensitivity, should be minimized if wear and corrosion phenomena are minimized. C1 US FDA, DIV MECH & MAT SCI, CTR DEVICES & RADIOL HLTH, OFF SCI & TECHNOL, ROCKVILLE, MD 20852 USA. RP Merritt, K (reprint author), US FDA, DIV LIFE SCI, CTR DEVICES & RADIOL HLTH, OFF SCI & TECHNOL, 12709 TWINBROOK PKWY, ROCKVILLE, MD 20852 USA. NR 71 TC 47 Z9 51 U1 2 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD AUG PY 1996 IS 329 SU S BP S233 EP S243 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA VC782 UT WOS:A1996VC78200020 PM 8769337 ER PT J AU Marinac, JS Balian, JD Foxworth, JW Willsie, SK Daus, JC Owen, R Flockhart, DA AF Marinac, JS Balian, JD Foxworth, JW Willsie, SK Daus, JC Owen, R Flockhart, DA TI Determination of CYP2C19 phenotype in black Americans with omeprazole: Correlation with genotype SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID S-MEPHENYTOIN METABOLISM; POLYMORPHIC HYDROXYLATION; CYTOCHROME-P450 2C19; GENETIC-POLYMORPHISM; DRUG-METABOLISM; BLADDER-CANCER; OXIDATION; POPULATION; DEBRISOQUINE; DISPOSITION AB Background: Our objective was to study omeprazole as a single-dose oral probe in the determination of CYP2C19 phenotype in black subjects and to determine the correlation between phenotype and genotype. Methods: This single-dose, open-label outpatient study was conducted at a community-based, university-affiliated teaching hospital outpatient clinic, Study subjects were 100 healthy, unrelated black adults (age range, 18 to 50 years) who were receiving no medications, Baseline omeprazole and 2-hour postingestion omeprazole and 5'-hydroxyomeprazole concentrations mere measured for phenotype determination, Identification of CTP2C19(ml) genotypes were performed with use of the polymerase chain reaction. Results: Results mere obtained for 28 men and 72 women. Ninety-eight subjects were found to be phenotypically extensive metabolizers and two to be poor metabolizers (one man; one smoker), Genotype determination revealed that the two poor metabolizers of omeprazole were homozygous for a single base pair mutation (m(1)/m(1)) in exon 5 of CTP2C19, Twenty-eight of the extensive metabolizers were heterozygous (m(1)/wt) and the remaining 70 were homozygous (wt/wt), No side effects were reported, Conclusions: The 2% prevalence rate of poor CYP2C19 metabolizers in this healthy black population residing in the Midwestern United States is similar to that reported in white subjects and in the Shona population of Zimbabwe but much less than in Asian subjects, Omeprazole is a safe and specific probe of the CYP2C19 enzyme system that correlates well with genotype. C1 GEORGETOWN UNIV,MED CTR,DEPT MED,WASHINGTON,DC 20057. GEORGETOWN UNIV,MED CTR,DEPT PHARMACOL,WASHINGTON,DC 20057. US FDA,WASHINGTON,DC 20204. RP Marinac, JS (reprint author), UNIV MISSOURI,SCH MED,DIV CLIN PHARMACOL,DEPT MED,2411 HOLMES ST,KANSAS CITY,MO 64108, USA. FU NIGMS NIH HHS [T32-GM 08386] NR 44 TC 50 Z9 51 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 AUG PY 1996 VL 60 IS 2 BP 138 EP 144 DI 10.1016/S0009-9236(96)90129-0 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VJ969 UT WOS:A1996VJ96900004 PM 8823231 ER PT J AU Ng, TH AF Ng, TH TI A note on conventional null hypothesis testing in active control equivalence studies - Reply SO CONTROLLED CLINICAL TRIALS LA English DT Letter RP Ng, TH (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 2 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 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD AUG PY 1996 VL 17 IS 4 BP 349 EP 350 DI 10.1016/S0197-2456(96)90752-7 PG 2 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA VK406 UT WOS:A1996VK40600010 ER PT J AU Calvo, MS Eyre, DR Gundberg, CM AF Calvo, MS Eyre, DR Gundberg, CM TI Molecular basis and clinical application of biological markers of bone turnover SO ENDOCRINE REVIEWS LA English DT Review ID RESISTANT ACID-PHOSPHATASE; PYRIDINIUM CROSS-LINKS; GAMMA-CARBOXYGLUTAMIC ACID; SKELETAL ALKALINE-PHOSPHATASE; HORMONE REPLACEMENT THERAPY; EARLY POSTMENOPAUSAL WOMEN; PROCOLLAGEN TYPE-I; WHEAT-GERM LECTIN; PERFORMANCE LIQUID-CHROMATOGRAPHY; CARBOXY-TERMINAL PROPEPTIDE C1 US FDA, CTR FOOD SAFETY & APPL NUTR, WASHINGTON, DC 20206 USA. UNIV WASHINGTON, MED CTR, DEPT ORTHOPAED, SEATTLE, WA 98195 USA. YALE UNIV, SCH MED, DEPT ORTHOPAED & REHABIL, NEW HAVEN, CT 06510 USA. FU NIAMS NIH HHS [R01 AR036794, R01-AR-37318, R01-AR-38460, R37 AR037318] NR 430 TC 364 Z9 384 U1 1 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD AUG PY 1996 VL 17 IS 4 BP 333 EP 368 DI 10.1210/er.17.4.333 PG 36 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VB427 UT WOS:A1996VB42700003 PM 8854049 ER PT J AU Kavlock, RJ Daston, GP DeRosa, C FennerCrisp, P Gray, LE Kaattari, S Lucier, G Luster, M Mac, MJ Maczka, C Miller, R Moore, J Rolland, R Scott, G Sheehan, DM Sinks, T Tilson, HA AF Kavlock, RJ Daston, GP DeRosa, C FennerCrisp, P Gray, LE Kaattari, S Lucier, G Luster, M Mac, MJ Maczka, C Miller, R Moore, J Rolland, R Scott, G Sheehan, DM Sinks, T Tilson, HA TI Research needs for the risk assessment of health and environmental effects of endocrine disruptors: A report of the US EPA-sponsored workshop SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE endocrine disruptors; hormones; risk assessment; carcinogenesis; reproductive toxicity; developmental toxicity; immunotoxicity; neurotoxicity; exposure assessment; research needs ID FISH-EATING BIRDS; CONTAMINANT BIOMONITORING PROGRAM; TROUT ONCORHYNCHUS-MYKISS; BREAST-CANCER INCIDENCE; LAWRENCE BELUGA WHALES; MINK MUSTELA-VISON; FRESH-WATER FISH; POLYCHLORINATED-BIPHENYLS; GREAT-LAKES; RAINBOW-TROUT AB The hypothesis has been put forward that humans and wildlife species have suffered adverse health effects after exposure to endocrine-disrupting chemicals. Reported adverse effects include declines in populations, increases in cancers, and reduced reproductive function. The U.S. Environmental Protection Agency sponsored a workshop in April 1995 to bring together interested parties in an effort to identify research gaps related to this hypothesis and to establish priorities for future research activities. Approximately 90 invited participants were organized into work groups developed around the principal reported health effects-carcinogenesis, reproductive toxicity, neurotoxicity, and immunotoxicity--as well as along the risk assessment paradigm--hazard identification, dose-response assessment, exposure assessment, and risk characterization. Attention focused on both ecological and human health effects. In general, the group felt that the hypothesis warranted a concerted research effort to evaluate its validity and that research should focus primarily on effects on development of reproductive capability, on improved exposure assessment, and on the effects of mixtures. This report summarizes the discussions of the work groups and details the recommendations for additional research. C1 PROCTER & GAMBLE CO,MIAMI VALLEY LABS,CINCINNATI,OH. AGCY TOX SUBST & DIS REGISTRY,ATLANTA,GA. US EPA,OFF PREVENT PESTICIDES & TOX SUBST,WASHINGTON,DC 20460. COLL WILLIAM & MARY,VIRGINIA INST MARINE SCI,WILLIAMSBURG,VA. NIEHS,RES TRIANGLE PK,NC 27709. NATL BIOL SERV,WASHINGTON,DC 20240. NATL RES COUNCIL,WASHINGTON,DC 20418. DOW CHEM CO USA,MIDLAND,MI 48674. INST EVALUATING HLTH RISKS,WASHINGTON,DC. WORLD WILDLIFE FUND,WASHINGTON,DC 20037. NATL MARINE FISHERIES SERV,CHARLESTON,SC. US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. RP Kavlock, RJ (reprint author), US EPA,NATL HLTH & ENVIRONM EFFECTS RES LAB,RES TRIANGLE PK,NC 27711, USA. OI gray jr, leon earl/0000-0002-1111-4754 NR 193 TC 693 Z9 743 U1 28 U2 217 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 1996 VL 104 SU 4 BP 715 EP 740 DI 10.2307/3432708 PG 26 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA VC106 UT WOS:A1996VC10600002 PM 8880000 ER PT J AU Nyman, PJ Canas, BJ Joe, FL Diachenko, GW AF Nyman, PJ Canas, BJ Joe, FL Diachenko, GW TI Screening method for the gas chromatographic mass spectrometric determination of microgram/litre levels of bromate in bottled water SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE ozone treatment; oxidation; bromate; bromide; bottled water ID POTASSIUM BROMATE; BREAD; MS AB Bromate can be formed as a by-product of ozone treatment that is sometimes used for the disinfection of municipal water supplies and bottled waters. The US Environmental Protection Agency has proposed a maximum contaminant level (MCL) of 10 mu g/l for bromate in public drinking water. Should the proposed MCL for bromate become final, it may then be considered for adoption as a bottled water quality standard by the US Food and Drug Administration. This paper reports the development of a gas chromatographic/mass spectrometric (GC/MS) method for the determination of parts-per-billion (mu g/l) levels of bromate (BrO3-) in bottled water. The GC/MS method was validated by using distilled and deionized Milli-Q(R) water; detection limits, quantitation limits, and recoveries were determined and identities were confirmed by MS on the basis of analyses of test portions fortified with BrO3- at 0.8, 3.8, 7.7, 1.5, and 46 mu g/l. The method also was evaluated on the basis of recoveries determined for two commercial brands of bottled water fortified with BrO at 3.8 and 7.7 mu g/l and two commercial brands fortified at 0.8, 3.8, and 7.7 mu g/l. For the Milli-Q(R) water, recoveries ranged from 100 to 121%; for the fortified commercial products, recoveries ranged from 87 to 115%. The limits of detection and quantitation were determined to be 0.4 and 0.7 mu g/l, respectively. Several commerical brands of bottled water were analysed, and BrO3- was found in these products at levels ranging from none to 38 mu g/l. RP Nyman, PJ (reprint author), US FDA,DIV PROD MANUFACTURE & USE,WASHINGTON,DC 20204, USA. NR 14 TC 19 Z9 21 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD AUG-SEP PY 1996 VL 13 IS 6 BP 623 EP 631 PG 9 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA VD662 UT WOS:A1996VD66200003 PM 8871119 ER PT J AU Warner, CR Daniels, DH Joe, FL Diachenko, GW AF Warner, CR Daniels, DH Joe, FL Diachenko, GW TI Measurement of bromate in bottled water by high-performance liquid chromatography with post-column flow reactor detection SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE bottled water; bromate; chlorite; iodate; ion interaction chromatography ID ION CHROMATOGRAPHY; DRINKING-WATER AB The objective of this work was to develop a reliable, rugged high-performance liquid chromatographic (HPLC) method for determination of trace levels of bromate (< 10 mu g/l) in bottled water. HPLC separation was achieved by ion interaction chromatography using a C-18 reversed-phase column and a mobile phase consisting of methanol/water (20:80, v/v) with tetrabutylammonium acetate as the ion interaction reagent. A post-column reaction based on oxidation of o-dianisidine in acidic solution to a product detected at 500 nn provided selective measurement of the oxidants. The limit of detection and the Limit of quantitation were 1 and 3 mu g/l, respectively. Iodate, chlorite, and nitrite were chromatographically separated from bromate and measured by monitoring the post-column reaction. Chloride and chlorate at levels that might be found in bottled water did not interfere with the determination of bromate. Bromate was detected in bottled waters at concentrations up to 40 mu g/l. RP Warner, CR (reprint author), US FDA,OFF PREMARKET APPROVAL,200 C ST SW,WASHINGTON,DC 20204, USA. NR 12 TC 30 Z9 31 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD AUG-SEP PY 1996 VL 13 IS 6 BP 633 EP 638 PG 6 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA VD662 UT WOS:A1996VD66200004 PM 8871120 ER PT J AU Nyman, PJ AF Nyman, PJ TI Determination of low nanogram/millilitre levels of volatile organic compounds in on-purpose and by-product hydrochloric acids SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE on-purpose; by-product; hydrochloric acid; volatile organic compounds AB Hydrochloric acid (HCl) is used in the food industry as a processing aid in the manufacture of certain foods. HCl is manufactured, either directly from inorganic sources, i.e. 'on-purpose' or indirectly as a by-product from the production of organic compounds generally intended for non-food applications. By-product HCl potentially may contain traces of the manufactured product, its precursors, and other reaction by-products. Many of the potential contaminants are volatile organic compounds (VOCs) such as vinyl chloride and benzene. A study was conducted to determine whether there were differences between the levels of VOCs found in HCl samples collected from two on-purpose HCl manufacturers and two by-product HCl manufacturers. Process water used to manufacture the HCl also was analysed. Twenty-nine VOCs were determined by purge-and-trap concentration and capillary gas chromatography/mass spectrometry. Of these, nine were found in the process water and in both the by-product and on-purpose HCl samples at total VOC levels of less than 116 ng/ml. The levels of total VOCs identified in the two on-purpose HCl samples were 58 and 80 ng/ml; the levels of total VOCs identified in the two by-product samples were 41 and 115 ng/ml. The process water appeared to be the source of most of the contaminants. These results show that the levels of VOCs found in the two types of acid are comparable. RP Nyman, PJ (reprint author), US FDA,DIV PROD MANUFACTURE & USE,WASHINGTON,DC 20204, USA. NR 9 TC 1 Z9 1 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD AUG-SEP PY 1996 VL 13 IS 6 BP 705 EP 715 PG 11 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA VD662 UT WOS:A1996VD66200012 PM 8871128 ER PT J AU Sheu, CW Rodriguez, I Eppley, RM Lee, JK AF Sheu, CW Rodriguez, I Eppley, RM Lee, JK TI Lack of transforming activity of fumonisin B-1 in BALB/3T3 A31-1-1 mouse embryo cells SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID HUMAN ESOPHAGEAL CANCER; FUSARIUM-MONILIFORME; MORPHOLOGICAL TRANSFORMATION; CORN; CARCINOGENICITY; MYCOTOXINS; TOXICITY AB The capacity of fumonisin B-1 (FB1) to induce morphological transformation of cultured mammalian cells was assessed using BALB/3T3 A31-1-1 mouse embryo cells. FB1 with 90% purity was prepared from Fusarium proliferatum grown on whole corn. Cell growth was not inhibited by 48 hr of exposure at concentrations up to 1000 mu g/ml. Moderate inhibition was induced by 6 days of exposure. In transformation assays with a 48-hr exposure, increases in transformed foci were observed at some concentrations; however, the responses were not reproducible. Prolonged exposure for up to 4 wk at 10, 100 and 500 mu g/ml failed to induce increases in transformed foci. Analysis of combined results showed that only the increase induced by a 48-hr exposure at 500 mu g/ml was significant. A trend test indicated the lack of a dose response for concentrations of 10-1000 mu g/ml. FB1 seems to lack in vitro transforming activity. Published by Elsevier Science Ltd. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,DIV NAT PROD,BIOANALYT CHEM BRANCH,WASHINGTON,DC 20204. US FDA,CTR FOOD SAFETY & APPL NUTR,DIV MATH,BIOMETR & RISK ASSESSMENT BRANCH,WASHINGTON,DC 20204. RP Sheu, CW (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV MOL BIOL RES & EVALUAT,GENET TOXICOL BRANCH,HFS227,WASHINGTON,DC 20204, USA. NR 17 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 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD AUG PY 1996 VL 34 IS 8 BP 751 EP 753 DI 10.1016/0278-6915(96)00034-8 PG 3 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA VP412 UT WOS:A1996VP41200011 PM 8883477 ER PT J AU Shank, FR Elliot, EL Wachsmuth, IK Losikoff, ME AF Shank, FR Elliot, EL Wachsmuth, IK Losikoff, ME TI US position on Listeria monocytogenes in foods SO FOOD CONTROL LA English DT Article DE Listeria monocytogenes; ready-to-eat; policy ID SLAUGHTERHOUSE LEVEL; EPIDEMIC LISTERIOSIS; SPORADIC LISTERIOSIS; POULTRY; MEAT; SUPERMARKET; PREVALENCE; OUTBREAK; SEAFOOD AB Public health and regulatory agencies in the USA have established a zero tolerance for Listeria monocytogenes in cooked, ready-to-eat food. This policy is science-based: the organism causes human illness, can grow at refrigeration temperatures and the infectious dose is unknown. The US response to listeriosis has included emphasis on Good Manufacturing Practices and Hazard Analysis Critical Control Point systems for processing, recommendations for sanitation and other measures for retail handling, and consumer education targeted to populations at highest risk for listeriosis. RP Shank, FR (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,200 C ST SW,WASHINGTON,DC 20204, USA. NR 29 TC 67 Z9 72 U1 3 U2 10 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 AUG-OCT PY 1996 VL 7 IS 4-5 BP 229 EP 234 DI 10.1016/S0956-7135(96)00041-2 PG 6 WC Food Science & Technology SC Food Science & Technology GA VW480 UT WOS:A1996VW48000009 ER PT J AU Knox, HH Gagne, RM AF Knox, HH Gagne, RM TI Alternative methods of obtaining the computed tomography dose index SO HEALTH PHYSICS LA English DT Article DE computed tomography; diagnostic radiology; dosimetry; radiation, ionizing AB The most direct way of getting the value of the multiple scan average dose (MSAD) in computed tomography is to employ a pencil chamber for integration of a single scan dose profile, Because the active length of the pencil chamber is fixed, the measurement can represent the value of the MSAD from a different number of contiguous scans depending on the slice thickness, This characteristic makes it difficult to compare the value of MSAD using the pencil chamber to the information required by Federal regulations on the computed tomography dose index (CTDI), The CTDI, which is the MSAD at the center of a set of 14 contiguous scans, is the dose descriptor used in the Federal Performance Standard, Two alternative methods were developed to make the CTDI measurements at the center of a CT dosimetry phantom. These alternative methods were compared to the results of thermoluminescent dosimeter (TLD) measurements from more than 20 different CT scanners, One alternative method involved the use of radio-opaque sleeves with the pencil chamber to limit the length of the single scan dose profile incident on the pencil chamber, In addition, the TLD data were also