FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Ault, KT Kenyon, K Jamrich, M AF Ault, KT Kenyon, K Jamrich, M TI A novel forkhead gene, XLPM, is involved in a unique patterning of ventral mesoderm along the anterior to posterior axis. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 US FDA,DEV BIOL LAB,DIV CELLULAR & GENE THERAPIES,ROCKVILLE,MD 20857. GEORGE WASHINGTON UNIV,PROGRAM NEUROSCI,WASHINGTON,DC 20037. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP B177 EP B177 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400560 ER PT J AU Kenyon, KL Moody, SA Jamrich, M AF Kenyon, KL Moody, SA Jamrich, M TI A novel Xenopus forkhead gene specifically identifies lens epidermis and plays a role in anterior head formation SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,NEUROSCI PROGRAM,WASHINGTON,DC 20037. US FDA,CBER,DIV CELLULAR & GENE THERAPY,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP B7 EP B7 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400392 ER PT J AU Mathers, P Grinberg, A Mahon, K Jamrich, M AF Mathers, P Grinberg, A Mahon, K Jamrich, M TI The Rx homeobox gene is required for vertebrate eye development SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. W VIRGINIA UNIV,SCH MED,MORGANTOWN,WV 26506. NIH,BETHESDA,MD 20892. BAYLOR COLL MED,HOUSTON,TX 77030. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP B19 EP B19 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400403 ER PT J AU Webb, P Streck, RD AF Webb, P Streck, RD TI Retinoid X receptor mRNAs are expressed in the rat fetus and limb bud in patterns which are district from the corresponding mRNAs in mouse and chick SO DEVELOPMENTAL BIOLOGY 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 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP B244 EP B244 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400627 ER PT J AU Pan, Q Rabbani, H Mills, FC Severinson, E Hammarstrom, L AF Pan, Q Rabbani, H Mills, FC Severinson, E Hammarstrom, L TI Allotype-associated variation in the human gamma 3 switch region as a basis for differences in IgG3 production SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEAVY-CHAIN SWITCH; NF-KAPPA-B; RECOMBINATION BREAKPOINTS; ANTIBODY-ACTIVITY; HUMAN-LYMPHOCYTES; SEQUENCE MOTIF; DNA-SEQUENCES; CIRCULAR DNA; HUMAN-SERUM; IMMUNOGLOBULIN AB High and low serum concentrations of IgG3 are associated with the human G3 m(b) and G3 m(g) allotypes, respectively, We previously hypothesized that a low frequency of switching is the most likely defect in (g) allotype-positive individuals, and therefore analyzed the structure, recombination breakpoints, and binding of nuclear proteins to the switch (S)gamma 3 regions of these two allotypes. There are no allotype-associated differences in the length and basic structure of the S gamma 3, since both contain eighteen 79-bp repeats, However, we found a number of allotype-associated nucleotide changes, As in the mouse system, there is a preferential switching to the B site, or switch nuclear protein/nuclear factor-kappa B motif, with a clustering of switch breakpoints at the most 5' residue of the B site. The B site sequence used most frequently in switching was found to be mutated at this nucleotide in the (g) allotype-associated S gamma 3. This change was shown by electrophoretic mobility shift assay to alter the binding of the switch nuclear protein/nuclear factor-kappa B protein to the B site. Taken together, these data suggest that polymorphism within S gamma 3 may contribute to allotype-associated differences in IgG3 switching, and that specific sequences within the S gamma 3 79-bp repeats could be mechanistically important for switch recombination. C1 HUDDINGE HOSP,KAROLINSKA INST,NOVUM,CTR BIOTECHNOL,S-14186 HUDDINGE,SWEDEN. US FDA,DIV HEMATOL PROD,BETHESDA,MD 20892. KAROLINSKA INST,DEPT CELL & MOL BIOL,STOCKHOLM,SWEDEN. RP Pan, Q (reprint author), HUDDINGE HOSP,DEPT CLIN IMMUNOL,S-14186 HUDDINGE,SWEDEN. NR 59 TC 22 Z9 22 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1997 VL 158 IS 12 BP 5849 EP 5859 PG 11 WC Immunology SC Immunology GA XE749 UT WOS:A1997XE74900035 PM 9190937 ER PT J AU Liesi, P Wright, JM Krauthamer, V AF Liesi, P Wright, JM Krauthamer, V TI BAPTA-AM and ethanol protect cerebellar granule neurons from the destructive effect of the weaver gene SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE BAPTA-AM; calcium; cerebellum; ethanol; granule neurons; rescue; weaver ID BRAIN MICROSOMES; MOUSE CEREBELLUM; CALCIUM; CHANNEL; CELLS; DEATH; MICE AB The mechanisms by which the weaver gene (Reeves et al., 1989; Patil et al., 1995) inhibits neurite extension and/or induces death of the granule neurons in homozygous weaver mouse cerebellum are not presently understood, Here we show that BAPTA-AM and ethanol, which either reduce cytosolic levels of free calcium or prevent calcium entry, promote neurite outgrowth of the weaver neurons similar to the L-type calcium channel blocker verapamil (Liesi and Wright, 1996), Importantly, BAPTA-AM, ethanol, and verapamil not only restore neurite outgrowth of the weaver neurons but adjust their depolarized resting membrane potentials to the levels of normal neurons, These results indicate that calcium-dependent mechanisms mediate the action of the weaver gene and that the weaver neurons can be normalized by blocking this calcium effect, We further report that BAPTA-AM and verapamil also have a neuroprotective effect on normal neurons exposed to high concentrations of ethanol. We suggest that verapamil should be evaluated as a drug for treatment of alcohol-induced brain damage and neurodegenerative disorders. (C) 1997 Wiley-Liss, Inc. C1 JOHNS HOPKINS UNIV, SCH MED, DEPT PHYSIOL, BALTIMORE, MD USA. US FDA, CTR DEVICES & RADIOL HLTH, ROCKVILLE, MD 20857 USA. RP Liesi, P (reprint author), NIAAA, NIH, MOL & CELLULAR NEUROBIOL LAB, 12501 WASHINGTON AVE, ROCKVILLE, MD 20852 USA. NR 19 TC 12 Z9 12 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUN 15 PY 1997 VL 48 IS 6 BP 571 EP 579 DI 10.1002/(SICI)1097-4547(19970615)48:6<571::AID-JNR10>3.0.CO;2-Y PG 9 WC Neurosciences SC Neurosciences & Neurology GA XH195 UT WOS:A1997XH19500010 PM 9210527 ER PT J AU Freyaldenhoven, TE Ali, SF Schmued, LC AF Freyaldenhoven, TE Ali, SF Schmued, LC TI Systemic administration of MPTP induces thalamic neuronal degeneration in mice SO BRAIN RESEARCH LA English DT Article DE MPTP; Parkinson's disease; substantia nigra; thalamus; neuronal degeneration; mice; Fluoro-Jade ID MOTOR ASYMPTOMATIC MONKEYS; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; PARKINSONS-DISEASE; BODY-TEMPERATURE; DOPAMINERGIC NEUROTOXICITY; CATECHOLAMINE NEURONS; STRIATAL DOPAMINE; SUBSTANTIA-NIGRA; CHRONIC EXPOSURE; TREATED MONKEYS AB 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a known neurotoxicant primarily selective for catecholaminergic neurons, including those of the nigrostriatal dopaminergic system, thereby mimicking the pathology of Parkinson's disease (PD). In this study, serial transbrain sectioning, followed by staining with a newly developed fluorochrome (Fluoro-Jade) specific for degenerating neurons, was used to detect additional sites of MPTP-induced neuronal degeneration in mice. Male CD-1 mice received a single 50 mg/kg dose of MPTP intraperitoneally at room temperature or at a reduced temperature (6 degrees C), which has been shown to potentiate striatal dopamine depletion. Neuronal degeneration was observed in the substantia nigra pars compacta (SN), ventral tegmental area (VTA) and retrorubral field (RRF) of only animals dosed in the low temperature environment. Neuronal degeneration was also observed in other catecholaminergic nuclei in both treatment groups. In addition, degenerating cell bodies and fibers were detected in the midline and intralaminar thalamic nuclei of all dosed animals, regardless of the dosing environment. Pharmacological manipulations which prevented nigral degeneration (deprenyl and nomifensine pretreatment) also prevented the degeneration of thalamic neurons. MK-801 pretreatment, however, resulted in a disproportionate protection of the thalamic neurons. These findings confirm and extend our previous observations regarding the protective effect of hyperthermia in CD-1 mice and also suggest that regions of the thalamus may be relevant to the pathophysiology of PD. (C) 1997 Elsevier Science B.V. C1 NATL CTR TOXICOL RES, US FDA, NEUROCHEM LAB, DIV NEUROTOXICOL, JEFFERSON, AR 72079 USA. UNIV ARKANSAS MED SCI HOSP, DEPT BIOCHEM & MOL BIOL, LITTLE ROCK, AR 72205 USA. NR 62 TC 64 Z9 64 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD JUN 6 PY 1997 VL 759 IS 1 BP 9 EP 17 DI 10.1016/S0006-8993(97)00045-0 PG 9 WC Neurosciences SC Neurosciences & Neurology GA XG026 UT WOS:A1997XG02600002 PM 9219857 ER PT J AU Schmued, LC Bowyer, JF AF Schmued, LC Bowyer, JF TI Methamphetamine exposure can produce neuronal degeneration in mouse hippocampal remnants SO BRAIN RESEARCH LA English DT Article DE methamphetamine; Indusium griseum; hippocampal remnant; seizure; neurodegeneration; fluoro-jade; glutamate; catecholamine ID RAT-BRAIN; INDUSIUM GRISEUM; NERVOUS-SYSTEM; NEUROTOXICITY; LOCALIZATION; CONNECTIONS; HYDROXYLASE; TOXICITY; SEIZURES; ANTIBODY AB Neuronal cell death in hippocampal remnants was seen after methamphetamine (METH) exposure. Two techniques (Fluoro-Jade labeling and argyrophylia) showed that neuronal degeneration occurred in the indusium griseum, tenia tecta and fasciola cinerea within 5 days post-METH exposure in 70% of the mice. Neurodegeneration also occasionally occurred in the piriform cortex, hippocampus and frontal/parietal cortex. This cell death, unlike striatal neurotoxicity, was not dependent on magnitude of hyperthermia occurring but did correlate with behavioral seizure activity during METH exposure. Excitotoxic mechanisms may be underlying the neuronal degeneration since co-administration of phenobarbital blocked cell death. RP Schmued, LC (reprint author), NATL CTR TOXICOL RES,DIV NEUROTOXICOL,HFT-132,JEFFERSON,AR 72079, USA. NR 28 TC 97 Z9 101 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 6 PY 1997 VL 759 IS 1 BP 135 EP 140 DI 10.1016/S0006-8993(97)00173-X PG 6 WC Neurosciences SC Neurosciences & Neurology GA XG026 UT WOS:A1997XG02600016 PM 9219871 ER PT J AU Mathers, PH Grinberg, A Mahon, KA Jamrich, M AF Mathers, PH Grinberg, A Mahon, KA Jamrich, M TI The Rx homeobox gene is essential for vertebrate eye development SO NATURE LA English DT Article ID XENOPUS-LAEVIS; NERVOUS-SYSTEM; EYELESS GENE; EXPRESSION; DROSOPHILA; ANIRIDIA; RETINA; MOUSE; HEAD AB Development of the vertebrate eye requires a series of steps including specification of the anterior neural plate, evagination of the optic vesicles from the ventral forebrain, and the cellular differentiation of the lens and retina. Homeobox-containing genes, especially the transcription regulator Pax6, play a critical role in vertebrate and invertebrate eye formation. Mutations in Pax6 function result in eye malformations known as Aniridia in humans and Small eye syndrome in mice(1-3). The Drosophila homologue of Pax6, eyeless, is also necessary for correct invertebrate eye development, and its misexpression leads to formation of ectopic eyes in Drosophila(4,5). Here we show that a conserved vertebrate homeobox gene, Rx, is essential for normal eye development, and that its misexpression has profound effects on eye morphology. Xenopus embryos injected with synthetic Rx RNA develop ectopic retinal tissue and display hyperproliferation in the neuroretina. Mouse embryos carrying a null allele of this gene do not form optic cups and so do not develop eyes. The Rx gene family plays an important role in the establishment and/or proliferation of retinal progenitor cells. C1 US FDA,DEV BIOL LAB,ROCKVILLE,MD 20852. NICHHD,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. NR 25 TC 465 Z9 476 U1 4 U2 26 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUN 5 PY 1997 VL 387 IS 6633 BP 603 EP 607 DI 10.1038/42475 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XC522 UT WOS:A1997XC52200056 PM 9177348 ER PT J AU Zambon, M Hay, A Schild, G Wood, J Gust, I Hampson, A Nerome, K Guo, Y AF Zambon, M Hay, A Schild, G Wood, J Gust, I Hampson, A Nerome, K Guo, Y TI Update: Influenza activity - United States and worldwide, 1996-97 season, and composition of the 1997-98 influenza vaccine (Reprinted from MMWR, vol 46, pg 325-330, 1997) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 NATL INST MED RES,LONDON NW7 1AA,ENGLAND. NATL INST BIOL STAND & CONTROLS,S MIMMS,HERTS,ENGLAND. COMMONWEALTH SERUM LABS,PARKVILLE,VIC 3052,AUSTRALIA. NATL INST HLTH,TOKYO 141,JAPAN. NATL CTR PREVENT MED,INST VIROL,BEIJING,PEOPLES R CHINA. WHO,NATL INFLUENZA CTR,CH-1211 GENEVA,SWITZERLAND. US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,ROCKVILLE,MD 20857. CDC,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,INFLUENZA BR,ATLANTA,GA 30333. RP Zambon, M (reprint author), CENT PUBL HLTH LAB,LONDON NW9 5HT,ENGLAND. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 4 PY 1997 VL 277 IS 21 BP 1666 EP 1667 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XB088 UT WOS:A1997XB08800009 ER PT J AU Liao, F Alkhatib, G Peden, KWC Sharma, G Berger, EA Farber, JM AF Liao, F Alkhatib, G Peden, KWC Sharma, G Berger, EA Farber, JM TI STRL33, a novel chemokine receptor-like protein, functions as a fusion cofactor for both macrophage-tropic and T cell line-tropic HIV-1 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; RECOMBINANT VACCINIA VIRUS; ENVELOPE GLYCOPROTEIN; IDENTIFICATION; SEARCH; ASSAY; GENES; CD4 AB The chemokine receptors CXCR4, CCR2B, CCR3, and CCR5 have recently been shown to serve along with CD4 as coreceptors for HIV-1. The tropisms of HIV-1 strains for subgroups of CD4(+) cells can be explained, at least partly, by the selective use of G protein-coupled receptors (GPCRs). We have identified a novel human gene, STRL33, located on chromosome 3 that encodes a GPCR with sequence similarity to chemokine receptors and to chemokine receptor-like orphan receptors. STRL33 is expressed in lymphoid tissues and activated T cells, and is induced in activated peripheral blood lymphocytes. When transfected into nonhuman NIH 3T3 cells expressing human CD4, the STRL33 cDNA rendered these cells competent to fuse with cells expressing HIV-1 envelope glycoproteins (Envs). Of greatest interest, STRL33, in contrast with CXCR4 or CCR5, was able to function as a cofactor for fusion mediated by Envs from both T cell line-tropic and macrophage-tropic HIV-1 strains. STRL33-transfected Jurkat cell lines also supported enhanced productive infection with HIV-1 compared with control Jurkat cells. Despite the sequence similarities between STRL33 and chemokine receptors, STRL33-transfected cell. lines did not respond to any in a panel of chemokines. Based on the pattern of tissue expression of the STRL33 mRNA, and given the ability of STRL33 to function with Envs of differing tropisms, STRL33 may play a role in the establishment and/or progression of HIV-1 infection. C1 NIAID,NIH,CLIN INVEST LAB,BETHESDA,MD 20892. NIAID,NIH,VIRAL DIS LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,LAB RETROVIRUS RES,BETHESDA,MD 20892. NR 41 TC 305 Z9 307 U1 0 U2 1 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 JUN 2 PY 1997 VL 185 IS 11 BP 2015 EP 2023 DI 10.1084/jem.185.11.2015 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XD350 UT WOS:A1997XD35000013 PM 9166430 ER PT J AU Vacchio, MS Ashwell, JD AF Vacchio, MS Ashwell, JD TI Thymus-derived glucocorticoids regulate antigen-specific positive selection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID RECEPTOR TRANSGENIC MICE; T-CELL REPERTOIRE; APOPTOSIS; ACTIVATION; THYMOCYTES; COMPLEX; DEATH; LYMPHOCYTES; TOLERANCE; DELETION AB While it is generally believed that the avidity of the T cell antigen receptor (TCR) for self antigen/major histocompatibility complex (MHC) determines a thymocyte's fate, how the cell discriminates between a stimulus that causes positive selection (survival) and one that causes negative selection (death) is unknown. We have previously demonstrated that glucocorticoids are produced in the thymus, and that they antagonize deletion caused by TCR cross-linking. To examine the role of glucocorticoids during MHC-dependent selection, we examined thymocyte development in organ cultures in which corticosteroid biosynthesis was inhibited. Inhibition of glucocorticoid production in thymi from alpha/beta-TCR transgenic mice resulted in the antigen- and MHC-specific loss of thymocytes that normally recognize self antigen/MHC with sufficient avidity to result in positive selection. Furthermore, inhibition of glucocorticoid production caused an increase in apoptosis only in CD(+)CD8(+) thymocytes bearing transgenic TCRs that recognized self antigen/MHC. These results indicate that the balance of TCR and glucocorticoid receptor signaling influences the antigen-specific thymocyte development by allowing cells with low-to-moderate avidity for self antigen/MHC to survive. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,IMMUNOL LAB,BETHESDA,MD 20852. NCI,LAB IMMUNE CELL BIOL,NIH,BETHESDA,MD 20892. NR 27 TC 113 Z9 114 U1 0 U2 1 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 JUN 2 PY 1997 VL 185 IS 11 BP 2033 EP 2038 DI 10.1084/jem.185.11.2033 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XD350 UT WOS:A1997XD35000015 PM 9166432 ER PT J AU Farshid, M Nedjar, S Mitchell, F Biswas, R AF Farshid, M Nedjar, S Mitchell, F Biswas, R TI Effect of hepatitis B virus X protein on the expression of retinoblastoma gene product SO ACTA VIROLOGICA LA English DT Article DE hepatitis B virus; X protein; retinoblastoma tumour suppressor protein; hepatocellular carcinoma ID HEPATOCELLULAR-CARCINOMA; BINDING; P53; ANTIGEN; HBX AB Hepatitis B virus X protein (HBX) was studied for its capacity to form a specific complex with the retinoblastoma tumour suppressor protein (pRB), and for its effect on the expression of pRB. HEX was synthesized by in vitro transcription and translation in the presence of [S-35]methionine. The synthesized HEX was assayed for its binding to a glutathione-S-transferase (GST)-pRB fusion protein bound to Sepharose beads. The in vivo binding was investigated by a co-immunoprecipitation and Western blot analysis of the cell extract from a CMV-HBX-transfected hepatoblastoma cell line, Hep G2 cells. These experiments demonstrated that HEX was unable to form a detectable complex with pRB. However, the level of pRB increased considerably in Hep G2 cells transfected with CMV-HBX clone. The alteration of pRB expression by HEX could be a mechanism, contributing to the development of hepatocellular carcinoma (HCC) in human. RP Farshid, M (reprint author), US FDA,CTR BIOL EVALUAT & RES,HEPATATIS LAB,DIV TRANSFUS TRANSMITTED DIS,HFM 325,ROCKVILLE,MD 20852, USA. NR 21 TC 11 Z9 13 U1 0 U2 0 PU SLOVAK ACADEMIC PRESS LTD PI BRATISLAVA PA PO BOX 57, NAM SLOBODY 6, 810 05 BRATISLAVA, SLOVAKIA SN 0001-723X J9 ACTA VIROL JI Acta Virol. PD JUN PY 1997 VL 41 IS 3 BP 125 EP 129 PG 5 WC Virology SC Virology GA YA570 UT WOS:A1997YA57000001 PM 9385399 ER PT J AU Rheinstein, PH AF Rheinstein, PH TI Significant FDA approvals in 1996 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 JUN PY 1997 VL 55 IS 8 BP 2855 EP 2858 PG 4 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA XE084 UT WOS:A1997XE08400027 PM 9191461 ER PT J AU Myers, MJ Farrell, DE EvockClover, CM McDonald, MW Steele, NC AF Myers, MJ Farrell, DE EvockClover, CM McDonald, MW Steele, NC TI Effect of growth hormone or chromium picolinate on swine metabolism and inflammatory cytokine production after endotoxin challenge exposure SO AMERICAN JOURNAL OF VETERINARY RESEARCH LA English DT Article ID TUMOR-NECROSIS-FACTOR; RECOMBINANT BOVINE SOMATOTROPIN; PITUITARY-ADRENAL AXIS; FACTOR-ALPHA; IMMUNE-SYSTEM; SUPPLEMENTAL CHROMIUM; PORCINE SOMATOTROPIN; MONOCLONAL-ANTIBODY; TNF-ALPHA; IN-VIVO AB Objective-To determine whether recombinant porcine somatotropin (PST) or chromium picolinate (CrP) affected cytokine production and metabolism in swine after endotoxin challenge exposure. Animals-20 Poland China x Landrace pigs, 5/group. Procedure-Pigs were given CrP-supplemented feed at body weight of 20 kg; PST treatment began at 60 kg, and both treatments continued through body weight of 90 kg, At 90 kg, pigs were challenge exposed with 20 mu g of lipopolysaccharide (LPS)/kg of body weight. Blood samples were obtained at various times through 24 hours after LPS challenge exposure. Results-in all pigs not given PST, glucose concentration decreased 2 to 4 hours after LPS. In PST-treated pigs, blood glucose concentration was decreased at 6 to 8 hours after LPS. Plasma insulin concentration paralleled changes in glucose concentration. Nonesterified fatty acid concentration was high 2 to 24 hours after IFS in pigs not given PST and at 6 to 24 h in PST-treated pigs. Plasma urea nitrogen concentration was high at 6 to 24 hours after LPS in pigs not given PST. The urea nitrogen values in PST-treated pigs were lower at ail times. Serum aspartate transaminase activity was high 6 to 24 hours after LPS in pigs not given PST, whereas PST treatment prevented the increase in this enzyme activity. In untreated (PST) pigs, plasma bilirubin (total and direct) concentrations were high 4 to 8 hours after LPS and returned to normal at 24 hours. The PST- and CrP-treated pigs maintained normal plasma bilirubin concentrations. interleukin 6 activity was unaffected by CrP and PST treatments. Treatment with CrP and PST decreased the tumor necrosis factor alpha response to IFS, compared with that in control pigs. Conclusions-PST, and to a lesser extent CrP, provide protection against the adverse metabolic effects of LPS-induced septic shock. C1 USDA ARS,GROWTH BIOL LAB,BELTSVILLE,MD 20705. US FDA,CTR VET MED,LAUREL,MD 20708. NR 51 TC 15 Z9 15 U1 0 U2 2 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0002-9645 J9 AM J VET RES JI Am. J. Vet. Res. PD JUN PY 1997 VL 58 IS 6 BP 594 EP 600 PG 7 WC Veterinary Sciences SC Veterinary Sciences GA XD125 UT WOS:A1997XD12500008 PM 9185964 ER PT J AU Horwitz, W Albert, R AF Horwitz, W Albert, R TI The concept of uncertainty as applied to chemical measurements SO ANALYST LA English DT Article DE uncertainty; measurements; error; variability; reproducibility; interlaboratory study AB The calculation of uncertainty as recommended for physical measurements cannot be transferred readily to chemical measurements, Physical measurements and chemical measurements have entirely different error patterns that behave differently on replication. Correctable local bias predominates in physical systems and random error is minor; random error predominates in chemical systems and bias is difficult to identify and eradicate, Therefore bias must be monitored by randomizing in the interlaboratory environment, a concept not handled by the conventional ISO treatment of uncertainty. RP Horwitz, W (reprint author), US FDA,HFS-500,WASHINGTON,DC 20204, USA. NR 6 TC 48 Z9 49 U1 3 U2 10 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0003-2654 J9 ANALYST JI Analyst PD JUN PY 1997 VL 122 IS 6 BP 615 EP 617 DI 10.1039/a703178e PG 3 WC Chemistry, Analytical SC Chemistry GA XH105 UT WOS:A1997XH10500024 PM 9282406 ER PT J AU Townes, JM Solomon, HM Griffin, PM AF Townes, JM Solomon, HM Griffin, PM TI The botulism hazard - In Reply SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 US FDA,WASHINGTON,DC 20204. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30333. RP Townes, JM (reprint author), OREGON DEPT HUMAN RESOURCES,PORTLAND,OR 97232, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 1 PY 1997 VL 126 IS 11 BP 919 EP 919 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA XA911 UT WOS:A1997XA91100024 ER PT J AU Rasooly, L Rose, NR Shah, DB Rasooly, A AF Rasooly, L Rose, NR Shah, DB Rasooly, A TI In vitro assay of Staphylococcus aureus enterotoxin a activity in food SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article AB Staphylococcus aureus enterotoxin A (SEA) is a leading cause of food poisoning. The current test for functional activity of SEA requires monkeys or kittens. The major drawbacks of animal assays are lack of quantitation, poor reproducibility, low sensitivity and high cost. In this report we describe and evaluate an alternative assay using T-cell proliferation to measure SEA activity in food. Human and rat lymphocytes proliferate in response to concentrations of SEA as low as 1 pg/ml, well below the pathogenic dose of 100 ng. This proliferation assay is highly sensitive, quantitative, and simple. Nonradioactive assays of T-cell proliferation were also suitable for detecting and measuring SEA, although with a 10-fold lower sensitivity. To evaluate the utility of this assay for food testing, four different food samples were mixed with SEA. In each sample, SEA was detected at a concentration of 1 ng/ml. Heat-inactivated SEA produced no detectable proliferation. These results demonstrate that an in vitro cell proliferation assay is an advantageous alternative to existing animal assays for measuring SEA activity in food. C1 US FDA,DIV MICROBIOL STUDIES,WASHINGTON,DC 20204. JOHNS HOPKINS UNIV,DEPT MOL MICROBIOL & IMMUNOL,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. NR 12 TC 13 Z9 14 U1 0 U2 2 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 JUN PY 1997 VL 63 IS 6 BP 2361 EP 2365 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA XB705 UT WOS:A1997XB70500038 PM 9172356 ER PT J AU DePaola, A McLeroy, S McManus, G AF DePaola, A McLeroy, S McManus, G TI Distribution of Vibrio vulnificus phage in oyster tissues and other estuarine habitats SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID GULF-COAST; CRASSOSTREA-VIRGINICA; TEMPERATURE; ENVIRONMENT; BACTERIA; SALINITY; SEAWATER; VIRUSES AB Phages lytic to Vibrio vulnificus were found in estuarine waters, sediments, plankton, crustacea, molluscan shellfish, and the intestines of finfish of the U.S. Gulf Coast, but no apparent relationship between densities of V. vulnificus and its phages was observed. Phage diversity and abundance in molluscan shellfish were much greater than in other habitats. V. vulnificus phages isolated from oysters did not lyse other mesophilic bacteria also isolated from oysters. Both V. vulnificus and its phages were found in a variety of oyster tissues and fluids with lowest densities in the hemolymph and mantle fluid. These findings suggest a close ecological relationship between V. vulnificus phages and molluscan shellfish. C1 UNIV CONNECTICUT,DEPT MARINE SCI,GROTON,CT 06340. RP DePaola, A (reprint author), US FDA,GULF COAST RES LAB,POB 158,DAUPHIN ISL,AL 36528, USA. OI DeGrasse, Stacey/0000-0001-7808-4193 NR 26 TC 28 Z9 28 U1 1 U2 6 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 JUN PY 1997 VL 63 IS 6 BP 2464 EP 2467 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA XB705 UT WOS:A1997XB70500055 PM 9172370 ER PT J AU Ahn, H Chen, JJ AF Ahn, H Chen, JJ TI Tree-structured logistic model for over-dispersed binomial data with application to modeling developmental effects SO BIOMETRICS LA English DT Article DE bootstrap; cross-validation; dose-response; over-dispersion; regression tree ID GENERALIZED LINEAR-MODELS; REGRESSION TREES; DOSE-RESPONSE; LONGITUDINAL DATA; FETAL WEIGHT; MALFORMATION; TERATOLOGY; TOXICITY AB This article proposes tree-structured logistic regression modeling for over-dispersed binomial data. Recursive partitioning is performed using a combination of statistical tests and residual analysis. The splitting criterion in cross-validation is based on the deviance function. A nested grid algorithm to estimate the bootstrap parameters is developed. The regression tree procedure provides a new approach for exploring in detail the relationship between the binomial response and explanatory variables. The proposed procedure is used to model the relationship between the incidence of malformation and dose and fetal weight using data from a developmental experiment conducted at the National Center for Toxicological Research. A conditional Gaussian chain model is used to account for the effect of fetal weight by dose. C1 US FDA,NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,JEFFERSON,AR 72079. RP Ahn, H (reprint author), SUNY STONY BROOK,DEPT APPL MATH & STAT,STONY BROOK,NY 11794, USA. NR 37 TC 16 Z9 16 U1 0 U2 2 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1997 VL 53 IS 2 BP 435 EP 455 DI 10.2307/2533948 PG 21 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA XE965 UT WOS:A1997XE96500004 PM 9235119 ER PT J AU Wang, SJ Hung, HMJ AF Wang, SJ Hung, HMJ TI Large sample tests for binary outcomes in fixed-dose combination drug studies SO BIOMETRICS LA English DT Article DE clinical trial; min test; Monte Carlo simulation; power; significance level AB Several test statistics are developed for testing the hypothesis that the combination of two drugs at a fixed-dose regimen is more effective than both of the single drugs used alone with respect to a dichotomous response variable. The response probability, legit, and arcsine-root scales are considered. The power function and the significance level are derived for large samples. For the sample size per group of 20 or greater, the power and type I error rate can be accurately calculated using the large sample power function when the response probability ranges from 0.2 to 0.8. These tests have similar power behaviors. In small samples, the large sample power functions of two of the tests can severely underestimate the type I error rate while overestimation can occur with one other test. The utilities of these tests are extended to unbalanced sample size cases. Generally speaking, there is a loss of power with unequal sample size allocation, but the loss is not severe. RP Wang, SJ (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV BIOMETR 1,HFD-710,ROOM 2034,WOODMONT 2,1451 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 6 TC 8 Z9 8 U1 0 U2 0 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1997 VL 53 IS 2 BP 498 EP 503 DI 10.2307/2533953 PG 6 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA XE965 UT WOS:A1997XE96500009 PM 9192448 ER PT J AU He, XM Shen, LJ AF He, XM Shen, LJ TI Linear regression after spline transformation SO BIOMETRIKA LA English DT Article DE b-spline; box-Cox transformation; canonical analysis; generalised linear model; model selection; slicing regression ID LINK AB In a transformation model h(Y)=X'beta+epsilon for some smooth and usually monotone function h, we are often interested in the direction of beta without knowing the exact form of h. We consider a projection of h onto a linear space of B-spline functions which has the highest correlation with the design variable X. As with the Box-Cox transformation, the transformed response may then be analysed by standard linear regression software. The direction estimate from canonical correlation calculations agrees with the least squares estimate for the approximating model subject to an identifiability constraint. This approach is also closely related to the slicing regression of Duan & Li (1991). The dimensionality of the space of spline transformations can be determined by a model selection principle. Typically, a very small number of B-spline knots is needed. A number of real and simulated data examples is presented to demonstrate the usefulness of this approach. C1 USA,FOOD & DRUG ADM,HFD725,ROCKVILLE,MD 20850. RP He, XM (reprint author), UNIV ILLINOIS,DEPT STAT,CHAMPAIGN,IL 61820, USA. NR 10 TC 13 Z9 14 U1 0 U2 0 PU BIOMETRIKA TRUST PI LONDON PA UNIV COLLEGE LONDON GOWER ST-BIOMETRIKA OFFICE, LONDON, ENGLAND WC1E 6BT SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD JUN PY 1997 VL 84 IS 2 BP 474 EP 481 DI 10.1093/biomet/84.2.474 PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA XK260 UT WOS:A1997XK26000018 ER PT J AU Yamauchi, A Bloom, ET AF Yamauchi, A Bloom, ET TI Control of cell cycle progression in human natural killer cells through redox regulation of expression and phosphorylation of retinoblastoma gene product protein SO BLOOD LA English DT Article ID HUMAN T-CELLS; SIGNAL-TRANSDUCTION; PHOSPHATASE-ACTIVITY; CD4(+) LYMPHOCYTES; CYTOKINE RECEPTORS; GLUTATHIONE; IMMUNODEFICIENCY; INTERLEUKIN-2; INDUCTION; KINASE AB Using thiol deprivation, we have previously shown that the response of natural killer (NK) cells to interleukin-2 (IL-2) is subject to redox regulation downstream of IL-2 binding and internalization. We have now used the IL-2-dependent cell line, NK3.3 to study redox regulation of NK cells further, and found that NK3.3 cells neither incorporated [H-3]-thymidine nor completed the G(1)-S phase transition in medium lacking the thiol-related compounds, L-cystine, and glutathione, despite the presence of sufficient IL-2. Thiol deprivation did not alter the induction of DNA interferon-gamma activated sequence (GAS)-binding activity in response to IL-2, However, the retinoblastoma gene product (RE), a cyclin-dependent kinase (CDK) substrate, was phosphorylated within 24 hours after IL-2 stimulation in standard medium, but its expression and phosphorylation were reduced in thiol-depleted medium in both NK3.3 cells and freshly isolated NK cells. These reductions were not associated with an increased level of p27(Kip1), an inhibitor of CDKs CDK6/2 in association with G1 cyclins, Reducing agents, N-acetylcysteine, reduced glutathione or 2-ME restored both RB phosphorylation and DNA synthesis in thiol-deprived NK3.3 cells, The in vitro kinase activities of CDK6 and CDK2 were prematurely increased by thiol deprivation, This enhancement was associated with CDK hyperphosphorylation and prolonged phosphorylation, and could be observed before and beyond IL-2 stimulation. The data suggest the possibility that the premature and prolonged enhancement of CDK activity in thiol-deprived NK cells is associated with, and therefore may contribute to, the reduced expression and phosphorylation of RE, and the associated cell cycle arrest. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,LAB CELLULAR IMMUNOL HFM518,BETHESDA,MD 20892. NR 36 TC 34 Z9 34 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 1997 VL 89 IS 11 BP 4092 EP 4099 PG 8 WC Hematology SC Hematology GA XD379 UT WOS:A1997XD37900025 PM 9166850 ER PT J AU Dale, EC Yang, XL Moore, SK Shyamala, G AF Dale, EC Yang, XL Moore, SK Shyamala, G TI Murine 86-kDa heat shock protein gene and promoter SO CELL STRESS & CHAPERONES LA English DT Article ID CHICKEN HSP90-BETA; EXPRESSION; CELLS; RECEPTORS; BINDING; ASSOCIATION; SEQUENCE; FAMILY; STRESS; KINASE AB The class of 90 kDa heat shock proteins (HspSO) is among the most abundant heat shock proteins (Hsps) in eukaryotic cells. In vertebrates, HspSO is encoded by two distinct gene families giving rise to products of 84 and 86 kDa. In mice the expression of these two genes, hsp84 and hsp86, vary with respect to each other in responses to stress, and also in response to signals for growth and development. Therefore, as a step towards understanding the molecular basis for the differential regulation of these two genes, we have isolated and characterized genomic clones of the murine hsp86 gene and its 5' flanking region. The gene is composed of eleven exons interrupted by 10 introns. The 5' region contains consensus TATA, several stimulatory protein-1 binding site (SP1) elements as well as six consensus heat shock elements (HSE) 5' of the transcription start site. An 806 bp fragment of the 5' promoter region conferred constitutive expression upon a reporter gene and this expression was increased upon heat shock. C1 UNIV CALIF BERKELEY,LAWRENCE BERKELEY LAB,DIV LIFE SCI,BERKELEY,CA 94720. US FDA,DIV METAB & ENDOCRINE DRUG PROD,ROCKVILLE,MD 20857. FU NCI NIH HHS [CA54828] NR 35 TC 16 Z9 16 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD JUN PY 1997 VL 2 IS 2 BP 87 EP 93 DI 10.1379/1466-1268(1997)002<0087:MKHSPG>2.3.CO;2 PG 7 WC Cell Biology SC Cell Biology GA XG200 UT WOS:A1997XG20000003 PM 9250399 ER PT J AU Maryanski, J AF Maryanski, J TI The regulatory position in the US SO CEREAL FOODS WORLD LA English DT Article RP Maryanski, J (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CEREAL CHEMISTS PI ST PAUL PA 3340 PILOT KNOB RD, ST PAUL, MN 55121-2097 SN 0146-6283 J9 CEREAL FOOD WORLD JI Cereal Foods World PD JUN PY 1997 VL 42 IS 6 BP 465 EP 466 PG 2 WC Food Science & Technology SC Food Science & Technology GA XD401 UT WOS:A1997XD40100021 ER PT J AU Hirata, RDC Gianinni, SD Salazar, LA Ozaki, AN Forti, N Diament, J Issa, JS Nguyen, NY Hirata, MH AF Hirata, RDC Gianinni, SD Salazar, LA Ozaki, AN Forti, N Diament, J Issa, JS Nguyen, NY Hirata, MH TI Influence of Ava II and Hinc II polymorphism of the LDL receptor gene on cholesterol levels in postmenopausal women. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 UNIV SAO PAULO,INST HEART,SAO PAULO,BRAZIL. UNIV SAO PAULO,FAC PHARMACEUT SCI,SAO PAULO,BRAZIL. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. RI Issa, Jaqueline/J-5693-2013; Hirata, Mario/C-9718-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1997 VL 43 SU 6 BP 706 EP 706 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA XD363 UT WOS:A1997XD36300705 ER PT J AU Burkhart, GA AF Burkhart, GA TI Race and angioedema SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Letter RP Burkhart, GA (reprint author), US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUN PY 1997 VL 61 IS 6 BP 700 EP 700 DI 10.1016/S0009-9236(97)90106-5 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XG209 UT WOS:A1997XG20900013 PM 9209254 ER PT J AU Shores, EW Love, PE AF Shores, EW Love, PE TI TCR zeta chain in T cell development and selection SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID RECEPTOR SIGNAL-TRANSDUCTION; ANTIGEN RECEPTOR; NEGATIVE SELECTION; POSITIVE SELECTION; MICE LACKING; BETA-CHAIN; CD4(+)CD8(+) THYMOCYTES; DEFICIENT MICE; ALPHA-BETA; IMMATURE THYMOCYTES AB Current data suggest that an important function of the multimeric structure of the TCR is to enable the assembly of structurally and functionally different forms of the TCR, the pre-TCR and alpha beta TCR complexes, at different stages in development. Four distinct TCR subunits (the CD3 gamma, delta, and epsilon chains and the zeta chain) contain signal transducing motifs; however, the zeta chain is notable for containing three of these elements. These motifs, especially those within the zeta chain, function to amplify signals generated by the TCR, and this property is especially critical during thymocyte selection. The results of several recent experiments argue that positive and negative selection of thymocytes may involve activation of distinct downstream signaling pathways. The outcome of thymocyte selection can also be influenced, however, by quantitative effects such as changes in ligand concentration or direct alteration of the TCR signaling potential. Recent studies pertaining to the kinetics of TCR-ligand interactions may provide insight into how signaling through the TCR can be regulated either quantitatively or qualitatively. C1 NICHHD,LAB MAMMALIAN GENES & DEV,NIH,BETHESDA,MD 20892. RP Shores, EW (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892, USA. NR 96 TC 40 Z9 41 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 1997 VL 9 IS 3 BP 380 EP 389 DI 10.1016/S0952-7915(97)80085-4 PG 10 WC Immunology SC Immunology GA XF675 UT WOS:A1997XF67500013 PM 9203416 ER PT J AU Misbin, R Green, L Stadel, B Gueriguain, J Gubbi, A Fleming, A AF Misbin, R Green, L Stadel, B Gueriguain, J Gubbi, A Fleming, A TI Metformin-associated lactic acidosis SO DIABETOLOGIA LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 34 EP 34 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300035 ER PT J AU Hart, RW Turturro, A AF Hart, RW Turturro, A TI Dietary restrictions and cancer SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Mechanisms and Prevention of Environmentally Caused Cancers CY 1995 CL SANTA FE, NM SP Lovelace Inst, US DOE, Bioserv Biotechnol, Johnson & Johnson Inc, Int Life Sci Inst, Dako Corp, VWR, SW Sci Res Inc DE dietary restriction; cancer; diet; spontaneous carcinogenesis; induced carcinogenesis; body weight and cancer; oxidative damage; cellular proliferation ID AGE-RELATED-CHANGES; CALORIC RESTRICTION; METABOLIC-ACTIVATION; FISCHER-344 RATS; BODY-WEIGHT; B6C3F1 MICE; DNA-DAMAGE; F344 RATS; MECHANISMS; EXPRESSION AB Dietary restriction (DR) alters a significant environmental factor in carcinogenesis, dietary intake, thus inhibiting both spontaneous and induced tumorigenesis. Potential mechanisms for the inhibition of spontaneous cancer may include the effects of DR to do the following: decrease body weight, which decreases cellular proliferation and increases apoptosis in a number of organs that increase and decrease with body size; decrease body temperature, thereby lowering the amount of endogenous DNA damage temperature generates; decrease oxidative damage, by increasing antioxidant damage defense systems; decrease, generally, cellular proliferation; and protect the fidelity of the genome by decreasing DNA damage, increasing DNA repair, and preventing aberrant gene expression. Potential mechanisms for reducing induced tumor incidence include lowering agent activation, changing agent disposition, decreasing the adducts most associated with agent toxicity, and inhibiting tumor progression through mechanisms similar to those that can effect spontaneous tumorigenesis. As a method to control a major source of environmental cancer, and as the major modulator of the agent induction of this disease, understanding how DR works may significantly contribute to the efforts to explain how diet impacts on development of cancer in the United States, and may suggest methods to reduce the adverse impacts of other environmental agents on the disease. RP Hart, RW (reprint author), NATL CTR TOXICOL RES, DIV BIOMETRY & RISK ASSESSMENT, HFT 020, 3900 NCTR DR, JEFFERSON, AR 72079 USA. NR 54 TC 39 Z9 39 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 1997 VL 105 SU 4 BP 989 EP 992 DI 10.2307/3433316 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA XN297 UT WOS:A1997XN29700042 PM 9255593 ER PT J AU Sgadari, C Angiolillo, A Farber, J TeruyaFeldstein, J Burd, P Tosato, G AF Sgadari, C Angiolillo, A Farber, J TeruyaFeldstein, J Burd, P Tosato, G TI The chemokines IP-10 and MIG identified as mediators of tumor necrosis in vivo SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 US FDA,CTR BIOL,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. RI Sgadari, Cecilia/H-4302-2016 OI Sgadari, Cecilia/0000-0003-0364-4912 NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUN PY 1997 VL 33 SU 5 BP 107 EP 107 PG 1 WC Oncology SC Oncology GA XG122 UT WOS:A1997XG12200108 ER PT J AU Major, ME Feinstone, SM AF Major, ME Feinstone, SM TI The molecular virology of hepatitis C SO HEPATOLOGY LA English DT Review ID VIRUS CORE PROTEIN; NON-B HEPATITIS; PUTATIVE NONSTRUCTURAL PROTEINS; DENSITY-GRADIENT CENTRIFUGATION; HUMORAL IMMUNE-RESPONSE; 5' UNTRANSLATED REGION; SERINE-TYPE PROTEINASE; IN-VITRO INFECTION; N-TERMINAL DOMAIN; HYPERVARIABLE REGION-1 RP Major, ME (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,LAB HEPATITIS VIRUSES,BLDG 29A,ROOM 1D16,HFM 448,BETHESDA,MD 20892, USA. NR 163 TC 231 Z9 240 U1 1 U2 3 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 JUN PY 1997 VL 25 IS 6 BP 1527 EP 1538 DI 10.1002/hep.510250637 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XC872 UT WOS:A1997XC87200036 PM 9185778 ER PT J AU Snellings, NJ Tall, BD Venkatesan, MM AF Snellings, NJ Tall, BD Venkatesan, MM TI Characterization of Shigella type 1 fimbriae: Expression, FimA sequence, and phase variation SO INFECTION AND IMMUNITY LA English DT Article ID URINARY-TRACT INFECTIONS; ESCHERICHIA-COLI; PILI; COLONIZATION; VIRULENCE; GENE; ENTEROBACTERIACEAE; HEMAGGLUTINATION; MUTANTS AB This study documents the presence of type I fimbriae on Shigella and confirms these mannose-sensitive adherence structures to be bona fide components of the Shigella surface, While laboratory-passaged Shigella strains and lyophilized clinical isolates failed to express type 1 fimbriae, 6 of 20 recent clinical isolates, including 1 Shigella flexneri strains, 1 Shigella boydii strain, and 1 Shigella dysenteriae strain, produced type I fimbriae as detected by mannose-sensitive hemagglutination (MSHA) and electron microscopy. Optimal production of a predominantly Fim(+) population required serial passage every 48 to 72 h in unshaken brain heart infusion broth at 37 degrees C, Fim(+) Shigella cultures were capable of reversibly switching ro a non-MSHA, afimbriated phase during serial aerobic cultivation on tryptic soy agar plates, The amino acid sequence of S, flexneri type I FimA contained 18 substitutions compared to that of Escherichia coli fimbrillin, Indirect immunoelectron microscopy suggested the presence of both shared and unique epitopes on E, coli and S, flexneri type 1 fimbriae. Random phase variation between fimbriated and afimbriated states in Shigella was accompanied by the genomic rearrangement associated with phase variation in E, coli. C1 WALTER REED ARMY INST RES,DEPT ENTER INFECT,DIV COMMUNICABLE DIS & IMMUNOL,WASHINGTON,DC 20307. US FDA,CTR FOOD SAFETY & NUTR,MICROBIAL ECOL BRANCH,WASHINGTON,DC 20204. OI Tall, Ben/0000-0003-0399-3629 NR 33 TC 21 Z9 22 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 1997 VL 65 IS 6 BP 2462 EP 2467 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XB562 UT WOS:A1997XB56200070 PM 9169792 ER PT J AU Robbins, PA Rota, PA Shapiro, SZ AF Robbins, PA Rota, PA Shapiro, SZ TI A broad cytotoxic T lymphocyte response to influenza type B virus presented by multiple HLA molecules SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE cytotoxic T lymphocyte; HLA-B8; HLA-DR1; influenza B virus; peptides ID HISTOCOMPATIBILITY ANTIGEN; MONOCLONAL-ANTIBODIES; NUCLEOPROTEIN GENE; IMMUNE-RESPONSE; HEMAGGLUTININ; SEQUENCE; INFECTION; EPITOPES; PEPTIDES; PERFORIN AB The HLA restriction and epitope specificity of cytotoxic T lymphocytes (CTL) involved in recovery from influenza type B infection have not been extensively characterized. Here lymphocytes obtained from a healthy individual contained virus-specific CTL restricted by class I HLA molecules, HLA-A1, A2, B7 and B8, and the class II HLA molecules, HLA-DR1 and DR3. Four conserved viral epitopes were predicted from allele-specific motifs for peptides interacting with HLA-B8 and HLA-DR1. Bulk CTL recognized three 9mer HLA-B8-restricted peptides from nucleoprotein, residues 30-38, 263-271 and 413-421, and a 13mer HLA-DR1-restricted peptide from hemagglutinin, residues 308-320. The epitopes presented by HLA-A1, HLA-B7 and HLA-DR3 remain undefined. Peptide-specific CTL lines recognized influenza type B virus-infected cells indicating the peptides are representative of naturally processed epitopes. A hemagglutinin peptide-specific CD4 CTL clone expressed similar to 200 molecules of perforin mRNA/cell, suggestive of a functional perforin pathway for target cell lysis. The results indicate a broad CTL response composed of both CD8 CTL and CD4 CTL recognizing viral epitopes presented by multiple HLA molecules. C1 CTR DIS CONTROL,NATL CTR INFECT DIS,ATLANTA,GA 30333. RP Robbins, PA (reprint author), NIH,CTR BIOL EVALUAT & RES,BLDG 10,BETHESDA,MD 20892, USA. NR 57 TC 14 Z9 14 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUN PY 1997 VL 9 IS 6 BP 815 EP 823 DI 10.1093/intimm/9.6.815 PG 9 WC Immunology SC Immunology GA XE891 UT WOS:A1997XE89100002 PM 9199964 ER PT J AU Griffin, BR Hobbs, MS Gollon, JL Schlenk, D Kadlubar, FF Brand, CD AF Griffin, BR Hobbs, MS Gollon, JL Schlenk, D Kadlubar, FF Brand, CD TI Effect of waterborne copper sulfate exposure on copper content in liver and axial muscle of channel catfish SO JOURNAL OF AQUATIC ANIMAL HEALTH LA English DT Article ID TROUT SALMO-GAIRDNERI; TISSUE CONTAMINANT ANALYSIS; EPISODIC METAL POLLUTION; RAINBOW-TROUT; DIETARY COPPER; ONCORHYNCHUS-MYKISS; TOXICITY; RICHARDSON; PUNCTATUS; DIGESTION AB Adult channel catfish lctalurus punctatus were continuously exposed to waterborne copper sulfate added at concentrations of 1.7. 2.7, or 3.6 mg/L for 10 weeks. Overall. there were no significant differences in the copper content of channel catfish axial muscle during the exposure period, and no significant copper accumulation resulted from exposure. Significantly higher concentrations of copper were present in liver tissue of catfish in all exposed groups 2 weeks after exposure to waterborne copper sulfate began. Extent of copper accumulation in the liver was gender and dose related. with higher concentrations in males at the highest dosage level. Exposures to waterborne copper sulfate were discontinued after 10 weeks. and copper concentrations in liver tissue subsequently returned to levels indistinguishable from controls in 4-8 more weeks. Results indicate that copper sulfate used as a waterborne disease therapeutant for channel catfish does not alter copper content of edible muscle of channel catfish and should not present any hazard to human consumers. C1 UNIV MISSISSIPPI,DEPT PHARMACOL,UNIVERSITY,MS 38677. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RP Griffin, BR (reprint author), US AGR RES SERV,STUTTGART NATL AQUACULTURE RES CTR,POB 860,STUTTGART,AR 72160, USA. NR 41 TC 13 Z9 14 U1 0 U2 0 PU AMER FISHERIES SOC PI BETHESDA PA 5410 GROSVENOR LANE SUITE 110, BETHESDA, MD 20814-2199 SN 0899-7659 J9 J AQUAT ANIM HEALTH JI J. Aquat. Anim. Health PD JUN PY 1997 VL 9 IS 2 BP 144 EP 150 DI 10.1577/1548-8667(1997)009<0144:EOWCSE>2.3.CO;2 PG 7 WC Fisheries; Veterinary Sciences SC Fisheries; Veterinary Sciences GA XN522 UT WOS:A1997XN52200008 ER PT J AU Stefanelli, P Mastrantonio, P Hausman, SZ Giuliano, M Burns, DL AF Stefanelli, P Mastrantonio, P Hausman, SZ Giuliano, M Burns, DL TI Molecular characterization of two Bordetella bronchiseptica strains isolated from children with coughs SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID PERTUSSIS TOXIN GENES; HAMSTER OVARY CELLS; MONOCLONAL-ANTIBODIES; FILAMENTOUS HEMAGGLUTININ; PARAPERTUSSIS; IDENTIFICATION; SUBUNITS; PROTEINS; MUTANTS; PATIENT AB During a surveillance program associated with the Italian clinical trial for the evaluation of new acellular pertussis vaccines, two bacterial isolates were obtained in cultures of samples from immunocompetent infants who had episodes of cough. Both clinical isolates were identified as Bordetella bronchiseptica by biochemical criteria, although both strains agglutinated with antisera specific for Bordetella parapertussis, suggesting that the strains exhibited some characteristics of both B. bronchiseptica and B. parapertussis. Both children from whom these strains were isolated exhibited an increase in serum antibody titer to pertussis toxin (PT), a protein that is produced by Bordetella pertussis but that is not thought to be produced by B. bronchiseptica. We therefore examined whether the clinical isolates were capable of producing PT. Neither strain produced PT under laboratory conditions, although both strains appeared to contain a portion of the pfx region that encodes the structural subunits of PT. In order to determine whether the ptx genes may encode functional proteins, we inserted an active promoter directly upstream of the ptx region of one of these strains. Biologically active PT was produced, suggesting that this strain contains the genetic information necessary to encode an active PT molecule. Sequence analysis of the ptx promoter region of both strains indicated that, while they shared homology with the B. bronchiseptica ATCC 4617 sequence, they contained certain sequence motifs that are characteristic of B. parapertussis and certain motifs that are characteristic of B. pertussis. Taken together, these findings suggest that variant strains of B. bronchiseptica exist and might be capable of causing significant illness in humans. C1 IST SUPER SANITA,DEPT BACTERIOL & MED MYCOL,I-00161 ROME,ITALY. US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,BETHESDA,MD 20892. RI STEFANELLI, PAOLA/B-8729-2016 OI STEFANELLI, PAOLA/0000-0003-1620-4385 NR 35 TC 30 Z9 31 U1 0 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 JUN PY 1997 VL 35 IS 6 BP 1550 EP 1555 PG 6 WC Microbiology SC Microbiology GA XA755 UT WOS:A1997XA75500049 PM 9163480 ER PT J AU Ette, EI AF Ette, EI TI Stability and performance of a population pharmacokinetic model SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID CROSS-VALIDATION; PREDICTION ERROR; BOOTSTRAP; REGRESSION; JACKKNIFE; RULE AB This study aimed to determine the stability fin terms of covariate selection) of a population pharmacokinetic model and evaluate its performance in the absence of a test data set. Data from 88 full-term infants, 21 of whom were human immunodeficiency virus (HIV)-seropositive, taking an antiinfective agent were analyzed using exploratory data analysis methods and the nonlinear mixed-effects modeling (NONMEM) program to obtain the final population pharmacokinetic model. The stability of the population pharmacokinetic model was tested using the nonparametric bootstrap approach in four steps: 1) with the base pharmacokinetic model, 100 bootstrap replicates of the original data were generated by sampling with replacement; 2) ascertainment that each bootstrap date! replicate was described by the basic structural model using the NONMEM objective function; 3) generalized additive modeling (GAM) applied to empiric Bayesian estimates for covariate selection at alpha = 0.05 and a frequency (f) cutoff value of 0.50; and 4) NONMEM population model building using covariates selected in the third step with alpha = 0.005. Performance of the population pharmacokinetic model was evaluated using 200 additional bootstrap replicates of the data by fitting the model obtained in step 4 to them. Parameters obtained were compared with those obtained in the model stability step, and improved prediction error, a measure of predictive accuracy as an index of internal validation, was computed. The reciprocal of serum creatinine (RSC; f = 0.73) and HIV (f = 0.70) were selected by GAM as predictors of clearance (Cl). The population pharmacokinetic model obtained without the determination of model stability included RSC as a predictor of Cl, but the final model from the model stability step included both HN and RSC as predictors of Cl. Final population pharmacokinetic parameters were obtained with this model fitted to the original data; however, the 95% confidence interval on the HIV status regression coefficient included zero, indicating no significance. The mean parameter estimates obtained with the additional 200 bootstrap replicates of data were within 25% of those obtained with the final model at the regression stability step. Bootstrap resampling procedure is useful for evaluating the stability and performance of a population model by repeatedly fitting it to the bootstrap samples when there is no test data set. RP Ette, EI (reprint author), US FDA,CTR DRUG EVALUAT & RES,OFF CLIN PHARMACOL & BIOPHARMACEUT,HFD-855,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 17 TC 193 Z9 203 U1 0 U2 8 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 JUN PY 1997 VL 37 IS 6 BP 486 EP 495 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XE032 UT WOS:A1997XE03200004 PM 9208355 ER PT J AU Segal, BM Klinman, DM Shevach, EM AF Segal, BM Klinman, DM Shevach, EM TI Microbial products induce autoimmune disease by an IL-12-dependent pathway SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; T-CELL RECEPTOR; MULTIPLE-SCLEROSIS; HEALTHY-INDIVIDUALS; SUSCEPTIBILITY; SUPERANTIGEN; TOLERANCE; INFECTION; LINES AB The development and exacerbation of autoimmune diseases are associated with antecedent infectious illness. Microbial products such as LPS, bacterial DNA, or oligonucleotides containing an unmethylated cytosine-guanine dinucleotide have cytokine modulating properties. These products converted quiescent myelin basic protein-specific T cells into effector cells capable of transferring experimental allergic encephalomyelitis. The disease-promoting properties of the microbial products were solely dependent on their capacity to induce the production of IL-12. C1 NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. OI Segal, Benjamin/0000-0002-0906-6319 NR 34 TC 145 Z9 149 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 JUN 1 PY 1997 VL 158 IS 11 BP 5087 EP 5090 PG 4 WC Immunology SC Immunology GA XA063 UT WOS:A1997XA06300006 PM 9164922 ER PT J AU Sawada, T Falk, LA Rao, P Murphy, WJ Pluznik, DH AF Sawada, T Falk, LA Rao, P Murphy, WJ Pluznik, DH TI IL-6 induction of protein-DNA complexes via a novel regulatory region of the inducible nitric oxide synthase gene promoter - Role of octamer binding proteins SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; INTERFERON-GAMMA; TRANSCRIPTION FACTOR; BACTERIAL LIPOPOLYSACCHARIDE; PERITONEAL-MACROPHAGES; MOUSE MACROPHAGES; SIGNAL TRANSDUCER; NUCLEAR-RNA; INTERLEUKIN-6; EXPRESSION AB Macrophage inducible nitric oxide synthase (iNOS) catalyzes the synthesis of NO. IL-6-stimulated macrophage differentiation of murine myeloid Mi cells is accompanied by iNOS gene induction and steady-state mRNA expression, Two regions within the iNOS promoter mediate transcriptional responsiveness to LPS and IFN-gamma. Region I contains several essential transcription factor binding motifs and promotes responsiveness to LPS, whereas region II potentiates the LPS response by IFN-gamma. Because region I possesses basal promoter activity and directly mediates iNOS gene activation, we attempted to identify the trans-acting factors involved in IL-6-stimulated induction of the murine iNOS gene through this region, Using an electrophoretic mobility shift assay and methylation interference, we show that IL-6 induced reciprocal changes in the binding activity of POU family members to the candidate nonconsensus octamer sequence of region I that correlated, temporally, with iNOS steady-state mRNA expression, Although DNA-protein binding activity of IL-6-stimulated whole-cell extracts also interacted with a radiolabeled canonical octamer motif, such DNA-protein complexes were not eliminated in competition assays using consensus nuclear factor KB Or IL-6 oligonucleotides, Specifically, our studies show that octamer binding protein-1-related protein binding activity decreased, while binding of octamer binding protein-2-related proteins increased during differentiation. Mutation of the octamer motif disrupted both binding of the IL-6-induced protein-DNA interactions and transcriptional activation through region I, revealing that this motif is absolutely essential for IL-6 induction of iNOS, Thus, differential activation of octamer binding transcriptional modulators from the POU family may be a novel mechanism of IL-6-mediated iNOS gene regulation. C1 US FDA,DIV HEMATOL PROD,CTR BIOL EVALUAT RES,ROCKVILLE,MD 20892. UNIV KANSAS,MED CTR,WILKINSON LAB CANC RES,KANSAS CANC CTR,KANSAS CITY,KS 66160. NR 34 TC 35 Z9 35 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 1997 VL 158 IS 11 BP 5267 EP 5276 PG 10 WC Immunology SC Immunology GA XA063 UT WOS:A1997XA06300029 PM 9164945 ER PT J AU Leininger, E Bowen, S RenauldMongenie, G Rouse, JH Menozzi, FD Locht, C Heron, I Brennan, MJ AF Leininger, E Bowen, S RenauldMongenie, G Rouse, JH Menozzi, FD Locht, C Heron, I Brennan, MJ TI Immunodominant domains present on the Bordetella pertussis vaccine component filamentous hemagglutinin SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID RESPIRATORY-EPITHELIAL-CELLS; MONOCLONAL-ANTIBODIES; BACTERIAL ADHESIN; ADHERENCE; INFECTION; SEQUENCE; HEPARIN; IDENTIFICATION; COLONIZATION; RECOGNITION AB To identify immunologically important domains on filamentous hemagglutinin (FHA), a Bordetella pertussis protein included in new acellular pertussis vaccines (ACPVs), a series of monoclonal antibodies, sera from infants vaccinated with ACPVs or whole cell pertussis vaccine (WCPV), and sera from patients with pertussis were analyzed by immunoblots containing FHA fragments and recombinant FHA proteins. Immunodominant domains located at the COOH-terminus of FHA (type I domain) and near the NH2-terminus (type II domain) were defined by the reactivity with monoclonal antibodies. The sera from patients with pertussis and sera from infants vaccinated with WCPV or with 6 different investigational ACPVs specifically recognized well-defined regions within the type I and type II domains. Identification of these prominent immunologic epitopes on FHA should be useful for the construction of more well-defined pertussis vaccines and for the interpretation of human serologic responses, which may correlate with efficacy of pertussis vaccines. C1 US FDA,DIV BACTERIAL PROD,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852. INST PASTEUR,INSERM,U447,LAB MICROBIOL GENET & MOL,F-59019 LILLE,FRANCE. STATE SERUM INST,COPENHAGEN,DENMARK. NR 34 TC 26 Z9 32 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 JUN PY 1997 VL 175 IS 6 BP 1423 EP 1431 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XC322 UT WOS:A1997XC32200018 PM 9180182 ER PT J AU Abassi, Z Kotob, S Pieruzzi, F Abouassali, M Keiser, KR Fratantoni, JC Alayash, AI AF Abassi, Z Kotob, S Pieruzzi, F Abouassali, M Keiser, KR Fratantoni, JC Alayash, AI TI Effects of polymerization on the hypertensive action of diaspirin cross-linked hemoglobin in rats SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID NITRIC-OXIDE; HEMODYNAMIC-RESPONSE; PULMONARY; DCLHB(TM); KIDNEY AB It is believed that the hypertensive effect of diaspirin crosslinked hemoglobin, a viable blood substitute, can be resolved by polymerization, which reduces the diffusion of this derivative into the interstitial space between nitric oxide-producing endothelium and the target vascular smooth muscle, We studied the systemic and renal responses to infusion of three cell-free human hemoglobins in anesthetized isovolemic rats: unmodified (HbAO), crosslinked (alpha-DBBF), and polymerized crosslinked (poly alpha-DBBF). HbAO produced a significant increase in mean arterial blood pressure (MAP) throughout the 60-minute infusion, alpha-DBBF, on the other hand, produced a more marked and prolonged increase in MAP over 120 minutes. Only a moderate increase in MAP was observed in rats after a 30-minute infusion with poly alpha-DBBF. The extent of renal insufficiency produced by these proteins, as determined by the glomerular filtration rate, was in the following order: HbAO > poly alpha-DBBF > alpha-DBBF. Infusion of poly alpha-DBBF, under hypovolemic but not isovolemic conditions in rats, produced an increase in heart rate, cardiac output, and stroke volume and a decrease in total peripheral resistance after 60 minutes. Chemical polymerization to increase the size of alpha-DBBF does not appear to improve its hemodynamic properties in rats, especially under partial exchange transfusion, a more clinically relevant indication for a hemoglobin-based blood substitute. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,LAB CELLULAR HEMATOL,BETHESDA,MD 20892. NHLBI,NIH,BETHESDA,MD 20892. NR 25 TC 68 Z9 70 U1 2 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD JUN PY 1997 VL 129 IS 6 BP 603 EP 610 DI 10.1016/S0022-2143(97)90194-3 PG 8 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA XC640 UT WOS:A1997XC64000005 PM 9178726 ER PT J AU Kashanchi, F Melpolder, JC Epstein, JS Sadaie, MR AF Kashanchi, F Melpolder, JC Epstein, JS Sadaie, MR TI Rapid and sensitive detection of cell-associated HIV-1 in latently infected cell lines and in patient cells using sodium-n-butyrate induction and RT-PCR SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE lymphocytic/monocytoid cells; PBMC; diagnostics ID HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD MONONUCLEAR-CELLS; PERIPHERAL-BLOOD; INSITU HYBRIDIZATION; VIRAL-RNA; EXPRESSION; TYPE-1; REPLICATION; INDIVIDUALS; LYMPHOCYTES AB To develop a rapid and sensitive means of detecting cell-associated human immunodeficiency virus (HIV), donor cells from HIV seropositive patients were treated with the potent viral activator sodium-n-butyrate (NaB) and subsequently assayed by both in situ RNA hybridization and a reverse transcriptase polymerase chain reaction (RT-PCR). The sensitivity of RT-PCR was estimated to be equivalent to 1 x 10(-16) grams (0.1 fg) or approximately 64 copies of the input standard viral RNA per reaction. The present study takes advantage of the ability of NaB to introduce changes in chromatin structure of latently infected cells, leading to increased HIV gene expression. Human ACH-2 and U1 cell lines were used as representatives of T-lymphocytic and monocytoid cells harboring latent inducible proviruses. HIV gene expression was readily detected when these cells were treated with NaB. Viral gag RNA was detected by both in situ and RT-PCR assays. When peripheral blood mononuclear cells (PBMCs) from acquired immunodeficiency syndrome (AIDS) patients, who were all negative for in situ hybridization and serum/ plasma p24 assays, were used for detection of viral gene expression, four categories with distinct patterns of induction were observed. The first set of patients showed HIV-positive PBMCs by RT-PCR without any added NaB, and suppression by added NaB or PHA. The second set of samples showed induction of viral RNA by NaB alone. The third set could be induced with PHA, but not NaB, and the fourth set required both NaB and PHA for induction of HIV gene expression. Our results suggest that direct treatment of the cells with HIV activators may be useful in increasing sensitivity of the RT-PCR intended to be used for detection of cell-associated viral RNAs. This approach may be used to confirm true status of the HIV infection when p24 results are negative or HIV RNAs in serum/plasma are below the threshold of detection. Moreover, this method may identify the presence of latent proviral genomes possibly reflecting the true rate of cell-associated viral load in vivo and without possible mutations brought about by long-term co-cultivation assays with cells from seronegative donors. (C) 1997 Wiley-Liss, Inc. C1 US FDA,CBER,LAB IMMUNOCHEM,DIV TRANSFUS TRANSMITTED DIS,ROCKVILLE,MD 20852. NCI,MOL VIROL LAB,NIH,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT TRANSFUS MED,INFECT DIS SECT,BETHESDA,MD 20892. NR 44 TC 21 Z9 21 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JUN PY 1997 VL 52 IS 2 BP 179 EP 189 DI 10.1002/(SICI)1096-9071(199706)52:2<179::AID-JMV11>3.0.CO;2-G PG 11 WC Virology SC Virology GA XB771 UT WOS:A1997XB77100011 PM 9179766 ER PT J AU Pogribny, IP James, SJ AF Pogribny, IP James, SJ TI A method to estimate the percent loss of cytosine methyl groups at defined CpG sites in liver DNA from methyl-deficient rats SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE 5-methyl cytosine; methylation; automated DNA sequencing AB Dietary methyl deficiency provides an ideal in vivo model system in which to study progressive alterations in DNA methylation patterns as they occur during multistage hepatocarcinogenesis. Weanling male F344 rats were given a semipurified diet deficient in the methyl-donors choline, methionine, and folic acid for a 36-week period with sampling intervals at 3,9,24, and 36 weeks. Using a genomic sequencing procedure based on the PCR amplification of bisulfite-modified DNA, the methylation status of individual CpG sites within exons 6 and 7 of the p53 gene in liver samples from control and deficient rats was assessed. Treatment of denatured nuclear DNA with sodium bisulfite converts unmethylated cytosine residues to uracil, which are then amplified as thymine in the PCR reaction. In contrast, methylated cytosines are resistant to bisulfite deamination under these reaction conditions and are amplified as cytosine. In this report, we describe a novel application of automated sequencing technology to estimate the proportion of methylated cytosines present at defined CpG sites within the total population of DNA molecules extracted. Using the bisulfite conversion-PCR genomic sequencing method, we demonstrate the validity of peak height analysis of co-eluting peaks in the autosequencer electropherogram to estimate the percent methylation at a defined CpG site. The sensitivity of this method is demonstrated by the progressive loss of methyl groups at a defined CpG site in the methyl-deficient rats after 9, 24, and 36 weeks. The application of this sequence-specific technology will allow site-specific definition of the methylation status of each CpG site within a coding sequence or promoter region and should provide new insights into mechanisms and consequences of methylation dysregulation as a result of dietary deprivation of methyl donors. (C) Elsevier Science Inc. 1997. C1 NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079. NR 5 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD JUN PY 1997 VL 8 IS 6 BP 355 EP 359 DI 10.1016/S0955-2863(97)00018-1 PG 5 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA XM569 UT WOS:A1997XM56900010 ER PT J AU Polli, JE Rekhi, GS Augsburger, LL Shah, VP AF Polli, JE Rekhi, GS Augsburger, LL Shah, VP TI Methods to compare dissolution profiles and a rationale for wide dissolution specifications for metoprolol tartrate tablets SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article; Proceedings Paper CT Drug-Information-Association Workshop on In Vitro Dissolution of Immediate Release (IR) Dosage Forms: Development, In Vitro Relevance and Quality Control Issues CY JUN, 1995 CL TORONTO, CANADA SP Drug Informat Assoc AB The objectives of this work were to apply several profile comparison approaches to dissolution data of four different but bioequivalent metoprolol tartrate tablet formulations to (1) identify the advantages and disadvantages of each approach, (2) quantify the metric for comparing dissolution profiles of each method, (3) determine metric limits that are consistent with the observed bioequivalence, and (4) rationalize the observed metric limits with respect to the role of dissolution in overall metoprolol absorption. Dissolution was performed by the USP monograph method on four formulations of metoprolol tartrate tablets (Lopressor plus fast, medium, and slow dissolving test formulations). Three general approaches to compare dissolution profiles were examined; they were ANOVA-based, model-independent, and model-dependent approaches, It is concluded that model-independent approaches and several model-dependent approaches yielded numerical results that can serve as objective and quantitative metrics for comparing entire dissolution profiles of the four metoprolol tartrate formulations. However, these methods presented complications. Some metrics were dependent on the length of the dissolution profile and the sampling scheme. Results from the pairwise procedures also depended on the pairing assignment of individual profiles. In spite of complications, these methods suggested wide dissolution specification limits. Wide dissolution specifications were rationalized through an analysis of in vitro-in vivo relationships, which indicated metoprolol dissolution from these formulations was not the rate-limiting step; hence, a range of dissolution profiles can be expected to yield equivalent plasma profiles. C1 US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20855. RP Polli, JE (reprint author), UNIV MARYLAND,SCH PHARM,BALTIMORE,MD 21201, USA. NR 21 TC 159 Z9 174 U1 1 U2 13 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 JUN PY 1997 VL 86 IS 6 BP 690 EP 700 DI 10.1021/js960473x PG 11 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA XC691 UT WOS:A1997XC69100007 PM 9188051 ER PT J AU Berger, V Sackrowitz, H AF Berger, V Sackrowitz, H TI Improving tests for superior treatment in contingency tables SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE ordered categorical data; stochastic order ID MANN-WHITNEY TEST; INDEPENDENCE; CANCER AB When comparing two treatments on the basis of ordinal data, a natural alternative is stochastic order. as it implies that more favorable outcomes receive greater probability. Results of Eaton can be used to provide a complete class of tests. We find that many tests in current use are not in this class and hence are inadmissible. More important, we present methods of improving such tests. Often, the increase in power is substantial although the size remains the same. C1 RUTGERS STATE UNIV,DEPT STAT,NEW BRUNSWICK,NJ 08903. RP Berger, V (reprint author), US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852, USA. NR 14 TC 13 Z9 13 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD JUN PY 1997 VL 92 IS 438 BP 700 EP 705 PG 6 WC Statistics & Probability SC Mathematics GA XE296 UT WOS:A1997XE29600035 ER PT J AU Troutman, LM Vaughn, SD Schmerfeld, G Beaulieu, AJ AF Troutman, LM Vaughn, SD Schmerfeld, G Beaulieu, AJ TI Impact of the Animal Drug Availability Act on veterinary practitioners and the animal health industry SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article C1 US FDA,CTR VET MED,ROCKVILLE,MD 20855. UNIV MARYLAND,BLACKSBURG,VA. VIRGINIA TECH,VIRGINIA MARYLAND REG COLL VET MED,BLACKSBURG,VA 24061. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD JUN 1 PY 1997 VL 210 IS 11 BP 1597 EP 1600 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA XB097 UT WOS:A1997XB09700011 PM 9170084 ER PT J AU Yamshchikov, VF Trent, DW Compans, RW AF Yamshchikov, VF Trent, DW Compans, RW TI Upregulation of signalase processing and induction of prM-E secretion by the flavivirus NS2B-NS3 protease: Roles of protease components SO JOURNAL OF VIROLOGY LA English DT Article ID YELLOW-FEVER VIRUS; NON-STRUCTURAL PROTEINS; NONSTRUCTURAL PROTEINS; IN-VITRO; PUTATIVE HELICASES; VIRAL REPLICATION; CLEAVAGE SITES; NS3; POLYPROTEIN; DOMAIN AB Recently, we have shown that the ability of the flavivirus NS2B-NS3 protease complex to promote efficient signalase processing of the C-prM precursor, as well as secretion of prM and E, does not appear to depend strictly on cleavage of the precursor at its Lys-Arg-Gly dibasic site by the protease, We suggested that the association of the protease with the precursor via NS2B may be sufficient by itself for the above effects, To study the proposed association in more detail, we have developed an assay in which processing at the C-prM dibasic cleavage site is abolished by Lys --> Gly conversion, We constructed deletion mutants and chimeras of the West Nile (WN) flavivirus NS2B protein and expressed them in the context of {5'-C --> NS3(243)} containing either wild-type C-prM or its cleavage site mutant. All NS2B variants were able to form active protease complexes, Deletion of the carboxy-terminal cluster of hydrophobic amino acids in NS2B had no apparent effect on the formation of prM and prM-E secretion for the cassettes containing either wild-type or mutated C-prM precursor, Deletion of the amino-terminal hydrophobic cluster in NS2B did not affect prM-E secretion for the cassettes with mild-type C-prM but abrogated prM(-)E secretion for the cassettes with the mutated dibasic cleavage site in C-prM, Similarly, the NS2B-NS3(178) protease of Japanese encephalitis (JE) virus, when substituted for the WN virus NS2B-NS3(243) protease, was able to promote prM-E secretion for the cassette with the wild-type C-prM precursor but not with the mutated one, Replacement of the deleted amino terminal hydrophobic cluster in the WN virus NS2B protein with an analogous JE virus sequence restored the ability of the protease to promote prM-E secretion, On the basis of these observations, roles of individual protease components in upregulation of C-prM signalase processing are discussed. C1 EMORY UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,ATLANTA,GA 30322. RP Yamshchikov, VF (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,BETHESDA,MD 20892, USA. RI Compans, Richard/I-4087-2013 OI Compans, Richard/0000-0003-2360-335X NR 37 TC 24 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 JUN PY 1997 VL 71 IS 6 BP 4364 EP 4371 PG 8 WC Virology SC Virology GA WZ571 UT WOS:A1997WZ57100022 PM 9151825 ER PT J AU Gabor, G AF Gabor, G TI The stability of nitric oxide in acid solutions SO MICROCHEMICAL JOURNAL LA English DT Article ID RELEASE; NO AB Aqueous acid solutions of nitric oxide (NO) are used as a source for this species in chemical and biological experiments. To utilize known quantities of NO, it is necessary to determine the escape rate of NO from these solutions. Escape rates at constant temperature are concentration dependent. The rate constants at 25 degrees C are 3.26 x 10(-6), 2.7 x 10(-7), and 1.44 x 10(-7) min(-1) far 0.2, 0.01, and 0.001 mol/L solutions, respectively. The escape rates are further reduced upon lowering the temperature. The half times of escape from 0.2 and 0.01 mol/L solutions are 18 and 280 min at 25 degrees C but 350 and 490 min at 0 degrees C, respectively. (C) 1997 Academic Press. RP Gabor, G (reprint author), US FDA,CTR BIOL EVALUAT & RES,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 18 TC 1 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 0026-265X J9 MICROCHEM J JI Microchem J. PD JUN PY 1997 VL 56 IS 2 BP 171 EP 176 DI 10.1006/mchj.1996.1446 PG 6 WC Chemistry, Analytical SC Chemistry GA XF818 UT WOS:A1997XF81800005 ER PT J AU Feng, P AF Feng, P TI Impact of molecular biology on the detection of foodborne pathogens SO MOLECULAR BIOTECHNOLOGY LA English DT Review DE molecular biology; antibody tests; nucleic acid probes; foods; detection; foodborne pathogens ID ACID AMPLIFICATION SYSTEM; LIGASE CHAIN-REACTION; LISTERIA-MONOCYTOGENES; BACTERIAL BIOLUMINESCENCE; ENVIRONMENTAL-SAMPLES; HYBRIDIZATION ASSAY; ICE NUCLEATION; FOOD ANALYSIS; SALMONELLA; IDENTIFICATION AB Molecular biological methods that use antibodies and nucleic acids to detect specific foodborne bacterial pathogens were scarcely known a decade and a half ago. Few scientists could have predicted that these tools of basic research would come to dominate the field of food diagnostics. Today, a large number of cleverly designed assay formats using these technologies are available commercially for the detection in foods of practically all major established pathogens and toxins, as well as of many emerging pathogens. These tests range from very simple antibody-bound latex agglutination assays to very sophisticated DNA amplification methods. Although molecular biological assays are more specific, sensitive and faster than conventional (often cultural) microbiological methods, the complexities of food matrices continue to offer unique challenges that may preclude the direct application of these molecular biological methods. Consequently, a short cultural enrichment period is still required for food samples prior to analysis with these assays. The greater detection sensitivity of molecular biological methods may also affect existing microbiological specifications for foods; this undoubtedly will have repercussions on the regulatory agencies, food manufacturers, and also consumers. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,HFS 516,WASHINGTON,DC 20204. NR 50 TC 57 Z9 59 U1 2 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD JUN PY 1997 VL 7 IS 3 BP 267 EP 278 DI 10.1007/BF02740817 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA XH573 UT WOS:A1997XH57300006 PM 9219240 ER PT J AU Wyngaarden, J Potts, J Cotter, F Martin, RR Mehta, V Eckstein, F Levin, A Weiss, B Black, L Cole, R Crooke, S Kreig, A Diasio, R AF Wyngaarden, J Potts, J Cotter, F Martin, RR Mehta, V Eckstein, F Levin, A Weiss, B Black, L Cole, R Crooke, S Kreig, A Diasio, R TI Antisense '97: A roundtable on the state of the industry SO NATURE BIOTECHNOLOGY LA English DT Editorial Material AB The following article is excerpted from the transcript of a one-hour roundtable discussion that concluded Nature Biotechnology's conference ''Antisense 97: Targeting the Molecular Basis of Disease,'' May 1-2, 1997 in Cambridge, MA. The purpose of the roundtable was to allow both speakers and conference attendees to address what they saw as the critical issues that had arisen during the two-day meeting. The transcript has been edited to address the major themes emerging from that discussion: the impact of first-generation vs. second-generation antisense drugs, the need to encourage dissemination of high-quality data, the reasons for the lack of reproducibility of certain data, whether genotoxicity should be a more closely studied issue, and what future directions may be for the field. C1 MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. INST CHILD HLTH, MOL HEMATOL UNIT, LONDON, ENGLAND. MAX PLANCK INST EXPT MED, D-37075 GOTTINGEN, GERMANY. ISIS PHARMACEUT, CARLSBAD, CA 92008 USA. ALLEGHENY UNIV HLTH SCI, PHILADELPHIA, PA 19102 USA. US FDA, CTR BIOL, ROCKVILLE, MD 20857 USA. UNIV N CAROLINA, CTR COMPREHENS CANC, CHAPEL HILL, NC USA. UNIV IOWA, DEPT INTERNAL MED, IOWA CITY, IA 52242 USA. UNIV ALABAMA, DEPT PHARMACOL, DIV CLIN PHARMACOL, BIRMINGHAM, AL 35294 USA. MRC, MOL BIOL LAB, CAMBRIDGE CB2 2QH, ENGLAND. MEHTA & ISALY, NEW YORK, NY USA. RP Wyngaarden, J (reprint author), HYBRIDON INC, CAMBRIDGE, MA USA. NR 0 TC 14 Z9 14 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUN PY 1997 VL 15 IS 6 BP 519 EP 524 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA XC772 UT WOS:A1997XC77200025 ER PT J AU Brown, ED Blakely, SR Babu, U Grundel, E Mitchell, GV AF Brown, ED Blakely, SR Babu, U Grundel, E Mitchell, GV TI Vegetable concentrates interact with canthaxanthin to affect carotenoid bioavailability and superoxide dismutase activity but not immune response in rats SO NUTRITION RESEARCH LA English DT Article DE carotenoids; canthaxanthin; tomato; spinach; interaction; bioavailability ID EXCESS VITAMIN-A; BETA-CAROTENE; LIQUID-CHROMATOGRAPHY; PLASMA; DEFICIENCY; SYSTEMS AB We examined tomato paste and dried spinach powder as dietary sources of lycopene and lutein and determined their interactions with canthaxanthin (CX) in water-soluble beadlets. Mature male rats, 10/group, were fed a basal diet containing 16% fat and 2 g per kg CX from beadlets (+CX) or placebo beadlets (-CX) for 8 weeks. Tomato paste or spinach powder was added to each of these diets at 0, 5 (low tomato, low spinach) and 15% (w/w) (high tomato, high spinach). The low and high levels of tomato paste and spinach powder contained 0.03 and 0.09 g lycopene and 0.02 and 0.06 g lutein per kg of diet, respectively. CX was detected in liver and plasma. High tomato decreased liver CX concentrations 5-fold and plasma CX 2-fold; low tomato had no effect. Liver lycopene concentrations increased as the concentration of tomato paste increased in the diet. However, feeding CX dramatically decreased liver lycopene concentrations. Feeding high tomato and no CX lowered liver superoxide dismutase activity. Neither dietary carotenoids nor CX treatment altered mitogenic response of splenic mononuclear cells to concanavalin (Con A) or lipopolysaccharide (LPS). These data from rats illustrate how a carotenoid-rich food may influence the bioavailability of a carotenoid supplement. Likewise, supplementation with a single purified carotenoid may antagonize the bioavailability of carotenoids in food matrices. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NR 28 TC 5 Z9 7 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD JUN PY 1997 VL 17 IS 6 BP 989 EP 998 DI 10.1016/S0271-5317(97)00063-8 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WW156 UT WOS:A1997WW15600006 ER PT J AU Chen, RT Glasser, JW Rhodes, PH Davis, RL Barlow, WE Thompson, RS Mullooly, JP Black, SB Shinefield, HR Vadheim, CM Marcy, SM Ward, JI Wise, RP Wassilak, SG Hadler, SC Swint, E Hardy, JR Payne, T Immanuel, V Benson, P Draket, J Drew, L Mendius, B Ray, P Lewis, N Fireman, BH Jing, J Wulfsohn, M Lugg, MM Osborne, P Rastogi, S Patriarca, P Caserta, V AF Chen, RT Glasser, JW Rhodes, PH Davis, RL Barlow, WE Thompson, RS Mullooly, JP Black, SB Shinefield, HR Vadheim, CM Marcy, SM Ward, JI Wise, RP Wassilak, SG Hadler, SC Swint, E Hardy, JR Payne, T Immanuel, V Benson, P Draket, J Drew, L Mendius, B Ray, P Lewis, N Fireman, BH Jing, J Wulfsohn, M Lugg, MM Osborne, P Rastogi, S Patriarca, P Caserta, V TI Vaccine Safety Datalink project: A new tool for improving vaccine safety monitoring in the United States SO PEDIATRICS LA English DT Article DE vaccines; immunization; adverse reactions; databases; record linkage; vaccine safety ID DIPHTHERIA-TETANUS-PERTUSSIS; INFANT DEATH SYNDROME; WHOOPING-COUGH; IMMUNIZATION; RISK; SYSTEM; EVENTS AB Objective. To fill the large ''gaps and limitations'' in current scientific knowledge of rare vaccine adverse events identified in recent reviews of the Institute of Medicine. Methods. Computerized information on immunization, medical outcomes, and potential confounders on more than 500 000 children 0 to 6 years of age is linked annually at several health maintenance organizations to create a large cohort for multiple epidemiologic studies of vaccine safety. Results. Analysis of 3 years of follow-up data shows that 549 488 doses of diphtheria-tetanus-pertussis (DTP) and 310 618 doses of measles-mumps-rubella (MMR) vaccines have been administered to children in the study cohort. Analyses for associations between vaccines and 34 medical outcomes are underway. Screening of automated data shows that seizures are associated with receipt of DTP on the same day (relative risk [RR], 2.1; 95% confidence interval [CI], 1.1 to 4.0) and 8 to 14 days after receipt of MMR (RR 3.0; 95% CI, 2.1 to 4.2). The diversity of vaccination exposures in this large cohort permits us to show that an apparent association of seizures 8 to 14 days after Haemophilus influenzae type b vaccine (RR, 1.6; 95% CI, 1.2 to 2.1) was attributable to confounding by simultaneous MMR vaccination; the association disappears with appropriate adjustment (RR, 1.0; 95% CI, 0.7 to 1.4). Conclusion. Preliminary design, data collection, and analytic capability of the Vaccine Safety Datalink project has been validated by replication of previous known associations between seizures and DTP and MMR vaccines. The diversity in vaccine administration schedules permits potential disentangling of effects of simultaneous and combined vaccinations. The project provides a model of public health-managed care collaborations in addition to an excellent infrastructure for safety and other studies of vaccines. C1 GRP HLTH COOPERAT PUGET SOUND,CTR HLTH STUDIES,SEATTLE,WA 98101. NW KAISER PERMANENTE,CTR HLTH RES,PORTLAND,OR. NO CALIF KAISER PERMANENTE,PEDIAT VACCINE STUDY CTR,OAKLAND,CA. HARBOR UCLA MED CTR,CTR VACCINE RES,TORRANCE,CA 90509. SO CALIF KAISER PERMANENTE,PASADENA,CA. US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20857. US HLTH RESOURCES & SERV ADM,DIV VACCINE INJURY COMPENSAT,ROCKVILLE,MD 20857. RP Chen, RT (reprint author), CTR DIS CONTROL & PREVENT,NATL IMMUNIZAT PROGRAM,MS-E61,ATLANTA,GA 30333, USA. NR 45 TC 206 Z9 210 U1 0 U2 10 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUN PY 1997 VL 99 IS 6 BP 765 EP 773 DI 10.1542/peds.99.6.765 PG 9 WC Pediatrics SC Pediatrics GA XC588 UT WOS:A1997XC58800014 PM 9164767 ER PT J AU Kessler, DA Wilkenfeld, JP Thompson, LJ AF Kessler, DA Wilkenfeld, JP Thompson, LJ TI The Food and Drug Administration's rule on tobacco: Blending science and law SO PEDIATRICS LA English DT Editorial Material ID CIGARETTE-SMOKING; PREVALENCE; CHILDREN; SMOKERS; RECOGNITION; ADOLESCENTS; DEPENDENCE; INDUSTRY; BEHAVIOR C1 US FDA,FOOD & DRUGS,OFF COMMISS,OFF PUBL AFFAIRS,ROCKVILLE,MD 20857. NR 54 TC 4 Z9 4 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUN PY 1997 VL 99 IS 6 BP 884 EP 887 DI 10.1542/peds.99.6.884 PG 4 WC Pediatrics SC Pediatrics GA XC588 UT WOS:A1997XC58800034 PM 9164785 ER PT J AU Scariati, PD GrummerStrawn, LM Fein, SB AF Scariati, PD GrummerStrawn, LM Fein, SB TI A longitudinal analysis of infant morbidity and the extent of breastfeeding in the United States SO PEDIATRICS LA English DT Article DE longitudinal analysis; diarrhea; ear infection; breastfeeding ID ARTIFICIALLY FED INFANTS; OTITIS-MEDIA; DEVELOPING-COUNTRIES; FEEDING PRACTICES; BREAST; PROTECTS; ILLNESS; HEALTH; GASTROENTERITIS; INFECTIONS AB Background. Studies on the health benefits of breastfeeding in developed countries have shown conflicting results. These studies often fail to account for confounding, reverse causality, and dose-response effects. We addressed these issues in analyzing longitudinal data to determine if breastfeeding protects US infants from developing diarrhea and ear infections. Methods. Mothers participating in a mail panel provided information on their infants at ages 2, 3, 4, 5, 6, and 7 months. Infants were classified as exclusively breastfed; high, middle, or low mixed breast- and formula-fed; or exclusively formula-fed. Diarrhea and ear infection diagnoses were based on mothers' reports. Infant age and gender; other liquid and solid intake; maternal education, occupation, and smoking; household size; family income; and day care use were adjusted for in the full models. Results. The risk of developing either diarrhea or ear infection increased as the amount of breast milk an infant received decreased. In the full models, the risk for diarrhea remained significant only in infants who received no breast milk compared with those who received only breast milk (odds ratio = 1.8); the risk for ear infection remained significant in the low mixed feeding group (odds ratio = 1.6) and among infants receiving no breast milk compared with those who received only breast milk (odds ratio = 1.7). Conclusions. Breastfeeding protects US infants against the development of diarrhea and ear infection. Breastfeeding does not have to be exclusive to confer this benefit. In fact, protection is afforded in a dose-response manner. The more breast milk an infant receives in the first 6 months of life, the less likely that he or she will develop diarrhea or ear infection. C1 CTR DIS CONTROL & PREVENT, EPIDEM INTELLIGENCE SERV, EPIDEMIOL PROGRAM OFF, ATLANTA, GA 30341 USA. US FDA, OFF SCI ANAL & SUPPORT, CTR FOOD SAFETY & APPL NUTR, WASHINGTON, DC 20204 USA. RP Scariati, PD (reprint author), CTR DIS CONTROL & PREVENT, DIV NUTR & PHYS ACT, NATL CTR CHRON DIS PREVENT & HLTH PROMOT, ATLANTA, GA 30341 USA. NR 35 TC 87 Z9 91 U1 0 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUN PY 1997 VL 99 IS 6 BP art. no. EP e5 DI 10.1542/peds.99.6.e5 PG 5 WC Pediatrics SC Pediatrics GA XC588 UT WOS:A1997XC58800005 PM 9164801 ER PT J AU Beer, JZ Zmudzka, BZ AF Beer, JZ Zmudzka, BZ TI UVB and PUVA therapies in HIV patients: are they safe? SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Article; Proceedings Paper CT Photomedicine Workshop at the Annual Meeting of the Photomedicine-Society CY MAR 20, 1997 CL SAN FRANCISCO, CA SP Photomed Soc DE UVB therapy; PUVA therapy; HIV ID PHOTOTHERAPY RP Beer, JZ (reprint author), US FDA,HFZ114,ROCKVILLE,MD 20857, USA. NR 11 TC 4 Z9 4 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0905-4383 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD JUN PY 1997 VL 13 IS 3 BP 91 EP 92 PG 2 WC Dermatology SC Dermatology GA YB849 UT WOS:A1997YB84900009 PM 9372524 ER PT J AU Tao, SH Bolger, PM AF Tao, SH Bolger, PM TI Hazard assessment of germanium supplements SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID CARBOXYETHYLGERMANIUM SESQUIOXIDE; INDUCED NEPHROPATHY; ORGANIC GERMANIUM; DIOXIDE; NEPHROTOXICITY; RATS; MYOPATHY; GE-132; HUMANS AB Germanium-containing dietary supplements became popular in the 1970s in Japan and later in other countries, as elixirs for certain diseases (e.g., cancer and AIDS). Germanium is not an essential element. Its acute toxicity is low. However, at least 31 reported human cases linked prolonged intake of germanium products with renal failure and even death. Signs of kidney dysfunction, kidney tubular degeneration, and germanium accumulation were observed. Other adverse effects were anemia, muscle weakness, and peripheral neuropathy. Recovery of renal function is slow and incomplete even long after germanium intake was stopped. The total dose of ingested germanium (as dioxide, carboxyethyl germanium sesquioxide, germanium-lactate-citrate, or unspecified forms) varied from 15 to over 300 g; the exposure duration varied from 2 to 36 months. In laboratory animals, elevated germanium in tissues and impaired kidney and liver function were observed in a life-time drinking water (5 ppm germanium) study. Other toxicities associated with ingested germanium products in human cases were also demonstrated in animal studies with germanium dioxide and sometimes other germanium compounds. Based on the evidence of persistent renal toxicity associated with germanium dioxide, the lack of conclusive findings of differential nephrotoxicity of organic germanium compounds, and the possibility of contamination of the organic germanium products with inorganic germanium, it is clear that germanium products present a potential human health hazard. (C) 1997 Academic Press. RP Tao, SH (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204, USA. NR 63 TC 47 Z9 52 U1 2 U2 11 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 JUN PY 1997 VL 25 IS 3 BP 211 EP 219 DI 10.1006/rtph.1997.1098 PG 9 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA XL383 UT WOS:A1997XL38300005 PM 9237323 ER PT J AU Valentine, CR Heflich, RH AF Valentine, CR Heflich, RH TI The association of nonsense mutation with exon-skipping in hprt mRNA of Chinese hamster ovary cells results from an artifact of RT-PCR SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE mRNA abundance; quantitative RT-PCR; relative enrichment ID NUCLEAR MESSENGER-RNA; CDNA RECOMBINANTS; SEQUENCE-ANALYSIS; DNA-SEQUENCE; GENE; MUTANTS; EXPRESSION; SELECTION; REPEATS; CODONS AB RT-PCR of RNA from CHO cells with nonsense mutations in the hprt gene frequently detects minor hprt mRNA species lacking one or more exons. Many nonsense mutants also contain greatly reduced concentrations of the major, normally spliced hprt mRNA. In this study, we examined the hypothesis that exon-deleted mRNAs are normal constituents of CHO cells, but are not detected in wild-type parental cells and most missense mutants because their amplification is suppressed by relatively high concentrations of normally spliced hprt mRNA. A protocol designed to specifically detect exon-deleted mRNAs was conducted using RNA from parental cells and identified all the exon-deleted species typical of nonsense mutants. Quantitative analysis of parental cell RNA measured these exon-deleted mRNAs at less than or equal to 0.7% of the abundance of the full-sized species. Nonsense and missense mutants had comparable amounts of exon-deleted mRNAs, which varied both above and below parental concentrations. The relative concentrations of particular exon-deleted species could be explained by the location of nonsense mutations remaining in the mRNA or by structural effects of mutations on splicing. Exon-deleted mRNAs were detected by RT-PCR when the concentration of the most abundant exon-deleted species was greater than or equal to 2% of the full-length mRNA. This occurred for mutants with nonsense mutations in internal exons. RT-PCR conditions were shown to suppress the amplification of exon-deleted species 40-fold when full-length mRNA was abundant, which occurred for parental lines and missense mutants. Our results verify that RT-PCR conditions can produce an artifactual association between nonsense mutation and exon-skipping when minor, exon-deleted mRNA is relatively enriched. RP Valentine, CR (reprint author), NATL CTR TOXICOL RES, DIV GENET TOXICOL, HFT-120, 3900 NCTR RD, JEFFERSON, AR 72079 USA. NR 34 TC 24 Z9 24 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD JUN PY 1997 VL 3 IS 6 BP 660 EP 676 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XB208 UT WOS:A1997XB20800011 PM 9174100 ER PT J AU Luecke, RH Wosilait, WD Young, JF AF Luecke, RH Wosilait, WD Young, JF TI Mathematical analysis for teratogenic sensitivity SO TERATOLOGY LA English DT Article ID HYDROXYUREA; PHARMACOKINETICS; MODEL; RATS AB A mathematical structure is described for determining teratogenic sensitivity or susceptibility from analysis of malformation incidence, dose-response, and pharmacokinetic data obtained during pregnancy as a result of exposure to a teratogenic agent. From the dosage or exposure of laboratory animals, embryonic and maternal concentrations of the xenobiotic are calculated using a physiologically based pharmacokinetic (PBPK) model. Malformations observed in the progeny ave linked to the PBPK-derived target tissue concentrations with a model for the sensitivity calculated as a function of the embryonic age. The PBPK model for internal disposition of chemicals during pregnancy was developed previously. This report focuses on the development of the mathematical relations for the sensitivity of the embryo and effect functions on different organs. The concentrations of a xenobiotic calculated for the site of action or target tissue(s) in the embryo are weighted using both a nonlinear dose-response curve and a sensitivity distribution function that depends on the age or stage of development of the embryo. This weighted ''exposure'' of the target tissue is regressed with the number of observed malformations to quantify the parameters of the model. This approach lends itself to integration of diverse sources of experimental data, with hydroxyurea data taken from several sources in the literature as an example. This sensitivity function obtained from laboratory animal data serves as a vehicle for prediction and extrapolation to human pregnancy for the teratogenic potential of a substance. (C) 1997 Wiley-Liss, Inc. C1 NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,JEFFERSON,AR 72079. UNIV MISSOURI,DEPT CHEM ENGN,COLUMBIA,MO 65211. UNIV MISSOURI,SCH MED,DEPT PHARMACOL,COLUMBIA,MO 65212. NR 14 TC 11 Z9 11 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0040-3709 J9 TERATOLOGY JI Teratology PD JUN PY 1997 VL 55 IS 6 BP 373 EP 380 PG 8 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA XV118 UT WOS:A1997XV11800003 PM 9294882 ER PT J AU Smith, HA Goldenthal, KL Vogel, FR Rabinovich, R Aguado, T AF Smith, HA Goldenthal, KL Vogel, FR Rabinovich, R Aguado, T TI Workshop on the control and standardization of nucleic acid vaccines - 8 February 1996, Natcher Conference Center, Bethesda, MD SO VACCINE LA English DT Editorial Material C1 NIAID,NIH,BETHESDA,MD 20892. WHO,GLOBAL PROGRAMME VACCINES & IMMUNIZAT,CH-1211 GENEVA 27,SWITZERLAND. RP Smith, HA (reprint author), US FDA,CTR BIOL EVALUAT & RES,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 2 TC 6 Z9 7 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 JUN PY 1997 VL 15 IS 8 BP 931 EP 933 PG 3 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XJ336 UT WOS:A1997XJ33600040 PM 9340950 ER PT J AU Paige, JC Tollefson, L Miller, M AF Paige, JC Tollefson, L Miller, M TI Public health impact on drug residues in animal tissues SO VETERINARY AND HUMAN TOXICOLOGY LA English DT Article ID INTESTINAL MICROFLORA; RISK AB Consumers have expressed concern regarding the health impact of drug residues in their food. Animal residues in animal tissues above the legal tolerance clearly have an impact on human health. Tolerances represent the maximal level or concentration of antimicrobial residues permitted in animal tissues at the time of slaughter. The tolerances are intended to ensure that residual drugs will have no harmful effects if ingested. This paper describes the existing evidence for specific health hazards for certain pharmacological classes of drugs and explains the risks associated with drug residues in meat and poultry above the established tolerance. The primary focus is on possible public health consequences that may occur as a result of acute exposure to illegal residues. In addition, long-term effects are discussed with added comments about the effect of residues on the intestinal flora. Most residues of veterinary drugs occur in food at such low levels that they rarely pose a chronic or long-term health hazard to consumers. The importance of food safety through the reduction of residues in our food supply cannot be overemphasized. Food safety remains a major challenge confronting contemporary society. C1 US FDA,CTR VET MED,DIV SURVEILLANCE & COMPLIANCE,ROCKVILLE,MD 20855. US FDA,CTR VET MED,HUMAN FOOD & CONSULTAT SERV,ROCKVILLE,MD 20855. RP Paige, JC (reprint author), US FDA,CTR VET MED,DIV EPIDEMIOL & SURVEILLANCE,7500 STANDISH PL,ROCKVILLE,MD 20855, USA. NR 21 TC 43 Z9 45 U1 0 U2 5 PU COMPARATIVE TOXICOLOGY LAB PI MANHATTAN PA KANSAS STATE UNIV, MANHATTAN, KS 66506-5606 SN 0145-6296 J9 VET HUM TOXICOL JI Vet. Human Toxicol. PD JUN PY 1997 VL 39 IS 3 BP 162 EP 169 PG 8 WC Toxicology; Veterinary Sciences SC Toxicology; Veterinary Sciences GA WZ705 UT WOS:A1997WZ70500008 PM 9167248 ER PT J AU Kirken, RA Malabarba, MG Xu, J Liu, XW Farrar, WL Hennighausen, L Larner, AC Grimley, PM Rui, H AF Kirken, RA Malabarba, MG Xu, J Liu, XW Farrar, WL Hennighausen, L Larner, AC Grimley, PM Rui, H TI Prolactin stimulates serine/tyrosine phosphorylation and formation of heterocomplexes of multiple Stat5 isoforms in Nb2 lymphocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR; TYROSINE PHOSPHORYLATION; SERINE PHOSPHORYLATION; GENE-EXPRESSION; HUMAN MONOCYTES; RECEPTOR; ACTIVATION; PROTEIN; KINASE; BINDING AB Transcription factors of the Stat gene family are selectively activated by many hormones and cytokines. Stat5 originally was cloned as a prolactin-stimulated DNA-binding protein, but is also activated by non-lactogenic cytokines in many cell types. The recent identification of two distinct Stat5 genes, which encode a 94-kDa Stat5a and a 92-kDa Stat5b as well as several lower molecular weight isoforms, suggests additional complexity and combinatorial possibilities for transcriptional regulation. We now report a biochemical analysis of prolactin activation of Stat proteins in Nb2 lymphocytes, which was associated with: 1) rapid tyrosine phosphorylation of Stat5a, Stat5b, a COOH-terminally truncated 80-kDa Stat5 form, Stat1 alpha, and Stat3; 2) rapid and selective formation of Stat5a/b heterodimers, without involvement of Stat1 alpha or Stat3; 3) marked serine, but not threonine phosphorylation of Stat5a and Stat5b; and 4) the appearance of two qualitatively distinct Stat5 protein complexes, which discriminated between oligonucleotides corresponding to the prolactin response elements of the beta-casein and interferon regulatory factor-1 gene promoters. Collectively, our analyses showed that Stat5a and Stat5b respond similarly to prolactin receptor activation, but also suggested that the two genes have evolved unique properties that may contribute to the specificity of receptors that utilize Stat5 signaling proteins. C1 UNIFORMED SERV UNIV HLTH SCI,SCH MED,DEPT PATHOL,BETHESDA,MD 20814. SCI APPLICAT INT CORP,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,MOL IMMUNOREGULAT LAB,FREDERICK,MD 21702. NIDDK,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20814. RI Malabarba, Maria Grazia/L-4805-2015 OI Malabarba, Maria Grazia/0000-0002-9457-2047 NR 44 TC 70 Z9 70 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 30 PY 1997 VL 272 IS 22 BP 14098 EP 14103 DI 10.1074/jbc.272.22.14098 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XB492 UT WOS:A1997XB49200022 PM 9162035 ER PT J AU Venable, RM Bizik, F Henderson, TJ Egan, W AF Venable, RM Bizik, F Henderson, TJ Egan, W TI Molecular dynamics simulations of an alpha-(2->8)-linked sialic acid tetramer in vacuum and solvent SO JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM LA English DT Article; Proceedings Paper CT Symposium of the American-Chemical-Society on Carbohydrate Modeling CY MAR, 1995 CL ANAHEIM, CA SP Amer Chem Soc DE alpha-(2->8)-linked sialic acid tetramer; molecular dynamics simulations; solvent; vacuum ID MENINGITIDIS SEROGROUP-B; CELL-ADHESION MOLECULE; NEISSERIA-MENINGITIDIS; NMR-SPECTROSCOPY; POLYSIALIC ACID; POLYSACCHARIDE; EPITOPE; OLIGOSACCHARIDES; TRANSITION; BINDING AB Molecular dynamics (MD) simulations of an alpha-(2 --> 8)-linked tetramer of sialic acid (N-acetyl neuraminic acid) were carried out in vacuum and in solvent (water), spanning 4 ns and 530 ps respectively. Protonated and deprotonated forms of the carboxylic acid groups of sialic acid were modeled in the vacuum-based simulations; only the deprotonated form was studied in the water-based simulations. Nuclear magnetic resonance (NMR) coupling constants and nuclear Overhauser effect (NOE) enhancements were calculated from the MD trajectories for the middle linkages of the tetramer and compared with experimental data for the polymer. A good agreement was not obtained between the experimental NMR data for the polymer and the NMR data extracted from the calculations on the tetramer. The question of whether the lack of agreement between experiment and simulation was due to the limited sampling of states during the MD simulations was addressed by means of Poisson simulations; these simulations indicated that it was unlikely that the disagreement was due to a sampling problem. (C) 1997 Elsevier Science B.V. C1 US FDA, BIOPHYS LAB, CTR BIOL EVALUAT & RES, ROCKVILLE, MD 20852 USA. NR 31 TC 2 Z9 2 U1 1 U2 1 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 MAY 26 PY 1997 VL 395 BP 375 EP 388 DI 10.1016/S0166-1280(96)04865-8 PG 14 WC Chemistry, Physical SC Chemistry GA XK396 UT WOS:A1997XK39600026 ER PT J AU Mikhailova, MV Littlefield, NA Hass, BS Poirier, LA Chou, MW AF Mikhailova, MV Littlefield, NA Hass, BS Poirier, LA Chou, MW TI Cadmium-induced 8-hydroxydeoxyguanosine formation, DNA strand breaks and antioxidant enzyme activities in lymphoblastoid cells SO CANCER LETTERS LA English DT Article DE oxidative DNA damage; DNA strand breaks; 8-hydroxy-2'-deoxyguanosine; cadmium ions; antioxidant enzymes ID ASCORBIC-ACID; DAMAGE; RADIATION; IRON; CARCINOGENS; RADICALS; PROTECTS AB The effect of cadmium ion (Cd) and ascorbic acid (Asc) on the induction of oxidative DNA damage and on the activities of antioxidant enzymes were investigated in human lymphoblastoid cells (AHH-1 TK+/-). Cd at low concentrations of 5-35 mu M induced the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and caused nuclear DNA strand breaks. The formation both of 8-OHdG and of DNA strand breaks was dose-dependent at the low Cd concentration; both parameters were linearly correlated with each other (R = 0.932 and P = 0.0209). 8-OHdG formation by Cd plateaued at a Cd concentration of 50 mu M. Asc also induced 8-OHdG formation, but it had no synergistic effect with Cd on the formation of 8-OHdG or DNA strand breaks. Cd at the concentration of 50 mu M induced the nuclear activity of the antioxidant enzymes, catalase and superoxide dismutase (SOD). Furthermore, Cd caused a decrease in the concentration of reduced glutathione (GSH) and an increase in concentration of the oxidized form (GSSG). While Asc had no observable effect on SOD activity, it did increase nuclear catalase activity in cells. This effect on catalase was synergistic with that of Cd. The linear correlation between 8-OHdG and DNA strand breaks induced by Cd at the lower Cd concentrations (less than or equal to 50 mu M), suggested that the extent of formation of DNA strand breaks induced by Cd may be offset by their induction of the formation of 8-OHdG and antioxidant enzyme activities. (C) 1997 Elsevier Science Ireland Ltd. C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 29 TC 75 Z9 83 U1 1 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD MAY 19 PY 1997 VL 115 IS 2 BP 141 EP 148 DI 10.1016/S0304-3835(97)04720-4 PG 8 WC Oncology SC Oncology GA WW332 UT WOS:A1997WW33200003 PM 9149117 ER PT J AU Brinkmann, U Webber, K DiCarlo, A Beers, R Chowdhury, P Chang, K Chaudhary, V Gallo, M Pastan, I AF Brinkmann, U Webber, K DiCarlo, A Beers, R Chowdhury, P Chang, K Chaudhary, V Gallo, M Pastan, I TI Cloning and expression of the recombinant FAb fragment of monoclonal antibody K1 that reacts with mesothelin present on mesotheliomas and ovarian cancers SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID SINGLE-CHAIN IMMUNOTOXINS; ESCHERICHIA-COLI; ANTIGEN CAK1; CELL-LINE; RENATURATION; CARCINOMA; PROTEINS; ANALOG; GENES; B3 AB The monoclonal antibody (MAb) KI recognizes an approximate 40 kDa glycoprotein, mesothelin, that is present on the surface of human mesothelial cells, mesotheliomas and ovarian cancers, We have cloned the cDNAs encoding the variable regions of MAb KI and constructed plasmids for expression of recombinant KI(FAb), Recombinant FAb was produced in Escherichia coli in inclusion bodies that were solubilized and refolded to active protein, Binding of KI MAb and FAb was compared by radioactive binding and competition assays and by surface plasmon resonance (BIAcore), Recombinant KI(FAb) binds to cells expressing KI-antigen with a similar affinity as papain derived FAb from KI(IgG) and with a 4- to 10-fold reduced affinity compared with bivalent IgG, The cloned FAb can be used to make higher affinity antibodies and immunoconjugates that could be useful for various types of immunotherapies. (C) 1997 Wiley-Liss, Inc. C1 NCI,MOL BIOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. US FDA,ROCKVILLE,MD 20857. UNIV DELHI,DEPT BIOCHEM,NEW DELHI,INDIA. NR 26 TC 12 Z9 12 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 16 PY 1997 VL 71 IS 4 BP 638 EP 644 PG 7 WC Oncology SC Oncology GA XB625 UT WOS:A1997XB62500021 PM 9178820 ER PT J AU Sagawa, K Swaim, W Zhang, J Unsworth, E Siraganian, RP AF Sagawa, K Swaim, W Zhang, J Unsworth, E Siraganian, RP TI Aggregation of the high affinity IgE receptor results in the tyrosine phosphorylation of the surface adhesion protein PECAM-1 (CD31) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; CYTOPLASMIC DOMAIN; SIGNAL-TRANSDUCTION; MONOCLONAL-ANTIBODIES; MAST-CELLS; IN-VIVO; MOLECULE-1 PECAM-1; HISTAMINE-RELEASE; KINASE P72(SYK); BINDING AB One of the earliest events after aggregation of the high affinity receptor for IgE (Fc epsilon RI) on mast cells is the activation of protein tyrosine kinases resulting in tyrosine phosphorylation of numerous proteins, Using a monoclonal antibody raised against the rat basophilic leukemia RBL-2H3 cells, we identified that platelet/endothelial cell adhesion molecule 1 (PECAM-1 or CD31) was tyrosine phosphorylated in these cells, Aggregation of PECAM-1 did not induce a detectable increase in its tyrosine phosphorylation, nor did it result in degranulation, However, the minimal tyrosine phosphorylation of PECAM-1 in nonstimulated cells was dramatically increased after Fc epsilon RI aggregation, This receptor-induced tyrosine phosphorylation of PECAM-1 was an early event, independent of Ca2+ influx or of the activation of protein kinase C and of cell adhesion, PECAM-1 is an adhesion molecule that is required for the transmigration of leukocytes across the endothelium into sites of inflammation, Therefore tyrosine phosphorylation of PECAM-1 may modulate its interaction with other molecules, thereby regulating the migration of basophils into inflammatory sites. C1 NIDR,IMMUNOL LAB,NIH,BETHESDA,MD 20892. US FDA,FACIL BIOTECHNOL RESOURCES,BETHESDA,MD 20892. NR 53 TC 43 Z9 43 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 MAY 16 PY 1997 VL 272 IS 20 BP 13412 EP 13418 DI 10.1074/jbc.272.20.13412 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ384 UT WOS:A1997WZ38400078 PM 9148965 ER PT J AU Corti, MC Guralnik, JM Salive, ME Harris, T Ferrucci, L Glynn, RJ Havlik, RJ AF Corti, MC Guralnik, JM Salive, ME Harris, T Ferrucci, L Glynn, RJ Havlik, RJ TI Clarifying the direct relation between total cholesterol levels and death from coronary heart disease in older persons SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CARDIOVASCULAR HEALTH; FOLLOW-UP; MORTALITY; RISK; PEOPLE; HYPERCHOLESTEROLEMIA; HYPOCHOLESTEROLEMIA; ASSOCIATION; MODELS; ADULTS AB Background: The importance of total cholesterol level as a risk factor for coronary heart disease in older adults is controversial. Objective: To determine whether findings showing that total cholesterol level is not an important risk factor for coronary heart disease in older adults are the result of inadequate adjustment for co-occurring diseases and frailty. Design: Multicenter, longitudinal study with 5-year follow-up for death. Participants: 4066 men and women from East Boston, Massachusetts; Iowa and Washington counties, Iowa; and New Haven, Connecticut. Measurements: In 1988, participants were interviewed about their health status and had blood samples taken. Mortality follow-up was through 1992. Results: In analyses that included all fatal coronary heart disease events (252 deaths) and did not adjust for risk factors for coronary heart disease and measures of frailty, persons with the lowest total cholesterol levels (less than or equal to 4.15 mmol/L [less than or equal to 160 mg/dL]) had the highest rate of death from coronary heart disease, whereas those with elevated total cholesterol levels (greater than or equal to 6.20 mmol/L [greater than or equal to 240 mg/dL]) seemed to have a lower risk for death from coronary heart disease (P for trend = 0.04). After adjustment for established risk factors for coronary heart disease and markers of poor health (including chronic conditions, low serum iron and albumin levels) and exclusion of 44 deaths from coronary heart disease that occurred within the first year, elevated total cholesterol levels predicted increased risk for death from coronary heart disease, and the risk for death from coronary heart disease decreased as cholesterol levels decreased (P for trend = 0.005). Conclusions: Elevated total cholesterol level is a risk factor for death from coronary heart disease in older adults, and the apparent adverse effects associated with low cholesterol levels are secondary to comorbidity and frailty. This suggests that excluding older persons from cholesterol screening is inappropriate, but interpretation of screening results in older persons requires clinical judgment. Results from controlled clinical trials are needed to clarify this issue. C1 US FDA, EPIDEMIOL BRANCH, CTR BIOL EVALUAT & RES, ROCKVILLE, MD 20852 USA. BRIGHAM & WOMENS HOSP, DEPT MED, DIV PREVENT MED, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. NATL INST RES & CARE ELDERLY, FIESOLE, ITALY. RP NIA, EPIDEMIOL DEMOG & BIOMETRY PROGRAM,NIH, 7201 WISCONSIN AVE,GATEWAY BLDG, ROOM 3C-309, BETHESDA, MD 20892 USA. FU NIA NIH HHS [N01-AG-02105, N01-AG-02106, N01-AG-02107] NR 38 TC 152 Z9 154 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 15 PY 1997 VL 126 IS 10 BP 753 EP + PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WZ823 UT WOS:A1997WZ82300003 PM 9148647 ER PT J AU Hendry, WJ Zheng, XL Leavitt, WW Branham, WS Sheehan, DM AF Hendry, WJ Zheng, XL Leavitt, WW Branham, WS Sheehan, DM TI Endometrial hyperplasia and apoptosis following neonatal diethylstilbestrol exposure and subsequent estrogen stimulation in both host and transplanted hamster uteri SO CANCER RESEARCH LA English DT Article ID PROGRAMMED CELL-DEATH; EPIDERMAL GROWTH-FACTOR; FREE CULTURE CONDITIONS; LUMINAL EPITHELIUM; BREAST-CANCER; FACTOR-ALPHA; MOUSE; PROLIFERATION; SERUM; RESPONSIVENESS AB Prenatal exposure to the synthetic estrogen diethylstilbestrol (DES) causes morphogenetic alterations and neoplasia in the human reproductive tract, In the hamster, neonatal DES exposure alters early uterine morphogenesis and induces endometrial adenocarcinomas in adults, We now demonstrate that the preneoplastic stages of this phenomenon in the hamster reflect an abnormal uterotropic response to estrogen that is characterized by hyperplastic lesions in the endometrial epithelium and includes an immune and/or inflammatory component, Interestingly, biochemical and in situ analysis revealed that the hyperplastic epithelium is also an active site of cell death by apoptosis, To further probe the mechanism of this phenomenon, uteri from 7-day-old control or DES-exposed donors were transplanted into the cheek pouches of control or neonatally DES-exposed adult hosts, and both host groups were treated to provide high circulating levels of estradiol, Among the four ectopic scenarios, histopathological lesions (epithelial hyperplasia, dysplasia, and apoptosis), segregated almost exclusively to the two that consisted of neonatally DES-exposed uteri, The virtual absence of lesions in control uteri transplanted to DES hosts eliminated host systemic factors as causative agents, Therefore, me conclude that DES or its metabolites alter the cellular physiology and/or composition of the developing uterus (initiating event) in such a way that it thereafter responds abnormally to estrogenic stimulation (promoting event), These observations serve to further define a unique experimental system for probing: (a) various aspects of the clinical ''DES Syndrome''; (b) how estrogen regulates normal uterine growth and morphogenesis; and (c) how this process can degenerate to the unregulated neoplastic state. C1 US FDA,NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079. RP Hendry, WJ (reprint author), WICHITA STATE UNIV,DEPT BIOL SCI,1845 FAIRMOUNT,WICHITA,KS 67260, USA. FU NCI NIH HHS [CA60250]; NICHD NIH HHS [HD 28074] NR 38 TC 25 Z9 25 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 1997 VL 57 IS 10 BP 1903 EP 1908 PG 6 WC Oncology SC Oncology GA WZ216 UT WOS:A1997WZ21600017 PM 9157983 ER PT J AU Beland, FA Melchior, WB Mourato, LLG Santos, MA Marques, MM AF Beland, FA Melchior, WB Mourato, LLG Santos, MA Marques, MM TI Arylamine-DNA adduct conformation in relation to mutagenesis SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 6th International Conference on Carcinogenic and Mutagenic N-Substituted Aryl Compounds CY NOV 04-08, 1995 CL MONTEREY, CA SP Flavor & Extract Manufacturers Assoc US, Int Flavors & Fragrances Inc, Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, US FDA, Natl Ctr Toxicol Res, NCI, NIEHS, Nestle S A, Toronto Res Chem Inc DE DNA adduct; methylaniline; ethylaniline; nuclear magnetic resonance; arylamine; N-hydroxy arylamine; N-acyloxy arylamine; conformation; mutagenesis ID 2 INTERCHANGEABLE CONFORMATIONS; PURINE NUCLEOSIDES; RAS PROTOONCOGENE; AROMATIC-AMINES; STRUCTURAL CHARACTERIZATION; SALMONELLA-TYPHIMURIUM; ENERGY MINIMIZATION; CIGARETTE-SMOKE; BLADDER-CANCER; NMR AB A considerable body of evidence has indicated that local conformational alterations induced by DNA adducts may provide the molecular basis for differences in mutational specificities exhibited by structurally similar adducts. To elucidate the relationships between adduct structure and mutation induction, the ability of several single-ring arylamines present in tobacco smoke (i.e., methylanilines, dimethylanilines, and ethylanilines) to form DNA adducts was investigated. In all cases, the major adducts were C8-substituted deoxyguanosine derivatives, which is consistent with what has been observed with more carcinogenic arylamines, such as 2-aminofluorene and 4-aminobiphenyl. Spectroscopic and theoretical data on the adducts indicated conformational differences depending upon the location of the alkyl substituents. Adducts containing alkyl groups ortho to the amine function (e.g., 2-methylaniline) had a greater percentage of syn conformers about the glycosyl bond than those not bearing such groups. Arylamines with ortho alkyl substituents tend to be more mutagenic and tumorigenic than analogues not containing an ortho alkyl substituent. This increase in biological activity may be due in part to the greater propensity of ortho alkylated adducts to adopt a syn conformation. C1 Univ Tecn Lisboa, CTR QUIM ESTRUTURAL, INST SUPER TECN, P-1096 LISBON, PORTUGAL. RP Beland, FA (reprint author), NATL CTR TOXICOL RES, DIV BIOCHEM TOXICOL, HFT-110, JEFFERSON, AR 72079 USA. RI Santos, M. Amelia /H-9409-2012; Marques, M. Matilde/E-2535-2012; Goncalves, Luisa/A-4120-2016; OI Santos, M. Amelia /0000-0002-4069-9368; Marques, M. Matilde/0000-0002-7526-4962; Goncalves, Luisa/0000-0002-3654-8612; Goncalves, Luisa/0000-0002-2385-7395 NR 36 TC 16 Z9 19 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 MAY 12 PY 1997 VL 376 IS 1-2 BP 13 EP 19 DI 10.1016/S0027-5107(97)00020-1 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA XE489 UT WOS:A1997XE48900004 PM 9202733 ER PT J AU Chae, YH Upadhyaya, P Ji, BY Fu, PP ElBayoumy, K AF Chae, YH Upadhyaya, P Ji, BY Fu, PP ElBayoumy, K TI Comparative metabolism and DNA binding of 1-, 2-, and 4-nitropyrene in rats SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 6th International Conference on Carcinogenic and Mutagenic N-Substituted Aryl Compounds CY NOV 04-08, 1995 CL MONTEREY, CA SP Flavor & Extract Manufacturers Assoc US, Int Flavors & Fragrances Inc, Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, US FDA, Natl Ctr Toxicol Res, NCI, NIEHS, Nestle S A, Toronto Res Chem Inc DE mono-nitropyrene; environmental mammary carcinogen; metabolism; DNA adduct ID SPRAGUE-DAWLEY RATS; CHEMICAL CARCINOGENESIS; ENVIRONMENTAL MUTAGEN; A/J MICE; 1-NITROPYRENE; ADDUCTS; 2-NITROPYRENE; INVITRO; TUMORIGENICITY; INDUCTION AB The metabolism and DNA binding studies of mono-NP isomers under identical conditions were conducted, as an initial investigation, in order to provide an understanding for the higher carcinogenic activity of 4-NP in the rat mammary gland. Urinary and fecal excretion patterns of 4-NP and 1-NP 24 h following administration to female CD rats (i.p.; 24 mg/kg body weight; 1.55 mCi/rat) were similar but higher than those of 2-NP. The identified metabolites were formed via nitroreduction and ring oxidation pathways. Neither the excretion patterns nor the nature of the metabolites readily explained why the mammary tumorigenic activity of these three isomers varied. Although overall levels of mono-NP bound to liver DNA did not account for the observed differences in the biological activity, further HPLC analysis of the liver DNA hydrolysates showed that only 4-NP had yielded putative multiple DNA adducts; none were detected in the case of 1-NP and 2-NP. 1-, 2-, and 4-NP were found to bind to mammary DNA at levels of 0.6, 0.3, and 2.1 pmol/mg DNA, respectively. The structure of DNA adducts in the mammary gland and in the liver of female CD rats following the i.p. administration of 4-NP has not been identified. Collectively, the results of this preliminary study indicate that the difference in levels of DNA binding in the mammary gland in vivo may reflect why 4-NP has higher carcinogenic activity. C1 AMER HLTH FDN, VALHALLA, NY 10595 USA. NATL CTR TOXICOL RES, JEFFERSON, AR 72079 USA. FU NCI NIH HHS [CA 35519] NR 29 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAY 12 PY 1997 VL 376 IS 1-2 BP 21 EP 28 DI 10.1016/S0027-5107(97)00021-3 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA XE489 UT WOS:A1997XE48900005 PM 9202734 ER PT J AU Fu, PP Qui, FY Jung, H VonTungeln, LS Zhan, DJ Lee, MJ Wu, YS Heflich, RH AF Fu, PP Qui, FY Jung, H VonTungeln, LS Zhan, DJ Lee, MJ Wu, YS Heflich, RH TI Metabolism of isomeric nitrobenzo[a]pyrenes leading to DNA adducts and mutagenesis SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 6th International Conference on Carcinogenic and Mutagenic N-Substituted Aryl Compounds CY NOV 04-08, 1995 CL MONTEREY, CA SP Flavor & Extract Manufacturers Assoc US, Int Flavors & Fragrances Inc, Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, US FDA, Natl Ctr Toxicol Res, NCI, NIEHS, Nestle S A, Toronto Res Chem Inc DE nitrobenzo[a]pyrene; nitro-polycyclic aromatic hydrocarbon; metabolism; DNA adduct; mutation; Chinese hamster ovary cell; Salmonella typhimurium; nitroreduction; ring-oxidation; hprt ID POLYCYCLIC AROMATIC-HYDROCARBONS; HAMSTER OVARY CELLS; DIRECT-ACTING MUTAGENICITY; NITRO-GROUP ORIENTATION; SALMONELLA-TYPHIMURIUM; 1-NITROBENZOPYRENE; 3-NITROBENZOPYRENE; ACTIVATION; 6-NITROBENZOPYRENE; NITROREDUCTION AB We have been interested in determining the structural and electronic features that may be useful in predicting the mutagenic activity of nitro-polycyclic aromatic hydrocarbons (nitro-PAHs). We have previously found that a correlation between structural and electronic features and direct-acting mutagenicity in Salmonella typhimurium cannot be made using nitro-PAHs with different molecular size. In this study, a series of structurally related nitro-PAHs, the environmental contaminants 1-,3-, and 6-nitrobenzo[a]pyrene (NBaP) and their derivatives, was used to determine structure-activity relationships. It was found that isomeric NBaPs are activated to DNA damaging and mutagenic derivatives by nitroreduction, ring-oxidation, or by a combination of these two pathways. A general finding was that NBaPs and derivatives with their nitro substituent oriented perpendicular to the aromatic system exhibit either very weak or no direct-acting mutagenicity in S. typhimurium strains TA98 and TA100. In this paper, we also discuss the effect of the location of the nitro group on the metabolism and the mutagenicity of NBaPs and the effect of oxygen-containing functional groups on the mutagenicity of NBaP derivatives. These findings provide a useful molecular basis for interpreting and predicting the direct-acting mutagenicity of nitro-PAHs. RP Fu, PP (reprint author), US FDA,NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,DEPT HLTH & HUMAN SERV,3900 NCTR DR,JEFFERSON,AR 72079, USA. NR 34 TC 13 Z9 13 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAY 12 PY 1997 VL 376 IS 1-2 BP 43 EP 51 DI 10.1016/S0027-5107(97)00024-9 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA XE489 UT WOS:A1997XE48900008 PM 9202737 ER PT J AU Huber, WW McDaniel, LP Kaderlik, KR Teitel, CH Lang, NP Kadlubar, FF AF Huber, WW McDaniel, LP Kaderlik, KR Teitel, CH Lang, NP Kadlubar, FF TI Chemoprotection against the formation of colon DNA adducts from the food-borne carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the rat SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 6th International Conference on Carcinogenic and Mutagenic N-Substituted Aryl Compounds CY NOV 04-08, 1995 CL MONTEREY, CA SP Flavor & Extract Manufacturers Assoc US, Int Flavors & Fragrances Inc, Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, US FDA, Natl Ctr Toxicol Res, NCI, NIEHS, Nestle S A, Toronto Res Chem Inc DE 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP); chemoprotection; food-borne carcinogen; rat ID GLUTATHIONE S-TRANSFERASES; HETEROCYCLIC AROMATIC-AMINES; DIETARY BUTYLATED HYDROXYANISOLE; METABOLIC-ACTIVATION; LIVER-MICROSOMES; MUTAGEN 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; COOKED FOODS; METHYLAZOXYMETHANOL ACETATE; CHEMOPREVENTIVE AGENTS; ORGANOSULFUR COMPOUNDS AB The mutagenic heterocyclic aromatic amine, 2-amina-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), is a pyrolysis product in cooked foods that has been shown to be a rat colon carcinogen and has been implicated in the etiology of human colon cancer. In order to identify chemoprotection strategies that could be carried out in humans, a pilot study was conducted in which PhIP-DNA-adduct levels were quantified in the colons of male F344 rats that had been subjected to 16 different putative chemoprotection regimens, followed by a gavage of PhIP (50 mg/kg) and sacrifice 24 h later. The 16 treatments (Oltipraz, benzylisothiocyanate, diallyl sulfide, garlic powder, ethoxyquin, butylated hydroxyanisole, glutathione, indole-3-carbinol, alpha-angelicalactone, kahweol/cafestol palmitates, quercetin, green tea, black tea, tannic acid, amylase-resistant starch, and physical exercise) comprised sulfur-containing compounds, antioxidants, flavonoids, diterpenes, polyphenols, high dietary fiber, etc. The strongest inhibition of PhIP-DNA adduct formation in the colon was observed upon pretreatment with black. tea, benzylisothiocyanate, and a mixture (1:1) of kahweol:cafestol palmitates, which resulted in 67, 66, and 54% decreases in colon PhIP-DNA adduct levels, as compared with controls. Preliminary studies on their mechanism of action indicated that only kahweol:cafestol caused a substantial induction of glutathione S-transferase isozymes (GSTs) that are thought to be important in the detoxification of PhIP. Notably, this induction occurred in the liver rather than in the colon. C1 ARKANSAS CANC RES CTR,LITTLE ROCK,AR 72205. RP Huber, WW (reprint author), NATL CTR TOXICOL RES,DIV MOL EPIDEMIOL HFT100,JEFFERSON,AR 72079, USA. NR 67 TC 85 Z9 86 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAY 12 PY 1997 VL 376 IS 1-2 BP 115 EP 122 DI 10.1016/S0027-5107(97)00033-X PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA XE489 UT WOS:A1997XE48900017 PM 9202746 ER PT J AU MacLeod, S Sinha, R Kadlubar, FF Lang, NP AF MacLeod, S Sinha, R Kadlubar, FF Lang, NP TI Polymorphisms of CYP1A1 and GSTM1 influence the in vivo function of CYP1A2 SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 6th International Conference on Carcinogenic and Mutagenic N-Substituted Aryl Compounds CY NOV 04-08, 1995 CL MONTEREY, CA SP Flavor & Extract Manufacturers Assoc US, Int Flavors & Fragrances Inc, Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, US FDA, Natl Ctr Toxicol Res, NCI, NIEHS, Nestle S A, Toronto Res Chem Inc DE cytochrome P4501A1; cytochrome P4501A2; glutathione S-transferase M1; polymorphism ID CAFFEINE URINARY METABOLITES; HETEROCYCLIC AROMATIC-AMINES; CARCINOGEN-METABOLISM; CYTOCHROME P4501A2; N-ACETYLTRANSFERASE; GENE DELETION; HUMAN-LIVER; SUSCEPTIBILITY; PHENOTYPE; GENOTYPE AB Differences in human cancer susceptibility have been attributed to polymorphisms of carcinogen metabolizing enzymes. Our efforts have focused on the systems responsible for metabolism of aromatic and heterocyclic amines found in cigarette smoke and in cooked foods. Cytochrome P4501A2 (CYP1A2), which catalyzes aromatic and heterocyclic amine N-oxidation, has been implicated as a risk factor in both urinary bladder and colorectal cancer. In the present study we used the results of caffeine phenotyping experiments to measure the effects of cigarette smoke and compounds present in meat cooked at high temperature on CYP1A2 activity. Subjects in the smoking cessation study had mean CYP1A2 activity of 17.8 (expressed as the urinary molar ratio of [17X + 17U]/137X) while smoking; however, this activity decreased to 10.9 three weeks after cessation of smoking. Subjects in the cooked meat feeding study had mean CYP1A2 activity of 9.01 after 1 week of consuming meat cooked at low temperature, but this value increased to 12.7 after I week of consuming meat cooked at high temperature. Because no association has been identified between differences in CYP1A2 activity and variations in the CYP1A2 structural gene, we sought to determine whether the activities of other carcinogen metabolizing enzymes are involved in the regulation of CYP1A2 activity. CYP1A2 activity was higher in individuals who express the GSTM1 null allele compared to those expressing the GSTM1*A,B allele, 10.2 vs. 8.5 for unexposed conditions and 15.0 vs. 12.3 for exposed conditions. CYP1A1 genotyping demonstrated that individuals possessing the Ile/Ile CYP1A1 genotype had greater mean CYP1A2 activity than those who had the heterozygous Ile/Val allelic variant of the CYP1A1 gene. However, upon exposure to cigarette smoke or high-temperature cooked meat, individuals possessing the heterozygous form of the CYP1A1 gene had significantly increased CYP1A2 activity (18.1) compared to those with the more common Ile/Ile CYP1A1 genotype (13.3). These results indicate that CYP1A2, CYP1A1, and GSTM1 gene-gene interactions could be important confounders in the interpretation of molecular epidemiology studies. C1 JOHN L MCCLELLAN MEM VET ADM MED CTR,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,LITTLE ROCK,AR 72205. NCI,NIH,BETHESDA,MD 20892. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU NCI NIH HHS [R01 CA55751-03] NR 27 TC 48 Z9 49 U1 1 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 MAY 12 PY 1997 VL 376 IS 1-2 BP 135 EP 142 DI 10.1016/S0027-5107(97)00036-5 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA XE489 UT WOS:A1997XE48900020 PM 9202749 ER PT J AU Poirier, MC Beland, FA AF Poirier, MC Beland, FA TI Aromatic amine DNA adduct formation in chronically-exposed mice: Considerations for human comparison SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 6th International Conference on Carcinogenic and Mutagenic N-Substituted Aryl Compounds CY NOV 04-08, 1995 CL MONTEREY, CA SP Flavor & Extract Manufacturers Assoc US, Int Flavors & Fragrances Inc, Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, US FDA, Natl Ctr Toxicol Res, NCI, NIEHS, Nestle S A, Toronto Res Chem Inc DE 4-aminobiphenyl; cancer; lifetime exposure; bladder; Mouse ID CHRONIC CARCINOGEN EXPOSURE; HUMAN URINARY-BLADDER; TUMOR-INCIDENCE; CANCER RISK; 2-ACETYLAMINOFLUORENE; 4-AMINOBIPHENYL; SMOKING; EXAMPLE; TOBACCO; MODELS AB Lifetime chronic exposure of mice to the aromatic amines 4-aminobiphenyl (ABP) and 2-acetylaminofluorene (AAF) produces liver and urinary bladder tumors. In parallel experiments, DNA adduct levels in target tissues reach a steady-state (a balance between adduct formation and removal) after about four weeks of either AAF or ABP ingestion. For these and other carcinogens, steady-state DNA adduct levels most frequently increase linearly with dose, but the formation of tumors also depends upon a variety of factors, including the proliferative capacity of the target tissue, the sex of the animal, genotoxic properties of the specific adducts formed, and other unknown events. Chronic dosing experiments in animal models are of interest for human risk assessment because human exposure is typically intermittent, involving repeated exposures. However, it is to be expected that in a genetically-diverse human population, where the lifetime averages > 70 years, the relationship between tumorigenesis and DNA adduct formation will be relatively more complex than that observed in mice. From our studies of chronic ABP exposure in male mice, we have obtained the daily dose of ABP and the steady-state level of N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP) adduct associated with a 50% mouse bladder tumor incidence. Our attempt at a human extrapolation for adducts and urinary bladder cancer in smoking males (20-40 cigarettes/day) is based on the ABP dose per cigarette, values for the dG-C8-ABP adduct in bladder biopsies of lifetime heavy smokers at age similar to 70, and the smoking-related bladder tumor incidence (absolute lifetime risk) for Caucasian males in the United States aged 65-84 years. The extrapolation has produced two major predictions, one related to adduct formation and the other related to tumorigenesis. First, the observed level of smoking-related dG-C8-ABP in DNA of human bladder epithelium, expressed as a function of daily ABP intake, is about 3500-times higher than similar data for mice, which suggests that humans may perform the biotransformation of ABP more efficiently than mice. Second, at a similar bladder tumor incidence, mouse bladder contained adduct concentrations that were much higher than those observed in human bladder; for example, at a 2.6% tumor incidence, mouse bladder contained an average of 55.5 fmol dG-C8-ABP/mu g DNA (1850 adducts/10(8) nucleotides), while bladders from Caucasian male smokers contained an average of 0.036 fmol dG-C8-ABP/mu g DNA (1.2 adducts/10(8) nucleotides). This suggests that factors other than ABP-DNA adducts, such as adducts of other carcinogens, the influence of promoters, and synergistic effects of all of these factors contribute substantially to smoking-related bladder cancer in humans. C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RP Poirier, MC (reprint author), NCI,NIH,BLDG 37,RM 3B25,MSC-4253,37 CONVENT DR,BETHESDA,MD 20892, USA. NR 21 TC 8 Z9 9 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 MAY 12 PY 1997 VL 376 IS 1-2 BP 177 EP 184 DI 10.1016/S0027-5107(97)00041-9 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA XE489 UT WOS:A1997XE48900025 PM 9202754 ER PT J AU Clausing, P Rushing, LG Newport, GD Bowyer, JF AF Clausing, P Rushing, LG Newport, GD Bowyer, JF TI Determination of D-fenfluramine, D-norfenfluramine and fluoxetine in plasma, brain tissue and brain microdialysate using high-performance liquid chromatography after precolumn derivatization with dansyl chloride SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE fenfluramine; norfenfluramine; fluoxetine ID ELECTRON-CAPTURE DETECTION; BIOLOGICAL SAMPLES; GAS-CHROMATOGRAPHY; ULTRAVIOLET DETECTION; NORFLUOXETINE; METABOLITE; SERUM; HPLC; DEXFENFLURAMINE; ANTIDEPRESSANT AB A HPLC method is described for the simultaneous determination of D-fenfluramine (FEN), D-norfenfluramine (NF) and fluoxetine (FLX) using fluorometric detection after precolumn derivatization with dansyl-chloride. The method has limits of quantitation of 200 fmol for FEN and NF, 500 fmol for FLX in brain microdialysate, and 1 pmol for NF and FEN, and 2 pmol for FLX in plasma. Brain tissue standards were linear between 5 and 200 pmol/mg for all three compounds. The inter-assay variability (relative standard deviation) was 6.6%, 6.9% and 9.3% for FEN, 4.6%, 3.7% and 7.9% for NF and 10.4%, 4.9% and 12.2% for FLX, for brain microdialysate (2 pmol/mu l), plasma (2 pmol/ mu l) and brain tissue (50 pmol/mg), respectively. Intra-assay variability was always lower, typically several times lower than inter-assay variability. Extraction recovery was 108% and 48% for FEN, 105% and 78% for NF and 94% and 45% for FLX, in plasma (2 pmol/mu l) and brain tissue (5 pmol/mg), respectively. Due to the stability of the dansyl-chloride derivatives this method is well suited for an autoinjector after manual derivatization with dansyl chloride at room temperature for 4 h. C1 NATL CTR TOXICOL RES,DIV NEUROTOXICOL,JEFFERSON,AR 72079. NATL CTR TOXICOL RES,DIV CHEM,JEFFERSON,AR 72079. NR 27 TC 26 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD MAY 9 PY 1997 VL 692 IS 2 BP 419 EP 426 DI 10.1016/S0378-4347(96)00528-2 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA XB520 UT WOS:A1997XB52000021 PM 9188832 ER PT J AU Hao, YW Hsia, CC Nakashima, Y Evangelista, A Tabor, E AF Hao, YW Hsia, CC Nakashima, Y Evangelista, A Tabor, E TI Binding of wild-type p53 by topoisomerase II and overexpression of topoisomerase II in human hepatocellular carcinoma SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID DNA TOPOISOMERASE; CANCER; GENE; TRANSACTIVATION; PROLIFERATION; SUPPRESSOR; ONCOGENE; MARKER; CELLS AB In order to study the mechanisms by which p53 function is regulated, human wild-type p53 cDNA was cloned into a vaccinia virus vector and the expressed p53 protein was used to investigate binding of the p53 by cellular proteins from a cDNA expression library from human liver. One protein that bound wild-type p53 had > 99% homology with DNA topoisomerase IIb. p53 protein was coimmunoprecipitated from topoisomerase II-rich cell lysates (but not from topoisomerase II-deficient cell lysates) by an antibody to topoisomerase IIa and IIb. This binding was shown to occur without a dsDNA intermediary. Hepatocellular carcinomas (HCCs) and adjacent nontumorous liver tissues from ten patients were studied to determine the level of expression of topoisomerase II and p53. Overexpressed topoisomerase II proteins were detected by western blot in six often HCCs (60%), including several in which presumed wild-type p53 was detected by immunohistochemistry. No topoisomerase II expression was detectable in the ten nontumorous liver tissues from the same patients or in a sample of normal human liver. (C) 1997 Academic Press. C1 US FDA,DIV TRANSFUS TRANSMITTED DIS,BETHESDA,MD 20852. NR 17 TC 0 Z9 0 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 8 PY 1997 VL 234 IS 1 BP 194 EP 197 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WZ565 UT WOS:A1997WZ56500040 ER PT J AU Nightingale, SL AF Nightingale, SL TI Action to prevent accidental iron poisonings in children 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,MAIL CODE HFI-40,ROCKVILLE,MD 20857, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 7 PY 1997 VL 277 IS 17 BP 1343 EP 1343 DI 10.1001/jama.277.17.1343 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WW261 UT WOS:A1997WW26100006 PM 9134926 ER PT J AU Nightingale, SL AF Nightingale, SL TI Treatment IND for drug used in advanced reproductive technology 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,MAIL CODE HFI-40,ROCKVILLE,MD 20857, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 7 PY 1997 VL 277 IS 17 BP 1343 EP 1343 DI 10.1001/jama.277.17.1343 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WW261 UT WOS:A1997WW26100005 PM 9134926 ER PT J AU Nightingale, SL AF Nightingale, SL TI Safety alert re risk of misdiagnosis of group B streptococcal infection 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,MAIL CODE HFI-40,ROCKVILLE,MD 20857, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 7 PY 1997 VL 277 IS 17 BP 1343 EP 1343 DI 10.1001/jama.277.17.1343 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WW261 UT WOS:A1997WW26100004 PM 9134926 ER PT J AU Shallow, S Daily, P Rothrock, G Reingold, A Vugia, D Waterman, S Fiorentino, T Marcus, R Ryder, R Mshar, P Hadler, JL Farley, M Bardsley, M Baughman, W Koehler, J Blake, P Toomey, KE Hogan, J Deneen, V Hedberg, C Osterholm, MT Cassidy, M Townes, J Shiferaw, B Cieslak, P Hedberg, K Fleming, D AF Shallow, S Daily, P Rothrock, G Reingold, A Vugia, D Waterman, S Fiorentino, T Marcus, R Ryder, R Mshar, P Hadler, JL Farley, M Bardsley, M Baughman, W Koehler, J Blake, P Toomey, KE Hogan, J Deneen, V Hedberg, C Osterholm, MT Cassidy, M Townes, J Shiferaw, B Cieslak, P Hedberg, K Fleming, D TI Foodborne diseases active surveillance network, 1996 (Reprinted from MMWR, vol 46, pg 258-261, 1997) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 UNIV CALIF BERKELEY,BERKELEY,CA 94720. CALIF DEPT HLTH SERV,SACRAMENTO,CA 95814. YALE UNIV,SCH MED,NEW HAVEN,CT. CONNECTICUT STATE DEPT PUBL HLTH,HARTFORD,CT. ATLANTA METROPOLITAN ACT SURVEILLANCE PROJECT,ATLANTA,GA. GEORGIA DEPT HUMAN RESOURCES,DIV PUBL HLTH,ATLANTA,GA 30334. MINNESOTA DEPT HLTH,MINNEAPOLIS,MN 55414. OREGON DEPT HUMAN RESOURCES,STATE HLTH DIV,PORTLAND,OR. US FDA,CTR FOOD SAFETY & APPL NUTR,ROCKVILLE,MD 20857. USDA,FOOD SAFETY & INSPECT SERV,WASHINGTON,DC 20250. CDC,NATL CTR INFECT DIS,OFF DIRECTOR,ATLANTA,GA 30333. CDC,FOODBORNE & DIARRHEAL DIS BRANCH,DIV BACTERIAL & MYCOT DIS,ATLANTA,GA 30333. NR 4 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 MAY 7 PY 1997 VL 277 IS 17 BP 1344 EP 1345 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WW261 UT WOS:A1997WW26100007 ER PT J AU Scarbrough, FE AF Scarbrough, FE TI Some food and drug administration perspectives of fat and fatty acids SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Workshop on Individual Fatty Acids and Cardiovascular Disease CY MAR 30-31, 1995 CL WASHINGTON, D.C. SP Int Life Sci Inst DE food labeling; Food and Drug Administration; US Department of Agriculture; n-3 fatty acid; n-6 fatty acid; fat; health claim; trans fatty acid; stearic acid AB Because of public health concerns about the amount of fat in the American diet, the Food and Drug Administration and the US Department of Agriculture have emphasized use of the recently reformed food label to inform consumers about the fat and fatty acid contents of foods. The health effects of specific fatty acids continue to be the subject of much research, discussion, and debate. Issues that must be addressed to further improve the communication effectiveness of the food label include health effects of n-3 and n-6 fatty acids; appropriate labeling of trans fatty acids, stearic acid, and other non-cholesterol-raising fatty acids; partially absorbed fats; and label claims, especially health claims, for specific fatty acids and fatty acids of biotechnologically altered foods. RP Scarbrough, FE (reprint author), US FDA, CTR FOOD SAFETY & APPL NUTR, 200 C ST SW HFS-150, WASHINGTON, DC 20204 USA. NR 4 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAY PY 1997 VL 65 IS 5 SU S BP 1578 EP 1580 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WW669 UT WOS:A1997WW66900002 ER PT J AU Mann, M Shelhamer, JH Masur, H Gill, VJ Travis, W Solomon, D Manischewitz, J Stock, F Lane, HC Ognibene, FP AF Mann, M Shelhamer, JH Masur, H Gill, VJ Travis, W Solomon, D Manischewitz, J Stock, F Lane, HC Ognibene, FP TI Lack of clinical utility of bronchoalveolar lavage cultures for cytomegalovirus in HIV infection SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PNEUMOCYSTIS-CARINII PNEUMONIA; NONSPECIFIC INTERSTITIAL PNEUMONITIS; VIRUS HIV; AIDS; DIAGNOSIS; MORTALITY; DISEASE; BLOOD; FLUID AB This study assessed the presence of cytomegalovirus (CMV) in bronchoalveolar ravage (BAL) in three subpopulations of HIV-infected patients and correlated its presence with clinical status during 3 mo of follow-up. Nineteen asymptomatic volunteers, six patients with CMV retinitis, and 46 patients with acute pulmonary symptoms underwent BAL and were assessed for CMV by cytopathology, conventional shell vial cultures, and antigen detection. Transbronchial biopsies were also obtained when possible and evaluated for histopathologic changes of CMV. All patients were followed for approximately 3 mo. Cytomegalovirus was detected in BAL in nine of 19 (47%) asymptomatic volunteers, in all six patients with CMV retinitis, and in 33 of 46 (72%) patients with pulmonary symptoms. Only one symptomatic patient with a positive CMV BAL culture developed clinically significant CMV pulmonary disease; this patient developed disseminated CMV and died. The only other death occurred in a patient with CMV retinitis who developed staphylococcal bacteremia. None of the asymptomatic volunteers or patients with CMV retinitis developed evidence of CMV pneumonia or any other organ disease with CMV. Cytomegalovirus is frequently detected in BAL from HIV-infected patients regardless of their pulmonary symptoms and its presence does not clinically predict significant pulmonary morbidity or mortality in 3 mo of follow-up. C1 NIH,DEPT CRIT CARE MED,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. NIH,DEPT CLIN PATHOL,WARREN G MAGNUSON CLIN CTR,SERV CLIN PATHOL,BETHESDA,MD 20892. NCI,PATHOL LAB,SURG PATHOL SECT,BETHESDA,MD 20892. NCI,PATHOL LAB,CYTOPATHOL SECT,BETHESDA,MD 20892. CTR BIOL EVALUAT & RES,DIV VIRAL PROD,BETHESDA,MD. NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. US FDA,DIV ANTIVIRAL DRUG PROD,ROCKVILLE,MD 20857. NR 28 TC 26 Z9 26 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 MAY PY 1997 VL 155 IS 5 BP 1723 EP 1728 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA WY793 UT WOS:A1997WY79300037 PM 9154883 ER PT J AU Ahn, CH Choi, WC Kong, JY AF Ahn, CH Choi, WC Kong, JY TI Chemosensitizing activity of caffeic acid in multidrug resistant MCF-7/Dox human breast carcinoma cells SO ANTICANCER RESEARCH LA English DT Article DE Caffeir acid; multidrug-resistance; breast cancer; chemosensitizing ID GROWTH-FACTOR-BETA; CANCER-CELLS; DRUG-RESISTANCE; TGF-BETA; INHIBITION; LINES; TRANSFERASE; EXPRESSION; PHENOTYPE; APOPTOSIS AB The chemosensitizing activity of caffeic acid was examined in parent MCF-7 and multidrug-resistant MCF-7/Dox human breast carcinoma cells. In clonogenic assays, MCF-7/Dox cell was about 135fold less sensitive to doxorubicin than MCF-7 cells. Caffeic acid (10 mu M) slightly altered the colony forming ability of MCF-7 cells, and markedly reduced the IC50 of doxorubicin (Dox) from 10.8+/-1.3 mu M to 0.83+/-0.21 mu M in MCF-7/Dox cells. When compared to MCF-7/Dox cells, intracellular accumulations of [C-14]Dox in MCF-7 cells for 1 hour and 12 hours were elevated 2.3-fold and about 6.4-fold respectively. Doxorubicin accumulations in MCF-7 and MCF-7/Dox cells were not altered in the presence of 10 mu M caffeic acid. Both TGF beta 1 and TGF beta 2 isotypes were detected in MCF-7/Dox cells, while only TGF beta 1 was found in MCF-7 cells. The level of TGF beta 1 in MCF-7/Dox cells was about 3-fold greater than that in MCF-7 cells. In cells pretreated with caffeic acid (10 mu M), TGF beta 1 and TGF beta 2 levels were overexpressed only in MCF-7/Dox cells by 90% and 60%, respectively. These results suggest that caffeic acid is potentially a chemosensitizing agent with greater selectivity to drug-resistant MCF-7/Dox cells over parent MCF-7 cells and that the chemosensitizing effect is not mediated by altered drug concentrations in the cells, but may be possibly correlated to the induction of TGF beta isotypes. RP US FDA, CDER, HFD 150, DIV ONCOL DRUG PROD, 5600 FISHERS LANE, ROCKVILLE, MD 20857 USA. NR 31 TC 6 Z9 6 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 EI 1791-7530 J9 ANTICANCER RES JI Anticancer Res. PD MAY-JUN PY 1997 VL 17 IS 3C BP 1913 EP 1917 PG 5 WC Oncology SC Oncology GA XH618 UT WOS:A1997XH61800010 PM 9216644 ER PT J AU Trapnell, CB JamisDow, C Klecker, RW Collins, JM AF Trapnell, CB JamisDow, C Klecker, RW Collins, JM TI Metabolism of rifabutin and its 25-desacetyl metabolite, LM565, by human liver microsomes and recombinant human cytochrome P-450 3A4: Relevance to clinical interaction with fluconazole SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PROPHYLAXIS; INFECTION; UVEITIS; PHARMACOKINETICS; CLARITHROMYCIN; AUTOINDUCTION; DERIVATIVES; INHIBITION AB Rifabutin and fluconazole are often given concomitantly as therapy to prevent opportunistic infections in individuals infected with the human immunodeficiency virus. Recent reports have shown increased levels of rifabutin and its 25-desacetyl metabolite, LM565, in plasma when rifabutin is administered with fluconazole. Since fluconazole is known to inhibit microsomal enzymes, this study was undertaken to determine if this rifabutin-fluconazole interaction was due to an inhibition of human hepatic enzymes. The metabolism of both rifabutin and LM565 was evaluated in human liver microsomes and recombinant human cytochrome P-450 (CYP) 3A4 in the presence of fluconazole and other probe drugs known to inhibit CYP groups 1A2, 2C9, 2D6, 2E1, and 3A. The concentrations of rifabutin (1 mu g/ml), LM565 (1 mu g/ml), and fluconazole (10 and 100 mu g/ml) used were equal to those observed in plasma after the administration of rifabutin and fluconazole at clinically relevant doses, high-performance liquid chromatography was used to assess the metabolism of rifabutin and LM565. Rifabutin was readily metabolized to LM565 by human microsomes, but the reaction was independent of NADPH and was not affected by the P450 inhibitors. No rifabutin metabolism by recombinant CYP 3A4 was found to occur, LM565 was also metabolized by human microsomes to two products, but metabolism was dependent on NADPH and was affected by certain P-450 inhibitors. In addition, LM565 was readily metabolized by the recombinant CYP 3A4 to the same two products found with its metabolism by human microsomes. Therefore, rifabutin is metabolized by human microsomes but not via cytochrome P-450 enzymes, whereas LM565 is metabolized by CYP 3A4. RP Trapnell, CB (reprint author), US FDA,CTR BIOL EVALUAT & RES,HFM-579,WOCI,ROOM 211B,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 24 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 1997 VL 41 IS 5 BP 924 EP 926 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA WX583 UT WOS:A1997WX58300008 PM 9145845 ER PT J AU Rumsey, JM Nace, K Donohue, B Wise, D Maisog, JM Andreason, P AF Rumsey, JM Nace, K Donohue, B Wise, D Maisog, JM Andreason, P TI A positron emission tomographic study of impaired word recognition and phonological processing in dyslexic men SO ARCHIVES OF NEUROLOGY LA English DT Article ID DEVELOPMENTAL DYSLEXIA; PET IMAGES; ACTIVATION; SKILLS; CORTEX; MEMORY AB Background: Developmental dyslexia is characterized by impaired word recognition, which is thought to result from deficits in phonological processing. Improvements during the course of development are thought to disproportionately involve orthographic components of reading; phonological deficits persist into adulthood. Objective: To localize the neural correlates of impaired word recognition and phonological processing in men with developmental dyslexia. Methods: Regional cerebral blood flow was measured with oxygen 15 positron emission tomography in 17 men with dyslexia and in 14 matched controls during the performance of phonological and orthographic tasks-pronunciation (reading aloud) and lexical decision making-designed to activate posterior and anterior perisylvian cortices, respectively. Results: Altered patterns of activation (reduced activation, unusual deactivation) were seen in dyslexic men in mid- to posterior temporal cortex bilaterally and in inferior parietal cortex, predominantly on the left, during both pronunciation and decision making. In contrast, dyslexic men demonstrated essentially normal activation of left inferior frontal cortex during both phonological and orthographic decision making. Conclusion: These, along with prior findings, are compatible with a hypothesis of bilateral involvement of posterior temporal and parietal cortices in dyslexia. C1 NIMH, PSYCHOL & PSYCHOPATHOL LAB, BETHESDA, MD 20892 USA. US FDA, DIV NEUROPHARMACOL DRUG PROD, ROCKVILLE, MD 20857 USA. RP Rumsey, JM (reprint author), NIMH, CHILD PSYCHIAT BRANCH, BLDG 10, ROOM 6N240, BETHESDA, MD 20892 USA. NR 41 TC 212 Z9 215 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 1997 VL 54 IS 5 BP 562 EP 573 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA WY809 UT WOS:A1997WY80900010 PM 9152113 ER PT J AU Dearden, JC Barratt, MD Benigni, R Bristol, DW Combes, RD Cronin, MTD Judson, PN Payne, MP Richard, AM Tichy, M Worth, AP Yourick, JJ AF Dearden, JC Barratt, MD Benigni, R Bristol, DW Combes, RD Cronin, MTD Judson, PN Payne, MP Richard, AM Tichy, M Worth, AP Yourick, JJ TI The development and validation of expert systems for predicting toxicity - The report and recommendations of an ECVAM/ECB workshop (ECVAM workshop 24) SO ATLA-ALTERNATIVES TO LABORATORY ANIMALS LA English DT Editorial Material ID NATIONAL-TOXICOLOGY-PROGRAM; AUTOMATED STRUCTURE EVALUATION; IDENTIFYING CONTACT ALLERGENS; RODENT CARCINOGENICITY; CHEMICAL-STRUCTURE; 44 CHEMICALS; SALMONELLA MUTAGENICITY; BIOLOGICAL-ACTIVITY; SAFETY EVALUATION; BIOASSAYS C1 LIVERPOOL JOHN MOORES UNIV, SCH PHARM & CHEM, LIVERPOOL L3 3AF, MERSEYSIDE, ENGLAND. UNILEVER RES, ENVIRONM SAFETY LAB, SHARNBROOK MK44 1LQ, BEDS, ENGLAND. IST SUPER SANITA, I-00161 ROME, ITALY. NIEHS, NIH, RES TRIANGLE PK, NC 27709 USA. FRAME, NOTTINGHAM NG1 4EE, ENGLAND. HEATHER LEA, HARROGATE HG3 1TE, ENGLAND. HLTH & SAFETY LAB, SHEFFIELD S3 7HQ, S YORKSHIRE, ENGLAND. US EPA, NHEERL, RES TRIANGLE PK, NC 27711 USA. NATL INST PUBL HLTH, PREDICT TOXICOL LAB, PRAGUE 10042 10, CZECH REPUBLIC. US FDA, COSMET TOXICOL BRANCH, LAUREL, MD 20708 USA. RP Dearden, JC (reprint author), COMMISS EUROPEAN COMMUNITIES, JOINT RES CTR, INST ENVIRONM, ECVAM, TP 580, I-21020 ISPRA, VA, ITALY. NR 79 TC 96 Z9 97 U1 1 U2 1 PU FRAME PI NOTTINGHAM PA RUSSELL & BURCH HOUSE 96-98 NORTH SHERWOOD ST, NOTTINGHAM NG1 4EE, NOTTS, ENGLAND SN 0261-1929 J9 ATLA-ALTERN LAB ANIM JI ATLA-Altern. Lab. Anim. PD MAY-JUN PY 1997 VL 25 IS 3 BP 223 EP 252 PG 30 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XC771 UT WOS:A1997XC77100009 ER PT J AU Medlock, KL Branham, WS Sheehan, DM AF Medlock, KL Branham, WS Sheehan, DM TI Effects of toremifene on neonatal rat uterine growth and differentiation SO BIOLOGY OF REPRODUCTION LA English DT Article ID BREAST-CANCER PATIENTS; ESTROGEN-RECEPTOR; FEMALE RATS; TAMOXIFEN; DIETHYLSTILBESTROL; UTERUS; CELLS; ANTIESTROGENS; METABOLITES; EPITHELIUM AB In the developing rodent uterus, the estrogen agonist activity of triphenylethylene antiestrogens such as tamoxifen alters uterine luminal epithelium morphology and inhibits uterine gland genesis. We examined uterine growth and differentiation in female offspring from date-mated Sprague-Dawley rats given the structurally related antiestrogen, toremifene, by s.c. injection in 10 mu l of sesame oil on postnatal days (PND) 1-5, 10-14, or 20-24. Toremifene given on PND 10-14, a period of rapid uterine gland differentiation, caused a dose-related increase in uterine weight, tripled luminal epithelium cell height, and completely inhibited uterine gland development on PND 14 at doses of 10 mu g or higher. Based on this dose-response analysis, a 10-mu g dose of toremifene was chosen to assess uterine development after neonatal exposure (PND 1-5). Uterine weights and luminal epithelium cell heights were significantly increased by toremifene on PND 5 but returned to control levels by PND 26. Uterine gland numbers were reduced to 50% those of controls on PND 26. Dose-related uterine weight and luminal