used to obtain a set of conversion factors for converting the results of a measurement with the pencil chamber without a radio-opaque sleeve to a value of the CTDI, The alternative methods of obtaining the CTDI agree on the average to better than 10% for all values of slice thickness on the different CT scanners. RP Knox, HH (reprint author), US FDA, CTR DEVICES & RADIOL HLTH, TWINBROOK PKWY, ROCKVILLE, MD 20857 USA. NR 6 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD AUG PY 1996 VL 71 IS 2 BP 219 EP 224 DI 10.1097/00004032-199608000-00015 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA UY099 UT WOS:A1996UY09900018 PM 8690607 ER PT J AU Zaitseva, M Golding, H Manischewitz, J Webb, D Golding, B AF Zaitseva, M Golding, H Manischewitz, J Webb, D Golding, B TI Brucella abortus as a potential vaccine candidate: Induction of interleukin-12 secretion and enhanced B7.1 and B7.2 and intercellular adhesion molecule 1 surface expression in elutriated human monocytes stimulated by heat-inactivated B-abortus SO INFECTION AND IMMUNITY LA English DT Article ID INTERFERON-GAMMA-PRODUCTION; LYMPHOCYTE MATURATION FACTOR; IL-12 P40 HOMODIMER; T-CELLS; HETERODIMERIC CYTOKINE; LIPOPOLYSACCHARIDE LPS; COSTIMULATORY SIGNAL; IMMUNE-RESPONSES; BINDING-PROTEIN; PROLIFERATION AB Development of a vaccine which is capable of generating a strong cellular immune response associated with gamma interferon (IFN-gamma) production and cytotoxic T-cell development requires that the immunogen be capable of inducing the secretion of interleukin-12 (IL-12), which is a pivotal factor for the differentiation of Th1 or Tc1 cells. We have previously shown that the heat-inactivated gram-negative bacterium Brucella abortus can induce IFN-gamma secretion by T cells, In the present study, we demonstrate that B. abortus and lipopolysaccharide (LPS) from B. abortus can induce IL-12 p40 mRNA expression and protein secretion by human elutriated monocytes (99% pure), p40 mRNA was detected within 4 h, and p40 protein could be measured at 24 h. This induction was abrogated by anti-CD14 monoclonal antibody, suggesting that monocytes recognize B. abortus via their receptor for LPS. The biological activity of IL-12 secreted by B. abortus-stimulated monocytes was demonstrated by its ability to upregulate IFN-gamma mRNA expression in T cells separated from monocytes and B. abortus by a transwell membrane. The B. abortus-induced IL-12 also enhanced NK cytolytic activity against K562 target cells, B. abortus was shown to rapidly increase the expression of the costimulatory molecules B7.1 and B7.2 and intercellular adhesion molecule 1 on human monocytes. Together, these data indicate that B. abortus can directly activate human monocytes and provide the cytokine milieu which would direct the immune response towards Th1-Tc1 differentiation. C1 US FDA,CTR BIOL EVALUAT & RES,LAB PLASMA DERIVAT,DIV HEMATOL,ROCKVILLE,MD 20852. US FDA,DIV VIRAL PROD,LAB RETROVIRUS RES,ROCKVILLE,MD 20852. US FDA,DIV CYTOKINE BIOL,LAB CYTOKINE RES,ROCKVILLE,MD 20852. NR 56 TC 42 Z9 42 U1 0 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 AUG PY 1996 VL 64 IS 8 BP 3109 EP 3117 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UY893 UT WOS:A1996UY89300034 PM 8757841 ER PT J AU Elkins, KL RhinehartJones, TR Culkin, SJ Yee, D Winegar, RK AF Elkins, KL RhinehartJones, TR Culkin, SJ Yee, D Winegar, RK TI Minimal requirements for murine resistance to infection with Francisella tularesis LVS SO INFECTION AND IMMUNITY LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACULTATIVE INTRACELLULAR BACTERIUM; LISTERIA-MONOCYTOGENES INFECTION; CELL-INDEPENDENT MECHANISM; NATURAL-KILLER-CELLS; KNOCK-OUT MICE; CD8 T-CELLS; INTERFERON-GAMMA; IMMUNE-RESPONSE; MACROPHAGE ACTIVATION AB Intraperitoneal or intravenous infection of mice with Francisella tularensis LVS is lethal, with an intraperitoneal 50% lethal dose (LD(50)) approaching a single bacterium, Intradermal (i.d.) LVS infection has a much higher LD(50), about 10(6) bacteria in BALB/cByJ mice, and survival of i.d. infection leads to solid generation of Immunity against lethal challenge, To define the minimal requirements for both initial and long-term survival of i.d. infection, we characterized the nature of i.d. LVS infection in lymphocyte-deficient BALB/cByJ scid (scid) mice, scid mice infected i.d. with strain LVS survived for about 20 days and then died from overwhelming disseminated infection. However, scid mice treated with monoclonal antibodies to gamma interferon, tumor necrosis factor alpha, or neutrophils-granulocytes all died within 1 week of infection, indicating that these were essential for early control of infection. Studies using GKO (gamma interferon knockout) mice emphasized that gamma interferon is absolutely required for initial survival of i.d. LVS infection. scid mice could be reconstituted for long-term survival of i.d. LVS infection and clearance of bacteria by intravenous transfer of splenic lymphocytes or purified B220(-)/T+ lymphocytes but not nu/nu lymphocytes. T cells are therefore required for long-term clearance and survival of i.d. LVS infection; efforts to determine whether CD4(+) T cells, CD8(+) T cells, or both are involved are ongoing. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,BRONX,NY 10461. RP Elkins, KL (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,LAB ENTER & SEXYALLY TRANSMITTED DIS,BETHESDA,MD 20852, USA. NR 46 TC 127 Z9 129 U1 0 U2 0 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 AUG PY 1996 VL 64 IS 8 BP 3288 EP 3293 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UY893 UT WOS:A1996UY89300059 PM 8757866 ER PT J AU Tavares, MA Silva, MC SilvaAraujo, A Xavier, MR Ali, SF AF Tavares, MA Silva, MC SilvaAraujo, A Xavier, MR Ali, SF TI Effects of prenatal exposure to amphetamine in the medial prefrontal cortex of the rat SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE amphetamine; dopamine; serotonin; hoephometry; rat; prefrontal cortex ID EXTRACELLULAR DOPAMINE LEVELS; COCAINE EXPOSURE; NERVOUS-SYSTEM; PYRAMIDAL CELL; FRONTAL-CORTEX; BRAIN; SEROTONIN; BEHAVIOR; VOLUMES; AGE AB This study was designed to investigate the effects of prenatal exposure to amphetamine in the organization of the medial prefrontal cortex of the rat, by an evaluation of growth, morphometric and neurochemical parameters. Pregnant Wistar rats were given 10 mg/kg body weight/day of D-amphetamine sulfate, subcutaneously, from gestational days 8 to 22. Control groups of pregnant rats were injected with saline, pair-fed or non-manipulated; litters were culled to eight pups (four males and four females), weighed every other day until postnatal day 30 and every week until day 90. The Gompertz model was used to study body weight evolution and the estimated growth parameters were not significantly different in the experimental groups. At postnatal days 14 and 30, the volumes of the prefrontal cortex, the fraction of neuropile occupied by neurons and the number of neurons per unit surface area were determined. The number of neurons per unit volume of reference area was calculated using the stereological technique of the dissector. For neurochemical analysis, the medial prefrontal cortex was dissected to measure the concentration of dopamine, serotonin and their metabolites. The allometric relationship of forebrain/body growth pointed to a mechanism of sparing and compensatory growth in the amphetamine exposed group. The changes found in the number of neurons per unit volume at postnatal day 14 show a catch-up at postnatal day 30. A decrease in serotonin levels was found in the amphetamine group compared with the pair-fed control, which was reflected in the ratio of serotonin to its metabolite, 5-hydroxyindolacetic acid. These changes, whether permanent or transitory, raise the possibility that some of the effects of prenatal exposure to amphetamine may be due to modifications in the neurotransmitter levels of serotonin. Copyright (C) 1996 ISDN. C1 UNIV PORTO, INST MOL & CELLULAR BIOL, P-4100 OPORTO, PORTUGAL. UNIV PORTO, INST BIOMED SCI ABEL SALAZAR, LAB BIOMETRY, P-4100 OPORTO, PORTUGAL. NATL CTR TOXICOL RES, DIV NEUROTOXICOL, NEUROCHEM LAB, JEFFERSON, AR 72079 USA. RP Tavares, MA (reprint author), MED SCH PORTO, INST ANAT, P-4200 OPORTO, PORTUGAL. OI Ferreira, Maria/0000-0001-6789-3796 NR 56 TC 12 Z9 12 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD AUG PY 1996 VL 14 IS 5 BP 585 EP 596 DI 10.1016/0736-5748(96)00036-6 PG 12 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA VT296 UT WOS:A1996VT29600006 PM 8930690 ER PT J AU Jackson, LS Hlywka, JJ Senthil, KR Bullerman, LB AF Jackson, LS Hlywka, JJ Senthil, KR Bullerman, LB TI Effects of thermal processing on the stability of fumonisin B-2 in an aqueous system SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE fumonisin B-2; thermal processing; stability; decomposition ID FUSARIUM-MONILIFORME; NATURAL OCCURRENCE; ESOPHAGEAL CANCER; CORN; MYCOTOXINS; PRODUCTS; LEUKOENCEPHALOMALACIA; CULTURES; TOXICITY; TRANSKEI C1 UNIV NEBRASKA,DEPT FOOD SCI & TECHNOL,LINCOLN,NE 68583. IIT,NATL CTR FOOD SAFETY & TECHNOL,SUMMIT ARGO,IL 60501. RP Jackson, LS (reprint author), US FDA,NATL CTR FOOD SAFETY & TECHNOL,SUMMIT ARGO,IL 60501, USA. NR 33 TC 21 Z9 21 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 AUG PY 1996 VL 44 IS 8 BP 1984 EP 1987 DI 10.1021/jf9601729 PG 4 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA VC709 UT WOS:A1996VC70900004 ER PT J AU Hilbert, SL Sword, LC Batchelder, KF Barrick, MK Ferrans, VJ AF Hilbert, SL Sword, LC Batchelder, KF Barrick, MK Ferrans, VJ TI Simultaneous assessment of bioprosthetic heart valve biomechanical properties and collagen crimp length SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article ID 15-YEAR EXPERIENCE; CARDIAC VALVES; STRESS; LEAFLETS; FAILURE AB A new morphologic method is described for the simultaneous quantitation of porcine aortic valve collagen crimp length and the assessment of biomechanical properties. This method utilizes the simultaneous real-time video recording of collagen crimp morphology and acquisition of crimp length data through the combination of polarized light microscopy and morphometry. We felt that the development of this method was warranted, due to the fundamental role played by collagen in porcine aortic valve performance. The development of this method involved the design and fabrication of a uniaxial microtensile stage, suitable for mounting on a standard microscope stage. The validation of our test method was accomplished by a comparison of untreated and glutaraldehyde-treated porcine aortic valve leaflet tissue, because the biomechanical and morphologic characteristics of the native and fixed aortic valve have been extensively studied. The method described in this communication enables the collection of morphologic and biomechanical data from a single tissue specimen, eliminating the need for independent studies of multiple specimens. Furthermore, this method obviates the need for making assumptions, which may be difficult to verify, concerning the homogeneity of different test specimens with respect to their morphology and corresponding mechanical response to different experimental conditions. (C) 1996 John Wiley & Sons, Inc. C1 JOHNS HOPKINS UNIV,GWC WHITING SCH ENGN,BALTIMORE,MD. NHLBI,PATHOL SECT,NIH,BETHESDA,MD 20892. RP Hilbert, SL (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,OFF SCI & TECHNOL,ROCKVILLE,MD 20852, USA. NR 21 TC 17 Z9 18 U1 0 U2 2 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 AUG PY 1996 VL 31 IS 4 BP 503 EP 509 DI 10.1002/(SICI)1097-4636(199608)31:4<503::AID-JBM10>3.0.CO;2-H PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA UY924 UT WOS:A1996UY92400010 PM 8836847 ER PT J AU Looker, AC Gunter, EW Calvo, MS AF Looker, AC Gunter, EW Calvo, MS TI Low vitamin D status appears common in both young and old US blacks SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NATL CTR HLTH STAT,CDC,HYATTSVILLE,MD 20782. US FDA,WASHINGTON,DC 20204. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP M542 EP M542 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500889 ER PT J AU Li, ZM Bai, GH vonReyn, CF Marino, P Brennan, MJ Gine, N Morris, SL AF Li, ZM Bai, GH vonReyn, CF Marino, P Brennan, MJ Gine, N Morris, SL TI Rapid detection of Mycobacterium avium in stool samples from AIDS patients by immunomagnetic PCR SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTION; TUBERCULOSIS; BACTEREMIA; WATER; INTRACELLULARE; IDENTIFICATION; ANTIGENS; PROTEIN AB Direct PCR detection of bacteria in clinical samples is often hindered by the presence of compounds that inhibit the PCR. To improve and accelerate the diagnosis of Mycobacterium aviam-M. intracellulare complex infections, an immunomagnetic PCR (IM-PCR) assay was developed. This IM-PCR procedure combines the separation of mycobacteria by antimycobacterial monoclonal antibody coupled to magnetic beads with an M. avium-M. intracellulare complex-specific PCR protocol based on 16S rRNA gene sequences. As few as 10 M. avium bacilli were detected in spiked human stool samples, a clinical specimen usually refractory to conventional PCR analysis, by the IM-PCR method, Moreover, M. avium organisms were detected in about 24 h in 18 of 22 culture-confirmed fecal samples from AIDS patients. This IM-PCR protocol should allow for the rapid and sensitive detection of M. avium isolates in clinical specimens. C1 US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,BETHESDA,MD 20892. DARTMOUTH HITCHCOCK MED CTR,INFECT DIS SECT,LEBANON,NH 03766. NR 28 TC 27 Z9 27 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD AUG PY 1996 VL 34 IS 8 BP 1903 EP 1907 PG 5 WC Microbiology SC Microbiology GA UW859 UT WOS:A1996UW85900007 PM 8818878 ER PT J AU Yoshikawa, T Hill, JM Stanberry, LR Bourne, N Kurawadwala, JF Krause, PR AF Yoshikawa, T Hill, JM Stanberry, LR Bourne, N Kurawadwala, JF Krause, PR TI The characteristic site-specific reactivation phenotypes of HSV-1 and HSV-2 depend upon the latency-associated transcript region SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HERPES-SIMPLEX VIRUS; RECURRENT GENITAL HERPES; TRIGEMINAL GANGLIA; GUINEA-PIGS; TYPE-1 TRANSCRIPTS; INFECTION; SEQUENCE; INVIVO; GENE; RNA AB After replication al sites oi initial inoculation, herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) establish lifelong latent infections of the sensory and autonomic neurons of the ganglia. sewing those sites. Periodically, the virus reactivates from these neurons, and travels centripetally along the neuronal all-oil to cause recurrent epithelial infection. The major clinically observed difference between infections with herpes simplex virus type 1 and type 2 is thr anatomic site specificity of recurrence. HSV-1 reactivates most efficiently and frequently from trigeminal ganglia, causing recurrent ocular and oral-facial lesions, while HSV-3-reactivates primarily fi-om sacral ganglia causing recurrent genital lesions. An intertypic recombinant virus was constructed and evaluated in animal models of recurrent ocular and genital herpes. Substitution oi a 2.8-kbp region from the HSV-1 latency-associated transcript (LAT) for native HSV-2 sequences caused HSV-2 to reactivate with an HSV-1 phenotype in both animal models. The HSV-2 phenotype was restored by replacing the mutated sequences with wild-type HSV-2 LAT-region sequences. These sequences or their products must act specifically in the cellular environments of trigeminal and sacral neurons to promote the reactivation patterns characteristic of each virus. C1 US FDA,DIV VIRAL PROD,CTR BIOL EVALUAT & RES,BETHESDA,MD. LOUISIANA STATE UNIV,MED CTR,SCH MED,EYE CTR,LIONS EYE RES LABS,NEW ORLEANS,LA. UNIV CINCINNATI,COLL MED,DEPT PEDIAT,CHILDRENS HOSP RES FDN,DIV INFECT DIS,CINCINNATI,OH. FU NEI NIH HHS [P30EY02377, EY06311]; NIAID NIH HHS [AI22667] NR 28 TC 40 Z9 40 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 AUG 1 PY 1996 VL 184 IS 2 BP 659 EP 664 DI 10.1084/jem.184.2.659 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VC337 UT WOS:A1996VC33700037 PM 8760819 ER PT J AU Venugopal, R Tollefson, L Hyman, FN Timbo, B Joyce, RE Klontz, KC AF Venugopal, R Tollefson, L Hyman, FN Timbo, B Joyce, RE Klontz, KC TI Recalls of foods and cosmetics by the US Food and Drug Administration SO JOURNAL OF FOOD PROTECTION LA English DT Article DE food; Listeria infections; botulism; cosmetics; recalls ID SPORADIC LISTERIOSIS; CONSUMPTION; CHILDREN AB Recalls of foods and cosmetics from the marketplace are an expeditious and effective method of removing violative products, particularly those that present a danger to health. Recalls are undertaken through a cooperative effort by industry and the U.S. Food and Drug Administration (FDA). Foods and cosmetics recalled from the period 1 October 1991 through 30 September 1992 were reviewed to determine the kinds of products recalled and the reasons for recall. A total of 230 recalls, involving 569 foods and cosmetics, occurred during the study period. Twenty-eight percent of the recalls were designated class I, defined as a situation in which there is a reasonable probability that the use of, or exposure to, a violative product will cause serious adverse health consequences. The problems for which foods or cosmetics were mast often recalled were misbranding and microbial contamination (37% and 25% of recalls, respectively). A recognized illness or injury was reported to have occurred in association with 32 food products and one cosmetic. This study indicates that recalls of foods and cosmetics are common and that various groups, including industry, consumers, state regulatory agencies, and the FDA, recognize problems leading to recall. C1 US FDA, EPIDEMIOL BRANCH, DIV MARKET STUDIES, WASHINGTON, DC 20204 USA. US FDA, CTR FOOD SAFETY & APPL NUTR, DIV ENFORCEMENT, WASHINGTON, DC 20204 USA. NR 17 TC 10 Z9 10 U1 1 U2 3 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X EI 1944-9097 J9 J FOOD PROTECT JI J. Food Prot. PD AUG PY 1996 VL 59 IS 8 BP 876 EP 880 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA VD346 UT WOS:A1996VD34600015 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 protein promotes chemotaxis and invasive behavior by monocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MONONUCLEAR PHAGOCYTES; AIDS PATIENTS; TAT PROTEINS; INFECTION; CELLS; MACROPHAGES AB Monocytes are susceptible to HIV infection and to activation by a regulatory gene product of the HIV genome, HIV-Tat. Recently, we have demonstrated that treatment with HIV-Tat up-regulates monocyte adhesion to the endothelium and increases metalloproteinase production. In the present study, we have examined the ability of the HIV-Tat protein to alter the migratory and invasive behavior of monocytes. Monocytes pretreated for 24 h with 10 ng/ml HIV-Tat exhibited enhanced migratory behavior compared with untreated monocytes in chemotaxis assays, both in the absence of a chemoattractant as well as in response to FMLP. In addition, HIV-Tat itself induced the migration of both untreated and HIV-Tat pretreated monocytes. Checkerboard analysis showed that monocytes migrated in response to an HIV-Tat concentration gradient, thus confirming the chemotactic characteristics of the HIV-Tat protein, Pretreatment of monocytes with 10 ng/ml HIV-Tat for 24 h also increased their ability to invade reconstituted extracellular membrane (Matrigel)coated filters by 5-fold in the absence of chemoattractant. The presence of FMLP or HIV-Tat further enhanced invasion by both untreated and HIV-Tat-pretreated monocytes by more than 10-fold. Monocyte invasion was partially inhibited by the inclusion of anti-beta(1) integrin Ab or tissue inhibitor of metalloproteinase (TIMP). Thus, for the first time, we present evidence that HIV-Tat can enhance the chemotactic and invasive behaviors of monocytes and propose an active role for HIV-Tat in the recruitment of monocytes into extravascular tissues, a process which may contribute to the destruction of tissues and cellular architecture often seen in patients with acquired immunodeficiency syndrome. C1 NIDR,DEV BIOL LAB,NIH,BETHESDA,MD 20892. NIDR,IMMUNOL LAB,NIH,BETHESDA,MD 20892. US FDA,IMMUNOPATHOL SECT,MOL VIROL LAB,DIV TRANSFUS TRANSMITTED DIS,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20857. OI Yamada, Kenneth/0000-0003-1512-6805 NR 20 TC 110 Z9 111 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1996 VL 157 IS 3 BP 974 EP 977 PG 4 WC Immunology SC Immunology GA VG999 UT WOS:A1996VG99900002 PM 8757599 ER PT J AU MireSluis, AR Das, RG Zoon, K Padilla, A Thorpe, R Meager, A AF MireSluis, AR Das, RG Zoon, K Padilla, A Thorpe, R Meager, A TI The biological properties, assay, and standardization of interferon-alpha: A need for a WHO Collaborative Study SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID CELL AB Interferon-alpha (IFN-alpha) exists as a range of closely related, biologically active proteins and has been the subject of extensive research and clinical investigation, Standardization of IFN-alpha and the uniform reporting of IFN-alpha activity in International Units (IU) is critical to preclinical research and the clinical development of IFN-alpha products as therapeutic agents, Currently, several different IFN-alpha-containing reference preparations, established as World Health Organization (WHO) International Standards (IS) for particular IFN-alpha proteins (mixtures or single molecular species) are available for assay calibration, Nevertheless, the heterogeneous nature of IFN-alpha has raised standardization issues relating to the activity of individual IFN-alpha proteins, henceforth termed subtypes, in the various biologic assays used for determining IFN-alpha levels, These issues include the question of parallelism of dose-response curves among particular IFN-alpha subtypes and different, naturally produced IFN-alpha subtype mixtures, for example, leukocyte IFN-alpha, and the applicablity of IU of IFN-alpha activity defined by antiviral assays to alternative biologic assays, for example, antiproliferative assays, To address such issues, a WHO Consultative Group on Cytokine Standardization requested that the National Institute for Biological Standards and Control (NIBSC) and the Centre for Biologics Evaluation and Research (CBER) organize an international collaborative study to compare the activities and relative potencies of the several available IFN-alpha preparations, including those derived from human cells containing mixtures of IFN-alpha subtypes and those derived by rDNA methods containing single IFN-alpha subtypes, in different assays, To date, 111 participants in 32 countries have been recruited to the study and have agreed to assay a total of 17 different natural and recombinant IFN-alpha preparations or a defined subset thereof in specific in-house assays, The assay results generated will be statistically analyzed and evaluated to address the stated issues and to assess whether any individual IFN-alpha preparation is suitable to serve as an IS for all IFN-alpha preparations or whether more than one IS will be needed for this purpose. C1 NATL INST BIOL STAND & CONTROLS,DIV INFORMAT,POTTERS BAR EN6 3QG,HERTS,ENGLAND. CTR BIOL EVALUAT & RES,BETHESDA,MD 20852. WHO,BIOL PROGRAMME,CH-1211 GENEVA 27,SWITZERLAND. RP MireSluis, AR (reprint author), NATL INST BIOL STAND & CONTROLS,DIV IMMUNOBIOL,BLANCHE LANE,S MIMMS,POTTERS BAR EN6 3QG,HERTS,ENGLAND. RI Thorpe, Robin/E-6853-2013 NR 18 TC 8 Z9 8 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 1996 VL 16 IS 8 BP 637 EP 643 DI 10.1089/jir.1996.16.637 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA VE551 UT WOS:A1996VE55100011 PM 8877735 ER PT J AU Bhave, SV Johannessen, JN Lash, LH Wakade, TD Wakade, AR AF Bhave, SV Johannessen, JN Lash, LH Wakade, TD Wakade, AR TI Age-dependent sensitivity of cultured peripheral sympathetic neurons to 1-methyl-4-phenylpyridinium: Role of glutathione SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE 1-methyl-4-phenylpyridinium; neuronal cultures; sympathetic neurons; glutathione; neurotoxicity; tetrabenazine; L-buthionine; [S, R]; sulfoximine ID PARKINSONISM-INDUCING NEUROTOXIN; PERFORMANCE LIQUID-CHROMATOGRAPHY; MESENCEPHALIC DOPAMINE NEURONS; DISTAL TUBULAR CELLS; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; MONOAMINE-OXIDASE; N-METHYL-4-PHENYLPYRIDINIUM ION; SELECTIVE DESTRUCTION; TRANSMITTER RELEASE; BRAIN MITOCHONDRIA AB We demonstrate that 1-methyl-4-phenylpyridinium (MPP(+)) is toxic to chick peripheral sympathetic neurons maintained in culture in the presence of nerve growth factor (NGF). When MPP(+) was added to the culture medium at the time the neurons were plated, cell loss after 3 days in culture was evident at concentrations as low as 3 nM, and near maximal at 1 mu M. Toxicity was blocked by brief preincubation with the norepinephrine (NE)-reuptake blocker desipramine (DMI; 10 mu M for 30 min). MPP(+) blocked the uptake of [H-3]NE by sympathetic neurons in a dose-dependent manner with a potency roughly equal to DMI. At concentrations up to 10 mu M, MPP(+) had no neurotoxic effect on the survival of sensory neurons maintained in the presence of NGF. The sensitivity of sympathetic neurons to the toxic effects of MPP(+) diminished gradually with increasing lengths of time in culture, When MPP(+) was added to the culture medium 48 h after plating, concentrations up to 100 mu M did not cause neuronal death. This increasing resistance of sympathetic neurons to MPP(+)-induced cell death could not be explained by an increasing capacity for sequestration of MPP(+) within synaptic vesicles. The loss of sensitivity with time in culture was, however, accompanied by a threefold increase in the levels of glutathione (GSH), Furthermore, addition of MPP(+) (1 mu M) to cultures previously maintained for 2 days in the presence of the GSH-synthesis inhibitor L-buthionine-[S,R]-sulfoximine (1 mu M) caused the same degree of cell death as when added to freshly plated neurons, These results suggest that the observed toxicity of MPP(+) in freshly plated chick sympathetic neurons may involve the formation of free radicals and that GSH plays a role in protecting sympathetic neurons in vivo from the toxicity of MPP(+). C1 WAYNE STATE UNIV,SCH MED,DEPT PHARMACOL,DETROIT,MI 48201. US FDA,HFS 507,DIV TOXICOL RES,LAUREL,MD. OI Lash, Lawrence/0000-0003-3239-4481 NR 59 TC 13 Z9 13 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 1996 VL 67 IS 2 BP 557 EP 565 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UX585 UT WOS:A1996UX58500013 PM 8764580 ER PT J AU Cheng, HY Gillespie, WR AF Cheng, HY Gillespie, WR TI Volumes of distribution and mean residence time of drugs with linear tissue distribution and binding and nonlinear protein binding SO JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS LA English DT Article DE volumes of distribution; mean residence time; nonlinear protein binding ID DISTRIBUTION TERMS; PHARMACOKINETICS; PLASMA; ELIMINATION; METABOLISM; PARAMETERS; CLEARANCE AB Based on a generalized model, equations for calculating the mean residence time in the body at single dose (MRT) and at steady state (MRT(ss)), apparent steady-state volume of distribution (<(V)over cap (ss)>), and steady-state volume of distribution (V-ss) are derived for a drug exhibiting nonlinear protein binding. interrelationships between <(V)over cap (ss)> and V-ss as well as between MRT and MRT(ss) are also discussed and illustrated with simulated data. In addition, a method for estimating the central volume of distribution of the bound drug and the sum of the central volume of distribution of the unbound drug and the area under the first moment curve of distribution function for drugs with nonlinear protein binding is proposed and illustrated with both simulated and published data. C1 MERCK SHARP & DOHME LTD,DEPT DRUG METAB,W POINT,PA 19486. US FDA,ROCKVILLE,MD 20857. NR 26 TC 5 Z9 6 U1 0 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0090-466X J9 J PHARMACOKINET BIOP JI J. Pharmacokinet. Biopharm. PD AUG PY 1996 VL 24 IS 4 BP 389 EP 402 DI 10.1007/BF02353519 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WH199 UT WOS:A1996WH19900005 PM 9044167 ER PT J AU Mossoba, MM Yurawecz, MP McDonald, RE AF Mossoba, MM Yurawecz, MP McDonald, RE TI Rapid determination of the total trans content of neat hydrogenated oils by attenuated total reflection spectroscopy SO JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY LA English DT Article DE attenuated total reflection; infrared; trans fatty acids ID FATTY-ACIDS; INFRARED-SPECTROSCOPY; CHOLESTEROL LEVELS; ISOMERS; WOMEN AB A Fourier transform infrared spectroscopy procedure is described for quantitating the levels of total trans triglycerides or their fatty acid methyl ester derivatives in neat fats and oils. It requires either warming or no preparation of the laboratory sample, and about 5 min for spectroscopic measurement, band area integration, and calculation of the trans content from a linear regression equation. To eliminate the strongly sloping background of the 966-cm(-1) trans band, the single-beam spectrum of the trans-containing fat is ''ratioed'' against that of an unhydrogenated oil or a reference material that contains only cis double bonds. Thus, a symmetric absorption band on a horizontal background is obtained. The area under the trans band can then be accurately integrated between the same limits, 990 and 945 cm(-1), for all trans levels investigated. To speed up the analysis, an attenuated total reflection liquid cell was used, into which oils, melted fats or their methyl esters were poured without weighing or quantitative dilution with the toxic and volatile carbon disulfide solvent. The trans levels determined by attenuated total reflection were closer to those found by capillary gas chromatography when the hydrogenated far was measured against the corresponding unhydrogenated oil than when it was measured against a cis reference material. Small differences were found between trans levels in hydrogenated fat test samples and the corresponding methyl ester derivatives (9.3 and 2.2% at about 2 and 41% trans, respectively). The lower limits of identification and quantitation were 0.2 and 1%, respectively. C1 US FDA,NATL CTR FOOD SAFETY & TECHNOL,SUMMIT ARGO,IL 60501. RP Mossoba, MM (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,HFS-717,200 C ST SW,WASHINGTON,DC 20204, USA. NR 26 TC 61 Z9 65 U1 1 U2 9 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0003-021X J9 J AM OIL CHEM SOC JI J. Am. Oil Chem. Soc. PD AUG PY 1996 VL 73 IS 8 BP 1003 EP 1009 DI 10.1007/BF02523408 PG 7 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA VC723 UT WOS:A1996VC72300008 ER PT J AU Kashanchi, F Khleif, SN Duvall, JF Sadaie, MR Radonovich, MF Cho, M Martin, MA Chen, SY Weinmann, R Brady, JN AF Kashanchi, F Khleif, SN Duvall, JF Sadaie, MR Radonovich, MF Cho, M Martin, MA Chen, SY Weinmann, R Brady, JN TI Interaction of human immunodeficiency virus type 1 Tat with a unique site of TFIID inhibits negative cofactor Dr1 and stabilizes the TFIID-TFIIA complex SO JOURNAL OF VIROLOGY LA English DT Article ID RNA-POLYMERASE-II; BOX-BINDING-PROTEIN; TRANSCRIPTION FACTOR; ACTIVATES TRANSCRIPTION; ELONGATION COMPLEXES; GENE-TRANSCRIPTION; KAPOSIS-SARCOMA; IN-VITRO; INITIATION; INVITRO AB We have previously reported the direct physical interaction between the human immunodeficiency virus (HIV) type 1 Tat protein and the basal transcription factor TBP/TFIID. Affinity chromatography demonstrated that wild-type Tat, but not a transactivation mutant of Tat, was capable of depleting TBP/TFIID from cell extracts. These experiments represented the first demonstration of a basal transcription factor that binds, in an activation-dependent manner, to Tat. We now report that the Tat-TBP interaction can be detected in HIV type 1-infected cells. The domain of TBP interacting with Tat has been mapped from amino acids 163 to 196 by using deletion and site-specific mutants of TBP. This domain of TBP, which includes the H1 and S2 domains, is distinct from the H2 binding site for other activator proteins, such as E1A. The interaction of Tat with TFIID regulates the binding of accessory proteins to TFIID. Tat stabilizes the interaction of TFIID with TFIIA in a gel shift assay. In addition, Tat competes for Drl interaction with TBP. bur results suggest that the basal transcription factor TBP/TFIID represents an important regulatory molecule in HIV transcription. C1 NCI,MOLEC VIROL LAB,NIH,BETHESDA,MD 20892. NCI,NAVY MED ONCOL BRANCH,NIH,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,ROCKVILLE,MD 20859. BRISTOL MYERS SQUIBB CO,DEPT MOLEC ONCOL & DRUG DEV,PRINCETON,NJ 08543. NR 59 TC 29 Z9 29 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 AUG PY 1996 VL 70 IS 8 BP 5503 EP 5510 PG 8 WC Virology SC Virology GA UX582 UT WOS:A1996UX58200073 PM 8764062 ER PT J AU Doran, JL Collinson, SK Clouthier, SC Cebula, TA Koch, WH Burian, J Banser, PA Todd, ECD Kay, WW AF Doran, JL Collinson, SK Clouthier, SC Cebula, TA Koch, WH Burian, J Banser, PA Todd, ECD Kay, WW TI Diagnostic potential of sefA DNA probes to Salmonella enteritidis and certain other O-serogroup D1 Salmonella serovars SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE SEF; pili; fimbriae; oligonucleotide; polymerase chain reaction (PCR) ID AGGREGATIVE FIMBRIAE; ESCHERICHIA-COLI; GENE; SEQUENCES; CLONING; THIN; TYPHIMURIUM; BACTEREMIA; RESISTANCE; INFECTIONS AB Salmonella enteritidis thin fimbriae, SEF14, were found to be restricted to S. dublin and the predominantly poultry-associated members of the Salmonella O-serogroup D1, S. enteritidis, S. berta, S. gallinarum and S. pullorum, when tested by Western and ELISA analyses from among 90 Salmonella isolates of 42 serovars, as well as from members of several related genera of the Enterobacteriaceae. These five serovars and a single isolate of S. typhi (D1) were also detected by hybridization of genomic DNA from 732 Salmonella isolates of 117 serogroups to gene probes derived from the S. enteritidis sefA (fimbrin gene), sefB (chaperone) or sefC (outer membrane protein) genes encoding proteins involved in SEF14 biosynthesis. None of 250 Enterobacteriaceae or 27 other eubacterial isolates tested hybridized to the sef probes. The sefA, sefB and sefC genes were amplified from these six Salmonella serovars by PCR using primer pairs designed from sefA, sefB or sefC of S. enteritidis. DNA sequencing of sefA genes from these five serovars indicated limited sequence variability among sefA genes and recognition of individual base pairs which could potentially differentiate certain strains of S. enteritidis, S. dublin and S. gallinarum. (C) 1996 Academic Press Limited C1 UNIV VICTORIA,DEPT BIOCHEM & MICROBIOL,VICTORIA,BC V8W 3P6,CANADA. UNIV VICTORIA,CANADIAN BACTERIAL DIS NETWORK,VICTORIA,BC V8W 3P6,CANADA. MICROTEK INT LTD,SAANICHTON,BC V8M 1Z8,CANADA. US FDA,CTR FOOD SAFETY & APPL NUTR,DIV MOL BIOL RES & EVALUAT,WASHINGTON,DC 20204. DEPT HLTH & WELF,HLTH PROTECT BRANCH,OTTAWA,ON K1A 0L2,CANADA. OI Todd, Ewen/0000-0001-7266-279X NR 57 TC 29 Z9 30 U1 0 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD AUG PY 1996 VL 10 IS 4 BP 233 EP 246 DI 10.1006/mcpr.1996.0033 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA VB776 UT WOS:A1996VB77600001 PM 8865172 ER PT J AU Sutkowski, EM Robbins, JD Tang, WJ Seamon, KB AF Sutkowski, EM Robbins, JD Tang, WJ Seamon, KB TI Irreversible inhibition of forskolin interactions with type I adenylyl cyclase by a 6-isothiocyanate derivative of forskolin SO MOLECULAR PHARMACOLOGY LA English DT Article ID HUMAN-PLATELET MEMBRANES; H-3 FORSKOLIN; GLUCOSE TRANSPORTER; RAT-BRAIN; MOLECULAR-CLONING; BINDING-SITES; HIGH-AFFINITY; EXPRESSION; PROTEIN; PROSTAGLANDIN-E1 AB Forskolin (Fsk) has been demonstrated to interact directly with the enzyme adenylyl cyclase (EC 4.6.1.1) in diverse tissues. However, the ability of Fsk to bind to and activate adenylyl cyclase varies depending on the tissue being studied. Different adenylyl cyclase subtypes have been cloned and expressed in a recombinant Sf9 expression system. This provides an opportunity to study the effects of chemically reactive derivatives of Fsk on individual adenylyl cyclase subtypes in the absence of G(s alpha). Reaction of type I adenylyl cyclase with an isothiocyanate derivative of Fsk (6-[[N-(2-isothiocyanatoethyl)amino]carbonyl]forskolin) causes irreversible inhibition of Fsk binding with an IC50 of 300 nM and irreversible inhibition of Fsk activation with an IC50 of 10 mu M, suggesting that there are two sites of 6-[[N-(2-isothiocyanatoethyl)amino]carbonyl]forskolin interaction. These studies establish the