epithelium cell height increases were also observed in rats given toremifene on PND 20-24. This estrogen agonist activity of toremifene, revealed primarily in the uterine luminal epithelium, indicates that toremifene is developmentally toxic. C1 US FDA,DEPT HLTH & HUMAN SERV,NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079. UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM,LITTLE ROCK,AR 72205. NR 36 TC 18 Z9 18 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 MAY PY 1997 VL 56 IS 5 BP 1239 EP 1244 DI 10.1095/biolreprod56.5.1239 PG 6 WC Reproductive Biology SC Reproductive Biology GA WV691 UT WOS:A1997WV69100022 PM 9160724 ER PT J AU James, SJ Pogribna, M Miller, BJ Bolon, B Muskhelishvili, L AF James, SJ Pogribna, M Miller, BJ Bolon, B Muskhelishvili, L TI Characterization of cellular response to silicone implants in rats: Implications for foreign-body carcinogenesis SO BIOMATERIALS LA English DT Article DE foreign-body reaction; silicone; proliferation; apoptosis; DNA strand breaks ID DNA STRAND BREAKS; INFLAMMATION; CANCER; CELLS; DAMAGE; MECHANISMS; INDUCTION; TOXICITY; ORIGIN AB Foreign-body (FB) carcinogenesis is a classic model of multistage tumour development in rodents. Previous studies have demonstrated that the physical characteristics of the implant, and not the chemical composition, are the critical determinants of tumour development. The recent controversy over silicone breast implants has raised questions regarding the potential carcinogenicity of lifetime tissue exposure to silicone products. The present study was designed to determine whether the inflammatory and fibrotic reactions associated with silicone implants are due to a non-specific foreign-body reaction or whether these responses reflect the unique chemical composition of silicone. F344 rats were implanted subcutaneously with one of three biomaterials: silicone elastomer (Group 1), impermeable cellulose acetate filters (Group 2, positive control); or porous cellulose acetate filters (Group 3, negative control). The silicone and cellulose implants of Groups 1 and 2 have been previously shown to induce fibrosarcomas in rodents, whereas the porous cellulose acetate implants of Group 3 have been shown to be non-carcinogenic. One week and two months after implantation, the pericapsular tissues were evaluated using histopathological and in situ immunohistochemical analyses. Endpoints included expression of leucocyte antigens CD4 (T helper/inducer), CD8 (T suppressor/cytotoxic) and CD11 b/c (macrophage), proliferating cell nuclear antigen (PCNA) as an indicator of proliferation, and in situ end-labelling (ISEL) of 3' OH DNA strand breaks as an indicator of DNA damage and apoptosis. The results indicated that the acute and chronic cellular responses to silicone (Group 1) were not different from impermeable cellulose filters (Group 2) of identical size and shape, suggesting that these responses were not unique to silicone. The inflammatory response to the carcinogenic cellulose and silicone implants (Groups 1 and 2) was attenuated and associated with the formation of a thick fibrotic capsule. In contrast, the porous cellulose filters (Group 3) induced a markedly different cellular response in which the inflammatory reaction was more extensive, prolonged and associated with minimal fibrosis. Within the fibrotic capsule surrounding the tumorigenic implants, but not the non-tumorigenic implants, cell proliferation and apoptotic cell death were increased and associated with persistent DNA strand breaks. Taken together, the results suggest that the micrometre-scale surface morphology of the implant determines the nature of the subsequent cellular response which may predispose to tumour development Further, these studies serve to emphasize the critical importance of appropriate physical controls in studies designed to evaluate carcinogenic or autoimmune manifestations associated with silicone implants in order to rule out the contribution of the chronic foreign-body reaction. Published by Elsevier Science Limited. C1 PATHOL ASSOCIATES INT,JEFFERSON,AR 72079. RP James, SJ (reprint author), US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 40 TC 32 Z9 32 U1 2 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD MAY PY 1997 VL 18 IS 9 BP 667 EP 675 DI 10.1016/S0142-9612(96)00189-5 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA WV920 UT WOS:A1997WV92000003 PM 9151998 ER PT J AU Hirata, RDC Hirata, MH Levy, DE Nguyen, NY AF Hirata, RDC Hirata, MH Levy, DE Nguyen, NY TI Optimized production of the soluble human interferon alpha receptor (IFNAR) expressed in E-coli SO BIOTECHNOLOGY TECHNIQUES LA English DT Article ID BETA AB An optimized procedure has been developed for production and purification of the human interferon or receptor (IFNAR) expressed in E. coli as fusion protein with glutathione S-transferase (GST). Expression induced at 30 degrees C and cell disruption performed at pH = 9.0 in presence of detergents reduced the inclusion body formation and generated up to 20% of the fusion protein in the soluble form. The recombinant IFNAR, recovered in soluble and renaturated forms, was able to block the antiviral and antiproliferative activities of IFN alpha B. C1 NYU,MED CTR,NEW YORK,NY 10016. US FDA,CTR BIOL EVALUAT & RES,FACIL BIOTECHNOL RESOURCES,BETHESDA,MD 20892. RP Hirata, RDC (reprint author), UNIV SAO PAULO,FAC CIENCIAS FARMACEUT,DEPT ANAL CLIN & TOXICOL,BR-05508900 SAO PAULO,BRAZIL. RI Hirata, Rosario/A-7284-2011; Hirata, Mario/C-9718-2013 NR 15 TC 0 Z9 0 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0951-208X J9 BIOTECHNOL TECH JI Biotechnol. Tech. PD MAY PY 1997 VL 11 IS 5 BP 301 EP 305 DI 10.1023/A:1018463227250 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA XC289 UT WOS:A1997XC28900007 ER PT J AU Rumsey, JM Horwitz, B Donohue, BC Nace, K Maisog, JM Andreason, P AF Rumsey, JM Horwitz, B Donohue, BC Nace, K Maisog, JM Andreason, P TI Phonological and orthographic components of word recognition - A PET-rCBF study SO BRAIN LA English DT Article DE PET; reading; phonological; orthographic; lexical decision making ID POSITRON EMISSION TOMOGRAPHY; HUMAN EXTRASTRIATE CORTEX; INFERIOR TEMPORAL-LOBE; HUMAN-BRAIN; READING ALOUD; FUNCTIONAL-ORGANIZATION; SCINTIGRAPHIC IMAGES; AUTOMATED-METHOD; STIMULUS RATE; ANATOMY AB Pronunciation (of irregular/inconsistent words and of pseudowords) and lexical decision-making tasks were used with O-15 PET to examine the neural correlates of phonological and orthographic processing in 14 healthy right-handed men (aged 18-40 years). Relative to a visual-fixation control task, all four experimental tasks elicited a left-lateralized stream of activation involving the lingual and fusiform gyri, perirolandic cortex, thalamus and anterior cingulate. Both pronunciation tasks activated the left superior temporal gyrus, with significantly greater activation seen there during phonological (pseudoword) than during orthographic (real word) pronunciation. The left inferior frontal cortex was activated by both decision-making tasks; more intense and widespread activation was seen there during phonological, than during orthographic, decision making, with the activation during phonological decision-making extending into the left insula. Correlations of reference voxels in the left superior temporal gyrus and left inferior frontal region with the rest of the brain were highly similar for the phonological and orthographic versions of each task type. These results are consistent with connectionist models of reading, which hypothesize that both real words and pseudowords are processed within a common neural network. C1 NIA, NEUROSCI LAB, BETHESDA, MD 20892 USA. NIA, NEUROSCI LAB, BETHESDA, MD 20892 USA. NIMH, PSYCHOL & PSYCHOPATHOL LAB, BETHESDA, MD 20892 USA. US FDA, DIV NEUROPHARMACOL DRUG PROD, ROCKVILLE, MD 20857 USA. RP Rumsey, JM (reprint author), NIMH, CHILD PSYCHIAT BRANCH, BLDG 10, ROOM 6N240, BETHESDA, MD 20892 USA. NR 81 TC 307 Z9 309 U1 2 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAY PY 1997 VL 120 BP 739 EP 759 DI 10.1093/brain/120.5.739 PN 5 PG 21 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XC938 UT WOS:A1997XC93800002 PM 9183247 ER PT J AU Pogribny, IP Miller, BJ James, SJ AF Pogribny, IP Miller, BJ James, SJ TI Alterations in hepatic p53 gene methylation patterns during tumor progression with folate/methyl deficiency in the rat SO CANCER LETTERS LA English DT Article DE p53 gene; cytosine methylation; methyl deficiency; hepatocarcinogenesis; tumor progression ID DNA-METHYLTRANSFERASE; CELLS; CANCER; HYPOMETHYLATION; SENSITIVITY; EXPRESSION; MUTATIONS AB Chronic dietary methyl deficiency in F344 rats was used as an in vivo mammalian model in which to evaluate the gene-specific alterations in DNA methylation patterns during multistage hepatocarcinogenesis. Using bisulfite mapping, the site-specific methylation profile within exons 6-7 of the 53 gene was determined in control liver, preneoplastic nodules (after 36 weeks of folate/methyl deficiency) and in hepatocellular carcinoma (after 54 weeks of deficiency). A progressive loss of methyl groups was observed at most CpG sites on both coding and non-coding strands during the first 36 weeks of folate/methyl deficiency, with the greatest loss occurring on the coding strand. When the same sequence was evaluated in tumor DNA after 54 weeks of deficiency, the majority of cytosines were unexpectedly found to have-become remethylated. CpG sites that had previously lost methyl groups on both strands during preneoplasia as well as CpG sites that had been constitutively non-methylated, had undergone de novo methylation in tumor DNA. Maintenance methyltransferase and de novo methyltransferase activity in nuclear extracts were assessed using hemimethylated and non-methylated DNA substrates, respectively. In tumor, de novo methyltransferase capacity was increased similar to 4-fold relative to control or preneoplastic Liver and associated with a relative increase in both p53 and genome-wide methylation density. In the preneoplastic nodules, the level p53 mRNA was increased and associated with hypomethylation in the coding region of the gene, whereas in tumor tissue, p53 mRNA was decreased and associated with relative hypermethylation. Taken together, these results provide additional insights into the dysregulation and instability in DNA methylation that accompanies the transition to tumor. (C) 1997 Elsevier Science Ireland Ltd. C1 US FDA,DIV BIOCHEM TOXICOL,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 34 TC 118 Z9 122 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD MAY 1 PY 1997 VL 115 IS 1 BP 31 EP 38 DI 10.1016/S0304-3835(97)04708-3 PG 8 WC Oncology SC Oncology GA WP888 UT WOS:A1997WP88800005 PM 9097976 ER PT J AU Perkins, SN Hursting, SD Haines, DC James, SJ Miller, BJ Phang, JM AF Perkins, SN Hursting, SD Haines, DC James, SJ Miller, BJ Phang, JM TI Chemoprevention of spontaneous tumorigenesis in nullizygous p53-deficient mice by dehydroepiandrosterone and its analog 16 alpha-fluoro-5-androsten-17-one SO CARCINOGENESIS LA English DT Article ID CELL-EXTRACTS; INHIBITION; DHEA; DEOXYRIBONUCLEOSIDES; LYMPHOPOIESIS; REVERSAL; RATS; P53; DNA AB Transgenic mice with both alleles of the p53 tumor suppressor gene product 'knocked out' by gene targeting are susceptible to early development of tumors, chiefly lymphomas and sarcomas. Compared with the control group, administration of dehydroepiandrosterone (DHEA) at 0.3% of the diet to male p53-deficient mice extended their lifespan by delaying death due to neoplasms (from 105 to 166 days on study, P = 0.002), primarily by suppressing lymphoblastic lymphoma (from 45 to 6% of neoplastic deaths, P = 0.010). Treatment with a synthetic DHEA analog, 16 alpha-fluoro-5-androsten-17-one (compound 8354), at 0.15% of the diet also increased lifespan, to 140 days for mice that developed tumors (P = 0.037). The effects of these steroids on lifespan and tumor development did not appear to be strongly related to inhibition of food consumption and weight gain, in that a group pair-fed with control diet to the reduced food consumption of the DHEA-treated group developed and died of the same types of neoplasms at the same rate as the controls fed ad libitum. The chemopreventive effect of these steroids has been proposed to be due to suppression of DNA synthesis by inhibition of glucose 6-phosphate dehydrogenase, the rate-limiting enzyme of the pentose phosphate pathway. Although DHEA and its analog are strong non-competitive inhibitors of this enzyme in vitro, treatment with DHEA did not deplete cellular nucleotide pools in the liver, as would have been predicted. The chemopreventive effect of DHEA in this model may be due to steroid-induced thymic atrophy and suppression of T cell lymphoma, permitting these mice to survive long enough to develop tumors with longer latency. C1 NCI,LAB NUTR & MOL REGULAT,FREDERICK CANC RES & DEV CTR,SAIC,FREDERICK,MD 21702. NCI,PATHOL HISTOTECHNOL LAB,SAIC,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 22 TC 38 Z9 38 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1997 VL 18 IS 5 BP 989 EP 994 DI 10.1093/carcin/18.5.989 PG 6 WC Oncology SC Oncology GA WZ324 UT WOS:A1997WZ32400016 PM 9163685 ER PT J AU Anderson, KE Hammons, GJ Kadlubar, FF Potter, JD Kaderlik, KR Ilett, KF Minchin, RF Teitel, CH Chou, HC Martin, MV Guengerich, FP Barone, GW Lang, NP Peterson, LA AF Anderson, KE Hammons, GJ Kadlubar, FF Potter, JD Kaderlik, KR Ilett, KF Minchin, RF Teitel, CH Chou, HC Martin, MV Guengerich, FP Barone, GW Lang, NP Peterson, LA TI Metabolic activation of aromatic amines by human pancreas SO CARCINOGENESIS LA English DT Article ID OXIDATIVE DRUG-METABOLISM; TOBACCO-SPECIFIC NITROSAMINES; HUMAN URINARY-BLADDER; HUMAN-LIVER; MICROSOMAL CYTOCHROME-P-450; CHEMICAL CARCINOGENESIS; GENETIC-POLYMORPHISM; DNA-ADDUCTS; RAT-LIVER; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP AB Epidemiologic studies have suggested that aromatic amines (and nitroaromatic hydrocarbons) may be carcinogenic for human pancreas, Pancreatic tissues from 29 organ donors (13 smokers, 16 non-smokers) were examined for their ability to metabolize aromatic amines and other carcinogens, Microsomes showed no activity for cytochrome P450 (P450) 1A2-dependent N-oxidation of 4-aminobiphenyl (ABP) or for the following activities (and associated P450s): aminopyrine N-demethylation and ethylmorphine N-demethylation (P450 3A4); ethoxyresorufin O-deethylation (P450 1A1) and pentoxyresorufin O-dealkylation (P450 2B6); p-nitrophenol hydroxylation and N-nitrosodimethylamine N-demethylation (P450 2E1); lauric acid omega-hydroxylation (P450 4A1); and 4-(methylnitrosamino)-1-(3-pyridyl-1-butanol) (NNAL) and 4-(methylnitrosamino)1-(3-pyridyl)-1-butanone (NNK) alpha-oxidation (P450 1A2, 2A6, 2D6). Antibodies were used to examine microsomal levels of P450 1A2, 2A6, 2C8/9/18/19, 2E1, 2D6, and 3A3/ 4/5/7 and epoxide hydrolase. Immunoblots detected only epoxide hydrolase at low levels; P450 levels were <1% of liver. Microsomal benzidine/prostaglandin hydroperoxidation activity was low. In pancreatic cytosols and microsomes, 4-nitrobiphenyl reductase activities were present at levels comparable to human liver. The O-acetyltransferase activity (AcCoA-dependent DNA-binding of [H-3]N-hydroxy-ABP) of pancreatic cytosols was high, about two-thirds the levels measured in human colon. Cytosols showed high activity for N-acetylation of p-aminobenzoic acid, but not of sulfamethazine, indicating that acetyltransferase-1 (NAT1) is predominantly expressed in this tissue. Cytosolic sulfotransferase was detected at low levels. Using P-32-post-labeling enhanced by butanol extraction, putative arylamine-DNA adducts were detected in most samples. Moreover, in eight of 29 DNA samples, a major adduct was observed that was chromatographically identical to the predominant ABP-DNA adduct, N-(deoxyguanosin-8-yl)-ABP. These results are consistent with a hypothesis that aromatic amines and nitroaromatic hydrocarbons may be involved in the etiology of human pancreatic cancer. C1 NATL CTR TOXICOL RES, DIV MOL EPIDEMIOL, JEFFERSON, AR 72079 USA. FRED HUTCHINSON CANC RES CTR, SEATTLE, WA 98104 USA. UNIV WESTERN AUSTRALIA, DEPT PHARMACOL, NEDLANDS, WA 6009, AUSTRALIA. VANDERBILT UNIV, DEPT BIOCHEM, NASHVILLE, TN 37232 USA. VANDERBILT UNIV, CTR MOL TOXICOL, NASHVILLE, TN 37232 USA. UNIV ARKANSAS MED SCI HOSP, DEPT SURG, LITTLE ROCK, AR 72205 USA. JOHN L MCCLELLAN MEM VET ADM MED CTR, DEPT SURG, LITTLE ROCK, AR 72205 USA. AMER HLTH FDN, DIV CHEM CARCINOGENESIS, VALHALLA, NY 10595 USA. RP Anderson, KE (reprint author), UNIV MINNESOTA, SCH PUBL HLTH, DIV EPIDEMIOL, 1300 S 2ND ST, SUITE 300, MINNEAPOLIS, MN 55454 USA. OI Potter, John/0000-0001-5439-1500; Peterson, Lisa/0000-0001-8715-4480 FU NCI NIH HHS [5T32 CA09607, CA44353, R01CA58697] NR 97 TC 72 Z9 73 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1997 VL 18 IS 5 BP 1085 EP 1092 DI 10.1093/carcin/18.5.1085 PG 8 WC Oncology SC Oncology GA WZ324 UT WOS:A1997WZ32400031 PM 9163700 ER PT J AU Allen, PT Poirier, LA AF Allen, PT Poirier, LA TI Suppression by phenobarbital of ethionine-induced hepatocellular carcinoma formation and hepatic S-adenosylethionine levels SO CARCINOGENESIS LA English DT Article ID FED METHYL-DEFICIENT; ACID-DEFINED DIETS; DNA METHYLATION; DL-ETHIONINE; RAT-LIVER; HEPATOCARCINOGENESIS; ADENOSYLMETHIONINE; CHOLINE; CARCINOGENESIS; ENHANCEMENT AB An 18-month carcinogenicity study was conducted in male weanling F344 rats (28/group) to examine the effects of the simultaneous feeding of selected concentrations of ethionine and 0.05% phenobarbital in a normal chow diet. The effects of a 1-6-week feeding of phenobarbital and ethionine on the hepatic levels of the related metabolites S-adenosylmethionine, S-adenosylhomocysteine and S-adenosylethionine were also examined. Ethionine at 0.3% or 0.1% induced hepatocellular carcinoma (HCCa) at incidences of 90% (19/21) and 89% (24/27), respectively, Adding phenobarbital to the 0.1% ethionine diet reduced the incidence of HCCa to 36% (10/28) and reduced the number of liver tumor-associated deaths occurring prior to terminal sacrifice from 10/27 to 1/28. No hepatic tumors were observed in rats fed 0, 0.003, 0.01, or 0.03% ethionine. Phenobarbital alone or combined with 0.03% ethionine produced no hepatic tumors. Dietary ethionine at 0.1% reduced the intracellular hepatic level of S-adenosylmethionine to <50% of that seen in control rats. Phenobarbital alone had little effect on either S-adenosylmethionine or S-adenosylhomocysteine levels. The combination of phenobarbital and 0.1% ethionine led to increases in the hepatic levels of S-adenosylmethionine of 40-60% after 3 and 6 weeks of feeding, compared to those seen in rats receiving 0.1% ethionine alone. Ethionine feeding resulted in high levels of S-adenosylethionine in the livers. Combining phenobarbital with ethionine in the diet led to 30-50% reductions in hepatic S-adenosylethionine content. The results indicate that phenobarbital inhibits hepatocarcinogenesis by ethionine, that ethionine may cause HCCa via methyl group insufficiency, and that at levels of less than or equal to 0.03% ethionine did not show evidence of tumorigenicity. C1 NATL CTR TOXICOL RES,DIV NUTR TOXICOL,JEFFERSON,AR 72079. NR 45 TC 6 Z9 6 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 MAY PY 1997 VL 18 IS 5 BP 1103 EP 1107 DI 10.1093/carcin/18.5.1103 PG 5 WC Oncology SC Oncology GA WZ324 UT WOS:A1997WZ32400033 PM 9163702 ER PT J AU Sacks, T Klinman, DM AF Sacks, T Klinman, DM TI Long-term effect of primary immunization on subsequent immune responsiveness SO CELLULAR IMMUNOLOGY LA English DT Article ID B-CELL REPERTOIRE; BALB-C MICE; INTERFERON-GAMMA; BRUCELLA-ABORTUS; MURINE LEISHMANIASIS; T-CELLS; INTERLEUKIN-4; LYMPHOKINE; RESPONSES; IL-4 AB Specific antigen/adjuvant combinations preferentially induce type 1 or type 2 cytokine responses. For example, BALB/c mice primed with TNP-ovalbumin in complete Freund's adjuvant (TNP-OVA/CFA) produce a type 3-dominated response characterized by the activation of IL-4-secreting cells and the production of IgG1 and IgE anti-TNP antibodies. In contrast, mice primed with TNP conjugated to Brucella abortus (TNP-BA) produce a type 1 response dominated by the secretion of IFN-gamma and IgG2a anti-TNP antibodies. We examined whether treating young mice with these antigen/adjuvant combinations altered the cytokine profile of their subsequent immune responses. Mice immunized with TNP-BA and boosted several months later with TNP-OVA/CFA developed a cytokine and antibody profile similar to the priming rather than boosting antigen. This was also observed in mice immunized with TNP-OVA/CFA and boosted with TNP-BA. Both the ratio of IL-4:IFN-gamma-secreting cells and the isotype of antibodies produced by these mice were altered by primary immunization. Analysis of Con A-responsive cells from these animals showed that long-lived changes in the frequency of T lymphocytes available to secrete type 1 versus type 2 cytokines were induced by strong primary immunogens. (C) 1997 Academic Press. RP Sacks, T (reprint author), US FDA,DIV VIRAL PROD,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892, USA. NR 36 TC 12 Z9 12 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD MAY 1 PY 1997 VL 177 IS 2 BP 162 EP 168 DI 10.1006/cimm.1997.1114 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA XB137 UT WOS:A1997XB13700008 PM 9178643 ER PT J AU Sheehan, DM AF Sheehan, DM TI Isoflavone content of breast milk and soy formulas: Benefits and risks SO CLINICAL CHEMISTRY LA English DT Letter ID PHYTOESTROGENS RP Sheehan, DM (reprint author), US FDA,NATL CTR TOXICOL RES,3900 NCTR RD,HFT-130,JEFFERSON,AR 72079, USA. NR 10 TC 13 Z9 13 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAY PY 1997 VL 43 IS 5 BP 850 EP 850 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA WY184 UT WOS:A1997WY18400026 PM 9166244 ER PT J AU Mildvan, D Landay, A DeGruttola, V Machado, SG Kagan, J AF Mildvan, D Landay, A DeGruttola, V Machado, SG Kagan, J TI An approach to the validation of markers for use in AIDS clinical trials SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; SYNCYTIUM-INDUCING PHENOTYPE; HIV-INFECTED PATIENTS; T-CELL FUNCTION; PLACEBO-CONTROLLED TRIAL; INTRAVENOUS-DRUG-USERS; ASYMPTOMATIC HOMOSEXUAL MEN; ZIDOVUDINE-TREATED PATIENTS; IMMUNE-DEFICIENCY-SYNDROME AB Dr. Mildvan and coauthors have thoroughly reviewed and documented what is known about the validation of surrogate markers for use in clinical trials, They have proposed a classification system based on the usefulness of available immunologic and virological assays as measures of prognosis, drug activity, and therapeutic efficacy. The latter, a type II marker in the proposed classification, should estimate the proportion of treatment effect explained by change in the marker induced by therapy and, if complete, can substitute for clinical endpoints, HIV clinical trialists have had a long-standing interest in using surrogates for clinical endpoints to facilitate conduct of experimental protocols and to decrease the time and effort required to develop new treatment strategies, The approach outlined in this review by experienced clinicians, biostatisticians, and immunologists provides a framework to evaluate currently available and potential surrogate markers. C1 RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL. HARVARD UNIV,SCH PUBL HLTH,SPAC,BOSTON,MA 02115. US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. NIAID,DIV AIDS,BETHESDA,MD 20892. RP Mildvan, D (reprint author), BETH ISRAEL MED CTR,DIV INFECT DIS,1ST AVE & 16TH ST,NEW YORK,NY 10003, USA. FU NIAID NIH HHS [5U01-AI27667-11] NR 184 TC 52 Z9 55 U1 0 U2 2 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 MAY PY 1997 VL 24 IS 5 BP 764 EP 774 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WX257 UT WOS:A1997WX25700002 PM 9142767 ER PT J AU Souza, E Windes, JM Quisenberry, SS Schotzko, DJ Lamb, PF Halbert, S Zemetra, RS Smith, CM AF Souza, E Windes, JM Quisenberry, SS Schotzko, DJ Lamb, PF Halbert, S Zemetra, RS Smith, CM TI Registration of Idaho 471A and Idaho 471B wheat germplasms SO CROP SCIENCE LA English DT Article C1 UNIV IDAHO,DEPT PLANT SOILS ENTOMOL SCI,MOSCOW,ID 83844. UNIV NEBRASKA,DEPT ENTOMOL,LINCOLN,NE 68583. FDACS,DIV PLANT PROTECT,GAINESVILLE,FL 32614. KANSAS STATE UNIV,DEPT ENTOMOL,MANHATTAN,KS 66506. RP Souza, E (reprint author), UNIV IDAHO,DEPT PLANT SOILS & ENTOMOL SCI,ABERDEEN RES & EXT CTR,ABERDEEN,ID 83210, USA. NR 3 TC 11 Z9 11 U1 0 U2 0 PU CROP SCIENCE SOC AMER PI MADISON PA 677 S SEGOE ROAD, MADISON, WI 53711 SN 0011-183X J9 CROP SCI JI Crop Sci. PD MAY-JUN PY 1997 VL 37 IS 3 BP 1031 EP 1031 PG 1 WC Agronomy SC Agriculture GA XD192 UT WOS:A1997XD19200094 ER PT J AU Souza, E Windes, JM Quisenberry, SS Schotzko, DJ Lamb, PF Halbert, S Zemetra, RS Smith, CM AF Souza, E Windes, JM Quisenberry, SS Schotzko, DJ Lamb, PF Halbert, S Zemetra, RS Smith, CM TI Registration of Idaho 472 wheat germplasm SO CROP SCIENCE LA English DT Article ID RESISTANCE C1 UNIV NEBRASKA,DEPT ENTOMOL,LINCOLN,NE 68583. FDACS,DIV PLANT PROTECT,GAINESVILLE,FL 32614. KANSAS STATE UNIV,DEPT ENTOMOL,MANHATTAN,KS 66506. RP Souza, E (reprint author), UNIV IDAHO,DEPT PLANT SOIL & ENTOMOL SCI,ABERDEEN RES & EXT CTR,ABERDEEN,ID 83210, USA. NR 3 TC 8 Z9 8 U1 0 U2 0 PU CROP SCIENCE SOC AMER PI MADISON PA 677 S SEGOE ROAD, MADISON, WI 53711 SN 0011-183X J9 CROP SCI JI Crop Sci. PD MAY-JUN PY 1997 VL 37 IS 3 BP 1032 EP 1032 PG 1 WC Agronomy SC Agriculture GA XD192 UT WOS:A1997XD19200095 ER PT J AU Chen, TL Kennedy, MJ Anderson, LW Kiraly, SB Black, KC Colvin, OM Grochow, LB AF Chen, TL Kennedy, MJ Anderson, LW Kiraly, SB Black, KC Colvin, OM Grochow, LB TI Nonlinear pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide/aldophosphamide in patients with metastatic breast cancer receiving high-dose chemotherapy followed by autologous bone marrow transplantation SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID PLASMA HALF-LIFE; PHASE-I; METABOLITES; CLEARANCE; CELLS AB The pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide/aldophosphamide has been evaluated in 12 patients with metastatic breast cancer undergoing high-dose chemotherapy followed by bone marrow transplantation. Each patient received an initial dose of 4 g/m(2) of cyclophosphamide over 90 min to prime peripheral blood progenitor cells (the first course), and 3 weeks later, 6 g/m(2) of cyclophosphamide with 800 mg/m2 of thiotepa by 96-hr infusion before marrow stem cell infusion (the second course), Whole blood cyclophosphamide and 4-hydroxycyclophosphamide/aldophosphamide concentrations were measured by a GC-EIMS method using deuterium labeled compounds as internal standards, In addition, plasma and urine cyclophosphamide concentrations were determined by a GC assay, Whole blood concentrations of cyclophosphamide and 4-hydroxycyclophosphamide/aldophosphamide vs, time data and urinary excretion of cyclophosphamide data from the first course were co-modeled using a one-compartment model with Michaelis-Menten saturable elimination in parallel with first-order renal elimination (N = 7) or first-order metabolic and renal elimination (N = 5) for cyclophosphamide and one-compartment model with first-order elimination for 4-hydroxycyclophosphamide/aldophosphamide The parallelism between cyclophosphamide and 4-hydroxycyclophosphamide/aldophosphamide disposition curves implies that the pharmacokinetics of 4-hydroxycyclophosphamide/aldophosphamide is formation limited; only the fractional 4-hydroxycyclophosphamide/aldophosphamide clearance rate (Cl-met/F-met) can be estimated. The mean V-max and K-m for cyclophosphamide were 0.78 mu M/min and 247 mu M, respectively, The mean nonrenal clearance (Cl-met) of cyclophosphamide for five patients with apparent first-order elimination of cyclophosphamide was 67 ml/min, The mean Cl-met/F-met of 4-hydroxycyclophosphamide/aldophosphamide was 2982 ml/min. The mean renal clearance (Cl-r) of cyclophosphamide was 29 ml/min and 24 ml/min for the first course and the second course, respectively, The correlations between cyclophosphamide AUCs and 4-hydroxycyclophosphamide/aldophosphamide AUCs were sought for both drug courses, Blood and plasma cyclophosphamide concentrations were remarkably similar, indicating that cyclophosphamide partitions equally in the red cell and plasma volume, Computer simulation of the effect of potential alterations in Michaelis-Menten saturable elimination and renal clearance on 4-hydroxycyclophosphamide/aldophosphamide has been used to illustrate the complex relationship between the exposure to parent compound and active metabolite. C1 JOHNS HOPKINS ONCOL CTR,DIV MED ONCOL,BALTIMORE,MD. US FDA,DIV CLIN PHARMACOL RES,ROCKVILLE,MD 20857. DUKE UNIV,MED CTR,DUKE COMPREHENS CANC CTR,DURHAM,NC 27710. RP Chen, TL (reprint author), JOHNS HOPKINS ONCOL CTR,DIV PHARMACOL & EXPT THERAPEUT,1-121,600 N WOLFE ST,BALTIMORE,MD 21287, USA. FU NCI NIH HHS [CA63437, CA15396] NR 28 TC 56 Z9 56 U1 0 U2 3 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 MAY PY 1997 VL 25 IS 5 BP 544 EP 551 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WZ115 UT WOS:A1997WZ11500003 PM 9152592 ER PT J AU Barker, CM Calvert, RJ Walker, CW Reinisch, CL AF Barker, CM Calvert, RJ Walker, CW Reinisch, CL TI Detection of mutant p53 in clam leukemia cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID SOFT-SHELL CLAMS; HUMAN PAPILLOMAVIRUS TYPE-16; TUMOR-SUPPRESSOR P53; MYA-ARENARIA; NEOPLASIA; MUTATIONS; PROTEIN; CANCER AB Leukemia in the soft-shell clam, Mya arenaria, is characterized by tumor cells which are detected initially in the hemolymph. This disease is much more common in clams inhabiting polluted waters, suggesting an environmental component to its pathogenesis. In this study, leukemia cells were identified using a murine monoclonal antibody, 1E10, which recognizes a leukemia-specific protein expressed by tumor cells. Mutant p53 protein was detected using a murine monoclonal antibody (PAb 240) which reacts with mutant p53. Using immunofluorescence, the reactivity of clam cells to the 1E10 antibody was evaluated along with mutant p53 protein reactivity. Reverse transcriptase-polymerase chain reactions followed by sequence analyses were utilized to examine clams with hemocytes reacting with the p53 antibody for possible p53 gene mutations. Mutant p53 protein was expressed by tumor cells from five animals with advanced disease (in which greater than 90% of cells reacted with 1E10). A C --> G transversion was detected at the end of exon 6 from two of the five animals that reacted with both the mutant p53 antibody and 1E10. This substitution changes the amino acid of this codon from proline to alanine. Overall, our results suggest that environmentally induced alterations in p53 can contribute to the pathogenesis of leukemia in soft-shell clams inhabiting polluted water and/or sediment. (C) 1997 Academic Press. C1 TUFTS UNIV,SCH VET MED,DEPT COMPARAT MED,NORTH GRAFTON,MA 01536. MARINE BIOL LAB,WOODS HOLE,MA 02543. US FDA,OFF SPECIAL NUTR,CLIN RES & REVIEW STAFF,LAUREL,MD 20708. UNIV NEW HAMPSHIRE,DEPT ZOOL,DURHAM,NH 03824. FU NCI NIH HHS [CA 44307] NR 23 TC 35 Z9 35 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY 1 PY 1997 VL 232 IS 2 BP 240 EP 245 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA WX489 UT WOS:A1997WX48900005 PM 9168798 ER PT J AU Guzick, DS Silliman, NP Adamson, GD Buttram, VC Canis, M Malinak, LR Schenken, RS AF Guzick, DS Silliman, NP Adamson, GD Buttram, VC Canis, M Malinak, LR Schenken, RS TI Prediction of pregnancy in infertile women based on the American Society for Reproductive Medicine's revised classification of endometriosis SO FERTILITY AND STERILITY LA English DT Article DE revised American Society for Reproductive Medicine's classification of endometriosis; infertility; pregnancy rates ID SURGICAL-TREATMENT; PELVIC PAIN; REPRODUCIBILITY; DISEASE; SYSTEMS; CURVES AB Objective: To estimate the empirical relationship between the revised American Society for Reproductive Medicine's classification of endometriosis and pregnancy rates after treatment. Design: Retrospective analysis. Patient(s): Patients seen by four practicing physicians. Intervention(s): Medical and/or surgical therapy for endometriosis. Main Outcome Measure(s): Pregnancy defined as ongoing or delivered. Result(s): There were no significant differences in pregnancy rates across stages of endometriosis. There was a slight decline in pregnancy rates among patients with Stage IV endometriosis, but statistical significance was not achieved. Conclusion(s): The use of an arbitrary weighted system for assigning scores to individual categories of disease, or for computing a total score, has limited the overall effectiveness of the classification system to predict pregnancy. (C) 1997 by American Society for Reproductive Medicine. C1 UNIV TEXAS,HLTH SCI CTR,DEPT OBSTET & GYNECOL,SAN ANTONIO,TX 78284. UNIV ROCHESTER,DEPT OBSTET & GYNECOL,ROCHESTER,NY 14627. US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. STANFORD UNIV,DEPT GYNECOL & OBSTET,STANFORD,CA 94305. UNIV TEXAS,DEPT OBSTET & GYNECOL,HOUSTON,TX. UNIV CLERMONT FERRAND,DEPT OBSTET GYNECOL & REPROD MED,CLERMONT FERRAN,FRANCE. BAYLOR COLL MED,DEPT OBSTET & GYNECOL,HOUSTON,TX 77030. NR 31 TC 84 Z9 94 U1 1 U2 4 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 1997 VL 67 IS 5 BP 822 EP 829 DI 10.1016/S0015-0282(97)81392-1 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA WV719 UT WOS:A1997WV71900005 PM 9130885 ER PT J AU Sahu, SC Gray, GC AF Sahu, SC Gray, GC TI Lipid peroxidation and DNA damage induced by morin and naringenin in isolated rat liver nuclei SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID OXYGEN RADICALS; DUAL ROLE; QUERCETIN; FLAVONOIDS; CARCINOGENICITY; MUTAGENESIS; RUTIN AB The pro-oxidant activities, as determined by lipid peroxidation and DNA strand breaks, of morin and naringenin, two polyphenolic flavonoids with molecular structures similar to quercetin, were investigated under aerobic conditions in a model system of isolated rat liver nuclei. Both flavonoids induced a concentration-dependent peroxidation of nuclear membrane lipids concurrent with DNA strand breaks. These reactions were enhanced by the metal ions iron or copper. Active oxygen scavengers catalase, superoxide dismutase and mannitol had no effect on the flavonoid-induced nuclear DNA damage in the presence of the metal ions; nuclear lipid peroxidation was partially inhibited only by mannitol. It appears that hydroxyl radicals are the initiators of the peroxidation of nuclear membrane lipids, producing peroxidation products such as peroxyl radicals that in turn may be responsible for the DNA strand breaks. Alternatively, the hydroxyl radicals produced close to the DNA backbone may induce direct site-specific strand breaks that are insensitive to the free radical scavengers. These results demonstrate the pro-oxidant activities of polyphenolic flavonoids, which are generally considered as antioxidants and anticarcinogens, and suggest their possible dual role in mutagenesis and carcinogenesis. (C) 1997 Elsevier Science Ltd. RP Sahu, SC (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV TOXICOL RES HFS509,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 29 TC 50 Z9 50 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD MAY PY 1997 VL 35 IS 5 BP 443 EP 447 DI 10.1016/S0278-6915(97)00011-2 PG 5 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA XH494 UT WOS:A1997XH49400002 PM 9216742 ER PT J AU Bueno, MP AF Bueno, MP TI Collaborative study: Determination of retinol and carotene by high-performance liquid chromatography SO FOOD CHEMISTRY LA English DT Article ID HPLC; VEGETABLES; SEPARATION; FOODS AB Seventeen laboratories participated in the analysis of 10 products for carotene and retinol by high-performance liquid chromatography. Test materials were saponified and the nonsaponifiables were extracted with petroleum ether. The extract was injected into the liquid chromatograph for determination of carotene at 450 nm/436 nm, using a C18 reversed-phase column with a mobile phase of acetonitrile:methylene chloride:methanol:water (70:20:8:2, v/v). Retinol was determined at 325 nm/313 nm by using a C18 reversed-phase column with a mobile phase of methanol:water (90:10, v/v). The biological activities of retinol and carotene expressed in international units were summed to give total activity. The repeatability (within laboratory) coefficients of variation ranged from 3.46-15.65%, and the reproducibility (among laboratories) coefficients of variation ranged from 5.34-15.77%. (C) 1997 Published by Elsevier Science Ltd. All rights reserved. RP Bueno, MP (reprint author), US FDA,OFF FOOD LABELING,DIV SCI & APPL TECHNOL,HFS-175,200C ST SW,WASHINGTON,DC 20204, USA. NR 9 TC 13 Z9 14 U1 0 U2 0 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 MAY PY 1997 VL 59 IS 1 BP 165 EP 170 DI 10.1016/S0308-8146(95)00227-8 PG 6 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA WL826 UT WOS:A1997WL82600024 ER PT J AU Wilson, CA Ng, TH Miller, AE AF Wilson, CA Ng, TH Miller, AE TI Evaluation of recommendations for replication-competent retrovirus testing associated with use of retroviral vectors SO HUMAN GENE THERAPY LA English DT Article ID MURINE LEUKEMIA VIRUSES; NONHUMAN-PRIMATES; INTERFERES; INFECTION; SEQUENCES; CELLS; GENE C1 US FDA,DIV BIOSTAT & EPIDEMIOL,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852. US FDA,DIV APPLICAT REVIEW & POLICY,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852. RP Wilson, CA (reprint author), US FDA,DIV CELLULAR & GENE THERAPIES,CTR BIOL EVALUAT & RES,1401 ROCKVILLE PIKE,HFM-530,ROCKVILLE,MD 20852, USA. NR 18 TC 36 Z9 37 U1 0 U2 0 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 MAY 1 PY 1997 VL 8 IS 7 BP 869 EP 874 DI 10.1089/hum.1997.8.7-869 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WY231 UT WOS:A1997WY23100008 PM 9143913 ER PT J AU Quakyi, EK Hochstein, HD Tsai, CM AF Quakyi, EK Hochstein, HD Tsai, CM TI Modulation of the biological activities of meningococcal endotoxins by association with outer membrane proteins is not inevitably linked to toxicity SO INFECTION AND IMMUNITY LA English DT Article ID TUMOR-NECROSIS-FACTOR; B NEISSERIA-MENINGITIDIS; SEPTIC SHOCK; DISEASE; VACCINE; SERUM; BACTEREMIA; PLASMA; OLIGOSACCHARIDES; INTERLEUKIN-1 AB Meningococcal sepsis results partly from overproduction of host cytokines after macrophages interact with endotoxin. To obtain less toxic and highly immunomodulatory meningococcal endotoxins for prophylactic purposes,,ve investigated the relationship between endotoxicity and immunomodulatory activity of several endotoxin preparations from Neisseria meningitidis group B. Using the D-galactosamine-sensitized mouse model to determine endotoxin lethality, we found that the toxicity of purified lipooligosaccharide (LOS) from M986, a group B disease strain, was three to four times higher than those of purified LOSs from the noncapsulated strains M986-NCV-1 and OP-, the truncated-LOS mutant. The LOSs of outer membrane vesicles (OMVs) and detergent-treated OMVs (D-OMVs) from the three strains were 2 to 3 and over 300 times less toxic than the purified LOSs, respectively. Intraperitoneal administration of these preparations induced production of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in serum 2 h after injections, However, repeated doses of low- and high-toxicity preparations induced lower amounts of TNF-alpha and IL-6, i.e., LOS tolerance, Injection of mice with low doses of LOS was as effective as injection with high doses in inducing tolerance. Peritoneal macrophages from tolerant mice pretreated with either high- or low-toxicity LOS preparations produced only a fraction of the amounts of TNF-alpha and IL-6 produced by control groups in response to LOS ex vivo. Despite tolerance to LOS induced by pretreatment with reduced-toxicity preparations, killing of N. meningitidis M986 by macrophages from these animals was enhanced. Protection,vas achieved when mice treated with LOS, and especially that of D-OMVs, were challenged with live N. meningitidis. The least toxic LOS, that in D-OMVs, was most effective in inducing hyporesponsiveness to endotoxin in mice but protected them against challenge with N. meningitidis. No inevitable link between toxicity. and host immune modulation and responses was shown. Our results show that LOS Is responsible for both toxicity and immunomodulation, When LOS is tightly associated with outer membrane proteins in D-OMV it reduces toxicity but enhances beneficial effects compared to results with its purified form, Thus, systematic and critical evaluation of D-OMVs as adjuvants or as portions of group B meningococcal vaccines may help improve survival and outcome in meningococcal sepsis. RP Quakyi, EK (reprint author), US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892, USA. NR 45 TC 12 Z9 12 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 MAY PY 1997 VL 65 IS 5 BP 1972 EP 1979 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WW398 UT WOS:A1997WW39800061 PM 9125592 ER PT J AU Hewlett, I Lee, S Molnar, J Weaver, JL Aszalos, A AF Hewlett, I Lee, S Molnar, J Weaver, JL Aszalos, A TI Inhibition of HIV infection of H9 cells by chlorpromazine derivatives SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE anti-Leu3a binding; syncytia formation; HIV infectivity; dioxo-chlorpromazine ID CD4 RECEPTOR; VIRUS; BINDING; GLYCOPROTEIN; ENVELOPE; PROTEIN; RGP120 AB The binding between the HIV surface protein. gp120, and the CD4 coreceptor is known to be initiated by electrostatic interactions. Because of the ability of chlorpromazine to interact with proteins by charge transfer, we tested several derivatives for their ability to block binding of HIV to CD4(+) cells. We have shown that 7,8-dioxo-chlorpromazine blocks binding of fluorescein isothiocyanate-labeled anti-Leu3a and rgp120 to peripheral human blood T4 cells and blocks syncytia formation between gp120- and CD4-expressing cells. We also found that 7,8-dioxo-chlorpromazine blocks HIV infectivity of H9 cells and acts synergistically with zidovudine. C1 US FDA,CTR DRUG EVALUAT & RES,DIV RES & TESTING,LAUREL,MD 20705. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. ALBERT SZENT GYORGYI MED UNIV,H-6701 SZEGED,HUNGARY. NR 16 TC 9 Z9 10 U1 1 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 MAY 1 PY 1997 VL 15 IS 1 BP 16 EP 20 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XH946 UT WOS:A1997XH94600003 PM 9215649 ER PT J AU Plakas, SM ElSaid, KR Jester, ELE Bencsath, FA Hayton, WL AF Plakas, SM ElSaid, KR Jester, ELE Bencsath, FA Hayton, WL TI Liquid chromatographic determination of acriflavine and proflavine residues in channel catfish muscle SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID FISH AB A liquid chromatographic (LC) method was developed for determination of acriflavine (ACR) and proflavine (PRO) residues in channel catfish muscle. Residues were extracted with acidified methanol solution, and extracts were cleaned up with C-18 solid-phase extraction columns. Residue concentrations were determined on an LC cyano column, with spectrophotometric detection at 454 nm. Catfish muscle was individually fortified with ACR (purified from commercial product) and PRO at concentrations of 5, 10, 20, 40, and 80 ppb (5 replicates per level). Mean recoveries from fortified muscle at each level ranged from 86 to 95%, with relative standard deviations (RSDs) of 2.5 to 5.7%. The method was applied to incurred residues of ACR and PRO in muscle after waterborne exposure of channel catfish to commercial acriflavine (10 ppm total dye for 4 h). RSDs for incurred residues of ACR and PRO were in the same range as those for fortified muscle. Low residue concentrations (<1% of exposure water concentration) suggested poor absorption of ACR and PRO in catfish. C1 OHIO STATE UNIV,COLL PHARM,COLUMBUS,OH 43210. RP Plakas, SM (reprint author), US FDA,GULF COAST SEAFOOD LAB,POB 158,DAUPHIN ISL,AL 36528, USA. NR 8 TC 4 Z9 4 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 MAY-JUN PY 1997 VL 80 IS 3 BP 486 EP 490 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA XA023 UT WOS:A1997XA02300005 PM 9170648 ER PT J AU Rogers, PL Staruszkiewicz, W AF Rogers, PL Staruszkiewicz, W TI Gas chromatographic method for putrescine and cadaverine in canned tuna and mahimahi and fluorometric method for histamine (minor modification of AOAC Official Method 977.13): Collaborative study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID FOODS; DECOMPOSITION; STORAGE; FISHES AB A collaborative study was conducted to test a modification to the AOAC fluorometric method for histamine (AOAC(R) Official Method 977.13) that substitutes 75% methanol as the extracting solvent. AII other steps remain unchanged. The extracts prepared with 75% methanol were also used to collaboratively test a gas chromatographic (GC) method for determination of putrescine and cadaverine in seafood. In the GC method, the extracted diamines are converted to fluorinated derivatives, the reaction mixtures are passed through solid-phase extraction columns, and the derivatives are quantitated by electron capture GC after separation on an OV-225 column. Fourteen laboratories using the GC method for putrescine and cadaverine and 16 laboratories using the fluorometric method for histamine analyzed 14 canned tuna and raw mahimahl (including blind duplicates and a spike) containing 0.2-2.6 ppm putrescine, 0.6-9.1 ppm cadaverine, and 0.6-154 ppm histamine, At the 5 ppm level, recoveries ranged from 71 to 102% for putrescine and 77 to 112% for cadaverine; the respective repeatability relative standard deviations (RSDr) were 5.2 and 15%, and the respective reproducibility relative standard deviations (RSDR) were 8.8 and 18%, At the 50 ppm level, histamine recoveries ranged from 84 to 125%, RSDr was 3.6%, and RSDR was 9.4%, The GC method for determination of putrescine in canned tuna and cadaverine in canned tuna and mahimahi has been adopted first action by AOAC INTERNATIONAL, and the AOAC Official Method 977.13, Histamine in Seafood, Fluorometric Method, has been modified. RP Rogers, PL (reprint author), US FDA,OFF SEAFOOD,200 C ST SW,WASHINGTON,DC 20204, USA. NR 18 TC 36 Z9 37 U1 2 U2 7 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1997 VL 80 IS 3 BP 591 EP 602 PG 12 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA XA023 UT WOS:A1997XA02300017 PM 9170656 ER PT J AU Sharpless, KE Schiller, SB Margolis, SA Thomas, JB Iyengar, GV Colbert, JC Gills, TE Wise, SA AF Sharpless, KE Schiller, SB Margolis, SA Thomas, JB Iyengar, GV Colbert, JC Gills, TE Wise, SA TI Certification of nutrients in Standard Reference Material 1846: Infant formula SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB In 1996, the National Institute of Standards and Technology (NIST) released Standard Reference Material 1846 (Infant Formula), which can be used as a control material for assigning values to in-house control materials and for validating analytical methods for measurement of proximates, vitamins, and minerals in infant formula and similar matrixes. The SRM was manufactured by preparing a spray-dried formula base containing fat, protein, carbohydrates, and minerals and then combining that formula base with a dry-blend vitamin premix that supplied the vitamins. The Certificate of Analysis for SRM 1846 provides assigned values for concentrations of proximates (fat, protein, etc.), vitamins, and minerals for which product labeling is required by the Infant Formula Act of 1980 and by the Nutrition Labeling and Education Act of 1990. These assigned values were based on agreement of measurements by NIST and/or collaborating laboratories. Certified values are provided for vitamins A (trans), E, C, B-2, and B-6 and niacin. Noncertified values are provided for solids, ash, fat, nitrogen, protein, carbohydrate, calories, vitamin D, delta-tocopherol, gamma-tocopherol, Vitamin B-1, vitamin B-12, folic acid, pantothenic acid, biotin, choline, inositol, calcium, phosphorus, magnesium, iron, zinc, copper, sodium, potassium, and chloride. Information values are provided for iodine, manganese, selenium, and vitamin K. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. USDA,BELTSVILLE,MD 20705. RP Sharpless, KE (reprint author), NATL INST STAND & TECHNOL,GAITHERSBURG,MD 20899, USA. NR 15 TC 42 Z9 42 U1 0 U2 5 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1997 VL 80 IS 3 BP 611 EP 621 PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA XA023 UT WOS:A1997XA02300019 PM 9170657 ER PT J AU Turujman, SA Wamer, WG Wei, RR Albert, RH AF Turujman, SA Wamer, WG Wei, RR Albert, RH TI Rapid liquid chromatographic method to distinguish wild salmon from aquacultured salmon fed synthetic astaxanthin SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ONCORHYNCHUS-TSHAWYTSCHA; NATURAL OCCURRENCE; MESO-ASTAXANTHIN; OPTICAL ISOMERS; CANTHAXANTHIN; PIGMENTATION; CAROTENOIDS; RESOLUTION; SALAR AB Analytical methods are needed to determine the presence of color additives in fish. We report a liquid chromatographic (LC) method developed to identify the synthetic form of the color additive astaxanthin in salmon, based on differences in the relative ratios of the configurational isomers of astaxanthin. The distributions of configurational isomers of astaxanthin in the flesh of wild Atlantic and wild Pacific salmon are similar, but significantly different from that in aquacultured salmon. Astaxanthin is extracted from the flesh of salmon, passed through a silica gel Sep-Pak cartridge, and analyzed directly by LC on a Pirkle covalent L-leucine column. No derivatization of the astaxanthin is required-an important advantage of our approach, which is a modification of our previously described method. This method can be used to distinguish between aquacultured and wild salmon. The method has general applicability and can also be used to identify astaxanthins derived from other sources such as Phaffia yeast and Haematococcus pluvialis algae. RP Turujman, SA (reprint author), US FDA,OFF COSMET & COLORS,200 C ST SW,WASHINGTON,DC 20204, USA. NR 22 TC 53 Z9 63 U1 1 U2 12 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1997 VL 80 IS 3 BP 622 EP 632 PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA XA023 UT WOS:A1997XA02300020 PM 9170658 ER PT J AU Hopper, ML AF Hopper, ML TI Extraction and cleanup of organochlorine and organophosphorus pesticide residues in fats by supercritical fluid techniques SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID CARBON-DIOXIDE; HELIUM AB A supercritical fluid extraction and cleanup procedure was developed for separating organochlorine and organophosphorus pesticides from fats. Supercritical carbon dioxide modified with 3% (v/v) acetonitrile was used to extract the pesticides at 60 degrees C and separate the pesticides from the fats at 4000 psi and 95 degrees C on an in-line C-1 silica-based column. The extraction and cleanup procedure gave good recoveries for 43 of 62 nonpolar to moderately polar organochlorine and organophosphorus pesticides from fats, whereas 49 were recovered through conventional Florisil column cleanup before quantitation. This procedure can extract and clean up pesticide residues from 0.65 g animal-based fat and 1.0 g oils. Coeluted residues in the pesticide fraction ranged from 2.5 mg for butterfat to 0.8 mg for corn oil. Results for samples analyzed with this integrated extraction cleanup procedure were reproducible and comparable with results obtained with the current Total Diet Study methodology. RP Hopper, ML (reprint author), US FDA,TOTAL DIET & PESTICIDE RES CTR,POB 15905,LENEXA,KS 66285, USA. NR 12 TC 18 Z9 18 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 MAY-JUN PY 1997 VL 80 IS 3 BP 639 EP 646 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA XA023 UT WOS:A1997XA02300022 PM 9170660 ER PT J AU Yourick, JJ Bronaugh, RL AF Yourick, JJ Bronaugh, RL TI Percutaneous absorption and metabolism of coumarin in human and rat skin SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE coumarin; skin; dermal; skin absorption; dermal penetration; fragrance; cosmetic; rat; human skin ID HUMAN LIVER-MICROSOMES; INVITRO; GERBIL AB Coumarin is widely used as a fragrance in cosmetics, perfumes and soaps. The Food and Drug Administration banned coumarin use in food because of reports that coumarin produced hepatotoxicity in rodents, Concerns about coumarin's safety have also been raised by toxicity testing conducted by the National Toxicology Program. Therefore, we initiated studies to measure the extent of coumarin absorption and metabolism in skin. [C-14]Coumarin (ca. 0.5 mu Ci per cell) absorption in skin was measured by using two vehicles: ethanol (15 mu l cm(-2)) and an oil-in-water emulsion (3 mg cm(-2)). Absorption was determined for 24 h by using flow-through diffusion cells (0.64 cm(2), exposed skin) with a receptor fluid consisting of HEPES-buffered Hank's balanced salt solution (pH 7.4). Coumarin metabolism was determined by high-performance liquid chromatography methodology. In rat skin (n = 3), the percentages of applied dose absorbed after 24 h were 54.9 +/- 0.63 (mean +/- SEM) and 86.8 +/- 5.4 for the ethanol and emulsion vehicles, respectively, with ca, 5% remaining in skin. In human skin (n = 2), the percentages of applied dose absorbed after 24 h were 64.4 +/- 0.29 and 98.0 +/- 5.3 for the ethanol and emulsion vehicles, respectively, with ca. 1% remaining in skin. The extent of skin absorption was greater from the emulsion vehicle than from the ethanol vehicle in both human and rat skin. Coumarin rapidly penetrated both rat and human skin with >75% and >95%, respectively, of the absorbed dose found in the receptor fluid within 6 h. No evidence of coumarin metabolism was found in either skin or receptor fluid fractions. These studies indicate that coumarin absorption is significant in skin. Systemic coumarin absorption must be expected after dermal contact with coumarin-containing products. (C) 1997 by John Wiley & Sons, Ltd. RP Yourick, JJ (reprint author), US FDA,COSMET TOXICOL BRANCH,SKIN ABSORPT & METAB SECT,OFF COSMET & COLORS,HFS 128,LAUREL,MD 20708, USA. NR 27 TC 40 Z9 41 U1 0 U2 7 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 MAY-JUN PY 1997 VL 17 IS 3 BP 153 EP 158 DI 10.1002/(SICI)1099-1263(199705)17:3<153::AID-JAT426>3.0.CO;2-E PG 6 WC Toxicology SC Toxicology GA XM162 UT WOS:A1997XM16200002 PM 9250536 ER PT J AU Fields, PI Blom, K Hughes, HJ Helsel, LO Feng, P Swaminathan, B AF Fields, PI Blom, K Hughes, HJ Helsel, LO Feng, P Swaminathan, B TI Molecular characterization of the gene encoding H antigen in Escherichia coli and development of a PCR-restriction fragment length polymorphism test for identification of E-coli O157:H7 and O157:NM SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; CAUSE HEMORRHAGIC COLITIS; INFANTILE DIARRHEA; SEROTYPE O157-H7; DNA PROBE; STRAINS; FLAGELLIN; SEQUENCE AB Recent outbreaks of disease caused by Escherichia coli O157:H7 have focused much attention on this newly emerged pathogen. Identification of the H7 flagellar antigen is critical for the confirmation of E. coli O157:H7; however, clinical isolates are frequently nonmotile and do not produce detectable H antigen. To further characterize nonmotile isolates (designated NM), we developed a PCR-restriction fragment length polymorphism (PCR-RFLP) test to identify and characterize the gene encoding the H antigen (fliC) in E. coli. The entire coding sequence of fliC was amplified by PCR, the amplicon was restricted with RsaI, and the restriction fragment pattern was examined after gel electrophoresis. Two hundred eighty E. coli isolates representing serotypes O157:H7 and O157:NM, flagellar antigen H7 groups associated with other O serogroups, and all other flagellar antigen groups were analyzed. A single restriction pattern (pattern A) was identified for O157:H7 isolates, O157:NM isolates that produced Shiga toxin (formerly Shiga-like toxin or verotoxin), and 16 of 18 O55:H7 isolates. Flagellar antigen group H7 isolates of non-O157 serotypes had one of three banding patterns distinct from pattern A, A wide variety of patterns were found among isolates of the other 52 flagellar antigen groups; however, none was identical to the O157:H7 pattern. Thirteen of 15 nonmotile strains that did not produce the A pattern had patterns that matched those of other known H groups. The PCR-RFLP in conjunction with O serogroup determination will be useful in identifying E. coli O157:H7 and related strains that do not express immunoreactive H antigen and could be expanded to include other clinically important E. coli strains. C1 US FDA,WASHINGTON,DC 20204. RP Fields, PI (reprint author), CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,FOODBORNE & DIARRHEAL DIS BRANCH,ATLANTA,GA 30333, USA. NR 29 TC 116 Z9 120 U1 1 U2 3 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 MAY PY 1997 VL 35 IS 5 BP 1066 EP 1070 PG 5 WC Microbiology SC Microbiology GA WV178 UT WOS:A1997WV17800005 PM 9114382 ER PT J AU OReilly, S Grochow, LB Donehower, RC Chen, TL Bowling, K Hartman, NR Struck, RF Rowinsky, EK AF OReilly, S Grochow, LB Donehower, RC Chen, TL Bowling, K Hartman, NR Struck, RF Rowinsky, EK TI Phase I and pharmacologic study of penclomedine, a novel alkylating agent, in patients with solid tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 9th National-Cancer-Institute / European-Organization-for-the-Research-and-Treatment-of-Cancer Symposium on New Drugs in Cancer Therapy CY MAR 12-15, 1996 CL AMSTERDAM, NETHERLANDS SP NCI, European Org Res & Treatment Canc ID PRECLINICAL ANTITUMOR-ACTIVITY; NSC-338720; BRAIN AB Purpose: To determine the maximum-tolerated dose (MTD), principal toxicities, and pharmacologic behavior of penclomedine, a novel alkylating agent, Patients and Methods: Penclomedine (45 to 550 mg/m(2)/d every 3 weeks) was administered as a 1- or 3-hour intravenous (IV) infusion for 5 consecutive days to patients with solid tumors, Results: On a 1-hour dosing schedule, ataxia, vertigo, nystagmus, and a motor aphasia were the principal toxicities of penclomedine, These neurologic effects were dose-related, and evolved from complaints of somnolence and dizziness, to more pronounced signs and symptoms of cerebellar dysfunction, Up to and including doses of 415 mg/m(2), these effects were well tolerated and resolved within 2 hours posttreatment. In contrast, both patients treated Err the 550-mg/m(2) dose level experienced ct dose-limiting constellation of perinfusional aphasia and vertigo, with either ataxia of over 2 weeks' duration or recurrent dizziness, Prolongation of the infusion duration to 3 hours at this dose level resulted in less neurotoxicity; however, delayed trilineage hematologic toxicity precluded timely administration on this schedule, A statistically significant relationship was demonstrated between the development of ataxia and maximum plasma concentrations of penclomedine. Conclusion: Neurotoxicity was the dose-limiting toxicity (DLT) of penclomedine administered as a 1-hour infusion daily for 5 days every 3 weeks, and the recommended dose for further evaluations was 415 mg/m(2). The nature of the principal toxicities and the lack of any detectible antitumor activity indicate that phase II evaluations of penclomedine on this administration schedule should be focused on specific disease settings, such as breast cancer and intracerebral tumors, in which antitumor activity has been demonstrated, (C) 1997 by American Society of Clinical Oncology. C1 JOHNS HOPKINS UNIV,SCH MED,JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21205. US FDA,CTR DRUG EVALUAT & RES,LAUREL,MD. SO RES INST,BIRMINGHAM,AL 35255. FU NCI NIH HHS [N01 CM 07302, CA 01709-03, CA 70095-02] NR 32 TC 9 Z9 9 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1997 VL 15 IS 5 BP 1974 EP 1984 PG 11 WC Oncology SC Oncology GA WZ564 UT WOS:A1997WZ56400035 PM 9164209 ER PT J AU Miele, L AF Miele, L TI Points to consider in the manufacture and testing of monoclonal antibody products for human use (1997) SO JOURNAL OF IMMUNOTHERAPY LA English DT Article ID INFECTION; ANTIGEN; VIRUSES RP Miele, L (reprint author), NIH,DIV MONOCLONAL ANTIBODIES,CBER,US FDA,CAMPUS BLDG 29B,RM 3NN18,HFM-555,BETHESDA,MD 20892, USA. NR 28 TC 7 Z9 8 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY PY 1997 VL 20 IS 3 BP 214 EP 243 PG 30 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA XA886 UT WOS:A1997XA88600007 ER PT J AU DePaola, A Motes, ML Cook, DW Veazey, J Garthright, WE Blodgett, R AF DePaola, A Motes, ML Cook, DW Veazey, J Garthright, WE Blodgett, R TI Evaluation of an alkaline phosphatase-labeled DNA probe for enumeration of Vibrio vulnificus in Gulf Coast oysters SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE DNA probe; enzyme immunoassay; oyster; Vibrio vulnificus ID CRASSOSTREA-VIRGINICA; IDENTIFICATION; TEMPERATURE; ENVIRONMENT; SHELLSTOCK; SEAWATER; STORAGE AB A direct plating method and an FDA method were compared for enumeration of Vibrio vulnificus in Gulf Coast oysters. The direct plating method was based on hybridization of colony lifts and used an alkaline phosphatase-labeled oligonucleotide probe that targeted the cytolysin gene (Direct-VVAP). The FDA method employs most probable number analysis with confirmation of suspect isolates by enzyme immunoassay (MPN-EIA). Indigenous V. vulnificus levels in oysters harvested from Florida, Alabama and Louisiana throughout the year and in Gulf Coast market oysters ranged from <10 to 10(5) g(-1). Similar V. vulnificus levels (r=0.66) were found with these two procedures in freshly harvested oysters collected between April and October. Measurement variance was much greater, however, with the MPN procedure (0.118) than with the DNA probe procedure (0.004). In market oysters, the MPN-EIA procedure gave 0.4 log(10) higher estimates than the Direct-VVAP method, but the methods were closely correlated (r=0.83). Confirmation procedures were in agreement >90% of the time, as suspect isolates confirmed by one procedure were identified by the other procedure. Except when V. vulnificus densities are low (<10 g(-1)), the Direct-VVAP method provides an alternative procedure that is more rapid and precise than the MPN-EIA analysis. (C) 1997 Elsevier Science B.V. C1 US FDA,RESIDENT POST,BATON ROUGE,LA. US FDA,DIV MATH,WASHINGTON,DC 20204. RP DePaola, A (reprint author), US FDA,GULF COAST RES LAB,DAUPHIN ISL,AL 36528, USA. NR 19 TC 33 Z9 33 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD MAY PY 1997 VL 29 IS 2 BP 115 EP 120 DI 10.1016/S0167-7012(97)00030-4 PG 6 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA XM163 UT WOS:A1997XM16300006 ER PT J AU Blakely, SR Rogers, A Hendrich, S AF Blakely, SR Rogers, A Hendrich, S TI Symposium: Animal diets for nutritional and toxicological research - Introduction SO JOURNAL OF NUTRITION LA English DT Editorial Material ID MICE C1 BOSTON UNIV,MED CTR,BOSTON,MA. IOWA STATE UNIV,AMES,IA 50011. RP Blakely, SR (reprint author), US FDA,WASHINGTON,DC 20204, USA. NR 13 TC 2 Z9 2 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 1997 VL 127 SU 5 BP S824 EP S825 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WZ923 UT WOS:A1997WZ92300009 ER PT J AU Jackson, CD Weis, C Miller, BJ James, SJ AF Jackson, CD Weis, C Miller, BJ James, SJ TI Dietary nucleotides: Effects on cell proliferation following partial hepatectomy in rats fed NIH-31, AIN-76A, or folate/methyl-deficient diets SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Animal Diets for Nutritional and Toxicological Research at Experimental Biology 96 CY APR 15, 1996 CL WASHINGTON, DC SP Amer Soc Nutr Sci, Natl Canc Inst, Int Life Sci Inst DE dietary nucleotides; cell proliferation; purified diets; F344 rats ID PANCREATIC CARCINOGENESIS; OROTIC-ACID; DNA; INHIBITION; MISINCORPORATION; PERTURBATIONS; LYMPHOCYTES; TOXICITY; LIVER; POOLS AB The requirement of a number of tissues for dietary nucleotides could explain some of the differences observed in animals fed natural ingredient diets vs. those fed purified diets lacking a source of dietary nucleotides. Lack of dietary nucleotides is exacerbated in animals fed folate- or methyl-deficient semipurified diets, in which both salvage and folate-dependent de novo synthetic pathways are diminished. We examined hepatocyte proliferation following partial hepatectomy in weanling male Fischer-344 rats fed natural ingredient NIH-31 diet, nucleotide-free purified AIN-76A diet or a basal diet similar to AIN-76A but deficient in the methyl donors folate, choline and methionine. Additional groups were fed AIN-76A or folate/methyl-deficient diets supplemented with 0.25% yeast RNA. Compared with NIH-31,AIN-76A increased dUMP/dTTP ratios, reduced the mitotic index (MI) and increased the ratio of proliferating cell index (PCI) to mitotic cells, an indication that hepatocytes were delayed in S-phase. Addition of yeast RNA to AIN-76A reversed (by approximately 50%) the effects of AIN-76A on dUMP/dTTP and cell proliferation. A folate/methyl-deficient diet also produced an increased dUMP/dTTP ratio and markedly reduced the MI, increasing the PCI/MI, which suggested even further delay of cells in S-phase. Addition of yeast RNA to the folate/methyl-deficient diet was effective in significantly reversing the effects of folate/methyl deficiency. RP Jackson, CD (reprint author), NATL CTR TOXICOL RES,DIV NUTR TOXICOL,JEFFERSON,AR 72079, USA. NR 33 TC 9 Z9 10 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 1997 VL 127 SU 5 BP S834 EP S837 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WZ923 UT WOS:A1997WZ92300012 PM 9164248 ER PT J AU Mahmood, I AF Mahmood, I TI A comparative computer simulation study of three different sparse-sampling methods for the estimation of steady-state area under the concentration-time curve (AUC) and maximum concentration (C-max) in toxicokinetics SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID PHARMACOKINETICS; MODEL AB A limited-sampling method is proposed to estimate the area under the curve (AUC) of concentration Versus time and maximum concentration (C-max,) following single or multiple oral doses of a hypothetical drug. The plasma concentration versus time data sets for 50 animals were generated by simulation. The limited-sampling model (LSM) was developed with samples from 10 animals at a single time point. The model was validated in another 40 animals who received either a 500-mg single dose or multiple doses orally. The model provided good population mean estimates of AUC and C-max. The proposed method was compared with the existing two methods; they are, naive sampling (five time points) and optimal sampling (three time points). The method described here may be useful in estimating AUC and C-max with one or two samples in toxicokinetic studies following single or multiple oral dosing without detailed pharmacokinetic studies. RP Mahmood, I (reprint author), US FDA,DIV PHARMACEUT EVALUAT 1,OFF CLIN PHARMACOL & BIOPHARMACEUT,HFD-860,ROOM 4054,ROCKVILLE,MD 20852, USA. NR 17 TC 14 Z9 14 U1 0 U2 0 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 MAY PY 1997 VL 86 IS 5 BP 579 EP 583 DI 10.1021/js960450i PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA WX101 UT WOS:A1997WX10100009 PM 9145382 ER PT J AU Revelle, LK Musser, SM Rowe, BJ Feldman, IC AF Revelle, LK Musser, SM Rowe, BJ Feldman, IC TI Identification of chlorothiazide and hydrochlorothiazide UV-A photolytic decomposition products SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article AB Methanol solutions of hydrochlorothiazide and chlorothiazide were irradiated with fluorescent UV-A lamps in order to simulate degradation under normal conditions. The degradation products were identified by comparison to synthetic standards featuring electrospray ionization mass spectroscopy, ultraviolet spectroscopy, and high performance liquid chromatography. The standards were characterized by high resolution fast atom bombardment MS and H-1 NMR. The photolysis of chlorothiazide resulted in photodehalogenation products exclusively, while the irradiation of hydrochlorothiazide primarily yielded photodehalogenation products with significant yields of photodehydrogenation products and minor amounts of thermal hydrolysis products. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,INSTRUMENTAT & BIOPHYS BRANCH,WASHINGTON,DC 20204. RP Revelle, LK (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV DRUG ANAL,1114 MARKET ST,ROOM 1002,ST LOUIS,MO 63101, USA. FU NCRR NIH HHS [P41RR0954] NR 10 TC 6 Z9 6 U1 1 U2 8 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 MAY PY 1997 VL 86 IS 5 BP 631 EP 634 DI 10.1021/js9601501 PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA WX101 UT WOS:A1997WX10100018 PM 9145391 ER PT J AU Tran, TT Yin, JJ AF Tran, TT Yin, JJ TI A modified AnaeroGen(TM) system for growth of Campylobacter spp SO JOURNAL OF RAPID METHODS AND AUTOMATION IN MICROBIOLOGY LA English DT Article AB A simple, rapid procedure to generate an oxygen-reduced atmosphere suitable for growing Campylobacter jejuni was investigated. A modified AnaeroGen(TM) system (MAS), consisting of a single AnaeroGen(TM) anaerobic sachet AM35 (Oxoid Unipath Ltd., Basingstoke, UK) activated in a 9 L anaerobic jar (BBL, Cockeysville, MD), was evaluated and compared with the conventional gassed jar system described in the 8th edition of the U.S. Food and Drug Administration's Bacteriological Analytical Manual (BAM). Enriched cultures of C. jejuni (six replicates at each of five inoculum levels: 10(2) to 10(2) cfu/mL in artificially contaminated raw milk, raw oyster, crab meat, or mushroom were streaked in duplicate onto four different selective isolation agars for simultaneous incubation in MAS and in the BAM system. No significant differences (p > 0.05) in recovery rates of C. jejuni were observed for the two systems. The type of isolation agar used did not affect these recovery rates. The quality of growth of C. jejuni at 24, 48 or 72 h was similar in both systems. MAS successfully reduced atmospheric oxygen to a level suitable for the growth of C. jejuni. It was simple and rapid compared to the BAM system, and cost effective compared to the Oxoid CampyGen(TM) system specifically designed for the growth of Campylobacter spp. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,DIV GEN SCI SUPPORT,WASHINGTON,DC 20204. RP Tran, TT (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV MIRCROBIOL STUDIES,HFS-516,200 C ST SW,WASHINGTON,DC 20204, USA. RI Yin, Jun Jie /E-5619-2014 NR 10 TC 3 Z9 3 U1 0 U2 0 PU FOOD NUTRITION PRESS INC PI TRUMBULL PA 6527 MAIN ST, P O BOX 374, TRUMBULL, CT 06611 SN 1060-3999 J9 J RAPID METH AUT MIC JI J. Rapid Methods Autom. Microbiol. PD MAY PY 1997 VL 5 IS 2 BP 139 EP 149 PG 11 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA XT370 UT WOS:A1997XT37000003 ER PT J AU Wright, PR RichfieldFratz, N Rasooly, A Weisz, A AF Wright, PR RichfieldFratz, N Rasooly, A Weisz, A TI Quantitative analysis of components of the color additives D&C Red Nos 27 and 28 (Phloxine B) by thin-layer chromatography and video densitometry SO JPC-JOURNAL OF PLANAR CHROMATOGRAPHY-MODERN TLC LA English DT Article; Proceedings Paper CT 110th AOAC International Annual Meeting and Exposition CY SEP 08-12, 1996 CL ORLANDO, FL SP AOAC DE HPTLC; video densitometry; color additives; D&C Red Nos 27 and 28; Phloxine B ID COUNTERCURRENT CHROMATOGRAPHY AB A simple and rapid TLC - videodensitometric method has been developed for the in situ quantification either of lower halogenated subsidiary colors (LHSC) or of the ethyl ester (EE) in multiple dye samples on the same analytical TLC plate. The results obtained by this method were compared with those obtained by an indirect TLC - spectrophotometric method and those obtained by HPLC. The total time for the TLC - videodensitometric assay of five standards and four samples applied to each plate was 45 min or less. This method for the determination of LHSC and EE in D&C Red Nos. 27 and 28 was found to be applicable for use in routine batch-certification analysis. C1 US FDA,OFF COSMET & COLORS,WASHINGTON,DC 20204. US FDA,OFF SPECIAL RES SKILLS,WASHINGTON,DC 20204. NR 8 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER HUNGARICA KIADO KFT PI BUDAPEST PA WESSELENYI U 28, H-1075 BUDAPEST, HUNGARY SN 0933-4173 J9 JPC-J PLANAR CHROMAT JI JPC-J. Planar Chromatogr.-Mod. TLC PD MAY-JUN PY 1997 VL 10 IS 3 BP 157 EP 162 PG 6 WC Chemistry, Analytical SC Chemistry GA XL149 UT WOS:A1997XL14900002 ER PT J AU Husain, SR Gill, P Kreitman, RJ Pastan, I Puri, RK AF Husain, SR Gill, P Kreitman, RJ Pastan, I Puri, RK TI Interleukin-4 receptor expression on AIDS-associated Kaposi's sarcoma cells and their targeting by a chimeric protein comprised of circularly permuted interleukin-4 and Pseudomonas exotoxin SO MOLECULAR MEDICINE LA English DT Article ID CARCINOMA-CELLS; HIGH-AFFINITY; SIGNAL-TRANSDUCTION; IL-4 RECEPTORS; GAMMA-CHAIN; GROWTH; BINDING; IDENTIFICATION; PATHOGENESIS; MECHANISMS AB Background: AIDS-associated Kaposi's sarcoma (AIDS-KS) represents one of the most common malignancies associated with human immunodeficiency virus infection. To target effective therapeutic agents to AIDS-KS, we have identified a new target in the form of interleukin-4 receptors (IL-4R). Materials and Methods: The expression of IL-4R on AIDS-KS cells and their subunit structure was determined by radioligand receptor binding, cross-linking, and Northern and RT-PCR analyses. The in vitro effect of IL-4 and recombinant fusion protein made up of circularly permuted IL-4 and a mutated form of Pseudomonas exotoxin, IL-4(38-37)-PH38KDEL, was examined by clonogenic and protein synthesis inhibition assays. Results: Five AIDS-KS cell lines expressed high-affinity IL-4R with a K-d of 23.5-219 pM. IL-4 appeared to cross-link to one major protein corresponding to 140 kDa and a broad band corresponding to 60-70 kDa. Both cross-linked proteins were immunoprecipitated with an antibody to human IL-4R beta chain. AIDS-KS cells exhibited IL-4R beta-specific mRNA. IL-4 caused a modest inhibition (31-34%) of colony formation in two AIDS-KS cell lines tested. IL-4(38-37)-PE38KDEL was found to be highly effective in inhibiting the protein synthesis in all five AIDS-KS examined. The IC50 ranged from 32 to 1225 pM. The cytotoxic action of IL-4 toxin was blocked by an excess of IL-4, exhibiting the specificity of IL-4(38-37)-PE38KDEL. The cytotoxicity of IL-4 toxin observed by a donogenic assay corroborated well with the IC50 obtained by protein synthesis inhibition assay. Normal human endothelial cells expressed a negligible number of IL-4R (<50 sites/cell) and were less sensitive or not sensitive to IL-4(38-37)-PE38KDEL. Conclusion: The presence of a new plasma membrane protein in the form of IL-4R on AIDS-KS cells may be targeted by IL-4(38-37)-PE38KDEL for its potential implication in the treatment of AIDS-KS. C1 NIH,LAB MOL TUMOR BIOL,DIV CELLULAR & GENEN THERAPIES,CTR BIOL EVALUAT & RES,FOOD AND DRUG ADM,BETHESDA,MD 20892. UNIV SO CALIF,SCH MED,LOS ANGELES,CA. NCI,MOL BIOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 54 TC 37 Z9 39 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 1076-1551 J9 MOL MED JI Mol. Med. PD MAY PY 1997 VL 3 IS 5 BP 327 EP 338 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA XC147 UT WOS:A1997XC14700005 PM 9205948 ER PT J AU Sassaman, DM Dombroski, BA Moran, JV Kimberland, ML Naas, TP DeBerardinis, RJ Gabriel, A Swergold, GD Kazazian, HH AF Sassaman, DM Dombroski, BA Moran, JV Kimberland, ML Naas, TP DeBerardinis, RJ Gabriel, A Swergold, GD Kazazian, HH TI Many human L1 elements are capable of retrotransposition SO NATURE GENETICS LA English DT Article ID HUMAN TRANSPOSABLE ELEMENT; REVERSE-TRANSCRIPTASE; SACCHAROMYCES-CEREVISIAE; DNA-SEQUENCES; INSERTION; LINE-1; MUTAGENESIS; GENE; IDENTIFICATION; FAMILY AB Using a selective screening strategy to enrich for active L1 elements, we isolated 13 full-length elements from a human genomic library. We tested these and two previously-isolated L1s (L1.3 and L1.4) for reverse transcriptase (RT) activity and the ability to retrotranspose in HeLa cells, Of the 13 newly-isolated L1s, eight had RT activity and three were able to retrotranspose. L1.3 and L1.4 possessed RT activity and retrotransposed at remarkably high frequencies. These studies bring the number of characterized active human L1 elements to seven. Based on these and other data, we estimate that 30-60 active L1 elements reside in the average diploid genome. C1 UNIV PENN, SCH MED, DEPT GENET, PHILADELPHIA, PA 19104 USA. RUTGERS STATE UNIV, DEPT MOL BIOL & BIOCHEM, PISCATAWAY, NJ 08855 USA. US FDA, BETHESDA, MD 20892 USA. NR 39 TC 278 Z9 282 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD MAY PY 1997 VL 16 IS 1 BP 37 EP 43 DI 10.1038/ng0597-37 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA WX024 UT WOS:A1997WX02400020 PM 9140393 ER PT J AU FitzSimmons, SC Burkhart, GA Borowitz, D Grand, RJ Hammerstrom, T Durie, PR LloydStill, JD Lowenfels, AB AF FitzSimmons, SC Burkhart, GA Borowitz, D Grand, RJ Hammerstrom, T Durie, PR LloydStill, JD Lowenfels, AB TI High-dose pancreatic-enzyme supplements and fibrosing colonopathy in children with cystic fibrosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID COLONIC STRICTURES; EPIDEMIOLOGY; DISEASE AB Background Fibrosing colonopathy has been reported in young children with cystic fibrosis, the majority of whom take high-strength pancreatic-enzyme supplements to control intestinal malabsorption. We conducted a case-control study in the United States to investigate the relation between dose and type of pancreatic-enzyme supplement and fibrosing colonopathy. Methods Children with histopathologically con firmed cases of fibrosing colonopathy who required colectomy for colonic strictures from January 1, 1990, through December 31, 1994, were identified. Each of these patients was matched according to age at the time of surgery and medical center with up to four controls with cystic fibrosis who did not have fibrosing colonopathy. Results We studied 29 patients (mean age, 5.0 years) with fibrosing colonopathy (case patients) and 105 controls (mean age, 5.2 years). The mean dose of pancreatic-enzyme supplement was 50,046 units of lipase per kilogram of body weight per day for the case patients and 18,985 units per kilogram per day for the controls. A history of gastrointestinal complications attributed to cystic fibrosis and the use of histamine H-2-receptor blockers, corticosteroids, or recombinant human DNase (dornase alfa) were associated with a higher incidence of fibrosing colonopathy. After adjustment for a history of such complications and the use of these medicines, the relative risk of fibrosing colonopathy that was associated with a dose of 24,001 to 50,000 units of lipase per kilogram per day, as compared with a close of 0 to 24,000 units per kilogram per day, was 10.9 (95 percent confidence interval, 1.6 to 71.8), and that associated with a dose of more than 50,000 units per kilogram per day was 199.5 (95 percent confidence interval, 9.9 to 4026.0). The strength, coating, and manufacturer of the products used were not associated with the risk of fibrosing colonopathy. Conclusions In young children with cystic fibrosis, we found a strong relation between high daily doses of pancreatic-enzyme supplements and the development of fibrosing colonopathy. Our findings support recommendations that the daily dose of pancreatic enzymes for most patients should remain below 10,000 units of lipase per kilogram. (C) 1997, Massachusetts Medical Society. C1 US FDA, CTR DRUG EVALUAT & RES, ROCKVILLE, MD 20857 USA. CHILDRENS HOSP BUFFALO, DEPT PEDIAT PULMONOL, BUFFALO, NY USA. TUFTS UNIV, SCH MED, DIV PEDIAT GASTROENTEROL & NUTR, BOSTON, MA 02111 USA. HOSP SICK CHILDREN, DIV PEDIAT GASTROENTEROL & NUTR, TORONTO, ON M5G 1X8, CANADA. RUSH MED COLL, DEPT PEDIAT, CHICAGO, IL 60612 USA. NEW YORK MED COLL, DEPT SURG & COMMUNITY & PREVENT MED, VALHALLA, NY 10595 USA. EUROPEAN INST ONCOL, MILAN, ITALY. RP CYST FIBROSIS FDN, DEPT MED, 6931 ARLINGTON RD, BETHESDA, MD 20814 USA. FU NIAID NIH HHS [AI06331] NR 21 TC 133 Z9 134 U1 0 U2 10 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 1 PY 1997 VL 336 IS 18 BP 1283 EP 1289 DI 10.1056/NEJM199705013361803 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA WW260 UT WOS:A1997WW26000003 PM 9113931 ER PT J AU Black, S Shinefield, H Ray, P Lewis, E Chen, R Glasser, J Hadler, S Hardy, J Rhodes, P Swint, E Davis, R Thompson, R Mullooly, J Marcy, M Vadheim, C Ward, J Rastogi, S Wise, R AF Black, S Shinefield, H Ray, P Lewis, E Chen, R Glasser, J Hadler, S Hardy, J Rhodes, P Swint, E Davis, R Thompson, R Mullooly, J Marcy, M Vadheim, C Ward, J Rastogi, S Wise, R TI Risk of hospitalization because of aseptic meningitis after measles-mumps-rubella vaccination in one- to two-year-old children: An analysis of the Vaccine Safety Datalink (VSD) Project SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE mumps; measles-mumps-rubella; aseptic meningitis AB Objective. To assess the level of increased risk, if any, of hospitalizations for aseptic meningitis after Jeryl-Lynn mumps strain measles-mumps-rubella (MMR) vaccine in the Vaccine Safety Datalink population. Study design. A possible increased risk of aseptic meningitis 8 to 14 days after receipt of MMR was observed in a preliminary screening analysis of automated data from the Vaccine Safety Datalink (VSD) project Year 2 analysis. To further evaluate this association a retrospective 10-year matched case-control study was undertaken in the four health maintenance organizations (HMOs) in the VSD project. Cases ascertained from a broad scan of the automated data were validated against a standard case definition. Two controls matched on age, sex, HMO and HMO membership were assigned per case. Results. The VSD project involves the cooperative collection of automated vaccination and medical outcome data from four large HMOs that currently have 500 000 children younger than 7 years of age under surveillance. Review of automated screening results from the first 2 years of data revealed a possible increased risk of aseptic meningitis 0 to 14 days after MMR with a relative risk of 3.61 (95% confidence interval, 1.0 to 13.1) although the total number of cases was small. Although the automated data had suggested a possible association of aseptic meningitis with MMR containing the Jeryl-Lynn strain of mumps, review of validated hospitalized cases during the observation period did not reveal evidence of an increased risk of aseptic meningitis after MMR containing the Jeryl-Lynn strain of mumps (odds ratio <1.0 for all analyses). Conclusion. Although it is recognized that hospitalized cases represent a minority of the total cases of aseptic meningitis, it is reassuring that in this evaluation no increased risk of aseptic meningitis after MMR vaccine was found. C1 KAISER PERMANENTE VACCINE STUDY CTR,OAKLAND,CA. CTR DIS CONTROL,NATL IMMUNIZAT PROGRAM,ATLANTA,GA. GRP HLTH COOPERAT PUGET SOUND,SEATTLE,WA. SO CALIF KAISER PERMANENTE,PANORAMA CITY,CA. UNIV CALIF LOS ANGELES,VACCINE STUDY CTR,TORRANCE,CA. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. 4 KAISER PERMANENTE NW REG,PORTLAND,OR. NR 11 TC 34 Z9 36 U1 0 U2 1 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 MAY PY 1997 VL 16 IS 5 BP 500 EP 503 DI 10.1097/00006454-199705000-00009 PG 4 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA WY861 UT WOS:A1997WY86100008 PM 9154545 ER PT J AU Chung, TH Kim, JC Lee, CY Moon, MK Chae, SC Lee, IS Kim, SH Hahn, KS Lee, IP AF Chung, TH Kim, JC Lee, CY Moon, MK Chae, SC Lee, IS Kim, SH Hahn, KS Lee, IP TI Potential antiviral effects of Terminalis chebula, Sanguisorba officinalis, Rubus coreanus and Rheum palmatum against duck hepatitis B virus (DHBV) SO PHYTOTHERAPY RESEARCH LA English DT Article DE duck hepatitis B virus; DHBV DNA polymerase; Korean medicinal plants ID DNA; MARKERS; SERUM AB The potential antiviral effects against duck hepatitis B virus were investigated using aqueous extracts of Terminalis chebula, Sanguisorba officinalis, Rubus coreanus and Rheum palmatum. Previously, these herbal extracts were shown to inhibit hepatitis B virus (HBV) DNA polymerase activity and to bind hepatitis B virus surface antigen (HBsAg), Antiviral effects of herbal extracts were determined using Peking ducks (Anas domesticus) infected with duck hepatitis B virus (DHBV). During a 4-week treatment period,vith selected plant extracts, serum DHBV DNA levels and DHBV DNA polymerase activity were measured as antiviral indicators, Although all extracts demonstrated antiviral activity against DHBV, Terminalis chebula appeared to exhibit the highest antiviral activity. (C) 1997 by John Wiley & Sons, Ltd. C1 KYUNGPOOK NATL UNIV,BASIC MED SCI RES INST,SCH MED,TAEGU 702701,SOUTH KOREA. US FDA,DIV TOXICOL RES,MOL MECH TEAM,LAUREL,MD 20708. KEI MYONG UNIV,DEPT FOOD SCI,TAGUE,SOUTH KOREA. GENET ENGN RES INST,DAEDUCK,TAJEON,SOUTH KOREA. RP Chung, TH (reprint author), KYUNGPOOK NATL UNIV,LIVER RES INST,SCH MED,101 DONG IN DONG JUNG GU,TAEGU 702701,SOUTH KOREA. NR 11 TC 11 Z9 11 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0951-418X J9 PHYTOTHER RES JI Phytother. Res. PD MAY PY 1997 VL 11 IS 3 BP 179 EP 182 DI 10.1002/(SICI)1099-1573(199705)11:3<179::AID-PTR50>3.0.CO;2-F PG 4 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WX042 UT WOS:A1997WX04200001 ER PT J AU Suleiman, OH Conway, BJ Quinn, P Antonsen, RG Rueter, FG Slayton, RJ Spelic, DC AF Suleiman, OH Conway, BJ Quinn, P Antonsen, RG Rueter, FG Slayton, RJ Spelic, DC TI Nationwide survey of fluoroscopy: Radiation dose and image quality SO RADIOLOGY LA English DT Article DE fluoroscopy, technology; gastrointestinal tract, radiography; phantoms; radiations, exposure to patients and personnel; radiations, measurement; test objects ID LUMBOSACRAL SPINE; FACILITIES AB PURPOSE: To determine the average abdominal entrance air kerma, low-contrast sensitivity, and spatial resolution in upper gastrointestinal tract fluoroscopy in the United States. MATERIALS AND METHODS: A random sample of fluoroscopic facilities was selected to be surveyed for the Nationwide Evaluation of X-ray Trends program. Measurements were performed by using a newly developed fluoroscopic phantom. The surveys were conducted by state radiation control personnel. RESULTS: Average air kerma rates 1 cm above the tabletop, free in air, were 43 mGy/min (n = 340). The rate increased to 64 mGy/min when a 1.6-mm-thick copper filter, which simulated the use of barium contrast medium, was added to increase attenuation. The average entrance air kerma, free in air, for radiographs was 3.4 mGy, and an average of 12 radiographs were obtained per examination. Of 352 facilities surveyed, 306 (87%) were able to resolve wire mesh with 20 or more lines per inch. Of 339 facilities for which percentage contrast could be calculated, 192 (57%) had minimum percentage contrast values of 4% or more. CONCLUSION: Spatial resolution for fluoroscopy is adequate for most of the facilities surveyed, but a substantial proportion of facilities could not visualize low-contrast test objects, which strongly suggests image quality problems. RP Suleiman, OH (reprint author), US FDA,CTR DEVICES & RADIOL HLTH HFZ240,DIV MAMMOG QUAL & RADIAT PROGRAMS,1350 PICCARD DR,ROCKVILLE,MD 20850, USA. NR 22 TC 18 Z9 19 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 MAY PY 1997 VL 203 IS 2 BP 471 EP 476 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WU532 UT WOS:A1997WU53200036 PM 9114107 ER PT J AU Ellenberg, SS AF Ellenberg, SS TI A conversation with John C. Bailar III SO STATISTICAL SCIENCE LA English DT Article AB John Christian Bailar III was born on October 9, 1932, in Urbana, Illinois. He received his B.A. degree from the University of Colorado in 1953, an M.D. from Yale University in 1955 and a Ph.D. in statistics from American University in 1973. He is a Fellow of the American Statistical Association, an elected member of the International Statistical Institute, a Fellow of the American College of Epidemiology, a Fellow of the American Association for the Advancement of Science, an elected member of the Collegium Ramazzini and a MacArthur Fellow (1990-1995). He was Editor-in-Chief of the Journal of the National Cancer Institute and has been on the Editorial Board of Cancer Research. He has served as Statistical Consultant for the New England Journal of Medicine and is currently a member of its Editorial Board. He has served as Chair of the Biometrics Section of the American Statistical Association, was Founding Chair of the Boston Chapter of the Society for Risk Analysis and was President of the Council of Biology Editors. His tenure at NIH included the years 1956-1970 and 1972-1980 on staff at the National Cancer Institute, with st stint at the Veterans Administration from 1970-1972. He began as a Field Investigator in the Biometry Branch, was appointed Head of the Demography Section and then Director of the Third National Cancer Survey. His last appointment at NCI was Deputy Associate Director for Cancer Control. He was awarded the Commendation Medal from the United States Public Health Service for his work on breast cancer screening. Since leaving NIH, he was a Senior Scientist at the Environmental Protection Agency and the Department of Health and Human Services, a Lecturer in Biostatistics at the Harvard School of Public Health, on staff at the Health Effects Institute and Professor and Chair of the Department of Epidemiology and Biostatistics at McGill University Faculty of Medicine. Since 1995, he has been Professor and Chair of the Department of Health Studies at the University of Chicago. RP Ellenberg, SS (reprint author), US FDA,DIV BIOSTAT & EPIDEMIOL,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU INST MATHEMATICAL STATISTICS PI HAYWARD PA IMS BUSINESS OFFICE-SUITE 6 3401 INVESTMENT BLVD, HAYWARD, CA 94545 SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD MAY PY 1997 VL 12 IS 2 BP 119 EP 124 PG 6 WC Statistics & Probability SC Mathematics GA XT268 UT WOS:A1997XT26800008 ER PT J AU Gessner, BD Bell, P Doucette, GJ Moczydlowski, E Poli, MA VanDolah, F Hall, S AF Gessner, BD Bell, P Doucette, GJ Moczydlowski, E Poli, MA VanDolah, F Hall, S TI Hypertension and identification of toxin in human urine and serum following a cluster of mussel-associated paralytic shellfish poisoning outbreaks SO TOXICON LA English DT Article ID SAXITOXIN-BINDING PROTEIN; SODIUM-CHANNELS; MUSCLE; TETRODOTOXIN; BULLFROG; RAT; SAXIPHILIN; CHEMISTRY; CHILE AB Following four outbreaks of paralytic shellfish poisoning on Kodiak Island, Alaska, during 1994, medical records of ill persons were reviewed and interviews were conducted, Urine and serum specimens were analyzed at three independent laboratories using four different saxitoxin binding assays, High-performance liquid chromatography was used to determine the presence of specific toxin congeners, Among 11 ill persons, three required mechanical ventilation and one died, Mean peak systolic and diastolic blood pressure measurements were 172 (range 128-247) and 102 (range 78-165) mmHg, respectively, and blood pressure measurements corresponded with ingested toxin dose, All four different laboratory methodologies detected toxin in serum at 2.8-47 nM during acute illness and toxin in urine at 65-372 nM after acute symptom resolution. The composition of specific paralytic shellfish poisons differed between mussels and human biological specimens, suggesting that human metabolism of toxins had occurred. The results of this study indicate that saxitoxin analogues may cause severe hypertension. In addition, we demonstrate that saxitoxins can be detected in human biological specimens, that nanomolar serum toxin levels may cause serious illness and that human metabolism of toxin may occur. Clearance of paralytic shellfish poisons from serum was evident within 24 hr and urine was identified as a major route of toxin excretion in humans. (C) 1997 Elsevier Science Ltd. C1 YALE UNIV, SCH MED, DEPT PHARMACOL, NEW HAVEN, CT 06520 USA. YALE UNIV, SCH MED, DEPT CELLULAR & MOL PHYSIOL, NEW HAVEN, CT 06520 USA. US DEPT COMMERCE, NOAA, SE FISHERIES SCI CTR, NATL MARINE FISHERIES SERV, CHARLESTON, SC 29422 USA. USA, MED RES INST INFECT DIS, FT DETRICK, MD 21702 USA. US FDA, WASHINGTON, DC 20204 USA. RP Gessner, BD (reprint author), ALASKA DIV PUBL HLTH, 1231 GAMBELL ST, 2ND FLOOR, ANCHORAGE, AK 99501 USA. RI Moczydlowski, Edward/A-9304-2009; Moczydlowski, Edward/D-1734-2013; Doucette, Gregory/M-3283-2013 NR 35 TC 61 Z9 65 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD MAY PY 1997 VL 35 IS 5 BP 711 EP 722 DI 10.1016/S0041-0101(96)00154-7 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA XE623 UT WOS:A1997XE62300010 PM 9203296 ER PT J AU Poli, MA Lewis, RJ Dickey, RW Musser, SM Buckner, CA Carpenter, LG AF Poli, MA Lewis, RJ Dickey, RW Musser, SM Buckner, CA Carpenter, LG TI Identification of Caribbean ciguatoxins as the cause of an outbreak of fish poisoning among US soldiers in Haiti SO TOXICON LA English DT Article ID PURIFICATION; CIGUATERA AB On 24 February 1995, six U.S. soldiers serving with the Multinational Force in Haiti became ill after eating a locally caught fish identified as the greater amberjack Seriola dumerili. The victims presented with nausea, vomiting, watery diarrhea and abdominal cramps 5-8 hr after consumption, Also present in some victims were numbness in the extremities or perioral region, bradycardia and scalp paresthesia. Patients were treated with i,v. hydration therapy and antiemetics. All recovered without sequelae over the course of 1-3 months. A portion of the cooked fish was obtained for analysis. A semipurified lipid extract was prepared according to standard methods and analyzed for the presence of Na+ channel site 5 binding activity using a brevetoxin receptor binding assay. By this assay, the fish sample contained the equivalent of approximately 20 ng Caribbean ciguatoxin/g flesh. The presence of the major Caribbean ciguatoxin (C-CTX-1) was confirmed by liquid chromatography-mass spectrometry. Using the receptor binding assay to monitor activity in TSK and PRP-1 column fractions, two minor toxins were detected in addition to C-CTX-1. One of these minor toxins was more polar, and the other less polar, than C-CTX-1. These data provide firm evidence that a family of C-CTX-1 is responsible for ciguatera in the Caribbean. Published by Elsevier Science Ltd. C1 UNIV QUEENSLAND,QUEENSLAND DEPT PRIMARY IND,BRISBANE,QLD,AUSTRALIA. US FDA,GULF COAST RES LAB,DAUPHIN ISL,AL 36528. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. TRIPLER ARMY MED CTR,HONOLULU,HI 96859. USA,INST SURG RES,SAN ANTONIO,TX 78234. RP Poli, MA (reprint author), USA,MED RES INST INFECT DIS,TOXINOL DIV,FT DETRICK,MD 21702, USA. RI Lewis, Richard/E-8674-2013 OI Lewis, Richard/0000-0003-3470-923X NR 17 TC 63 Z9 69 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0041-0101 J9 TOXICON JI Toxicon PD MAY PY 1997 VL 35 IS 5 BP 733 EP 741 DI 10.1016/S0041-0101(96)00166-3 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA XE623 UT WOS:A1997XE62300012 PM 9203298 ER PT J AU McNeilly, PJ Torchin, CD Anderson, LW Kapetanovic, IM Kupferberg, HJ Strong, JM AF McNeilly, PJ Torchin, CD Anderson, LW Kapetanovic, IM Kupferberg, HJ Strong, JM TI In vitro glucuronidation of D-23129, a new anticonvulsant, by human liver microsomes and liver slices SO XENOBIOTICA LA English DT Article ID N-GLUCURONIDATION; UDP-GLUCURONOSYLTRANSFERASES; ANALGESIC FLUPIRTINE; HEPATIC MICROSOMES; RAT; METABOLISM; BIOTRANSFORMATION; PHARMACOKINETICS; TETRAZOLE; DRUG AB 1. The metabolic profile of D-23129, a new anticonvulsant agent, was studied in vitro using human liver microsomes and fresh liver slices. 2. Oxidative metabolism appeared to be minimal with D-23129. The percent mean total radioactivity not associated with the parent compound recovered from oxidative metabolism studies from three individual liver donors was 0.7%+/-0.6% SD and was not significantly different from [C-14]-D-23129 incubated with heat inactivated microsomes, mean = 0.5%+/-0.4 SD. 3. Phase II conjugation dominated the metabolism of D-23129 producing two distinct N-glucuronides as the primary metabolites. These metabolites were identified by electrospray ionization LC/MS. 4. The apparent K-m for one of the glucuronide metabolites was determined in human liver microsome preparations from two individual liver donors to be 131 and 264 mu m respectively. V-max determined for the same microsomal preparations yielded 48.9 and 59.9 pmol/min/mg protein. C1 NATL INST NEUROL DISORDERS & STROKE,PRECLIN PHARMACOL SECT,EPILEPSY BRANCH,NATL INST HLTH,ROCKVILLE,MD 20857. RP McNeilly, PJ (reprint author), US FDA,LAB CLIN PHARMACOL,OFF PHARMACEUT SCI,CTR DRUG EVALUAT & RES,LAUREL,MD 20708, USA. NR 22 TC 25 Z9 25 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD MAY PY 1997 VL 27 IS 5 BP 431 EP 441 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA XA423 UT WOS:A1997XA42300003 PM 9179986 ER PT J AU Siegel, JP AF Siegel, JP TI An overview of statistical methods for multiple failure time data in clinical trials - Discussion SO STATISTICS IN MEDICINE LA English DT Editorial Material RP Siegel, JP (reprint author), US FDA,CTR BIOL EVALUAT & RES,1401 ROCKVILLE PIKE,SUITE 200S,HFM-500,ROCKVILLE,MD 20852, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD APR 30 PY 1997 VL 16 IS 8 BP 849 EP 851 PG 3 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA WY902 UT WOS:A1997WY90200009 ER PT J AU Sheikh, NM Philen, RM Love, LA AF Sheikh, NM Philen, RM Love, LA TI Chaparral-associated hepatotoxicity SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID COMFREY HERB TEA; VENO-OCCLUSIVE DISEASE; NORDIHYDROGUAIARETIC ACID; GRANULOMATOUS HEPATITIS; LARREA-TRIDENTATA; ARACHIDONIC-ACID; LIVER-DAMAGE; SUPPLEMENTS; INGESTION; MEDICATION AB Background: Personal health care practices that may include the use of dietary supplements are common in the United States. Products marketed as dietary supplements are diverse and may include botanicals, vitamins, and/or minerals. Chaparral (Larrea tridentata) is a botanical dietary supplement made from a desert shrub and used for its antioxidant properties. Several reports of chaparral-associated hepatitis have been published since 1990, but a complete picture of the clinical presentation is still unclear. Materials and Methods: We reviewed the 18 case reports of adverse events associated with the ingestion of chaparral reported to the Food and Drug Administration between 1992 and 1994. These reports were from health care professionals, state health departments, and individual consumers. Results: Of 18 reports of illnesses associated with the ingestion of chaparral, there was evidence of hepatotoxicity in 13 cases. Clinical presentation, characterized as jaundice with a marked increase in serum liver chemistry values, occurred 3 to 52 weeks after the ingestion of chaparral, and it resolved 1 to 17 weeks after most individuals stopped their intake of chaparral. The predominant pattern of liver injury was characterized as toxic or drug-induced cholestatic hepatitis; in 4 individuals, there was progression to cirrhosis; and in 2 individuals, there was acute fulminant liver failure that required liver transplants. Conclusions: These data indicate that the use of chaparral may be associated with acute to chronic irreversible liver damage with fulminant hepatic failure, and they underscore the potential for certain dietary supplement ingredients to cause toxic effects on the liver. Health professionals should be encouraged to inquire routinely about the use of dietary supplements and other products, to be alert to potential adverse effects that may be associated with these products, and, finally, to report any serious adverse events associated with these products through the MEDWatch Program of the Food and Drug Administration. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,OFF SPECIAL NUTR,CLIN RES & REVIEW STAFF,WASHINGTON,DC 20204. CTR DIS CONTROL & PREVENT,NATL CTR ENVIRONM HLTH,DIV ENVIRONM HAZARDS & HLTH EFFECTS,ATLANTA,GA. NR 38 TC 104 Z9 106 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 28 PY 1997 VL 157 IS 8 BP 913 EP 919 DI 10.1001/archinte.157.8.913 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA WV850 UT WOS:A1997WV85000010 PM 9129552 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 receptors by nerve growth factor in PC12 cells is p140(trk)-, Ras-, and Src-dependent SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; NEURONAL DIFFERENTIATION; SIGNAL-TRANSDUCTION; TYROSINE KINASE; PHEOCHROMOCYTOMA CELLS; AFFINITY; BINDING; PHOSPHORYLATION; MODULATION; MECHANISM AB Nerve growth factor (NGF) treatment causes a profound down-regulation of epidermal growth factor receptors during the differentiation of PC12 cells. This process is characterized by a progressive decrease in epidermal growth factor (EGF) receptor level measured by I-125-EGF binding, tyrosine phosphorylation, and Western blotting. Treatment of the cells with NGF for 5 days produces a 95% reduction in the amount of [S-35]methionine-labeled EGF receptors. This down-regulation does not occur in PC12nnr5 cells, which lack the p140(trk) NGF receptor. However, in PC12nnr5 cells stably transfected with p140(trk), the NGF-induced heterologous down-regulation of EGF receptors is reconstituted in part. NGF-induced heterologous down-regulation, but not EGF-induced homologous down-regulation of EGF receptors, is blocked in Ras- and Src-dominant-negative PC12 cells. Treatment with either pituitary adenylate cyclase-activating peptide (PACAP) or staurosporine stimulates neurite outgrowth in PC12 cell variants, but neither induces down-regulation of EGF receptors. NGF treatment of PC12 cells in suspension induces downregulation of EGF receptors in the absence of neurite outgrowth. These results strongly suggest a p140(trk)-, Has- and Src-dependent mechanism of NGF-induced down-regulation of EGF receptors and separate this process from NGF-induced neurite outgrowth in PC12 cells. C1 NICHHD,GROWTH FACTORS SECT,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. RI Shibutani, Makoto/C-2510-2013 NR 41 TC 27 Z9 27 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 APR 25 PY 1997 VL 272 IS 17 BP 11026 EP 11034 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WW009 UT WOS:A1997WW00900011 PM 9110995 ER PT J AU Hackett, RH Wang, YD Sweitzer, S Feldman, G Wood, WI Larner, AC AF Hackett, RH Wang, YD Sweitzer, S Feldman, G Wood, WI Larner, AC TI Mapping of a cytoplasmic domain of the human growth hormone receptor that regulates rates of inactivation of Jak2 and Stat proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING PROTEINS; TYROSINE PHOSPHORYLATION; INTERFERON-GAMMA; MOTH-EATEN; PHOSPHATASE; KINASE; GENE; ERYTHROPOIETIN; IDENTIFICATION; TRANSCRIPTION AB It has been previously demonstrated that growth hormone (GH)-stimulated tyrosine phosphorylation of Jak2 and Stat5a and Stat5b occurs in FDP-C1 cells expressing either the entire GH receptor or truncations of the cytoplasmic domain expressing only the membrane-proximal 80 amino acids, However, other receptor domains that might modulate rates of GH activation and inactivation of this cascade have not been examined, Here we have defined a region in the human GH receptor between amino acids 520 and 540 in the cytoplasmic domain that is required for attenuation of GH-activated Jak/Stat signaling, Immunoprecipitations with antibodies to Jak2 indicate that the protein tyrosine phosphatase SHP-1 is associated with this kinase in cells exposed to GH. To address the possibility that SHP-1 could function as a negative regulator of GH signaling, liver extracts from motheaten mice deficient in SHP-1 or unaffected littermates were analyzed for activation of Stats and Jak2, Extracts from motheaten mice displayed prolonged activation of the Stat proteins as measured by their ability to interact with DNA and prolonged tyrosine phosphorylation of Jak2. These results delineate a novel domain in the GH receptor that regulates the inactivation of the Jak/Stat pathway and appears to be modulated by SHP-1. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. GENENTECH INC,DEPT MOL BIOL,S SAN FRANCISCO,CA 94080. NR 26 TC 61 Z9 61 U1 1 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 APR 25 PY 1997 VL 272 IS 17 BP 11128 EP 11132 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WW009 UT WOS:A1997WW00900025 PM 9111009 ER PT J AU Krauthamer, V Jones, JL AF Krauthamer, V Jones, JL TI Calcium dynamics in cultured heart cells exposed to defibrillator-type electric shocks SO LIFE SCIENCES LA English DT Article DE optical recording; fura-2 defibrillation; cardiac myocytes; electric field ID FIELD STIMULATION; VENTRICULAR MUSCLE; POTENTIAL CHANGES; MYOCARDIAL-CELLS; CONDUCTION; MYOCYTES AB Spatial and temporal changes in intracellular calcium ion concentration and transmembrane voltage were recorded optically from single-isolated cultured chick-embryo heart cells exposed to high-voltage, defibrillator-type shocks. Fluorescence changes were measured during 5 msec electric shocks of field strengths up to 56 volts/cm in single myocytes stained with a Ca++-sensitive or voltage-sensitive dye. Shocks caused a reversible period of depolarization, elevated cytosolic Ca++, and refractoriness. Intracellular Ca++ elevation had two temporal phases: first, a Ca++ spike with morphology independent of shock intensity; and second, a prolonged Ca++ elevation with a shock-intensity-dependent magnitude and duration, and with greatest Ca++ elevation at the poles of the cell adjacent to the electrodes. The prolonged elevation (second phase) was initiated earlier at the anode-facing pole of the cell than at the cathode-facing pole. These results suggest that postshock Ca++ entry consists of two parts: early normal entry through excitation channels plus a prolonged elevation which may be related to cellular damage. C1 VET AFFAIRS MED CTR,WASHINGTON,DC 20422. GEORGETOWN UNIV,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20422. RP Krauthamer, V (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,OFF SCI & TECHNOL HFZ133,DIV PHYS SCI,12721 TWINBROOK PKWY,ROCKVILLE,MD 20857, USA. FU NHLBI NIH HHS [HL24606, HL49089] NR 23 TC 28 Z9 30 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD APR 25 PY 1997 VL 60 IS 22 BP 1977 EP 1985 DI 10.1016/S0024-3205(97)00162-8 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA WX502 UT WOS:A1997WX50200005 PM 9180351 ER PT J AU Drachman, DA Leber, P AF Drachman, DA Leber, P TI Treatment of Alzheimer's disease - Searching for a brearkthrough, settling for less SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID DEMENTIA C1 US FDA,ROCKVILLE,MD 20857. RP Drachman, DA (reprint author), UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA 01655, USA. NR 11 TC 40 Z9 40 U1 1 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 APR 24 PY 1997 VL 336 IS 17 BP 1245 EP 1247 DI 10.1056/NEJM199704243361710 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA WV332 UT WOS:A1997WV33200010 PM 9110915 ER PT J AU Appel, NM Rapoport, SI OCallaghan, JP Bell, JM Freed, LM AF Appel, NM Rapoport, SI OCallaghan, JP Bell, JM Freed, LM TI Sequelae of parenteral domoic acid administration in rats: Comparison of effects on different metabolic markers in brain SO BRAIN RESEARCH LA English DT Article DE neurotoxicity; autoradiography; fatty acid; palmitic acid; arachidonic acid; 2-deoxyglucose; brain metabolism; gliosis; glial fibrillary acidic protein; seizure ID SUSTAINED ELECTRICAL-STIMULATION; MONKEYS MACACA-FASCICULARIS; TEMPORAL-LOBE EPILEPSY; KAINIC ACID; FATTY-ACIDS; UNANESTHETIZED RATS; HIPPOCAMPAL DAMAGE; REACTIVE GLIOSIS; PERFORANT PATH; AMINO-ACID AB Parenterally administered domoic acid, a structural analog of the excitatory amino acids glutamic acid and kainic acid, has specific effects on brain histology in rats, as measured usung different anatomic markers. Domoic acid-induced convulsions affects Limbic structures such as hippocampus and entorhinal cortex, and different anatomic markers can detect these neurotoxic effects to varying degrees, Here we report effects of domoic acid administration on quantitative indicators of brain metabolism and gliosis. Domoic acid, 2.25 mg/kg i.p., caused stereotyped behavior and convulsions in approximately 60% of rats which received it. Six to eight days after domoic acid or vehicle administration, the animals were processed to measure regional brain incorporation of the long-chain fatty acids [1-C-14]arachidonic acid ([C-14]AA) and [9,10-H-3]palmitic acid ([H-3]PA), or regional cerebral glucose utilization (rCMR(glc)) using 2-[1-C-14]deoxy-D-glucose, by quantitative autoradiography. Others rats were processed to measure brain glial fibrillary acidic protein (GFAP) by enzyme-linked immunosorbent assay. Domoic acid increased GFAP in the anterior portion of cerebral cortex, the caudate putamen and thalamus compared with vehicle. However, in rats that convulsed after domoic acid GFAP was significantly increased throughout the cerebral cortex, as well as in the hippocampus, septum, caudate putamen, and thalamus. Domoic acid, in the absence of convulsions, decreased relative [C-14]AA incorporation in the claustrum and pyramidal cell layer of the hippocampus compared with vehicle-injected controls, In the presence of convulsions, relative [C-14]AA incorporation was decreased in hippocampus regions CAl and CA2. Uptake of [H-3]PA into brain was unaffected. Relative rCMR(glc) decreased in entorhinal cortex following domoic acid administration with or without convulsions. These results suggest that acute domoic acid exposure affects discrete brain circuits by inducing convulsions, and that domoic acid-induced convulsions cause chronic effects on brain function that are reflected in altered fatty acid metabolism and gliosis. (C) 1977 Elsevier Science B.V. C1 NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892. US EPA,HLTH EFFECTS RES LAB,DIV NEUROTOXICOL,RES TRIANGLE PK,NC 27711. US FDA,CTR DRUG EVALUAT & RES,DIV NEUROPHARMACOL DRUG PROD,OFF DRUG EVALUAT 1,ROCKVILLE,MD 20852. RP Appel, NM (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV APPL PHARMACOL RES,OFF TESTING & RES,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. RI O'Callaghan, James/O-2958-2013 NR 62 TC 10 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 18 PY 1997 VL 754 IS 1-2 BP 55 EP 64 DI 10.1016/S0006-8993(97)00042-5 PG 10 WC Neurosciences SC Neurosciences & Neurology GA WW306 UT WOS:A1997WW30600007 PM 9134959 ER PT J AU Dillon, JG Schroeder, LW AF Dillon, JG Schroeder, LW TI Permeability and material characteristics of vulcanized latex film during and following cyclic fatigue in a saline environment SO JOURNAL OF APPLIED POLYMER SCIENCE LA English DT Article DE latex; gloves; fatigue; rubber; permeability ID GLOVES AB The importance of stress or fatigue as a source of latex glove failure has been mentioned in several recent studies, but little work has been done to examine the underlying mechanism of these failures. The present work was undertaken to develop techniques for very early detection of structural changes in glove barriers. This was accomplished by monitoring the ion permeability and electrical properties of vulcanized latex glove material during cyclic fatigue in saline. Alteration in the conductance and capacitance of the membrane during the fatigue cycle showed that catastrophic failure of the material was preceded by deviation in the conductance of the membrane 8-10 min before rupture of the material. Disruption of the material coincided with capacitive ''discharge'' of and ion transport across the membrane. Follow-up examination by optical (100x) and scanning electron microscopy (SEM) revealed failure of the original fibril network structure surrounding the latex particles. Failure corresponded to processes consistent with repeated stress and rupture of the fibrils responsible for maintaining membrane integrity. Cyclic creep-strain measurements were carried out on the latex glove material. The estimated strain during cyclic fatigue was consistent with use during normal flexing of the glove finger. The fatigue life-time of the glove material was found to be about 2 h. Based on these studies, we conclude that failure of the glove material due to hole formation is preceded by gradual thinning (and weakening) of the membrane in localized regions. This suggests that latex inhomogeneities (defects) are the ultimate cause of failure. These findings confirm the importance of stress in explaining the source of some glove material failures, especially those failures not obviously accompanied by sharp instrument or needle penetrations. The results of the fatigue study emphasize the importance of changing gloves during prolonged use. (C) 1997 John Wiley & Sons, Inc. RP Dillon, JG (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,OFF SCI & TECHNOL,DIV MECH & MAT SCI,CHEM GRP,12200 WILKINS AVE,ROCKVILLE,MD 20852, USA. NR 32 TC 6 Z9 6 U1 1 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-8995 J9 J APPL POLYM SCI JI J. Appl. Polym. Sci. PD APR 18 PY 1997 VL 64 IS 3 BP 553 EP 566 DI 10.1002/(SICI)1097-4628(19970418)64:3<553::AID-APP12>3.0.CO;2-Z PG 14 WC Polymer Science SC Polymer Science GA WP836 UT WOS:A1997WP83600012 ER PT J AU Silverman, BG Brown, SL Bright, RA AF Silverman, BG Brown, SL Bright, RA TI Epidemiology of silicone breast implants - Response SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID EOSINOPHILIA RP Silverman, BG (reprint author), US FDA,ROCKVILLE,MD 20850, USA. RI Bright, Roselie/D-2240-2016; OI Silverman, Barbara/0000-0002-0337-4919 NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 15 PY 1997 VL 126 IS 8 BP 667 EP 668 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WT580 UT WOS:A1997WT58000035 ER PT J AU Sgadari, C Farber, JM Angiolillo, AL Liao, F TeruyaFeldstein, J Burd, PR Yao, L Gupta, G Kanegane, C Tosato, G AF Sgadari, C Farber, JM Angiolillo, AL Liao, F TeruyaFeldstein, J Burd, PR Yao, L Gupta, G Kanegane, C Tosato, G TI Mig, the monokine induced by interferon-gamma, promotes tumor necrosis in vivo SO BLOOD LA English DT Article ID EPSTEIN-BARR-VIRUS; X-C CHEMOKINE; INDUCIBLE PROTEIN-10; BURKITTS-LYMPHOMA; IN-VIVO; B-CELLS; FAMILY; IP-10; ANGIOGENESIS; CYTOKINES AB Mig, the monokine induced by interferon-gamma, is a CXC chemokine active as a chemoattractant for activated T cells. Mig is related functionally to interferon-inducible protein 10 (IP-10), with which it shares a receptor, CXCR3, Previously, IP-10 was found to have antitumor activity in vivo, In the present study, murine Mig RNA was found to be expressed at higher levels in regressing Burkitt's lymphoma tumors established in nude mice compared with progressively growing tumors, Daily inoculations of purified recombinant human Mig into Burkitt's tumors growing subcutaneously in nude mice consistently caused tumor necrosis associated with extensive vascular damage. These effects were indistinguishable from those produced by intratumor inoculations of Burkitt's tumors with IP-10, These results support the notion that Mig, like IP-10, has antitumor activity in vivo, This is a US government work. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,DEPT HEMATOL ONCOL,WASHINGTON,DC 20010. NCI,HEMATOPATHOL SECT,PATHOL LAB,BETHESDA,MD 20892. RI Sgadari, Cecilia/H-4302-2016 OI Sgadari, Cecilia/0000-0003-0364-4912 NR 30 TC 205 Z9 207 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 1997 VL 89 IS 8 BP 2635 EP 2643 PG 9 WC Hematology SC Hematology GA WV146 UT WOS:A1997WV14600002 PM 9108380 ER PT J AU Klinman, DM Yamshchikov, G Ishigatsubo, Y AF Klinman, DM Yamshchikov, G Ishigatsubo, Y TI Contribution of CpG motifs to the immunogenicity of DNA vaccines SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PLASMID DNA; IMMUNE-RESPONSES; CIRCUMSPOROZOITE PROTEIN; CELLS; INJECTION; MICE; ACTIVATION; CYTOKINE; TYPE-1; PROTECTION AB We previously showed that bacterial DNA contains immunostimulatory motifs consisting Of unmethylated CpG dinucleotides flanked by two 5' purines and two 3' pyrimidines. These motifs rapidly trigger an innate immune response, characterized by the production of IL-6, IL-12, and IFN-gamma, Since DNA vaccines are constructed from plasmids of bacterial DNA, we examined whether CpG motifs present in these plasmids contributed to the immunogenicity of DNA vaccines. In vitro experiments showed that DNA plasmids induced production of the same cytokines stimulated by bacterial DNA, an effect eliminated by DNase treatment. In vivo experiments showed that the immunogenicity of a DNA vaccine was significantly reduced by methylating its CpG motifs and was significantly increased by coadministering exogenous CpG-containing DNA. These findings support the conclusion that CpG motifs in the plasmid backbone of DNA vaccines play an important role in the induction of Ag-specific immunity. C1 YOKOHAMA CITY UNIV,MED CTR,DEPT INTERNAL MED 1,YOKOHAMA,KANAGAWA 232,JAPAN. RP Klinman, DM (reprint author), US FDA,CTR BIOL EVALUAT & RES,SECT RETROVIRAL IMMUNOL,BLDG 29A,ROOM 3D10,HFM 454,BETHESDA,MD 20892, USA. NR 34 TC 383 Z9 407 U1 1 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1997 VL 158 IS 8 BP 3635 EP 3639 PG 5 WC Immunology SC Immunology GA WT196 UT WOS:A1997WT19600012 PM 9103425 ER PT J AU Robertson, DE AF Robertson, DE TI Careers with the Food and Drug Administration 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 APR 13 PY 1997 VL 213 BP 7 EP CHAL PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18502196 ER PT J AU Schmuff, NR AF Schmuff, NR TI AIDS information: An FDA perspective SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,CTR DRUG EVALUAT & RES,OFF PHARMACEUT SCI,DIV NEW DRUG CHEM 3,HFD 530,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 APR 13 PY 1997 VL 213 BP 25 EP CINF PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18502103 ER PT J AU Tong, WD Perkins, R Strelitz, R AF Tong, WD Perkins, R Strelitz, R TI QSAR studies of estrogen receptor binding affinity. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 ROW SCI,JEFFERSON,AR 72079. UNIV MISSOURI,DEPT CHEM,ST LOUIS,MO 63121. DEPT HLTH & HUMAN SERV,NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,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 APR 13 PY 1997 VL 213 BP 37 EP COMP PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18502669 ER PT J AU Luo, WH Hansen, EB Ang, CYW Deck, J Freeman, JP Thompson, HC AF Luo, WH Hansen, EB Ang, CYW Deck, J Freeman, JP Thompson, HC TI Simultaneous determination of amoxicillin and ampicillin in bovine milk by HPLC with fluorescence detection. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 U1 1 U2 2 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 APR 13 PY 1997 VL 213 BP 42 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18500043 ER PT J AU Canas, BJ AF Canas, BJ TI Formation and occurrence of ethyl carbamate in wine: A review. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,DIV NAT PROD,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR 13 PY 1997 VL 213 BP 45 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18500046 ER PT J AU NguyenPho, AAN Roscher, NM Doyle, TD AF NguyenPho, AAN Roscher, NM Doyle, TD TI Enantiomeric resolution of alpha-methylbenzylamine and 1-cyclohexylethylamine derivatives on HPLC chiral stationary phases. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,DIV RES & TESTING,WASHINGTON,DC 20204. AMERICAN UNIV,DEPT CHEM,WASHINGTON,DC 20016. NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR 13 PY 1997 VL 213 BP 77 EP ANYL PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18500432 ER PT J AU Allen, LB Thompson, HC AF Allen, LB Thompson, HC TI Determination of copper, iron and lead in edible oils by ICP-AES and GFAAS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NATL CTR TOXICOL RES,DIV CHEM,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 83 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18500084 ER PT J AU Allen, LB Thompson, HC AF Allen, LB Thompson, HC TI Application of aerosol phase assisted digestion and aerosol phase digestion to the determination of metal contamination in foods 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 APR 13 PY 1997 VL 213 BP 84 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18500085 ER PT J AU Luo, WH Ang, CYW Thompson, HC AF Luo, WH Ang, CYW Thompson, HC TI A rapid method for the determination of ampicillin residues in animal muscle tissues by HPLC with fluorescence detection. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 93 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18500094 ER PT J AU Ang, CYW Luo, WH Call, R Righter, HF AF Ang, CYW Luo, WH Call, R Righter, HF TI Analysis of amoxicillin and ampicillin residues in milk by HPLC and microbial assays following administration of antibiotics to cows. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. ARKANSAS DEPT HLTH,LITTLE ROCK,AR 72205. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 94 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18500095 ER PT J AU Fu, TJ AF Fu, TJ TI Safety considerations for food ingredients produced by plant cell and tissue culture. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,NATL CTR FOOD SAFETY & TECHNOL,SUMMIT ARGO,IL 60501. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 103 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18500104 ER PT J AU Beru, N AF Beru, N TI Food ingredients from plant cell and tissue culture: Regulatory considerations. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,CTR FOOD SAFETY & APPL NUTR,BIOTECHNOL POLICY BRANCH,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 APR 13 PY 1997 VL 213 BP 106 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18500106 ER PT J AU Hansen, PA AF Hansen, PA TI Non-thermal food processing methods - Regulatory perspective. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 141 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18500141 ER PT J AU Diachenko, GW DiNovi, M Ekelman, K Fisher, S AF Diachenko, GW DiNovi, M Ekelman, K Fisher, S TI Overview of chloropropanols in acid hydrolyzed proteins. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 177 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18500176 ER PT J AU Jackson, LS Fingerhut, DD Bullerman, LB AF Jackson, LS Fingerhut, DD Bullerman, LB TI Effect of processing on the mycotoxin content of food. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,NATL CTR FOOD SAFETY & TECHNOL,SUMMIT ARGO,IL. IIT,NCFST,SUMMIT ARGO,IL 60501. UNIV NEBRASKA,DEPT FOOD SCI & TECHNOL,LINCOLN,NE 68583. NR 0 TC 0 Z9 0 U1 0 U2 3 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 APR 13 PY 1997 VL 213 BP 192 EP AGFD PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18500191 ER PT J AU Picciolo, GL Lyle, D Goldman, D Eggerman, TL Durfor, CN Knight, E Bradlaw, J Hellman, KB AF Picciolo, GL Lyle, D Goldman, D Eggerman, TL Durfor, CN Knight, E Bradlaw, J Hellman, KB TI Research initiative for tissue engineering regulatory test methods SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20852. CDRH,ROCKVILLE,MD 20852. CBER,ROCKVILLE,MD 20852. CFSAN,ROCKVILLE,MD 20852. US FDA,INTERCENTER TISSUE ENGN WORKING GRP,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 APR 13 PY 1997 VL 213 BP 281 EP BIOT PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18500874 ER PT J AU Sharf, R Meraro, D Azriel, A Thornton, AM Ozato, K Petricoin, EF Larner, AC Schaper, F Hauser, H Levi, BZ AF Sharf, R Meraro, D Azriel, A Thornton, AM Ozato, K Petricoin, EF Larner, AC Schaper, F Hauser, H Levi, BZ TI Phosphorylation events modulate the ability of interferon consensus sequence binding protein to interact with interferon regulatory factors and to bind DNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STIMULATED RESPONSE ELEMENT; TRANSCRIPTION FACTOR IRF-1; CELL-GROWTH INHIBITION; FACTOR FAMILY; GAMMA-INTERFERON; GENE-EXPRESSION; INDUCIBLE GENES; FACTOR-I; TYROSINE; IFN AB Two families of transcription factors mediate interferon (IFN) signaling, The first family, signal transducers and activators of transcription (STATs), is activated within minutes of IFN treatment. Specific phosphorylation events lead to their translocation to the nucleus, formation of transcriptional complexes, and the induction of the second family of transcription factors termed interferon regulatory factors (IRFs). Interferon consensus sequence binding protein (ICSBP) is a member of IRF family that is expressed only in cells of the immune system and acts as a transcriptional repressor. ICSBP binds DNA through the association with other transcription factors such as IRF-1 or IRF-2. In this communication, the domain that is involved in protein-protein interactions was mapped to the carboxyl terminus of ICSBP. This domain is also important for mediating ICSBP repressing activity. In vitro studies demonstrated that direct binding of ICSBP to DNA is prevented by tyrosine (Tyr) phosphorylation. Yet, Tyr-phosphorylated ICSBP can bind target DNA only through the association with IRF-2 and IRF-1. This type of phosphorylation is essential for the formation of heterocomplexes. Tyr-phosphorylated ICSBP and IRF-2 are detected in expressing cells constitutively, and Tyr-phosphorylated IRF-1 is induced by IFN-gamma. These results strongly suggest that like the STATs, the IRFs are also modulated by Tyr phosphorylation that affects their biological activities. C1 TECHNION ISRAEL INST TECHNOL,DEPT FOOD ENGN & BIOTECHNOL,IL-32000 HAIFA,ISRAEL. NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT,DIV CYTOKINE BIOL,BETHESDA,MD 20892. GESELL BIOTECHNOL FORSCH MBH,D-38124 BRAUNSCHWEIG,GERMANY. RI Schaper, Fred/F-1403-2013 NR 43 TC 140 Z9 143 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 APR 11 PY 1997 VL 272 IS 15 BP 9785 EP 9792 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU039 UT WOS:A1997WU03900031 PM 9092512 ER PT J AU Kijak, PJ Jackson, J Shaikh, B AF Kijak, PJ Jackson, J Shaikh, B TI Determination of gentamicin in bovine milk using liquid chromatography with post-column derivatization and fluorescence detection SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE gentamicin ID SULFATE; KIDNEY AB A method capable of separating and quantifying the three major and one minor components of gentamicin in milk has been developed. The method is capable of detecting 15 ng/ml gentamicin, based on a total of the four components. Milk samples are centrifuged at 4 degrees C, the fat layer removed, and the samples deproteinated with 30% trichloracetic acid. After a second centrifugation, the supernatant is passed through a C-18 solid-phase extraction column. The column is washed with water, water-methanol (50:50) and methanol. Ammonium hydroxide (16%) in methanol is used to elute the gentamicin. The eluent is evaporated to near dryness and taken up with water. An aliquot of the sample is then mixed with an ion-pairing reagent for chromatography. Separation is achieved using pentanesulfonic acid in a water-methanol mobile phase on a C,, reversed-phase column. The o-phthalaldehyde fluorescence derivatives of gentamicin are formed post-column and are detected with excitation at 340 nm and emission at 430 nm. The percent recovery of gentamicin averaged 72, 78 and 88% from milk samples fortified at 15, 30 and 60 ng/ml, respectively. RP Kijak, PJ (reprint author), US FDA,CTR VET MED,BARC E,BLDG 328-A,BELTSVILLE,MD 20705, USA. NR 14 TC 29 Z9 30 U1 0 U2 7 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 APR 11 PY 1997 VL 691 IS 2 BP 377 EP 382 DI 10.1016/S0378-4347(96)00445-8 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WY402 UT WOS:A1997WY40200015 PM 9174274 ER PT J AU Angiolillo, AL Kanegane, H Sgadari, C Reaman, GH Tosato, G AF Angiolillo, AL Kanegane, H Sgadari, C Reaman, GH Tosato, G TI Interleukin-15 promotes angiogenesis in vivo SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ACTIVATED KILLER-CELLS; RECEPTOR-BETA-CHAIN; IL-2 RECEPTOR; GROWTH-FACTOR; INTEGRIN ALPHA(V)BETA(3); POTENT INHIBITOR; GAMMA-CHAIN; ALPHA-CHAIN; PROLIFERATION; CYTOKINE AB IL-15, a cytokine with biological functions on cells of lymphoid lineage similar to those of IL-2, mediates its activities through the beta and gamma chains of the IL-2/15R and its own alpha chain. Unlike IL-2, IL-15 also binds to endothelial cells with high affinity. We report here that IL-15 is a stimulator of angiogenesis in vivo. When injected subcutaneously into nude mice, IL-15 consistently induced neovascularization of Matrigel plugs. Endothelial cells were found to express the lL-15R alpha chain and the IL-2/15R beta and common gamma chains. IL-15 induced the rapid tyrosine phosphorylation of proteins in endothelial cells, but did not stimulate endothelial cell proliferation in vitro. These findings document a previously unrecognized biological property of IL-15 and emphasize the role of IL-15 as an important mediator outside the immune system. (C) 1997 Academic Press. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. RP Angiolillo, AL (reprint author), CHILDRENS NATL MED CTR,DEPT HEMATOL ONCOL,WASHINGTON,DC 20010, USA. RI Sgadari, Cecilia/H-4302-2016 OI Sgadari, Cecilia/0000-0003-0364-4912 NR 38 TC 75 Z9 77 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 7 PY 1997 VL 233 IS 1 BP 231 EP 237 DI 10.1006/bbrc.1997.6435 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WV136 UT WOS:A1997WV13600046 PM 9144429 ER PT J AU Kanegane, H Kanegane, C Yachie, A Miyawaki, T Tosato, G AF Kanegane, H Kanegane, C Yachie, A Miyawaki, T Tosato, G TI Infectious mononucleosis as a disease of early childhood in Japan caused by primary Epstein-Barr virus infection SO ACTA PAEDIATRICA JAPONICA LA English DT Article DE Epstein-Barr virus; infectious mononucleosis ID T-CELLS; ANTIBODIES; INFANTS; EBV; LYMPHOCYTES; LYMPHOMA; CHILDREN; SUBSETS; DNA AB The present study investigated 54 pediatric patients with acute Epstein-Barr virus (EBV)-induced infectious mononucleosis (IM) in Japan. Most of the acute cases clustered within the first 5 years of life, and the peak incidence was observed at around 4 years of age, These patients were arbitrarily separated into three age groups (less than 3 years, 3-5 years, and 6-14 years). Fever, pharyngitis, lymphadenopathy and hepatomegaly were detected in more than 80% of all cases, Tonsillitis and splenomegaly were present in about 60% of cases, Skin manifestations and eyelids edema were less often detected in the older age group than in the younger age groups. In addition to an increase of total white blood cell and lymphocyte counts in the peripheral blood, a significant increase in the percentage of CD3(+) CD8(+) HLA-DR+ T cells was always observed. Epstein-Barr virus seropositivity increased soon after birth and reached approximately 70% around 3 years of ape. Close to 100% of the adult controls were EBV seropositive. The results suggest that EBV-induced acute IM is a disease of early childhood in Japan. C1 KANAZAWA UNIV,SCH MED,DEPT PEDIAT,KANAZAWA,ISHIKAWA 920,JAPAN. TOYAMA MED & PHARMACEUT UNIV,SCH MED,DEPT PEDIAT,TOYAMA,JAPAN. RP Kanegane, H (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BLDG 29A,ROOM 2D06,HFM-538,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. RI Yachie, Akihiro/C-4660-2015 NR 26 TC 12 Z9 15 U1 0 U2 0 PU BLACKWELL SCIENCE PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON VICTORIA 3053, AUSTRALIA SN 0374-5600 J9 ACTA PAEDIATR JAPON JI Acta Pediatr. Jpn. PD APR PY 1997 VL 39 IS 2 BP 166 EP 171 PG 6 WC Pediatrics SC Pediatrics GA WY271 UT WOS:A1997WY27100002 PM 9141248 ER PT J AU Kondo, Y Ipsen, H Lowenstein, H Karpas, A Hsieh, LS AF Kondo, Y Ipsen, H Lowenstein, H Karpas, A Hsieh, LS TI Comparison of concentrations of Cry j 1 and Cry j 2 in diploid and triploid Japanese cedar (Cryptomeria japonica) pollen extracts SO ALLERGY LA English DT Article DE Cry j 1; Cry j 2; Japanese cedar or sugi (Cryptomeria japonica); major allergen; pollinosis; triploid ID MAJOR ALLERGEN AB Japanese cedar (Cryptomeria japonica) pollinosis has been a serious allergic disease in Japan. There are two kinds of Japanese cedar trees; the popular one is diploid, the less popular is triploid. These trees are not very different morphologically. However, the relative allergenicity of their pollens is unknown, although both major allergens, Cry j 1 and Cry j 2, have been purified and cloned from the diploid line. Triploid trees are sterile and the allergenicity of their pollen may differ. Using Japanese-cedar-allergic patient sera, we compared the concentration of these two major allergens in both kinds of pollen. Pollen collected from different years and regions was also studied. The results indicate that triploid tree pollen extract has lower concentrations of both major allergens; therefore, the pollen may be less allergenic. C1 FDA,CBER,DAPP,HFM 422,ROCKVILLE,MD 20852. FUJITA HLTH UNIV,SCH MED,DEPT PEDIAT,TOYOAKE,AICHI 47011,JAPAN. ALK LAB,HORSHOLM,DENMARK. NICHHD,DEV & MOL IMMUN LAB,NIH,BETHESDA,MD. NR 13 TC 8 Z9 8 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-4538 J9 ALLERGY JI Allergy PD APR PY 1997 VL 52 IS 4 BP 455 EP 459 DI 10.1111/j.1398-9995.1997.tb01029.x PG 5 WC Allergy; Immunology SC Allergy; Immunology GA XA221 UT WOS:A1997XA22100019 PM 9188931 ER PT J AU Douglass, JS Chew, SB Li, RH Petersen, BJ Hendricks, TC Pennington, JAT AF Douglass, JS Chew, SB Li, RH Petersen, BJ Hendricks, TC Pennington, JAT TI Use of an international interface standard for food databases in comparing food-related data sets SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Meeting Abstract DE computer; database; food code; ingredient; food composition C1 TECH ASSESSMENT SYST INC, WASHINGTON, DC USA. US FDA, WASHINGTON, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1997 VL 65 IS 4 SU S BP 1332 EP 1332 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WR606 UT WOS:A1997WR60600145 ER PT J AU Pennington, JAT AF Pennington, JAT TI Food monitoring and dietary assessment SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Meeting Abstract DE food supply; monitoring; policy; database; laboratory analysis C1 US FDA, CTR FOOD SAFETY & APPL NUTR, WASHINGTON, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1997 VL 65 IS 4 SU S BP 1341 EP 1341 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WR606 UT WOS:A1997WR60600173 ER PT J AU Collantes, ER Duta, R Welsh, WJ Zielinski, WL Brower, J AF Collantes, ER Duta, R Welsh, WJ Zielinski, WL Brower, J TI Preprocessing of HPLC trace impurity patterns by wavelet packets for pharmaceutical fingerprinting using artificial neural networks SO ANALYTICAL CHEMISTRY LA English DT Article ID RECOGNITION; DECOMPOSITION; TRANSFORM; MODELS AB The immediate objective of this research program is to evaluate several computer-based classifiers as potential tools for pharmaceutical fingerprinting based on analysis of HPLC trace organic impurity patterns, In the present study, wavelet packets (WPs) are investigated for use as a preprocessor of the chromatographic data taken from commercial samples of L-tryptophan (LT) to extract input data appropriate for classifying the samples according to manufacturer using artificial neural networks (ANNs) and the standard classifiers KNN and SIMCA. Using the Haar function, WP decompositions for levels L = 0-10 were generated for the trace impurity patterns of 253 chromatograms corresponding to LT samples that had been produced by six commercial manufacturers. Input sets of N = 20, 30, 40, and 50 inputs were constructed, each one consisting of the first N/2 WP coefficients and corresponding positions from the overall best level (L = 2). The number of hidden nodes in the ANNs was also varied to optimize performance, Optimal ANN performance based on percent correct classifications of test set data was achieved by ANN-30-30-6 (97%) and ANN-20-10-6 (94%), where the integers refer to the numbers of input, hidden, and output nodes, respectively, This performance equals or exceeds that obtained previously (Welsh, W. J.; et al, Anal. Chem, 1996, 68, 3473) using 46 inputs from a so-called Window preprocessor (93%). KNN performance with 20 inputs (97%) or 30 inputs (90%) from the WP preprocessor also exceeded that obtained from the Window preprocessor (85%), while SIMCA performance with 20 inputs (86%) or 30 inputs (82%) from the WP preprocessor was slightly inferior to that obtained from the Window preprocessor (87%), These results indicate that, at least for the ANN and KNN classifiers considered here, the WP preprocessor can yield superior performance and with fewer inputs compared to the Window preprocessor. C1 UNIV MISSOURI,DEPT CHEM,ST LOUIS,MO 63121. US FDA,DIV DRUG ANAL,ST LOUIS,MO 63101. NR 21 TC 55 Z9 56 U1 2 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD APR 1 PY 1997 VL 69 IS 7 BP 1392 EP 1397 DI 10.1021/ac9608836 PG 6 WC Chemistry, Analytical SC Chemistry GA WQ777 UT WOS:A1997WQ77700026 PM 9105180 ER PT J AU Holman, SJ Robinson, RA Beardsley, D Stewart, SFC Klein, L Stevens, RA AF Holman, SJ Robinson, RA Beardsley, D Stewart, SFC Klein, L Stevens, RA TI Hyperbaric dye solution distribution characteristics after pencil-point needle injection in a spinal cord model SO ANESTHESIOLOGY LA English DT Article DE anesthetic techniques, spinal, pencil point needles; anesthetics, local, lidocaine; complications, neurological, maldistribution ID CAUDA-EQUINA SYNDROME; TRANSIENT RADICULAR IRRITATION; INTENDED EPIDURAL-ANESTHESIA; NEUROLOGIC DEFICIT; LIDOCAINE; NERVE; 2-CHLOROPROCAINE; NEUROTOXICITY; INFUSION; RAT AB Background: The flow-rate limiting and directional characteristics of caudally directed microcatheters, which lead to intrathecal maldistribution of hyperbaric 5% lidocaine, are believed to have contributed to at least 11 cases of cauda equina syndrome, The authors investigated the distribution characteristics of hyperbaric dye solutions via caudally directed side-port needles at various rates of injection in a spinal cord model to determine the potential for maldistribution. Methods: Using a digital video image processing technique, we injected a hyperbaric solution of phthalocyanine blue dye through caudally directed side-port needles into a supinely oriented transparent spinal canal model filled with simulated cerebrospinal fluid. Injections via commonly used spinal needles (24-gauge and 25-gauge Sprotte, and 25-gauge and 27-gauge Whitacre) were recorded using five injection rates (2, 4, 6, 8, and 16 ml/min), Results: For all needles tested, injection rate had a significant effect on the peak dye concentration (P < 0.0001). Injection rates greater than or equal to 6 ml/min (2 ml/20 s) resulted in peak dye concentrations of less than 168 mg/l (extrapolated concentration of 1% lidocaine). Injection via the 24-gauge Sprotte needle, which has a larger orifice area and internal diameter, resulted in significantly lower peak dye concentrations than via the smaller Whitacre needles tested (P < 0.05). Conclusions: Sacral maldistribution could be minimized by using injection rates greater than or equal to 6 ml/min (2 ml/20 s), for all of the side-port spinal needles used in this model study, When very slow injection rates (2 ml/min) are used, peak dye concentrations varied inversely and significantly with needle internal diameter and orifice area. C1 UNIFORMED SERV UNIV HLTH SCI, DEPT ANESTHESIOL, BETHESDA, MD 20814 USA. NATL NAVAL MED CTR, DEPT ANESTHESIOL, BETHESDA, MD USA. LOYOLA UNIV, STRITCH SCH MED, MAYWOOD, IL 60153 USA. US FDA, ROCKVILLE, MD 20857 USA. RP Holman, SJ (reprint author), PORTSMOUTH NAVAL MED CTR, DEPT ANESTHESIOL CODE 0601, PORTSMOUTH, VA 23708 USA. NR 33 TC 33 Z9 38 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 APR PY 1997 VL 86 IS 4 BP 966 EP 973 DI 10.1097/00000542-199704000-00027 PG 8 WC Anesthesiology SC Anesthesiology GA WT008 UT WOS:A1997WT00800029 PM 9105241 ER PT J AU Palmisano, B Landow, L AF Palmisano, B Landow, L TI Ultiva SO ANESTHESIOLOGY LA English DT Editorial Material RP Palmisano, B (reprint author), US FDA,SECT ANESTHESIA & CRIT CARE,ROCKVILLE,MD 20857, USA. 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 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 1997 VL 86 IS 4 BP A33 EP A34 PG 2 WC Anesthesiology SC Anesthesiology GA WT008 UT WOS:A1997WT00800002 ER PT J AU Sagripanti, JL Routson, LB Bonifacino, AC Lytle, CD AF Sagripanti, JL Routson, LB Bonifacino, AC Lytle, CD TI Mechanism of copper-mediated inactivation of herpes simplex virus SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HYDROGEN-PEROXIDE; GENITAL HERPES; DNA DAMAGE; ACYCLOVIR; INFECTIONS; IONS; ANTIVIRALS; STRAND; BASES; IRON AB The inactivation of herpes simplex virus (HSV) by copper was enhanced by the following reducing agents at the indicated relative level: ascorbic acid much greater than hydrogen peroxide > cysteine. Treatment of HSV-infected cells with combinations of Cu(II) and ascorbate completely inhibited virus plaque formation to below 0.006% of the infectious virus input, while it maintained 30% viability for the host mammalian cells, The logarithm of the surviving fraction of HSV mediated by 1 mg of Cu(II) per liter and 100 mg of reducing agent per liter followed a linear relationship,vith the reaction time, in which the kinetic rate constant for each reducing agent was -0.87 min(-1) (r = 0.93) for ascorbate, -0.10 min(-1) (r = 0.97) for hydrogen peroxide, and -0.04 min(-1) (r = 0.97) for cysteine, The protective effects of metal chelators and catalase, the lack of effect of superoxide dismutase, and the partial protection conferred by free-radical scavengers suggest that the mechanism of copper-mediated HSV inactivation is similar to that previously reported for copper-mediated DNA damage, The sensitivity exhibited by HSV to Cu(II) and reducing agents, particularly ascorbate, might be useful in the development of therapeutic antiviral agents. RP Sagripanti, JL (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,MOL BIOL BRANCH HFZ113,DIV LIFE SCI,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 37 TC 39 Z9 39 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 1997 VL 41 IS 4 BP 812 EP 817 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA WR166 UT WOS:A1997WR16600019 PM 9087495 ER PT J AU Huang, F Yamaguchi, A Tsuchiya, N Ikawa, T Tamura, N Virtala, MMK Granfors, K Yasaei, P Yu, DTY AF Huang, F Yamaguchi, A Tsuchiya, N Ikawa, T Tamura, N Virtala, MMK Granfors, K Yasaei, P Yu, DTY TI Induction of alternative splicing of HLA-B27 by bacterial invasion SO ARTHRITIS AND RHEUMATISM LA English DT Article ID HLA-CLASS-I; MOLECULES; TRANSCRIPTS; EXPRESSION; ARTHRITIS; ANTIGEN; PLASMA; MUTANT; FORMS; CELL AB Objective. Alternative splicing of certain class I major histocompatibility complex pre-messenger RNA (pre-mRNA) is known to lead to generation of a cell-free soluble protein analog, This study was undertaken to examine whether this process occurs with HLA-B27, whether the process is modified by arthritis-causing bacteria, and whether the assembly of the soluble molecules follows the same pathway as the integral parent molecules. Methods. Alternative splicing of pre-mRNA was analyzed by reverse transcriptase-polymerase chain reaction, and assembly of soluble HLA-B27 by immuno-precipitation followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Results. There was alternative splicing of the pre-mRNA of HLA-B27, The process could be amplified by invasion with Salmonella or Yersinia bacteria, The soluble HLA-B27 was assembled in a pathway similar to that of the parent molecule. Conclusion. The association between arthritis-causing bacteria and HLA-B27 positive cells is a complex event, Soluble HLA-B27 is a potential key player. C1 UNIV CALIF LOS ANGELES,DIV RHEUMATOL,REHABIL CTR 35 40,LOS ANGELES,CA 90095. UNIV TOKYO,TOKYO,JAPAN. NATL PUBL HLTH INST,TURKU,FINLAND. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. OI Tsuchiya, Naoyuki/0000-0002-6776-5580 NR 23 TC 24 Z9 27 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD APR PY 1997 VL 40 IS 4 BP 694 EP 703 DI 10.1002/art.1780400414 PG 10 WC Rheumatology SC Rheumatology GA WR366 UT WOS:A1997WR36600013 PM 9125251 ER PT J AU Waltrip, RW Lieberman, JA Robinson, DG Bilder, RM Alvir, JM King, LR Summerfelt, A Rubin, SA Carbone, KM AF Waltrip, RW Lieberman, JA Robinson, DG Bilder, RM Alvir, JM King, LR Summerfelt, A Rubin, SA Carbone, KM TI Borna disease virus seroconversion in first episode schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 MARYLAND PSYCHIAT RES CTR,BALTIMORE,MD 21228. US FDA,LAB PEDIAT VIRAL DIS & RESP VIRUSES,CBER,OVRR,DVP,ROCKVILLE,MD 20857. UNIV N CAROLINA,DEPT PSYCHIAT,CHAPEL HILL,NC 27515. RI Bilder, Robert/A-8894-2008 OI Bilder, Robert/0000-0001-5085-7852 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 396 EP 396 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900395 ER PT J AU Cebula, TA LeClerc, JE AF Cebula, TA LeClerc, JE TI Hypermutability and homeologous recombination: Ingredients for rapid evolution SO BULLETIN DE L INSTITUT PASTEUR LA English DT Review ID ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; MUTATOR STRAINS; GENE-TRANSFER; O-ANTIGEN; BACTERIA; POPULATIONS; SELECTION; GENOME; POLYMORPHISM AB We examine basic tenets of evolution, i.e., the relative roles that mutation and recombination play in instituting the genetic diversity upon which selection works to establish bacteria in particular niches. Specifically, we delve into the importance of particular mutator phenotypes and their potential contributions to homeologous recombination in bacteria. The implications for rapid evolution and the emergence of new pathogens are discussed. RP Cebula, TA (reprint author), US FDA, MOL BIOL BRANCH, CTR FOOD SAFETY & APPL NUTR HFS 235, WASHINGTON, DC 20204 USA. NR 62 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0020-2452 J9 B I PASTEUR JI Bull. Inst. Pasteur PD APR-JUN PY 1997 VL 95 IS 2 BP 97 EP 106 DI 10.1016/S0020-2452(97)83917-6 PG 10 WC Immunology; Microbiology; Virology SC Immunology; Microbiology; Virology GA XM510 UT WOS:A1997XM51000005 ER PT J AU Hammons, GJ Milton, D Stepps, K Guengerich, FP Tukey, RH Kadlubar, FF AF Hammons, GJ Milton, D Stepps, K Guengerich, FP Tukey, RH Kadlubar, FF TI Metabolism of carcinogenic heterocyclic and aromatic amines by recombinant human cytochrome P450 enzymes SO CARCINOGENESIS LA English DT Article ID CIGARETTE-SMOKE CONDENSATE; HUMAN LIVER-MICROSOMES; ESCHERICHIA-COLI; COOKED FOOD; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; MUTAGENIC ACTIVATION; FURAFYLLINE; OXIDATION; PURIFICATION; INHIBITION AB The N-hydroxylation of carcinogenic arylamines represents an initial step in their metabolic activation, Animal studies have shown that this reaction is catalyzed by the cytochrome P450 (P450) enzymes P450 1A1 and P450 1A2. In this study, utilizing enzymes expressed in Escherichia coli (and purified) or in human B-lymphoblastoid cells, the catalytic activities of recombinant human P450 1A1, P450 1A2, and P450 3A4 for N-hydroxylation of several carcinogenic arylamines were determined. P450 1A2 from both expression systems catalyzed the N-hydroxylation of 4-aminobiphenyl and the heterocyclic amines, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazol[4,5-f]quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhLP), Rates were similar, with values of 1.1-7.8 nmol/min/nmol P450, In contrast, P450 1A1 catalyzed N-hydroxylation of only PhIP, and no activity was observed with P450 3A4, Further kinetic analysis with purified P450 1A2 showed similar K-m and V-max values for N-hydroxylation of the arylamines, Furafylline and fluvoxamine, inhibitors of P450 1A2 activity in human liver microsomes, were found to be inhibitory of the recombinant P450 1A2 N-hydroxylation activity, Results from this study are supportive of a major role for human P450 1A2 in the metabolic activation of arylamines. C1 VANDERBILT UNIV SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37232. VANDERBILT UNIV SCH MED,CTR MOL TOXICOL,NASHVILLE,TN 37232. UNIV CALIF SAN DIEGO,CTR CANC,LA JOLLA,CA 92093. RP Hammons, GJ (reprint author), NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 48 TC 100 Z9 101 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 1997 VL 18 IS 4 BP 851 EP 854 DI 10.1093/carcin/18.4.851 PG 4 WC Oncology SC Oncology GA WT305 UT WOS:A1997WT30500036 PM 9111224 ER PT J AU BarditchCrovo, P Witter, F Hamzeh, F McPherson, J Stratton, P Alexander, NJ Trapnell, CB AF BarditchCrovo, P Witter, F Hamzeh, F McPherson, J Stratton, P Alexander, NJ Trapnell, CB TI Quantitation of vaginally administered nonoxynol-9 in premenopausal women SO CONTRACEPTION LA English DT Article DE nonoxynol-9; spermicide; HIV prevention; STD prevention ID CONTRACEPTION AB A feasibility study was performed in 11 healthy nonpregnant premenopausal women to determine a method for collection and recovery of vaginally administered nonoxynol-9. We also determined ii nonoxynol-9 could be quantitated in vaginal lavage fluid obtained 2 h after instillation of a standard precoital dose of a foam formulation of nonoxynol-9. Samples were analyzed in batch using a validated normal phase high-performance liquid chromatography (HPLC) method. Two hours after instillation of one dose of Delfen(R) Contraceptive Foam (100 mg), the quantity of nonoxynol-9 collected ranged from 10.8 to 67.8 mg (mean: 35.4 mg). This corresponds to a recovery of 11-70% of the administered dose. Quantitation of vaginally administered nonoxynol-9 is both practical and feasible. These data represent a critical first step in the evaluation of the safety and effectiveness of nonoxynol-9-containing products in the prevention of sexually transmitted diseases. (C) 1997 Elsevier Science Inc. C1 JOHNS HOPKINS UNIV, SCH MED, DEPT MED, DIV CLIN PHARMACOL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT OBSTET & GYNECOL, BALTIMORE, MD 21205 USA. NICHHD, CONTRACEPT DEV BRANCH, ROCKVILLE, MD USA. US FDA, CTR DRUG EVALUAT & RES, ROCKVILLE, MD 20857 USA. FU NCRR NIH HHS [RR00722]; PHS HHS [223-93-3011] NR 11 TC 7 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0010-7824 J9 CONTRACEPTION JI Contraception PD APR PY 1997 VL 55 IS 4 BP 261 EP 263 DI 10.1016/S0010-7824(97)00003-6 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XC512 UT WOS:A1997XC51200010 PM 9179459 ER PT J AU Whiteley, M Kassis, JA AF Whiteley, M Kassis, JA TI Rescue of Drosophila engrailed mutants with a highly divergent mosquito engrailed cDNA using a homing, enhancer-trapping transposon SO DEVELOPMENT LA English DT Article DE engrailed; mosquito; P-element homing; enhancer-trapping; gene therapy; Drosophila ID SEQUENCE HOMOLOGY; GENE; EXPRESSION; ELEMENT; EMBRYOGENESIS; PATTERN; MOUSE; MELANOGASTER; COMPARTMENT; CLONING AB Specific fragments of Drosophila regulatory DNA can alter the insertional specificity of transposable elements causing them to 'home' to their parent gene. We used this property to insert a transposon-encoded functional coding region near a defective one and rescue a null mutation. This approach differs from homologous recombination in that the endogenous defective coding region is left in place and the genomic DNA is altered by the addition of the therapeutic transposon. We constructed a P-element-based transposon in which an engrailed cDNA from Anopheles gambiae (a mosquito) is expressed from a Drosophila engrailed minimal promoter. The promoter fragment used includes 2.6 kb of regulatory DNA that causes transposons to home to the endogenous Drosophila engrailed gene at high frequencies. We inserted this transposon onto a Drosophila chromosome that produces no functional engrailed proteins. When this transposon integrated near the engrailed promoter, adult viability was restored to engrailed mutant flies showing that the highly divergent mosquito engrailed protein can replace the Drosophila engrailed protein at all stages of development. Insertion of this transposon into the adjacent invected gene, which is transcribed in a pattern similar to engrailed, led to only embryonic rescue, suggesting an important difference in the regulation of these two genes. RP Whiteley, M (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,29 LINCOLN DR,BETHESDA,MD 20892, USA. OI Kassis, Judith/0000-0001-9268-3213 NR 46 TC 14 Z9 15 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD APR PY 1997 VL 124 IS 8 BP 1531 EP 1541 PG 11 WC Developmental Biology SC Developmental Biology GA WZ580 UT WOS:A1997WZ58000010 PM 9108369 ER PT J AU Patterson, TA Binienda, ZK Lipe, GW Gillam, MP Slikker, W Sandberg, JA AF Patterson, TA Binienda, ZK Lipe, GW Gillam, MP Slikker, W Sandberg, JA TI Transplacental pharmacokinetics and fetal distribution of azidothymidine, its glucuronide, and phosphorylated metabolites in late-term rhesus macaques after maternal infusion SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ZIDOVUDINE AZIDOTHYMIDINE; HIV INFECTION; PREGNANCY; AZT; 3'-AZIDO-3'-DEOXYTHYMIDINE; 2',3'-DIDEOXYINOSINE; CHILDREN; TOXICITY; WOMEN AB 3'-Azido-3'-deoxythymidine (AZT) is currently prescribed to pregnant women infected with human immunodeficiency virus to reduce the risk of vertical transmission of the virus to the fetus. Consequently, more information is needed concerning the placental transfer and tissue distribution of AZT and its metabolites. In the present study, the placental transfer and fetal accumulation of AZT, its glucuronide metabolite [3'-azido-3'-deoxythymidine-beta-D-glucuronide (AZTG)], and phosphorylated metabolites were examined at steady-state in near-term rhesus macaques. One to 2 weeks before a chronic infusion, an intravenous bolus of 8 mg/kg AZT was administered to pregnant animals to determine the dose of AZT needed to reach steady-state plasma concentrations. On the day of hysterotomy, the mother was administered an intravenous loading dose of AZT, followed by a 3-hr steady-state intravenous infusion that also included a trace of [H-3]AZT. After 3 hr of infusion, the mother was anesthetized, and the fetus was delivered. Plasma and amniotic fluid were analyzed for AZT and AZTG by HPLC, and tissue samples were analyzed for AZT, AZTG, and phosphorylated metabolites by strong anion exchange HPLC. Maternal steady-state plasma concentrations were 1.3-2.2 mu g/ml for AZT and 2.3-8.0 mu g/ml for AZTG. Fetal AZT and AZTG plasma concentrations were both lower (0.98-2.3 mu g/ml and 1.3-5.4 mu g/ml, respectively) than maternal concentrations, with fetal-to-maternal plasma ratios of 0.63-1.0 for AZT. Fetal tissue distribution of tritium was highest in the kidney and lowest in the brain. Although the active triphosphorylated metabolite was not detected in the fetus, the AZT-monophosphate was detected in almost all fetal tissues examined. Our data indicate that AZT is rapidly converted to the glucuronide and monophosphate metabolites in the fetus after maternal infusion. RP Patterson, TA (reprint author), US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,HFT-132,3900 NCTR RD,JEFFERSON,AR 72079, USA. FU NIEHS NIH HHS [IAG Y01-ES-10187] NR 38 TC 24 Z9 24 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 APR PY 1997 VL 25 IS 4 BP 453 EP 459 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WT742 UT WOS:A1997WT74200010 PM 9107545 ER PT J AU Goldstein, J Mostowsky, H Tung, J Hon, H Brunswick, M Kozlowski, S AF Goldstein, J Mostowsky, H Tung, J Hon, H Brunswick, M Kozlowski, S TI Naive alloreactive CD8 T cells are activated by purified major histocompatibility complex class I and antigenic peptide SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE cytotoxic T lymphocyte; major histocompatibility complex; cellular activation; CD8 ID MOUSE MHC ANTIGENS; TRANSGENIC MICE; MONOCLONAL-ANTIBODIES; LYMPHOCYTES-T; PLANAR MEMBRANES; RECEPTOR; AFFINITY; EXPRESSION; REQUIREMENTS; ASSOCIATION AB In this report, we demonstrate stimulation of T cell receptor (TCR) transgenic CD8 T cells by isolated major histocompatibility complex (MHC) class I H-2L(d) complexes and antigenic peptide. This is the first demonstration of CDS T cells activated by MHC and antigenic peptide in the absence of antigen priming. Furthermore, isolated MHC and a potent peptide antigen can stimulate phenotypically naive CD44(-) T cells to become CTL effecters and to produce interleukin-2 in nanogram per milliliter amounts. These results demonstrate that particular TCR antigen pairs may overcome the need for specialized antigen-presenting cells and have implications for mechanisms of autoimmunity and tolerance induction. C1 US FDA,CTR BIOL EVALUAT & RES,DIV MONOCLONAL ANTIBODIES,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV CELL & GENE THERAPY,BETHESDA,MD 20892. NR 42 TC 16 Z9 16 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD APR PY 1997 VL 27 IS 4 BP 871 EP 878 DI 10.1002/eji.1830270411 PG 8 WC Immunology SC Immunology GA WU326 UT WOS:A1997WU32600011 PM 9130638 ER PT J AU Rader, JI Weaver, CM Patrascu, L Ali, LH Angyal, G AF Rader, JI Weaver, CM Patrascu, L Ali, LH Angyal, G TI alpha-Tocopherol, total vitamin A and total fat in margarines and margarine-like products SO FOOD CHEMISTRY LA English DT Article ID OILS AB Consumers' interest in dietary guidelines advising them to reduce their intake of fat has contributed to the development of new low- and fat-free margarine-like products. We measured vitamin E (alpha-tocopherol) and vitamin A (retinol and beta-carotene) in margarines and margarine-like products labeled as containing 0-80% fat. Test portions were saponified, extracted with petroleum ether, and analyzed by high performance liquid chromatography. Margarines of approximately 80% fat content contained 4-30 IU alpha-tocopherol/100 8. Reduced-fat margarines (fat content 14-53%) contained 4-15 IU alpha-tocopherol/100 g, while fat-free margarines (<1% fat) contained <1 IU alpha-tocopherol/100 g. alpha-Tocopherol in the products varied both with total fat content and with the vegetable oil ingredients. Total vitamin A measured in margarine products fell between 59 and 196% of label declarations. Published by Elsevier Science Ltd. RP Rader, JI (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,OFF FOOD LABELING,200 C ST SW,WASHINGTON,DC 20204, USA. NR 13 TC 12 Z9 13 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 APR PY 1997 VL 58 IS 4 BP 373 EP 379 DI 10.1016/S0308-8146(96)00260-9 PG 7 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA WE397 UT WOS:A1997WE39700014 ER PT J AU Garthright, WE AF Garthright, WE TI The three-phase linear model of bacterial growth: A response SO FOOD MICROBIOLOGY LA English DT Editorial Material AB Buchanan et al. compare a Three-phase linear model of bacterial growth with the Gompertz and Baranyi nonlinear models. The three-phase linear model imposes horizontal line fits on the lag and stationary periods and uses least squares regression to allocate observations to the three phases, as well as to the coordinates of the three lines themselves. This extension of the early graphical methods of microbiologists is mechanistic and very simple, and appears fully adequate far use as a primary model to support multi-parameter environmental modeling of bacterial growth. (C) 1997 Academic Press Limited. RP Garthright, WE (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,200 C ST SW,WASHINGTON,DC 20204, USA. NR 3 TC 4 Z9 4 U1 0 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD APR PY 1997 VL 14 IS 2 BP 193 EP 195 DI 10.1006/fmic.1996.0081 PG 3 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA WX268 UT WOS:A1997WX26800012 ER PT J AU Yetley, EA Moore, RJ AF Yetley, EA Moore, RJ TI Medical foods: A regulatory paradox SO FOOD TECHNOLOGY LA English DT Editorial Material RP Yetley, EA (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,OFF SPECIAL NUTRIT,200 C ST SW,WASHINGTON,DC 20204, USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA SUITE 300 221 N LASALLE ST, CHICAGO, IL 60601-1291 SN 0015-6639 J9 FOOD TECHNOL-CHICAGO JI Food Technol. PD APR PY 1997 VL 51 IS 4 BP 136 EP 136 PG 1 WC Food Science & Technology SC Food Science & Technology GA WT542 UT WOS:A1997WT54200016 ER PT J AU Saito, T Sherman, GJ Kurokohchi, K Guo, ZP Donets, M Yu, MYW Berzofsky, JA Akatsuka, T Feinstone, SM AF Saito, T Sherman, GJ Kurokohchi, K Guo, ZP Donets, M Yu, MYW Berzofsky, JA Akatsuka, T Feinstone, SM TI Plasmid DNA-based immunization for hepatitis C virus structural proteins: Immune responses in mice SO GASTROENTEROLOGY LA English DT Article ID CYTOTOXIC T-CELLS; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; PERSISTENT VIRAL-INFECTION; NON-B HEPATITIS; MAMMALIAN-CELLS; HYPERVARIABLE REGION-1; MEDIATED IMMUNIZATION; PROTECTIVE IMMUNITY; SURFACE-ANTIGEN; BLOOD-DONORS AB Background & Aims: Plasmid DNA-based immunization has been shown to be an effective means of vaccination in animal models. In this study, the immune responses to various hepatitis C virus structural protein antigens weve evaluated using this technique. Methods: Six recombinant plasmids were constructed. These include, individually, the coding regions for the core protein (pC); E1 (pE1) and E2 (pE2); as well as cove, E1, and E2 together (pCE1E2); E1 and E2 together (pE1E2); and finally an E2 construct from which the N-terminal hypervariable region had been deleted (pE2 Delta HVR). These plasmids were transfected into mammalian cells to test their protein expression and were injected into the quadriceps muscles of BALB/c mice to measure specific antibodies and cytotoxic T-lymphocyte responses. Results: All the recombinant plasmids weve shown to express specific antigens transiently in cells and elicited specific antibody responses to core, El, and E2 in mice. Specific cytotoxic T lymphocyte responses were detected only in mice injected with plasmid constructs encoding the core. Conclusions: Genetic immunization can aid the development of hepatitis C virus vaccines by allowing for the rapid construction and evaluation of different expression plasmids as potential immunogens. C1 US FDA,CTR BIOL EVALUAT & RES,HEPATITIS VIRUSES LAB,DIV VIRAL PROD,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,PLASMA DERIVAT LAB,BETHESDA,MD 20892. NCI,METAB BRANCH,MOL IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20892. NR 66 TC 57 Z9 60 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 BP 1321 EP 1330 DI 10.1016/S0016-5085(97)70146-X PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WT504 UT WOS:A1997WT50400036 PM 9098018 ER PT J AU Laine, L Hopkins, RJ Girardi, LS AF Laine, L Hopkins, RJ Girardi, LS TI Has the impact of H-pylori therapy on duodenal ulcer recurrence in the US been overstated: A meta-analysis of rigorously-designed trials. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV SO CALIF, LOS ANGELES, CA 90089 USA. US FDA, ROCKVILLE, MD 20857 USA. NR 0 TC 22 Z9 22 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A192 EP A192 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41900764 ER PT J AU Harvey, BE Alpert, S AF Harvey, BE Alpert, S TI Regulatory policy and computer assisted imaging technologies: Is ''virtual colonoscopy'' an implied claim? SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 US FDA,CTR DEVICES & RADIOL HLTH,OFF DEVICE EVALUAT,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1997 VL 45 IS 4 SU S BP 26 EP 26 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WU214 UT WOS:A1997WU21400026 ER PT J AU Franzoso, G Carlson, L SchartonKersten, T Shores, EW Epstein, S Grinberg, A Tran, T Shacter, E Leonardi, A Anver, M Love, P Sher, A Siebenlist, U AF Franzoso, G Carlson, L SchartonKersten, T Shores, EW Epstein, S Grinberg, A Tran, T Shacter, E Leonardi, A Anver, M Love, P Sher, A Siebenlist, U TI Critical roles for the Bcl-3 oncoprotein in T cell-mediated immunity, splenic microarchitecture, and germinal center reactions SO IMMUNITY LA English DT Article ID NF-KAPPA-B; CANDIDATE PROTOONCOGENE BCL-3; PERIPHERAL LYMPHOID ORGANS; LYN-DEFICIENT MICE; TARGETED DISRUPTION; NEONATAL LETHALITY; AUTOIMMUNE-DISEASE; TOXOPLASMA-GONDII; PRECURSOR P105; DNA-BINDING AB Chromosomal translocations of bcl-3 are associated with chronic B cell lymphocytic leukemias. Previously, we have shown that Bcl-3, a distinct member of the I kappa B family, may function as a positive regulator of NF-kappa B activity, although its physiologic roles remained unknown. To uncover these roles, we generated Bcl-3-deficient mice. Mutant mice, but not their littermate controls, succumb to T. gondii owing to failure to mount a protective T helper 1 immune response. Bcl-3-deficient mice are also impaired in germinal center reactions and T-dependent antibody responses to influenza virus. The results reveal critical roles for Bcl-3 in antigen-specific priming of T and B cells. Altered microarchitecture of secondary lymphoid organs in mutant mice, including partial loss of B cells, may underlie the immunologic defects. The implied role of Bcl-3 in maintaining B cells in wild-type mice may related to its oncogenic potential. C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. NICHHD,MOL GENET LAB,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,BETHESDA,MD 20892. SCI APPLICAT INT CORP,PATHOL HISTOTECHNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. OI LEONARDI, Antonio/0000-0001-8636-9623 NR 69 TC 131 Z9 135 U1 2 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD APR PY 1997 VL 6 IS 4 BP 479 EP 490 DI 10.1016/S1074-7613(00)80291-5 PG 12 WC Immunology SC Immunology GA XC619 UT WOS:A1997XC61900013 PM 9133427 ER PT J AU FernandezPrada, CM Hoover, DL Tall, BD Venkatesan, MM AF FernandezPrada, CM Hoover, DL Tall, BD Venkatesan, MM TI Human monocyte-derived macrophages infected with virulent Shigella flexneri in vitro undergo a rapid cytolytic event similar to oncosis but not apoptosis SO INFECTION AND IMMUNITY LA English DT Article ID PROGRAMMED CELL-DEATH; IL-1 RECEPTOR ANTAGONIST; EPITHELIAL-CELLS; MURINE MACROPHAGES; INTERLEUKIN-1; CLEAVAGE; DNA; FRAGMENTATION; CYTOKINES; ANTIBODY AB Infection of human monocyte-derived macrophages in vitro with virulent Shigella flexneri resulted in cell death which involved rupture of the plasma membrane, cell swelling, disintegration of ultrastructure, and generalized karyolysis, These features bore resemblance to oncosis and are in striking contrast to previously described observations of mouse macrophages, where a similar infection by virulent Shigella resulted in cell death by apoptosis, Cell death by oncosis in human macrophages was confirmed by lactate dehydrogenase release, light microscopy, electron microscopy, terminal deoxynucleotidyltransferase end labeling of DNA ends, DNA fragmentation assays, and fluorescence-activated cell sorter analysis of propidium-labeled nuclei. Thus, the phenomena of cell death induced by virulent Shigella in human and mouse macrophages reflect different biochemical pathways. Interleukin-1 beta (IL-1 beta) was released in culture supernatants of human macrophages infected with virulent bacteria, Inhibition with IL-lp-converting enzyme inhibitors indicated, however, that this release occurred as a passive event of cell lysis, The patterns of intracellular survival of Shigella strains within human and mouse macrophages reflect differences that exist not only between Shigella serotypes but also between the two different macrophage cell types. C1 WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,DEPT ENTER INFECT,DIV COMMUN DIS & IMMUNOL,WASHINGTON,DC 20307. GEORGE WASHINGTON UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,WASHINGTON,DC 20204. US FDA,CTR FOOD SAFETY & APPL NUTR,MICROBIAL ECOL BRANCH,WASHINGTON,DC 20204. OI Tall, Ben/0000-0003-0399-3629 NR 51 TC 60 Z9 65 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 APR PY 1997 VL 65 IS 4 BP 1486 EP 1496 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WQ298 UT WOS:A1997WQ29800049 PM 9119491 ER PT J AU Feigal, EG VonRoenn, J Justice, R Yarchoan, R Krown, S Pluda, J Arbuck, S Murgo, A McCabe, M Ungerleider, R Wittes, R AF Feigal, EG VonRoenn, J Justice, R Yarchoan, R Krown, S Pluda, J Arbuck, S Murgo, A McCabe, M Ungerleider, R Wittes, R TI Kaposi's sarcoma response criteria: Issues identified by the National Cancer Institute, Food and Drug Administration, and the AIDS Malignancy Consortium. SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. NCI,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 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 24 EP 24 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100059 ER PT J AU Musser, SM Plattner, RD AF Musser, SM Plattner, RD TI Fumonisin composition in cultures of Fusarium moniliforme, Fusarium proliferatum, and Fusarium nygami SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE fumonisins; mass spectrometry; analysis ID LIQUID-CHROMATOGRAPHIC DETERMINATION; MYCOTOXINS; CORN; B-1; TOXICITY; FOODS; FEEDS; RATS AB Total fumonisin composition of 22 cultures of Fusaria was determined by liquid chromatography-mass spectrometry. All cultures contained primarily FB1-3 and FA(1-2) With little or no variation in the relative percentage of each. In addition to the five principal fumonisins, seven other fumonisins were identified in all cultures; however their concentrations never exceeded 10% relative to FB1. Of the 22 cultures surveyed, 5 produced low levels (<2 mol %) of the P series of fumonisins and 5 cultures produced high levels of the P series. In cultures producing high levels of FP1, levels ranged from 20 to 35 mol % of the FB1 produced by the culture. High-level production of the P series of fumonisins in culture was found to require anaerobic conditions. In cultures grown aerobically, the level of FP1 never reached more than 2-4% of the FB1; however cultures grown anaerobically produced levels of 20-35% of FB1. C1 USDA ARS, NATL CTR AGR UTILIZAT RES, PEORIA, IL 61604 USA. RP Musser, SM (reprint author), US FDA, INSTRUMENTAT & BIOPHYS BRANCH, CTR FOOD SAFETY & APPL NUTR, HFS-717, 200 C ST SW, WASHINGTON, DC 20204 USA. NR 30 TC 85 Z9 90 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD APR PY 1997 VL 45 IS 4 BP 1169 EP 1173 DI 10.1021/jf960663t PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA WU773 UT WOS:A1997WU77300025 ER PT J AU Luo, WH Hansen, EB Ang, CYW Deck, J Freeman, JP Thompson, HC AF Luo, WH Hansen, EB Ang, CYW Deck, J Freeman, JP Thompson, HC TI Simultaneous determination of amoxicillin and ampicillin in bovine milk by HPLC with fluorescence detection SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE amoxicillin; ampicillin; antibiotics; milk; HPLC ID LIQUID-CHROMATOGRAPHY; PENICILLIN-G; RESIDUES AB A sensitive liquid chromatographic analytical method using fluorescence detection was developed for the simultaneous determination of amoxicillin and ampicillin residues in raw and processed bovine milk. Aliquots of raw or processed milk (5 mL) were diluted to 30 mL with 0.01 M KH2PO4 (pH 4.5) buffer, and the soluble proteins were precipitated with the addition of sodium tungstate and sulfuric acid followed by centrifugation. The drug residues were concentrated by passing the supernatant through a C-18 solid phase extraction cartridge. Amoxicillin and ampicillin were eluted from the cartridge and reacted with salicylaldehyde to form fluorescent derivatives, which were then analyzed with liquid chromatography and fluorescence detection. Average recoveries of spiked amoxicillin and ampicillin at 5, 10, and 20 ng/mL were >80%, with coefficients of variation (CV) <5%. The limit of detection (LOD) and limit of quantitation (LOQ) for amoxicillin were 1.1 and 2.4 ng/mL, respectively. The LOD and LOQ for ampicillin were 1.0 and 1.7 ng/mL, respectively. C1 US FDA, NATL CTR TOXICOL RES, DEPT HLTH & HUMAN SERV, DIV BIOCHEM TOXICOL, JEFFERSON, AR 72079 USA. RP Luo, WH (reprint author), US FDA, NATL CTR TOXICOL RES,DHHS,HFT 230,DIV CHEM, 3900 NCTR RD, JEFFERSON, AR 72079 USA. NR 18 TC 30 Z9 33 U1 2 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 EI 1520-5118 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD APR PY 1997 VL 45 IS 4 BP 1264 EP 1268 DI 10.1021/jf960739l PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA WU773 UT WOS:A1997WU77300041 ER PT J AU Camire, ME Violette, D Dougherty, MP McLaughlin, MA AF Camire, ME Violette, D Dougherty, MP McLaughlin, MA TI Potato peel dietary fiber composition: Effects of peeling and extrusion cooking processes SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE dietary fiber; starch; peeling; potato; extrusion ID TWIN-SCREW EXTRUSION; IN-VITRO BINDING; CORN MEAL; STARCH; WHEAT; BRAN AB Potato peels are a potential source of dietary fiber. The abrasion peeling method used by chip manufacturers results in more starch and less dietary fiber than the steam peeling procedure used for production of dehydrated potatoes. The objective of this study was to identify differences in dietary fiber composition between these types of peels and the effects of extrusion on fiber. Peels were extruded in a twin screw extruder at barrel temperatures of 110 or 150 degrees C and feed moistures of 30% or 35%. Extrusion cooking reduced starch content and increased total dietary fiber in steam peels. Total dietary fiber in abrasion peels was not affected by extrusion. Extrusion increased soluble nonstarch polysaccharides in both types of peels. More glucose was recovered from insoluble fiber of extruded steam peels than from abrasion peels, suggesting that resistant starch may have been formed. Lignin increased in extruded steam peels but decreased in extruded abrasion peels. C1 US FDA,NAT PROD DIV,WASHINGTON,DC 20204. RP Camire, ME (reprint author), UNIV MAINE,DEPT FOOD SCI & HUMAN NUTR,5736 HOLMES HALL,ORONO,ME 04469, USA. NR 20 TC 38 Z9 40 U1 6 U2 22 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 APR PY 1997 VL 45 IS 4 BP 1404 EP 1408 DI 10.1021/jf9604293 PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA WU773 UT WOS:A1997WU77300068 ER PT J AU Hahn, DW Wolfarth, DL Parks, NL AF Hahn, DW Wolfarth, DL Parks, NL TI Analysis of polyethylene wear debris using micro-Raman spectroscopy: A report on the presence of beta-carotene SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article ID NORMAL-COORDINATE ANALYSIS; INFRARED BANDS; SEALANT FILMS; RABBIT KNEE; IMPLANTATION; SPECTRA; ISOMERS; ASSIGNMENTS; ANTIOXIDANT; PARTICLES AB This paper describes micro-Raman spectroscopy of ultrahigh molecular weight polyethylene wear debris isolated from revised knee replacements. The novel application of micro-Raman spectroscopy to the analysis of in vivo-generated wear debris was used to evaluate the chemical nature of individual, retrieved polyethylene particles. The analysis revealed the presence of beta-carotene on particles from both synovial fluid and tissue samples. Raman analysis of retrieved polyethylene tibial inserts also revealed localized beta-carotene signals within the primary wear region. In this paper, a mechanism is suggested that may account for the coupling of beta-carotene and polyethylene wear debris. We also discuss the origin of beta-carotene within the implanted joint and the implications that beta-carotene, an antioxidant, has for the overall host response to polyethylene orthopedic components. (C) 1997 John Wiley & Sons, Inc. C1 US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857. ANDERSON ORTHOPAED RES INST,ARLINGTON,VA. RP Hahn, DW (reprint author), SANDIA NATL LABS,MS 9053,LIVERMORE,CA 94551, USA. NR 37 TC 13 Z9 13 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 APR PY 1997 VL 35 IS 1 BP 31 EP 37 DI 10.1002/(SICI)1097-4636(199704)35:1<31::AID-JBM4>3.0.CO;2-N PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA WQ683 UT WOS:A1997WQ68300004 PM 9104696 ER PT J AU Takimoto, CH Dahut, W Marino, MT Nakashima, H Liang, MD Harold, N Lieberman, R Arbuck, SG Band, RA Chen, AP Hamilton, JM Cantilena, LR Allegra, CJ Grem, JL AF Takimoto, CH Dahut, W Marino, MT Nakashima, H Liang, MD Harold, N Lieberman, R Arbuck, SG Band, RA Chen, AP Hamilton, JM Cantilena, LR Allegra, CJ Grem, JL TI Pharmacodynamics and pharmacokinetics of a 72-hour infusion of 9-aminocamptothecin in adult cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TOPOISOMERASE-I INHIBITOR; PHASE-I; CAMPTOTHECIN; TOPOTECAN; CPT-11; XENOGRAFTS; ANALOGS; TRIAL AB Purpose: To investigate the pharmacokinetics and pharmacodynamics of 9-aminocamptothecin (9-AC) infused over 72 hours at doses of 5 to 74 mu g/m(2)/h. Patients and Methods: 9-AC lactone and total (lactone plus carboxylate) plasma concentrations were measured in 44 patients with solid tumors using a high-performance liquid chromatography (HPLC) assay, Fifteen patients underwent extended pharmacokinetic sampling to determine the distribution and elimination kinetics of 9-AC. Results: At steady-state, 8.7% +/- 4.7% (mean +/- SD) of the totes drug circulated in plasma as the active 9-AC lactone, Clearance of 9-AC lactone was uniform (24.5 +/- 7.3 L/h/m(2)) over the entire dose range examined; however, total 9-AC clearance was nonlinear and increased at higher dose levels, In 15 patients treated at dose levels greater than or equal to 47 mu g/m(2)/h, the volume of distribution at steady-state for 9-AC lactone was 195 +/- 114 L/m(2) and for total 9-AC if was 23.6 +/- 10.6 L/m(2). The elimination half-life was 4.47 +/- 0.53 hours for 9-AC lactone and 8.38 +/- 2.10 hours for total 9-AC. In pharmacodynamic studies, dose-limiting neurtropenia correlated with steady-state lactone concentrations (Css) (R-2 = .77) and drug dose (R-2 = .71). Conclusion: Plasma 9-AC concentrations rapidly declined to low levels following the end of a 72-hour infusion and the mean fraction of total 9-AC circulating in plasma as the active lactane was less than 10%. The pharmacokinetics of 9-AC may have a great impact on its clinical activity and should be considered in the design of future clinical trials of this topoisomerase I inhibitor. C1 NCI, CANC THERAPY EVALUAT PROGRAM, BETHESDA, MD 20892 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT INTERNAL MED, DIV CLIN PHARMACOL, BETHESDA, MD 20814 USA. US FDA, CTR DRUG EVALUAT & RES, ROCKVILLE, MD 20857 USA. WALTER REED ARMY MED CTR, WALTER REED ARMY INST RES, DEPT PHARMACOL, DIV EXPT THERAPEUT, WASHINGTON, DC 20307 USA. RP Takimoto, CH (reprint author), NATL NAVAL MED CTR, NCI,NAVY MED ONCOL BRANCH,DIV CLIN SCI,BLDG 8, ROOM 5101, BETHESDA, MD 20889 USA. NR 26 TC 41 Z9 42 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1997 VL 15 IS 4 BP 1492 EP 1501 PG 10 WC Oncology SC Oncology GA WX651 UT WOS:A1997WX65100028 PM 9193345 ER PT J AU Cook, DW AF Cook, DW TI Refrigeration of oyster shellstock: Conditions which minimize the outgrowth of Vibrio vulnificus SO JOURNAL OF FOOD PROTECTION LA English DT Article DE Vibrio vulnificus; oysters; aerobic plate count; time/temperature abuse ID GULF-COAST AB The multiplication of Vibrio vulnificus in summer harvest oyster shellstock held without refrigeration was followed over a 14 h postharvest period. Mean (n = 7) increases were 0.75, 1.30, 1.74, and 1.94 log units at 3.5 h, 7 h, 10.5 h, and 14 h postharvest, respectively. Aerobic plate counts (spread plates on plate count agar [PCA] containing 1% NaCl, 25 degrees C) but not standard plate counts (pour plates, PCA, 35 degrees C) showed a similar trend in increase. Reducing the time oyster shellstock remains outside refrigeration can decrease consumer exposure to high numbers of V. vulnificus, but shellstock must be cooled immediately after harvest to eliminate postharvest growth of this bacterium. RP Cook, DW (reprint author), US FDA,GULF COAST SEAFOOD LAB,DAUPHIN ISL,AL 36528, USA. NR 12 TC 25 Z9 26 U1 0 U2 1 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2838 SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD APR PY 1997 VL 60 IS 4 BP 349 EP 352 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA WW305 UT WOS:A1997WW30500001 ER PT J AU McCarthy, SA AF McCarthy, SA TI Incidence and survival of Listeria monocytogenes in ready-to-eat seafood products SO JOURNAL OF FOOD PROTECTION LA English DT Article DE Listeria monocytogenes; crawfish; crabmeat; smoked salmon ID SMOKED SALMON; PROCESSING PLANTS; FISH; STORAGE; GROWTH; FOODS; TEMPERATURES; BEHAVIOR; SMOKING; MEAT AB The effects of processing and postprocess storage conditions on the incidence and survival of Listeria monocytogenes on crawfish (Procambaris sp.), crabmeat (Callinectus sapidus), and smoked salmon (Salmo salar) were evaluated. L. monocytogenes was recovered from 3% of whole boiled market crawfish samples and 17% of frozen vacuum-packaged partially cooked crawfish tail meat, but not from boiled crabmeat or smoked salmon. Contamination was most likely due to postprocess handling as commonly used methods of cooking (5 min boil or 20 min steep) reduced L. monacytogenes to nondetectable levels in laboratory-contaminated crawfish. In postprocess storage temperature abuse studies, cooked whole crawfish were inoculated internally and externally with 3.0 log CFU of L. monocytogenes per g and incubated at 22 or 30 degrees C for 6 h. The greatest increase in numbers of cells, 1.9 log CFU/g (determined by standard plate count), occurred at 30 degrees C on externally contaminated crawfish. There was little change in numbers of L. monocytogenes during cold storage (6 degrees C, 5 days; -20 degrees C, 15 days). There was Little change in cell numbers associated with products stored at 22 or -20 degrees C. At 6 degrees C, numbers of cells associated with crabmeat increased by 3.8 log MPN/g after 6 days; however, there was no increase in numbers of cells associated with salmon. The results show that the survival and growth characteristics of L. monocytogenes are dependent on storage time and temperature and the nature of the seafood product. RP McCarthy, SA (reprint author), US FDA,GULF COAST SEAFOOD LAB,DAUPHIN ISL,AL 36528, USA. NR 30 TC 35 Z9 36 U1 1 U2 3 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2838 SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD APR PY 1997 VL 60 IS 4 BP 372 EP 376 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA WW305 UT WOS:A1997WW30500006 ER PT J AU McCarthy, S AF McCarthy, S TI Evaluation of the Listertest(TM) method for quantitation of Listeria monocytogenes in seafoods SO JOURNAL OF FOOD PROTECTION LA English DT Article DE Listeria monocytogenes; quantitation; seafood; Listertest(TM) AB The U.S. Food and Drug Administration most probable number (MPN) method and the Listertest(TM) (immunomagnetic capture) were used to enumerate Listeria monocytogenes on laboratory-inoculated cooked crabmeat (Callinectus sapidus) and cold-smoked salmon (Salmo salar). The products were inoculated with < 1.0 to 4.0 log CFU of L. monocytogenes per g and analyzed immediately. In the analyses of crabmeat, the results obtained by the MPN method were significantly lower (P < 0.05) than counts produced by the Listertest(TM). There was no significant difference (P < 0.05) between results produced by MPN and the Listertest(TM) in analyses of smoked salmon. The methods had the same variance in the quantitation of L. monocytogenes in these seafood products. RP McCarthy, S (reprint author), US FDA,GULF COAST SEAFOOD LAB,DAUPHIN ISL,AL 36528, USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2838 SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD APR PY 1997 VL 60 IS 4 BP 424 EP 425 PG 2 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA WW305 UT WOS:A1997WW30500014 ER PT J AU Culkin, SJ RhinehartJones, T Elkins, KL AF Culkin, SJ RhinehartJones, T Elkins, KL TI A novel role for B cells in early protective immunity to an intracellular pathogen, Francisella tularensis strain LVS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; RECEPTOR-GAMMA-DELTA; T-CELLS; INTRAEPITHELIAL LYMPHOCYTES; MACROPHAGE ACTIVATION; INDEPENDENT MECHANISM; INTERFERON-GAMMA; LEISHMANIA-MAJOR; FACTOR-ALPHA; SCID MICE AB Normal BALB/cByJ mice given a sublethal infection of Francisella tularensis strain LVS survived 10(6) LD(50)s Of lethal challenge given only 3 days later. Here, we determine the cell types responsible for this very strong early protective immunity. Early protection is observed in athymic nu/nu mice but not fully immunodeficient scid mice, implicating a lymphocyte in this response. Using scid mice that are reconstituted with various purified cell subpopulations, as well as mice with genetically targeted disruptions in lymphocyte subpopulations (knockout mice), we demonstrate that strong early protection is highly dependent on B cells. This protective mechanism, which limits bacterial growth in the organs of the reticuloendothelial system very quickly after infection, requires IFN-gamma but is unlikely to involve specific Ab. C1 US FDA,LAB MYCOBACTERIA,DIV BACTERIAL PROD,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852. NR 40 TC 50 Z9 50 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 APR 1 PY 1997 VL 158 IS 7 BP 3277 EP 3284 PG 8 WC Immunology SC Immunology GA WQ643 UT WOS:A1997WQ64300031 PM 9120284 ER PT J AU Kessler, DA Natanblut, SL Wilkenfeld, JP Lorraine, CC Mayl, SL Bernstein, IBG Thompson, L AF Kessler, DA Natanblut, SL Wilkenfeld, JP Lorraine, CC Mayl, SL Bernstein, IBG Thompson, L TI Nicotine addiction: A pediatric disease SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID CHILDREN RP Kessler, DA (reprint author), US FDA, OFF COMMISSIONER, ROCKVILLE, MD 20857 USA. NR 51 TC 63 Z9 64 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD APR PY 1997 VL 130 IS 4 BP 518 EP 524 DI 10.1016/S0022-3476(97)70232-4 PG 7 WC Pediatrics SC Pediatrics GA WT417 UT WOS:A1997WT41700007 PM 9108846 ER PT J AU Goswami, BB Burkhardt, W Cebula, TA AF Goswami, BB Burkhardt, W Cebula, TA TI Identification of genetic variants of hepatitis A virus SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE hepatitis A virus; PCR; RFLP; SSCP; HAV identification ID POLYMERASE CHAIN-REACTION; POLYMORPHISM SSCP TECHNIQUE; A VIRUS; REVERSE TRANSCRIPTION; MESSENGER-RNA; QUANTITATION; PCR; MUTATIONS; STRAINS; DNA AB Although detection of hepatitis A virus (HAV) has been greatly aided by the development of polymerase chain reaction (PCR) technology, identification of genetic variants requires sequencing PCR products, which necessarily limits the length of the HAV genome (typically 2%) that can be analyzed. From a regulatory standpoint, identification of the specific strain detected by PCR is a prerequisite not only to overrule contamination of test samples in the diagnostic laboratory, but also to possibly locate the origin of the virus detected by PCR. We explored alternatives to sequencing PCR products to achieve these goals. The findings indicate that restriction fragment length polymorphism (RFLP) analysis of PCR products from two noncontiguous regions of the HAV genome encompassing 765 nucleotides (approximately 10% of the genome) by the restriction endonucleases HinfI and AluI, which cut frequently within the HAV genome, can distinguish the common tissue culture adapted strains of HAV from stool isolates. The resolution can be greatly enhanced by combining single strand conformation polymorphism (SSCP) analysis with restriction enzyme digestion, when most of the seventeen strains analyzed could be identified. (C) 1997 Elsevier Science B.V. RP Goswami, BB (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV MOL BIOL RES & EVALUAT,200 C ST SW,HFS-237,WASHINGTON,DC 20204, USA. NR 30 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD APR PY 1997 VL 65 IS 1 BP 95 EP 103 DI 10.1016/S0166-0934(97)02179-4 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA WT807 UT WOS:A1997WT80700011 PM 9128866 ER PT J AU Levenbook, I Nomura, T AF Levenbook, I Nomura, T TI Development of a neurovirulent testing system for oral poliovirus vaccine with transgenic mice SO LABORATORY ANIMAL SCIENCE LA English DT Article; Proceedings Paper CT XI General Assembly and Joint Conference of ICLAS / ScandLAS / FinLAS / Frontiers in Laboratory Animal Science CY JUL 02-06, 1996 CL HELSINKI, FINLAND SP ICLAS, ScandLAS, FinLAS ID GENETIC STABILITY; RECEPTOR GENE; MONKEY TEST; EXPRESSION; SEQUENCE; STRAIN; MODEL; VIRUS AB Because only primates are susceptible to polioviruses, the neurovirulent safety and consistency of oral poliovirus vaccine (OPV) were assayed in the monkey neurovirulence test, After the development of transgenic (Tg) mice carrying the gene for human poliovirus receptor (PVR), the suitability of these mice to replace monkeys for OPV testing was evaluated, Two lines of Tg mice, TgPVR1 and TgPVR21, were tested, The TgPVR21 mice, inoculated in the spinal cord, were as sensitive as monkeys in discriminating between type-3 and type-2 OPV lots that had passed and those that had failed the monkey neurovirulence test, Results of the new molecular assay by polymerase chain reaction and restriction enzyme cleavage indicated that each OPV lot contained minuscule amounts of neurovirulent revertants in the viral genome. All type-3 OPV lots that failed the monkey neurovirulence test had higher percentages of 472-C revertants than did lots that passed this test, Analysis of multiple type-3 OPV lots also indicated a good correlation between the contents of 472-C revertants and results of the TgPVR2 mouse test. An overview of a significant set of data suggests that the TgPVR21 mouse model is suitable for the evaluation of type-3 and type-2 OPV. The necessity of the TgPVR mouse test for the neurovirulence of type-1 OPV, which is the most stable of the three Sabin strains, is under consideration. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20014. CENT INST EXPT ANIM,KAWASAKI,KANAGAWA 216,JAPAN. NR 28 TC 3 Z9 8 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD APR PY 1997 VL 47 IS 2 BP 118 EP 120 PG 3 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA WX988 UT WOS:A1997WX98800002 PM 9150487 ER PT J AU Khan, AA Cerniglia, CE AF Khan, AA Cerniglia, CE TI Rapid and sensitive method for the detection of Aeromonas caviae and Aeromonas trota by polymerase chain reaction SO LETTERS IN APPLIED MICROBIOLOGY LA English DT Article ID TRAVELERS-DIARRHEA; LISTERIA-MONOCYTOGENES; HYDROPHILA; DNA; CHEESE; GENE; PCR; AMPLIFICATION; STRAINS; ANIMALS AB A 16S rDNA-based polymerase chain reaction (PCR) method was developed for the detection of Aeromonas caviae and Aeromonas trota. These two species were identified from other Aeromonas spp. and closely related species by primers set (AER1 and AER2). The amplified product was 316 bp. The identity of the amplified product was confirmed by DNA-DNA hybridization. Two sets of primers (AER8 and AER9) were used for specific identification of Aer. caviae. Amplifying the 260 bp fragment of 16S rRNA gene region and digesting it with AluI restriction enzyme, yielded 180- and 80-bp fragments. For PCR assay, template DNA was released by mixing equal volumes of homogenized seeded crab meat with Aer. caviae and Chelex 100 (6%) incubated for 10 min at 56 degrees C followed by addition of an equal volume of 0.1% Triton-X-100 and boiled for 10 min. The detection limit was between 50 and 100 cells g(-1) of crab meat. This method is very rapid and obviates the need for DNA isolation from complex food matrices and is specific for detecting two Aeromonas species. C1 US FDA,NATL CTR TOXICOL RES,DIV MICROBIOL,JEFFERSON,AR 72079. NR 28 TC 22 Z9 23 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0266-8254 J9 LETT APPL MICROBIOL JI Lett. Appl. Microbiol. PD APR PY 1997 VL 24 IS 4 BP 233 EP 239 DI 10.1046/j.1472-765X.1997.00380.x PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA WV224 UT WOS:A1997WV22400002 PM 9134769 ER PT J AU Duffy, PH Feuers, RJ Pipkin, JL Turturro, A Hart, RW AF Duffy, PH Feuers, RJ Pipkin, JL Turturro, A Hart, RW TI Age and temperature related changes in behavioral and physiological performance in the Peromyscus leucopus mouse SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE age; temperature; physiology; behavior; mouse ID CHRONIC CALORIC RESTRICTION; ENERGY-METABOLISM; RAT; MICE; LIVER AB Age-related and ambient temperature-related changes in motor activity, body temperature, body weight (b.w.), and food consumption were studied in the long-lived Peromyscus leucopus mouse at environmental temperatures of 29 and 21 degrees C. Major changes in physiological performance were observed between the young (6 months) and old (60-72 month) age groups. The number of daily activity episodes, and total activity output was significantly lower in old mice. Maximum, average and minimum daily body temperature was lower in the old mice and a significant ambient temperature-by-age interaction was found. Maximum, minimum, and average daily b.w. was higher in old mice. Motor activity was evenly distributed over the active (night) phase in young mice but in old mice activity was significantly greater in the late night partition of the active cycle than in the early night partition. Both groups were significantly more active at night than during the day. Most of the food consumption in both groups occurred at night, but young mice consumed significantly more during the late night partition than the early night partition, and the consumption rates for old mice were not significantly different between early and late night partitions. The percentage of activity episodes involved with food consumption in both groups was significantly higher during the night partition, but the percentage during the early night partition was significantly higher in old mice than in young mice. Significant episodes of circadian torpor occurred in a high percentage of old mice at 06:00, on consecutive days, at both environmental temperatures, but young mice expressed no evidence of torpor. (C) 1997 Elsevier Science Ireland Ltd. RP Duffy, PH (reprint author), NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,HFT-020,JEFFERSON,AR 72079, USA. NR 31 TC 9 Z9 9 U1 2 U2 7 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 APR PY 1997 VL 95 IS 1-2 BP 43 EP 61 DI 10.1016/S0047-6374(96)01834-9 PG 19 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA WX427 UT WOS:A1997WX42700004 PM 9152960 ER PT J AU Ghosh, C Nandy, RK Dasgupta, SK Nair, GB Hall, RH Ghose, AC AF Ghosh, C Nandy, RK Dasgupta, SK Nair, GB Hall, RH Ghose, AC TI A search for cholera toxin (CT), toxin coregulated pilus (TCP), the regulatory element ToxR and other virulence factors in non-01/non-0139 Vibrio cholerae SO MICROBIAL PATHOGENESIS LA English DT Article DE non-O1 V-cholerae; cholera toxin; toxin coregulated pilus; virulence factors ID POLYMERASE CHAIN-REACTION; OUTER-MEMBRANE PROTEINS; EL-TOR; INTESTINAL COLONIZATION; EPIDEMIC CHOLERA; NON-O1 STRAINS; O139 BENGAL; GENES; VIBRIO-CHOLERAE-O1; INDIA AB Twenty-four selected non-O1/non-O139 Vibrio cholerae strains were examined for the presence of virulence associated genes like ctxA, tcpA, toxR and the repetitive sequence (RS element). Seventeen of these were isolated from diarrhoeal stool samples while the remaining seven were of local environmental origin. Nine and four respectively of these strains were positive for ctxA and tcpA by Multiplex PCR analysis. The majority (16 out of 18 tested) of the strains (including the four tcpA + strains) contained toxR sequences as determined by another PCR assay. The presence of RS element was demonstrable in ctxA(+) strains only. Interestingly, three of these non-O1/non-O139 strains were shown to contain all the three virulence associated genes (ctxA, tcpA and toxR) as well as the RS element. Two of these belonged to serogroups 037 (V2) and 064 (CG15) while the third one (V315-1) was untypable. These three strains also produced cholera toxin, expressed toxin coregulated pilus (TCP) and/or TcpA related antigens when grown under appropriate culture conditions. Southern hybridization analysis of their chromosomal DNA fragments using DNA probes representing ctxA, zot, ace and RS element revealed that the strains V2 and CG15 contained, at least, two complete copies of the CTX genetic element, while the strain V315-1 had three or more copies of the same. Presence of the RS element in these strains led to tandem duplication of the CTX genetic element in the chromosome of V2 and V315-1, but not in CG15 where the copies were likely to be present at different loci. These results also indicate the presence of additional copies of incomplete 'core region' with zot and ace genes, but not ctxA, in strains V2 and CG15. The significance of these results in terms of the pathogenic and epidemic potential of V. cholerae strains is discussed. (C) 1997 Academic Press Limited. C1 BOSE INST,DEPT MICROBIOL,CALCUTTA 700054,W BENGAL,INDIA. NATL INST CHOLERA & ENTER DIS,DEPT MICROBIOL,CALCUTTA 700010,W BENGAL,INDIA. US FDA,DIV VIRULENCE ASSESSMENT,WASHINGTON,DC 20204. NR 51 TC 55 Z9 57 U1 1 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD APR PY 1997 VL 22 IS 4 BP 199 EP 208 DI 10.1006/mpat.1996.0105 PG 10 WC Immunology; Microbiology SC Immunology; Microbiology GA WU896 UT WOS:A1997WU89600002 PM 9140915 ER PT J AU Rosenthal, DS Ding, RC SimbulanRosenthal, CMG Cherney, B Vanek, P Smulson, M AF Rosenthal, DS Ding, RC SimbulanRosenthal, CMG Cherney, B Vanek, P Smulson, M TI Detection of DNA breaks in apoptotic cells utilizing the DNA binding domain of poly(ADP-ribose) polymerase with fluorescence microscopy SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MAMMALIAN-CELLS; REPAIR; INHIBITION; GENE; EXPRESSION; MECHANISM; PROTEASE; SEQUENCE; DAMAGE; MODEL AB The DNA binding domain (DBD) of poly(ADP-ribose) polymerase (PARP) has proved to be a novel, highly sensitive probe for detecting DNA breaks in intact cells undergoing apoptosis. A recombinant peptide spanning the DNA binding domain of PARP was expressed, purified and used to detect DNA strand breaks in fixed cells. Fluorescence microscopy with this probe followed by detection with anti-PARP antisera initially revealed an increased binding following treatment of cells with DNA strand-breaking agents (such as N-methyl-N'-nitro-N-nitrosoguanidine) and,subsequently, using biotinylated PARP DBD, during the later stages of apoptosis in several cell systems, when internucleosomal strand breaks became evident. This procedure was found to be at least as sensitive and required fewer steps to detect DNA strand breaks than those utilizing Klenow incorporation of biotinylated nucleotides. C1 GEORGETOWN UNIV,SCH MED,DEPT BIOCHEM & MOL BIOL,WASHINGTON,DC 20007. US FDA,BETHESDA,MD 20892. TREVIGEN INC,GAITHERSBURG,MD 20898. FU NCI NIH HHS [CA13195] NR 25 TC 20 Z9 20 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR 1 PY 1997 VL 25 IS 7 BP 1437 EP 1441 DI 10.1093/nar/25.7.1437 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WR295 UT WOS:A1997WR29500018 PM 9060441 ER PT J AU Gopalakrishnan, R Weghorst, CM Lehman, TA Calvert, RJ Bijur, G Sabourin, CLK Mallery, SR Schuller, DE Stoner, GD AF Gopalakrishnan, R Weghorst, CM Lehman, TA Calvert, RJ Bijur, G Sabourin, CLK Mallery, SR Schuller, DE Stoner, GD TI Mutated and wild-type p53 expression and HPV integration in proliferative verrucous leukoplakia and oral squamous cell carcinoma SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID TUMOR-SUPPRESSOR GENE; HUMAN PAPILLOMAVIRUS TYPE-16; MUTATIONS; CANCER; HEAD; ASSOCIATION; DEGRADATION; INFECTION; INCREASES; LESIONS AB The frequencies of overexpression and mutation in the p53 tumor suppressor gene were examined in proliferative verrucous leukoplakia and oral squamous cell carcinoma with immunohistochemistry and single-strand conformation polymorphism analysis of DNA fragments amplified by polymerase chain reaction. Ten samples each of normal oral mucosa, proliferative verrucous leukoplakia, and squamous cell carcinoma were immunostained with antibodies against p53 protein; 8 of 10 cases of proliferative verrucous leukoplakia cases and 7 of 10 cases of oral squamous cell carcinoma were positive for p53 protein. Minimal staining was observed in normal oral tissues. The quantified labeling indexes demonstrated a range that corresponded to lesion progression. Single-strand conformation polymorphism analysis revealed p53 gene mutations within exons 5 to 8 in 40% (4 of 10) of the squamous cell carcinoma samples. Two of the 4 mutated squamous cell carcinoma samples lacked p53 expression. No p53 mutations were detected in proliferative verrucous leukoplakia tissues. Human papillomavirus 16 was identified in 2 of 7 p53 positive oral squamous cell carcinoma samples, Human papillomavirus 16 and 18 were identified in two of eight p53 positive proliferative verrucous leukoplakia samples. One p53 negative squamous cell carcinoma sample was positive for human papillomavirus 16 and had a mutation in exon 6 of the p53 gene. Human papillomavirus infection along with p53 expression plays a yet to be defined role in the pathogenesis of a limited number of cases of proliferative verrucous leukoplakia and squamous cell carcinoma. p53 Immunohistochemistry, p53 gene mutations, and human papillomavirus infection prevalence do not provide a means to differentiate between leukoplakia and carcinoma and do not provide a predictive test for progression of leukoplakia to carcinoma. C1 OHIO STATE UNIV,SCH PUBL HLTH,COLUMBUS,OH 43210. OHIO STATE UNIV,CANC ETIOL & CHEMOPREVENT LAB,CHRI,COLUMBUS,OH 43210. OHIO STATE UNIV,DEPT PATHOL,COLUMBUS,OH 43210. US FDA,OFF SPECIAL NUTRIT,CLIN RES & REVIEW STAFF,ROCKVILLE,MD 20857. OHIO STATE UNIV,COLL DENT,DEPT MAXILLOFACIAL SURG PATHOL,COLUMBUS,OH 43210. OHIO STATE UNIV,DEPT OTOLARYNGOL,COLUMBUS,OH 43210. FU NCI NIH HHS [CA 16058-20, IR 43CA62715-01] NR 32 TC 39 Z9 39 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD APR PY 1997 VL 83 IS 4 BP 471 EP 477 DI 10.1016/S1079-2104(97)90148-7 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WV238 UT WOS:A1997WV23800014 PM 9127380 ER PT J AU Greenlees, KJ AF Greenlees, KJ TI Laboratory studies for the approval of aquaculture drugs SO PROGRESSIVE FISH-CULTURIST LA English DT Article AB All drugs approved by the U.S. Food and Drug Administration (FDA) must be shown to be safe and efficacious. The data required to demonstrate the safety and efficacy of a new animal drug are typically produced through controlled studies conducted by pharmaceutical firms that invest considerable time and money into the process. Factors that have contributed to the paucity of approved drugs for U.S. aquaculture include the relatively limited market for aquaculture drugs and the difficulty involved in conducting studies traditionally carried out in the drug approval process in an aquatic environment. One approach to this problem has been the development of data from other sources. In recent years, government, academic, and private researchers have conducted studies in an attempt to produce the data necessary to satisfy the requirements for the approval of new animal drugs in aquaculture. The data may then be made publicly available and can be used by a sponsor of the drug product to satisfy part of the requirements for the approval of a new animal drug application by the FDA. The studies necessary to demonstrate that a new animal drug is safe and efficacious typically consist of field studies and laboratory studies. Field studies are generally conducted under the control of an investigational new animal drug exemption provided by the FDA. These studies are conducted under the same conditions that would be anticipated under the proposed use of the drug. Laboratory studies may be conducted in traditional indoor laboratories or in less traditional ''laboratory'' ponds or raceways; the common feature of laboratory studies is rigorous control of the experimental conditions. This paper briefly discusses those laboratory studies that are routinely, and perhaps not so routinely, conducted for the approval of a new animal drug in U.S. aquaculture. RP Greenlees, KJ (reprint author), US FDA,CTR VET MED,HFV-153,7500 STANDISH PL,ROCKVILLE,MD 20855, USA. NR 7 TC 14 Z9 14 U1 0 U2 1 PU AMER FISHERIES SOC PI BETHESDA PA 5410 GROSVENOR LANE SUITE 110, BETHESDA, MD 20814-2199 SN 0033-0779 J9 PROG FISH CULT JI Progress. Fish-Cult. PD APR PY 1997 VL 59 IS 2 BP 141 EP 148 DI 10.1577/1548-8640(1997)059<0141:LSFTAO>2.3.CO;2 PG 8 WC Fisheries SC Fisheries GA XB916 UT WOS:A1997XB91600007 ER PT J AU Contrera, JF Jacobs, AC DeGeorge, JJ AF Contrera, JF Jacobs, AC DeGeorge, JJ TI Carcinogenicity testing and the evaluation of regulatory requirements for pharmaceuticals SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID FALSE-POSITIVE RATES; LONG-TERM; CHEMICAL CARCINOGENS; TRANSGENIC MODELS; RAS GENE; MICE; TOXICOLOGY; BIOASSAYS; TUMORIGENESIS; CANCER AB The results of rat and mouse carcinogenicity studies for 282 human pharmaceuticals in the FDA database were analyzed and compared as part of an International Conference on Harmonization (ICH) evaluation of rodent carcinogenicity studies and their utility for carcinogenicity testing. A majority of the carcinogenicity studies in the FDA database were carried out in Sprague-Dawley-derived rats and Swiss-Webster-derived CD-1 mice in contrast to Fisher 344 rats and B6C3F1 mice employed in National Toxicology Program (NTP) studies. Despite the differences in rodent strains, the relative proportion of compounds with positive findings (44.3%) and the degree of overall concordance between rats and mice (74.1%) in the FDA database were similar to the NTP rodent carcinogenicity database. Carcinogenicity studies in two rodent species are necessary primarily to identify trans-species tumorigens, which are considered to pose a relatively greater potential risk to humans than single species positive compounds. Two-year carcinogenicity studies in both rats and mice may not be the only means of identifying transspecies tumorigens. Sufficient experience is now available for some alternative in vivo carcinogenicity models to support their application as complementary studies in combination with a single 2-year carcinogenicity study to identify trans-species tumorigens. Our analysis of the rodent carcinogenicity studies supports such an approach for assessing carcinogenic potential without compromising the public health. (C) 1997 Academic Press. C1 US FDA,OFF REV MANAGEMENT,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. RP Contrera, JF (reprint author), US FDA,OFF TESTING & RES,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857, USA. NR 35 TC 87 Z9 87 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD APR PY 1997 VL 25 IS 2 BP 130 EP 145 DI 10.1006/rtph.1997.1085 PG 16 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA WZ686 UT WOS:A1997WZ68600006 PM 9185889 ER PT J AU DeGeorge, JJ Ahn, CH Andrews, PA Brower, ME Choi, YS Chun, MY Du, T Doo, YLH McGuinn, WD Pei, LQ Sancilio, LF Schmidt, W Sheevers, HV Sun, CJ Tripathi, S Vogel, WM Whitehurst, V Williams, S Taylor, AS AF DeGeorge, JJ Ahn, CH Andrews, PA Brower, ME Choi, YS Chun, MY Du, T Doo, YLH McGuinn, WD Pei, LQ Sancilio, LF Schmidt, W Sheevers, HV Sun, CJ Tripathi, S Vogel, WM Whitehurst, V Williams, S Taylor, AS TI Considerations for toxicology studies of respiratory drug products SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID I CLINICAL-TRIALS AB The standard approaches for the preclinical development of chronically administered drugs also apply to most respiratory drugs. Modifications from the standard preclinical development plan, however, may be necessary if the drug is administered intranasally or by inhalation. Administration by these routes may result in airway toxicity and the intended patient population is often particularly susceptible. Current and former representatives of the Division of Pulmonary Drug Products (CDER, U.S. FDA) present this article to describe general principles of preclinical development for respiratory drug indications. The article addresses drugs intended for administration by the intranasal or inhalation routes. The article describes the types of studies recommended, considers the initial human dose, and discusses dose-escalation strategies in clinical trials. Other areas of special concern with intranasal or inhalation administration include immunotoxicity, reproductive toxicity, types of dosing apparatus, excipients and extractables, and formulation changes. The approaches described in this article are intended as general information and should be adapted to the scientific considerations and circumstances of a particular drug under development. (C) 1997 Academic Press. C1 US FDA,DIV PULM DRUG PROD,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. US FDA,DIV ONCOL DRUG PROD,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. US FDA,CTR DRUG EVALUAT,OFF REVIEW MANAGEMENT,ROCKVILLE,MD 20857. NR 15 TC 17 Z9 19 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD APR PY 1997 VL 25 IS 2 BP 189 EP 193 DI 10.1006/rtph.1997.1099 PG 5 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA WZ686 UT WOS:A1997WZ68600011 PM 9185894 ER PT J AU Appel, NM Rapoport, SI OCallaghan, JP AF Appel, NM Rapoport, SI OCallaghan, JP TI Sequelae of parenteral domoic acid administration in rats: Comparison of effects on different anatomical markers in brain SO SYNAPSE LA English DT Article DE neurotoxicity; silver; argyrophilia; immunohistochemistry; lectin histochemistry; Griffonia simplicifolia; gliosis; glial fibrillary acidic protein; astroglia; microglia; convulsion; seizure ID GLUTAMATE-BINDING-SITES; MONKEYS MACACA-FASCICULARIS; -LABELED KAINIC ACID; PUTATIVE KAINATE RECEPTOR; CENTRAL-NERVOUS-SYSTEM; NEURONAL DEGENERATION; QUANTITATIVE ASPECTS; REACTIVE GLIOSIS; INDUCED SEIZURES; MESSENGER-RNA AB Brain damage following administration of domoic acid, a structural analog of the excitatory amino acids glutamic acid and kainic acid, was compared using different anatomic markers in adult rats. Seven days after administration of domoic acid (2.25 mg/kg i.p.) or vehicle, brains were collected and sectioned and stained to visualize Nissl substance using thionin, argyrophilia using a cupric silver staining method, astroglia using immunohistochemistry to detect glial fibrillary acidic protein-like immunoreactivity (GFAP-ir), and activated microglia using lectin histochemistry to detect Griffonia simplicifolia I-B-4 isolectin (GSI-B-4) binding in adjacent sections. In approximately 60% of rats to which it was administered, domoic acid caused stereotyped behavior within 60 min, followed by convulsions within 2-3 h. Brains of domoic acid-administered rats that did not manifest stereotyped behavior or convulsions did not differ from brains from vehicle-administered controls. In animals that had manifested stereotyped behavior and convulsions, Nissl staining was mostly unremarkable in brain sections. In contrast, there was intense argyrophilia in anterior olfactory nucleus, CA1 hippocampus, lateral septum, parietal (layer IV), piriform, and entorhinal cortices, ventral posterolateral thalamus, and amygdala. This pattern was reminiscent of that seen in postmortem specimens from humans who consumed domoic acid-tainted mussels and in experimental animals after kainic acid administration. Adjacent sections displayed astrogliosis, evidenced by increased GFAP-ir, which was more diffuse than the argyrophilic reaction. Activated microglia were revealed using GSI-B-4 histochemistry. These data suggest activation of discrete brain circuits in rats that convulse following domoic acid administration and subsequent pathological alterations. The data strongly suggest that neuropathology following domoic acid occurs only in animals manifesting domoic acid-induced sterotypy and convulsions. The data do not rule out more insidious damage in behaviorally normal rats that receive domoic acid. (C) 1997 Wiley-Liss, Inc. C1 NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892. US EPA,NATL HLTH & ENVIRONM EFFECTS RES LAB,DIV NEUROTOXICOL,RES TRIANGLE PK,NC 27711. RP Appel, NM (reprint author), US FDA,CTR DRUG EVALUAT & RES,OFF TESTING & RES,DIV APPL PHARMACOL RES,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. RI O'Callaghan, James/O-2958-2013 FU NIDA NIH HHS [DA 224-91-130] NR 79 TC 24 Z9 25 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD APR PY 1997 VL 25 IS 4 BP 350 EP 358 DI 10.1002/(SICI)1098-2396(199704)25:4<350::AID-SYN6>3.0.CO;2-9 PG 9 WC Neurosciences SC Neurosciences & Neurology GA WQ983 UT WOS:A1997WQ98300006 PM 9097394 ER PT J AU Wise, LD Beck, SL Beltrame, D Beyer, BK Chahoud, I Clark, RL Clark, R Druga, AM Feuston, MH Guittin, P Henwood, SM Kimmel, CA Lindstrom, P Palmer, AK Petrere, JA Solomon, HM Yasuda, M York, RG AF Wise, LD Beck, SL Beltrame, D Beyer, BK Chahoud, I Clark, RL Clark, R Druga, AM Feuston, MH Guittin, P Henwood, SM Kimmel, CA Lindstrom, P Palmer, AK Petrere, JA Solomon, HM Yasuda, M York, RG TI Terminology of developmental abnormalities in common laboratory mammals (version 1) SO TERATOLOGY LA English DT Article AB This paper presents the first version of an internationally-developed glossary of terms for structural developmental abnormalities in common laboratory animals. The glossary is put forward by the International Federation of Teratology Societies (IFTS) Committee on International Harmonization of Nomenclature in Developmental Toxicology, and represents considerable progress toward harmonization of terminology in this area. The purpose of this effort is to provide a common vocabulary that will reduce confusion and ambiguity in the description of developmental effects, particularly in submissions to regulatory agencies worldwide. The glossary contains a primary term or phrase, a definition of the abnormality, and notes, where appropriate. Selected synonyms or related terms, which reflect a similar or closely related concept, are noted. Nonpreferred terms are indicated where their usage may be incorrect. Modifying terms used repeatedly in the glossary (e.g., absent, branched) are listed and defined separately, instead of repeating their definitions for each observation. Syndrome names are generally excluded from the glossary, but are listed separately in an appendix. The glossary is organized into broad sections for external, visceral, and skeletal observations, then subdivided into regions, structures, or organs in a general overall head to tail sequence. Numbering is sequential, and not in any regional or hierarchical order. Uses and misuses of the glossary are discussed. Comments, questions, suggestions, and additions from practitioners in the field of developmental toxicology are welcomed on the organization of the glossary as well as on the specific terms and definitions. Updates of the glossary are planned based on the comments received. (C) 1997 Wiley-Liss, Inc. C1 DE PAUL UNIV,DEPT BIOL SCI,CHICAGO,IL 60614. PHARMACIA & UPJOHN INC,WORLDWIDE TOXICOL,MILAN,ITALY. BRISTOL MYERS SQUIBB,PHARMACEUT RES INST,EVANSVILLE,IN 47721. FREE UNIV BERLIN,INST TOXICOL & EMBRYOPHARMACOL,D-1000 BERLIN,GERMANY. RHONE POULENC RORER,RES & DEV,DEPT TOXICOL,COLLEGEVILLE,PA 19426. INST DRUG RES LTD,DIV SAFETY STUDIES,BUDAPEST,HUNGARY. SANOFI RES,MALVERN,PA 19355. RHONE POULENC RORER,DRUG SAFETY,GEN & REPROD TOXICOL DEPT,VITRY SUR SEINE,FRANCE. COVANCE LABS INC,MADISON,WI 53707. US EPA,NCEA,WASHINGTON,DC 20460. QUINTILES INC,REGULATORY AFFAIRS,RES TRIANGLE PK,NC 27709. SMITHKLINE BEECHAM PHARMACEUT,DIV RES & DEV,KING OF PRUSSIA,PA 19406. WARNER LAMBERT PARKE DAVIS,PARKE DAVIS PHARMACEUT RES DIV,PATHOL EXPT TOXICOL DEPT,ANN ARBOR,MI 48105. HIROSHIMA UNIV,SCH MED,HIROSHIMA,JAPAN. ARGUS RES LABS,HORSHAM,PA 19044. US FDA,STANDARDIZED NOMENCLATURE PROGRAM,ROCKVILLE,MD 20857. RP Wise, LD (reprint author), MERCK RES LABS,SAFETY ASSESSMENT,W45-1,W POINT,PA 19486, USA. NR 0 TC 106 Z9 113 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0040-3709 J9 TERATOLOGY JI Teratology PD APR PY 1997 VL 55 IS 4 BP 249 EP 292 DI 10.1002/(SICI)1096-9926(199704)55:4<249::AID-TERA5>3.0.CO;2-W PG 44 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA XG721 UT WOS:A1997XG72100005 PM 9216042 ER PT J AU Sathyamoorthy, V Huntley, JS Hall, AC Hall, RH AF Sathyamoorthy, V Huntley, JS Hall, AC Hall, RH TI Biochemical and physiological characteristics of HlyA, a pore-forming cytolysin of Vibrio cholerae serogroup O1 SO TOXICON LA English DT Article ID BIOTYPE-EL-TOR; THERMOSTABLE DIRECT HEMOLYSIN; ESCHERICHIA-COLI HEMOLYSIN; STRUCTURAL GENE HLYA; NUCLEOTIDE-SEQUENCE; NON-O1; PARAHAEMOLYTICUS; PURIFICATION; MEMBRANES; TOXINS AB Among the various toxins produced by the bacterial species Vibrio cholerae is HlyA, a cytolytic protein commonly called the El Tor hemolysin. HlyA is synthesized and processed in a complex manner involving various processed or degraded forms, that may co-purify and complicate the interpretation of biochemical and physiological experiments. In this study a single form of HlyA was purified by gel filtration and chromatofocusing using fast protein liquid chromatography in the presence of protease inhibitors. A 45-fold purification was obtained, with a final recovery of 17% of pure 60,000 mol. wt HlyA. A significant improvement in specific activity to 8.5 x 10(6) Chinese hamster ovary tissue culture units per mg protein was obtained. Physiological activity studies indicated that cytolysis of erythrocytes (hemolysis) was inhibited by oxygen: storage of HlyA under oil, and experimentation in N-2-flushed buffers maintained activity. HlyA-mediated lysis of human erythrocytes was characterized by a significant lag phase, followed by a rapid induction of hemolysis. Hemolysis was inhibited by sucrose, an osmotic protectant, suggesting that the initial action of HlyA on erythrocytes is to raise the basal cation permeability of the cell membrane. The most likely cytolytic mechanism is thus the formation of transmembrane lesions such as homopolymer pores in target cells, as has been found for toxins from numerous other bacterial pathogens. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. UNIV OXFORD,PHYSIOL LAB,OXFORD OX1 3PT,ENGLAND. FU Wellcome Trust NR 26 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 0041-0101 J9 TOXICON JI Toxicon PD APR PY 1997 VL 35 IS 4 BP 515 EP 527 DI 10.1016/S0041-0101(96)00163-8 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA WU152 UT WOS:A1997WU15200003 PM 9133706 ER PT J AU Galen, JE GomezDuarte, OG Losonsky, GA Halpern, JL Lauderbaugh, CS Kaintuck, S Reymann, MK Levine, MM AF Galen, JE GomezDuarte, OG Losonsky, GA Halpern, JL Lauderbaugh, CS Kaintuck, S Reymann, MK Levine, MM TI A murine model of intranasal immunization to assess the immunogenicity of attenuated Salmonella typhi live vector vaccines in stimulating serum antibody responses to expressed foreign antigens SO VACCINE LA English DT Article ID GLUTATHIONE-S-TRANSFERASE; TOXIN FRAGMENT-C; BIVALENT VACCINE; HETEROLOGOUS ANTIGENS; RECOMBINANT BACTERIA; ORAL IMMUNIZATION; DIPHTHERIA-TOXIN; IMMUNE-SYSTEM; NIRB PROMOTER; ANIMAL-MODELS AB The lack of a practical small animal model to study the immunogenicity of Salmonella typhi-based five vector vaccines expressing foreign antigens has seriously impeded the vaccine development process. For some foreign antigens, stimulation of serum IgG antibody is the desired protective immune response. We administered to mice, by orogastric or intranasal (i.n.) routes, attenuated Delta aroC Delta aroD S. typhi CVD 908 carrying a plasmid encoding fragment C (fragC) of tetanus toxin fused to the eukaryotic cell receptor binding domain of diphtheria toxin (fragC-bDt), and monitored serum antibody. White orogastric inoculation of three doses was not immunogenic, in. immunization elicited high titers of serum IgG tetanus antitoxin, generating peak ELISA geometric mean titers (GMT) of 27024 and 35658 with 10(8) and 10(9) c.f.u. dosages, respectively; 10(9) c.f.u. i.n. of an Delta aroA S. typhimurium live vector stimulated apeak antitoxin GMT of 376 405. Mice immunized with the S. typhi live vector were 100% protected against challenge with 100 50% lethal doses of tetanus toxin that rapidly killed all control mice. Intranasal immunization with two doses of S. typhi expressing unfused fragment C under control of art anaerobically-activated promoter derived from nirB stimulated significantly higher titers of serum neutralizing antitoxin than fused fragC-bDt controlled by the same promoter (GMT 0.10 AU ml(-1) vs 0.01 AU ml(-1), P=0.0095). Two i.n. doses of S typhi encoding fragC under control of powerful constitutive promoter Ipp led to significantly higher peak serum neutralizing antitoxin titers than the otherwise identical construct utilizing the nirB promoter (peak GMT 0.72 AU ml(-1) vs 0.10 AU ml(-1), P=0.022). The in. route of inoculation of mice may constitute a practical breakthrough that could expedite the development of some S. typhi-based live vector vaccines by allowing, for the first time, quantitative measurement of serum antibody responses to candidate constructs following Ln, mucosal immunization. (C) 1997 Elsevier Science Ltd. C1 UNIV MARYLAND,SCH MED,DEPT PEDIAT,DIV INFECT DIS & TROP PEDIAT,BALTIMORE,MD 21201. US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,BETHESDA,MD 20892. RP Galen, JE (reprint author), UNIV MARYLAND,SCH MED,CTR VACCINE DEV,DEPT MED,DIV GEOG MED,685 W BALTIMORE ST,HSF BLDG,ROOM 480,BALTIMORE,MD 21201, USA. FU NIAID NIH HHS [N01 AI45251, R01 AI29471, N01 AI15096] NR 45 TC 86 Z9 89 U1 0 U2 1 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 APR-MAY PY 1997 VL 15 IS 6-7 BP 700 EP 708 DI 10.1016/S0264-410X(96)00227-7 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XA425 UT WOS:A1997XA42500018 PM 9178472 ER PT J AU Tollefson, L AF Tollefson, L TI Poisoning antidote now approved SO VETERINARY MEDICINE LA English DT Letter RP Tollefson, L (reprint author), US FDA,CTR VET MED,OFF SURVEILLANCE & COMPLIANCE,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU VETERINARY MEDICINE PUBL CO PI LENEXA PA 15333 W 95TH STREET, LENEXA, KS 66219 SN 8750-7943 J9 VET MED-US JI Vet. Med. PD APR PY 1997 VL 92 IS 4 BP 315 EP 315 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA WV674 UT WOS:A1997WV67400004 ER PT J AU Wang, SW Krinks, M Lin, KM Luyten, FP Moos, M AF Wang, SW Krinks, M Lin, KM Luyten, FP Moos, M TI Frzb, a secreted protein expressed in the Spemann organizer, binds and inhibits Wnt-8 SO CELL LA English DT Article ID XENOPUS-EMBRYOS; EARLY EMBRYOGENESIS; VENTRAL MESODERM; GENE; LAEVIS; LIMB; INDUCTION; XWNT-8; POLARITY; PATTERN AB We isolated a Xenopus homolog of Frzb, a newly described protein containing an amino-terminal Frizzled motif. It dorsalized Xenopus embryos and was expressed in the Spemann organizer during early gastrulation. Unlike Frizzled proteins, endogenous Frzb was soluble. Frzb was secretable and could act across cell boundaries. In several functional assays, Frzb antagonized Xwnt-8, a proposed ventralizing factor with an expression pattern complementary to that of Frzb. Furthermore, Frzb blocked induction of MyoD, an action reported recently for a dominant-negative Xwnt-8. Frzb coimmunoprecipitated with Wnt proteins, providing direct biochemical evidence for Frzb-Wnt interactions. These observations implicate Frzb in axial patterning and support the concept that Frzb binds and inactivates Xwnt-8 during gastrulation, preventing inappropriate ventral signaling in developing dorsal tissues. C1 NIDR,CRANIOFACIAL & SKELETAL DIS BRANCH,NIH,BETHESDA,MD 20892. RP Wang, SW (reprint author), US FDA,CTR BIOL EVALUAT & RES,DEV BIOL LAB,BETHESDA,MD 20892, USA. RI Moos, Malcolm/F-3673-2011; OI Moos, Malcolm/0000-0002-9575-9938; Wang, Shouwen/0000-0001-8484-1795 NR 67 TC 381 Z9 396 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD MAR 21 PY 1997 VL 88 IS 6 BP 757 EP 766 DI 10.1016/S0092-8674(00)81922-4 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WQ100 UT WOS:A1997WQ10000008 PM 9118219 ER PT J AU Parsons, BL Heflich, RH AF Parsons, BL Heflich, RH TI Evaluation of MutS as a tool for direct measurement of point mutations in genomic DNA SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE MutS; mismatch binding protein; mutation detection; H-ras; genotypic selection; single nucleotide primer extension ID POLYMERASE CHAIN-REACTION; ETHYL-N-NITROSOUREA; RAS GENE; GENOTYPIC ANALYSIS; SYSTEM; TUMORS; LIVER; CELLS; MOUSE AB The MutEx assay is a technique that was developed to detect and map mutations. This assay takes advantage of the Escherichia coli mismatch binding protein MutS, which binds and protects mismatched, heteroduplex DNA from subsequent exonuclease digestion. The plausibility of using the MutEx assay as part of a genotypic selection scheme was investigated. Heteroduplexes were formed between mouse H-ras gene PCR products or restriction fragments that contained wild-type sequence and sequence with a single base change at codon 61 (wild-type, CAA and mutant, AAA). The heteroduplexes were incubated with MutS and then treated with the exonuclease activity of T7 DNA polymerase. MutS-protected DNA sequences were amplified by PCR. When this method was linked to single nucleotide primer extension (SNuPE) for mutant base identification, original mutant fractions of 1 in 50 000 and above were detected. Using comparable DNA template mixtures, the sensitivity of sNuPE alone was 1 in 5 or 1 in 50, depending on the direction of SNuPE priming and the particular base being incorporated. We conclude that the MutEx assay was able to enrich the mutant sequence approximately 1000-fold and, therefore, has considerable potential as a tool for mutation detection. RP Parsons, BL (reprint author), NATL CTR TOXICOL RES,DIV GENET TOXICOL,HFT-120,3900 NCTR DR,JEFFERSON,AR 72079, USA. NR 25 TC 23 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAR 21 PY 1997 VL 374 IS 2 BP 277 EP 285 DI 10.1016/S0027-5107(96)00245-X PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA WQ994 UT WOS:A1997WQ99400012 PM 9100851 ER PT J AU Rothenberg, K Fuller, B Rothstein, M Duster, T Kahn, MJE Cunningham, R Fine, B Hudson, K King, MC Murphy, P Swergold, G Collins, F AF Rothenberg, K Fuller, B Rothstein, M Duster, T Kahn, MJE Cunningham, R Fine, B Hudson, K King, MC Murphy, P Swergold, G Collins, F TI Genetic information and the workplace: Legislative approaches and policy challenges SO SCIENCE LA English DT Article C1 UNIV HOUSTON,CTR LAW,HLTH LAW & POLICY INST,HOUSTON,TX 77004. UNIV CALIF BERKELEY,INST STUDY SOCIAL CHANGE,BERKELEY,CA 94720. NORTHWESTERN UNIV,SCH MED,EVANSTON,IL 60208. NIH,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. UNIV WASHINGTON,DIV MED GENET,SEATTLE,WA 98195. ONCORMED,GAITHERSBURG,MD. US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20857. RP Rothenberg, K (reprint author), UNIV MARYLAND,SCH LAW,LAW & HLTH CARE PROGRAM,500 W BALTIMORE ST,BALTIMORE,MD 21201, USA. NR 10 TC 97 Z9 99 U1 1 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAR 21 PY 1997 VL 275 IS 5307 BP 1755 EP 1757 DI 10.1126/science.275.5307.1755 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WP056 UT WOS:A1997WP05600030 PM 9122681 ER PT J AU Heredia, A Vallejo, A Soriano, V Gutierrez, M Puente, S Epstein, JS Hewlett, IK AF Heredia, A Vallejo, A Soriano, V Gutierrez, M Puente, S Epstein, JS Hewlett, IK TI Evidence of HIV-2 infection in equatorial Guinea (Central Africa): Partial genetic analysis of a B subtype virus SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID SEQUENCE C1 US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS & TRANSMITTED DIS,MOL VIROL LAB,ROCKVILLE,MD 20852. INST SALUD CARLOS III,INFECT DIS SERV,MADRID 28010,SPAIN. RI Vallejo, Alejandro/I-5881-2015 OI Vallejo, Alejandro/0000-0001-5360-878X NR 9 TC 5 Z9 5 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 MAR 20 PY 1997 VL 13 IS 5 BP 439 EP 440 DI 10.1089/aid.1997.13.439 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA WQ049 UT WOS:A1997WQ04900011 PM 9075486 ER PT J AU Mathers, PH Mahon, KA Grinberg, A Jamrich, M AF Mathers, PH Mahon, KA Grinberg, A Jamrich, M TI Misexpression and knockout studies show the Rx homeobox gene is essential for vertebrate eye development SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 W VIRGINIA UNIV,SCH MED,MORGANTOWN,WV 26506. US FDA,BETHESDA,MD 20014. NICHHD,NIH,BETHESDA,MD 20892. BAYLOR COLL MED,HOUSTON,TX 77030. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 3250 EP 3250 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500075 ER PT J AU Hill, JM Garza, HH Stanberry, LR Bourne, N Krause, PR AF Hill, JM Garza, HH Stanberry, LR Bourne, N Krause, PR TI Site-specific ocular and genital reactivation frequencies of HSV-1 and HSV-2 are determined by the latently associated transcript (LAT) region. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 LOUISIANA STATE UNIV,CTR EYE,NEW ORLEANS,LA 70112. UNIV CINCINNATI,COLL MED,DIV INFECT DIS,CINCINNATI,OH 45267. US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 3347 EP 3347 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500172 ER PT J AU Schmued, LC Albertson, C Slikker, W AF Schmued, LC Albertson, C Slikker, W TI Fluoro-Jade: A novel fluorochrome for the sensitive and reliable histochemical localization of neuronal degeneration SO BRAIN RESEARCH LA English DT Article DE fluoro-Jade; neuronal degeneration; fluorescent tracer; neuropathology ID DOMOIC ACID; NEUROTOXICITY; MANGANESE; DAMAGE; RAT; LESIONS; CORTEX; BRAIN; CELLS AB Fluoro-Jade is an anionic fluorochrome capable of selectively staining degenerating neurons in brain slices. The histochemical application of Fluoro-Jade results in a simple, sensitive and reliable method for staining degenerating neurons and their processes. The technique will detect neuronal degeneration resulting from exposure to a variety of neurotoxic insults. Fluoro-Jade can be combined with other fluorescent methodologies including immunofluorescence, fluorescent axonal tract tracing, and fluorescent Nissl counterstaining. Compared to conventional methodologies, Fluoro-Jade is a more sensitive and definitive marker of neuronal degeneration than hematoxylin and eosin (H&E) or Nissl type stains, while being comparably sensitive yet considerably simpler and more reliable than suppressed silver techniques. (C) 1997 Elsevier Science B.V. RP Schmued, LC (reprint author), US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,HFT-132,3900 NCTR RD,JEFFERSON,AR 72079, USA. RI Kipke, Daryl/A-2167-2009 NR 31 TC 732 Z9 747 U1 2 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 14 PY 1997 VL 751 IS 1 BP 37 EP 46 DI 10.1016/S0006-8993(96)01387-X PG 10 WC Neurosciences SC Neurosciences & Neurology GA WR178 UT WOS:A1997WR17800005 PM 9098566 ER PT J AU Fenichel, RR AF Fenichel, RR TI Nifedipine for hypertensive emergencies SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP Fenichel, RR (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 12 PY 1997 VL 277 IS 10 BP 790 EP 790 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WM082 UT WOS:A1997WM08200025 PM 9052706 ER PT J AU Nightingale, SL AF Nightingale, SL TI Over-the-counter test system for drugs of abuse 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 MAR 5 PY 1997 VL 277 IS 9 BP 703 EP 703 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WK026 UT WOS:A1997WK02600010 PM 9042830 ER PT J AU Nightingale, SL AF Nightingale, SL TI Proposal for treatment use of investigational devices 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 MAR 5 PY 1997 VL 277 IS 9 BP 703 EP 703 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WK026 UT WOS:A1997WK02600007 PM 9042830 ER PT J AU Nightingale, SL AF Nightingale, SL TI Ivermectin approved for strongyloidiasis and onchocerciasis 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 MAR 5 PY 1997 VL 277 IS 9 BP 703 EP 703 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WK026 UT WOS:A1997WK02600008 PM 9042830 ER PT J AU Nightingale, SL AF Nightingale, SL TI Action plan for providing useful prescription information 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 MAR 5 PY 1997 VL 277 IS 9 BP 703 EP 703 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WK026 UT WOS:A1997WK02600009 PM 9042830 ER PT J AU Shores, EW Tran, T Grinberg, A Sommers, CL Shen, H Love, PE AF Shores, EW Tran, T Grinberg, A Sommers, CL Shen, H Love, PE TI Role of the multiple T cell receptor (TCR)-zeta chain signaling motifs in selection of the T cell repertoire SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ANTIGEN RECEPTOR; ZETA-CHAIN; TRANSGENIC MICE; POSITIVE SELECTION; TYROSINE KINASES; THYMOCYTES; TRANSDUCTION; DIFFERENTIATION; INTERMEDIATE; ACTIVATION AB Immature thymocytes undergo a selection process within the thymus based on their T cell antigen receptor (TCR) specificity that results either in their maturation into functionally competent, self-MHC-restricted T cells (positive selection) or their deletion (negative selection). The outcome of thymocyte selection is thought to be controlled by signals transduced by the TCR that vary in relation to the avidity of the TCR-ligand interaction. The TCR is composed of four distinct signal transducing subunits (CD3-gamma, -delta, -epsilon, and zeta) that contain either one (CD3-gamma, -delta, -epsilon) or three (-zeta) signaling motifs (ITAMs) within their intracytoplasmic domains. A possible function for multiple TCR ITAMs could be to amplify signals generated by the TCR during selection. To determine the importance of the multiple TCR-S chain ITAMs in thymocyte selection, transgenes encoding alpha/beta TCRs with known specificity were bred into mice in which zeta chains lacking one or more ITAMs had been genetically substituted for endogenous zeta. A direct relationship was observed between the number of zeta chain ITAMs within the TCR complex and the efficiency of both positive and negative selection. These results reveal a role for multiple TCR ITAMs in thymocyte selection and identify a function for TCR signal amplification in formation of the T cell repertoire. C1 NICHHD,LAB MAMMALIAN GENES & DEV,NIH,BETHESDA,MD 20892. RP Shores, EW (reprint author), US FDA,DIV HEMATOL PROD,CTR BIOL EVALUAT & RES,HFM 538,BLDG 29A,RM 2B23,29 LINCOLN DR,BETHESDA,MD 20892, USA. NR 32 TC 102 Z9 102 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 MAR 3 PY 1997 VL 185 IS 5 BP 893 EP 900 DI 10.1084/jem.185.5.893 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WM240 UT WOS:A1997WM24000011 PM 9120395 ER PT J AU Rheinstein, PH McGinnis, TJ Nightingale, SL AF Rheinstein, PH McGinnis, TJ Nightingale, SL TI Children and tobacco: The FDA's final rule SO AMERICAN FAMILY PHYSICIAN LA English DT Article RP Rheinstein, PH (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 12 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 MAR PY 1997 VL 55 IS 4 BP 1441 EP 1444 PG 4 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA WN491 UT WOS:A1997WN49100044 PM 9092294 ER PT J AU Braun, MM Patriarca, PA Ellenberg, SS AF Braun, MM Patriarca, PA Ellenberg, SS TI Syncope after immunization SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID BLOOD; ACQUISITION; PHOBIA; INJURY AB Objective: To describe the individual characteristics, clinical features, and morbidity associated with syncope following immunization. Design: Large case series. Setting: United States, 1990 through 1995. Subjects: Reports to the national Vaccine Adverse Event Reporting System (VAERS), a passive surveillance system. An additional 3 reports of head injury (documented by medical records) were obtained through the National Vaccine Injury Compensation Program. Main Outcome Measures: Syncope, syncope and hospitalization, or syncope and head injury within 12 hours of vaccination. Results: A total of 697 cases of syncope after vaccination was reported. Age younger than 20 years was reported for 77.4%; 57.5% were female. Hospitalization was reported in 9.6%. Of the 571 syncope events with known time, 511 occurred 1 hour or less after vaccination. Of these, 323 (63.2%) occurred 5 minutes or less, 454 (88.8%) occurred 15 minutes or less, and 500 (97.8%) occurred 30 minutes or less after vaccination. Tonic or clonic movements, which have been associated with the anoxia of vasovagal syncope, were reported in 30.4% of syncopal episodes occurring 15 minutes or less after and in 12.8% of those occurring 15 minutes or longer after vaccination (P<.001). Six patients suffered skull fracture, cerebral bleeding, or cerebral contusion after falls; 3 of these patients required neurosurgery. Falls occurred 15 minutes or less after vaccination, in or near the clinic or office. Ages ranged from 12 to 28 years; 5 of 6 were male. Follow-up revealed substantial residual impairment in 2 patients. Conclusions: Prevention of injury from syncope after vaccination and of syncope itself may be possible in many cases. Vaccinators should be aware that patients exhibiting presyncopal signs and symptoms around the time of immunization need to be evaluated carefully and may need to be assisted to sit or lie down after immunization until free of symptoms. RP Braun, MM (reprint author), US FDA,HFM 220,CTR BIOL EVALUAT & RES,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 18 TC 42 Z9 47 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD MAR PY 1997 VL 151 IS 3 BP 255 EP 259 PG 5 WC Pediatrics SC Pediatrics GA WN486 UT WOS:A1997WN48600006 PM 9080932 ER PT J AU Pillemer, SR Fowler, SE Tilley, BC Alarcon, GS Heyse, SP Trentham, DE Neuner, R Clegg, DO Leisen, JCC Cooper, SM Duncan, H Tuttleman, M AF Pillemer, SR Fowler, SE Tilley, BC Alarcon, GS Heyse, SP Trentham, DE Neuner, R Clegg, DO Leisen, JCC Cooper, SM Duncan, H Tuttleman, M TI Meaningful improvement criteria sets in a rheumatoid arthritis clinical trial SO ARTHRITIS AND RHEUMATISM LA English DT Article ID OUTCOME MEASURES; PLACEBO; METHOTREXATE AB Objective. To compare 3 sets of criteria for meaningful improvement in a rheumatoid arthritis (RA) clinical trial, and to evaluate the implications of these criteria sets for RA trial design. Methods. Data were obtained from the Minocycline in Rheumatoid Arthritis (MIRA) trial (primary outcome measures: 50% improvement in joint tenderness and 50% improvement in joint swelling, based on joint scores), These MIRA data were evaluated against 1) the Paulus criteria (20% improvement in 4 of 6 measures: joint tenderness scores, joint swelling scores, physician's and patient's global assessments, erythrocyte sedimentation rate [ESR], and morning stiffness); and 2) the American College of Rheumatology (ACR) criteria (20% improvement in joint tenderness and joint swelling counts, and in 3 of 5 other measures: physician's and patient's global assessments, ESR, modified Health Assessment Questionnaire, and patient's pain assessment), The ACR criteria were modified using 3 of 4 remaining measures, since baseline pain assessment data were not available. Results. Percentages of minocycline-treated patients versus placebo-treated patients showing meaningful improvement were as follows: by MIRA criteria, for joint tenderness, 56% versus 41% (P = 0.021), and for joint swelling, 54% versus 39% (P = 0.023); by Paulus criteria, 41% versus 28% (P = 0.040); and by ACR criteria, 44% versus 26% (P = 0.004), Both the modified ACR criteria and the Paulus criteria demonstrated a reduced placebo response rate, Compared with the MIRA criteria, the ACR criteria increased, and the Paulus criteria decreased, absolute between-group differences in improvement; however, both criteria sets increased relative percentages of patients showing improvement in the minocycline group versus the placebo group, Study design considerations indicated that application of the ACR criteria would reduce the required sample size. Conclusion. Different placebo response rates and treatment group differences were found using the 3 RA improvement criteria sets, These findings support the use of the ACR criteria for defining improvement in RA clinical trials. C1 HENRY FORD HLTH SYST,DETROIT,MI. UNIV ALABAMA,BIRMINGHAM,AL. NIAID,BETHESDA,MD 20892. BETH ISRAEL HOSP,BOSTON,MA 02215. FED DRUG ADM,CTR DRUG EVALUAT & RES,ROCKVILLE,MD. UNIV UTAH,MED CTR,SALT LAKE CITY,UT. HENRY FORD HOSP,DETROIT,MI 48202. UNIV VERMONT,BURLINGTON,VT. RP Pillemer, SR (reprint author), NIAMSD,OFF DIRECTOR,NIH,BLDG 45,ROOM 5AS-37G,45 CTR DR,MSC 6500,BETHESDA,MD 20892, USA. FU NIAMS NIH HHS [N01-AR-1-2203, N01-AR-1-2202, N01-AR-1-2205] NR 16 TC 20 Z9 21 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 MAR PY 1997 VL 40 IS 3 BP 419 EP 425 DI 10.1002/art.1780400305 PG 7 WC Rheumatology SC Rheumatology GA WN158 UT WOS:A1997WN15800004 PM 9082927 ER PT J AU Hung, HMJ ONeill, RT Bauer, P Kohne, K AF Hung, HMJ ONeill, RT Bauer, P Kohne, K TI The behavior of the P-value when the alternative hypothesis is true SO BIOMETRICS LA English DT Article DE power; phyp plot; meta-analysis; significance AB The P-value is a random variable derived from the distribution of the test statistic used to analyze a data set and to test a null hypothesis. Under the null hypothesis, the P-value based on a continuous test statistic has a uniform distribution over the interval [0, 1], regardless of the sample size of the experiment. In contrast, the distribution of the P-value under the alternative hypothesis is a function of both sample size and the true value or range of true values of the tested parameter. The characteristics, such as mean and percentiles, of the P-value distribution can give valuable insight into how the P-value behaves for a variety of parameter values and sample sizes. Potential applications of the P-value distribution under the alternative hypothesis to the design, analysis, and interpretation of results of clinical trials are considered. C1 CDER,US FDA,OFF EPIDEMIOL & BIOMETR,ROCKVILLE,MD 20857. UNIV VIENNA,INST MED STAT,A-1090 VIENNA,AUSTRIA. UNIV COLOGNE,INST MED DOKUMENTAT & STAT,D-50924 COLOGNE,GERMANY. RP Hung, HMJ (reprint author), CDER,US FDA,DIV BIOMETR 1,HFD-710,ROOM 5062,1451 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 6 TC 59 Z9 61 U1 2 U2 14 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 1997 VL 53 IS 1 BP 11 EP 22 DI 10.2307/2533093 PG 12 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA WN180 UT WOS:A1997WN18000002 PM 9147587 ER PT J AU Mahmood, I Sahlroot, JT AF Mahmood, I Sahlroot, JT TI A limited sampling method for the estimation of flunarizine area under the curve (AUC) and maximum plasma concentration (C-max) SO BIOPHARMACEUTICS & DRUG DISPOSITION LA English DT Article DE flunarizine; limited sampling; prediction of AUC and C-max ID MAINTENANCE-DOSE PREDICTION; PHARMACOKINETICS; LITHIUM; MODEL AB A limited sampling model has been developed for flunarizine following a 30 mg oral dose in epileptic patients who were receiving phenytoin or carbamazepine or both, to estimate the area under the curve (AUC) and maximum plasma concentration (C-max). The model was developed using training data sets from 30, 20, 15, or 10 patients at one or two time points. The equations describing the models for AUC using two time points (3 and 24 h) and C-max for the training data set of 30 subjects were [GRAPHICS] The model was validated on 64 patients who received flunarizine orally. The model provided reasonably good estimates for both AUC and C-max. The mean predicted AUC of flunarizine was 1230 +/- 717 ng h mL(-1), whereas the observed AUC was 1203 +/- 900 ng h mL(-1). The bias of the prediction was 2% and precision was 28%. The mean predicted C-max of flunarizine was 86 +/- 32 ng mL(-1) as compared to an observed mean C-max of 90 +/- 42 ng mL(-1). The bias and precision of the prediction were 4% and 24%, respectively. The method described here may be used to estimate AUC and C-max for flunarizine without detailed pharmacokinetic studies. (C) 1997 by John Wiley & Sons, Ltd. C1 US FDA,DIV BIOMETR,ROCKVILLE,MD 20852. RP Mahmood, I (reprint author), US FDA,DIV PHARMACEUT EVALUAT 1,OFF CLIN PHARMACOL & BIOPHARMACEUT,WOODMONT OFF CTR 2,HFD-860,ROCKVILLE,MD 20852, USA. NR 15 TC 12 Z9 12 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0142-2782 J9 BIOPHARM DRUG DISPOS JI Biopharm. Drug Dispos. PD MAR PY 1997 VL 18 IS 2 BP 117 EP 126 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WP557 UT WOS:A1997WP55700003 PM 9099448 ER PT J AU StetlerStevenson, M Mansoor, A Lim, M Fukushima, P Kehrl, J Marti, G Ptaszynski, K Wang, J StetlerStevenson, WG AF StetlerStevenson, M Mansoor, A Lim, M Fukushima, P Kehrl, J Marti, G Ptaszynski, K Wang, J StetlerStevenson, WG TI Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in reactive and neoplastic lymphoid cells SO BLOOD LA English DT Article ID ERYTHROID-POTENTIATING ACTIVITY; GROWTH-PROMOTING ACTIVITY; IV COLLAGENASE; T-CELLS; EXTRACELLULAR-MATRIX; GELATINASE; LEUKEMIA; PROTEIN; TIMP-2; GENE AB We have studied the expression of gelatinase A, gelatinase B, interstitial collagenase, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in reactive lymphoid cells, as well as in a series of cell lines derived from neoplasms of B- and T-cell lineage. Using both Northern blot analysis and zymography, gelatinase B activity was detected by zymography in two Burkitt cell lines and in a tonsillar cell suspension, while gelatinase A and interstitial collagenase activities were not detected by either method. TMP-1 expression was demonstrated by Northern blot analysis in the multipotential neoplastic K-562 cell line, the high grade Burkitt's B-cell lymphoma lines, isolated tonsillar B cells and at low levels in peripheral blood T cells, but was not expressed in any of the neoplastic T-cell lines or isolated peripheral blood B cells. In contrast, TIMP-2 expression was restricted to tissues containing cells of T-cell lineage with high levels being observed in the neoplastic T-cell lines and lower levels in normal peripheral blood T cells and hyperplastic tonsil. Expression of TIMP-1 and TIMP-2 was confirmed at the protein level by reverse zymography and immunofluorescence assays using antihuman TIMP polyclonal antibodies. Expression of gelatinase B by the high grade B-cell Burkitt's lymphoma cell lines is consistent with previous findings in large cell immunoblastic lymphomas and indicates that this enzyme may play an important role in high grade non-Hodgkin's lymphomas. TIMP expression correlated with cell lineage in that TIMP-1 was primarily observed in B cells and TIMP-2 was restricted to T cells. C1 NCI,HEMATOPATHOL SECT,FLOW CYTOMETRY UNIT,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,FLOW & IMAGE CYTOMETRY SECT,LAB MED & MOL GENET,BETHESDA,MD. RP StetlerStevenson, M (reprint author), NCI,EXTRACELLULAR MATRIX PATHOL SECT,PATHOL LAB,DIV CLIN SCI,NIH,BLDG 10,ROOM 2A-33,BETHESDA,MD 20892, USA. RI Stetler-Stevenson, William/H-6956-2012; OI Stetler-Stevenson, William/0000-0002-5500-5808; Kehrl, John/0000-0002-6526-159X NR 45 TC 98 Z9 100 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 MAR 1 PY 1997 VL 89 IS 5 BP 1708 EP 1715 PG 8 WC Hematology SC Hematology GA WK477 UT WOS:A1997WK47700029 PM 9057654 ER PT J AU Waud, WR Tiwari, A Schmid, SM Shih, TW Strong, JM Hartman, NR OReilly, S Struck, RF AF Waud, WR Tiwari, A Schmid, SM Shih, TW Strong, JM Hartman, NR OReilly, S Struck, RF TI 4-demethylpenclomedine, an antitumor-active, potentially nonneurotoxic metabolite of penclomedine SO CANCER RESEARCH LA English DT Article ID NSC-338720 AB Penclomedine [3,5-dichloro-4,6-dimethoxy-2-(trichloromethyl)pyridine], an antitumor agent, is currently in Phase I clinical trials and is believed to be a prodrug. In these studies, cerebellar effects have been dose limiting. Previous studies identified 4-demethylpenclomedine (4-DM-PEN) as the major plasma metabolite in rodents and humans, 4-DM-PEN was demonstrated to be an antitumor-active metabolite of penclomedine in vivo when evaluated against the penclomedine-sensitive MX-1 human breast tumor xenograft implanted either s.c. or intracerebrally and is believed to be on the metabolic activation pathway of penclomedine. Because earlier studies revealed an absence of neurotoxic cerebellar effects for 4-DM-PEN in contrast to penclomedine in a rat model, this metabolite may be a candidate for an alternative to penclomedine in the clinic for treatment of breast cancer or brain tumors, if the cerebellar effects of penclomedine preclude its further clinical development. Because neither penclomedine nor 4-DM-PEN were very active in vitro, the metabolism of penclomedine was also investigated using rat liver microsomes in an attempt to identify the ultimate active form of the drug. Metabolites and putative metabolites mere prepared by chemical synthesis for antitumor evaluation in vitro and in vivo, A reductive metabolite, alpha,alpha-didechloro-PEN, was observed to be much more cytotoxic than penclomedine or 4-DM-PEN in vitro, but evaluation of this and the other metabolites and putative metabolites in vivo against the MX-1 tumor failed to identify any active metabolite among the structures evaluated other than 4-DM-PEN. The limited activity of 4-DM-PEN in vitro indicates that it, like penclomedine, is also a prodrug, demonstrating a need for additional studies on the metabolic activation of penclomedine to identify the ultimate active form of the drug. C1 SO RES INST,BIRMINGHAM,AL 35205. US FDA,CTR DRUG EVALUAT & RES,LAUREL,MD 20708. JOHNS HOPKINS UNIV,CTR ONCOL,BALTIMORE,MD 21287. FU NCI NIH HHS [P01 CA34200, N01-CM-17560-01] NR 9 TC 12 Z9 12 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 MAR 1 PY 1997 VL 57 IS 5 BP 815 EP 817 PG 3 WC Oncology SC Oncology GA WK897 UT WOS:A1997WK89700007 PM 9041177 ER PT J AU Hayward, DG AF Hayward, DG TI Determination of polychlorinated dibenzo-p-dioxin and dibenzofuran background in milk and cheese by quadrupole ion storage collision induced dissociation MS/MS SO CHEMOSPHERE LA English DT Article; Proceedings Paper CT 15th International Symposium on Chlorinated Dioxins, PCB and Related Compounds CY AUG 21-25, 1995 CL EDMONTON, CANADA DE mass spectrometry mass spectrometry; quadrupole ion storage; polychlorinated dibenzo-p-dioxin; polychlorinated dibenzofuran; milk and cheese analysis ID SPECTROMETRY MASS-SPECTROMETRY; ENVIRONMENTAL-SAMPLES; PCDDS; PCDFS; FOOD; GERMANY; PCBS AB Recent developments in quadrupole ion storage scanning techniques have made possible the acquisition of mass spectrometry/mass spectrometry (MS/MS) data with high sensitivity, selectivity and reproducibility. Retail dairy products were analyzed successfully for bioincurred or background contamination by all 17 of the 2,3,7,8 substituted polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). Analytes were measured by both full scan electron impact low resolution MS (EI-LRMS) and collision induced dissociation MS/MS (CID MS/MS). Results were comparable using either technique. MS/MS, however, provided higher sensitivity and selectivity on many congeners. Results for the MS/MS technique were reproducible, with little reduction in sensitivity or spectral quality during the analyses of all test samples. The MS/MS signal to noise ratio (S/N) was 10 to 100 times greater than low resolution electron impact performed with the same instrument in food matrices. Signal to noise ratios increased on most parent ions as well as for all daughter ions. Further development of this technique may provide a cost effective alternative to traditional HRMS analyses of PCDDs and PCDFs in food. (C) 1997 Elsevier Science Ltd. RP Hayward, DG (reprint author), US FDA,METHODS RES BRANCH,DIV PESTICIDES & IND CHEM,200 C ST SW,WASHINGTON,DC 20204, USA. NR 17 TC 16 Z9 17 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD MAR-APR PY 1997 VL 34 IS 5-7 BP 929 EP 939 DI 10.1016/S0045-6535(97)00396-2 PG 11 WC Environmental Sciences SC Environmental Sciences & Ecology GA WR677 UT WOS:A1997WR67700003 PM 9134668 ER PT J AU Maslanka, SE Gheesling, LL Libutti, DE Donaldson, KBJ Harakeh, HS Dykes, JK Arhin, FF Devi, SJN Frasch, CE Huang, JC KrizKuzemenska, P Lemmon, RD Lorange, M Peeters, CCAM Quataert, S Tai, JY Carlone, GM Mills, EL Ashton, FE Diepevaen, J Bielecki, J Bybel, M Cloutier, M Poolman, JT AF Maslanka, SE Gheesling, LL Libutti, DE Donaldson, KBJ Harakeh, HS Dykes, JK Arhin, FF Devi, SJN Frasch, CE Huang, JC KrizKuzemenska, P Lemmon, RD Lorange, M Peeters, CCAM Quataert, S Tai, JY Carlone, GM Mills, EL Ashton, FE Diepevaen, J Bielecki, J Bybel, M Cloutier, M Poolman, JT TI Standardization and a multilaboratory comparison of Neisseria meningitidis serogroup A and C serum bactericidal assays SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; CAPSULAR POLYSACCHARIDE; GROUP-A; ANTIBODY; VACCINE; PROTECTION; CHILDREN; EFFICACY; DURATION; AGE AB A standardized serum bactericidal assay (SEA) is required to evaluate the functional activity of antibody produced in response to Neisseria meningitidis serogroup A and C vaccines. We evaluated assay parameters (assay buffer, target strains, growth of target cells, target cell number, complement source and concentration, and methods for growth of surviving bacteria) which may affect the reproducibility of SEA titers. The various assay parameters and specificity of anticapsular antibody to five serogroup A strains (A1, ATCC 13077, F8238, F9205, and F7485) and four serogroup C strains (C11, G7880, G8050, and 1002-90) were evaluated with Centers for Disease Control and Prevention meningococcal quality control sera. The critical assay parameters for the reproducible measurement of SEA titers were found to include the target strain, assay incubation time, and complement. The resulting standardized SEA was used by 10 laboratories to measure functional anticapsular antibody against serogroup A strain F8238 and serogroup C strain C11. In the multilaboratory study, SBA titers were measured in duplicate for 14 pairs of sera (seven adults and seven children) before and after immunization with a quadrivalent polysaccharide (A C, Y, and W-135) vaccine. The standardized SEA was reliable in all laboratories regardless of experience in performing SBAs. For most sera, intralaboratory reproducibility was +/-1 dilution; interlaboratory reproducibility was +/-2 dilutions. The correlation between median titers (interlaboratory) and enzyme-linked immunosorbent assay total antibody concentrations was high for both serogroup A (r = 0.86; P < 0.001; slope 0.5) and serogroup C (n = 0.86; P < 0.001; slope = 0.7). The specified assay, which includes the critical parameters of target strain, incubation time, and complement source, will facilitate interlaboratory comparisons of the functional antibody produced in response to current or developing serogroup A and C meningococcal vaccines. C1 MCGILL UNIV,MONTREAL,PQ H3A 2T5,CANADA. LAB CTR DIS CONTROL,OTTAWA,ON K1A 0L2,CANADA. QUEBEC PUBL HLTH LAB,QUEBEC CITY,PQ,CANADA. US FDA,BETHESDA,MD 20892. NATL PUBL HLTH INST,PRAGUE,CZECH REPUBLIC. CONNAUGHT LABS INC,SWIFTWATER,PA 18370. NATL INST PUBL HLTH & ENVIRONM PROTECT,NL-3720 BA BILTHOVEN,NETHERLANDS. LEDERLE PRAXIS BIOL INC,W HENRIETTA,NY 14586. N AMER VACCINE INC,BELTSVILLE,MD 20705. RP Maslanka, SE (reprint author), CTR DIS CONTROL & PREVENT,CHILDHOOD & RESP DIS BRANCH,NATL CTR INFECT DIS,1600 CLIFTON RD,ATLANTA,GA 30333, USA. RI Krizova, Pavla/M-6120-2015; OI Bielecki, Joanna/0000-0002-1830-4219 NR 40 TC 287 Z9 295 U1 0 U2 4 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 MAR PY 1997 VL 4 IS 2 BP 156 EP 167 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WL504 UT WOS:A1997WL50400009 PM 9067649 ER PT J AU Li, G Waltham, M Anderson, NL Unsworth, E Treston, A Weinstein, JN AF Li, G Waltham, M Anderson, NL Unsworth, E Treston, A Weinstein, JN TI Rapid mass spectrometric identification of proteins from two-dimensional polyacrylamide gels after in gel proteolytic digestion SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT 2nd Siena 2D Electrophoresis - From Genome to Proteome CY SEP 16-18, 1996 CL SIENA, ITALY DE matrix assisted laser desorption ionization - mass spectrometry; two-dimensional polyacrylamide gel electrophoresis; proteolytic digestion; peptides; protein identification ID SEPARATED PROTEINS; SEQUENCE DATABASES; GENE-REGULATION; ELECTROPHORESIS; IONIZATION; ACRYLAMIDE; FRAGMENTS AB We report a rapid method for identifying proteins resolved by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) using matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS). In-gel digestion was performed in a way such that the volume ratio of trypsin solution to gel plug was quantitatively controlled to promote reproducible digestion and to maximize the digestion yield. To make the digestion samples more compatible with MALDI-MS, the volatile salt ammonium bicarbonate in the digestion buffer was largely removed prior to peptide extraction. Samples of mixed tryptic peptides from in-gel digestion were used without purification to obtain molecular weights by MALDI-MS with a-cyano, 4-hydroxy-cinnamic acid as the matrix. Modifications of MALDI sample loading procedures improved the detection sensitivity by one half to one order of magnitude. The peptide mass peaks in MALDI-MS spectra were distinguished from those of impurities by using several types of controls, and masses were corrected by using trypsin autodigestion fragments as internal calibration standards. Two different peptide-matching computer programs were used to interrogate sequence databases and identify proteins. Identification was enhanced by generation of orthogonal data sets (by using different proteases) and by including experimental values of isoelectric point (pI) and molecular weight to exclude false entries in the candidate lists. Approximately 1% of the material from a spot was used in each sample loading, and nine protein spots from rat liver 2-D PAGE gels were identified correctly, as judged by comparison with identification results previously obtained from Edman sequencing. A previously identified low-abundance spot was not identified by MALDI-MS, presumably because there was insufficient material in a single gel. The sample handling procedure reported here should permit us to identify many 2-D PAGE protein spots of medium abundance. C1 NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. LARGE SCALE BIOL CORP,ROCKVILLE,MD. US FDA,BETHESDA,MD 20014. NCI,BIOMARKERS & PREVENT RES BRANCH,DIV CANC PREVENT & CONTROL,ROCKVILLE,MD. RI Waltham, Mark/A-1728-2009; OI Li, Guang/0000-0002-9022-2883 NR 38 TC 72 Z9 72 U1 1 U2 3 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD MAR-APR PY 1997 VL 18 IS 3-4 BP 391 EP 402 DI 10.1002/elps.1150180313 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WW358 UT WOS:A1997WW35800012 PM 9150917 ER PT J AU Rodgers, K Klykken, P Jacobs, J Frondoza, C Tomazic, V Zelikoff, J AF Rodgers, K Klykken, P Jacobs, J Frondoza, C Tomazic, V Zelikoff, J TI Immunotoxicity of medical devices SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID POLYDIMETHYLSILOXANE SILICONE FLUID; TOTAL HIP REPLACEMENTS; TEX SURGICAL MEMBRANE; FEMALE B6C3F1 MICE; 32-PERCENT DEXTRAN-70; BONE-RESORPTION; PERITONEAL-FLUID; INTERFACIAL MEMBRANES; ANAPHYLACTIC REACTION; ADHESION REFORMATION AB Determination of the ability of a medical device to interact with the immune system currently involves assessment of the immunogenic potential and biocompatibility of the device or an extract of the device. However, implants are often in the body for extended periods of time and/or are placed by a surgical procedure that in and of itself will generate an acute inflammatory response, This symposium discussed studies that have been performed to evaluate the immunogenicity of various devices consisting of several different compositions (i.e., silicone, metals, and latex) in contact with different anatomical sites, the ability of a device to modulate an inflammatory response generated by a surgical procedure or trauma, and the response of the body to a material left in place for extended periods of time, This symposium brought together scientists from many different disciplines to begin to identify and fill in the gaps in this area. (C) 1997 Society of Toxicology. C1 DOW CORNING CORP,MIDLAND,MI 48686. RUSH UNIV,RUSH ARTHRIT & ORTHOPED INST,RUSH MED COLL,DEPT ORTHOPED SURG,CHICAGO,IL 60612. GOOD SAMARITAN HOSP,JOHNS HOPKINS ORTHOPED,BALTIMORE,MD 21239. US FDA,CTR MED DEV,ROCKVILLE,MD 20857. NYU,MED CTR,NELSON INST ENVIRONM MED,TUXEDO PK,NY 10987. RP Rodgers, K (reprint author), UNIV SO CALIF,SCH MED,LIVINGSTON RES CTR,1321 N MISS RD,LOS ANGELES,CA 90033, USA. OI Jacobs, Joshua/0000-0003-3902-7334 NR 103 TC 26 Z9 26 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 MAR PY 1997 VL 36 IS 1 BP 1 EP 14 DI 10.1006/faat.1996.2279 PG 14 WC Toxicology SC Toxicology GA WP302 UT WOS:A1997WP30200001 PM 9073462 ER PT J AU Devi, SJN Zollinger, WD Snoy, PJ Tai, JY Costantini, P Norelli, F Rappuoli, R Frasch, CE AF Devi, SJN Zollinger, WD Snoy, PJ Tai, JY Costantini, P Norelli, F Rappuoli, R Frasch, CE TI Preclinical evaluation of group B Neisseria meningitidis and Escherichia coli K92 capsular polysaccharide-protein conjugate vaccines in juvenile rhesus monkeys SO INFECTION AND IMMUNITY LA English DT Article ID INFLUENZAE TYPE-B; URINARY-TRACT INFECTION; POLYSIALIC ACID; MONOCLONAL-ANTIBODY; MENINGOCOCCAL POLYSACCHARIDE; K1; BRAIN; BINDING; IMMUNOGENICITY; ANTIGENS AB We reported the first use of group B meningococcal conjugate vaccines in a nonhuman primate model (S. J. N. Devi, C. E. Frasch, W. Zollinger, and P. J. Snoy, p. 427-429, in J. S. Evans, S. E. Yost, M. C. J. Maiden, and I. M. Feavers, ed., Proceedings of the Ninth International Pathogenic Neisseria Conference, 1994), Three different group B Neisseria meningitidis capsular polysaccharide (B PS)-protein conjugate vaccines and an Escherichia coli K92 capsular polysaccharide-tetanus toroid (K92-TT) conjugate vaccine are here evaluated for safety and relative immunogenicities in juvenile rhesus monkeys with or without adjuvants, Monkeys were immunized intramuscularly with either B PS-cross-reactive material 197 conjugate, B PS-outer membrane vesicle (B-OMV) conjugate, or N-propionylated B PS-outer membrane protein 3 (N-pr. B-OMP3) conjugate vaccine with or without adjuvants at weeks 0, 6, and 14. A control group of monkeys received one injection of the purified B PS alone, and another group received three injections of B PS noncovalently complexed,vith OMV. Antibody responses as measured by enzyme-linked immunosorbent assay varied among individual monkeys, All vaccines except B PS and the K92-TT conjugate elicited a twofold or greater increase in total B PS antibodies after one immunization, All vaccines, including the K92-TT conjugate, elicited a rise in geometric mean B PS antibody levels of ninefold or more over the preimmune levels following the third immunization. Antibodies elicited by N-pr. B-OMP3 and B-OMV conjugates were directed to the N-propionylated or to the spacer-containing B PS antigens as well as to the native B PS complexed with methylated human serum albumin, None of the vaccines caused discernible safety-related symptoms. C1 US FDA,DIV BACTERIAL PROD,OFF VACCINE RES & REVIEW,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852. US FDA,DIV VET MED,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852. WALTER REED ARMY INST RES,DEPT BACTERIAL DIS,WASHINGTON,DC 20307. N AMER VACCINE INC,BELTSVILLE,MD 20705. CHIRON BIOCINE,I-53100 SIENA,ITALY. NR 46 TC 30 Z9 30 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 MAR PY 1997 VL 65 IS 3 BP 1045 EP 1052 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WK953 UT WOS:A1997WK95300028 PM 9038314 ER PT J AU Zollinger, WD Moran, EE Devi, SJN Frasch, CE AF Zollinger, WD Moran, EE Devi, SJN Frasch, CE TI Bactericidal antibody responses of juvenile rhesus monkeys immunized with group B Neisseria meningitidis capsular polysaccharide-protein conjugate vaccines SO INFECTION AND IMMUNITY LA English DT Article ID ESCHERICHIA-COLI K1; INFLUENZAE TYPE-B; MONOCLONAL-ANTIBODY; COMPLEMENT; MICE; IMMUNOGENICITY; ANTIGENS; IGG1 AB Reports on the bactericidal activities of antibodies to group B Neisseria meningitidis capsular polysaccharide (B PS) are conflicting, Using three different complement sources, we analyzed the bactericidal activities of sera of juvenile rhesus monkeys immunized with five conjugate vaccines of B PS synthesized by different schemes, an Escherichia coli K92 conjugate, and a noncovalent complex of B PS with group B meningococcal outer membrane vesicles (B+OMV) (S. J. N. Devi, W. D. Zollinger, P. J. Snoy, J. Y. Tai, P. Costantini, F. Norelli, R. Rappuoli, and C. E. Frasch, Infect. Immun. 65:1045-1052, 1997). With rabbit complement, nearly all preimmune sera showed relatively high bactericidal titers, and all vaccines, except the K92 conjugate, induced a fourfold or greater increase in bactericidal titers in most of the monkeys vaccinated, In contrast, with human complement, most prevaccination sera showed no bactericidal activity and in most of the vaccine groups, little or no increase in bactericidal titer was observed, However, the covalent conjugation of P BS and OMV (B-OMV) administered with and without the Ribi adjuvant induced relatively high bactericidal titers which persisted up to 30 weeks, An analysis of the specificities of bactericidal antibodies revealed that absorption with E. coli K1 cells did not change the bactericidal titer with human complement but reduced the titers observed with the rabbit and monkey complements, A significant increase in anti-lipopolysaccharide (LPS) antibodies was elicited by the B-OMV conjugates, and nearly all of the bactericidal activity with human complement could be inhibited with the purified group B meningococcal L3,7,8 LPS. B-OMV covalently coupled via adipic acid dihydrazide elicited significantly elevated levels (P less than or equal to 0.02) of anti-OMV antibodies compared to those of the noncovalently complexed B+OMV, An initial small-scale evaluation of B PS conjugates in adult human males appears feasible, with careful monitoring, to settle the inconsistent reports of the importance of source of complement in eliciting bacteriolysis, Subsequent analysis of resultant human antibodies for bacteriolysis, opsonophagocytosis, and protective efficacy in animal models may be the first step toward answering safety-and efficacy-related concerns about B PS conjugate vaccines. C1 US FDA,DIV BACTERIAL PROD,OFF VACCINE RES & REVIEW,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852. RP Zollinger, WD (reprint author), WALTER REED ARMY INST RES,DEPT BACTERIAL DIS,WASHINGTON,DC 20307, USA. NR 38 TC 38 Z9 39 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 MAR PY 1997 VL 65 IS 3 BP 1053 EP 1060 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WK953 UT WOS:A1997WK95300029 PM 9038315 ER PT J AU Tai, SS Wang, TR Lee, CJ AF Tai, SS Wang, TR Lee, CJ TI Characterization of hemin binding activity of Streptococcus pneumoniae SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEIN; INFLUENZAE TYPE-B; NEISSERIA-GONORRHOEAE; IRON ACQUISITION; SURFACE PROTEIN; HEMOPHILUS-INFLUENZAE; TRANSPORT-SYSTEM; A PSPA; HEMOGLOBIN; TRANSFERRIN AB Streptococcus pneumoniae is a causative agent of bacterial pneumonia, otitis media, meningitis, and bacteremia. It causes considerable morbidity and mortality throughout the world, especially among children, the elderly, and immunocompromised individuals, We have demonstrated previously that the growth of S. pneumoniae is limited under iron-depleted conditions and can be restored by the addition of either hemin or hemoglobin. In the present study, we showed that S. pneumoniae had the ability to bind hemin and that the level of hemin binding activity was not affected by supplementation of the growth medium with iron. Approximately 70 to 80% of the hemin binding activity was mediated by proteinase-resistant components, and the remainder was mediated by proteins. Hemin binding proteins were located in both soluble extract and envelope fractions of pneumococcal cells. By batch affinity chromatography, a major hemin binding polypeptide with an apparent molecular mass of 43 kDa was identified in the cell lysate of S. pneumoniae. Polyclonal antibodies against this polypeptide were raised. By immunoblot analysis, this hemin binding polypeptide was localized in the envelope and did not exhibit any variation in molecular weight among all serotypes tested. The subcellular distribution of hemin binding activity may have functional implications. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. RP Tai, SS (reprint author), HOWARD UNIV,COLL MED,DEPT MICROBIOL,520 W ST NW,WASHINGTON,DC 20059, USA. NR 52 TC 26 Z9 26 U1 0 U2 4 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 MAR PY 1997 VL 65 IS 3 BP 1083 EP 1087 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WK953 UT WOS:A1997WK95300033 PM 9038319 ER PT J AU Betz, JM Gay, ML Mossoba, MM Adams, S Portz, BS AF Betz, JM Gay, ML Mossoba, MM Adams, S Portz, BS TI Chiral gas chromatographic determination of ephedrine-type alkaloids in dietary supplements containing Ma Huang SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the American-Society-of-Pharmacognosy CY JUL 23-27, 1995 CL UNIV OF MISSISSIPPI, OXFORD, MS SP Amer Soc Pharmacognosy HO UNIV OF MISSISSIPPI ID PERFORMANCE LIQUID-CHROMATOGRAPHY; CAPILLARY ZONE ELECTROPHORESIS; DOUBLE-BLIND; PHARMACEUTICAL FORMULATIONS; CHEMILUMINESCENCE DETECTION; ENANTIOMERIC SEPARATION; HEALTHY-VOLUNTEERS; BETA-CYCLODEXTRIN; OBESE SUBJECTS; URINE SAMPLES AB Ma Huang is a traditional Chinese medicine derived from the aerial parts of several Ephedra species (Ephedraceae), These plants produce (-)-ephedrine, (+)-pseudoephedrine, (-)-norephedrine, (+)-norpseudoephedrine, (-)-N-methylephedrine, and (+)-N-methylpseudoephedrine. Racemic and (-)-ephedrine, (+)-pseudoephedrine, and (+/-)-norephedrine (phenylpropanolamine) are used clinically in the United States and are largely synthetic in origin, Current interest in Ma Huang is spurred by reports describing a ''thermogenic'' (calorie burning) effect provided by mixtures of ephedrine, caffeine, and aspirin, Products providing the key thermogenic compounds from natural sources are available as dietary supplements in retail outlets. Reports of potentially unsafe levels of the alkaloids, as well as possible fortification of Ma Huang-containing products with synthetic Ephedra alkaloids, prompted the development of a chiral gas chromatographic (GC) method that allows determination of alkaloid patterns and identification of isomerically impure synthetic alkaloids. Nine products were analyzed on a I cyclodextrin capillary GC column, Identity of the alkaloids was verified by GC/mass spectrometry (MS) and GC/matrix isolation/Fourier transform infrared spectroscopy, No synthetic isomers were found in the dietary supplements analyzed, Three products contained only one of the ephedrine-type alkaloids. One product that listed Ma Huang as an ingredient contained no detectable ephedrine-type alkaloid, In products containing measurable quantities of these compounds, total alkaloid levels ranged from 0.3 to 56 mg/g. C1 US FDA,DENVER GEN CHEM SECT,DENVER,CO 80225. RP Betz, JM (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,200 C ST SW,WASHINGTON,DC 20204, USA. NR 142 TC 52 Z9 54 U1 3 U2 8 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1997 VL 80 IS 2 BP 303 EP 315 PG 13 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WP016 UT WOS:A1997WP01600005 PM 9086588 ER PT J AU Lytle, CD Duff, JE Fleharty, B Bidinger, RL Cyr, WH Routson, LB AF Lytle, CD Duff, JE Fleharty, B Bidinger, RL Cyr, WH Routson, LB TI A sensitive method for evaluating condoms as virus barriers SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID SURROGATE VIRUSES; TRANSMISSION; PERMEABILITY; EFFICACY; TESTS AB A standard test is needed to evaluate condoms as barriers against sexually transmitted diseases, particularly those caused by viruses. The proposed method presented here consists of a previously published simple method using physiologic-based conditions plus improvements to increase test sensitivity and decrease confounding factors such as contamination. Limitations of the method were determined by measuring virus penetration through small, well-defined holes. The method can detect penetration of 2 nL (2 x 10(-6) mL) of challenge virus suspension as well as a hole of 2 mu m diameter in a latex condom. The data also indicated that virus penetration of latex condoms occurred quickly, and the hole was then apparently closed or blocked. C1 SFA INC,LANDOVER,MD 20785. RP Lytle, CD (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,OFF SCI & TECHNOL,12709 TWINBROOK PKWY,ROCKVILLE,MD 20857, USA. NR 23 TC 14 Z9 15 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1997 VL 80 IS 2 BP 319 EP 324 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WP016 UT WOS:A1997WP01600007 PM 9086589 ER PT J AU Ting, S AF Ting, S TI Liquid chromatographic determination of scopolamine, hyoscyamine, and phenobarbital in tablets SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID SOLID-PHASE EXTRACTION; TROPANE ALKALOIDS; HPLC ANALYSIS; PLANTS; FEEDSTUFFS; ATROPINE AB A liquid chromatographic method using a reversed-phase C-18 column and octanesulfonic acid sodium salt-methanol as the mobile phase was developed for the simultaneous determination of phenobarbital, scopolamine, and hyoscyamine in tablets, The mixture of the 3 drugs was resolved in <8 min, Detector responses were linear for 10 mu L injections of the following: scopolamine hydrobromide, 8.25-206.3 mu g/mL; hyoscyamine sulfate, 15.01-750.76 mu g/mL; and phenobarbital, 250-751 mu g/mL, Recoveries from tablets were 100.8% for scopolamine hydrobromide, 100.1% for hyoscyamine sulfate, and 100.3% for phenobarbital. Replicate injections of scopolamine hydrobromide, hyoscyamine sulfate, and phenobarbital gave an overall relative standard deviation of <1.0% (n = 10), The method detected as little as 3.3 ng scopolamine hydrobromide. RP Ting, S (reprint author), US FDA,850 3RD AVE,BROOKLYN,NY 11232, USA. NR 16 TC 7 Z9 9 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 MAR-APR PY 1997 VL 80 IS 2 BP 331 EP 333 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WP016 UT WOS:A1997WP01600009 ER PT J AU Hammack, TS Feng, P Amaguana, RM June, GA Sherrod, PS Andrews, WH AF Hammack, TS Feng, P Amaguana, RM June, GA Sherrod, PS Andrews, WH TI Comparison of sorbitol MacConkey and hemorrhagic coli agars for recovery of Escherichia coli O157:H7 from brie, ice cream, and whole milk SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID HEMOLYTIC UREMIC SYNDROME; WATERBORNE OUTBREAK; SEROTYPE O157-H7; FOOD; IDENTIFICATION; DIARRHEA; GENE AB The relative efficacies of hemorrhagic coli (HC) agar and several formulations of sorbitol MacConkey (SorMac) agar, with and without 0.1% (w/v) 4-methyllumbelliferyl-beta-D-glucuronide (MUG), in recovering unstressed and heat-stressed Escherichia coli O157:H7 from Brie cheese, ice cream, and whole milk were determined, Recovery of unstressed E. coli O157:H7 was determined quantitatively by spread-plating diluted samples onto different agars and performing plate counts, Recovery of stressed E. coli O157:H7 was determined qualitatively by enriching samples in modified trypticase soy broth, streaking the incubated enrichments, and isolating E. coli O157:H7 colonies from the agars, HC agar and the SorMac agar formulations did not differ significantly in their ability to recover unstressed E. coli O157:H7 from ice cream and whole milk; however, HC agar recovered significantly more unstressed E. coli O157:H7 from Brie cheese than did the SorMac agar formulations, Bacteriological Analytical Manual and Oxoid SorMac agar formulations made from individual ingredients, did not differ significantly in recovering unstressed E. coli O157:H7 from Brie cheese, The efficiency of the commercially available Oxoid SorMac agar could not be determined because of overgrowth by indigenous microflora, HC and SorMac agars did not differ significantly in recovering stressed E. coli O157:H7 from Brie cheese, ice cream, and whole milk MUG had no apparent effect on recovery of either stressed or unstressed E. coli O157:H7 from the dairy foods examined. RP Hammack, TS (reprint author), US FDA, DIV MICROBIOL STUDIES, WASHINGTON, DC 20204 USA. NR 30 TC 15 Z9 15 U1 1 U2 5 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 MAR-APR PY 1997 VL 80 IS 2 BP 335 EP 340 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WP016 UT WOS:A1997WP01600010 PM 9086590 ER PT J AU Boucher, PE Murakami, K Ishihama, A Stibitz, S AF Boucher, PE Murakami, K Ishihama, A Stibitz, S TI Nature of DNA binding and RNA polymerase interaction of the Bordetella pertussis BvgA transcriptional activator at the fha promoter SO JOURNAL OF BACTERIOLOGY LA English DT Article ID C-TERMINAL REGION; ALPHA-SUBUNIT; VIRULENCE FACTORS; ESCHERICHIA-COLI; OXYR PROTEIN; GENE; EXPRESSION; MUTATIONS; IDENTIFICATION; RECOGNITION AB The expression of virulence factor genes in Bordetella pertussis is mediated by the BvgA-BvgS two-component signal transduction system, The response regulator, BvgA, acts directly as a transcriptional activator at the loci encoding pertussis toxin (ptx) and filamentous hemagglutinin (fha), Previous studies have demonstrated that these two loci are differentially regulated by BvgA, As an initial step in gaining insight into the mechanism underlying this differential regulation, we initiated DNA binding and in vitro transcription analyses to examine the activities of BvgA and RNA polymerase (RNAP) purified from both B. pertussis and Escherichia coli at the fha promoter, We discovered that unphosphorylated BvgA binds to a single region (-100 to -70, relative to the start of transcription), whereas phosphorylated BvgA binds both this region and another, farther downstream, that extends to the -35 nucleotide, In the absence of BvgA, RNAP binds a region farther upstream than expected (-104 to -35), However, occupation of both sites by BvgA phosphate repositions RNAP to the site used in vivo, The binding of BvgA phosphate to the downstream site correlates with in vitro transcriptional activity at the fha promoter, As the DNA binding and transcription activities of the E. coli-derived RNAP are similar to those observed for the B. pertussis enzyme, we employed several mutant E. coli proteins in in vitro transcription analyses. We observed that polymerases carrying either a deletion of the C-terminal domain of the alpha subunit or substitution of alanine at either of two critical residues within this domain were severely impaired in the ability to mediate BvgA-activated transcription at fha. C1 NATL INST GENET,DEPT MOL GENET,MISHIMA,SHIZUOKA 411,JAPAN. RP Boucher, PE (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 48 TC 79 Z9 81 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAR PY 1997 VL 179 IS 5 BP 1755 EP 1763 PG 9 WC Microbiology SC Microbiology GA WP415 UT WOS:A1997WP41500042 PM 9045838 ER PT J AU Mopper, B Sciacchitano, CJ AF Mopper, B Sciacchitano, CJ TI Capillary electrophoresis for regulatory analysis: Is it ready? SO JOURNAL OF CAPILLARY ELECTROPHORESIS LA English DT Article DE capillary electrophoresis; CE; tuna; histamine; collaborative study AB Recently, the Northeast Regional Laboratory of the Food and Drug Administration conducted a collaborative study on the method to determine histamine in tuna by capillary electrophoresis. This study, under the guidance of the AOAC International, was the first of its kind involving the use of CE and was undertaken to establish official monograph status. The results of the collaborative study, however, were highly variable. Percent recovery data obtained by 11 collaborators ranged from 54 to 281%, with an average of 111%. In this paper, problems with reproducibility, and factors such as low sensitivity, noisy baselines, and variable migration times encountered by collaborators using various commercial capillary electrophoresis units are discussed. C1 US FDA,NE REG LAB,BROOKLYN,NY 11232. NR 1 TC 12 Z9 12 U1 0 U2 0 PU I S C TECHNICAL PUBLICATIONS, INC PI SHELTON PA 30 CONTROLS DR, BOX 828, SHELTON, CT 06484-0828 SN 1079-5383 J9 J CAPILLARY ELECTROP JI J. Capillary Electrophor. PD MAR-APR PY 1997 VL 4 IS 2 BP 73 EP 76 PG 4 WC Biochemistry & Molecular Biology; Electrochemistry SC Biochemistry & Molecular Biology; Electrochemistry GA YD602 UT WOS:A1997YD60200005 PM 9624572 ER PT J AU Morris, GL Collins, S Bell, W Sahlroot, JT Matula, M Cereghino, JJ AF Morris, GL Collins, S Bell, W Sahlroot, JT Matula, M Cereghino, JJ TI Losigamone: A putative antiepileptic drug SO JOURNAL OF EPILEPSY LA English DT Article DE antiepileptic drugs; controlled clinical trial; losigamone; partial seizures; drug toxicity AB Losigamone (LSG) has shown anticonvulsant efficacy and low neurotoxicity in preclinical testing and has been tolerated in Phase I clinical trials. We report an open-label, add-on tolerability study of sb ascending LSG dosage levels from 600 to 2,100 mg daily in patients receiving phenytoin (PHT), carbamazepine (CBZ), or combination PHT/CBZ. Dosage was escalated weekly, with assessment including reports of adverse events (AE), seizure diary, neurologic and physical examination, electrocardiogram (EGG), and laboratory tests. No serious AE were reported, and those most common AE were headache and dizziness. No significant alteration in PHT, CDZ, or CBZ-epoxide(CBZ-E) levels was noted. No clinically significant change in laboratory tests was noted. A median seizure reduction during LSG treatment as compared with baseline of 39% was achieved during the study. All 9 patients continued into an extension study, and 3 have remained seizure-free for as long as 2 years. Some brief increases in seizure frequency were evident at the 1,800- and 2,100-mg daily dosage levels. We conclude that continued evaluation of LSG for the treatment of partial seizures is indicated. (C) 1997 by G. L. Morris III et al. C1 MED COLL WISCONSIN,DEPT NEUROL,MILWAUKEE,WI. NINCDS,EPIDEMIOL BRANCH,BETHESDA,MD 20892. NIAID,DIV BIOMETR,FOOD DRUG ADMIN,PORTLAND,OR. DIV AIDS,PORTLAND,OR. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NR 8 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0896-6974 J9 J EPILEPSY JI J. Epilepsy PD MAR-APR PY 1997 VL 10 IS 2 BP 62 EP 66 DI 10.1016/S0896-6974(96)00085-0 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA WU517 UT WOS:A1997WU51700004 ER PT J AU Woldemariam, TZ Betz, JM Houghton, PJ AF Woldemariam, TZ Betz, JM Houghton, PJ TI Analysis of aporphine and quinolizidine alkaloids from Caulophyllum thalictroides by densitometry and HPLC SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Caulophyllum thalictroides; Berberidaceae; Blue Cohosh; HPLC; densitometry; alkaloids AB High-performance liquid chromatographic (HPLC) and densitometry procedures were developed to determine the principal alkaloids in the roots of C. thalictroides. In both techniques the alkaloids content was assessed using cytisine as an internal standard. The purity and identity of the peaks of the alkaloids was examined by diode array detection and by comparison with the standards. The content of individual alkaloids was found to be in the range 0.02-1.1% w/w. (C) 1997 Elsevier Science B.V. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,DIV NAT PROD,WASHINGTON,DC 20204. RP Woldemariam, TZ (reprint author), UNIV LONDON KINGS COLL,DEPT PHARM,MANRESA RD,LONDON SW3 6LX,ENGLAND. NR 9 TC 19 Z9 19 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD MAR PY 1997 VL 15 IS 6 BP 839 EP 843 DI 10.1016/S0731-7085(96)01919-X PG 5 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA WW960 UT WOS:A1997WW96000017 PM 9172110 ER PT J AU Daveby, YD Aman, P Betz, JM Musser, SM Obermeyer, WR AF Daveby, YD Aman, P Betz, JM Musser, SM Obermeyer, WR TI The variation in content and changes during development of Soyasaponin I in dehulled Swedish peas (Pisum sativum L) SO JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE LA English DT Article DE Pisum sativum; dehulled seeds; hulls; soyasaponins; developmental changes ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SAPONIN CONTENT; SOYBEAN SEED; UNDESIRABLE TASTE; ROOT SAPONINS; 13 VARIETIES; GLYCINE-MAX; IDENTIFICATION; LEGUME; SOYA AB The variation in content and changes during development of soyasaponin I in dehulled Swedish peas (Pisum sativum L) were investigated. The content of soyasaponin I in 40 dehulled pea samples ranged from 0.82 to 2.5 g kg(-1) with a mean of 1.5 g kg(-1). No significant differences in soyasaponin content were found between light- and dark-coloured peas. No soyasaponin I was found in the hulls. The content of soyasaponin I in the dehulled peas decreased considerably during maturation. Two light-coloured varieties had a higher initial content and a much more pronounced decrease during development than a dark-coloured variety. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. RP Daveby, YD (reprint author), SWEDISH UNIV AGR SCI,DEPT FOOD SCI,POB 7014,S-75007 UPPSALA,SWEDEN. NR 21 TC 14 Z9 14 U1 0 U2 5 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0022-5142 J9 J SCI FOOD AGR JI J. Sci. Food Agric. PD MAR PY 1997 VL 73 IS 3 BP 391 EP 395 DI 10.1002/(SICI)1097-0010(199703)73:3<391::AID-JSFA740>3.0.CO;2-O PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA WP874 UT WOS:A1997WP87400018 ER PT J AU Rittner, R Braibante, MEF deKowalewski, DG Pla, JC Mazzola, EP AF Rittner, R Braibante, MEF deKowalewski, DG Pla, JC Mazzola, EP TI H-1 NMR chemical shifts and coupling constants of some 3-monosubstituted 2-methylpropenes SO MAGNETIC RESONANCE IN CHEMISTRY LA English DT Article DE 2-methylpropenes; substituent effects; allylic couplings; H-1 chemical shifts ID AB-INITIO CALCULATIONS; VIBRATIONAL ASSIGNMENT; INTERNAL-ROTATION; CONFORMATION; STABILITY; BARRIERS AB H-1 NMR chemical shifts and proton-proton coupling constants for some 3-substituted 2-methylpropenes [YCH2C(Me)CH2, Y = H, Cl, Br, I, OH, OMe, OEt, SH, SMe, SEt, NMe(2) and NEt(2)] are reported. Resonances of the olefinic protons were assigned through lanthanide-induced shifts. Chemical shifts of the olefinic protons (H-A and H-B) showed a dependence on the substituent at C-3 of the allylic fragment. Long-range allylic coupling constants ((4)J(choid) for H-A and CH2 and H-B and Me;(4)J(transoid) for H-B and CH2 and H-A and Me) were determined by spectral expansion and simulation. (C) 1997 by John Wiley & Sons, Ltd. C1 UNIV FED SANTA MARIA,DEPT QUIM,BR-97119900 SANTA MARIA,RS,BRAZIL. UNIV BUENOS AIRES,FAC CIENCIAS EXACTAS & NAT,DEPT FIS,RA-1428 BUENOS AIRES,DF,ARGENTINA. US FDA,WASHINGTON,DC 20204. RP Rittner, R (reprint author), UNIV ESTADUAL CAMPINAS,INST QUIM,CAIXA POSTAL 6154,BR-13083970 CAMPINAS,SP,BRAZIL. NR 18 TC 2 Z9 2 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0749-1581 J9 MAGN RESON CHEM JI Magn. Reson. Chem. PD MAR PY 1997 VL 35 IS 3 BP 147 EP 152 PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA WN696 UT WOS:A1997WN69600001 ER PT J AU Yao, RJ Burr, DH Guerry, P AF Yao, RJ Burr, DH Guerry, P TI CheY-mediated modulation of Campylobacter jejuni virulence SO MOLECULAR MICROBIOLOGY LA English DT Article ID SALMONELLA-TYPHIMURIUM; FLAGELLIN GENES; INTESTINAL COLONIZATION; SHIGELLA-FLEXNERI; PROTEINS; INVASION; CHEMOTAXIS; MOTILITY; IDENTIFICATION; INFECTION AB Four motile, non-adherent and non-invasive mutants of Campylobacter jejuni 81-176 generated by a site-specific insertional mutagenesis scheme were characterized at the molecular level and all contained a duplication of the same region of the chromosome. When this region was cloned from wild-type 81-176 and transferred into 81-176 on a shuttle plasmid, the same non-invasive phenotype as the original mutants was observed, suggesting that the region contained a repressor of adherence and invasion. The smallest piece of DNA identified which was capable of repressing adherence and invasion was a 0.8 kb fragment encoding the cheY gene of C. jejuni. To confirm further that CheY was responsible for the observed non-adherent and non-invasive phenotypes, the cheY gene was inserted into the arylsulfatase gene of 81-176 to generate a strain with two chromosomal copies of cheY. This diploid strain displayed the same nonadherent and non-invasive phenotype as the original mutants. Insertional inactivation of the choY gene in 81-176 resulted in an approx. threefold increase in adherence and invasion in vitro, but this strain was unable to colonize or cause disease in animals. The diploid choY strain, although able to colonize mice, was attenuated in a ferret disease model. C1 USN,MED RES INST ANNEX,ENTER DIS PROGRAM,BETHESDA,MD 20852. US FDA,WASHINGTON,DC 20204. FU PHS HHS [224-93-2444] NR 57 TC 115 Z9 121 U1 0 U2 4 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAR PY 1997 VL 23 IS 5 BP 1021 EP 1031 DI 10.1046/j.1365-2958.1997.2861650.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA WL764 UT WOS:A1997WL76400016 PM 9076738 ER PT J AU Kwon, OS Sandberg, JA Slikker, W AF Kwon, OS Sandberg, JA Slikker, W TI Effects of fumonisin B-1 treatment on blood-brain barrier transfer in developing rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-for-Neuroscience CY NOV 11-16, 1995 CL SAN DIEGO, CA SP Soc Neurosci, USDA, ARS, CSRS, OGPS DE fumonisin B-1; mycotoxin; sphinganine; sphingosine; blood-brain barrier; pharmacokinetics ID CHAIN SPHINGOID BASES; PROTEIN-KINASE-C; FUSARIUM-MONILIFORME; CELLS; SPHINGANINE; MYCOTOXINS; INHIBITION; CANCER; AREAS; LEUKOENCEPHALOMALACIA AB Fumonisin B-1 (FB1), a toxic metabolite of the fungus Fusarium moniliforme found in contaminated corn, is considered an etiologic agent of equine leukoencephalomalacia. Because FB1 exposure is associated with alteration of sphingolipid metabolism; the purpose of this study was to elucidate whether blood sphinganine (Sa) levels affect brain Sa levels. Sa and sphingosine (So) levels in brain tissue and plasma were analyzed by HPLC. Area under the curve (AUC(0-->24h)) ratios of brain Sa to plasma Sa levels were about 40 after a single 0.8 or 8 mg/kg SC dose of FB1. The AUC(0-->12h) ratio of brain FB1 to plasma FB1 was 0.02. The fact that FB1 alters brain Sa levels and Sa/So ratios indicates that sphingolipid metabolism in the central nervous system of developing rats is vulnerable to FB1 exposure. These data support our hypothesis that alterations of the brain Sa levels are related to the direct action of FB1 on the brain rather than transport of peripheral Sa to the brain. (C) 1997 Elsevier Science Inc. C1 US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL HFT132,JEFFERSON,AR 72079. UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & TOXICOL,LITTLE ROCK,AR 72205. NR 31 TC 10 Z9 11 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAR-APR PY 1997 VL 19 IS 2 BP 151 EP 155 DI 10.1016/S0892-0362(96)00217-6 PG 5 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA WW391 UT WOS:A1997WW39100007 PM 9136132 ER PT J AU Scariati, PD GrummerStrawn, LM Fein, SB Yip, R AF Scariati, PD GrummerStrawn, LM Fein, SB Yip, R TI Risk of diarrhea related to iron content of infant formula: Lack of evidence to support the use of low-iron formula as a supplement for breastfed infants SO PEDIATRICS LA English DT Article DE infant food; diarrhea; breastfeeding; iron ID DECLINING PREVALENCE; DEFICIENCY; ANEMIA; RESISTANCE AB Background. Concern has been raised by infant feeding experts that supplementing breastfed infants with iron-fortified formula rather than low-iron formula may have an undesirable impact on their gastrointestinal flora. Thus far, there have been no clinical studies to address this issue directly. We compared the reported frequency of diarrhea for breastfed infants given iron-fortified formula with those fed low-iron formula. Methods. Mothers participating in a mail panel provided feeding and diarrhea information on their infants at 2, 3, 4, 5, 6, 7, 9, and 12 months (n = 1743). Infants were grouped into five feeding categories: (1) breast milk only, (2) breast milk and low-iron formula, (3) breast milk and iron-fortified formula, (4) low-iron formula only, and (5) iron-fortified formula only. We calculated the number of diarrheal episodes per week for each feeding category and used rate ratios to estimate the relative impact of low-iron and iron-fortified formulas. Results. Among infants who received both breast milk and formula, the rate ratio for iron-fortified formula versus low-iron formula was 1.06 (confidence interval, 0.84 to 1.34), indicating that the type of formula a breastfed infant receives does not significantly affect the frequency of diarrhea. Conclusions. We found no evidence to support the hypothesis that breastfed infants given iron-fortified formula are at greater risk of having diarrhea. This, in addition to the fact that iron-fortified formula has played a major role in preventing childhood iron deficiency anemia, supports the current recommendation that any formula given to infants be fortified with iron. C1 CTR DIS CONTROL & PREVENT, EPIDEM INTELLIGENCE SERV, EPIDEMIOL PROGRAM OFF, ATLANTA, GA 30341 USA. US FDA, CTR FOOD SAFETY & APPL NUTR, OFF SCI ANAL & SUPPORT, WASHINGTON, DC 20204 USA. RP Scariati, PD (reprint author), CTR DIS CONTROL & PREVENT, DIV NUTR & PHYS ACTIV, NATL CTR CHRON DIS PREVENT & HLTH PROMOT, ATLANTA, GA 30341 USA. NR 17 TC 7 Z9 7 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 1997 VL 99 IS 3 BP art. no. EP e2 DI 10.1542/peds.99.3.e2 PG 4 WC Pediatrics SC Pediatrics GA WR147 UT WOS:A1997WR14700027 PM 9099767 ER PT J AU Hossain, M Wright, E Baweja, R Ludden, T Miller, R AF Hossain, M Wright, E Baweja, R Ludden, T Miller, R TI Nonlinear mixed effects modeling of single dose and multiple dose data for an immediate release (IR) and a controlled release (CR) dosage form of alprazolam SO PHARMACEUTICAL RESEARCH LA English DT Article DE alprazolam; controlled release; relative bioavailability; NONMEM; P450; covariate analysis; interoccasion variability ID REUPTAKE-INHIBITOR ANTIDEPRESSANTS; CIGARETTE-SMOKING; POPULATION PHARMACOKINETICS; CLINICAL PHARMACOKINETICS; IN-VITRO; FLUVOXAMINE; BIOAVAILABILITY; METABOLISM; NONMEM; PHARMACODYNAMICS AB Purpose. NONMEM was applied to single dose and multiple dose bioavailability data for an immediate release (IR) and a controlled release (CR) dosage form of alprazolam to acquire additional information from the data which are not easily obtainable by traditional means. Methods. The objective function value (OBJ) and diagnostic plots were used as measures of goodness of fit of the model to the data. A change in the OBJ value of 7.9 was necessary to show statistical significance (p < 0.005) between two models when the two models differed by 1 parameter. Results. A two-compartment linear model with first-order absorption and elimination best describes the data. Including a lag time, two different rates of absorption (KA(IR) and KA(CR)), and bioavailability for the CR relative to the IR dosage form significantly improved the fit of the model to the data. Cigarette smoking was associated with a 100% increase in clearance of alprazolam as compared to non-smokers. The higher residual variability observed in this study, where interoccasion variability (IOV) was not initially modeled, could be explained to a large extent by the presence of significant interoccasion variability (IOV). Conclusions. Since alprazolam has been suggested to be mainly metabolized by the CYP3A4 isozyme in humans, it appears that tobacco could be an inducer of CYP3A4 and/or alprazolam may be metabolized by other isozyme(s) (specifically, CYP1A1/1A2) that are induced by cigarette smoke. The population pharmacokinetic model approach combined with exploratory graphical data analysis is capable of identifying important covariates from well-controlled ''data rich'' Phase I studies early in drug development. C1 UPJOHN CO,CLIN PHARMACOKINET UNIT,KALAMAZOO,MI 49007. RP Hossain, M (reprint author), US FDA,CTR DRUG EVALUAT & RES,OFF CLIN PHARMACOL & BIOPHARMACEUT,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 35 TC 11 Z9 11 U1 1 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD MAR PY 1997 VL 14 IS 3 BP 309 EP 315 DI 10.1023/A:1012041920119 PG 7 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA WR383 UT WOS:A1997WR38300007 PM 9098872 ER PT J AU Zmudzka, BZ Strickland, AG Beer, JZ BenHur, E AF Zmudzka, BZ Strickland, AG Beer, JZ BenHur, E TI Photosensitized decontamination of blood with the silicon phthalocyanine Pc 4: No activation of the human immunodeficiency virus promoter SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID NF-KAPPA-B; TRANSCRIPTION FACTOR; METHYLENE-BLUE; RADIATION; TYPE-1; DNA; PSORALENS; DAMAGE; CELLS; UVA AB Photochemical decontamination of red blood cell concentrates (RBCC) with the silicon phthalocyanine Pc4 and red light is being studied to enhance the viral safety of blood transfusion. Recent reports indicate that treatments with radiation and various phototsensitizing agents can activate the promoter of human immunodeficiency virus (HIV). This raises the possibility that an inadequate, sublethal photochemical treatment of RBCC could induce HIV in latently infected cells, This question has been addressed using HeLa cells stably transfected with the chloramphenicol acetyl transferase gene under the control of the HIV promoter. In control studies, 8-methoxypsoralen (8-MOP) excited by UVA light caused activation of the HIV promoter in a dose- and time-dependent manner. At 0.1 mu g/mL of 8-MOP, maximal activation occurred with 18 J/cm(2), 30 h after light exposure. With Pc 4 at 20 nM, over 90% of HeLa cells were killed after 24 h when exposed to 1 J/cm(2) of red light. During that time interval and over a wide range of light doses no activation of the HIV promoter occurred. It is concluded that RBCC sterilization with Pc 4 and red light is unlikely to induce HIV production in latently infected cells. C1 VITEX,AUDUBON CTR,NEW YORK,NY 10032. US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857. FU NHLBI NIH HHS [2RO1-HL41221] NR 21 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAR PY 1997 VL 65 IS 3 BP 461 EP 464 DI 10.1111/j.1751-1097.1997.tb08590.x PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WP722 UT WOS:A1997WP72200020 PM 9077132 ER PT J AU Wamer, WG Wei, RR AF Wamer, WG Wei, RR TI In vitro photooxidation of nucleic acids by ultraviolet A radiation SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID HAIRLESS MICE; DNA; DAMAGE; UVA; FIBROBLASTS; KERATINOCYTES; WAVELENGTHS; CULTURE; CELLS; RNA AB Although ultraviolet A radiation (UVA, 315-400 nm) has been shown to induce oxidative stress in mammalian cells and skin, the critical chromophore(s) and molecular target(s) involved have not been identified. We examined the role of oxidative damage to nucleic acids induced by UVA. To assess photooxidation of cellular DNA and RNA by UVA, we irradiated human skin fibroblasts with up to 765 kJ/m(2) UVA, Cellular DNA and RNA were isolated immediately and enzymatically hydrolyzed to nucleosides, 8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a primary oxidation product in DNA, and 8-oxo-7,8-dihydroguanosine (8-oxoG), resulting from hydroxylation of guanine in RNA, were measured by HPLC with electrochemical detection, We determined that irradiation of skin fibroblasts with levels of UVA that produced moderate toxicity also resulted in significant levels of guanine hydroxylation in RNA, Lower levels of photooxidation were observed in DNA, These results suggest that measurement of guanine hydroxylation in nucleic acids, particularly in cellular RNA, may be a powerful tool for investigating the photobiological activity of UVA. RP Wamer, WG (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,HFS-128,200 C ST SW,WASHINGTON,DC 20204, USA. NR 25 TC 40 Z9 41 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 MAR PY 1997 VL 65 IS 3 BP 560 EP 563 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WP722 UT WOS:A1997WP72200035 PM 9077142 ER PT J AU Donoghue, DJ Hairston, H Henderson, M Mcdonald, M Gaines, S Donoghue, AM AF Donoghue, DJ Hairston, H Henderson, M Mcdonald, M Gaines, S Donoghue, AM TI Modeling drug residue uptake by eggs: Yolks contain ampicillin residues even after drug withdrawal and nondetectability in the plasma SO POULTRY SCIENCE LA English DT Article DE eggs; drug residues; modeling; ampicillin; half life AB The present study was conducted to determine whether: 1) preovulatory yolks may be an important storage depot for drug residues in eggs laid days to weeks after drug withdrawal; and 2) the prediction model based on the pattern of drug incorporation in developing yolks is predictive of the pattern of residues contained in the sequence of eggs laid during and after drug withdrawal. To test these possibilities, 24 hens were dosed for either 1, 2, or 3 d with ampicillin, and the content and pattern of residues in laid eggs were evaluated during and after dosing. Hens were bled 24 h after the final dosing, and plasma ampicillin concentrations were determined. Ampicillin was used in this study because it has an extremely short plasma half-life in laying hens that Limits additional drug transfer after drug withdrawal. Ampicillin concentrations were not detectable in plasma from hens injected with ampicillin for either 1, 2 or 3 d (assay sensitivity of 0.6 ng/ml or 0.6 ppb). Hens from all three injection groups produced eggs containing detectable ampicillin residues for 6 d after the last injection. These data demonstrate that drug residues are contained in eggs laid a number of days after drug withdrawal. Because plasma ampicillin was not detectable even 24 h after final dosing, the majority, if not all, of the incurred ampicillin residues contained in eggs laid after drug withdrawal were due to incorporation and storage of drug in preovulatory yolks during the dosing period. Additionally, accounting for ampicillin's stability, our model is predictive of the pattern of residues contained in eggs. These data emphasize the importance of transfer and storage of drugs in preovulatory yolks as a significant contributing mechanism for the production of incurred drug residues in eggs. RP Donoghue, DJ (reprint author), US FDA,CTR VET MED,DIV ANIM RES,8401 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 17 TC 27 Z9 27 U1 1 U2 1 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874 SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PD MAR PY 1997 VL 76 IS 3 BP 458 EP 462 PG 5 WC Agriculture, Dairy & Animal Science SC Agriculture GA WM410 UT WOS:A1997WM41000006 PM 9068044 ER PT J AU Schwetz, BA AF Schwetz, BA TI Summary of session IV: Prospects for improving human risk estimation SO REPRODUCTIVE TOXICOLOGY LA English DT Editorial Material RP Schwetz, BA (reprint author), US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD MAR-JUN PY 1997 VL 11 IS 2-3 BP 461 EP 463 DI 10.1016/S0890-6238(96)00162-1 PG 3 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA WQ840 UT WOS:A1997WQ84000042 ER PT J AU Lytle, CD Routson, LB Seaborn, GB Dixon, LG Bushar, HF Cyr, WH AF Lytle, CD Routson, LB Seaborn, GB Dixon, LG Bushar, HF Cyr, WH TI An in vitro evaluation of condoms as barriers to a small virus SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID LATEX CONDOMS; TESTS AB Background: Because of the possible presence of small holes, the effectiveness of condoms as barriers to virus transmission is controversial. Goals: To determine the proportion of condoms that allow virus penetration and the amounts of virus that penetrate. Study Design: A sensitive, static test was used to evaluate different condom types as barriers to a small virus, including brands with or without lubrication and ones of different materials. The test included some physiologic-based parameters and some parameters that exaggerated expected actual use conditions. Results: Under test conditions, 2.6% (12 of 470) of the latex condoms allowed some virus penetration; the median level of penetration was 7 x 10(-4) ml. Lubricated condoms performed similarly to nonlubricated ones. Polyurethane condoms yielded results higher than but not statistically different from those for latex condoms. Conclusions: Few condoms allowed any virus penetration. The median amount of penetration for latex condoms when extrapolated to expected actual use conditions was 1 x 10(-5) ml (volume of semen), Thus, even for the few condoms that do allow virus penetration, the typical level of exposure to semen would be several orders of magnitude lower than for no condom at all. C1 SFA INC,LANDOVER,MD 20785. US FDA,SE REG LAB,ATLANTA,GA. RP Lytle, CD (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,12709 TWINBROOK PKWY,ROCKVILLE,MD 20857, USA. NR 14 TC 42 Z9 43 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD MAR PY 1997 VL 24 IS 3 BP 161 EP 164 DI 10.1097/00007435-199703000-00007 PG 4 WC Infectious Diseases SC Infectious Diseases GA WM755 UT WOS:A1997WM75500007 PM 9132983 ER PT J AU Hellman, KB Picciolo, GL Mikos, AG Vacanti, CA AF Hellman, KB Picciolo, GL Mikos, AG Vacanti, CA TI Workshop on tissue engineering: Foreword SO TISSUE ENGINEERING LA English DT Editorial Material C1 US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20852. RICE UNIV,DEPT CHEM ENGN,HOUSTON,TX 77005. UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA 01655. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD SPR PY 1997 VL 3 IS 1 BP 65 EP 66 DI 10.1089/ten.1997.3.65 PG 2 WC Cell & Tissue Engineering SC Cell Biology GA XN989 UT WOS:A1997XN98900006 ER PT J AU Picciolo, GL AF Picciolo, GL TI Enabling biomaterials technology for tissue engineering: Introduction SO TISSUE ENGINEERING LA English DT Editorial Material ID BIOTECHNOLOGY AB Studies using biotechnology-derived biomaterials have resulted in enormous breakthroughs for application to the repair, reconstruction, and regeneration of human living tissue. In fact, this field has come to be called ''tissue engineering''. These materials are capable of establishing the structure and controlling the function in a predesigned manner by interacting with cells that are incorporated into the medical produce and/or with the host cells and tissue. Practically all human tissue is capable of being repaired by tissue-engineered products, with different degrees of success with some having reached clinical use. C1 US FDA,DIV MECH & MAT SCI,OFF SCI & TECHNOL,ROCKVILLE,MD 20852. NR 7 TC 4 Z9 4 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD SPR PY 1997 VL 3 IS 1 BP 67 EP 70 DI 10.1089/ten.1997.3.67 PG 4 WC Cell & Tissue Engineering SC Cell Biology GA XN989 UT WOS:A1997XN98900007 ER PT J AU Christenson, L Mikos, AG Gibbons, DF Picciolo, GL AF Christenson, L Mikos, AG Gibbons, DF Picciolo, GL TI Biomaterials for tissue engineering: Summary SO TISSUE ENGINEERING LA English DT Editorial Material C1 MED COMMUN,HAMDEN,CT 06514. RICE UNIV,DEPT CHEM ENGN,HOUSTON,TX 77005. US FDA,ROCKVILLE,MD 20852. 3M CTR,LIFE SCI LAB,ST PAUL,MN 55144. NR 0 TC 18 Z9 18 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD SPR PY 1997 VL 3 IS 1 BP 71 EP 76 DI 10.1089/ten.1997.3.71 PG 6 WC Cell & Tissue Engineering SC Cell Biology GA XN989 UT WOS:A1997XN98900008 PM 11543370 ER PT J AU Hellman, KB AF Hellman, KB TI Biotechnology biomaterials: A global regulatory perspective for tissue-engineered products: A preface SO TISSUE ENGINEERING LA English DT Editorial Material C1 US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20852. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD SPR PY 1997 VL 3 IS 1 BP 77 EP 78 DI 10.1089/ten.1997.3.77 PG 2 WC Cell & Tissue Engineering SC Cell Biology GA XN989 UT WOS:A1997XN98900009 ER PT J AU Burlington, DB AF Burlington, DB TI FDA's approach to international harmonization of biomaterials and tissue-engineered products SO TISSUE ENGINEERING LA English DT Article; Proceedings Paper CT Tissue Engineering Workshop, at the 5th World Biomaterials Congress CY MAY 29, 1996 CL TORONTO, CANADA AB The possibilities for global regulation of tissue-engineered products are discussed. While issues of national sovereignty are likely to present difficulties, the international medical device community shares fundamental goals, and the potential benefits to global harmonization are substantial. The Food and Drug Administration (FDA) is collaborating currently with international organizations on an approach to attain these goals, with excellent results. The devices approach to harmonization presented at the meetings of the Global Harmonization Task Force in June 1995 is described. FDA believes a stepwise approach to harmonization is an effective and efficient approach to making progress. To do this, all parties must agree on steps to achieve harmonization in each area. It is highly desirable that each country reach the same definitions of tissue and tissue-engineered products and jurisdictional assignments for regulatory review, avoiding overlaps, so that the industry can deal more economically with regulatory oversight. The controls that the FDA applies to tissue-engineered products are discussed as well as the need to determine which major consensus standards group can organize the development of global, not just European, standards for tissue-engineered products. The FDA pledges its support to work toward regulatory harmonization of these products. C1 US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857. NR 0 TC 1 Z9 1 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD SPR PY 1997 VL 3 IS 1 BP 79 EP 83 DI 10.1089/ten.1997.3.79 PG 5 WC Cell & Tissue Engineering SC Cell Biology GA XN989 UT WOS:A1997XN98900010 ER PT J AU Eggerman, TL Patterson, AP AF Eggerman, TL Patterson, AP TI The United States Food and Drug Administration paradigm for the regulation of tissue-engineered products SO TISSUE ENGINEERING LA English DT Article; Proceedings Paper CT Tissue Engineering Workshop, at the 5th World Biomaterials Congress CY MAY 29, 1996 CL TORONTO, CANADA AB As tissue engineering products are evolving, so too are the regulatory approaches to these products. Tissue engineering product development for the United States market is facilitated by an understanding of how the U.S. Food and Drug Administration (FDA) regulates tissue engineering products. New product innovations often require a coordinated effort by industry, academic investigators, and regulatory bodies to develop a degree of oversight that retains appropriate safeguards, incorporates public discussion, yet facilitates product development. A worldwide market has highlighted the importance of harmonized regulations and the world authorities are working together to standardize requirements. Xenotransplantation provides an example of an emerging technology that has significant public health ramifications which can best be addressed by public discussion, international collaboration, and a scientifically sound regulatory approach. The U.S. Public Health Service Guideline on Infectious Disease Issues in Xenotransplantation has been developed to address these issues (61 FR 49920, September 23, 1996). C1 US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPY,BETHESDA,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD SPR PY 1997 VL 3 IS 1 BP 109 EP 113 DI 10.1089/ten.1997.3.109 PG 5 WC Cell & Tissue Engineering SC Cell Biology GA XN989 UT WOS:A1997XN98900015 ER PT J AU Durfor, CN AF Durfor, CN TI Biotechnology biomaterials: A global regulatory perspective for tissue-engineered products: Summary report and future directions SO TISSUE ENGINEERING LA English DT Article; Proceedings Paper CT Tissue Engineering Workshop, at the 5th World Biomaterials Congress CY MAY 29, 1996 CL TORONTO, CANADA C1 US FDA,CTR DEVICES & RADIOL HLTH,OFF DEVICE EVALUAT,ROCKVILLE,MD 20850. NR 3 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD SPR PY 1997 VL 3 IS 1 BP 115 EP 120 DI 10.1089/ten.1997.3.115 PG 6 WC Cell & Tissue Engineering SC Cell Biology GA XN989 UT WOS:A1997XN98900016 ER PT J AU Schwetz, B AF Schwetz, B TI Evolving picture of carcinogenicity evaluation within the food and drug administration SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material RP Schwetz, B (reprint author), NATL CTR TOXICOL RES,HFT-1,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 3 TC 1 Z9 1 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 MAR-APR PY 1997 VL 25 IS 2 BP 239 EP 239 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA WV024 UT WOS:A1997WV02400017 PM 9125785 ER PT J AU Hewlett, IK Epstein, JS AF Hewlett, IK Epstein, JS TI Food and drug administration conference on the feasibility of genetic technology to close the HIV window in donor screening SO TRANSFUSION LA English DT Editorial Material ID TIME RP Hewlett, IK (reprint author), US FDA,MOL VIROL LAB,DIV TRANSFUS TRANSMITTED DIS,OFF BLOOD RES & REVIEW,ROCKVILLE,MD 20852, USA. NR 4 TC 21 Z9 25 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 MAR PY 1997 VL 37 IS 3 BP 346 EP 351 DI 10.1046/j.1537-2995.1997.37397240219.x PG 6 WC Hematology SC Hematology GA WP266 UT WOS:A1997WP26600017 PM 9122911 ER PT J AU Epstein, JS Schochetman, GC AF Epstein, JS Schochetman, GC TI Relative sensitivity of United States and European assays for screening blood donors for antibodies to human immunodeficiency viruses - Reply SO TRANSFUSION LA English DT Letter C1 CTR DIS CONTROL & PREVENT,DIV AIDS,STD & TB LAB RES,ATLANTA,GA. RP Epstein, JS (reprint author), US FDA,OFF BLOOD RES & REVIEW,ROCKVILLE,MD 20857, USA. NR 1 TC 0 Z9 0 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 MAR PY 1997 VL 37 IS 3 BP 353 EP 354 PG 2 WC Hematology SC Hematology GA WP266 UT WOS:A1997WP26600019 ER PT J AU Stein, KE AF Stein, KE TI Overcoming obstacles to monoclonal antibody product development and approval SO TRENDS IN BIOTECHNOLOGY LA English DT Article AB Using current monoclonal antibody technology one can now produce a humanized antibody to virtually any target antigen that can be identified. Consequently, one would expect there to be more approved monoclonal antibody products. Inadequate product development at both the preclinical and clinical stages has contributed to the overall lack of success. This article discusses some of the obstacles to successful product development and offers suggestions to overcoming them. The key to monoclonal antibody development, as with other biological products, is understanding the properties of the product itself, to have some proof of concept before embarking on clinical studies, and to adequately design and power the pivotal trial. RP Stein, KE (reprint author), US FDA,DIV MONOCLONAL ANTIBODIES,OFF THERAPEUT RES & REVIEW,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892, USA. NR 3 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD MAR PY 1997 VL 15 IS 3 BP 88 EP 90 DI 10.1016/S0167-7799(96)10075-5 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA WM680 UT WOS:A1997WM68000003 PM 9080714 ER PT J AU Zhang, DL Hansen, EB Deck, J Heinze, TM Henderson, A Korfmacher, WA Cerniglia, CE AF Zhang, DL Hansen, EB Deck, J Heinze, TM Henderson, A Korfmacher, WA Cerniglia, CE TI Fungal transformations of antihistamines: Metabolism of cyproheptadine hydrochloride by Cunninghamella elegans SO XENOBIOTICA LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; DRUG-METABOLISM; CYTOCHROME-P-450; DISPOSITION; RATS; 1-AMINOBENZOTRIAZOLE; P450 AB 1. Metabolites formed during incubation of the antihistamine cyproheptadine hydrochloride with the zygomycete fungus Cunminghamella elegans in liquid culture were determined. The metabolites were isolated by hplc and identified by mass spectrometric and proton nmr spectroscopic analysis. Two C. elegans strains, ATCC 9245 and ATCC 36112, were screened and both produced essentially identical metabolites. 