usefulness of the isothiocyanate derivative of Fsk in localizing the site(s) of Fsk interaction with type I adenylyl cyclase. C1 UNIV CHICAGO, DEPT PHARMACOL & PHYSIOL SCI, CHICAGO, IL 60637 USA. RP US FDA, CTR BIOL EVALUAT & RES, 1401 ROCKVILLE PIKE HFM-505, ROCKVILLE, MD 20852 USA. OI Tang, Wei-Jen/0000-0002-8267-8995 NR 38 TC 9 Z9 10 U1 2 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X EI 1521-0111 J9 MOL PHARMACOL JI Mol. Pharmacol. PD AUG PY 1996 VL 50 IS 2 BP 299 EP 305 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VB335 UT WOS:A1996VB33500012 PM 8700137 ER PT J AU Hussain, S Slikker, W Ali, SF AF Hussain, S Slikker, W Ali, SF TI Role of metallothionein and other antioxidants in scavenging superoxide radicals and their possible role in neuroprotection SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article; Proceedings Paper CT Workshop on Antioxidants CY NOV 12, 1994 CL HOLLYWOOD, FL ID GROWTH-INHIBITORY FACTOR; OXIDATIVE STRESS; HYDROXYLAMMONIUM-CHLORIDE; NITRITE FORMATION; RADIATION; DISMUTASE; CELLS; GLUTATHIONE; RESISTANCE; MECHANISM AB Based on the inhibition of nitrite formation by generating superoxide from xanthine/xanthine oxidase (X/XO) reaction system, metallothionein (MT) and other sulfhydryl containing amino acids have been selected to test their abilities to scavenge superoxide radicals. Different concentrations of metallothionein and other sulfhydryl containing molecules e.g. cysteine, N-acetyl-cysteine and glutathione, were used to assess superoxide scavenging properties. Metallothionein scavenges superoxide radical in a dose-dependent manner with increasing concentrations as evidenced by the inhibition of nitrite formation. Similar abilities to scavenge superoxide radicals were shown by cysteine, N-acetyl-cysteine. Glutathione also scavenges superoxide radical in a dose-dependent manner. In vitro experiments demonstrated that metallothionein is superior in scavenging superoxide radicals compared to other sulfhydryl molecules such as cysteine, N-acetyl-cysteine and even glutathione. The data, further, suggest that metallothionein-II has a 6-fold higher capacity to scavenge superoxide radical than metallothionein-I. In addition, metallothionein-like protein was isolated from different regions of mouse brain treated with zinc. Brain metallothionein-like protein inhibits nitrite formation as demonstrated by other scavengers; however, the extent of inhibition is different by this protein isolated from different brain regions. The present study suggests that metallothioneins and metallothionein-like proteins isolated from mouse brain act as neuroprotective agents by scavenging superoxide radicals. Published by Elsevier Science Ltd. C1 NATL CTR TOXICOL RES,US FDA,HFT 132,DIV NEUROTOXICOL,NEUROCHEM LAB,JEFFERSON,AR 72079. 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. NR 38 TC 86 Z9 92 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD AUG PY 1996 VL 29 IS 2 BP 145 EP 152 DI 10.1016/0197-0186(95)00114-X PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UY764 UT WOS:A1996UY76400007 PM 8837043 ER PT J AU Boal, JH Wilk, A Harindranath, N Max, EE Kempe, T Beaucage, SL AF Boal, JH Wilk, A Harindranath, N Max, EE Kempe, T Beaucage, SL TI Cleavage of oligodeoxyribonucleotides from controlled-pore glass supports and their rapid deprotection by gaseous amines SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PROTECTING GROUPS; OLIGONUCLEOTIDE SYNTHESIS; DNA AB A novel method for the deprotection of oligodeoxyribonucleotides has been developed. Gaseous amines such as ammonia or methylamine were employed under pressure to achieve mild and rapid deprotection conditions. For example, oligodeoxyribonucleotides having a (tent-butyl)phenoxyacetyl group for the protection of the exocyclic amino function of cytosine, adenine and guanine were released from controlled-pore glass supports and fully deprotected by ammonia or methylamine under gas phase conditions, at room temperature, within 35 or 2 min respectively. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. BARRSKOGEN INC,BOWIE,MD 20720. NR 14 TC 27 Z9 27 U1 1 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG 1 PY 1996 VL 24 IS 15 BP 3115 EP 3117 DI 10.1093/nar/24.15.3115 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB832 UT WOS:A1996VB83200038 PM 8760903 ER PT J AU Perrin, J Erenberg, G LaCamera, R Nackashi, JA Poncher, JR Randall, V Ruppert, E Wachtel, RC Ziring, PR Berlin, CM May, DG Notterman, DA Ward, RM Weismann, DN Wilson, GS Wilson, JT AF Perrin, J Erenberg, G LaCamera, R Nackashi, JA Poncher, JR Randall, V Ruppert, E Wachtel, RC Ziring, PR Berlin, CM May, DG Notterman, DA Ward, RM Weismann, DN Wilson, GS Wilson, JT TI Medication for children with attentional disorders SO PEDIATRICS LA English DT Article ID DEFICIT DISORDER; SOCIAL-BEHAVIOR; HYPERACTIVITY; METHYLPHENIDATE; ADOLESCENTS; DESIPRAMINE AB Increasing numbers of children with attentional difficulties have been treated with medication, especially during the last 25 years, and now adolescents and adults are also being recognized with attentional difficulties. This policy statement provides information on the role and the pharmacology of medications used to treat children with attention deficit disorders. Indications and use of medications are discussed and recommended drugs and dose levels are outlined. Information on adverse effects and common side effects is presented. C1 AMER ACAD PHYS MED & REHABIL,CHICAGO,IL. US DEPT EDUC PROGRAMS,WASHINGTON,DC. US SOCIAL SECUR ADM,WASHINGTON,DC. CTR DIS CONTROL & PREVENT,CTR ENVIRONM HLTH & INJURY CONTROL,ATLANTA,GA 30341. MATERNAL & CHILD HLTH BUR,ROCKVILLE,MD. AMER ACAD PEDIAT,COMM DRUGS,ELK GROVE VILLAGE,IL. AMER ACAD CHILD & ADOLESCENT PSYCHIAT,WASHINGTON,DC. AMER MED ASSOC,CHICAGO,IL 60610. AMER COLL OBSTETRICIANS & GYNECOLOGISTS,WASHINGTON,DC. HLTH PROTECT BRANCH HSB,OTTAWA,ON,CANADA. CANADIAN PEDIAT SOC,OTTAWA,ON,CANADA. US FDA,ROCKVILLE,MD 20857. NIH,BETHESDA,MD 20892. RP Perrin, J (reprint author), AMER ACAD PEDIAT,COMM CHILDREN DISABIL,141 NW POINT BLVD,ELK GROVE VILLAGE,IL 60009, USA. NR 24 TC 27 Z9 27 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 AUG PY 1996 VL 98 IS 2 BP 301 EP 304 PN 1 PG 4 WC Pediatrics SC Pediatrics GA UZ850 UT WOS:A1996UZ85000026 ER PT J AU Beer, JZ Zmudzka, BZ AF Beer, JZ Zmudzka, BZ TI Effects of UV on HIV and other infections introduction SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; ULTRAVIOLET; PSORIASIS; RADIATION; DISEASE; CELLS RP Beer, JZ (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,RADIAT BIOL BRANCH,HFZ-114,ROCKVILLE,MD 20857, USA. NR 14 TC 10 Z9 10 U1 0 U2 2 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 AUG PY 1996 VL 64 IS 2 BP 231 EP 233 DI 10.1111/j.1751-1097.1996.tb02449.x PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VC588 UT WOS:A1996VC58800001 PM 8760559 ER PT J AU Zmudzka, BZ Miller, SA Jacobs, ME Beer, JZ AF Zmudzka, BZ Miller, SA Jacobs, ME Beer, JZ TI Medical UV exposures and HIV activation SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article; Proceedings Paper CT Symposium and Workshop on UV, HIV, and AIDS, at the 23rd Annual Meeting of the American-Society-for-Photobiology CY JUN 19-20, 1996 CL WASHINGTON, DC SP Amer Soc Photobiol ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; SUCTION BLISTER FLUID; ULTRAVIOLET-RADIATION; 8-METHOXYPSORALEN KINETICS; INVIVO ACTIVATION; LANGERHANS CELLS; TRANSGENIC MICE; ACTION SPECTRUM; DNA DAMAGE AB This paper presents the first attempt to evaluate the potential of clinical UV exposures to induce the human immunodeficiency (HIV) promoter and, thus, to upregulate HIV growth in those skin cells that are directly affected by the exposure. Using the data for HIV promoter activation in vitro, we computed UVB and psoralen plus UVA (PUVA) doses that produce 50% of the maximal promoter activation (AD(50)). Then, using (a) literature data for UV transmittance in the human skin, (b) a composite action spectrum for HIV promoter and pyrimidine dimer induction by UVB and (c) an action spectrum for DNA synthesis inhibition by PUVA, we estimated the distribution of medical UVB and PUVA doses in the skin. This allowed us to estimate how deep into the skin the HIV-activating doses might penetrate in an initial and an advanced stage of UVB or PUVA therapy. Such analysis was done for normal type II skin and for single exposures. The results allow us to predict where in the skin the HIV promoter may be induced by selected small and large therapeutic UVB or PUVA doses. To accommodate changes in skin topography due to disease and UV therapy, our considerations would require further refinements. For UVB we found that, when the incident dose on the surface of the skin is 500 J/m(2) (290-320 nm) (initial stage of the therapy), the dose producing 50% of the maximal HIV promoter activation (AD(50)(UVB)) is limited to the stratum corneum. However, with an incident dose of 5000 J/m(2) (an advanced stage of the therapy), AD(50)(UVB) may be delivered as far as the living cells of the epidermis and even to some parts of the upper dermis. For PUVA we found that, when the incident UVA doses are 25 or 100 kJ/m(2) (320-400 nm) (an initial and an advanced stage of therapy, respectively), and the 8-methoxypsoralen concentration in the blood is 0.1 mu g/mL (the desired level), the combined doses to the mid epidermis (and some areas of the upper dermis) are well below the 50% HIV promoter-activating PUVA dose (AD(50)(PUVA)). Only under the worst scenario conditions, i.e. an exceptionally high drug concentration in the patient's tissues and localization of HIV in the nearest proximity to the skin surface, would the combined PUVA dose expected during photochemotherapy exceed AD(50)(PUVA). These results suggest that the probability of HIV activation in the epidermis by direct mechanisms is higher for UVB than for PUVA treatment. However, complexities of the UV-inducible HIV activation and immunomodulatory phenomena are such that our results by themselves should not be taken as an indication that UVB therapy carries a higher risk than PUVA therapy when administered to HIV-infected patients. RP Zmudzka, BZ (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,RADIAT BIOL BRANCH,HFZ-114,ROCKVILLE,MD 20857, USA. NR 62 TC 16 Z9 16 U1 0 U2 1 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 AUG PY 1996 VL 64 IS 2 BP 246 EP 253 DI 10.1111/j.1751-1097.1996.tb02453.x PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VC588 UT WOS:A1996VC58800005 PM 8760563 ER PT J AU Kedas, AM Byrd, LJ Kisielewski, RW AF Kedas, AM Byrd, LJ Kisielewski, RW TI Residual metal shavings and fragments associated with large-core breast biopsy SO RADIOLOGY LA English DT Letter ID LESIONS RP Kedas, AM (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,OFF SURVEILLANCE & BIOMETR,DIV POSTMARKET SURVEILLANCE,ROCKVILLE,MD 20850, USA. NR 3 TC 4 Z9 4 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 AUG PY 1996 VL 200 IS 2 BP 585 EP 585 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UY078 UT WOS:A1996UY07800059 PM 8685367 ER PT J AU Gaylor, DW Chen, JJ AF Gaylor, DW Chen, JJ TI Precision of benchmark dose estimates for continuous (Nonquantal) measurements of toxic effects SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID RISK ASSESSMENT AB The benchmark dose (BMD) corresponding to a low level of the risk of induced disease, e.g., 1 to 10%, has been proposed by various authors as a replacement for the no observed adverse effect level for noncancer endpoints in the regulation of the conditions of exposure to chemicals. This paper focuses on the variability of estimates of the BMD for nonquantal (continuous measurements) of biological endpoints such as are encountered for hematological data, clinical chemistry, and studies of neurotoxic effects. For biological endpoints that can be described by a normal distribution, estimates of the mean and standard deviation are required to calculate the BMD. Estimates of the standard deviation generally are quite variable, particularly for small sample sizes. The purpose of this paper is to examine the precision of the estimates of risk and of the BMD resulting from the inherent variability of the estimates of the standard deviations particularly for bioassays that employ a small number of animals. When the standard deviation is underestimated, the BMD and the regulatory ''safe'' dose are underestimated. Conversely, when the standard deviation is overestimated, the BMD and safe dose are overestimated. Overestimation of the BMD can be reduced or eliminated by using a lower confidence limit. The worst cases arise where only a few animals are used per dose and the dose response is supralinear (changes rapidly at low doses and levels off at higher doses). If the standard deviation is constant across doses (for lognormally distributed data if the coefficient of variation is constant), a pooled estimate across doses of the standard deviation can be used. In this case, for bioassays employing a total of 40 to 50 animals, the calculation of the BMD will generally be within a factor of 2 of the true value. When the standard deviation is not constant across dose groups, it is desirable to have more than 10 animals per dose group. (C) 1996 Academic Press, Inc. RP Gaylor, DW (reprint author), US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 8 TC 9 Z9 9 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 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD AUG PY 1996 VL 24 IS 1 BP 19 EP 23 DI 10.1006/rtph.1996.0060 PN 1 PG 5 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA VN670 UT WOS:A1996VN67000004 PM 8921542 ER PT J AU Shaw, LM Bonner, H Lieberman, R AF Shaw, LM Bonner, H Lieberman, R TI Pharmacokinetic profile of amifostine SO SEMINARS IN ONCOLOGY LA English DT Article ID RHESUS-MONKEY; WR-2721; WR-1065; WR2721; PLASMA; DISPOSITION; HYDROLYSIS; TISSUES; BLOOD; ASSAY C1 UNIV PENN,MED CTR,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. NR 19 TC 47 Z9 47 U1 0 U2 0 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 AUG PY 1996 VL 23 IS 4 SU 8 BP 18 EP 22 PG 5 WC Oncology SC Oncology GA VG260 UT WOS:A1996VG26000003 PM 8783662 ER PT J AU Lieberman, R McMichael, J AF Lieberman, R McMichael, J TI Role of pharmacokinetic-pharmacodynamic principles in rational and cost-effective drug development SO THERAPEUTIC DRUG MONITORING LA English DT Article; Proceedings Paper CT 4th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology CY SEP 04-08, 1995 CL VIENNA, AUSTRIA SP Int Assoc Therapeut Drug Monitoring & Clin Toxicol, German Soc Clin Soc, Austrian Soc Clin Chem DE pharmacokinetics; pharmacodynamics; cost-effective drug development ID AUTOIMMUNE DISORDERS; FK506 AB An important goal of drug development is to define dose and concentration-response relationships for new drugs and biologics. Such critical information from controlled clinical trials can provide primary evidence of efficacy and safety and an informative database for devising dosing instructions for clinical use. This article describes applications of pharmacologic principles [pharmacokinetic-pharmacodynamic (PK-PD)] and modeling methods for drugs in which the evaluation process is guided by and/or identifies significant PK and/or PD variability in drug response. In the case of the recently registered immunosuppressive agent, tacrolimus, preclinical PK-PD in model systems can be used to rationally design safe and effective immunomodulatory dosing regimens for phase 1 clinical studies. Furthermore, a study design based on concentration control guided by a novel artificial intelligence modeling system (AIMS) can be efficiently applied to conduct randomized clinical trials in autoimmunity and to implement cost-effective therapeutic drug monitoring of tacrolimus and cyclosporine in clinical transplantation. In the case of a cardioselective beta-adrenergic blocking agent, betaxolol, marketed for essential hypertension, population PD modeling can be shown to be a more efficient method for estimating dose response compared with standard statistical tests. Using a sigmoid E(max) PD model, only a fraction (40 of 300) of the randomized patients was needed to demonstrate dose response. Therefore, two methods, i.e., PD modeling of dose response and AIMS-guided dosing, can achieve significant cost benefits for drug developers, patient care, and the health care system. C1 UNIV PITTSBURGH,TRANSPLANT INST,PITTSBURGH,PA. RP Lieberman, R (reprint author), US FDA,CDER,STAFF COLL,PARKLAWN BLDG ROOM 9B-04,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 11 TC 14 Z9 14 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD AUG PY 1996 VL 18 IS 4 BP 423 EP 428 DI 10.1097/00007691-199608000-00019 PG 6 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA UZ196 UT WOS:A1996UZ19600019 PM 8857562 ER PT J AU McMichael, J Lieberman, R McCauley, J Irish, W Marino, I Doyle, H AF McMichael, J Lieberman, R McCauley, J Irish, W Marino, I Doyle, H TI Computer-guided randomized concentration-controlled trials of tacrolimus in autoimmunity: Multiple sclerosis and primary biliary cirrhosis SO THERAPEUTIC DRUG MONITORING LA English DT Article; Proceedings Paper CT 4th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology CY SEP 04-08, 1995 CL VIENNA, AUSTRIA SP Int Assoc Therapeut Drug Monitoring & Clin Toxicol, German Soc Clin Soc, Austrian Soc Clin Chem DE tacrolimus; concentration; response; autoimmunity ID DOSING SYSTEM; FK-506; INTELLIGENT; DISORDERS; THERAPY AB A randomized concentration-controlled clinical trial (RCCCT) is a trial design in which patients are randomized to predefined blood drug concentrations (low, medium, high). If the concentration ranges are sufficiently separated, this study design can reveal important blood concentration-response relations. Tacrolimus is a potent yet ''infant'' immunosuppressant for the treatment and prevention of graft rejection and has been shown to exhibit significant clinical activity in some immune-mediated disorders. A tacrolimus artificial intelligence modeling system (AIMS) was used to guide patient dosing to achieve target concentrations specified by the study protocols. In the Multiple Sclerosis study group, we were able to define a concentration range (0.3-0.7 ng/ml) that appeared to show efficacy and minimal tacrolimus toxicity. Patients randomized to the high zone (0.6-1.2 ng/ml) in the Primary Biliary Cirrhosis study group showed significant reduction (similar to 50%) in surrogate efficacy markers [aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT)] compared with patients in the low zone (0.1-0.6 ng/ml). Therefore the RCCCT allowed the detection and delineation of clinically significant concentration-response relations in an ethical and efficient manner. C1 US FDA,CTR DRUG EVALUAT & RES,STAFF COLL,ROCKVILLE,MD 20857. RP McMichael, J (reprint author), UNIV PITTSBURGH,INST TRANSPLANTAT,3515 5TH AVE,PITTSBURGH,PA 15213, USA. NR 7 TC 7 Z9 7 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD AUG PY 1996 VL 18 IS 4 BP 435 EP 437 DI 10.1097/00007691-199608000-00021 PG 3 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA UZ196 UT WOS:A1996UZ19600021 PM 8857564 ER PT J AU Kim, C Manning, RO Brown, RP Bruckner, JV AF Kim, C Manning, RO Brown, RP Bruckner, JV TI Use the vial equilibration technique for determination of metabolic rate constants for dichloromethane SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID METHYLENE-CHLORIDE; LIVER-MICROSOMES; PARTITION-COEFFICIENTS; PHARMACOKINETIC MODELS; CYTOCHROME-P-450 IIE1; DRUG-METABOLISM; CARBON-MONOXIDE; RISK ASSESSMENT; HYDROCARBONS; OXIDATION AB Metabolism of methylene chloride, or dichloromethane (DCM), plays a key role in determining the kinetics and carcinogenicity of the halocarbon. The objectives of this study were: to evaluate and optimize the vial equilibration technique, originally described by Sate and Nakajima (1979a), in order to characterize the hepatic metabolism of DCM by Sprague-Dawley rats; to employ different hepatic microsomal preparations to examine buffer effects on DCM metabolism; and to assess the relative importance and metabolic constants of the mixed-function oxidase (MFO) and glutathione (GSH) S-transferase (CST) metabolic pathways. A crude liver homogenate (20% w/v) was prepared from perfused livers of male Sprague-Dawley (S-D) rats (275-325 g). A 30% glycerol buffer was found to significantly inhibit DCM metabolism, while 0.25 M sucrose buffer containing 10 mM EDTA and 1.15% KCl did not. DCM was incubated with the liver 10,000g supernatant or microsomes and cofactors in sealed headspace vials. Disappearance of DCM, as a measure of the chemical's metabolism, was monitored by headspace gas chromatography. Different trials were conducted to elucidate time-, enzyme-, and substrate-activity relationships, The scaled-up K-m and V-max values for the microsomal fraction were quite similar to optimized in vivo values reported by other investigators. In the current study, DCM appeared to be metabolized preferentially by cytochrome P450 IIE1, since substrates (e.g., pyrazole, ethanol, and glycerol) for this isozyme completely inhibited DCM metabolism, Thus, glycerol should not be used as a P450 stabilizer for preparation or storage of microsomes. Phorone pretreatment caused marked hepatic GSH depletion, but had little effect on the overall rate of DCM metabolism. Quantitatively, the GST pathway in the cytosol played a very minor role in DCM metabolism. It was not possible to accurately calculate metabolic constants for this pathway in S-D rats. The vial equilibration technique, as described here, is a relatively simple and reliable method, which should be broadly applicable for measuring the microsomal metabolism of DCM and other VOCs. (C) 1996 Academic Press, Inc. C1 US FDA,HLTH SCI BRANCH,ROCKVILLE,MD 20852. RP Kim, C (reprint author), UNIV GEORGIA,COLL PHARM,DEPT PHARMACOL & TOXICOL,ATHENS,GA 30602, USA. NR 36 TC 10 Z9 10 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 AUG PY 1996 VL 139 IS 2 BP 243 EP 251 DI 10.1006/taap.1996.0163 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA VD515 UT WOS:A1996VD51500004 PM 8806840 ER PT J AU Harris, GR AF Harris, GR TI Are current hydrophone low frequency response standards acceptable for measuring mechanical/cavitation indices? SO ULTRASONICS LA English DT Article DE ultrasonic hydrophone calibration; PVDF hydrophones; mechanical/cavitation indices AB The purpose of this paper is to determine the error introduced by ultrasonic hydrophones used to measure current or proposed Mechanical (MI) and Cavitation (CI) Indices, assuming that the hydrophones meet bandwidth specifications contained in US and IEC measurement standards. These indices are based on the peak rarefactional pressure, p(r). Since the portion of the pressure waveform where p(r) occurs is dominated by low frequency components, attention was placed on the low frequency hydrophone response specifications. Both simulated and actual diagnostic pressure pulses (with center frequency f(c)) were subjected to single-pole high-pass filtering for a range of -3 dB cut-off frequencies (f(a)). The error in the indices introduced by this filtration was evaluated. At both f(a)=0.5 f(c) (the US requirement) and f(a)=0.86 f(c) (calculated from the IEC -6 dB bandwidth specification at 0.5 f(c)), results showed that errors exceeding -30% could be expected. Furthermore, to reduce errors to less than 5%, the low frequency hydrophone response should extend at least an order of magnitude below the center frequency of the pressure wave. For example, for a 3.5 MHz transducer, the hydrophone should have a lower cut-off frequency of less than 350 kHz, which at present constitutes a challenge because of the lack of commerical hydrophones calibrated below 1 MHz. RP Harris, GR (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,12721 TWINBROOK PKWY,MAIL CODE HFZ-132,ROCKVILLE,MD 20852, USA. NR 8 TC 16 Z9 16 U1 0 U2 4 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0041-624X J9 ULTRASONICS JI Ultrasonics PD AUG PY 1996 VL 34 IS 6 BP 649 EP 654 DI 10.1016/0041-624X(96)00052-2 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA VJ131 UT WOS:A1996VJ13100005 PM 8844965 ER PT J AU Tortorello, ML Stewart, DS Cray, WC AF Tortorello, ML Stewart, DS Cray, WC TI Rapid identification of Escherichia coli O157:H7 in bovine feces using the antibody-direct epifluorescent filter technique (Ab-DEFT) SO VETERINARY MICROBIOLOGY LA English DT Article DE Escherichia coli O157:H7; cattle; diagnosis bacteria; Ab-DEFT ID SEROTYPE O157-H7; ENUMERATION; 0157-H7; CATTLE; BEEF AB The antibody-direct epifluorescent filter technique (Ab-DEFT) was adapted for direct detection of Escherichia coli O157:H7 in bovine feces. The method involved suspension of bovine feces in buffer, centrifugation for 30 s, treatment of the supernatant with trypsin and Triton X-100 at 50 degrees C for 10 min, pre-filtration through 5 and 12 mu m pore filters, and filtration through a 0.4 mu m pore filter. The final filter was stained with fluorescein-labeled polyclonal antibody specific for the O157 antigen acid examined by epifluorescence microscopy. The Ab-DEFT was correlated with viable plate counts for enumeration of the pathogen in artificially inoculated bovine feces (r = 0.96). The limit of detection was approximately 10(4)-10(5) CFU/g feces. The procedure provided a clean background for microscopic visualization of cells; however, cell loss and inaccurate quantitation sometimes resulted, E. coli O157:1-17 was detected in feces of an inoculated calf for more than 3 weeks post-inoculation. The Ab-DEFT may be useful for rapid screening of cattle for the presence of the E. coli O157:H7 and as an analytical method in ecological studies of the pathogen. C1 USDA, NATL ANIM DIS CTR, AMES, IA 50010 USA. RP Tortorello, ML (reprint author), US FDA, NATL CTR FOOD SAFETY & TECHNOL, SUMMIT ARGO, IL 60501 USA. FU FDA HHS [FD-000431] NR 10 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1135 J9 VET MICROBIOL JI Vet. Microbiol. PD AUG PY 1996 VL 51 IS 3-4 BP 343 EP 349 DI 10.1016/0378-1135(96)00041-7 PG 7 WC Microbiology; Veterinary Sciences SC Microbiology; Veterinary Sciences GA VD360 UT WOS:A1996VD36000013 PM 8870195 ER PT J AU Romanova, LY Alexandrov, IA Schwab, G Hilbert, DM Mushinski, JF Nordan, RP AF Romanova, LY Alexandrov, IA Schwab, G Hilbert, DM Mushinski, JF Nordan, RP TI Mechanism of apoptosis suppression by phorbol ester in IL-6-starved murine plasmacytomas: Role of PKC modulation and cell cycle SO BIOCHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; MYC-INDUCED APOPTOSIS; DNA FRAGMENTATION; LYMPHOMA CELLS; LEUKEMIA-CELLS; DEATH; FIBROBLASTS; INDUCTION; PHOSPHORYLATION; ACTIVATION AB We show here that the mode of cell death in IL-6-starved T1165 and T1198 plasmacytoma cell lines is apoptosis, and that it can be suppressed by phorbol ester (PMA) treatment in a protein kinase C (PKC)-mediated process that involves alpha and/or delta isozymes. PMA-induced PKC activation, but not the depletion that follows it, participates in the suppression of apoptosis. Extended PKC activation is necessary but not sufficient for the apoptosis suppression. In addition, the cells must be in a ''competent'' state, which appears not to be determined by PKC. We observed two points of ''competence'' during the time between withdrawal of IL-6 and the start of massive cell death: one, immediately after withdrawal, and another, just before onset of apoptosis, at the time corresponding to maximal accumulation of cells in a G0/G1 black imposed by IL-6 withdrawal, Treatment with PMA and other PKC activators resulted in a shift of the cell population to S phase, Lifting the G0/G1 block, We propose a model in which cells are rescued in a certain stage of the G1 phase of cell cycle. Death suppression occurs when a transient PMA-induced PKC activation occurs when a significant number of cells are in this part of G1. allowing them to pass the restriction point safely without initiating the cell death program. C1 US FDA, CTR BIOL EVALUAT & RES, DIV MONOCLONAL ANTIBODIES, BETHESDA, MD 20892 USA. NCI, GENET LAB, NIH, BETHESDA, MD 20892 USA. NR 32 TC 32 Z9 32 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 JUL 30 PY 1996 VL 35 IS 30 BP 9900 EP 9906 DI 10.1021/bi9525886 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VA025 UT WOS:A1996VA02500031 PM 8703964 ER PT J AU Pradhan, S Wu, AT Lesko, LJ Chen, ML Williams, RL AF Pradhan, S Wu, AT Lesko, LJ Chen, ML Williams, RL TI Bioavailability measurements of methazolamide in plasma, red blood cells and whole blood: Implications for bioequivalence studies SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE methazolamide; whole blood; red blood cell; plasma; dose proportionality; distribution; pharmacokinetic parameters; bioequivalence study ID CARBONIC-ANHYDRASE INHIBITOR AB The kinetics of methazolamide (MTZ) in human whole blood, red blood cells (RBCs) and plasma have been investigated. The study was conducted over a wide dose range using three single-dose (25, 50 or 100 mg)and two multiple-dose (50 mg q 12 h x 3 or 100 mg q 12 h x 3) schedules. The results of the study indicate that the increase of drug concentrations in both whole blood and RBCs is dose-proportional over a range of 25 mg to 150 mg doses, while that in plasma is dose-proportional only from 100 mg to 150 mg. As plasma drug concentrations at 100 mg dose is too low to provide a reliable measure, and a dose higher than this may cause adverse reactions in healthy individuals, the pharmacokinetic parameters derived from whole blood analysis at the 100 mg dose is adequate for bioequivalence evaluation of the drug product obtained from two different sources. C1 US FDA,DEPT HLTH & HUMAN SERV,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20855. RP Pradhan, S (reprint author), US FDA,DEPT HLTH & HUMAN SERV,CTR DRUG EVALUAT & RES,OFF GENER DRUGS,DIV BIOEQUIVALENCE,ROCKVILLE,MD 20855, USA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARM JI Int. J. Pharm. PD JUL 26 PY 1996 VL 138 IS 2 BP 207 EP 213 DI 10.1016/0378-5173(96)04536-X PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VC504 UT WOS:A1996VC50400009 ER PT J AU Thompson, SA Harris, A Hoang, DE Ferrer, M Johnson, GR AF Thompson, SA Harris, A Hoang, DE Ferrer, M Johnson, GR TI COOH-terminal extended recombinant amphiregulin with bioactivity comparable with naturally derived growth factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAMMARY EPITHELIAL-CELLS; HUMAN GASTRIC CARCINOMAS; FACTOR RECEPTOR; FACTOR-ALPHA; IMMUNOHISTOCHEMICAL DETECTION; ESCHERICHIA-COLI; HEPARAN-SULFATE; FACTOR FAMILY; EXPRESSION; BINDING AB The mature secreted form of the epidermal growth factor (EGF) receptor ligand amphiregulin (AR) is reported to be an 84-amino acid residue polypeptide, which is generated by proteolytic processing of a 252-amino acid precursor. This form of recombinant AR (rAR84) and two forms with COOH-terminal extensions corresponding to sequences from the AR precursor (rAR87 and rAR92) were expressed at high levels in Escherichia coli, oxidized to the correct disulfide arrangement, and purified to homogeneity. rAR84 competed poorly for binding of radiolabeled EGF to the EGF receptor and had little ability to stimulate growth of Balb/c/3T3 cells. In striking contrast, rAR87 and rAR92 possessed 42- and 20-fold greater receptor binding activity and 55- and 14-fold greater bioactivity, respectively. Furthermore, addition of the COOH-terminal four amino acids from transforming growth factor cu to the COOH terminus of rAR84 improved the activity of rAR84 by 100- and 1000-fold, respectively, in these assays. rAR87 was found to have similar to 32% of the specific activity of natural AR from MCF-7 cells when compared in two different bioassays. These findings strongly suggest that the 84-amino acid sequence is not the correct structure of the naturally occurring secreted form of AR and that natural AR contains additional amino acid residues at the COOH-terminal end. C1 BERLEX BIOSCI,DEPT PROT CHEM & BIOPHYS,RICHMOND,CA 94804. NATL CTR TOXICOL RES,DEPT GENET TOXICOL,JEFFERSON,AR 72079. US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. NR 40 TC 17 Z9 17 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 JUL 26 PY 1996 VL 271 IS 30 BP 17927 EP 17931 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UY935 UT WOS:A1996UY93500052 PM 8663535 ER PT J AU Wysowski, DK Bacsanyi, J AF Wysowski, DK Bacsanyi, J TI Cisapride and fatal arrhythmia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Wysowski, DK (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 6 TC 230 Z9 235 U1 0 U2 1 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 JUL 25 PY 1996 VL 335 IS 4 BP 290 EP 291 DI 10.1056/NEJM199607253350416 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA UZ532 UT WOS:A1996UZ53200030 PM 8657260 ER PT J AU Chambers, J Somerfeldt, S Mackey, L Nichols, S Ball, R Roberts, D Dufford, N Reddick, A Gibson, J AF Chambers, J Somerfeldt, S Mackey, L Nichols, S Ball, R Roberts, D Dufford, N Reddick, A Gibson, J TI Outbreaks of Cyclospora cayetanensis infection - United States, 1996 (Reprinted from MMWR, vol 45, pg 549-551, 1996) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 S CAROLINA DEPT HLTH & ENVIRONM CONTROL,COLUMBIA,SC 29201. US FDA,CTR FOOD SAFETY & APPL NUTR,ROCKVILLE,MD 20857. US FDA,OFF REGULATORY AFFAIRS,ROCKVILLE,MD 20857. CDC,DIV FIELD EPIDEMIOL,EPIDEMIOL PROGRAM OFF,ATLANTA,GA 30333. CDC,FOODBORNE & DIARRHEAL DIS BRANCH,DIV BACTERIAL & MYCOT DIS,ATLANTA,GA 30333. CDC,EPIDEMIOL BRANCH,DIV PARASIT DIS,NATL CTR INFECT DIS,ATLANTA,GA 30333. NR 1 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 JUL 17 PY 1996 VL 276 IS 3 BP 183 EP 183 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UW469 UT WOS:A1996UW46900010 ER PT J AU Li, SP Goldman, ND AF Li, SP Goldman, ND TI Regulation of human C-reactive protein gene expression by two synergistic IL-6 responsive elements SO BIOCHEMISTRY LA English DT Article ID ACUTE-PHASE RESPONSE; TRANSCRIPTIONAL ACTIVATOR PROTEIN; HEPATOCYTE-STIMULATING FACTOR; LEUCINE ZIPPER PROTEINS; NUCLEAR FACTOR; DNA-BINDING; C/EBP FAMILY; MESSENGER-RNA; CELLS; PROMOTER AB To study the mechanism of interleukin-6 (IL-6) induction of human C-reactive protein (CRP) gene expression, we have utilized a human hepatoma (PLC/PRF/5) cell culture system to analyze the trans-acting factors which bind to the 300 bp 5'-flanking region of human CRP gene. in vitro gel mobility shift analyses and methylation interference assays demonstrated that NFIL-6 alpha interacted with two IL-6 responsive elements, and HNF-1 alpha and HNF-3/Octamer-like factors interacted with the downstream IL-6 responsive element in the human CRP promoter. In vivo functional analysis by transient transfection of plasmid constructs containing site-specific mutations in one or two IL-6 responsive elements in the CRP promoter fused to a reporter gene, chloramphenicol acetyl transferase (CAT), demonstrated that the binding of NFIL-6 alpha to two IL-6 responsive elements resulted in synergistic induction of the gene. When HNF-1 alpha or HNF-3/Octamer-like factors were independently bound to their corresponding sites, they had either a positive or negative effect, respectively, on IL-6 inducible transcriptional activity. C1 US FDA,CTR BIOL EVALUAT & RES,DIV ALLERGEN PROD & PARASITOL,ROCKVILLE,MD 20852. NR 64 TC 73 Z9 73 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 JUL 16 PY 1996 VL 35 IS 28 BP 9060 EP 9068 DI 10.1021/bi953033d PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UX738 UT WOS:A1996UX73800008 PM 8703909 ER PT J AU VonTungeln, LS Bucci, TJ Hart, RW Kadlubar, FF Fu, PP AF VonTungeln, LS Bucci, TJ Hart, RW Kadlubar, FF Fu, PP TI Inhibitory effect of caloric restriction on tumorigenicity induced by 4-aminobiphenyl and 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP) in the CD1 newborn mouse bioassay SO CANCER LETTERS LA English DT Article DE caloric restriction; neonatal mouse; tumor inhibition; liver tumors; 4-aminobiphenyl; 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine ID CANCER AB The tumorigenicity of 4-aminobiphenyl (4-ABP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were studied in combination with caloric restriction in the male neonatal CD1 mouse bioassay. 