2. Within 72h cyproheptadine was extensively biotransformed to at]east eight oxidative phase-1 metabolites primarily via aromatic hydroxylation metabolic pathways. Cyproheptadine was biotransformed predominantly to 2-hydroxpcyproheptadine. Other metabolites identified were 1- and 3-hydroxycyproheptadine, cyproheptadine 10,11-epoxide, N-desmethylcyproheptadine, N-desmethyl-2-hydroxycyproheptadine, cyproheptadine N-oxide, and 2-hydroxycyproheptadine N-oxide. Although a minor fungal metabolite, cyproheptadine 10,11-epoxide represents the first stable epoxide isolated from the microbial biotransformation of drugs. 3. The enzymatic mechanism for the formation of the major fungal metabolite, 2-hydroxycyproheptadine was investigated. The oxygen atom was derived from molecular oxygen as determined from O-18-labelling experiments. The formation of 2-hydroxycyproheptadine was inhibited 35, 70 and 97 % by cytochrome P450 inhibitors metyrapone, proadifen and 1-aminobenzotriazole respectively. Cytochrome P450 was detected in the microsomal fractions of C. elegans. In addition, 2-hydroxylase activity was found in cell-free extracts of C. elegans. This activity was inhibited by proadifen and CO, and was inducible by naphthalene. These results are consistent with the fungal epoxidation and hydroxylation reactions being catalysed by cytochrome P450 monooxygenases. 4. The effects of types of media on the biotransformation of cyproheptadine were investigated. It appears that the glucose level significantly affects the biotransformation rates of cyproheptadine; however, it did not change the relative ratios between metabolites produced. C1 NATL CTR TOXICOL RES,DEPT HLTH & HUMAN SERV,FOOD & DRUG ADM,DIV MICROBIOL,JEFFERSON,AR 72079. NATL CTR TOXICOL RES,DEPT HLTH & HUMAN SERV,FOOD & DRUG ADM,DIV CHEM,JEFFERSON,AR 72079. NATL CTR TOXICOL RES,DEPT HLTH & HUMAN SERV,FOOD & DRUG ADM,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079. NR 34 TC 17 Z9 18 U1 1 U2 5 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD MAR PY 1997 VL 27 IS 3 BP 301 EP 315 PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA WQ949 UT WOS:A1997WQ94900006 PM 9141237 ER PT J AU Angyal, G Weaver, CM Rader, JI AF Angyal, G Weaver, CM Rader, JI TI Pre-fortification levels of folate in enriched cereal-grain products. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,OFF FOOD LABELING,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 1361 EP 1361 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53001361 ER PT J AU Lee, H Gerrior, S Smith, J AF Lee, H Gerrior, S Smith, J TI Energy compensation by reduced-fat milk drinkers. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. USDA,CNPP,WASHINGTON,DC 20036. ARS,USDA,WASHINGTON,DC 20090. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 2077 EP 2077 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53002075 ER PT J AU Satchithanandam, S Calvert, RJ AF Satchithanandam, S Calvert, RJ TI Effect of feeding coconut oil and sesame oil on liver and serum lipid parameters. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,DIV SCI & APPL TECHNOL,LAUREL,MD. US FDA,CLIN RES & REV STAFF,LAUREL,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 2193 EP 2193 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53002195 ER PT J AU Kim, CS Johnson, WA Ross, IA Johnson, W Hoppel, CL AF Kim, CS Johnson, WA Ross, IA Johnson, W Hoppel, CL TI The effect of aging on carnitine palmitoyltransferase activity in the miniswine choroid plexus. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,WASHINGTON,DC 20204. CASE WESTERN RESERVE UNIV,SCH MED,CLEVELAND,OH 44106. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 3635 EP 3635 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53003636 ER PT J AU Waltrip, RW Buchanan, RW William, TC Kirkpatrick, B Summerfelt, A Breier, A Rubin, SA Carbone, KM AF Waltrip, RW Buchanan, RW William, TC Kirkpatrick, B Summerfelt, A Breier, A Rubin, SA Carbone, KM TI Borna disease virus antibodies and the deficit syndrome of schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Borna disease virus; schizophrenia; deficit syndrome ID ABNORMALITIES; RATS; INFECTION; CELLS; BRAIN; RNA AB We detected anti-Borna disease virus (BDV) antibodies at a 14.4% rate in patients with schizophrenia. The hypothesis of a higher rate of BDV seropositivity in deficit syndrome was borne out in a subset of 64 patients categorized according to the Schedule for the Deficit Syndrome with 5/15 seropositive deficit and 4/49 seropositive nondeficit (p<0.05). This suggests that the antibodies and possibly a BDV-like virus are pathogenetically linked to this form of schizophrenia. C1 NIMH,EXPT THERAPEUT BRANCH,UNIT PATHOPHYSIOL & TREATMENT,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,NEUROIMMUNOPATHOGENESIS SECT,LAB PEDIAT VIRAL DIS & RESP VIRUSES,BETHESDA,MD. RP Waltrip, RW (reprint author), UNIV MARYLAND,MARYLAND PSYCHIAT RES CTR,DEPT PSYCHIAT,CATONSVILLE,MD 21228, USA. FU NIMH NIH HHS [MH40279, MH00814, MH44211] NR 34 TC 66 Z9 67 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB 28 PY 1997 VL 23 IS 3 BP 253 EP 257 DI 10.1016/S0920-9964(96)00114-4 PG 5 WC Psychiatry SC Psychiatry GA WM020 UT WOS:A1997WM02000009 PM 9075304 ER PT J AU Araujo, JC Doniger, J Stoppler, H Sadie, MR Rosenthal, LJ AF Araujo, JC Doniger, J Stoppler, H Sadie, MR Rosenthal, LJ TI Cell lines containing and expressing the human herpesvirus 6A ts gene are protected from both H-ras and BPV-1 transformation SO ONCOGENE LA English DT Article DE transformation suppression; cellular oncogene promoter suppressor; viral oncogene promoter suppressor; retroviral mediated gene transfer ID IMMUNODEFICIENCY-VIRUS TYPE-1; LONG TERMINAL REPEAT; BOVINE PAPILLOMAVIRUS; BINDING PROTEIN; REGION; DNA; INHIBITION; ELEMENTS; RNA; REPLICATION AB Human herpesvirus 6A (HHV-6A) strain U1102 was previously shown to contain a 1473 bp transformation suppressor gene (ts) (Araujo et al,, 1995), Ts inhibited transformation of NIH3T3 cells by H-vas and transcription of the H-uas and human immunodeficiency type 1 (HIV-1) promoters in transient transfection experiments. In the current study, stable NIH3T3 cell lines expressing ts protein were established by transfection with pRc-ts containing the ts gene under the control of the Rous sarcoma virus (RSV) long terminal repeat (LTR) and a neomycin selectable marker. Selected cell lines contained approximately one to two copies per cell of intact ts sequences, expressed ts protein and grew at approximately the same rate as parental NIH3T3 cells. These cell lines were protected from H-ras transformation while parental and NIH3T3 cells containing the ts gene cloned in the antisense orientation were not. Expression of the chloramphenicol acetyl transferase (CAT) gene under the control of the EJ-H-ras promoter was also suppressed in the ts cell lines but not when the CAT gene was under the control of the murine osteosarcoma virus LTR or human cytomegalovirus immediate early promoter. When NIH3T3 cell lines expressing ts protein were established by infection with the retrovirus, LNCts, the cells expressed ts protein and were protected from H-ras transformation, Furthermore, bovine papillomavirus type 1 (BPV-1) transformation was also suppressed in cells cotransfected with BPV-1 plus ts and in ts expressing cell lines transfected with BPV-1. The BPV-1 p89 and p2443 promoters were down-regulated in 3T3-ts lines. Because the human papillomavirus type 16 (HPV-16) p97 promoter has similarity to the BPV-1 p89 promoter, the ability of ts to suppress p97 was also tested. Like the H-ras and BPV-1 promoters, HPV-16 p97 was downregulated in 3T3-ts lines. The data indicate the utility of ts against H-ras, BPV-1 and HPV-16 promoters and their respective oncogenes. C1 GEORGETOWN UNIV,MED CTR,DEPT MICROBIOL & IMMUNOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC CTR,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20007. US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,ROCKVILLE,MD 20852. NR 28 TC 8 Z9 9 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 27 PY 1997 VL 14 IS 8 BP 937 EP 943 DI 10.1038/sj.onc.1200899 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WK344 UT WOS:A1997WK34400007 PM 9050993 ER PT J AU Ding, M Hao, YW Mitchell, F Biswas, R Ndimbie, OK Farshid, M AF Ding, M Hao, YW Mitchell, F Biswas, R Ndimbie, OK Farshid, M TI Sequence characterization of the 5' noncoding region of GB virus C hepatitis G virus SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID NON-A; GENOME AB The nucleotide sequences of the 5' noncoding region of the GE virus C/hepatitis G virus (GBV-C/HGV) were determined in 18 isolates from the United States, Two genotyges have been classified based on the sequence heterogeneity within the 5' noncoding region of GBV-V/HGV. The most distantly related isolates between the two genotypes were 84.6% identical, Sequence identity of the isolates within a genotype was 95-99%, The 5' noncoding region of this virus contains four highly conserved domains, These conserved elements would facilitate the selection of optimal primers for the sensitive detection of GBV-C/HGV RNA by PCR, In addition, they suggest a crucial role for this region in viral replication and/or gene expression. Detection of viral replication and/or gene expression. Detection of variation among GBV-C/HGV infected individuals may provide further insight into the possible pathogenicity and into the transmission of the virus. (C) 1997 Academic Press. C1 UNIV PITTSBURGH,MED CTR,PITTSBURGH,PA 15213. RP Ding, M (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,HEPATATIS LAB,BETHESDA,MD 20892, USA. NR 17 TC 5 Z9 5 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 24 PY 1997 VL 231 IS 3 BP 606 EP 609 DI 10.1006/bbrc.1997.6159 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WK484 UT WOS:A1997WK48400020 PM 9070855 ER PT J AU Lin, LA Tomlinson, JA Satzger, RD AF Lin, LA Tomlinson, JA Satzger, RD TI Detection of clenbuterol in bovine retinal tissue by highperformance liquid chromatography with electrochemical detection SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 20th International Symposium on High Performance Liquid Phase Separations and Related Techniques CY JUN 16-21, 1996 CL SAN FRANCISCO, CA DE clenbuterol; beta-agonists ID RESIDUES; URINE AB A method for the detection of the P-agonist drug clenbuterol in bovine retinal tissue has been developed. The extraction procedure involves sonication and centrifugation. followed by the addition of ethylenediaminetetraacetic acid (EDTA) to the supernatant. The pH of the supernatant is then brought to 12.2, which is then allowed to sit for 2 h. This is followed by a diethylether extraction. The diethylether extract is dried under nitrogen and the residue is dissolved in 1% formic acid. The quantitation of clenbuterol was accomplished by high-performance liquid chromatography with electrochemical detection. The electrochemical detector was an amperometric detector. The detector was set in the pulsed mode. The oxidizing potential of a carbon electrode was 1.3 V vs. a Ag/AgCl reference electrode and was pulsed to a reduction potential of -2.0 V vs. a Ag/AgCl reference electrode. The limit of detection for this method was 5 ng/ml of clenbuterol (S/N=3). Typical spiked recoveries are 75%. RP Lin, LA (reprint author), US FDA,FORENS CHEM CTR,1141 CENT PKWY,CINCINNATI,OH 45202, USA. NR 9 TC 32 Z9 40 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD FEB 21 PY 1997 VL 762 IS 1-2 BP 275 EP 280 DI 10.1016/S0021-9673(96)00728-5 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WP082 UT WOS:A1997WP08200028 PM 9098986 ER PT J AU Ambrosone, CB Freudenheim, JL Shields, PG AF Ambrosone, CB Freudenheim, JL Shields, PG TI Genetic polymorphisms and breast cancer risk - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NATL CANC INST, BETHESDA, MD USA. SUNY BUFFALO, BUFFALO, NY USA. RP Ambrosone, CB (reprint author), NATL CTR TOXICOL RES, JEFFERSON, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 19 PY 1997 VL 277 IS 7 BP 534 EP 534 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WH297 UT WOS:A1997WH29700026 ER PT J AU Albert, R Horwitz, W AF Albert, R Horwitz, W TI A heuristic derivation of the Horwitz curve SO ANALYTICAL CHEMISTRY LA English DT Letter AB The Horwitz curve is a simple exponential relationship between the relative standard deviation among laboratories to concentration, C, expressed in mass/mass units, Examination of almost 10 000 interlaboratory data sets shows that the curve is more or less independent of analyte, matrix, method, and time of publication, over the range from pure materials, C = 1 (100%), to trace polychlorinated aromatic contaminants (PCCs), C approximate to 10(-12). The functional relationship can be derived simply by assuming that the infinitesimal fractional change in standard deviation is proportional to the infinitesimal fractional change in C, by integrating, and by determining the constant of integration from empirical results, Mycotoxin and PCC data show that the limit of measurement in the interlaboratory environment is C approximate to 10(-9), where results become uninterpretable because of the appearance of excessive numbers of false positive and false negative values, Lower values are possible only because of the extraordinary specifications for quality control for these analyses. C1 US FDA,WASHINGTON,DC 20204. US FDA,S BOSTON,MA 02127. NR 6 TC 94 Z9 94 U1 1 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD FEB 15 PY 1997 VL 69 IS 4 BP 789 EP 790 DI 10.1021/ac9608376 PG 2 WC Chemistry, Analytical SC Chemistry GA WH357 UT WOS:A1997WH35700039 ER PT J AU Mor, G Singla, M Steinberg, AD Hoffman, SL Okuda, K Klinman, DM AF Mor, G Singla, M Steinberg, AD Hoffman, SL Okuda, K Klinman, DM TI Do DNA vaccines induce autoimmune disease? SO HUMAN GENE THERAPY LA English DT Article ID B-CELL ACTIVATION; SYSTEMIC LUPUS-ERYTHEMATOSUS; DIRECT GENE-TRANSFER; BACTERIAL-DNA; PLASMID DNA; CIRCUMSPOROZOITE PROTEIN; IMMUNE-RESPONSES; NORMAL MICE; ANTIBODIES; IMMUNIZATION AB This report examines whether plasmid DNA vaccines induce the production of anti-DNA or anti-muscle cell autoantibodies. A three-fold increase in the number of B cells secreting immunoglobulin G (IgG) anti-DNA autoantibodies was detected in BALB/c mice immunized and boosted with any of three DNA plasmids (p < 0.004). This correlated with a transient increase in serum anti-DNA autoantibody titers but was not associated with the development of glomerulonephritis or autoimmune disease. None of the DNA vaccines examined stimulated the production of anti-muscle cell autoantibodies or the development of myositis. The effect of DNA vaccines on the development of nascent autoimmunity in lupus-prone (NZB x NZW)F-1 mice was also examined. Repeated vaccination did not alter the onset or course of disease in these animals. These findings suggest that DNA vaccines neither initiate nor accelerate the development of systemic autoimmunity. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,SECT RETROVIRAL IMMUNOL,BETHESDA,MD 20892. MITRETEK SYST,MCLEAN,VA 22102. USN,MED RES INST,MALARIA PROGRAM,BETHESDA,MD 20889. YOKOHAMA CITY UNIV,SCH MED,DEPT BACTERIOL,YOKOHAMA,KANAGAWA 236,JAPAN. NR 42 TC 124 Z9 133 U1 1 U2 8 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 FEB 10 PY 1997 VL 8 IS 3 BP 293 EP 300 DI 10.1089/hum.1997.8.3-293 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WH938 UT WOS:A1997WH93800006 PM 9048196 ER PT J AU Nightingale, SL AF Nightingale, SL TI Fertility drug shortage over 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 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 5 PY 1997 VL 277 IS 5 BP 370 EP 370 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WE771 UT WOS:A1997WE77100007 PM 9010159 ER PT J AU Nightingale, SL AF Nightingale, SL TI FDA proposes to withdraw terfenadine approval 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 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 5 PY 1997 VL 277 IS 5 BP 370 EP 370 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WE771 UT WOS:A1997WE77100008 PM 9010159 ER PT J AU Nightingale, SL AF Nightingale, SL TI Ruminant-to-ruminant feeding ban proposed to reduce risk of transmissible spongiform encephalopathies 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 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 5 PY 1997 VL 277 IS 5 BP 370 EP 370 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WE771 UT WOS:A1997WE77100006 PM 9010159 ER PT J AU Kessler, DA Barnett, PS Witt, A Zeller, MR Mande, JR Schultz, WB AF Kessler, DA Barnett, PS Witt, A Zeller, MR Mande, JR Schultz, WB TI The legal and scientific basis for FDA's assertion of jurisdiction over cigarettes and smokeless tobacco SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID NICOTINE; SMOKING; DEPENDENCE AB On August 28, 1996, the US Food and Drug Administration (FDA) asserted jurisdiction over cigarettes and smokeless tobacco under the Federal Food, Drug, and Cosmetic Act. Under this Act, a product is a ''drug'' or ''device'' subject to FDA jurisdiction if it is ''intended to affect the structure or any function of the body.'' The FDA determined that nicotine in cigarettes and smokeless tobacco does ''affect the structure or any function of the body'' because nicotine causes addiction and other pharmacological effects. The FDA then determined that these pharmacological effects are ''intended'' because (1) a scientific consensus has emerged that nicotine is addictive; (2) recent studies have shown that most consumers use cigarettes and smokeless tobacco for pharmacological purposes, including satisfying their addiction to nicotine; and (3) newly disclosed evidence from the tobacco manufacturers has revealed that the manufacturers know that nicotine causes pharmacological effects, including addiction, and design their products to provide pharmacologically active doses of nicotine. The FDA thus concluded that cigarettes and smokeless tobacco are subject to FDA jurisdiction because they contain a ''drug,'' nicotine, and a ''device'' for delivering this drug to the body. RP Kessler, DA (reprint author), US FDA,DEPT HLTH & HUMAN SERV,5600 FISHERS LN,14-71 PKLN,ROCKVILLE,MD 20857, USA. NR 31 TC 27 Z9 28 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 FEB 5 PY 1997 VL 277 IS 5 BP 405 EP 409 DI 10.1001/jama.277.5.405 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA WE771 UT WOS:A1997WE77100031 PM 9010173 ER PT J AU Wilkin, JK AF Wilkin, JK TI Potential subversion of pregnancy prevention program in the managed care setting SO ARCHIVES OF DERMATOLOGY LA English DT Letter RP Wilkin, JK (reprint author), US FDA,DIV DERMATOL & DENT DRUG PROD,CTR DRUG EVALUAT & RES,HFD-540,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 2 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 FEB PY 1997 VL 133 IS 2 BP 243 EP 244 PG 2 WC Dermatology SC Dermatology GA WH067 UT WOS:A1997WH06700022 PM 9041846 ER PT J AU Pothuluri, JV Evans, FE Doerge, DR Churchwell, MI Cerniglia, CE AF Pothuluri, JV Evans, FE Doerge, DR Churchwell, MI Cerniglia, CE TI Metabolism of metolachlor by the fungus Cunninghamella elegans SO ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY LA English DT Article ID MICROBIAL TRANSFORMATION; HERBICIDE METOLACHLOR; ALACHLOR; SOIL; BIODEGRADATION; ENZYMES AB The metabolism of metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide] by the fungus Cunninghamella elegans ATCC 36112 was determined. The six metabolites identified comprised 81% of the total [C-14]-metolachlor metabolized by C. elegans. These metabolites were separated by reversed-phase high-performance liquid chromatography and identified by H-1 nuclear magnetic resonance, UV, and atmospheric pressure chemical ionization (APCT) mass spectral techniques. Metabolites I and II were identified as stereoismers of 2-chloro-N-[2-ethyl-6-hydroxymethylphenyl)]-N-(2-hydroxy-1-methylethyl)acetamide. Metabolites III and IV have been tentatively identified as stereoismers of 2-chloro-N-[2-(1-hydroxyethyl)-6-methylphenyl]-N-(2-methoxy-1-methylethyl)acetatamide. Metabolites V and VI were identified as stereoismers of 2-chloro-N-(2-ethyl-6-hydroxy-methylphenyl)-N-(2-methoxy-1-methylethyl) acetamide and 2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-hydroxy-1-methylethyl)acetamide, respectively. The fungus Cunninghamella elegans was able to biotransform metolachlor. Multiple site oxidation of metolachlor by C. elegans occurred predominantly by O-demethylation of the N-alkyl side chain and benzylic hydroxylation of the arylalkyl side chain. RP Pothuluri, JV (reprint author), US FDA,NATL CTR TOXICOL RES,DIV MICROBIOL,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 24 TC 21 Z9 24 U1 0 U2 9 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0090-4341 J9 ARCH ENVIRON CON TOX JI Arch. Environ. Contam. Toxicol. PD FEB PY 1997 VL 32 IS 2 BP 117 EP 125 PG 9 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA WQ768 UT WOS:A1997WQ76800001 PM 9069185 ER PT J AU Lewis, EN Kidder, LH Pentchev, P Levin, IW Lester, DS AF Lewis, EN Kidder, LH Pentchev, P Levin, IW Lester, DS TI Infrared spectroscopic imaging studies of brain tissue derived from the mutant Niemann Pick C mouse SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK,PHYS CHEM LAB,NIH,BETHESDA,MD 20892. NINCDS,DEV & METAB NEUROL BRANCH,NIH,BETHESDA,MD 20892. US FDA,CTR DRUG EVALUAT & RES,LAUREL,MD 20708. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MPME5 EP MPME5 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700121 ER PT J AU Petrache, H Feller, S Nagle, JF AF Petrache, H Feller, S Nagle, JF TI Determination of volumes of components of lipid bilayers from simulations SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 CARNEGIE MELLON UNIV,PITTSBURGH,PA 15213. WHITMAN COLL,WALLA WALLA,WA 99362. US FDA,ROCKVILLE,MD 20857. RI Nagle, John/B-1917-2015 OI Nagle, John/0000-0002-9844-5934 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP247 EP MP247 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700382 ER PT J AU James, SJ Miller, BJ Basnakian, AG Pogribny, IP Pogribna, M Muskhelishvili, L AF James, SJ Miller, BJ Basnakian, AG Pogribny, IP Pogribna, M Muskhelishvili, L TI Apoptosis and proliferation under conditions of deoxynucleotide pool imbalance in liver of folate/methyl deficient rats SO CARCINOGENESIS LA English DT Article ID CHOLINE-DEVOID DIET; FED METHYL-DEFICIENT; DNA STRAND BREAKS; PROGRAMMED CELL-DEATH; ACID-DEFINED DIETS; HEPATOCELLULAR CARCINOMAS; POLY(ADP-RIBOSE) POLYMERASE; FOLATE-DEFICIENCY; MAMMALIAN-CELLS; NAD METABOLISM AB Weanling male F344 rats were fed either a semi-purified diet low in methionine and lacking in choline and folic acid (folate/methyl deficient) or a supplemented control diet for periods of 2, 5, 7 days, 3 weeks, and 9 weeks, Two days after initiating the folate/methyl deficient diet in weanling F344 rats, the incidence of apoptotic bodies, identified by in situ end-labeling of 3'-OH DNA strand breaks, was significantly increased in liver sections from the deficient rats, Apoptotic cell death was confirmed biochemically by an increase in nuclear Ca2+/Mg2+-dependent endonuclease activity that paralleled the increase in apoptotic bodies over the 9-week feeding period, There was no morphologic evidence of necrotic foci or necrosis-associated inflammatory response over the 9-week period, Confirming that cell turnover is chronically elevated in this model, the increase in apoptotic rate was accompanied by a sustained increase in the mitotic index (MI). The DNA repair-associated enzyme, poly(ADPribose) polymerase (PARP), was similarly elevated and was associated with significant decreases in the substrate for ADPribose polymer synthesis, nicotinamide adenine dinucleotide (NAB), Because folate metabolites are essential for de novo purine and thymidine biosynthesis, prolonged deficiency in folic acid can induce an imbalance in the deoxynucleotide precursors for DNA replication/repair and negatively affect the fidelity of DNA synthesis, Using an HPLC method, hepatic deoxyuridine triphosphate (dUTP) levels were increased at 3 and 9 weeks after initiation of the deficient diet and levels of thymidine triphosphate (dTTP) were reduced, An increase in dUTP/dTTP ratio is consistent with a block in folate-dependent de novo thymidylate biosynthesis and may predispose to uracil misincorporation and DNA repair-related DNA strand breaks. RP James, SJ (reprint author), NATL CTR TOXICOL RES,DIV NUTR TOXICOL,JEFFERSON,AR 72079, USA. NR 68 TC 91 Z9 97 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 1997 VL 18 IS 2 BP 287 EP 293 DI 10.1093/carcin/18.2.287 PG 7 WC Oncology SC Oncology GA WK667 UT WOS:A1997WK66700008 PM 9054620 ER PT J AU Husain, SR Obiri, NI Gill, P Zheng, T Pastan, I Debinski, W Puri, RK AF Husain, SR Obiri, NI Gill, P Zheng, T Pastan, I Debinski, W Puri, RK TI Receptor for interleukin 13 on AIDS-associated Kaposi's sarcoma cells serves as a new target for a potent Pseudomonas exotoxin-based chimeric toxin protein SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR; CYTOKINES; EXPRESSION; PATHOGENESIS; MACROPHAGES; AUTOCRINE; PARACRINE; HIV-1 AB AIDS-associated Kaposi's sarcoma (AIDS-KS), the most common malignant complication of human immunodeficiency virus infection, is characterized by neoplastic proliferation of mesenchymal cells, AIDS-KS cells release and respond to an array of cytokines through specific plasma membrane receptors, Specific targeting of potent cytotoxic agents to cell surface receptors/antigens on Kaposi's sarcoma cells may provide effective therapy for this malignancy, We have identified a new target in the form of an interleukin 13 (IL-13) receptor that is overexpressed in the five AIDS-KS cell lines examined. Radio-labeled IL-13 cross-linked to a single protein of about M-r 70,000 in AIDS KS cells, We utilized a chimeric cytotoxic protein composed of IL-13 and a truncated Pseudomonas exotoxin (IL13-PE38QQR), which was found to be specifically and highly cytotoxic to AIDS-KS cells, as determined by protein synthesis inhibition and clonogenic assays, IL13-PE38QQR demonstrated significant antitumor activity in a human epidermoid carcinoma xenograft model. Normal human umbilical vein-derived endothelial, lymphoid, and bone marrow precursor cells expressed low levels of IL-13 receptors, and IL-13 toxin was not cytotoxic to them. Thus, IL-13 receptor on AIDS-KS cells may represent a novel plasma membrane protein(s) that could be utilized to target therapeutic agents. C1 NIH, LAB MOL TUMOR BIOL,DIV CELLULAR & GENE THERAPIES, CTR BIOL EVALUAT & RES,FOOD & DRUG ADM, BETHESDA, MD 20892 USA. UNIV SO CALIF, SCH MED, LOS ANGELES, CA 90033 USA. NCI, MOL BIOL LAB, DIV BASIC SCI, BETHESDA, MD 20892 USA. PENN STATE UNIV, COLL MED, DIV NEUROSURG, HERSHEY, PA 17033 USA. PENN STATE UNIV, MILTON S HERSHEY MED CTR, HERSHEY, PA 17033 USA. NR 26 TC 76 Z9 78 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB PY 1997 VL 3 IS 2 BP 151 EP 156 PG 6 WC Oncology SC Oncology GA WY366 UT WOS:A1997WY36600002 PM 9815666 ER PT J AU Klein, J Bailey, B McMartin, KI Morris, P Koren, G AF Klein, J Bailey, B McMartin, KI Morris, P Koren, G TI Transplacental pharmacokinetics of cocaine (C) and benzoylecgonine (BZE) in plasma and hair of rhesus monkeys. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 HOSP SICK CHILDREN,DIV CLIN PHARMACOL,TORONTO,ON M5G 1X8,CANADA. US FDA,DIV NEUROTOX,NAT CENT TOX RES,JEFFERSON,AR. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1997 VL 61 IS 2 BP OIII2 EP OIII2 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ684 UT WOS:A1997WJ68400339 ER PT J AU Donahue, SR Collins, JM Flockhart, DA Abernethy, DR Trapnell, CB AF Donahue, SR Collins, JM Flockhart, DA Abernethy, DR Trapnell, CB TI Thalidomide pharmacokinetics do not change with chronic administration SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 GEORGETOWN UNIV,WASHINGTON,DC. US FDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1997 VL 61 IS 2 BP PIV89 EP PIV89 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ684 UT WOS:A1997WJ68400391 ER PT J AU Fadiran, EO Miller, R Ludden, T Karkowsky, A Parekh, A Ferry, J AF Fadiran, EO Miller, R Ludden, T Karkowsky, A Parekh, A Ferry, J TI Population pharmacokinetics (PK) pharmacodynamics (PD) of minoxidil (MNX). SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. UNIV NEBRASKA,MED CTR,DEPT PHARM SCI,OMAHA,NE 68198. UPJOHN CO,UPJOHN LABS,KALAMAZOO,MI 49001. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1997 VL 61 IS 2 BP PII46 EP PII46 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ684 UT WOS:A1997WJ68400273 ER PT J AU Klecker, RW Collins, JM AF Klecker, RW Collins, JM TI Stereo-selective metabolism of fenoldopam and its metabolites in human liver microsomes, cytosol and slices. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,CLIN PHARMACOL LAB,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1997 VL 61 IS 2 BP PII59 EP PII59 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ684 UT WOS:A1997WJ68400286 ER PT J AU Kramer, ED Longmire, AW Ma, ZJ Winchell, CJ Wright, C Scheinbaum, ML AF Kramer, ED Longmire, AW Ma, ZJ Winchell, CJ Wright, C Scheinbaum, ML TI Nicotine replacement and myocardial infarction SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1997 VL 61 IS 2 BP PI101 EP PI101 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ684 UT WOS:A1997WJ68400211 ER PT J AU Li, CQ Longmire, AW Kramer, ED Wright, C Rockville, FDA AF Li, CQ Longmire, AW Kramer, ED Wright, C Rockville, FDA TI Doses of nicotine replacement therapy (NRT) SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1997 VL 61 IS 2 BP PI100 EP PI100 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ684 UT WOS:A1997WJ68400210 ER PT J AU Lockwood, PA Miller, R Mandema, JW Butler, J Devane, J AF Lockwood, PA Miller, R Mandema, JW Butler, J Devane, J TI A PK/PD model for pain relief (PR) following a single dose of two NSAID formulations with different in vivo release rates SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. STANFORD UNIV,STANFORD,CA 94305. ELAN CORP,ATHLONE,IRELAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1997 VL 61 IS 2 BP PI70 EP PI70 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ684 UT WOS:A1997WJ68400070 ER PT J AU Mehta, MU Lesko, LJ AF Mehta, MU Lesko, LJ TI A survey of clinical pharmacology (CP) and biopharmaceutics (BP) studies submitted in NDAS during the period of October 1994 to September 1995. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 FDA,OFF CLIN PHARMACOL & BIOPHARMACEUT,CTR DRUG EVALUAT & RES,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1997 VL 61 IS 2 BP PII5 EP PII5 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ684 UT WOS:A1997WJ68400117 ER PT J AU Pradhan, RS AF Pradhan, RS TI Role of interoccasion variation in estimation of bioequivalence: A Bayesian approach SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,OCPB,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1997 VL 61 IS 2 BP PII85 EP PII85 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ684 UT WOS:A1997WJ68400195 ER PT J AU Spyker, DA Harvey, ED Harvey, BE Harvey, AM Rumack, BH Peck, CC Atkinson, AJ Woosley, RL Abernethy, DR Cantilena, LR AF Spyker, DA Harvey, ED Harvey, BE Harvey, AM Rumack, BH Peck, CC Atkinson, AJ Woosley, RL Abernethy, DR Cantilena, LR TI Assessment of clinical pharmacology information (CPI) in drug labeling. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 FDA,ROCKVILLE,MD. BAYSTATE MED CTR,SPRINGFIELD,MA. MED ECON INC,DENVER,CO. GEORGETOWN UNIV,WASHINGTON,DC. USUHS,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1997 VL 61 IS 2 BP PII4 EP PII4 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ684 UT WOS:A1997WJ68400116 ER PT J AU Whitehurst, V Alleva, F Zhang, J Vick, J AF Whitehurst, V Alleva, F Zhang, J Vick, J TI A unique model for studying pulmonary airway resistance and cardiovascular changes in genetically prone ''asthmatic rats'' SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,DPDP,ODEII,CDER,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1997 VL 61 IS 2 BP PIV49 EP PIV49 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ684 UT WOS:A1997WJ68400370 ER PT J AU Winchell, CJ Wright, C Burke, L Kramer, ED Longmire, AW Scheinbaum, ML AF Winchell, CJ Wright, C Burke, L Kramer, ED Longmire, AW Scheinbaum, ML TI Long-term abstinence in users of OTC nicotine replacement SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1997 VL 61 IS 2 BP PI103 EP PI103 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ684 UT WOS:A1997WJ68400213 ER PT J AU Fitzsimmons, ME Collins, JM AF Fitzsimmons, ME Collins, JM TI Selective biotransformation of the human immunodeficiency virus protease inhibitor saquinavir by human small-intestinal cytochrome P4503A4 - Potential contribution to high first-pass metabolism SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID HUMAN-LIVER CYTOCHROME-P-450; HUMAN HEPATIC MICROSOMES; ELECTROCARDIOGRAPHIC PHARMACODYNAMICS; TERFENADINE METABOLISM; CYCLOSPORINE; OXIDATION; PHARMACOKINETICS; HYDROXYLATION; FURAFYLLINE; RO-31-8959 AB Saquinavir is a HIV1 protease inhibitor used in the treatment of patients with acquired immunodeficiency syndrome, but its use is limited by low oral bioavailability. The potential of human intestinal tissue to metabolize saquinavir was assessed in 17 different human small-intestinal microsomal preparations. Saquinavir was metabolized by human small-intestinal microsomes to numerous mono- and dihydroxylated species with K-M values of 0.3-0.5 mu M. The major metabolites M-2 and M-7 were single hydroxylations on the octahydro-2-(1H)-isoquinolinyl and (1,1-dimethylethyl)amino groups, respectively. Ketoconazole and troleandomycin, selective inhibitors of cytochrome P4503A4 (CYP3A4), were potent inhibitors for all oxidative metabolites of saquinavir. The cytochrome P450-selective inhibitors furafylline, fluvoxamine, sulfaphenazole, mephenytoin, quinidine, and chlorzoxazone had little inhibitory effect. All saquinavir metabolites were highly correlated with testosterone 6 beta-hydroxylation and with each other. Human hepatic microsomes and recombinant CYP3A4 oxidized saquinavir to the same metabolic profile observed with human small-intestinal microsomes. Indinavir, a potent HIV protease inhibitor and a substrate for human hepatic CYP3A4, was a comparatively poor substrate for human intestinal microsomes and inhibited the oxidative metabolism of saquinavir to all metabolites with a K-l of 0.2 mu M. In addition, saquinavir inhibited the human, small-intestinal, microsomal CYP3A4-dependent detoxication pathway of terfenadine to its alcohol metabolite with a K-l value of 0.7 mu M. These data indicate that saquinavir is metabolized by human intestinal CYP3A4, that this metabolism may contribute to its poor oral bioavailability, and that combination therapy with indinavir or other protease inhibitors may attenuate its low relative bioavailability. RP Fitzsimmons, ME (reprint author), US FDA,DIV CLIN PHARMACOL RES,CTR DRUG EVALUAT & RES,LAB CLIN PHARMACOL,4 RES COURT,ROOM 311,ROCKVILLE,MD 20850, USA. NR 44 TC 202 Z9 202 U1 3 U2 7 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 FEB PY 1997 VL 25 IS 2 BP 256 EP 266 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WH293 UT WOS:A1997WH29300016 PM 9029057 ER PT J AU Primus, TM Tawara, JN Johnston, JJ Cummings, JL Volz, SA Goodall, MJ Hurlbut, DB Griffin, DL Turnipseed, S AF Primus, TM Tawara, JN Johnston, JJ Cummings, JL Volz, SA Goodall, MJ Hurlbut, DB Griffin, DL Turnipseed, S TI Identification of degradation products of the avicide 3-chloro-p-toluidine hydrochloride in Louisiana rice fields SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LA English DT Article ID 3,4-DICHLOROANILINE AB An investigation of the mig ration of 3-chloro-p-toluidine hydrochloride (CPTH) on treated rice baits to soils in Louisiana rice fields was completed. The persistence of free CPTH in these soils was evaluated with field and laboratory experiments. These soils were also screened for the presence of CPTH degradation products. Soils treated with CPTH-fortified rice bait and aqueous solutions of CPTH were exposed under actual field conditions for a 13-day period. Control soil samples were also treated with CPTH and incubated under simulated field conditions in an environmental chamber. Soil samples were then screened for CPTH residues and degradation products by HPLC. Possible degradation products were identified with the assistance of LC/MS and GC/MS. The concentration of 2% CPTH on treated rice baits placed in Louisiana rice fields decreased by approximately 55% over 3 days. Several CPTH degradation products were detected in rice field soils, treated with an aqueous solution of CPTH, at concentrations too low for spectral identification. Multiple CPTH degradation products were detected in a laboratory soil metabolism study including the previously unreported compounds, cis- and trans-azo-3-chloro-p-toluidine (azo-CPT). Neither azo compound was detected in soils collected from fields that were treated with CPTH rice baits. C1 FDA,ANIM DRUGS RES CTR,DENVER FED CTR,DENVER,CO 80225. RP Primus, TM (reprint author), US ANIM & PLANT HLTH INSPECT SERV,DENVER WILDLIFE RES CTR,USDA,DENVER FED CTR,BLDG 16,DENVER,CO 80225, USA. NR 23 TC 4 Z9 4 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0013-936X J9 ENVIRON SCI TECHNOL JI Environ. Sci. Technol. PD FEB PY 1997 VL 31 IS 2 BP 346 EP 350 DI 10.1021/es9600789 PG 5 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA WG343 UT WOS:A1997WG34300027 ER PT J AU Iatropoulos, MJ WilliamS, GM Abdo, KM Kari, FW Hart, RW AF Iatropoulos, MJ WilliamS, GM Abdo, KM Kari, FW Hart, RW TI Mechanistic studies on genotoxicity and carcinogenicity of salicylazosulfapyridine an anti-inflammatory medicine SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY LA English DT Article DE genotoxicity; carcinogenicity; salicylazosulfapyridine (SASP); toxicity testing methodology; risk assessment; rodent human extrapolation ID BONE-MARROW ERYTHROCYTES; ULCERATIVE-COLITIS; COLORECTAL-CANCER; MICRONUCLEUS TEST; DEFICIENT RATS; BOWEL-DISEASE; DNA DAMAGE; SULFASALAZINE; INVITRO; METABOLITES AB Salicylazosulfapyridine (SASP), which has been in clinical use for over 50 years, was reported by the National Toxicology Program to increase rat (F344 strain) urinary bladder and mouse (B6C3F(1) hybrid) liver tumors under ad libitum (AL) feeding conditions, while under a feed restriction (FR) regimen, these tumors were not increased. The present investigations were undertaken to assess the implications of these results for the safety of SASP in humans. SASP and its 2 major metabolites, 5-aminosalicylic acid (ASA) and sulfapyridine (SP) were tested for in vivo induction of micronuclei in mouse bone marrow cells with or without prefolic treatment and for in vivo formation of DNA adducts in rat and mouse liver and urinary bladder. None exhibited mutagenicity or DNA reactivity. SASP and SP have induced sister chromatid exchanges and micronuclei (MN) in cultured human lymphocytes in the absence of liver activation enzymes and in B6C3F, mice (but not in rats) MN in bone marrow and peripheral RBC. Treatment with folate reduces the frequency of MN. Perhaps the short (28 days) RBC lifespan in mouse underlies the sensitivity of this species. Thus, SASP without folate supplementation is an aneuploidogen. In a 2-year study in AL fed SASP-treated (high dose 337.5 mg/kg) rats, urinary pH was increased and urinary specific gravity was reduced at 60 weeks. At the end, this SASP group showed urothelial hyperplasia and papillomas in the urinary bladders of male rats primarily. In the FR high dose SASP group, the hyperplasia was reduced from 82 % to 14 %. At the end of 2 years, the incidence of multiorgan leukemia was reduced in both AL and FR high dose SASP groups. Thus, SASP caused intraluminal bladder changes in the rat (especially males) consisting of chronic urothelial stimulation, concretions, hyperplasia which resulted in neoplasia. In the mouse, because of species differences in liver ratios (mouse > rat) and, increasing (3 times higher) liver perfusion in the mouse, compared to the rat, there was hepatocellular toxicity and resulting preneoplasia and neoplasia within 2 years. These findings occurred in all AL SASP groups (flat curve without dose response); but were reduced under FR conditions. In this species, the multiorgan lymphoma incidence was reduced in both AL and FR high dose SASP groups. Thus, SASP and its major metabolites are not genotoxic. Folate deficiency associated with SASP administration is probably responsible for aneuploidy in lymphocytes and erythrocytes. SASP does not induce neoplasia directly in either livers, urinary bladders or other organs. Accordingly, SASP is judged to pose no carcinogenic risk to humans. C1 NIEHS,RES TRIANGLE PK,NC 27709. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RP Iatropoulos, MJ (reprint author), AMER HLTH FDN,1 DANA RD,VALHALLA,NY 10595, USA. NR 78 TC 8 Z9 9 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0940-2993 J9 EXP TOXICOL PATHOL JI Exp. Toxicol. Pathol. PD FEB PY 1997 VL 49 IS 1-2 BP 15 EP 28 PG 14 WC Pathology; Toxicology SC Pathology; Toxicology GA WP789 UT WOS:A1997WP78900003 PM 9085070 ER PT J AU Tedeschi, V Akatsuka, T Shih, JWK Battegay, M Feinstone, SM AF Tedeschi, V Akatsuka, T Shih, JWK Battegay, M Feinstone, SM TI A specific antibody response to HCV E2 elicited in mice by intramuscular inoculation of plasmid DNA containing coding sequences for E2 SO HEPATOLOGY LA English DT Article ID HEPATITIS-C VIRUS; HYPERVARIABLE REGION; PROTECTIVE IMMUNITY; GLYCOPROTEIN; ENVELOPE; INFECTION; PROTEINS; VACCINATION; CHIMPANZEES; EPITOPES AB As the chimpanzee, the only reliable animal model for hepatitis C virus (HCV) infection, is impractical for early stage testing of HCV vaccine candidates, we have evaluated the immune response in mice to an experimental plasmid based HCV vaccine, We used this system because DNA vaccines can be rapidly constructed without the necessity of large scale protein production and purification, In this preliminary study we tested the immune response in mice to HCV envelope glycoprotein, E2, induced by a eukaryotic expression plasmid, Protein expression was monitored by immunofluorescence in transfected tissue culture cells, Each mouse was inoculated intramuscular with 100 mu g plasmid DNA and some mice were boosted after 5 weeks, Among 12 BALB/C mice inoculated, 10 developed antibody to E2 by the second week, The antibody levels increased steadily before reaching a plateau in mice receiving the booster, but in the nonboosted mice the antibody declined over time, The serum from one mouse was tested against a series of overlapping peptides covering most of E2. This serum contained antibodies recognizing two distinct epitopes beginning at amino acid 57 and amino acid 113 but no antibody was directed against peptides representing the hypervariable region of E2, antibody to which is thought to be important in HCV neutralization, We have shown that the use of plasmid based vaccines can induce a specific immune response in mice against HCV antigens, This system should be useful as the first step in vaccine development. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,HEPATITIS VIRUSES LAB,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT TRANSFUS MED,BETHESDA,MD 20892. NIDDKD,LIVER DIS SECT,BETHESDA,MD 20892. NR 29 TC 33 Z9 34 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 1997 VL 25 IS 2 BP 459 EP 462 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WG103 UT WOS:A1997WG10300034 PM 9021964 ER PT J AU Huntley, JS Sathyamoorthy, V Hall, RH Hall, AC AF Huntley, JS Sathyamoorthy, V Hall, RH Hall, AC TI Membrane attack induced by HlyA, a pore-forming toxin of Vibrio cholerae SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Article DE HlyA; Vibrio cholerae; El Tor; bacterial toxin; haemolysis; red blood cell ID BIOTYPE-EL-TOR; THERMOSTABLE DIRECT HEMOLYSIN; CYTOLYSIN; NON-O1; PARAHAEMOLYTICUS; PURIFICATION; SEQUENCE; GENE; O1 AB Determining the activity of purified toxins has generally provided the basis for establishing their role in the host-pathogen relationship. The bacterial genus Vibrio produces a number of exotoxins in addition to cholera toxin, including haemolysin A (HlyA; Vibrio cholerae) and thermostable direct haemolysin (TDH; Vibrio parahaemolyticus), both of which possess membrane-targeting cytolytic activity. The action of HlyA has been analyzed using protocols previously applied to TDH: lysis and flux experiments on human erythrocytes showed that HlyA similarly causes lysis after cell swelling (by colloid osmosis) due to an elevation of cation permeability. However, kinetic measurements of flux, haemolysis and cation selectivity showed that HlyA and TDH form pores with distinct and characteristic features. C1 UNIV EDINBURGH,SCH MED,DEPT PHYSIOL,EDINBURGH EH8 9AG,MIDLOTHIAN,SCOTLAND. US FDA,CTR FOOD SAFETY & APPL NUTR,DIV VIRULENCE ASSESSMENT,WASHINGTON,DC 20204. UNIV OXFORD,PHYSIOL LAB,OXFORD OX1 3PT,ENGLAND. OI Huntley, James/0000-0003-1826-4007 FU Wellcome Trust NR 19 TC 3 Z9 3 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0144-5952 J9 HUM EXP TOXICOL JI Hum. Exp. Toxicol. PD FEB PY 1997 VL 16 IS 2 BP 101 EP 105 PG 5 WC Toxicology SC Toxicology GA WJ022 UT WOS:A1997WJ02200005 PM 9051414 ER PT J AU Moore, DF Rosenfeld, MR Gribbon, PM Winlove, CP Tsai, CM AF Moore, DF Rosenfeld, MR Gribbon, PM Winlove, CP Tsai, CM TI Alpha-1-acid (AAG, orosomucoid) glycoprotein: Interaction with bacterial lipopolysaccharide and protection from sepsis SO INFLAMMATION LA English DT Article ID TUMOR-NECROSIS-FACTOR; C-REACTIVE PROTEIN; ENDOTOXIN; TOXICITY; SEQUENCE; BINDING AB In the acute phase response to a variety of insults a rise in the levels of the acute phase proteins, including elevations of serum cui acid glycoprotein (AAG) occurs. The physiological role of AAG is unknown, however, the time course of AAG production in the acute phase response together with its strong affinity for basic compounds suggests that AAG may function as an immune modulator to bind both exogenous and endogenous inflammatory mediators. Using E. coli lipopolysaccharide (LPS), an initiator of the acute inflammatory response associated with septic shock, we demonstrate that AAG-LPS complexes can activate mouse macrophages in vitro. In a mouse animal model of sepsis, AAG was shown to protect against meningococcal endotoxin. To pursue the mechanism of AAG action we demonstrated that AAG interacts directly with LPS using dynamic light scattering particle sizing and particle mobility. We also determined the enthalpy of interaction of AAG and LPS and showed that AAG leads to agglutination of LPS impregnated rabbit red blood cells. These studies suggest that AAG may function as an immune-modulator in the acute phase response, possibly by counter-regulating the activity of macrophage proinflammatory cytokines. C1 MEM SLOAN KETTERING CANC CTR,DEPT NEUROL,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,COTZIAS LAB NEUROONCOL,NEW YORK,NY 10021. UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,CTR BIOL & MED SYST,PHYSIOL FLOW STUDIES GRP,LONDON SW7 2BX,ENGLAND. NIH,CTR BIOL EVALUAT & RES,LAB BACTERIAL POLYSACCHARIDES,BETHESDA,MD 20892. RP Moore, DF (reprint author), CORNELL UNIV,MED CTR,DEPT NEUROL,NEW YORK,NY 10021, USA. NR 28 TC 43 Z9 46 U1 0 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0360-3997 J9 INFLAMMATION JI Inflammation PD FEB PY 1997 VL 21 IS 1 BP 69 EP 82 DI 10.1023/A:1027342909423 PG 14 WC Cell Biology; Immunology SC Cell Biology; Immunology GA XC494 UT WOS:A1997XC49400007 PM 9179623 ER PT J AU Ferguson, SA Holson, RR AF Ferguson, SA Holson, RR TI Methylazoxymethanol-induced micrencephaly in the Brown Norway strain: Behavior and brain weight SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE methylazoxymethanol; micrencephaly; strain differences; Brown Norway ID DIFFERENT GESTATIONAL DAYS; RAT STRAINS; PRENATAL EXPOSURE; BIOSYNTHETIC-ENZYMES; RESIDENTIAL MAZE; POSTNATAL-GROWTH; LABORATORY RAT; STRESS; HYPERACTIVITY; NEUROTOXICITY AB A single injection of 20 mg/kg methylazoxymethanol acetate (MAM) on gestational day 14 in Brown Norway rats produced micrencephalic offspring (whole brain approximate to 65% of control). Despite the micrencephaly, MAM-induced alterations in behavior assessed here were relatively mild. The MAM-treated rats exhibited increased activity under darkened conditions in a complex maze and marginally increased activity after a challenge of methamphetamine. Open field activity, running wheel activity, and emergence behavior using a light/dark apparatus were not significantly affected. Compared with a similar study of Sprague-Dawley micrencephalics [Ferguson S. A., Racey F. D., Paule M. G. and Holson R. R. (1993) Behavioral effects of methyloxymethanol-induced microencephaly. Behav. Neurosci. 107, 1-10], frontal cortex and striatum weights were more reduced in Brown Norway micrencephalics. The MAM-induced behavioral alterations in the Brown Norway strain may have appeared attenuated compared to alterations shown by MAM-treated Sprague-Dawley rats due to differences in baseline behavior between these two strains. Compared to control Sprague-Dawley rats in the previous study, control Brown Norway rats were more active in the open field and running wheels, but less active in the complex maze, exhibiting little to no learning. Emergence tests indicated increased dark preference in Brown Norway rats. Baseline behavior (increased activity and light shyness) of control Brown Norway rats was similar to that of MAM-treated Sprague-Dawley rats; a potential confound in the detection of behavioral effects of a compound. These findings emphasize the effects that strain selection may have on the outcome and interpretation of toxicological/teratological studies. RP Ferguson, SA (reprint author), NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,HFT-132,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 45 TC 13 Z9 14 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 FEB PY 1997 VL 15 IS 1 BP 75 EP 86 PG 12 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA WR765 UT WOS:A1997WR76500009 PM 9099619 ER PT J AU Komolprasert, V Lawson, AR AF Komolprasert, V Lawson, AR TI Considerations for reuse of poly(ethylene terephthalate) bottles in food packaging: Migration study SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE reused PETE; migration; residual contaminants; food simulant ID DEGRADATION KINETICS; PESTICIDES; ORGANOPHOSPHORUS; WATERS AB Experiments were performed to evaluate the significance of potential contamination of postconsumer poly(ethylene terephthalate) (PETE) on the reuse of such material as food packaging. The protocol in the FDA document Points to Consider for the Use of Recycled Plastics in Food Packaging: Chemistry Considerations (FDA, 1992) that are routinely employed to evaluate recycling processes for removal of potential contaminants were used. Two-liter PETE bottles were contaminated separately with benzene, butyric acid, malathion, and lindane at 40 degrees C for 2 weeks, rinsed, dried, and cut into small chips. The contaminated chips were washed at 73 degrees C, dried with an IR lamp, and extracted using 8% aqueous ethanol solution at 49+/-1 degrees C for 30 days. After 30 days, approximately 60% of the benzene, 30% of the butyric acid, and 30% of the Lindane had migrated from the contaminated chips into the 8% ethanol solution, but no measurable concentration of malathion was observed. C1 NATL CTR FOOD SAFETY & TECHNOL,SUMMIT ARGO,IL 60501. RP Komolprasert, V (reprint author), US FDA,DIV FOOD PROC & PACKAGING,6502 S ARCHER RD,SUMMIT ARGO,IL 60501, USA. NR 11 TC 8 Z9 8 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 FEB PY 1997 VL 45 IS 2 BP 444 EP 448 DI 10.1021/jf9603801 PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA WJ269 UT WOS:A1997WJ26900026 ER PT J AU Schmitt, MP AF Schmitt, MP TI Utilization of host iron sources by Corynebacterium diphtheriae: Identification of a gene whose product is homologous to eukaryotic heme oxygenases and is required for acquisition of iron from heme and hemoglobin SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DNA-SEQUENCE ANALYSIS; TOXIN REPRESSOR DTXR; ESCHERICHIA-COLI; TRANSPORT-SYSTEM; BREVIBACTERIUM-LACTOFERMENTUM; NUCLEOTIDE-SEQUENCE; PATHOGENIC BACTERIA; MOLECULAR-CLONING; VIBRIO-CHOLERAE; PROTEIN AB Corynebacterium diphtheriae was examined for the ability to utilize various host compounds as iron sources. C. diphtheriae C7(-) acquired iron from heme, hemoglobin, and transferrin. A siderophore uptake mutant of strain C7 was unable to utilize transferrin but was unaffected in acquisition of iron from heme and hemoglobin, which suggests that C. diphtheriae possesses a novel mechanism for utilizing heme and hemoglobin as iron sources. Mutants of C. diphtheriae and Corynebacterium ulcerans that are defective in acquiring iron from heme and hemoglobin were isolated following chemical mutagenesis and streptonigrin enrichment. A recombinant clone, pCD293, obtained from a C7(-) genomic plasmid library complemented several of the C. ulcerans mutants and three of the C. diphtheriae mutants. The nucleotide sequence of the gene (hmuO) required for complementation was determined and shown to encode a protein with a predicted mass of 24,123 Da. Sequence analysis revealed that HmuO has 33% identity and 70% similarity with the human heme oxygenase enzyme HO-1, Heme oxygenases, which have been well characterized in eukaryotes but have not been identified in prokaryotes, are involved in the oxidation of heme and subsequent release of iron from the heme moiety. It is proposed that the HmuO protein is essential for the utilization of heme as an iron source by C. diphtheriae and that the heme oxygenase activity of HmuO is involved in the release of iron from heme. This is the first report of a bacterial gene whose product has homology to heme oxygenases. RP Schmitt, MP (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,LAB BACTERIAL TOXINS,BLDG 29,ROOM 111,BETHESDA,MD 20892, USA. NR 57 TC 170 Z9 174 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD FEB PY 1997 VL 179 IS 3 BP 838 EP 845 PG 8 WC Microbiology SC Microbiology GA WE440 UT WOS:A1997WE44000036 PM 9006041 ER PT J AU Epstein, SL Lo, CY Misplon, JA Lawson, CM Hendrickson, BA Max, EE Subbarao, K AF Epstein, SL Lo, CY Misplon, JA Lawson, CM Hendrickson, BA Max, EE Subbarao, K TI Mechanisms of heterosubtypic immunity to lethal influenza A virus infection in fully immunocompetent, T cell-depleted, beta(2)-microglobulin-deficient, and J chain-deficient mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID A VIRUS; IMMUNOGLOBULIN-A; VACCINIA VIRUS; MONOCLONAL-ANTIBODIES; INTRACELLULAR NEUTRALIZATION; HETEROTYPIC IMMUNITY; MURINE INFLUENZA; EPITHELIAL-CELLS; INTERFERON-GAMMA; NUCLEOPROTEIN AB Immunity that is cross-protective between different influenza A virus subtypes (termed heterosubtypic immunity) can be demonstrated readily in some animals but only rarely in humans. Induction of heterosubtypic immunity in humans by vaccines would provide public health benefit, perhaps offering some protection against pandemics or other new influenza A strains. Therefore, we studied mechanisms mediating heterosubtypic immunity in mice. Immunization with either A/H1N1 or A/H3N2 virus protected mice against mortality following heterosubtypic challenge while providing modest reductions in lung virus titers. No cross-protection was seen with distantly related type B influenza virus. Depletion of CD4(+) or CD8(+) T cells or both around the time of challenge had no significant effect on survival, indicating that these cells are not required at the effector stage. beta(2)-microglobulin knockout mice could be protected readily against heterosubtypic challenge, confirming that class I-restricted T cells are not required. In beta(2)-microglobulin -/- mice, depletion of CD4(+) T cells partially abrogated heterosubtypic immunity, showing that they play a role in these mice. Passive transfer of Abs to naive recipients protected against subsequent challenge with homologous but not heterosubtypic virus. Because a role for secretory Abs has been suggested, we studied dependence on the I chain, which is required for polymeric Ig receptor-mediated IgA transport. I chain knockout mice were readily protected by heterosubtypic immunity, indicating that polymeric Ig receptor-mediated transport is not required. Better understanding of heterosubtypic immunity should be valuable in analyzing new vaccines, including peptide and DNA vaccines, intended to induce broadly cross-reactive immunity. C1 US FDA, CTR BIOL EVALUAT & RES, DIV CELLULAR & GENE THERAPIES, MOL IMMUNOL LAB, BETHESDA, MD 20892 USA. NIAID, INFECT DIS LAB, NIH, BETHESDA, MD 20892 USA. UNIV CHICAGO, WYLER CHILDRENS HOSP, SECT PEDIAT INFECT DIS, CHICAGO, IL 60637 USA. US FDA, CTR BIOL EVALUAT & RES, DIV HEMATOL PROD, BETHESDA, MD 20892 USA. NR 60 TC 109 Z9 114 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1997 VL 158 IS 3 BP 1222 EP 1230 PG 9 WC Immunology SC Immunology GA WE020 UT WOS:A1997WE02000025 PM 9013963 ER PT J AU Taffs, RE Chernokhvostova, YV Dragunsky, EM Nomura, T Hioki, K Beuvery, EC Fitzgerald, EA Levenbook, IS Ash, DM AF Taffs, RE Chernokhvostova, YV Dragunsky, EM Nomura, T Hioki, K Beuvery, EC Fitzgerald, EA Levenbook, IS Ash, DM TI Inactivated poliovirus vaccine protects transgenic poliovirus receptor mice against type 3 poliovirus challenge SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Symposium on Replacement, Reduction and Refinement of Animal Experiments in the Development and Control of Biological Products CY NOV 02-04, 1994 CL LANGEN, GERMANY SP Int Assoc Biol Standardizat, European Ctr Validat Alternat Methods, Ispra, Paul Ehrlich Inst, Langen, Natl Inst Public Hlth & Environm Protect ID NEUROVIRULENCE; POTENCY; MODEL AB Transgenic (Tg) mice expressing the human poliovirus receptor (PVR) were vaccinated with inactivated poliovirus vaccine (IPV) and evaluated for induced immunity against type 3 poliomyelitis. One injection of monovalent type 3 IPV elicited protective immunity against wild-type poliovirus, In contrast, 2 injections of trivalent IPV were required for protection. Neutralizing antibody response and protection were vaccine dose-dependent. Administration of polio-immune mouse plasma protected unimmunized mice, demonstrating that neutralizing antibody was sufficient for immunity. IPV heated to remove its D antigen component did not induce protection in Tg PVR mice, IPV derived from a wild-type poliovirus strain gave better protection against wild-type viral challenge than IPV derived from an attenuated poliovirus strain, The newly developed Tg PVR mouse-protection test may be useful in evaluating existing IPV potency tests and for attempts to improve formulations of trivalent IPV or combined vaccines for childhood immunization schedules. C1 US FDA,ROCKVILLE,MD 20857. CENT INST EXPT ANIM,KAWASAKI,KANAGAWA,JAPAN. RIJKSINST VOLKSGEZONDHEID MILIEUHYG,BILTHOVEN,NETHERLANDS. NR 15 TC 10 Z9 10 U1 2 U2 3 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 FEB PY 1997 VL 175 IS 2 BP 441 EP 444 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WF063 UT WOS:A1997WF06300027 PM 9203668 ER PT J AU Patriarca, PA Sutter, RW Oostvogel, PM AF Patriarca, PA Sutter, RW Oostvogel, PM TI Outbreaks of paralytic poliomyelitis, 1976-1995 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Review ID ORAL POLIOVIRUS VACCINE; SOUTH-AFRICA; DEVELOPING-COUNTRIES; INFECTIOUS-DISEASES; CLINICAL EFFICACY; CASE CONFIRMATION; WILD POLIOVIRUS; NATAL KWAZULU; ERADICATION; EPIDEMIC AB During 1976-1995, 48 outbreaks of paralytic poliomyelitis with a cumulative total of similar to 17,000 cases were reported worldwide. Outbreaks occurred on most continents, affected from 0.1 to 52 persons per 100,000 total population (median, 4.4), lasted 2-25 months (median, 7), typically involved unvaccinated or inadequately vaccinated subgroups within highly immunized communities, and were primarily caused by poliovirus type 1 (74%). Cases in developing countries occurred predominantly among children <2 years of age, while those in industrialized countries tended to occur in older persons who had escaped natural infection earlier in life and who had not been vaccinated or had received poliovirus vaccine of inadequate potency. Partial genomic sequencing studies indicated that at least 15 outbreaks resulted from importation of wild polioviruses, primarily from the Indian subcontinent. These findings illustrate the potential for wide dissemination of wild poliovirus infection and underscore the critical need for maintaining high levels of immunity in all countries and for more aggressive vaccination efforts in areas in which polio is endemic. C1 CTR DIS CONTROL & PREVENT,NATL IMMUNIZATION PROGRAM,ATLANTA,GA. NATL INST PUBL HLTH & ENVIRONM PROTECT,VIROL LAB,NL-3720 BA BILTHOVEN,NETHERLANDS. RP Patriarca, PA (reprint author), US FDA,CTR BIOL EVALUAT & RES,HRM 445,1401 ROCKVILLE PIKE,BETHESDA,MD 20852, USA. NR 116 TC 51 Z9 51 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB PY 1997 VL 175 SU 1 BP S165 EP S172 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WG180 UT WOS:A1997WG18000029 PM 9203711 ER PT J AU Chou, MW Chen, W AF Chou, MW Chen, W TI Food restriction reduces aflatoxin B-1 (AFB(1))-DNA adduct formation, AFB(1)-glutathione conjugation, and DNA damage in AFB(1)-treated male F344 rats and B6C3F(1) mice SO JOURNAL OF NUTRITION LA English DT Article DE rats; mice; food restriction; aflatoxin B-1-DNA adducts; aflatoxin B-1-glutathione conjugates ID DRUG-METABOLIZING-ENZYMES; HUMAN LIVER-MICROSOMES; CALORIC RESTRICTION; DIETARY RESTRICTION; MODIFYING ROLE; CARCINOGENESIS; OXIDATION; INVITRO; STERIGMATOCYSTIN; CYTOCHROME-P-450 AB The objective of this study was to examine effects of food restriction (FR) on the metabolic activation of aflatoxin B-1 (AFB(1)) in rats and mice, which are AFB(1)-sensitive and -resistant rodent species, respectively, Forty percent FR [60% of ad libitum (AL) food consumption] reduced the metabolic activation of AFB(1) in both rats and mice, causing formation of hepatic AFB(1)-DNA adducts to be 43% and 31% lower, respectively, The AFB(1)-DNA adduct 8,9-dihydro-8-(N-7-guanyl)-9-hydroxyaflatoxin B-1 (AFB(1)-N-7-Gua) was predominantly formed in rat liver DNA; the formation of the ring-open analogue of AFB(1)-N-7-Gua, AFB(1)-formamidopyrimidine (AFB(1)-FAP), was predominantly found in mouse liver DNA, In contrast to the in vivo results, the in vitro AFB(1)-DNA adduct formation mediated by the microsomes of liver, kidney or lung from FR-mice was greater than the formation of AFB(1)-DNA adducts mediated by the tissue microsomes from the AL-mice, Food restriction induced hepatic glutathione S-transferase (GST) activity, as measured by the formation of AFB(1)-glutathione conjugates (AFB(1)-SG), in both rats and mice; AFB(1)-SG was also formed in mouse kidney, Food restriction-induced GST activity assayed in an in vitro system, using [H-3]AFB(1)-8,9-epoxide and glutathione (GSH) as substrates, was also found when mouse kidney and lung cytosolic fractions were used, Food restriction inhibited the AFB(1)-induced DNA double strand breaks in mouse kidney, The reduction of levels of AFB(1)-DNA adduct formation in mouse kidney was comparable to the degree of AFB(1)-induced DNA strand breakages. The results of this study indicate that the metabolic activation of AFB(1) can be modulated by FR through the alteration of the formation of AFB(1)-DNA adducts and AFB(1)-SG conjugation, However, species and tissue specificities exist: regarding the metabolic activation of AFB(1). RP Chou, MW (reprint author), NATL CTR TOXICOL RES,DIV NUTR TOXICOL,JEFFERSON,AR 72079, USA. NR 41 TC 8 Z9 9 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 1997 VL 127 IS 2 BP 210 EP 217 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WK390 UT WOS:A1997WK39000003 PM 9039820 ER PT J AU Borga, O Borga, B AF Borga, O Borga, B TI Serum protein binding of nonsteroidal antiinflammatory drugs: A comparative study SO JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS LA English DT Article DE NSAIDs; protein binding; serum; unbound fraction; binding site; binding constant; HPLC; ultrafiltration ID EQUILIBRIUM DIALYSIS; DICLOFENAC SODIUM; SYNOVIAL-FLUID; PLASMA; FLURBIPROFEN; PHARMACOKINETICS; NAPROXEN; DISPOSITION; KINETICS; ALBUMIN AB The unbound fraction in serum, f(u), is a critical parameter in describing and understanding the pharmacokinetics of NSAIDs. We compared f(u), for 6 different NSAIDs using ultrafiltration of pooled serum at pH 7.4 and 24C. Measurements covered a wide concentration range in order to define binding affinity and number of binding sites. HPLC was used to measure drug concentrations in serum and ultrafiltrate. Direct injection of ultrafiltrate and serum (diluted 250x) permitted quantitation down to approximately 70 nM for most of the NSAIDs, i.e., approximately 15-20 ng/ml. Assuming binding only to albumin, the data were fitted to a model of two classes of binding sites with dissociation constants K1 and K2. The lowest K1 (highest affinity) was found with flurbiprofen, 0.0658 mu M, the highest with ketoprofen, 5.23 mu M, an 80-fold difference. At low drug concentrations, f(u) becomes virtually constant and approaches a lower limit, f(u)(min). The following f(u)(min) values were calculated: diclofenac 0.21%; fenoprofen 0.25%, flurbiprofen 0.022%, ketoprofen 0.52%, naproxen 0.039%, and tolmetin 0.37%. Thus the least bound NSAID, ketoprofen, had a value 24-fold that of the most highly bound, flurbiprofen. The NSAIDs also differed widely with regard to the extent of variation in f(u) within the range of therapeutic concentrations, and hence with regard to their potential as displacers of other drugs. C1 US FDA,CTR DRUG EVALUAT & RES,OFF CLIN PHARMACOL & BIOPHARMACEUT,ROCKVILLE,MD 20857. NR 38 TC 60 Z9 60 U1 1 U2 10 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 FEB PY 1997 VL 25 IS 1 BP 63 EP 77 DI 10.1023/A:1025719827072 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YC715 UT WOS:A1997YC71500004 PM 9353694 ER PT J AU Mossoba, MM McDonald, RE Roach, JAG Fingerhut, DD Yurawecz, MP Sehat, N AF Mossoba, MM McDonald, RE Roach, JAG Fingerhut, DD Yurawecz, MP Sehat, N TI Spectral confirmation of trans monounsaturated C-18 fatty acid positional isomers SO JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of American-Oil-Chemists-Society CY APR 28-MAY 01, 1996 CL INDIANAPOLIS, IN SP Amer Oil Chem Soc DE 4,4-dimethyl oxazoline (DMOX); direct deposition; trans double bonds; fatty acid methyl esters (FAME); gas chromatography; infrared spectroscopy; mass spectrometry; monounsaturated fatty acids; positional isomers ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; LOCATION AB The trans octadecenoic acid methyl ester isomers were obtained from a partially hydrogenated soybean oil sample and isolated by silver-ion high-performance liquid chromatography. The double bond configuration was confirmed to be trans by using gas chromatography-direct deposition-fourier transform infrared spectroscopy. The double bond positions for nine individual trans octadecenoic acid positional isomers were confirmed by gas chromatography-electron ionization mass spectrometry after derivatization to 2-alkenyl-4,4-dimethyloxazoline. These nine trans positional isomers were resolved on either one of the two polar 100% cyanopropylpolysiloxane 100-m capillary columns, SP 2560 and Cp-Sil 88, at an isothermal temperature of 140 degrees C. These nine isomers were confirmed to have double bonds at carbons C-8 through C-16. The pair of trans octadecenoic acid positional isomers with double bonds at C-13 and C-14 are reported for the first time to be resolved by gas chromatography. C1 US FDA,NATL CTR FOOD SAFETY & TECHNOL,OFF PLANT & DAIRY FOODS & BEVERAGES,SUMMIT ARGO,IL 60501. IIT,SUMMIT ARGO,IL 60501. US FDA,CTR FOOD SAFETY & APPL NUTR,OFF FOOD LABELING,WASHINGTON,DC 20204. RP Mossoba, MM (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,OFF GEN SCI SUPPORT,HFS-717,WASHINGTON,DC 20204, USA. NR 15 TC 36 Z9 36 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 FEB PY 1997 VL 74 IS 2 BP 125 EP 130 DI 10.1007/s11746-997-0156-3 PG 6 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA WJ717 UT WOS:A1997WJ71700010 ER PT J AU Regan, PM Margolin, AB AF Regan, PM Margolin, AB TI Development of a nucleic acid capture probe with reverse transcriptase-polymerase chain reaction to detect poliovirus in groundwater SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE groundwater; nucleic acid capture; poliovirus; reverse transcriptase-polymerase chain reaction (RT-PCR) ID HEPATITIS-A VIRUS; MAGNETIC BEADS; TAP WATER; ENTEROVIRUSES; AMPLIFICATION; HYBRIDIZATION; CDNA; DNA AB There is a need to develop a practical method for the detection of viral contaminates in water supplies. In this study, poliovirus was used as a model to develop a nucleic acid capture technique. This technique was used to recover viral RNA from concentrated groundwater samples. Poliovirus RNA was isolated using magnetic bead technology. A biotinylated oligonucleotide probe was hybridized to poliovirus-RNA in solution. Streptavidin coated magnetic beads were then added to isolate the RNA-oligonucleotide hybrid. The procedure allows for the recovery of viral RNA suitable for amplification by reverse transcription-polymerase chain reaction (RT-PCR). This nucleic acid capture system was effective in both concentrating, and purifying poliovirus RNA while removing environmental RT-PCR inhibitors. A detection sensitivity of one plaque forming unit (PFU) in 250 mu l of a concentrated environmental sample was routinely attained. This was the same detection level found with seeded purified water. It was shown that the sensitivity of nucleic acid capture RT-PCR was significantly greater than direct RT-PCR, when applied to environmental samples. The amplified product was sequenced to ensure specificity. Furthermore, this technique is rapid, reliable and can be readily adapted to detect other viral pathogens. Copyright (C) 1997 Elsevier Science B.V. C1 UNIV NEW HAMPSHIRE,DEPT MICROBIOL,DURHAM,NH 03824. RP Regan, PM (reprint author), US FDA,WINCHESTER ENGN & ANALYT CTR,WINCHESTER,MA 01890, USA. NR 18 TC 10 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD FEB PY 1997 VL 64 IS 1 BP 65 EP 72 DI 10.1016/S0166-0934(96)02141-6 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA WF110 UT WOS:A1997WF11000008 PM 9029531 ER PT J AU Kozak, SL Platt, EJ Madani, N Ferro, FE Peden, K Kabat, D AF Kozak, SL Platt, EJ Madani, N Ferro, FE Peden, K Kabat, D TI CD4, CXCR-4, and CCR-5 dependencies for infections by primary patient and laboratory-adapted isolates of human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID SOLUBLE CD4; ENVELOPE GLYCOPROTEIN; RECEPTOR-BINDING; TRANSMEMBRANE GLYCOPROTEIN; NEUTRALIZATION SENSITIVITY; MOLECULAR CLONES; LEUCINE ZIPPER; HUMAN-BRAIN; GP120; FUSION AB We have used a focal infectivity method to quantitatively analyze the CD4, CXCR-4, and CCR-5 dependencies for infections by diverse primary patient (PR) and laboratory-adapted (LA) isolates of human immunodeficiency virus type 1 (HIV-1). Infectivities of T-cell-tropic viruses were analyzed in a panel of HeLa CD4 cell clones that have distinct quantities of CD4 and in human astroglioma U87MG-CD4 cells that express a large quantity of CD4 and become highly susceptible to infection after transfection with a CXCR-4 expression vector. The latter analysis indicated that PR as well as LA T-cell-tropic viruses efficiently employ CXCR-4 as a coreceptor in an optimal human cell line that contains abundant CD4. Previous uncertainties regarding coreceptor usage by PR T-cell-tropic HIV-1 isolates may therefore have derived from the assay conditions. As reported previously, unrelated LA and PR T cell-tropic HIV-1 isolates differ in infectivities for the HeLa-CD4 clonal panel, with LA viruses infecting all clones equally and PR viruses infecting the clones in proportion to cellular CD4 quantities (D. Kabat, S. L. Kozak, K. Wherly, and B. Chesebro, J. Virol. 68:2570-2577, 1994). To analyze the basis for this difference, we used the HeLa CD4 panel to compare a molecularly cloned T-cell-tropic PR virus (ELI1) with six of its variants that grow to different extents in CD4-positive leukemic cell lines and that differ only at specific positions in their gp120 and gp41 envelope glycoproteins, All mutations in gp120 or gp41 that contributed to laboratory adaptation preferentially enhanced infectivity for cells that had little CD4 and thereby decreased the CD4 dependencies of the infections. There was a close correlation between abilities of T-cell-tropic ELI viruses to grow in an expanded repertoire of leukemic cell lines, the reduced CD4 dependencies of their infections of the HeLa-CD4 panel, and their sensitivities to inactivation by soluble CD4 (sCD4), Since all of the ELI viruses can efficiently use CXCR-4 as a coreceptor, we conclude that an increase in viral affinity for CD4 rather than a switch in coreceptor specificity is principally responsible for laboratory adaption of T cell-tropic HIV-1. Syncytium-inducing activities of the ELI viruses, especially when analyzed on cells with low amounts of CD4, were also highly correlated,vith their laboratory-adapted properties. Results with macrophage-tropic HIV-1 were strikingly different in both coreceptor and CD4 dependencies. When assayed in HeLa-CD4 cells transfected with an expression vector for CCR-5, macrophage-tropic HIV-1 isolates that had been molecularly cloned shortly after removal from patients were equally infectious for cells that had low or high CD4 quantities. Moreover, despite their substantial infectivities for cells that bad only a trace of CD4, macrophage-tropic isolates were relatively resistant to inactivation by sCD4, We conclude that T-cell-tropic PR viruses bind weakly to CD4 and preferentially infect cells that coexpress CXCR-4 and large amounts of CD4. Their laboratory adaptation involves corresponding increases in affinities for CD4 and in abilities to infect cells that have relatively little CD4, In contrast, macrophage-tropic HIV-1 appears to interact weakly with CD4 although it can infect cells that coexpress CCR-5 and small quantities of CD4. We propose that cooperative binding of macrophage-tropic HIV-1 onto CCR-5 and CD4 may enhance virus adsorption and infectivity for cells that have only a trace of CD4. C1 OREGON HLTH SCI UNIV,DEPT BIOCHEM & MOL BIOL,PORTLAND,OR 97201. US FDA,CTR BIOL EVALUAT & RES,LAB RETROVIRUS RES,BETHESDA,MD 20892. FU NCI NIH HHS [CA67358] NR 66 TC 210 Z9 210 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1997 VL 71 IS 2 BP 873 EP 882 PG 10 WC Virology SC Virology GA WC305 UT WOS:A1997WC30500003 PM 8995603 ER PT J AU Ellenberg, SS Rida, WN AF Ellenberg, SS Rida, WN TI HIV vaccines SO LANCET LA English DT Letter C1 NIAID,DIV AIDS,BETHESDA,MD 20892. RP Ellenberg, SS (reprint author), US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852, USA. NR 2 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 FEB 1 PY 1997 VL 349 IS 9048 BP 361 EP 361 DI 10.1016/S0140-6736(05)62865-6 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WF794 UT WOS:A1997WF79400063 PM 9024406 ER PT J AU Chen, SJ Wang, CH Fu, PP AF Chen, SJ Wang, CH Fu, PP TI A facile synthesis of 9-hydroxybenzo[a]pyrene SO ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL LA English DT Article ID METABOLITES; HYDROCARBONS; EPOXIDE RP Chen, SJ (reprint author), NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079, USA. NR 16 TC 3 Z9 3 U1 0 U2 0 PU ORGANIC PREP PROCEDURES INC PI NEWTON HIGHLANDS PA PO BOX 9, NEWTON HIGHLANDS, MA 02161 SN 0030-4948 J9 ORG PREP PROCED INT JI Org. Prep. Proced. Int. PD FEB PY 1997 VL 29 IS 1 BP 131 EP 134 PG 4 WC Chemistry, Organic SC Chemistry GA WH446 UT WOS:A1997WH44600007 ER PT J AU Berlin, CM McCarver, DG Notterman, DA Ward, RM Weismann, DN Wilson, GS Wilson, JT Bennett, DR Mulinare, J Hoskins, IA Kaufman, P Rieder, MJ Troendle, G Yaffe, SJ Cote, CJ Szefler, SJ Smolinske, SC AF Berlin, CM McCarver, DG Notterman, DA Ward, RM Weismann, DN Wilson, GS Wilson, JT Bennett, DR Mulinare, J Hoskins, IA Kaufman, P Rieder, MJ Troendle, G Yaffe, SJ Cote, CJ Szefler, SJ Smolinske, SC TI ''Inactive'' ingredients in pharmaceutical products: Update (subject review) SO PEDIATRICS LA English DT Review ID BIRTH-WEIGHT INFANTS; INDUCED HISTAMINE-RELEASE; BENZYL ALCOHOL TOXICITY; PROPYLENE-GLYCOL; BENZALKONIUM CHLORIDE; DOUBLE-BLIND; ADVERSE REACTIONS; CHILDHOOD ASTHMA; DRUG ADDITIVES; INTRAVENTRICULAR HEMORRHAGE AB Because of an increasing number of reports of adverse reactions associated with pharmaceutical excipients, in 1985 the Committee on Drugs issued a position statement(1) recommending that the Food and Drug Administration mandate labeling of over-the-counter and prescription formulations to include a qualitative list of inactive ingredients. However, labeling of inactive ingredients remains voluntary. Adverse reactions continue to be reported, although some are no longer considered clinically significant, and other new reactions have emerged. The original statement, therefore, has been updated and its information expanded. C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30333. US FDA,ROCKVILLE,MD 20857. NIH,BETHESDA,MD 20892. RP Berlin, CM (reprint author), AMER MED ASSOC,US PHARMACOPEIA,515 N STATE ST,CHICAGO,IL 60610, USA. NR 187 TC 82 Z9 84 U1 2 U2 8 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD FEB PY 1997 VL 99 IS 2 BP 268 EP 278 PG 11 WC Pediatrics SC Pediatrics GA WE302 UT WOS:A1997WE30200026 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 Hadler, S Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR Schwartz, B 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 Hadler, S Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR Schwartz, B TI Acellular pertussis vaccine: Recommendations for use as the initial series in infants and children SO PEDIATRICS LA English DT Article ID EFFICACY; TETANUS; TRIAL AB In 1991 and 1992, the US Food and Drug Administration approved two acellular pertussis vaccines combined with diphtheria and tetanus toxoids for use as the fourth and fifth doses after the initial three-dose primary series with the standard whole-cell pertussis vaccine administered at 2, 4, and 6 months of age. Recently completed trials of acellular pertussis vaccines conducted in Europe have documented the efficacy of these vaccines when administered as a primary series in infancy. Based on these studies, two acellular pertussis vaccines, Tripedia (Connaught Laboratories, Swiftwater, PA) and ACEL-IMUNE (Wyeth-Lederle Laboratories, Pearl River, NY), were licensed by the Food and Drug Administration for the initial three-dose series. Additional acellular pertussis vaccines are likely to be licensed for use in infants in the future. The recommendations in this statement supplement previous American Academy of Pediatrics guidelines for the use of acellular pertussis vaccines.