4-ABP and PhIP exhibited moderate and weak tumorigenicity, respectively, in ad libitum fed mice; however, none of the caloric restricted mice developed tumors. These results indicate that caloric restriction, even when begun 3 months after the conclusion of compound treatment, markedly inhibited 4-ABP- and PhIP-induced tumors in the CD1 mouse C1 NATL CTR TOXICOL RES,DEPT BIOCHEM TOXICOL,JEFFERSON,AR 72079. NR 18 TC 12 Z9 12 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 JUL 12 PY 1996 VL 104 IS 2 BP 133 EP 136 DI 10.1016/0304-3835(96)04232-2 PG 4 WC Oncology SC Oncology GA UQ938 UT WOS:A1996UQ93800002 PM 8665480 ER PT J AU Sahu, SC Gray, GC AF Sahu, SC Gray, GC TI Pro-oxidant activity of flavonoids: Effects on glutathione and glutathione S-transferase in isolated rat liver nuclei SO CANCER LETTERS LA English DT Article DE flavonoids; glutathione; glutathione S-transferase; oxidative stress ID DNA DAMAGE; LIPID-PEROXIDATION; QUERCETIN; INHIBITION; OXYGEN; ISOENZYMES AB The effects of three representative flavonoids, quercetin, myricetin and kaempferol, on the nuclear antioxidant defense glutathione (GSH) and glutathione S-transferase (GST) were investigated in a model system of isolated rat liver nuclei. The three flavonoids induced a concentration-dependent decrease of both the nuclear GSH content and GST activity. Myricetin, which has the maximum number of hydroxyl groups, was the most active. The results demonstrate the pro-oxidant activity of these polyphenolic flavonoids. The impairment of the nuclear antioxidant defense GSH and GST by the polyphenolic flavonoids can lead to oxidative DNA damage, which may be responsible for their mutagenicity. RP Sahu, SC (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV TOXICOL RES HFS509,LAUREL,MD 20708, USA. NR 26 TC 65 Z9 70 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUL 12 PY 1996 VL 104 IS 2 BP 193 EP 196 DI 10.1016/0304-3835(96)04251-6 PG 4 WC Oncology SC Oncology GA UQ938 UT WOS:A1996UQ93800009 PM 8665487 ER PT J AU Mahmood, I Balian, JD AF Mahmood, I Balian, JD TI Interspecies scaling: A comparative study for the prediction of clearance and volume using two or more than two species SO LIFE SCIENCES LA English DT Article DE interspecies scaling; clearance; volume ID ANIMAL DATA; PHARMACOKINETICS; PARAMETERS; HUMANS AB The prediction of pharmacokinetic parameters in humans from data obtained in lower animals can be of considerable importance in the process of drug development. Successful extrapolation will facilitate drug dosing transitions from animals to man and accelerate the drug testing process. Existing literature indicates that for the prediction of pharmacokinetic parameters, data from at least three animal species are used. Some investigators have used only two species to predict clearance and volume in humans. The objective of this paper is to investigate and try to determine if a two species scaleup model is as reliable as a three or more species model. Twelve compounds were chosen randomly from literature and clearance and volume of distribution were scaled-up from two species and compared to predictions obtained from more than two species. The findings in this study indicate that: (1) three or more species are needed for a reliable prediction of clearance; and (2) volume of distribution of a compound is predicted equally well using data from two species or more. RP Mahmood, I (reprint author), US FDA,WOODMONT OFF CTR 2,OFF CLIN PHARMACOL & BIOPHARMACEUT,1451 ROCKVILLE PIKE,ROOM 4054,ROCKVILLE,MD 20852, USA. NR 18 TC 37 Z9 38 U1 0 U2 2 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 JUL 12 PY 1996 VL 59 IS 7 BP 579 EP 585 DI 10.1016/0024-3205(96)00339-6 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA UY265 UT WOS:A1996UY26500009 PM 8761347 ER PT J AU Puri, RK Leland, P Obiri, NI Husain, SR Mule, J Pastan, I Kreitman, RJ AF Puri, RK Leland, P Obiri, NI Husain, SR Mule, J Pastan, I Kreitman, RJ TI An improved circularly permuted interleukin 4-toxin is highly cytotoxic to human renal cell carcinoma cells SO CELLULAR IMMUNOLOGY LA English DT Article ID RECEPTOR-GAMMA-CHAIN; AFFINITY IL-4 RECEPTORS; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; FUNCTIONAL COMPONENT; TUMOR-CELLS; EXPRESSION; GROWTH; INHIBITION; BINDING AB We have previously demonstrated that a chimeric protein composed of human IL-4 and Pseudomonas exotoxin, termed IL4-PE(4E), is cytotoxic to primary cells derived from human renal cell carcinoma (RCC). To improve the cytotoxicity of IL4-toxins such as IL4-PE(4E) and IL4-PE38KDEL to IL-4 receptor (IL-4R) positive tumor cells, a circularly permutated chimeric toxin was prepared by fusing a truncated PE gene encoding PE38KDEL 3' to a circularly permutated IL-4 mutant gene encoding IL4 amino acids 38-129, the linker GGNGG, and IL4 amino acids 1-37. The resulting chimeric protein, termed IL4(38-37)-PE38KDEL, was tested on five RCC cell lines and its cytotoxicity was compared to that of the native IL4-toxins IL4-PE(4E) and IL4-PE38KDEL. IL4(38-37)-PE38KDEL was found to be 5 to 10 times more cytotoxic to all cell cultures tested compared to either native IL4-toxin. The cytotoxic activity of IL4(38-37)-PE38KDEL was competable by excess IL4 and was confirmed by clonogenic assay. IL4(38-37)-PE38KDEL bound to IL-4R on RCC cells with 6- to 12-fold higher affinity than IL4-PE38KDEL or IL4-PE(4E), RCC tumor cells were found to lack the common gamma chain (gamma(c)) of the IL-4R reported to be present on immune cells. The stable transfection of RCC cells with the gamma(c), chain gene did not significantly change their sensitivity to IL4(38-37)-PE38KDEL, Taken together, our results indicate that the CPIL4-toxin IL4(38-37)-PE38KDEL is highly cytotoxic to human RCC cells due to increased binding affinity to IL-4R while it is not cytotoxic or slightly cytotoxic to T and B cells, monocytic cell. lines, and fresh resting or activated bone marrow-derived cells. The gamma(c) does not seem to increase the internalization rate and/or processing of IL4-toxins in RCC cells, CPIL4-toxin may be a useful agent for the treatment of human RCC. (C) 1996 Academic Press, Inc. C1 UNIV MICHIGAN,DEPT SURG,ANN ARBOR,MI 48109. NCI,MOLEC BIOL LAB,DIV CANC BIOL,NIH,BETHESDA,MD 20892. RP Puri, RK (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,LAB MOLEC TUMOR BIOL,NIH,BLDG 29B,BETHESDA,MD 20892, USA. NR 36 TC 38 Z9 39 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JUL 10 PY 1996 VL 171 IS 1 BP 80 EP 86 DI 10.1006/cimm.1996.0176 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA UY134 UT WOS:A1996UY13400013 PM 8660841 ER PT J AU Weir, JP Dacquel, EJ Aronovitz, J AF Weir, JP Dacquel, EJ Aronovitz, J TI Herpesvirus vector-mediated gene delivery to human monocytes SO HUMAN GENE THERAPY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN GLUCOCEREBROSIDASE GENE; PLACEBO-CONTROLLED TRIAL; HIV-INFECTION; MONONUCLEAR PHAGOCYTES; DELETION MUTANTS; INTERFERON-ALPHA; BONE-MARROW; TYPE-1; EXPRESSION AB In vitro delivery of interferon-alpha (IFN-alpha) to cultured human monocytes by means of a replication-incompetent herpesvirus vector inhibits human immunodeficiency virus (HIV) replication. To explore the possibility of IFN-alpha gene delivery by vector-infected human monocytes, monocytes were isolated and the culture conditions necessary for efficient vector infection and gene expression were examined. Monocytes were efficiently infected between 1 and 7 days after isolation. Expression of IFN-alpha was greater in cells infected 7 days after isolation compared to 1 day after isolation, but the levels of expression were equivalent regardless of whether cells were maintained in suspension or monolayer culture. When suspension-cultured monocytes were treated with vd120/IFN-alpha and added to monolayer cultures of HIV-infected monocytes, IFN-alpha was expressed and replication of HIV was inhibited. HIV replication was arrested even when HIV had spread through much of the monolayer. The persistence of the viral vector in infected cells was examined by a superinfection rescue assay using a second replication-incompetent herpes simplex virus, 5d/1.2. The initial replication-incompetent vector remained in a recoverable form for at least 7 days after delivery, even though foreign gene expression was transient. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,BETHESDA,MD 20892. HENRY M JACKSON FDN,ROCKVILLE,MD 20850. WALTER REED ARMY INST RES,ROCKVILLE,MD 20850. NR 37 TC 6 Z9 6 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL 10 PY 1996 VL 7 IS 11 BP 1331 EP 1338 DI 10.1089/hum.1996.7.11-1331 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WD320 UT WOS:A1996WD32000003 PM 8818720 ER PT J AU David, M Zhou, GC Pine, R Dixon, JE Larner, AC AF David, M Zhou, GC Pine, R Dixon, JE Larner, AC TI The SH2 domain-containing tyrosine phosphatase PTP1D is required for interferon alpha/beta-induced gene expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SH2-CONTAINING PHOSPHOTYROSINE PHOSPHATASE; TRANSCRIPTION FACTOR ISGF3; GAMMA SIGNAL-TRANSDUCTION; INVITRO ACTIVATION; KINASE; RECEPTOR; PHOSPHORYLATION; CORKSCREW; PATHWAY; HOMOLOG AB Interferons (IFNs) induce early response genes by stimulating Janus family (Jak) tyrosine kinases, leading to tyrosine phosphorylation of Stat (signal transducer and activator of transcription) proteins. Previous studies demonstrated that a protein-tyrosine phosphatase (PTP) is required for activation of the ISGF3 transcription complex by IFN alpha/beta, but the specific PTP responsible remained unidentified. We now show that the SH2 domain containing tyrosine phosphatase PTP1D (also designated as SHPTP2, SHPTP3, PTP2C, or Syp) is constitutively associated with the IFN alpha/beta receptor and becomes tyrosine-phosphorylated in response to ligand. Furthermore, transient expression of a phosphatase-inactive mutant or the COOH-terminal SH2 domain of PTP1D causes a dominant negative effect on IFN alpha/beta-induced early response gene expression. These results provide strong evidence that PTP1D functions as a positive regulator of the IFN alpha/beta-induced Jak/Stat signal transduction pathway. C1 US FDA,DIV CYTOKINE BIOL,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. UNIV MICHIGAN,SCH MED,DEPT BIOL CHEM,ANN ARBOR,MI 48109. PUBL HLTH RES INST,NEW YORK,NY 10016. FU PHS HHS [18849] NR 37 TC 93 Z9 96 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 JUL 5 PY 1996 VL 271 IS 27 BP 15862 EP 15865 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UW352 UT WOS:A1996UW35200005 PM 8663536 ER PT J AU Robbins, JD Boring, DL Tang, WJ Shank, R Seamon, KB AF Robbins, JD Boring, DL Tang, WJ Shank, R Seamon, KB TI Forskolin carbamates: Binding and activation studies with type I adenylyl cyclase SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID EXPRESSION; 7-DESACETYLFORSKOLIN; DERIVATIVES AB Three series of analogs were regioselectively prepared from a protected forskolin precursor to afford 7-carbamoyl-7-desacetylforskolins (series 1), 6-carbamoyl-7-desacetylforskolins (series 2), and 6-carbamoylforskolins (series 3). The analogs were pharmacologically evaluated for binding (IC50) to and activation (EC(50)) of type I adenylyl cyclase in membranes from stably transfected Sig cell lines expressing a single adenylate cyclase subtype. The following ranges were determined for the IC50's and EC(50)'s of each individual series: series 1, IC50 = 43-1600 nM, EC(50) = 0.5-9.6 mu M; series 2, IC50 = 65-680 nM, EC(50) = 0.63-6.5 mu M; series 3, IC50 = 21-271 nM, EC(50) = 0.5-8.1 mu M (forskolin IC50 = 41 nM and EC(50) = 0.5 mu M). Activation paralleled binding; however, some analogs exhibited poor binding and good activation whereas others demonstrated good binding but poor activation. Steric bulk tended to diminish binding and activation when at the 6- or 7-position, although bulk was accommodated at the 6-position if the 7-site was reacetylated. Acylation of the 7-position by the carbamoyl linker or acetyl was important for obtaining good binding and activation; however, the effect was more pronounced with binding. For both binding and activation, small, linear, lipophilic substituents (propyl, allyl, isopropyl) are well tolerated at the 7-position but less so in the 6-position, even when the 7-site is reacetylated. Planar aromatic moieties (phenyl and 2-pyridinyl) demonstrated moderate to good potency for binding and activation when located at either the 6- or 7-positions. There is an overall trend toward increasing potency for both binding and activation with polar substituents. C1 US FDA, CTR BIOL EVALUAT & RES, DIV CYTOKINE BIOL, BIOL CHEM LAB, BETHESDA, MD 20892 USA. CTR DRUG EVALUAT & RES, OFF PHARMACEUT SCI, DIV NEW DRUG CHEM 3, DIV ANTIVIRAL DRUG PROD, ROCKVILLE, MD 20850 USA. UNIV TEXAS, SW MED CTR, DALLAS, TX 75235 USA. OI Tang, Wei-Jen/0000-0002-8267-8995 NR 23 TC 13 Z9 13 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD JUL 5 PY 1996 VL 39 IS 14 BP 2745 EP 2752 DI 10.1021/jm960191+ PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA UW510 UT WOS:A1996UW51000014 PM 8709105 ER PT J AU Nightingale, SL AF Nightingale, SL TI Dexfenfluramine approved 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 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 JUL 3 PY 1996 VL 276 IS 1 BP 14 EP 14 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UU439 UT WOS:A1996UU43900006 PM 8667525 ER PT J AU Nightingale, SL AF Nightingale, SL TI Comments requested on direct-to-consumer promotion 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 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 JUL 3 PY 1996 VL 276 IS 1 BP 14 EP 14 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UU439 UT WOS:A1996UU43900005 PM 8667525 ER PT J AU Nightingale, SL AF Nightingale, SL TI HIV home test system approved 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 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 JUL 3 PY 1996 VL 276 IS 1 BP 14 EP 14 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UU439 UT WOS:A1996UU43900007 PM 8667525 ER PT J AU Alexander, NJ Alexander, V Allen, S Dorflinger, L Dommel, WF Duerr, A Elias, C Feigal, D Gollub, E Gabelnick, H Harris, M Hitchcock, PJ Karam, M Kazempour, K Lange, J Roddy, R Rowe, P Rosenberg, Z Perriens, J Stone, A Stratton, P AF Alexander, NJ Alexander, V Allen, S Dorflinger, L Dommel, WF Duerr, A Elias, C Feigal, D Gollub, E Gabelnick, H Harris, M Hitchcock, PJ Karam, M Kazempour, K Lange, J Roddy, R Rowe, P Rosenberg, Z Perriens, J Stone, A Stratton, P TI Recommendations for the development of vaginal microbicides SO AIDS LA English DT Article DE HIV prevention; sexually transmitted disease prevention; vaginal microbicides ID NONOXYNOL-9; WOMEN; HIV AB Vaginal microbicides are products for vaginal administration that can be used to prevent HIV infection and other sexually transmitted diseases (STD). We recognize two potential sources of vaginal microbicides: existing spermicides and new products (new products may or may not be spermicidal). This document is meant to serve as a general guide for development and evaluation of existing and new products. For new products preclinical studies will be required. Depending upon indication, in vitro activity against HIV, target STD, and sperm should also be assessed. Compatibility with barrier method materials should also be evaluated. The physical-chemical properties of the active agent and the clinical formulation should be assessed. Animals studies should be conducted to assess its safety and predict dosing; use of various models to assess local toxicity is indicated and microbicidal activity of the product may be evaluated if appropriate models are available. Carcinogenicity testing and segment III reproduction studies (perinatal and post-natal studies in rats) may be performed concurrently with Phase III clinical trials. All vaginal microbicides, including existing spermicides and new products, should be clinically evaluated for safety and efficacy. Safety studies are necessary because irritation of vaginal and cervical mucosae has been recently associated with spermicide use and those lesions might increase HIV transmission. Efficacy studies to assess prevention of HIV infection and/or STD, depending upon the product indication, should then be conducted with products that have been evaluated for safety and appear to be non-toxic to tissue. For spermicidal microbicides contraceptive efficacy studies will be needed. C1 NICHHD,NIH,BETHESDA,MD 20892. COMMUNITY FAMILY PLANNING COUNCIL,NEW YORK,NY. ADV HLTH TECHNOL,WASHINGTON,DC. FAMILY HLTH INT,RES TRIANGLE PK,NC 27709. NIH,OFF PROTECT RES RISKS,BETHESDA,MD 20892. CTR DIS CONTROL & PREVENT,DIV REPROD HLTH,ATLANTA,GA 30341. POPULAT COUNCIL,BANGKOK,THAILAND. US FDA,DIV ANTIVIRAL DRUG PROD,ROCKVILLE,MD 20857. AIDS COORDINATING OFF,PHILADELPHIA,PA. CONRAD PROGRAM,ARLINGTON,VA. SOC WOMEN & AIDS AFRICA,FREETOWN,SIERRA LEONE. NIAID,NIH,BETHESDA,MD 20892. WHO,GLOBAL PROGRAMME AIDS,CH-1211 GENEVA,SWITZERLAND. WHO,SPECIAL PROGRAMME RES DEV & RES TRAINING HUMA,CH-1211 GENEVA,SWITZERLAND. MRC,LONDON W1N 4AL,ENGLAND. RP Alexander, NJ (reprint author), UNAIDS,INT WORKING GRP VAGINAL MICROBICIDES,20 AVE APPIA,CH-1211 GENEVA 27,SWITZERLAND. NR 16 TC 0 Z9 0 U1 0 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD JUL PY 1996 VL 10 IS 8 BP 1 EP 6 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA UW089 UT WOS:A1996UW08900026 ER PT J AU Rheinstein, PH McGinnis, TJ AF Rheinstein, PH McGinnis, TJ TI Ways to access FDA information SO AMERICAN FAMILY PHYSICIAN LA English DT Article RP Rheinstein, PH (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD JUL PY 1996 VL 54 IS 1 BP 353 EP & PG 5 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA UW459 UT WOS:A1996UW45900031 PM 8677842 ER PT J AU Collantes, ER Tong, WD Welsh, WJ Zielinski, WL AF Collantes, ER Tong, WD Welsh, WJ Zielinski, WL TI Use of moment of inertia in comparative molecular field analysis to model chromatographic retention of nonpolar solutes SO ANALYTICAL CHEMISTRY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; GAS; SHAPE; INDEXES; PHASE; INHIBITORS; PREDICTION; SEPARATION; REGRESSION; BIPHENYLS AB A quantitative structure-retention relationship (QSRR) was developed from chromatographic data on 31 unsubstituted 3-6-ring polycyclic aromatic hydrocarbons (PAHs) using the 3D-QSAR method known as comparative molecular held analysis (CoMFA). The resulting CoMFA model gave an excellent correlation to high-performance liquid chromatography retention data for these PAHs yielding r(2) values of 0.947 (conventional) and 0.865 (cross-validated). The steric and electrostatic contributions to the CoMFA model were 100% and 0%, respectively. A unique feature of this study was the use of moment of inertia, I, as a basis for CoMFA alignment of the PAH molecules. The moment of inertia also provided an alternative method for calculating the solute length-to-breadth ratio (L/B), which has been applied in previous QSRR studies as a molecular descriptor for PAH retention. By virtue of its mathematical simplicity and lack of ambiguity, the present derivation of L/B from I offers several advantages over other geometry-based schemes. Finally, I-x was evaluated for use as a molecular descriptor in QSRR regression analysis to predict the log of the retention index (log I) for these PAHs. The correlation with PAH retention was weak when the moment of inertia was considered alone but improved dramatically (r(2) = 0.928) when the moment of inertia and connectivity index chi were used in combination as descriptors. C1 UNIV MISSOURI,DEPT CHEM,ST LOUIS,MO 63121. UNIV MISSOURI,CTR MOLEC ELECTR,ST LOUIS,MO 63121. US FDA,DIV DRUG ANAL,ST LOUIS,MO 63101. NR 25 TC 52 Z9 55 U1 0 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 JUL 1 PY 1996 VL 68 IS 13 BP 2038 EP 2043 DI 10.1021/ac951116u PG 6 WC Chemistry, Analytical SC Chemistry GA UW367 UT WOS:A1996UW36700015 PM 9027220 ER PT J AU Styrt, BA PiazzaHepp, TD Chikami, GK AF Styrt, BA PiazzaHepp, TD Chikami, GK TI Clinical toxicity of antiretroviral nucleoside analogs SO ANTIVIRAL RESEARCH LA English DT Review DE nucleoside analogs, retroviral; toxicity, nucleoside analogs; zidovudine; didanosine; zalcitabine; stavudine; lamivudine ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-RELATED COMPLEX; ZIDOVUDINE-INDUCED HEPATOTOXICITY; IMPAIRED MITOCHONDRIAL-FUNCTION; FULMINANT HEPATIC-FAILURE; PLACEBO-CONTROLLED TRIAL; DEFICIENCY-SYNDROME AIDS; HIV-INFECTION; 2',3'-DIDEOXYCYTIDINE DDC; TYPE-1 INFECTION C1 US FDA,CTR DRUG EVALUAT & RES,DIV EPIDEMIOL & SURVEILLANCE,ROCKVILLE,MD 20857. US FDA,CTR DRUG EVALUAT & RES,DIV ANTIVIRAL DRUG PROD,ROCKVILLE,MD 20857. NR 122 TC 38 Z9 40 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JUL PY 1996 VL 31 IS 3 BP 121 EP 135 DI 10.1016/0166-3542(96)85209-0 PG 15 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA UV942 UT WOS:A1996UV94200001 PM 8811197 ER PT J AU Bezalel, L Hadar, Y Fu, PP Freeman, JP Cerniglia, CE AF Bezalel, L Hadar, Y Fu, PP Freeman, JP Cerniglia, CE TI Metabolism of phenanthrene by the white rot fungus Pleurotus ostreatus SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; PHANEROCHAETE-CHRYSOSPORIUM; TRANS-DIHYDRODIOLS; BIODEGRADATION; DEGRADATION; OXIDATION AB The white rot fungus Pleurotus ostreatus, grown for 11 days in basidiomycetes rich medium containing [C-14] phenanthrene, metabolized 94% of the phenanthrene added. Of the total radioactivity, 3% was oxidized to CO2. Approximately 52% of phenanthrene was metabolized to trans-9,10-dihydroxy-9,10-dihydrophenanthrene (phenanthrene trans-9, 10-dihydrodiol) (28%), 2,2'-diphenic acid (17%), and unidentified metabolites (7%). Nonextractable metabolites accounted for 35% of the total radioactivity. The metabolites were extracted with ethyl acetate, separated by reversed-phase high-performance liquid chromatography, and characterized by H-1 nuclear magnetic resonance, mass spectrometry, and UV spectroscopy analyses. O-18(2)-labeling experiments indicated that one atom of oxygen was incorporated into the phenanthrene trans-9,10-dihydrodiol. Circular dichroism spectra of the phenanthrene trans-9,10-dihydrodiol indicated that the absolute configuration of the predominant enantiomer was 9R,10R, which is different from that of the principal enantiomer produced by Phanerochaete chrysosporium. Significantly less phenanthrene trans-9,10-dihydrodiol was observed in incubations with the cytochrome P-450 inhibitor SKF 525-A (77% decrease), 1-aminobenzotriazole (83% decrease), or fluoxetine (63% decrease). These experiments with cytochrome P-450 inhibitors and O-18(2) labeling and the formation of phenanthrene trans-9R,10R-dihydrodiol as the predominant metabolite suggest that P. ostreatus initially oxidizes phenanthrene stereoselectively by a cytochrome P-450 monoxygenase and that this is followed by epoxide hydrolase-catalyzed hydration reactions. C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. HEBREW UNIV JERUSALEM,FAC AGR,DEPT PLANT PATHOL & MICROBIOL,IL-76100 REHOVOT,ISRAEL. NR 46 TC 104 Z9 119 U1 1 U2 4 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 JUL PY 1996 VL 62 IS 7 BP 2547 EP 2553 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA UV792 UT WOS:A1996UV79200052 PM 8779594 ER PT J AU Bezalel, L Hadar, Y Fu, PP Freeman, JP Cerniglia, CE AF Bezalel, L Hadar, Y Fu, PP Freeman, JP Cerniglia, CE TI Initial oxidation products in the metabolism of pyrene, anthracene, fluorene, and dibenzothiophene by the white rot fungus Pleurotus ostreatus SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; PHANEROCHAETE-CHRYSOSPORIUM; CUNNINGHAMELLA-ELEGANS; STEREOSELECTIVE METABOLISM; RING FISSION; BIODEGRADATION; PHENANTHRENE; DEGRADATION; IDENTIFICATION; SOIL AB The initial metabolites in the degradation of pyrene, anthracene, fluorene, and dibenzothiophene by Pleurotus ostreatus were isolated by high-pressure liquid chromatography and characterized by UV-visible, gas-chromatographic, mass-spectrometric, and H-1 nuclear magnetic resonance spectral techniques. The metabolites from pyrene, dibenzothiophene, anthracene, and, fluorene amounted to 45, 84, 64, and 96% of the total organic-solvent-extractable metabolites, respectively. Pyrene was metabolized predominantly to pyrene trans-4,5-dihydrodiol. Anthracene was metabolized predominantly to anthracene trans-1,2-dihydrodiol and 9,10-anthraquinone. In contrast, fluorene and dibenzothiophene were oxidized at the aliphatic bridges instead of the aromatic rings. Fluorene was oxidized to 9-fluorenol and 9-fluorenone; diberizothiophene was oxidized to the sulfoxide and sulfone. Circular dichroism spectroscopy revealed that the major enantiomer of anthracene trans-1,2-dihydrodiol was predominantly in the S,S configuration and the major enantiomer of the pyrene trans-4,5-dihydrodiol was predominantly RE. These results indicate that the white rot fungus P. ostreatus initially metabolizes polycyclic aromatic hydrocarbons' by reactions similar to those previously reported for nonligninolytic fungi. However, P. ostreatus, in contrast to nonligninolytic fungi, can mineralize these polycyclic aromatic hydrocarbons. The identity of the dihydrodiol metabolites implicates a cytochrome P-450 monooxygenase mechanism. C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. HEBREW UNIV JERUSALEM,FAC AGR,DEPT PLANT PATHOL & MICROBIOL,IL-76100 REHOVOT,ISRAEL. NR 47 TC 118 Z9 131 U1 3 U2 12 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 JUL PY 1996 VL 62 IS 7 BP 2554 EP 2559 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA UV792 UT WOS:A1996UV79200053 PM 16535361 ER PT J AU Burns, SA Ediger, MN RichardsKortum, RR AF Burns, SA Ediger, MN RichardsKortum, RR TI Optical technology in medicine and biology: Introduction SO APPLIED OPTICS LA English DT Editorial Material C1 US FDA,ROCKVILLE,MD 20857. UNIV TEXAS,DEPT ELECT & COMP ENGN,AUSTIN,TX 78712. RP Burns, SA (reprint author), SCHEPENS EYE RES INST,20 STANIFORD ST,BOSTON,MA 02114, USA. RI Richards-Kortum, Rebecca/P-4074-2014; Burns, Stephen/D-9259-2011 OI Richards-Kortum, Rebecca/0000-0003-2347-9467; Burns, Stephen/0000-0001-5348-035X NR 0 TC 0 Z9 0 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 SN 0003-6935 J9 APPL OPTICS JI Appl. Optics PD JUL 1 PY 1996 VL 35 IS 19 BP 3313 EP 3313 DI 10.1364/AO.35.003313 PG 1 WC Optics SC Optics GA UW460 UT WOS:A1996UW46000001 PM 21102716 ER PT J AU Pettit, GH Ediger, MN AF Pettit, GH Ediger, MN TI Corneal-tissue absorption coefficients for 193- and 213-nm ultraviolet radiation SO APPLIED OPTICS LA English DT Article DE cornea; tissue optics; photorefractive keratectomy ID EXCIMER-LASER ABLATION; OPTICAL-PROPERTIES; EXPOSURE AB The small-signal absorption coefficients of 193- and 213-nm nanosecond laser pulses in bovine corneal tissue have been studied. The absolute reflectance of a planar quartz-cornea interface was measured at various angles of incidence for low-intensity laser irradiation (i.e., pulse fluences 3 orders of magnitude below the ablation threshold). The reflectance-versus-angle data were analyzed by the use of Fresnel theory to estimate the effective complex index of refraction of the tissue. This analysis indicated corneal absorption coefficients of 39,900 +/- 9800 cm(-1) at 193 nm and 21,400 +/- 4900 cm(-1) at 213 nm. RP Pettit, GH (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857, USA. NR 32 TC 37 Z9 42 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 SN 0003-6935 J9 APPL OPTICS JI Appl. Optics PD JUL 1 PY 1996 VL 35 IS 19 BP 3386 EP 3391 DI 10.1364/AO.35.003386 PG 6 WC Optics SC Optics GA UW460 UT WOS:A1996UW46000011 PM 21102726 ER PT J AU Goldman, LR Huggett, RJ Olden, K Medford, RL Rosenstock, L Johnson, BL Schultz, WB Hunker, JA AF Goldman, LR Huggett, RJ Olden, K Medford, RL Rosenstock, L Johnson, BL Schultz, WB Hunker, JA TI Untitled - Response 2 SO ARCHIVES OF ENVIRONMENTAL HEALTH LA English DT Letter C1 US EPA,OFF RES & DEV,WASHINGTON,DC. NIEHS,RES TRIANGLE PK,NC 27709. US FDA,ROCKVILLE,MD 20857. RP Goldman, LR (reprint author), US EPA,OFF PREVENT PESTICIDES & TOX SUBST,WASHINGTON,DC 20460, USA. RI Goldman, Lynn/D-5372-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 SN 0003-9896 J9 ARCH ENVIRON HEALTH JI Arch. Environ. Health PD JUL-AUG PY 1996 VL 51 IS 4 BP 342 EP 342 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA VC547 UT WOS:A1996VC54700016 ER PT J AU Rivest, C Miller, FW Love, LA Turgeon, PP Blier, C Senecal, JL AF Rivest, C Miller, FW Love, LA Turgeon, PP Blier, C Senecal, JL TI Focal myositis presenting as pseudothrombophlebitis of the neck in a patient with mixed connective tissue disease SO ARTHRITIS AND RHEUMATISM LA English DT Article ID LOCALIZED NODULAR MYOSITIS; POLYMYOSITIS; AUTOANTIBODIES; FORM AB This report describes a case of focal myositis in a patient with mixed connective tissue disease. The patient presented with diffuse neck swelling and pseudo-thrombophlebitis of the left internal jugular vein, Other clinical features included a high fever, elevated erythrocyte sedimentation rate, and prompt improvement after administration of high-dose intravenous corticosteroid therapy. Criteria for polymyositis were absent, serum levels of creatine kinase remained normal, and there was no sign of recurrence during 3 years of followup. Results of immunoprecipitation for anti-Jo-1 and other myositis-specific autoantibodies remained negative in serial serum samples obtained before, during, and after the episode. C1 UNIV MONTREAL,SCH MED,HOP NOTRE DAME,MONTREAL,PQ H3C 3J7,CANADA. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,ROBERT B BRIGHAM MULTIPURPOSE & ARTHRITIS & MUSCU,BOSTON,MA 02115. OI Miller, Frederick/0000-0003-2831-9593 NR 33 TC 12 Z9 12 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 JUL PY 1996 VL 39 IS 7 BP 1254 EP 1258 DI 10.1002/art.1780390728 PG 5 WC Rheumatology SC Rheumatology GA UX384 UT WOS:A1996UX38400027 PM 8670340 ER PT J AU Kanegane, H Tosato, G AF Kanegane, H Tosato, G TI Activation of naive and memory T cells by interleukin-15 SO BLOOD LA English DT Article ID RHEUMATOID-ARTHRITIS; INDUCER; SUBSETS; RECEPTOR; DIFFERENTIATION; EXPRESSION; ANTIGENS AB Interleukin-15 (IL-15), a product of monocytes and other cells, has biological activities similar to those of IL-2, including growth stimulation of activated T cells, induction of cytolytic effector cells, and B-cell costimulation for proliferation and lg production. We report that IL-15 at optimal concentrations rapidly induced memory (CD45RO(+)) CD4(+) and CD8(+) T cells and naive (CD45RO(-)) CD8(+) T cells to express the CD69 activation marker followed by proliferation. By contrast, IL-15 failed to induce naive (CD45RO(-)) CD4(+) T cells to express CD69 or to proliferate. Similar findings were obtained with IL-2. Unlike the other T-cell subsets, CD4(+) T cells with a naive phenotype expressed little or no IL-2R beta chain, a shared component of the IL-2 and IL-15 receptors required for receptor function. A monoclonal antibody to the IL-2R beta chain, Mik beta 1, reduced CD69 expression and proliferation in CD4(+) memory, CD8(+) memory, and CD8(+) naive T cells activated by IL-15. These results confirm the biological similarities of IL-2 and IL-15. They further document that the pool of naive CD4(+) cells, unlike the pool of memory CD4(+), memory CD8(+), and naive CD8(+) cells, is not regulated directly by the T-cell growth factors IL-2 or IL-15. RP Kanegane, H (reprint author), US FDA,CTR BIOL EVALUAT & RES,DHP,BLDG 29A,ROOM 2D06,HFM-535,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 39 TC 134 Z9 142 U1 0 U2 3 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 JUL 1 PY 1996 VL 88 IS 1 BP 230 EP 235 PG 6 WC Hematology SC Hematology GA UV297 UT WOS:A1996UV29700025 PM 8704178 ER PT J AU Scallet, AC Ye, X Rountree, RL Schmued, LC Ati, SF AF Scallet, AC Ye, X Rountree, RL Schmued, LC Ati, SF TI Ibogaine, a putative treatment for drug addiction: Neuropathology in rats and mice SO BRAIN PATHOLOGY LA English DT Meeting Abstract C1 US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,EXPTL NEUROPATHOL LAB,JEFFERSON,AR 72079. US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,NEUROCHEM LAB,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI ZURICH PA ISN JOURNAL PO BOX, CH-8033 ZURICH, SWITZERLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JUL PY 1996 VL 6 IS 3 BP 356 EP 356 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA UY659 UT WOS:A1996UY65900038 ER PT J AU Temple, RJ AF Temple, RJ TI The clinical pharmacologist in drug regulation: The US perspective SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT Festschrift in Honour of Professor Sir Colin Dollery CY JUN 20-21, 1996 CL HAMMERSMITH HOSPITAL, ROYAL POSTGRAD MED SCH, LONDON, ENGLAND HO HAMMERSMITH HOSPITAL, ROYAL POSTGRAD MED SCH DE clinical pharmacologists; pharmacodynamics ID CHLORTHALIDONE; TERFENADINE; OXIDATION AB 1 Drug development has moved into a new era - a time of particular interest in individualization of treatment and dose-response - that is of particular interest to clinical pharmacologists. 2 Clinical pharmacologists' skills are especially applicable to identifying subgroup differences in pharmacokinetics and the consequences of those differences through such techniques as the pharmacokinetic screen and evaluation of metabolic differences and drug-drug interactions. Clinical pharmacologists also can contribute to the discovery of true differences in pharmacodynamic response. 3 Clinical pharmacologists are trained to take a broad view of drugs, recognizing that they not only have the pharmacologic property of primary interest but often other properties as well, that a 'drug' is really many drugs (isomers, active metabolites) with different properties, and that the properties of drugs should affect how they are dosed and used. RP Temple, RJ (reprint author), US FDA,CTR DRUG EVALUAT & RES,OFF DRUG EVALUAT 1,1451 ROCKVILLE PIKE,RM 6014,ROCKVILLE,MD 20852, USA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0306-5251 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD JUL PY 1996 VL 42 IS 1 BP 73 EP 79 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UU197 UT WOS:A1996UU19700012 PM 8807147 ER PT J AU Midthun, K Kapikian, AZ AF Midthun, K Kapikian, AZ TI Rotavirus vaccines: An overview SO CLINICAL MICROBIOLOGY REVIEWS LA English DT Review ID ORAL POLIOVIRUS VACCINE; REOVIRUS-LIKE AGENT; FORMULA-FED INFANTS; RHESUS-ROTAVIRUS; YOUNG-CHILDREN; NEUTRALIZING ANTIBODIES; VIRAL GASTROENTERITIS; VENEZUELAN INFANTS; CANDIDATE VACCINE; RURAL BANGLADESH AB Rotavirus vaccine development has focused on the delivery of live attenuated rotavirus strains by the oral route. The initial ''Jennerian'' approach involving bovine (RIT4237, WC3) or rhesus (RRV) rotavirus vaccine candidates showed that these vaccines were safe, well tolerated, and immunogenic but induced highly variable rates of protection against rotavirus diarrhea. The goal of a rotavirus vaccine is to prevent severe illness that can lead to dehydration in infants and young children in both developed and developing countries. These studies led to the concept that a multivalent vaccine that represented each of the four epidemiologically important VP7 serotypes might be necessary to induce protection in young infants, the target population for vaccination. Human-animal rotavirus reassortants whose gene encoding VP7 was derived from their human rotavirus parent but whose remaining genes were derived from the animal rotavirus parent were developed as vaccine candidates. The greatest experience with a multivalent vaccine to date has been gained with the quadrivalent preparation containing RRV (VP7 serotype 3) and human-RRV reassortants of VP7 serotype 1, 2, and 4 specificity. Preliminary efficacy trial results in the United States have been promising, whereas a study in Peru has shown only limited protection. Human-bovine reassortant vaccines, including a candidate that contains the VP4 gene of a human rotavirus (VP4 serotype 1A), are also being studied. RP Midthun, K (reprint author), US FDA,DIV VACCINES & RELATED PROD APPLICAT,1401 ROCKVILLE PIKE,RM 300N,ROCKVILLE,MD 20852, USA. NR 153 TC 98 Z9 103 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0893-8512 J9 CLIN MICROBIOL REV JI Clin. Microbiol. Rev. PD JUL PY 1996 VL 9 IS 3 BP 423 EP & PG 13 WC Microbiology SC Microbiology GA UV839 UT WOS:A1996UV83900010 PM 8809469 ER PT J AU Mahmood, I AF Mahmood, I TI Interspecies scaling: Predicting clearance of anticancer drugs in humans. A comparative study of three different approaches using body weight or body surface area SO EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS LA English DT Article DE predicting clearance; anticancer drugs; man; body weight; body surface area ID PHARMACOKINETICS; TOXICITY; RABBITS; MICE; RATS AB From this study it is proposed that the clearance of anti-cancer drugs may be best estimated if they follow the following trend: (i) that if the exponent of the allometric equation (clearance vs body weight) lies between 0.55-0.75 (0.75 was chosen after Kleiber's power rule (18)), then a simple allometric equation can predict the clearance reasonably well; (ii) if the exponent of the allometric equation lies between 0.75 to approximately 0.90, clearance can be reasonably predicted using CL x MLP; and (iii) if the exponent of the allometric equation is greater than or equal to 0.90, the clearance can be predicted using the product of clearance and brain weight. RP Mahmood, I (reprint author), US FDA,OFF CLIN PHARMACOL & BIOPHARMACEUT HFD 860,DIV PHARMACEUT EVALUAT 1,WOODMONT OFF CTR 2,ROCKVILLE,MD 20852, USA. NR 18 TC 5 Z9 5 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 JUL-SEP PY 1996 VL 21 IS 3 BP 275 EP 278 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VZ022 UT WOS:A1996VZ02200013 PM 8980928 ER PT J AU Simon, CJ Nardinelli, C AF Simon, CJ Nardinelli, C TI The talk of the town: Human capital, information, and the growth of English cities, 1861 to 1961 SO EXPLORATIONS IN ECONOMIC HISTORY LA English DT Article ID INDUSTRIAL AB The growth of cities virtually always accompanies modern economic growth. Many observers attribute the relationship to the rise of urban factories or improvements in transportation. We believe that information-based human capital, particularly as embodied in business professionals, provides a better explanation for the growth of cities. Cities grew because concentrated human capital raised productivity. in a study of English cities from 1861 to 1961 we found that cities whose work forces contained high proportions of business professionals grew more rapidly. The talk of the bourgeoisie, not the smoke of the factory, was the defining characteristic of the modern city economy. (C) 1996 Academic Press, Inc. C1 US FDA,ROCKVILLE,MD 20857. RP Simon, CJ (reprint author), CLEMSON UNIV,CLEMSON,SC 29631, USA. NR 43 TC 45 Z9 45 U1 0 U2 8 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4983 J9 EXPLOR ECON HIST JI Explor. Econ. Hist. PD JUL PY 1996 VL 33 IS 3 BP 384 EP 413 DI 10.1006/exeh.1996.0021 PG 30 WC Economics; History Of Social Sciences SC Business & Economics; Social Sciences - Other Topics GA UU463 UT WOS:A1996UU46300006 ER PT J AU Devi, SJN Karpas, AB Frasch, CE AF Devi, SJN Karpas, AB Frasch, CE TI Binding diversity of monoclonal antibodies to alpha(2->8) polysialic acid conjugated to outer membrane vesicle via adipic acid dihydrazide SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE conjugate vaccine; monoclonal antibody; polysialic acid; epitope ID B NEISSERIA-MENINGITIDIS; ESCHERICHIA-COLI K1; CAPSULAR POLYSACCHARIDE; MENINGOCOCCAL POLYSACCHARIDES; BACTERICIDAL ACTIVITY; PROTECTIVE EFFICACY; IMMUNE-RESPONSE; SEROGROUP-B; SPECIFICITY; ANTIGENS AB Murine monoclonal antibodies (mAbs) were generated using group B Neisseria meningitidis and Escherichia coli K1 polysaccharides (PSs) conjugated to outer membrane vesicle (OMV) via adipic acid dihydrazide, and were used to identify the immunodeterminants expressed on these capsular PSs. Ten mAbs representative of IgM and all subclasses of IgG were obtained which recognized diverse immunodeterminants on alpha(2 --> 8) polysialic acid (PSA). The specificity of mAbs to different antigenic determinants was assessed by their differential binding to PSA attached to a solid phase by different methods and confirmed by absorption studies. Two mAbs from the E. coli K1 fusion were directed to the O-acetyl epitope and the rest reacted with both the PSs only when attached to a solid phase by certain means. The methods by which PSA was coated on the solid phase had an impact on the epitope expression and binding pattern. At the concentrations used, the O-acetyl-specific mAbs, IgG1 and IgG3 mAbs were not bactericidal against group B N. meningitidis, whereas other mAbs were. The conjugates B and K1 PSs present to the murine immune system different antigenic determinants, some of which elicit bactericidal antibodies. C1 US FDA,DIV ALLERGEN PROD & PARASITOL,OFF VACCINE RES & REVIEW,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852. RP Devi, SJN (reprint author), US FDA,DIV BACTERIAL PROD,OFF VACCINE RES & REVIEW,CTR BIOL EVALUAT & RES,HFM 428,ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 37 TC 2 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD JUL PY 1996 VL 14 IS 4 BP 211 EP 220 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VB044 UT WOS:A1996VB04400004 PM 8856320 ER PT J AU Capar, SG Yess, NJ AF Capar, SG Yess, NJ TI US Food and Drug Administration survey of cadmium, lead and other elements in clams and oysters SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE cadmium; lead; clams; oysters; shellfish AB In Fiscal Years 1985/1986, the US Food and Drug Administration conducted a survey of cadmium, lead and other elements in fresh clams and oysters collected from US coastal areas in use for shellfish production. Shellfish were analysed for cadmium and lead by using a dry ash-anodic stripping voltammetric method. Other elements (aluminium, arsenic, beryllium, calcium, chromium, cobalt, copper, iron, magnesium, manganese, molybdenum, nickel, phosphorus, potassium, selenium, sodium, strontium, vanadium and zinc) were determined by using inductively coupled plasma-atomic emission spectrometry, direct current plasma-atomic emission spectrometry or hydride generation atomic absorption spectrometry. A total of 75 hardshell clam, 59 softshell clam, 104 Eastern oyster and 40 Pacific oyster samples were analysed for cadmium and lead. Average levels found were 0.09, 0.05, 0.51 and 1.1 mg/kg wet weight for cadmium and 0.24, 0.30, 0.11 and 0.06 mg/kg wet weight for lead in hardshell clams, softshell clams, Eastern oysters and Pacific oysters, respectively. The other 19 elements were determined in 10-104 samples of the four types of shellfish. These data provide baseline values for elements in clams and oysters harvested from US coastal waters. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NR 15 TC 12 Z9 12 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD JUL PY 1996 VL 13 IS 5 BP 553 EP 560 PG 8 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA UT450 UT WOS:A1996UT45000006 PM 8799717 ER PT J AU Gaylor, DW Slikker, W AF Gaylor, DW Slikker, W TI The use of uncertainty factors in estimating health risks - Reply SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Letter C1 NATL CTR TOXICOL RES,FDA,DIV NEUROTOXICOL,JEFFERSON,AR 72079. RP Gaylor, DW (reprint author), NATL CTR TOXICOL RES,FDA,DIV BIOMETRY & RISK ASSESSMENT,JEFFERSON,AR 72079, USA. NR 5 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 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD JUL PY 1996 VL 32 IS 1 BP 127 EP 127 DI 10.1006/faat.1996.0115 PG 1 WC Toxicology SC Toxicology GA UW753 UT WOS:A1996UW75300016 ER PT J AU Lindler, LE Hadfield, TL Tall, BD Snellings, NJ Rubin, FA VandeVerg, LL Hoover, D Warren, RL AF Lindler, LE Hadfield, TL Tall, BD Snellings, NJ Rubin, FA VandeVerg, LL Hoover, D Warren, RL TI Cloning of a Brucella melitensis group 3 antigen gene encoding Omp28, a protein recognized by the humoral immune response during human brucellosis SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEINS; MONOCLONAL-ANTIBODIES; ABORTUS INFECTION; ENVELOPE PROTEIN; O-POLYSACCHARIDE; MICE; STRAINS; CELL; PROTECTION; IDENTIFICATION AB Brucella group 3 antigens (Ags) are outer membrane proteins (OMPs) with a molecular mass ranging from 25 to 30 kDa. The OMPs are of interest partially because of their potential use as vaccine and diagnostic reagents. We used human convalescent antibody (Ab) to clone a gene that encoded a 28-kDa protein from a lambda gt11 library of Brucella melitensis 16M genomic DNA. DNA sequence analysis revealed a single open reading frame that would encode a protein of 26,552 Da. The 28-kDa protein had a primary amino acid sequence that was 43% similar to a previously described Brucella abortus group 3 Ag, Omp25 (P. de Wergifosse, P. Lintermans, J. N. Limet, and A. Cloeckaert, J. Bacteriol. 177:1911-1914, 1995). The similarity to a known group 3 OMP, immunoreactivity with Ab prepared against B. abortus group Ags, immunolabeling of whole cells, and Southern hybridization led to our conclusion that the B. melitensis 28-kDa protein was a group 3 protein distinct from B. abortus Omp25. We designated the B. melitensis protein Omp28. Human convalescent sera from patients infected with B. abortus and Brucella suis as well as rabbit antisera prepared against killed B. abortus whole cells recognized B. melitensis Omp28 on Western blots (immunoblots). Furthermore, mice and goats infected with smooth strains of B. melitensis produced Abs against Omp28. Our results may begin to explain the variability in molecular weight seen in Brucella group Ags and point toward their possible use in vaccination against infection as well as diagnosis of the disease. C1 ARMED FORCES INST PATHOL,DEPT INFECT & PARASIT DIS,WASHINGTON,DC 20306. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. RP Lindler, LE (reprint author), WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,DEPT BACTERIAL DIS,WASHINGTON,DC 20307, USA. OI Tall, Ben/0000-0003-0399-3629 NR 45 TC 45 Z9 52 U1 0 U2 0 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 JUL PY 1996 VL 64 IS 7 BP 2490 EP 2499 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UT657 UT WOS:A1996UT65700018 PM 8698471 ER PT J AU Binienda, Z Holson, RR Chen, FX Oriaku, E Kim, CS Flynn, TJ Slikker, W Paule, MG Feuers, RJ Ferguson, SA AF Binienda, Z Holson, RR Chen, FX Oriaku, E Kim, CS Flynn, TJ Slikker, W Paule, MG Feuers, RJ Ferguson, SA TI Effects of ischemia-hypoxia induced by interruption of uterine blood flow on fetal rat liver and brain enzyme activities and offspring behavior SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE hypoxia; liver; brain; enzymes; behavior ID PERINATAL ASPHYXIA; CEREBRAL INJURY; ACID; CARBOHYDRATE; METABOLISM AB The effects of acute perinatal ischemia-hypoxia on fetal liver and brain energy metabolism, fetal brain total free fatty acid concentration and subsequent offspring behavior were investigated in rats. Ischemia-hypoxia was induced at term either by ligation of the uterine blood vessels or submersion of the entire uterine horn in warmed saline. Fetuses of the adjacent horn served as within-dam controls for all assessments and fetuses of dams which had not undergone the surgical stress served as independent controls for enzyme assays. Ischemia-hypoxia was associated with reduced activity of fatty acid synthase in the liver and brain. Total free fatty acid concentration significantly increased in the fetal hypoxic brain. Pups not used for enzyme analyses were cross-fostered for behavioral assessments. Relative to the enzymatic alterations, there were few behavioral alterations associated with ischemia-hypoxia. At postnatal day 30, rats made hypoxic by ligation of the uterine blood vessels had decreased caudate nucleus and brain stem weights relative to within-dam controls. At postnatal day 85, rats made hypoxic by submersion of the uterine horn had decreased olfactory bulb weight. The results of this study indicate an initial acute response to a brief period of ischemia-hypoxia at term pregnancy in the fetal rat brain and liver. C1 US FDA,NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079. US FDA,NATL CTR TOXICOL RES,DIV GENET TOXICOL,JEFFERSON,AR 72079. US FDA,CTR FOOD SAFETY & APPL NUTR,DIV TOXICOL STUDIES,WASHINGTON,DC 20204. RP Binienda, Z (reprint author), US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,HFT-132 3900 NCTR DR,JEFFERSON,AR 72079, USA. OI Flynn, Thomas/0000-0002-7248-0643 NR 34 TC 3 Z9 3 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD JUL PY 1996 VL 14 IS 4 BP 399 EP 408 PG 10 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA VH834 UT WOS:A1996VH83400004 PM 8884373 ER PT J AU Clausing, P Ali, SF Taylor, LD Newport, GD Rybak, S Paule, MG AF Clausing, P Ali, SF Taylor, LD Newport, GD Rybak, S Paule, MG TI Central and peripheral neurochemical alterations and immune effects of prenatal ethanol exposure in rats SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE prenatal ethanol exposure; norepinephrine; dopamine; serotonin; spleen; thymus; lymphocyte subsets; rat ID FETAL ALCOHOL SYNDROME; CATECHOLAMINE CONTENT; LYMPHOID ORGANS; FEMALE RATS; LIQUID DIET; BRAIN; INUTERO; ALTERS; SYSTEM; MICE AB In contrast to the well known effects of prenatal ethanol exposure on the central nervous system, data about its peripheral effects are scarce. Here, Sprague-Dawley rats were fed a liquid diet (gestational days 0-20) containing 36% ethanol-derived calories (EDCs, group H) or were pair-fed with 18% EDCs (group L) or 0% EDCs (group C). On postnatal day 20, one male and one female from each of 10 litters per group were killed. Norepinephrine (NE) was analyzed in the frontal cortex, spleen and thymus, and dopamine, 5-hydroxytryptamine (serotonin, 5-HT) and their metabolites 3,4-dihydroxyphenylacetic acid, homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were analyzed in the striatum by highperformance liquid chromatography with electrochemical detection. Lymphocyte subpopulations in the spleen and thymus were also assessed in half of these litters. Significant decreases in splenic NE concentration were seen in both sexes of group H (males 27%, females 28%). Decreases in striatal 5-HT and 5-HIAA of group H subjects appeared to be sex specific (only females were significantly affected: 23% decrease in 5-HT, 37% decrease in 5-HIAA). Pronounced, dose-dependent reductions in T cell percentages were observed in both the thymus and spleen. Splenic CD8(+) and CD4(+) cell percentages were positively correlated with the splenic NE concentrations. It is concluded that the decreases seen in splenic T cell percentages subsequent to prenatal ethanol exposure may be caused, at least partially, by impaired noradrenergic control of this organ. Copyright (C) 1996 ISDN. C1 UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & TOXICOL,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM & MOL BIOL,LITTLE ROCK,AR 72205. NATL CTR TOXICOL RES,DIV GENET TOXICOL,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 Clausing, P (reprint author), NATL CTR TOXICOL RES,DIV NEUROTOXICOL,HFT-132,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 48 TC 9 Z9 10 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD JUL PY 1996 VL 14 IS 4 BP 461 EP 469 PG 9 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA VH834 UT WOS:A1996VH83400010 PM 8884379 ER PT J AU Allen, LB Siitonen, PH Thompson, HC AF Allen, LB Siitonen, PH Thompson, HC TI Aerosol-phase assisted sample digestion for the determination of trace metals in organic samples by plasma atomic emission spectrometry SO JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY LA English DT Article DE sample digestion/preparation; membrane desolvation; inductively coupled plasma atomic emission spectrometry; ultrasonic nebulization AB This report provides evidence of on-line, aerosol-phase assisted sample digestion with ICP-AES detection. In brief, sucrose samples were subjected to a preliminary digestion and were then analysed with and without a membrane separator/desolvator. In the presence of the desolvator, spike recoveries, for various metals including As, Cd, Cu, Pb and Sn, were higher and demonstrated better precision compared with results obtained for digests analysed without the membrane desolvator. This suggests that additional decomposition was occurring in the aerosol phase and that the decomposition products (gaseous NO2 and CO2) were removed from the aerosol flow stream by the membrane desolvator. For sucrose samples spiked at 100 ng g(-1) with Pb and digested by an open-vessel procedure, the average recovery (n=5) improved from 25 to 106% when the digests were analysed with the desolvator. The RSD improved from 76 to 7.3% by the addition of the desolvator. Improved performance without the desolvator could only be achieved by the addition and evaporation of an excess of oxidizing agents which increases cost, analysis time and the chance for environmental contamination. With closed-vessel digestion, sucrose samples spiked with lead at 1.0 mu g g(-1) demonstrated improvement in the average recovery from 19 to 84% when analysed with the desolvator. Similarly, the RSD decreased from 21 to 4.6% by the addition of the desolvator. In addition to Pb, similar improvements were demonstrated for As, Cd, Cu and Sn by the closed vessel procedure. RP Allen, LB (reprint author), US FDA,NATL CTR TOXICOL RES,DIV CHEM,HFT-230,JEFFERSON,AR 72079, USA. NR 10 TC 11 Z9 11 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 JUL PY 1996 VL 11 IS 7 BP 529 EP 532 DI 10.1039/ja9961100529 PG 4 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA UY744 UT WOS:A1996UY74400013 ER PT J AU Hanna, GM LauCam, CA AF Hanna, GM LauCam, CA TI Simple H-1 NMR spectroscopic method for assay of salts of the contrast agent diatrizoate in commercial solutions SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A simple, accurate, and specific H-1 NMR spectroscopic method was developed for the assay of diatrizoate meglumine or the combination diatrizoate meglumine and diatrizoate sodium in commercial solutions for injection, A mixture of injectable solution and sodium acetate, the internal standard, was diluted with D2O and the H-1 NMR spectrum of the solution was obtained. Two approaches were used to calculate the drug content, based on the integral values for the -N-CO-CH3 protons of diatrizoic acid at 2.23 ppm, the N-CH3 protons of meglumine at 2.73 ppm, and the CH3-CO-protons of sodium acetate at 1.9 ppm, Recoveries (mean +/- standard deviation) of diatrizoic acid and meglumine from 10 synthetic mixtures of various amounts of these compounds with a fixed amount of internal standard were 100.3 +/- 0.55% and 100.1 +/- 0.98%, respectively, In addition to providing a direct means of simultaneously assaying diatrizoic acid and meglumine, the proposed NMR method can also be used to identify diatrizoate meglumine and each of its molecular components. C1 ST JOHNS UNIV,COLL PHARM & ALLIED HLTH PROFESS,JAMAICA,NY 11439. RP Hanna, GM (reprint author), US FDA,NE REG LAB,BROOKLYN,NY 11232, USA. NR 15 TC 10 Z9 10 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 JUL-AUG PY 1996 VL 79 IS 4 BP 833 EP 838 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA UX853 UT WOS:A1996UX85300005 PM 8757438 ER EF