(1-4) C1 US FDA,ROCKVILLE,MD 20857. NIH,BETHESDA,MD 20892. RP Halsey, NA (reprint author), CTR DIS CONTROL & PREVENT,ATLANTA,GA 30333, USA. NR 22 TC 20 Z9 21 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 FEB PY 1997 VL 99 IS 2 BP 282 EP 288 PG 7 WC Pediatrics SC Pediatrics GA WE302 UT WOS:A1997WE30200028 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 Breiman, R Hadler, SC Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR Schwartz, B McCracken, GH Kaplan, SL Jorgensen, JH 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 Breiman, R Hadler, SC Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR Schwartz, B McCracken, GH Kaplan, SL Jorgensen, JH TI Therapy for children with invasive pneumococcal infections SO PEDIATRICS LA English DT Article ID RESISTANT STREPTOCOCCUS-PNEUMONIAE; BETA-LACTAM ANTIBIOTICS; EXPERIMENTAL PENICILLIN-RESISTANT; HIGH-LEVEL PENICILLIN; SICKLE-CELL DISEASE; BACTERIAL-MENINGITIS; CEREBROSPINAL-FLUID; UNITED-STATES; ANTIMICROBIAL RESISTANCE; HAEMOPHILUS-INFLUENZAE AB This statement provides guidelines for therapy of children with serious infections possibly caused by Streptococcus pneumoniae. Resistance of invasive pneumococcal strains to penicillin, cefotaxime, and ceftriaxone has increased over the past few years. Reports of failures of cefotaxime or ceftriaxone in the treatment of children with meningitis caused by resistant S pneumoniae necessitates a revision of Academy recommendations. For nonmeningeal infections, modifications of the initial therapy need to be considered only for patients who are critically ill and those who have a severe underlying or potentially immunocompromising condition or patients from whom a highly resistant strain is isolated. Because vancomycin is the only antibiotic to which all S pneumoniae strains are susceptible, its use should be restricted to minimize the emergence of vancomycin-resistant organisms. Patients with probable aseptic (viral) meningitis should not be treated with vancomycin. These recommendations are subject to change as new information becomes available. C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30333. US FDA,ROCKVILLE,MD 20857. NIH,BETHESDA,MD 20892. NR 82 TC 115 Z9 121 U1 1 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD FEB PY 1997 VL 99 IS 2 BP 289 EP 299 PG 11 WC Pediatrics SC Pediatrics GA WE302 UT WOS:A1997WE30200029 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 Breiman, R Hardegree, MC Jacobs, RF Orenstein, WA Rabinovich, NR Schwartz, B 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 Breiman, R Hardegree, MC Jacobs, RF Orenstein, WA Rabinovich, NR Schwartz, B TI Poliomyelitis prevention: Recommendations for use of inactivated poliovirus vaccine and live oral poliovirus vaccine SO PEDIATRICS LA English DT Article ID UNITED-STATES; IMMUNIZATION; IMMUNITY; EPIDEMIOLOGY; CHILDREN; DISEASE; VIRUS AB A change in the recommendations for routine immunization of children is indicated because of the reduced risk of exposure to wild-type polio viruses and the continued occurrence of vaccine-associated paralytic poliomyelitis after oral polio vaccine (OPV). All children should receive four doses of vaccine before the child enters school. Regimens of sequential inactivated polio vaccine (IPV) and OPV, IPV only, or OPV only are acceptable. Each regimen has advantages and disadvantages. In special circumstances, one of the regimens is preferred or recommended. Because logistical problems with the current childhood immunization schedule may make these new recommendations difficult to implement immediately, their adoption likely will be gradual. Nevertheless, assuming continued progress toward global eradication and the development of new combination products, the routine use of an IPV-only regimen is likely to become desirable and feasible in future years. C1 US FDA,ROCKVILLE,MD 20857. NR 29 TC 29 Z9 30 U1 2 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD FEB PY 1997 VL 99 IS 2 BP 300 EP 305 PG 6 WC Pediatrics SC Pediatrics GA WE302 UT WOS:A1997WE30200030 ER PT J AU Nightingale, SL McGinnis, TJ AF Nightingale, SL McGinnis, TJ TI The role of the US Food and Drug Administration's patient information initiative in cost-effective drug therapy SO PHARMACOECONOMICS LA English DT Article ID MEDICATIONS; BENEFITS; LEAFLETS AB The use of drug and biological Products often entails complex risk-benefit deliberations by prescribers. Yet, there is often little or no information shared by prescribers or dispensers with patients about the potential risks and benefits of taking a prescription drug as part of the patient's therapeutic regimen. In 1994, drug-related morbidity and mortality has been estimated to cost $US76.6 billion. The largest component of this cost was associated with patient misadventures with their prescription medications. Industry experts, practitioners, and consumers agree that patients must have some basic information about prescription drugs to adhere successfully to their prescribed drug therapy. Patients today are discharged from hospitals more quickly than in the past and are expected to assume greater responsibility for their own care on discharge. Recently, there has been new and encouraging evidence that a greater percentage of patients are now receiving written information with their prescriptions. Developments in computer technology have made it relatively easy for pharmacies and physicians' offices to store and generate written information for patients. The US Food and Drug Administration (FDA) believes written information should be used to support, enhance and reinforce oral counselling. The FDA also believes that improved patient education will improve adherence to prescribed regimens and will give patients the information they need to make truly informed decisions about the drugs they take, thereby decreasing costly and unnecessary physician visits and hospitalisations. C1 US FDA,ROCKVILLE,MD 20857. NR 23 TC 5 Z9 5 U1 0 U2 2 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PD FEB PY 1997 VL 11 IS 2 BP 119 EP 125 PG 7 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA WJ871 UT WOS:A1997WJ87100002 PM 10165823 ER PT J AU Morse, DE Davis, HD Popke, EJ Brown, KJ ODonoghue, VA Grunberg, NE AF Morse, DE Davis, HD Popke, EJ Brown, KJ ODonoghue, VA Grunberg, NE TI Effects of ddC and AZT on locomotion and acoustic startle I: Acute effects in female rats SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE AZT; ddC; rat; locomotion; acoustic startle ID D-AMPHETAMINE; 2',3'-DIDEOXYCYTIDINE DDC; CEREBROSPINAL-FLUID; PHARMACOKINETICS; NICOTINE; DIDEOXYCYTIDINE; NEUROPATHY; REFLEX; AIDS; NEUROTOXICITY AB Several synthetic nucleoside analogues, including AZT(RETROVIR), ddC (HIVID), ddI (VIDEX), and d4T (ZERIT), are currently being used in the treatment of HIV infection. Unfortunately, in clinical use the appearance of severe and sometimes debilitating peripheral neuropathy and pain has been associated with the long-term use of several of these drugs (i.e., ddC, ddI and d4T), although not with AZT. To date, standard pre-clinical animal toxicity studies have failed to reveal any adverse neurologic effects of these compounds. However, previously reported preliminary findings suggest that ddC may alter several neuro-behavioral parameters (including locomotor activity, acoustic startle responding, and aggression) in rats and mice following presentation in the animals' drinking water for 7 days. The current series of experiments examined effects of acutely administered ddC and AZT on spontaneous locomotor activity and acoustic startle responses (with and without pre-pulse) in female Sprague-Dawley rats. Following intragastric administration, ddC reduced locomotion at all but the highest dose, whereas AZT had no significant effect on locomotor activity. Acutely administered ddC had no effect on ASR, whereas AZT increased ASR at the highest stimulus intensity. These data support the use of behavioral testing in the development of the antiviral nucleoside analogues, as behavioral testing may be more effective in identifying the neurologically active agents than is standard toxicity testing. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MED & CLIN PSYCHOL,BETHESDA,MD 20814. US FDA,DIV ANTIVIRAL DRUG PROD,ROCKVILLE,MD 20857. US FDA,ANTIVIRAL RES LAB,ROCKVILLE,MD 20857. FU PHS HHS [224-92-3004] NR 40 TC 13 Z9 13 U1 4 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD FEB PY 1997 VL 56 IS 2 BP 221 EP 228 DI 10.1016/S0091-3057(96)00214-6 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA WJ643 UT WOS:A1997WJ64300009 PM 9050078 ER PT J AU Schultz, DG Wagner, RF Campbell, G AF Schultz, DG Wagner, RF Campbell, G TI Science is alive and well at the food and drug administration SO RADIOLOGY LA English DT Editorial Material C1 US FDA,CTR DEVICES & RADIOL HLTH,OFF SCI & TECHNOL,ROCKVILLE,MD 20850. US FDA,CTR DEVICES & RADIOL HLTH,OFF SURVEILLANCE & BIOMETR,ROCKVILLE,MD 20850. RP Schultz, DG (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,OFF DEV EVALUAT,RFZ-470,9200 CORP BLVD,ROCKVILLE,MD 20850, USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 1997 VL 202 IS 2 BP 317 EP 318 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WD822 UT WOS:A1997WD82200005 PM 9015049 ER PT J AU Gaylor, DW Zheng, Q AF Gaylor, DW Zheng, Q TI A note on the relationship between lifetime tumor risk and expected time to tumor SO RISK ANALYSIS LA English DT Article ID MODEL RP Gaylor, DW (reprint author), US FDA,NATL CTR TOXICOL RES,ROCKVILLE,MD 20857, USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD FEB PY 1997 VL 17 IS 1 BP 5 EP 7 DI 10.1111/j.1539-6924.1997.tb00838.x PG 3 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA WV857 UT WOS:A1997WV85700002 PM 9131823 ER PT J AU Tammara, V Mahmood, I Yu, DK Hileman, GA AF Tammara, V Mahmood, I Yu, DK Hileman, GA TI A limited sampling method for the estimation of vigabatrin maximum plasma concentration and area under the curve SO THERAPEUTIC DRUG MONITORING LA English DT Article DE vigabatrin; area-under-the-curve prediction; maximum plasma concentration prediction; limited sampling model ID MAINTENANCE-DOSE PREDICTION; PHARMACOKINETICS; LITHIUM; MODEL AB A limited sampling model (LSM) was developed to estimate the area under the curve (AUC) and maximum plasma concentration (C-max) for a 1-g oral dose of vigabatrin. The model was developed using the data from 10 healthy subjects and one time point. The following equations describe the model for AUC and C-max: AUC((predicted)) = 5.4 x C-3h + 70 and C-max(predicted) = 0.18 x AUC((0-infinity)) + 9.4. The model was validated in 49 subjects who orally received 1-g vigabatrin. This LSM was also used to predict AUC and C-max volunteers who received 2- and 4-g vigabatrin doses and in renal failure patients who were given a 0.75-g dose. The model provided good estimates of both AUC and C-max in all groups of subjects except renal dysfunction patients. The method described here may be used to estimate AUC and C-max of vigabatrin without detailed pharmacokinetic studies. C1 US FDA,OFF CLIN PHARMACOL & BIOPHARMACEUT,DIV PHARMACEUT EVALUAT 1,ROCKVILLE,MD 20852. HOECHST & MARION ROUSSEL INC,KANSAS CITY,MO. NR 11 TC 13 Z9 13 U1 0 U2 0 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 FEB PY 1997 VL 19 IS 1 BP 79 EP 82 DI 10.1097/00007691-199702000-00014 PG 4 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA XT166 UT WOS:A1997XT16600014 PM 9029752 ER PT J AU Linden, JV Tourault, MA Scribner, CL AF Linden, JV Tourault, MA Scribner, CL TI Decrease in frequency of transfusion fatalities SO TRANSFUSION LA English DT Letter C1 US FDA,OFF COMPLIANCE,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20857. US FDA,OFF BLOOD RES & REV,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20857. RP Linden, JV (reprint author), NEW YORK STATE DEPT HLTH,POB 509,ALBANY,NY 12201, USA. NR 3 TC 33 Z9 35 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 FEB PY 1997 VL 37 IS 2 BP 243 EP 244 DI 10.1046/j.1537-2995.1997.37297203534.x PG 2 WC Hematology SC Hematology GA WJ594 UT WOS:A1997WJ59400025 PM 9051106 ER PT J AU Miele, L AF Miele, L TI Plants as bioreactors for biopharmaceuticals: Regulatory considerations SO TRENDS IN BIOTECHNOLOGY LA English DT Article ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; TRANSGENIC PLANTS; MONOCLONAL-ANTIBODIES; BIOLOGICAL-ACTIVITY; EXPRESSION; GLYCOSYLATION; INTERFERON; ANTIGEN; CHAINS; CELLS AB Plants are one of several novel hosts that can be used for the production of recombinant biopharmaceuticals such as cytokines, hormones, monoclonal antibodies, enzymes and vaccines. The novelty of this technology and its wide range of potential applications require an assessment of possible regulatory concerns in the clinical development of plant-derived biopharmaceuticals. General principles extrapolated from experience gained with biotechnology products from other sources can serve as a foundation to develop scientifically sound strategies for the large-scale production and clinical development of safe and effective biopharmaceuticals in plant hosts. RP Miele, L (reprint author), US FDA, DIV MONOCLONAL ANTIBODIES, OFF THERAPEUT RES & REVIEW, CTR BIOL EVALUAT & RES, BETHESDA, MD 20892 USA. NR 38 TC 78 Z9 81 U1 1 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD FEB PY 1997 VL 15 IS 2 BP 45 EP 50 DI 10.1016/S0167-7799(97)84202-3 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA WH459 UT WOS:A1997WH45900003 PM 9081298 ER PT J AU Rushing, LG Thompson, HC AF Rushing, LG Thompson, HC TI Simultaneous determination of malachite green, gentian violet and their leuco metabolites in catfish or trout tissue by high-performance liquid chromatography with visible detection SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE malachite green; gentian violet; leucomalachite green; leucogentian violet ID LEUCOGENTIAN VIOLET; ELECTROCHEMICAL DETECTION; CHICKEN FAT; FEED AB A sensitive analytical procedure for the determination of residues of leucomalachite green (LMG)-malachite green (MG) and leucogentian violet (LGV)-gentian violet (GV) in catfish or trout tissue is presented. Frozen (-20 degrees C) fish fillets were cut into small pieces and blended in a Waring blender. A 20-g amount of homogenized fish tissue was extracted with acetonitrile-buffer, partitioned against methylene chloride, and cleaned up on tandem neutral alumina and propylsulfonic acid cation-exchange solid-phase extraction cartridges. Samples of 100 mu l (0.8 g equiv.) were chromatographed isocratically in 10 min using an acetonitrile-buffer mobile phase on a short-chain deactivated (SCD) reversed-phase column (250x4.6 mm I.D.) in-line with a post-column PbO2 oxidation reactor. The PbO2 post-column reactor efficiently oxidized LMG to the chromatic MG, and LGV to the chromatic GV permitting visible detection at 588 nm for all four compounds. Linearity was demonstrated with standards over the range of 0.5-50 ng per injection. Recoveries of LMG, MG, LGV and GV from catfish tissues fortified at 10 ng/g were 75.4+/-3.0, 61.3+/-4.1, 72.6+/-3.7 and 87.9+/-2.5, respectively, while trout tissues fortified at 10 ng/g yielded recoveries of 82.6+/-2.3, 48.6+/-1.8, 72.1+/-2.1 and 83.8+/-4.6 (mean+/-S.D., n=4), respectively. RP Rushing, LG (reprint author), US FDA,NATL CTR TOXICOL RES,PUBL HLTH SERV,DEPT HLTH & HUMAN SERV,3900 NCTR DR,JEFFERSON,AR 72079, USA. NR 11 TC 39 Z9 52 U1 0 U2 2 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 JAN 24 PY 1997 VL 688 IS 2 BP 325 EP 330 DI 10.1016/S0378-4347(96)00298-8 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WV312 UT WOS:A1997WV31200019 PM 9061471 ER PT J AU Singer, SJ PiazzaHepp, TD Girardi, LS Moledina, NR AF Singer, SJ PiazzaHepp, TD Girardi, LS Moledina, NR TI Lupuslike reaction associated with minocycline SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP Singer, SJ (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 2 TC 16 Z9 16 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 22 PY 1997 VL 277 IS 4 BP 295 EP 296 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WC458 UT WOS:A1997WC45800018 PM 9002484 ER PT J AU Nakajima, H Shores, EW Noguchi, M Leonard, WJ AF Nakajima, H Shores, EW Noguchi, M Leonard, WJ TI The common cytokine receptor gamma chain plays an essential role in regulating lymphoid homeostasis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; RESTRICTED ANTIGEN RECEPTOR; T-CELLS; APOPTOSIS; MICE; THYMOCYTES; EXPRESSION; LYMPHOCYTES; ACTIVATION; BCL-2 AB In the immune system, there is a careful regulation not only of lymphoid development and proliferation, but also of the fate of activated and proliferating cells. Although the manner in which these diverse events are coordinated is incompletely understood, cytokines are known to play major roles. Whereas IL-7 is essential for lymphoid development, IL-2 and IL-4 are vital for lymphocyte proliferation. The receptors for each of these cytokines contain the common cytokine receptor gamma chain (gamma(c)), and it was previously shown that gamma(c)-deficient mice exhibit severely compromised development and responsiveness to IL-2, IL-4, and IL-7. Nevertheless, these mice exhibit an age-dependent accumulation of splenic CD4(+) T cells, the majority of which have a phenotype typical of memory/activated cells. When gamma(c)-deficient mice were mated to DO11.10 T cell receptor (TCR) transgenic mice, only the T cells bearing endogenous TCRs had this phenotype, suggesting that its acquisition was TCR dependent. Not only do the CD4(+) T cells from gamma(c)-deficient mice exhibit an activated phenotype and greatly enhanced incorporation of bromodeoxyuridine but, consistent with the lack of gamma(c)-dependent survival signals, they also exhibit an augmented rate of apoptosis. However, because the CD4(+) T cells accumulate, it is clear that the rate of proliferation exceeds the rate of cell death. Thus, surprisingly, although gamma(c)-independent signals are sufficient to mediate expansion of CD4(+) T cells in these mice, gamma(c)-dependent signals are required to regulate the fate of activated CD4(+) T cells, underscoring the importance of gamma(c)-dependent signals in controlling lymphoid homeostasis. C1 NHLBI,LAB MOL IMMUNOL,BETHESDA,MD 20892. US FDA,DIV HEMATOL PROD,BETHESDA,MD 20892. NR 33 TC 134 Z9 136 U1 0 U2 1 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 JAN 20 PY 1997 VL 185 IS 2 BP 189 EP 195 DI 10.1084/jem.185.2.189 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WE644 UT WOS:A1997WE64400002 PM 9016868 ER PT J AU Kashanchi, F Sadaie, MR Brady, JN AF Kashanchi, F Sadaie, MR Brady, JN TI Inhibition of HIV-1 transcription and virus replication using soluble Tat peptide analogs SO VIROLOGY LA English DT Article ID GENE-EXPRESSION; BINDING PROTEIN; RNA-POLYMERASE; IN-VITRO; TRANSACTIVATOR; TYPE-1; ACTIVATORS; SUBUNIT; MUTANT; DOMAIN AB The human immunodeficiency virus type 1 (HIV-1) transactivator Tat protein is essential for efficient viral gene expression and virus replication. The Tat core domain, a stretch of 12 amino acids between the cysteine-rich and the basic domain, is conserved in all HIV isolates and required for interaction with a number of cellular transcriptional regulatory proteins. Here we demonstrate that soluble peptide analogs of the Tat core domain (amino acid 36-50) are able to effectively block LTR transactivation. In transfection experiments, Tat core peptide analogs containing amino acid substitutions at position 41 and 44 inhibited Tat transactivation of an HIV-I LTR-CAT reporter construct up to 80-fold. In contrast, inhibition of other promoters such as HTLV-I and CMV was approximately 2-fold. Tat peptide analog 36-50 (41/44) inhibited HIV virus replication by 85% in latently infected U1 cells induced with Tat. Furthermore, U1 cells treated with the Tat peptide 36-50 (41/44) analog showed markedly delayed virus transmission when cocultivated with parental U937 cells. Interestingly, while both short and long peptide analogs (amino acids 36-50 vs 36-72) inhibited Tat transactivation in transient assays, the short peptides were more effective inhibitors of virus replication in U1 cells. The Tat peptide analog did not decrease expression of cellular genes including beta-actin, GAPDH, and histone H2B. (C) 1997 Academic Press C1 NCI,VIRUS TUMOR BIOL SECT,MOL VIROL LAB,NIH,BETHESDA,MD 20892. US FDA,MOL IMMUNOL SECT,LAB IMMUNOCHEM,DIV TRANSFUS TRANSMITTED DIS,CBER,ROCKVILLE,MD 20852. NR 26 TC 25 Z9 27 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 JAN 20 PY 1997 VL 227 IS 2 BP 431 EP 438 DI 10.1006/viro.1996.8346 PG 8 WC Virology SC Virology GA WD572 UT WOS:A1997WD57200017 PM 9018142 ER PT J AU Murata, T Obiri, NI Puri, RK AF Murata, T Obiri, NI Puri, RK TI Human ovarian-carcinoma cell lines express IL-4 and IL-13 receptors: Comparison between IL-4- and IL-13-induced signal transduction SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID INTERLEUKIN-4 RECEPTOR; GAMMA-CHAIN; SIMILARITIES; ACTIVATION; PROTEINS; CYTOKINE; INSULIN AB We have reported that human ovarian carcinoma cell lines express high-affinity IL-4 receptor. Since IL-4R has been hypothesized to share a chain with IL-13R, we investigated whether ovarian cancer cells express IL-13 receptor. In the present study, we report that the ovarian-carcinoma cell lines IGROV-1 and PA-1 express varying numbers of high-affinity IL-13 receptors. Furthermore, IL-13 inhibited the binding of IL-4 on both ovarian-carcinoma cell lines, while IL-4 did not inhibit IL-13 binding on IGROV-1 cell line. IL-13 and IL-4 induced the phosphorylation of JAK1, JAK2 and Tyk2 janus kinases in PA-1 cells. In contrast, JAK3 tyrosine kinase was expressed in PA-1 cells, but IL-4 or IL-13 did not augment its phosphorylation. In IGROV-1 cells, Tyk2 was constitutively phosphorylated and this phosphorylation was augmented by IL-4 or IL-13. JAK1 and JAK2 but not JAK3 were expressed but only JAK2 was faintly phosphorylated in response to either IL-13 or IL-4 respectively. IRS (insulin-receptor substrate)-1 and IRS-2 were also phosphorylated constitutively in both ovarian cancer cell lines examined, but only the phosphorylation of IRS-1 was augmented in response to IL-4 or IL-13. STAT6 was phosphorylated and activated in response to IL-4 and IL-13 in all cell lines examined. Our results demonstrate that ovarian cancer cell lines may express 2 types of IL-13R and the IL-13- or IL-4-induced signaling patterns may be slightly different in each type of receptor. (C) 1997 Wiley-Liss, Inc. C1 US FDA,LAB MOL TUMOR BIOL,DIV CELLULAR & GENE THERAPIES,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 21 TC 57 Z9 57 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 17 PY 1997 VL 70 IS 2 BP 230 EP 240 DI 10.1002/(SICI)1097-0215(19970117)70:2<230::AID-IJC15>3.0.CO;2-M PG 11 WC Oncology SC Oncology GA WF370 UT WOS:A1997WF37000015 PM 9009165 ER PT J AU Babu, US Bunning, VK Wiesenfeld, P Raybourne, RB ODonnell, M AF Babu, US Bunning, VK Wiesenfeld, P Raybourne, RB ODonnell, M TI Effect of dietary flaxseed on fatty acid composition, superoxide, nitric oxide generation and antilisterial, activity of peritoneal, macrophages from female Sprague-Dawley rats SO LIFE SCIENCES LA English DT Article DE flaxseed; peritoneal exudate cells; superoxide; Listeria monocytogenes; fatty acids ID ALPHA-LINOLENIC ACID; TUMOR-NECROSIS-FACTOR; PLATELET-ACTIVATING-FACTOR; MOUSE MACROPHAGES; RESPIRATORY BURST; BALB/C MICE; FISH OIL; MODULATION; BALANCE; ARTHRITIS AB The impact of ground flaxseed (FS) or flaxseed meal (FSM) diets on the fatty acid composition and functions of rat peritoneal exudate cells (PEG) was determined. Female weanling Sprague-Dawley rats (10/group) were fed isocaloric AIN-76 diets supplemented with 0.0, 10.0% (w/w) FS or 6.2% (w/w) FSM. A the end of 56-days, rat serum and thiogrycollate-elicited PEC were analyzed for total lipid fatty acids. Production of nitric oxide (NO) and superoxide (O-2(-)), Listeria monocytonenes (LM) phagocytic index and antilisterial activity of resident PEC were also assessed. A significant increase in a-linolenic (C18:3), eicosapentanoic (C20:5) and docosahexanoic (C22:6) acids, as well as a significant reduction in arachidonic acid (C20:4) was observed in the serum of rats fed 10% FS. Dietary FS caused a significant reduction in palmitic acid (C16:0) and an increase in stearic acid (C18:0) of PEC. Defatted FSM produced a significant increase in long chain fatty acids, which included eicosadienoic acid (C20:2) in PEC and C22:6 in serum. PEC from rats fed 10.0% FS produced significantly less (about 50%) O-2(-) in response to phorbol myristate acetate (PMA), than did PEC from control animals; dietary treatment had no effect on O-2(-) in response to LM. FSM had no impact on the O-2(-) production by PEC in response to PMA or LM. Antilisterial activity of PEC was determined by comparing bacterial uptake after 1 hr with recovery 24 hrs later. Despite comparably equivalent bacterial uptake, few viable intracellular LM were recovered at T=24 for all test samples, indicating that, regardless of the dietary treatment, PEC were able to handle the in vitro LM infection. This bacterial clearance was accompanied by equivalent NO generation by PEC from each dietary group in response to LM. Summarily, dietary FS produced significant changes in fatty acid composition of serum and PEG, inhibited O-2(-) generation by PEG, and was ineffectual to both NO production by and antilisterial activity of PEC. C1 US FDA,OFF SPECIAL NUTR,DIV SCI & APPL TECHNOL,LAUREL,MD 20708. US FDA,DIV VIRULENCE ASSESSMENT,IMMUNOL BRANCH,LAUREL,MD 20708. US FDA,DIV MATH,EXPT DESIGN & EVALUAT BRANCH,LAUREL,MD 20708. NR 39 TC 9 Z9 9 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JAN 17 PY 1997 VL 60 IS 8 BP 545 EP 554 DI 10.1016/S0024-3205(96)00638-8 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA WF009 UT WOS:A1997WF00900006 PM 9042389 ER PT J AU Young, HA Klinman, DM Reynolds, DA Grzegorzewski, KJ Nii, A Ward, JM WinklerPickett, RT Ortaldo, JR Kenny, JJ Komschlies, KL AF Young, HA Klinman, DM Reynolds, DA Grzegorzewski, KJ Nii, A Ward, JM WinklerPickett, RT Ortaldo, JR Kenny, JJ Komschlies, KL TI Bone marrow and thymus expression of interferon-gamma results in severe B-cell lineage reduction, T-cell lineage alterations, and hematopoietic progenitor deficiencies SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; IFN-GAMMA; TRANSGENIC MICE; STEM-CELLS; SYNDROME TRISOMY-21; GENE-EXPRESSION; IMMUNE-RESPONSE; MOUSE; PROLIFERATION; LIPOPOLYSACCHARIDE AB Interferon-gamma (IFN-gamma) is an immunoregulatory lymphokine that is primarily produced by T cells and natural killer cells. It has effects on T-cell, B-cell, and macrophage differentiation and maturation. We have developed transgenic mice that express elevated levels of IFN-gamma mRNA and protein by inserting multiple copies of murine IFN-gamma genomic DNA containing an Ig lambda-chain enhancer in the first intron. The founder line carrying eight copies of this transgene has eightfold to 15-fold more IFN-gamma-producing cells in the bone marrow and spleen than do nontransgenic littermates. Transgenic mice show a pronounced reduction in B-lineage cells in the bone marrow, spleen, and lymph nodes. In addition, single positive (CD4(+),CD8(-) and CD4(-),CD8(+)) thymocyte numbers are increased twofold, yet the number of splenic T cells is reduced by 50%. There is also a twofold to threefold decrease in the frequency and total number of myeloid progenitors in the bone marrow. Granulomatous lesions and residual degenerating cartilaginous masses are also present in the bones of these mice. Overall, our data show that the abnormal expression of IFN-gamma in these transgenic mice results in multiple alterations in the immune system. These animals provide an important model to examine the role of IFN-gamma expression on lymphoid and myeloid differentiation and function. This is a US government work. There are no restrictions on its use. C1 NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES SUPPORT PROGRAM,SCI APPLICAT INT CORP FREDERICK,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,FREDERICK,MD 21702. US FDA,SECT RETROVIRAL RES,DIV VIRAL PROD,BETHESDA,MD 20014. RP Young, HA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,EXPT IMMUNOL LAB,DIV BASIC SCI,BLDG 560,ROOM 31-93,FREDERICK,MD 21702, USA. NR 67 TC 53 Z9 53 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 JAN 15 PY 1997 VL 89 IS 2 BP 583 EP 595 PG 13 WC Hematology SC Hematology GA WD034 UT WOS:A1997WD03400027 PM 9002962 ER PT J AU Obiri, NI Leland, P Murata, T Debinski, W Puri, RK AF Obiri, NI Leland, P Murata, T Debinski, W Puri, RK TI The IL-13 receptor structure differs on various cell types and may share more than one component with IL-4 receptor SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN INTERLEUKIN-4 RECEPTOR; CARCINOMA-CELLS; SIGNAL-TRANSDUCTION; CHIMERIC PROTEIN; GAMMA-CHAIN; B-CELLS; T-CELLS; SUPERFAMILY; RESPONSES; EXOTOXIN AB We have reported on the expression and characteristics of IL-13R and have demonstrated that IL-13 competes for IL-4 binding white IL-4 did not compete for the IL-13 binding on some cell types. Based on these observations, and the size of IL-13 and IL-4 cross-linked proteins, we concluded that the receptor for IL-13 is complex and shares a subunit with the receptor for IL-4. To explore the complexity of the IL-13R, a wide variety of cell types was examined for IL-13 and IL-4 binding. We report in this work that IL-4 does not always bind well to cells that bind IL-13, but the reverse is also true. We also found that IL-4 can compete more effectively for IL-13 binding than IL-13 itself. Cross-linking studies support these observations and demonstrate that I-125-labeled IL-13 bound exclusively to a single 65- to 70-kDa protein in MA-RCC and U251: cells, while in TF-1 cells it cross-linked to two membrane proteins of 65 to 70 kDa and 140 kDa. Furthermore, by using a chimeric protein composed of IL-13 and Pseudomonas exotoxin A, we observed that IL-4 neutralized the cytotoxicity of the IL-13 toxin on COS-7 cells by blocking a common form of the two cytokine receptors. We propose that the 65- to 70-kDa form of the IL-13R is the predominant common component shared between IL-13 and IL-4R. However, the primary IL-4 binding (p140) protein also participates in the formation of the IL-13R complex in some cell types. In addition, the gamma(c) or another interactive subunit may influence IL-13 binding to its receptor complex. Thus, we propose that there are at least four forms of IL-13R. C1 US FDA,CTR BIOL EVALUAT & RES,LAB MOL TUMOR BIOL,DIV CELLULAR & GENE THERAPIES,BETHESDA,MD 20892. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT SURG,DIV NEUROSURG,HERSHEY,PA 17033. NR 23 TC 142 Z9 147 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 JAN 15 PY 1997 VL 158 IS 2 BP 756 EP 764 PG 9 WC Immunology SC Immunology GA WC638 UT WOS:A1997WC63800028 PM 8992992 ER PT J AU Matthews, AM Hinson, JA Roberts, DW Pumford, NR AF Matthews, AM Hinson, JA Roberts, DW Pumford, NR TI Comparison of covalent binding of acetaminophen and the regioisomer 3'-hydroxyacetanilide to mouse liver protein SO TOXICOLOGY LETTERS LA English DT Article DE acetaminophen; 3'-hydroxyacetanilide; protein covalent binding; toxicity; immunoblot ID NON-HEPATOTOXIC REGIOISOMER; INDUCED HEPATIC NECROSIS; REACTIVE METABOLITES; ADDUCTS; ASSAY AB The hepatotoxicity of the analgesic acetaminophen has been previously attributed to metabolic activation by cytochrome P450 to the reactive intermediate N-acetyl-p-benzoquinone imine. At therapeutic doses this species is detoxified by reaction with glutathione; however, following a hepatotoxic dose, liver glutathione levels are depleted and the metabolite covalently binds primarily to cysteine groups on proteins as 3-(cystein-S-yl)acetaminophen adducts. Altered function of critical proteins has been postulated to be the mechanism of hepatotoxicity. Covalent binding has been studied by both radiochemical methods and immunochemical methods. Utilizing Western blot analysis with an antiserum which recognizes acetaminophen we have previously shown that covalent binding occurs on a number of proteins in various hepatic fractions. In an effort to better understand the role of covalent binding in the toxicity, others have studied the non-hepatotoxic isomer 3'-hydroxyacetanilide. Administration of large doses of radiolabeled acetaminophen or 3'-hydroxyacetanilide resulted in similar levels of covalent binding to proteins. To better understand the role of covalent binding in toxicity we have administered mice 3'-hydroxyacetanilide and acetaminophen, and analyzed liver fractions for protein adducts using anti-3-(cystein-S-yl)acetaminophen and anti-arylacetamide antisera in Western blot assays. Analysis of liver fractions from acetaminophen-treated mice, with both antisera showed, as has been previously reported, that acetaminophen covalently binds to a number of hepatic proteins. In liver from 3'-hydroxyacetanilide-treated mice, covalent adducts were detected with an anti-arylacetamide antiserum only. A major 3'-hydroxyacetanilide protein adduct was observed in microsomes at 50 kDa. Minor adducts were observed at 47 kDa in microsomes and 56 kDa in cytosol. 3'-Hydroxyacetanilide protein adducts were not observed in the 10 000 x g pellet. Densitometric analysis of a time course of 3'-hydroxyacetanilide protein adducts indicated that peak levels of the 50 kDa microsomal protein adduct occurred at 1 h and subsequently decreased. Copyright (C) 1997 Elsevier Science Ireland Ltd. 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 [R01GM48749] NR 20 TC 22 Z9 23 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 JAN 15 PY 1997 VL 90 IS 1 BP 77 EP 82 DI 10.1016/S0378-4274(96)03831-3 PG 6 WC Toxicology SC Toxicology GA WE685 UT WOS:A1997WE68500010 PM 9020405 ER PT J AU Murata, T Puri, RK AF Murata, T Puri, RK TI Comparison of IL-13- and IL-4-induced signaling in EBV-immortalized human B cells SO CELLULAR IMMUNOLOGY LA English DT Article ID CYTOKINE RECEPTOR SUPERFAMILY; JAK-3 JANUS KINASE; TYROSINE PHOSPHORYLATION; INTERLEUKIN-4 RECEPTOR; MYELOID CELLS; T-CELLS; ACTIVATION; STAT; TRANSDUCTION; ASSOCIATION AB Interleukin 4 (IL-4) and Interleukin 13 (IL-13) have been shown to have numerous similar effects on human B cells; however, the mechanism of signal transduction is not known. We have examined IL-4- and IL-13-induced signal transduction in Epstein-Barr virus (EBV)-immortalized B cells. me demonstrate that Janus kinase 3 (JAK3) and Tyk2 but not JAK1 and JAK2 tyrosine kinases were constitutively phosphorylated in three EBV B cell lines. The phosphorylation level of Tyk2 was augmented at a low level in response to IL-13 and IL-4 in two of three cell lines; however, IL-13 did not induce or augment phosphorylation of the other JAK kinases. On the other hand, IL-4 further augmented phosphorylation of JAK3 and induced the phosphorylation of JAK1 kinases. IL-4 receptor p140 protein was also constitutively phosphorylated in two of three EBV E cell lines examined and both IL-4 and IL-13 further augmented its phosphorylation. Insulin receptor substrate (IRS)-1 or IRS-S proteins were not constitutively phosphorylated nor did IL-13 and IL-4 induce phosphorylation of these proteins. In contrast to JAKs, IL-4-specific signal transducer and activator of transcription (STAT6) was not constitutively phosphorylated or activated in these cell lines, but both IL-4 and IL-13 induced their phosphorylation and activation. These findings suggest that in EBV-immortalized B cells JAK3 and Tyk2 proteins were constitutively phosphorylated but STAT6 protein was not constitutively phosphorylated. In addition, despite major similarities in biological effects between IL-4 and IL-13, phosphorylation patterns of JAK kinases in response to IL-13 in EBV-immortalized B cells appear to be different from those of IL-4. (C) 1997 Academic Press C1 US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPY,LAB MOL TUMOR BIOL,BETHESDA,MD 20892. NR 38 TC 43 Z9 43 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JAN 10 PY 1997 VL 175 IS 1 BP 33 EP 40 DI 10.1006/cimm.1996.1051 PG 8 WC Cell Biology; Immunology SC Cell Biology; Immunology GA WC938 UT WOS:A1997WC93800005 PM 9015186 ER PT B AU Durkin, AJ Ediger, MN Matchette, LS Pettit, GH AF Durkin, AJ Ediger, MN Matchette, LS Pettit, GH BE Thompson, RB TI Raman spectroscopy for quantification of polydimethylsiloxane concentration in turbid samples SO ADVANCES IN FLUORESCENCE SENSING TECHNOLOGY III SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Advances in Fluorescence Sensing Technology III CY FEB 09-11, 1997 CL SAN JOSE, CA SP Soc Photo Opt Instrumentat Engineers, Chiron Diag Corp, Ciencia Inc, Coherent Inc Laser Grp, ISS Inc, Jobin Yvon SPEX Instruments SA Inc, LiCONiX, Opt Sensors Inc, Perkin Elmer Corp, PicoQuant, Adv Photon Int, Programmed Test Sources Inc, Spectronics Inc, SpectRx Inc DE Raman spectroscopy; optical spectroscopy; biomedical diagnostics; Partial Least Squares; polydimethylsiloxane (PDMS); breast implant leakage; silicone AB This paper presents a preliminary application of Raman spectroscopy in conjunction with the chemometric method of Partial Least Squares to predict silicone concentrations in homogenous turbid samples. The chemometric technique is applied to Raman spectra to develop an empirical, linear model relating sample spectra to polydimethysiloxane (silicone) concentration. This is done using a training set of samples having optical properties and known concentrations representative of those unknown samples to be predicted. Partial Least Squares, performed via cross-validation. was able to predict silicone concentrations in good agreement with true values. The detection limit obtained for this preliminary investigation is on par with that of magnetic resonance spectroscopy. The data acquisition time for this Raman based method is 200 seconds, which compares favorably with the 17 hour acquisition required for magnetic resonance spectroscopy to obtain a similar sensitivity. The combination of Raman spectroscopy and chemometrics shows promise as a tool for quantification of silicone concentrations from turbid samples. RP Durkin, AJ (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,ELECTROOPT BRANCH,ROCKVILLE,MD 20852, USA. NR 0 TC 1 Z9 1 U1 1 U2 3 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2391-2 J9 P SOC PHOTO-OPT INS PY 1997 VL 2980 BP 217 EP 226 PG 10 WC Medicine, Research & Experimental; Optics; Spectroscopy SC Research & Experimental Medicine; Optics; Spectroscopy GA BH84B UT WOS:A1997BH84B00026 ER PT B AU Avalos, J Jacobs, A Wilkin, JK AF Avalos, J Jacobs, A Wilkin, JK BE Green, K Edelhauser, HF Hackett, RB Hull, DS Potter, DE Tripathi, RC TI Toxicity testing for ocular drug products SO ADVANCES IN OCULAR TOXICOLOGY LA English DT Proceedings Paper CT 5th Congress of the International-Society-of-Ocular-Toxicology CY OCT 13-17, 1996 CL ASHEVILLE, NC SP Int Soc Ocular Toxicol RP Avalos, J (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV DERMATOL & DENTAL DRUG PROD,ROCKVILLE,MD 20857, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45614-1 PY 1997 BP 261 EP 268 PG 8 WC Ophthalmology; Toxicology SC Ophthalmology; Toxicology GA BH98H UT WOS:A1997BH98H00024 ER PT J AU Soriano, V Martin, R delRomero, J Heredia, A Dietrich, U Mas, A Adrados, M Martinez, P Hewlett, I GonzalezLahoz, J AF Soriano, V Martin, R delRomero, J Heredia, A Dietrich, U Mas, A Adrados, M Martinez, P Hewlett, I GonzalezLahoz, J TI Outcome in a cohort of long-term non-progressors in Madrid: Virological and immunological findings SO AIDS LA English DT Letter ID HIV-1 INFECTION C1 CTR SANDOVAL COMUNIDAD,MADRID,SPAIN. US FDA,MOL VIROL LAB,BETHESDA,MD 20014. GEORGE SPEYER HAUS,MOL VIROL LAB,FRANKFURT,GERMANY. RP Soriano, V (reprint author), CTR AYUNTAMIENTO,INST SALUD CARLOS III,INFECT DIS SERV,MADRID,SPAIN. RI Adrados, Magdalena/H-8123-2015; Mas, Antonio/F-2505-2011 OI Adrados, Magdalena/0000-0003-3317-670X; Mas, Antonio/0000-0003-2563-570X NR 5 TC 1 Z9 1 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 JAN PY 1997 VL 11 IS 1 BP 123 EP 124 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA WB212 UT WOS:A1997WB21200022 PM 9110088 ER PT J AU Thal, LJ Carta, A Doody, R Leber, P Mohs, R Schneider, L Shimohama, S Silber, C AF Thal, LJ Carta, A Doody, R Leber, P Mohs, R Schneider, L Shimohama, S Silber, C TI Prevention protocols for Alzheimer disease - Position paper from the International Working Group on Harmonization of Dementia Drug Guidelines SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article ID COMMUNITY POPULATION; APOLIPOPROTEIN-E; PREDICTION; PREVALENCE; ALLELE; RISK C1 BAYLOR COLL MED,DEPT NEUROL,HOUSTON,TX 77030. WORLDWIDE CLIN TRIALS LTD,LONDON,ENGLAND. US FDA,DIV NEUROPHARMACOL DRUG PROD,ROCKVILLE,MD 20857. VET ADM MED CTR,DEPT PSYCHIAT,BRONX,NY. UNIV SO CALIF,DEPT PSYCHIAT,LOS ANGELES,CA. KYOTO UNIV,FAC MED,DEPT NEUROL,KYOTO 606,JAPAN. ABBOTT LABS,CHICAGO,IL. RP Thal, LJ (reprint author), UNIV CALIF SAN DIEGO,SCH MED,DEPT NEUROSCI,9500 GILMAN DR,LA JOLLA,CA 92093, USA. FU PHS HHS [10483] NR 14 TC 25 Z9 25 U1 0 U2 1 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. PY 1997 VL 11 SU 3 BP 46 EP 49 PG 4 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA XX144 UT WOS:A1997XX14400012 PM 9305516 ER PT J AU Bodick, N Forette, F Hadler, D Harvey, RJ Leber, P McKeith, IG Riekkinen, PJ Rossor, MN Scheltens, P Shimohama, S Spiegel, R Tanaka, S Thal, LJ Urata, Y Whitehouse, P Wilcock, G AF Bodick, N Forette, F Hadler, D Harvey, RJ Leber, P McKeith, IG Riekkinen, PJ Rossor, MN Scheltens, P Shimohama, S Spiegel, R Tanaka, S Thal, LJ Urata, Y Whitehouse, P Wilcock, G TI Protocols to demonstrate slowing of Alzheimer disease progression - Position paper from the International Working Group on Harmonization of Dementia Drug Guidelines SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE Alzheimer disease progression; clinical trials; experimental design ID RATING-SCALE AB Two suggested clinical trial designs for assessing progression of Alzheimer disease are the randomized withdrawal design and the randomized start design. The most promising of these, the randomized start design, has the potential to demonstrate a delay in progression, but there remain problematic design, ethical, and statistical issues to be solved before the protocol can be used in a clinical trial. The development of biological markers of the disease process using neuroimaging or other measures also may provide a robust method of measuring disease progression and demonstrating the biological effect of a drug on the disease process. C1 UCL NATL HOSP NEUROL & NEUROSURG, DEMENTIA RES GRP, LONDON WC1N 3BG, ENGLAND. ELI LILLY & CO, INDIANAPOLIS, IN 46285 USA. HOSP BROCA, FDN NATL GERONTOL, PARIS, FRANCE. TAKEDA EUROPE R&D CTR GMBH, FRANKFURT, GERMANY. US FDA, WASHINGTON, DC 20204 USA. NEWCASTLE GEN HOSP, INST HLTH ELDERLY, NEWCASTLE UPON TYNE NE4 6BE, TYNE & WEAR, ENGLAND. UNIV KUOPIO, AI VIRTANEN INST, FIN-70211 KUOPIO, FINLAND. FREE UNIV AMSTERDAM HOSP, DEPT NEUROL, NL-1007 MB AMSTERDAM, NETHERLANDS. KYOTO UNIV, FAC MED, DEPT NEUROL, KYOTO 606, JAPAN. SANDOZ PHARMACEUT LTD, BASEL, SWITZERLAND. DAIICHI PHARMACEUT CO LTD, MED RES & DEV DEPT, KITAKASI, TOKYO, JAPAN. UNIV CALIF SAN DIEGO, SCH MED, SAN DIEGO, CA 92103 USA. JAPAN TOBACCO INC, OSAKA, JAPAN. UNIV HOSP CLEVELAND, CLEVELAND, OH 44106 USA. UNIV BRISTOL, FRENCHAY HOSP, DEPT CARE ELDERLY, BRISTOL, AVON, ENGLAND. NR 5 TC 28 Z9 30 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 EI 1546-4156 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PY 1997 VL 11 SU 3 BP 50 EP 53 PG 4 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA XX144 UT WOS:A1997XX14400013 PM 9305517 ER PT J AU Leber, P AF Leber, P TI Slowing the progression of Alzheimer disease: Methodologic issues SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article; Proceedings Paper CT Roundtable on Slowing the Progress of Alzheimers Disease - Methodology and Ethical Issues at the 5th International Conference on Alzheimers Disease and Related Disorders CY JUL 24-29, 1996 CL OSAKA, JAPAN SP Janssen Pharm DE Alzheimer disease; dementia; clinical trial designs; discontinuation design ID PARKINSONS-DISEASE; DEPRENYL AB The evidence to support a claim that a new drug will slow the progression of Alzheimer disease (AD) must derive from epistemologically valid research methods. Although agency regulations do not specify the magnitude of an effect that a drug must possess to be granted a claim as a treatment for AD, the evidence to support any claim must be adduced in adequate and well-controlled clinical investigations and muse meet the standard of ''substantial evidence.'' Because a claim presented in drug product labeling may not be false or misleading in any particular, a distinction must be made between treatments that provide a ''symptomatic'' benefit and those that alter the course of dementia. Examples of some of the difficulties likely to be encountered by sponsors seeking to develop evidence to support a claim that a new drug slows the progression of dementia are presented. A suggestion is made for a clinical trial design, designated as the ''randomized start design,'' that may be useful in such a question. Why this design might overcome many of the difficulties, both practical and ethical, present in the ''discontinuation'' design, the design ordinarily proposed to assess a drug's effect on disese progression, is discussed. RP Leber, P (reprint author), US FDA,CTR DRUG EVALUAT & RES,OFF NEW DRUG EVALUAT 1,DIV NEUROPHARMACOL DRUG PROD,ROCKVILLE,MD 20857, USA. NR 6 TC 76 Z9 76 U1 0 U2 1 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. PY 1997 VL 11 SU 5 BP S10 EP S20 PG 11 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA YC127 UT WOS:A1997YC12700005 PM 9348423 ER PT J AU Teisl, M Roe, B Hicks, R AF Teisl, M Roe, B Hicks, R TI Can eco-labels tune a market? Evidence from dolphin-safe labeling. SO AMERICAN JOURNAL OF AGRICULTURAL ECONOMICS LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Univ Maryland, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 2 U2 6 PU AMER AGRICULTURAL ECONOMICS ASSOC PI AMES PA 1110 BUCKEYE AVE, AMES, IA 50010-8063 USA SN 0002-9092 J9 AM J AGR ECON JI Am. J. Agr. Econ. PY 1997 VL 79 IS 5 SI SI BP 1707 EP 1707 PG 1 WC Agricultural Economics & Policy; Economics SC Agriculture; Business & Economics GA ZN774 UT WOS:000073681300160 ER PT J AU Roe, B Levy, A Derby, B AF Roe, B Levy, A Derby, B TI The effect of health claims on label reading, purchase intentions, and product evaluation. SO AMERICAN JOURNAL OF AGRICULTURAL ECONOMICS LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER AGRICULTURAL ECONOMICS ASSOC PI AMES PA 1110 BUCKEYE AVE, AMES, IA 50010-8063 USA SN 0002-9092 J9 AM J AGR ECON JI Am. J. Agr. Econ. PY 1997 VL 79 IS 5 SI SI BP 1713 EP 1713 PG 1 WC Agricultural Economics & Policy; Economics SC Agriculture; Business & Economics GA ZN774 UT WOS:000073681300224 ER PT J AU Kim, YI Pogribny, IP Basnakian, AG Miller, JW Selhub, J James, SJ Mason, JB AF Kim, YI Pogribny, IP Basnakian, AG Miller, JW Selhub, J James, SJ Mason, JB TI Folate deficiency in rats induces DNA strand breaks and hypomethylation within the p53 tumor suppressor gene SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT 86th Annual Meeting of the American-Association-for-Cancer-Research CY MAR 15-22, 1995 CL TORONTO, CANADA SP Amer Assoc Canc Res DE folate; DNA methylation; DNA damage; p53; carcinogenesis ID FED METHYL-DEFICIENT; CHOLINE-DEVOID DIET; ACID-DEFINED DIETS; S-ADENOSYLMETHIONINE; COORDINATE REGULATION; CHROMATIN STRUCTURE; EMBRYO CELLS; FOLIC-ACID; CANCER; METABOLISM AB Folate is essential for the de novo biosynthesis of purines and thymidylate, and is an important mediator in the transfer of methyl groups for DNA methylation. Folate deficiency, therefore, could contribute to abnormal DNA integrity and methylation patterns. We investigated the effect of isolated folate deficiency in rats on DNA methylation and DNA strand breaks both at the genomic level and within specific sequences of the p53 tumor suppressor gene. Our data indicate that folate deficiency induces DNA strand breaks and hypomethylation within the p53 gene. Such alterations either did not occur or were chronologically delayed when examined on a genome-wide basis, indicating some selectivity for the exons examined within the p53 gene. Folate insufficiency has been implicated in the development of several human and experimental cancers, and aberrations within these regions of the p53 gene that were examined in this study are thought to play an integral role in carcinogenesis. The aforementioned molecular alterations may therefore be a means by which dietary folate deficiency enhances carcinogenesis. C1 TUFTS UNIV,JEAN MAYER USDA,HUMAN NUTR RES CTR AGING,VITAMIN BIOAVAILABIL LAB,BOSTON,MA 02111. US FDA,NATL CTR TOXICOL RES,DIV NUTR TOXICOL,JEFFERSON,AR 72079. FU NCI NIH HHS [1UO1 CA63812-01] NR 49 TC 237 Z9 245 U1 1 U2 8 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 1997 VL 65 IS 1 BP 46 EP 52 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WA658 UT WOS:A1997WA65800007 PM 8988912 ER PT B AU Levenbook, I Dragunsky, E Chumakov, K Taffs, R Chernokhvostova, Y Nomura, T Hioki, K Gardner, D Cogan, J Asher, D AF Levenbook, I Dragunsky, E Chumakov, K Taffs, R Chernokhvostova, Y Nomura, T Hioki, K Gardner, D Cogan, J Asher, D BE vanZutphen, LFM Balls, M TI Transgenic mice and a molecular assay as alternatives to the monkey neurovirulence test of oral poliovirus vaccine SO ANIMAL ALTERNATIVES, WELFARE, AND ETHICS SE DEVELOPMENTS IN ANIMAL AND VETERINARY SCIENCES LA English DT Proceedings Paper CT 2nd World Congress on Alternatives and Animal Use in the Life Sciences CY OCT 20-24, 1996 CL UTRECHT, NETHERLANDS SP Johns Hopkins Univ, Ctr Alternat Anim Testing, European Cosmet Toiletry & Perfumery Assoc, European Commiss DGXI, European Commiss ECVAM, L Oreal, Procter & Gamble, Solvay Duphar, Wella AB Oral poliovirus Vaccine (OPV) is evaluated in the monkey neurovirulence test (MNVT). Type 3 OPV is the most unstable in its attenuation and is linked to a majority of vaccine-associated cases. Molecular analysis by PCR and restriction enzyme cleavage (MAPREC) predicted the outcome of the MNVT by quantifying the frequency of neurovirulent revertants at position 472 of the type 3 OPV genome and can serve as a screening test for reducing the number of MNVTs. Transgenic mice with human receptors for poliovirus (TgPVR) are suitable for the replacement of the MNVT for type 3 OPV testing. The frequency of back-mutants in type 3 OPV lots was quantified by MAPREC. TgPVR21 mice were inoculated with test and reference OPV lots, and the clinical scores were compared. TgPVR21 mice detected all seven Vaccine lots with an excessive amount of neurovirulent back-mutants, including one that passed the MNVT. Results of the mouse test strictly correlated with the MAPREC data. TgPVR mice were no less sensitive than monkeys for the detection of type 3 OPV lots with slightly increased neurovirulence. MAPREC has a potential for the replacement of animals tests by monitoring the stability of the Vaccine Virus genome. C1 FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852. RP Dragunsky, E (reprint author), FDA,CTR BIOL EVALUAT & RES,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 0-444-82424-3 J9 DEV AN VET PY 1997 VL 27 BP 1013 EP 1016 PG 4 WC Medicine, Research & Experimental; Pharmacology & Pharmacy; Toxicology; Veterinary Sciences; Zoology SC Research & Experimental Medicine; Pharmacology & Pharmacy; Toxicology; Veterinary Sciences; Zoology GA BJ87M UT WOS:A1997BJ87M00136 ER PT B AU OConnor, AM AF OConnor, AM BE vanZutphen, LFM Balls, M TI Barriers to regulatory acceptance SO ANIMAL ALTERNATIVES, WELFARE, AND ETHICS SE DEVELOPMENTS IN ANIMAL AND VETERINARY SCIENCES LA English DT Proceedings Paper CT 2nd World Congress on Alternatives and Animal Use in the Life Sciences CY OCT 20-24, 1996 CL UTRECHT, NETHERLANDS SP Johns Hopkins Univ, Ctr Alternat Anim Testing, European Cosmet Toiletry & Perfumery Assoc, European Commiss DGXI, European Commiss ECVAM, L Oreal, Procter & Gamble, Solvay Duphar, Wella AB Challenges to the regulatory acceptance of new toxicological methods are discussed. Barriers may include perceived risks in the acceptance of new methods, on the part of both regulatory and industry scientists, and biases toward traditional methods of testing. The US Food and Drug Administration is committed to the development of methods that are more predictive of human safety and to help achieve this goal is supporting the development of alternative methods in its laboratories. The agency is also actively involved in several policy initiatives to encourage the advancement of alternative methods. RP OConnor, AM (reprint author), US FDA,OFF SCI,HF-33 5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 0-444-82424-3 J9 DEV AN VET PY 1997 VL 27 BP 1173 EP 1176 PG 4 WC Medicine, Research & Experimental; Pharmacology & Pharmacy; Toxicology; Veterinary Sciences; Zoology SC Research & Experimental Medicine; Pharmacology & Pharmacy; Toxicology; Veterinary Sciences; Zoology GA BJ87M UT WOS:A1997BJ87M00158 ER PT J AU Molnar, J Hever, A Fakla, I Fischer, J Ocsovski, I Aszalos, A AF Molnar, J Hever, A Fakla, I Fischer, J Ocsovski, I Aszalos, A TI Inhibition of the transport function of membrane proteins by some substituted phenothiazines in E-coli and multidrug resistant tumor cells SO ANTICANCER RESEARCH LA English DT Article DE phenothiazines; mdr P-glycoprotein in bacteria; cancer; brain capillaries ID P-GLYCOPROTEIN; DRUG-RESISTANCE AB Efflux-pumps mediated by P-glycoprotein increase the level of resistance to antibiotics in bacteria and to cytostatics in tumor cells due to decreased drug accumulation, and are also involved in the operation of blood brain barrier. Different compounds are able to enhance drug retention in the cells by inhibiting the efflux-pump mechanism of multidrug resistant (mdr) cancer cells and bacteria. The effects of substituted chlorpromazines were studied on a hemolysin producing and antibiotic resistant plasmid carrying E. coli, and rhodamine uptake of multidrug resistant (mdr 1 gene expressing) mouse lymphoma cells. Hemolysin transporter protein encoding plasmids were eliminated from E. coli by a representative phenothiazine namely promethazine. Minimal inhibitory concentrations of tetracyclin and promethazine were lower for plasmidless bacteria as compared to the parent, plasmid carrying strains. The antibiotic resistance plasmid was cured of the R-plasmid of E. coli JE 2571, however, the ring substituted derivatives were less effective then parent compounds. The effect of some substituted phenothiazines on P-glycoprotein efflux-pump of mouse lymphoma cells were studied. The majority of ring substituted derivatives reversed the mdr of tumor cells. The 3,7,8,-trihydroxy- and 7,8-dihydroxy derivatives of chlorpromazine were effective as P-glycoprotein blockers, however, 7,8-diacetoxy-, 7,8dimetoxy-, 7-semicarbazone-, and 5-oxo-chlorpromazine derivatives had only moderate effect. A tomato lectin, specific for blood brain capillary endothelium was able to modify the activity of P-glycoprotein in tumor cells. Phenothiazine and tomato lectin had some antagonism in tumor cells. Our results suggest that the inhibition of P-glycoprotein function in murine tumor cells and inhibition of transporter protein in E. coli bacteria may depend on pi-electron superdelocalizibility and electrophile binding of the compounds to the transporter proteins. The intracellular accumulation of antibiotics or chemotherapeutics increased as a consequence of decreased drug efflux in both bacterial and tumor cell systems. The inhibition of the drug efflux-pump is the same for all individual cells of the population. These results can be realized by combination chemotherapy, however, antiplasmid effect itself cannot be exploited in this respect because the resistance was reversed in a part of the population only. The similarity with mdr P-glycoprotein in tumor cells and brain capillary endothels provides a good model for molecules opening the blood brain barrier. C1 ALBERT SZENT GYORGYI MED UNIV, INST BIOCHEM, H-6720 SZEGED, HUNGARY. US FDA, DEPT HLTH & HUMAN SERV, WASHINGTON, DC 20204 USA. RP Molnar, J (reprint author), ALBERT SZENT GYORGYI MED UNIV, INST MICROBIOL, DOM TER 10, H-6720 SZEGED, HUNGARY. NR 22 TC 54 Z9 54 U1 0 U2 4 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JAN-FEB PY 1997 VL 17 IS 1A BP 481 EP 486 PG 6 WC Oncology SC Oncology GA WK048 UT WOS:A1997WK04800077 PM 9066699 ER PT J AU Silberstein, E Kaplan, G Taboga, O Duffy, S Palma, E AF Silberstein, E Kaplan, G Taboga, O Duffy, S Palma, E TI Foot-and-mouth disease virus-infected but not vaccinated cattle develop antibodies against recombinant 3AB1 nonstructural protein SO ARCHIVES OF VIROLOGY LA English DT Article ID AMINO-ACID SUBSTITUTIONS; PERSISTENT INFECTION; ESCHERICHIA-COLI; IDENTIFICATION; REPLICATION; ANTIGENS; SEQUENCE AB Foot-and-mouth disease (FMD) vaccines induce antibodies against structural and some nonstructural proteins present in vaccine preparations. To differentiate between FMDV-infected and vaccinated animals, we developed immunochemical assays capable of detecting antibodies against a FMDV nonstructural protein. Recombinant nonstructural 3AB1 protein was expressed in E. coli and in insect cells and used to detect anti-3AB1 antibodies. ELISA and Western blot analysis showed that sera fi-om cattle infected with FMDV reacted with recombinant 3AB1 protein whereas sera from cattle which had been vaccinated against FMDV, mock-infected, or infected with different bovine viruses did not recognize the 3AB1 protein. In contrast, anti-virus infection associated antigen (VIAA) antibodies were present in both FMDV-infected and vaccinated animals. Detection of anti-3AB1 antibodies in sera of experimentally infected cattle obtained between 7 and 560 days postinfection indicated that immunological tests based on the detection of recombinant 3AB1 protein could be used for the diagnosis of FMDV infection. C1 INTA,CTR INVEST CIENCIAS VET,INST BIOTECNOL,RA-1708 MORON,BUENOS AIRES,ARGENTINA. US FDA,CTR BIOL EVALUAT & RES,OVRR,BETHESDA,MD. INTA,CTR INVEST CIENCIAS VET,INST PATOBIOL,BUENOS AIRES,DF,ARGENTINA. NR 33 TC 51 Z9 65 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1997 VL 142 IS 4 BP 795 EP 805 DI 10.1007/s007050050119 PG 11 WC Virology SC Virology GA WU855 UT WOS:A1997WU85500012 PM 9170505 ER PT B AU Geary, N AF Geary, N GP AMER SOC QUAL CONTROL AMER SOC QUAL CONTROL TI Will wonders ever cease? SO ASQC'S 51ST ANNUAL QUALITY CONGRESS PROCEEDINGS LA English DT Meeting Abstract CT 51st Annual Quality Control Congress of the American-Society-for-Quality-Control CY MAY 05-07, 1997 CL ORLANDO, FL SP Amer Soc Qual Control C1 US FDA, Off External Affairs, Small Business Liaison Staff, Rockville, MD 20857 USA. RP Geary, N (reprint author), US FDA, Off External Affairs, Small Business Liaison Staff, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC QUALITY CONTROL PI MILWAUKEE PA 611 E WISCONSIN AVENUE, MILWAUKEE, WI 53202 USA PY 1997 BP 105 EP 105 PG 1 WC Engineering, Industrial; Management SC Engineering; Business & Economics GA BK34H UT WOS:000071845700016 ER PT S AU Tall, A Sharp, D Zhong, S Hayek, T MasucciMagoulas, L Rubin, EM Breslow, JL AF Tall, A Sharp, D Zhong, S Hayek, T MasucciMagoulas, L Rubin, EM Breslow, JL BE Numano, F Ross, R TI Cholesteryl ester transfer protein and atherogenesis SO ATHEROSCLEROSIS IV: RECENT ADVANCES IN ATHEROSCLEROSIS RESEARCH: THE FOURTH SARATOGA INTERNATIONAL CONFERENCE ON ATHEROSCLEROSIS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Atherosclerosis IV - Recent Advances in Atherosclerosis Research, at the 4th Saratoga International Conference on Atherosclerosis CY FEB 06-08, 1996 CL HI SP Tokyo Med & Dental Univ, Japan Arteriosclerosis Soc, Japan Angiol Soc, Japan Heart Fdn, Japan Arteriosclerosis Res Fdn ID HIGH-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-A-I; TRANSGENIC MICE; HYPERTRIGLYCERIDEMIA; DEFICIENCY; METABOLISM; TRANSPORT; MUTATION; DISEASE; GENE C1 KUAKINI MED CTR, HONOLULU HEART PROGRAM, HONOLULU, HI 96817 USA. FED DRUG ADM, CTR BIOL EVALUAT & RES, DIV CELLULAR & GENE THERAPIES, BETHESDA, MD 20892 USA. TECHNION ISRAEL INST TECHNOL, RAMBAM MED CTR, FAC MED, IL-31096 HAIFA, ISRAEL. UNIV CALIF BERKELEY, LAWRENCE BERKELEY LAB, DIV CELL & MOL BIOL, BERKELEY, CA 94720 USA. ROCKEFELLER UNIV, NEW YORK, NY 10021 USA. RP Tall, A (reprint author), COLUMBIA UNIV, DEPT MED, DIV MOL MED, 630 W 168TH ST, PH 8 101, NEW YORK, NY 10032 USA. RI Breslow, Jan/B-7544-2008 NR 23 TC 13 Z9 14 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 1-57331-022-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 811 BP 178 EP 184 DI 10.1111/j.1749-6632.1997.tb52000.x PG 7 WC Medicine, Research & Experimental; Multidisciplinary Sciences; Peripheral Vascular Disease SC Research & Experimental Medicine; Science & Technology - Other Topics; Cardiovascular System & Cardiology GA BH93V UT WOS:A1997BH93V00018 PM 9186596 ER PT J AU Clausing, P Mothes, HK Opitz, B Kormann, S AF Clausing, P Mothes, HK Opitz, B Kormann, S TI Differential effects of communal rearing and preweaning handling on open-field behavior and hot-plate latencies in mice SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE early experience; postnatal handling communal rearing; open field; hot plate; nociception; mice ID ENVIRONMENTAL ENRICHMENT; LOCOMOTOR-ACTIVITY; ADULT-RATS; NOVELTY; EMOTIONALITY; HIPPOCAMPUS; INCREASES; MORPHINE; EXPOSURE; BRAIN AB On day 2 after delivery, dam of the DBA/1 mouse inbred strain (n=20/group) with their litter were allocated to one of the following groups: NH21, nonhandling, housed 1 litter/cage, weaned on postnatal day (PND) 21; H21, handling, housed 1 litter/cage, weaned on PND 21; NH30, nonhandling, group-housed (5 litters/cage), weaned on PND 30; H30, handling, group-housed (5 litters/cage), weaned on PND 30. Two male pups of each litter were color marked on PND 2. From PND 8-21 they were removed from their cage, gently held in the experimenter's hand for 5 min/day. The two marked males of each litter were housed together after weaning, and tested in the open-field on PNDs 51-53, and one of each of these siblings was tested for hot-plate latencies on PND 54. Being raised in group-housing and weaned on PND 30 resulted in offspring exhibiting shorter latencies to initiate behavior and higher percentages of centerfield entries in the open field, hot-plate latencies, however, remained unaffected. Preweaning handling increased hot-plate latencies and the number of grooming episodes in the open field, and it decreased defecation, percent centerfield entries and open-field activity in general. It is concluded that the two forms of early experience have different effects on neurobehavioral endpoints 8 weeks after birth. C1 UNIV HALLE WITTENBERG, SCH MED, INST BIOL, D-06108 HALLE, GERMANY. RP Clausing, P (reprint author), NATL CTR TOXICOL RES, DIV NEUROTOXICOL, HFT-132, 3900 NCTR DR, JEFFERSON, AR 72079 USA. NR 36 TC 18 Z9 19 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD JAN PY 1997 VL 82 IS 2 BP 179 EP 184 DI 10.1016/S0166-4328(97)80987-4 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA WE443 UT WOS:A1997WE44300006 PM 9030399 ER PT S AU Hellman, KB AF Hellman, KB BE Prokop, A Hunkeler, D Cherrington, AD TI Bioartificial organs as outcomes of tissue engineering - Scientific and regulatory issues SO BIOARTIFICIAL ORGANS: SCIENCE, MEDICINE, AND TECHNOLOGY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Bioartificial Organs - Science and Technology CY JUL 21-26, 1996 CL NASHVILLE, TENNESSEE SP Engn Fdn C1 US FDA, Rockville, MD 20852 USA. RP Hellman, KB (reprint author), US FDA, 5600 Fishers Lane, Rockville, MD 20852 USA. NR 4 TC 17 Z9 21 U1 0 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-098-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 831 BP 1 EP 9 PG 9 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Medicine, Research & Experimental; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Engineering; Research & Experimental Medicine; Science & Technology - Other Topics GA BK30T UT WOS:000071743100001 PM 9616697 ER PT S AU Chapekar, MS AF Chapekar, MS BE Prokop, A Hunkeler, D Cherrington, AD TI Regulatory considerations in the development of encapsulated cells SO BIOARTIFICIAL ORGANS: SCIENCE, MEDICINE, AND TECHNOLOGY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Bioartificial Organs - Science and Technology CY JUL 21-26, 1996 CL NASHVILLE, TENNESSEE SP Engn Fdn ID TUMOR-NECROSIS-FACTOR; INDUCTION C1 US FDA, Div Applicat Review & Policy, Off Therapeut Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Chapekar, MS (reprint author), US FDA, Div Applicat Review & Policy, Off Therapeut Res & Review, Ctr Biol Evaluat & Res, HFM-591,1401 Rockville Pike, Rockville, MD 20852 USA. NR 8 TC 0 Z9 0 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-098-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 831 BP 10 EP 12 PG 3 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Medicine, Research & Experimental; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Engineering; Research & Experimental Medicine; Science & Technology - Other Topics GA BK30T UT WOS:000071743100002 PM 9616698 ER PT J AU Saito, K Seishima, M Heyes, MP Song, H Fujigaki, S Maeda, S Vickers, JH Noma, A AF Saito, K Seishima, M Heyes, MP Song, H Fujigaki, S Maeda, S Vickers, JH Noma, A TI Marked increases in concentrations of apolipoprotein in the cerebrospinal fluid of poliovirus-infected macaques: Relations between apolipoprotein concentrations and severity of brain injury SO BIOCHEMICAL JOURNAL LA English DT Article ID CENTRAL NERVOUS-SYSTEM; A-I; LIPOPROTEINS; REGENERATION; CELLS AB Apolipoproteins in cerebrospinal fluid (CSF) might have important functional roles in the pathophysiology of brain and lipid metabolism in the vascular component. The present study examined apolipoprotein A-I (ape-A-I) and apolipoprotein E (apo-E) levels in CSF and serum from poliovirus-infected macaques. Poliovirus-infected macaques developed motor deficits and were classified into three groups: (1) muscle weakness in one or both legs; (2) partial paralysis in one or both legs; (3) complete paralysis in one or both legs. No motor deficits were evident in the control or sham-treated macaques. Ape-A-I concentrations in CSF were markedly elevated in poliovirus-infected macaques with weakness, partial or complete paralysis, in comparison with either control or sham-treated animals, and were proportional to the severity of motor impairment. Apo-E concentrations in CSF were also significantly elevated in poliovirus-infected macaques with complete paralysis. The magnitude of increase in CSF apo-A-I or apo-E concentrations was also closely associated with the degree of histologic neurological damage and inflammation (lesion scores). However, no changes in serum ape-A-I and apo-E concentrations were observed in the poliovirus-infected macaques compared with control macaques. Furthermore there were no significant correlations ape-A-I or apo-E concentrations between serum and CSF. We hypothesize that the elevation of ape-A-I and apo-E concentrations after poliovirus infection is caused by immune stimulation within the central nervous system (CNS). Measures of CSF ape-A-I and apo-E levels might serve as a useful marker for the severity and/or the range of CNS injury. C1 NIMH,NEUROTOXICOL LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,PATHOBIOL & PRIMATOL LAB,BETHESDA,MD 20892. RP Saito, K (reprint author), GIFU UNIV,SCH MED,DEPT LAB MED,GIFU 500,JAPAN. NR 19 TC 20 Z9 21 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JAN 1 PY 1997 VL 321 BP 145 EP 149 PN 1 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WB619 UT WOS:A1997WB61900018 PM 9003413 ER PT J AU Lyle, DB Fuchs, TA Casamento, JP Davis, CC Swicord, ML AF Lyle, DB Fuchs, TA Casamento, JP Davis, CC Swicord, ML TI Intracellular calcium signaling by Jurkat T-lymphocytes exposed to a 60 Hz magnetic field SO BIOELECTROMAGNETICS LA English DT Article DE ELF; magnetic fields; calcium; Jurkat; flow-cytometry ID ELECTROMAGNETIC-FIELDS; CELL-LINE; BIOLOGICAL-SYSTEMS; MOBILIZATION; OSCILLATIONS; STIMULATION; CALMODULIN; CANCER AB To explore possible biochemical mechanisms whereby electromagnetic fields of around 0.1 mT might affect immune cells or developing cancer cells, we studied intracellular calcium signaling in the model system Jurkat E6-1 human T-leukemia cells during and following exposure to a 60 Hz magnetic field. Cells were labeled with the intracellular calcium-sensitive fluorescent dye Fluo-3, stimulated with a monoclonal antibody against the cell surface structure CD3 (associated with ligand-stimulated T-cell activation), and analyzed on a FACScan flow-cytometer for increases in intensity of emissions in the range of 515-545 nm. Cells were exposed during or before calcium signal-stimulation to 0.15 mT(rms) 60 Hz magnetic field. The total DC magnetic field of 78.2 mu T was aligned 17.5 degrees off the vertical axis. Experiments used both cells cultured at optimal conditions at 37 degrees C and cells grown under suboptimal conditions of 24 degrees C, lowered external calcium, or lowered anti-CD3 concentration. These experiments demonstrate that intracellular signaling in Jurkat E6-1 was not affected by a 60 Hz magnetic field when culture and calcium signal-stimulation were optimal or suboptimal. These results do not exclude field-induced calcium-related effects further down the calcium signaling path way, such as on calmodulin or other calcium-sensitive enzymes. (C) 1997 Wiley-Liss, Inc. C1 UNIV MARYLAND, COLLEGE PK, MD 20742 USA. RP Lyle, DB (reprint author), US FDA, CTR DEVICES & RADIOL HLTH, RADIAT BIOL BRANCH, FDA-HFZ-114, 5600 FISHERS LANE, ROCKVILLE, MD 20857 USA. NR 27 TC 40 Z9 41 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0197-8462 J9 BIOELECTROMAGNETICS JI Bioelectromagnetics PY 1997 VL 18 IS 6 BP 439 EP 445 DI 10.1002/(SICI)1521-186X(1997)18:6<439::AID-BEM6>3.0.CO;2-3 PG 7 WC Biology; Biophysics SC Life Sciences & Biomedicine - Other Topics; Biophysics GA XP275 UT WOS:A1997XP27500006 PM 9261541 ER PT J AU Gu, Y Branham, WS Sheehan, DM Streck, RD AF Gu, Y Branham, WS Sheehan, DM Streck, RD TI Developmental expression of insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) in the early postnatal rat uterus. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 US FDA,NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 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. PY 1997 VL 56 SU 1 BP 4 EP 4 PG 1 WC Reproductive Biology SC Reproductive Biology GA XG865 UT WOS:A1997XG86500046 ER PT J AU Chen, JJ Kodell, RL Pearce, BA AF Chen, JJ Kodell, RL Pearce, BA TI Significance levels of randomization trend tests in the event of rare occurrences SO BIOMETRICAL JOURNAL LA English DT Article DE animal carcinogenicity; Cochran-Armitage; Fisher's exact test; Mantel-Haenszel; small frequency AB In the statistical evaluation of data from a dose-response experiment, it is frequently of interest to test for dose-related trend: an increasing trend in response with increasing dose. The randomization trend test, a generalization of Fisher's exact test, has been recommended for animal tumorigenicity testing when the numbers of tumor occurrences are small. This paper examines the type I error of the randomization trend test, and the Cochran-Armitage and Mantel-Haenszel tests. Simulation results show that when the tumor incidence rates are less than 10%, the randomization test is conservative; the test becomes very conservative when the incidence rate is less than 5%. The Cockran-Armitage and Mantel-Haenszel tests are slightly anti-conservative (liberal) when the incidence rates are lar er than 3%. Further, we propose a less conservatived method of calculating the p-value of the randomization trend test by excluding some permutations whose probabilities of occurrence are greater than the probability of the the observed outcome. C1 US FDA,NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,JEFFERSON,AR 72079. NR 17 TC 4 Z9 4 U1 0 U2 0 PU AKADEMIE VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 1997 VL 39 IS 3 BP 327 EP 337 DI 10.1002/bimj.4710390307 PG 11 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA XV658 UT WOS:A1997XV65800006 ER PT J AU Ahn, H Chen, JJ Lin, TYD AF Ahn, H Chen, JJ Lin, TYD TI A two-way analysis of covariance model for classification of stability data SO BIOMETRICAL JOURNAL LA English DT Article DE batch; classification; expiration date; Monte Carlo; shelf life ID BATCH AB This paper proposes a procedure for testing and classifying data with multiple factors. A two-way analysis of covariance is used to classify the differences among the batches as well as another factor such as package type and/or product strength. In the test procedure, slopes and intercepts of the main effects are tested using a combination of simultaneous and sequential F-tests. Based on the test procedure results, the data are classified into one of four different groups. For each group, shelf life can be calculated accordingly. We examine if the procedure produces satisfactory control of the probability of a Type I error and the power of detecting the difference of degradation rates and intercepts for different nominal levels. The method is evaluated with a Monte Carlo simulation study. The proposed procedure is compared with the current FDA procedure using real data. C1 SUNY STONY BROOK,DEPT APPL MATH & STAT,STONY BROOK,NY 11794. US FDA,NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,JEFFERSON,AR 72079. US FDA,CTR DRUG EVALUAT & RES,DIV BIOMETR 4,ROCKVILLE,MD 20857. NR 10 TC 0 Z9 0 U1 1 U2 1 PU AKADEMIE VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 1997 VL 39 IS 5 BP 559 EP 576 DI 10.1002/bimj.4710390505 PG 18 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA YE351 UT WOS:A1997YE35100004 ER PT J AU Zheng, Q AF Zheng, Q TI On a birth-and-death process induced distribution SO BIOMETRICAL JOURNAL LA English DT Article DE probability generating function; Mobius transform; generalized distribution; linear birth-and-death processes AB A type of distribution induced by the linear birth-and-death processes is useful in modeling certain biological phenomena. In addition to extending some existing results, new findings are presented concerning the mathematical properties of the distribution. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU AKADEMIE VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 1997 VL 39 IS 6 BP 699 EP 705 DI 10.1002/bimj.4710390608 PG 7 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA YP110 UT WOS:000071243700006 ER PT J AU Roy, J Saha, P Sultana, S Kenyon, AS AF Roy, J Saha, P Sultana, S Kenyon, AS TI Rapid screening of marketed paracetamol tablets: Use of thin-layer chromatography and a semiquantitative spot test SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Article ID PHARMACEUTICALS AB Evaluated is the use of thin-layer chromatography (TLC) to determine the qualify of paracetamol tablets marketed in Bangladesh. The procedure was carried out using a cheap and rapid TLC method developed by the U.S. Food and Drug Administration. Reported also is a semiquantitative specific spot test for screening paracetamol tablets. The results obtained indicate that, of the 38 brands tested, three were spurious, while 11 were of borderline qualify. In some cases, the results were also verified using the British Pharmacopoeia method. The simplified tests described in this article cannot replace the British Pharmacopoeia or U.S. Pharmacopeia methods but can be employed as initial screening tests. C1 US FDA,DIV DRUG ANAL,ST LOUIS,MO 63101. JAHANGIRNAGAR UNIV,DEPT PHARM,DHAKA,BANGLADESH. NR 7 TC 21 Z9 21 U1 0 U2 2 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA DISTRIBUTION AND SALES, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PY 1997 VL 75 IS 1 BP 19 EP 22 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WV440 UT WOS:A1997WV44000003 PM 9141746 ER PT J AU Sipowicz, MA Weghorst, CM Shiao, YH Buzard, GS Calvert, RJ Anver, MR Anderson, LM Rice, JM AF Sipowicz, MA Weghorst, CM Shiao, YH Buzard, GS Calvert, RJ Anver, MR Anderson, LM Rice, JM TI Lack of p53 and ras mutations in Helicobacter hepaticus-induced liver tumors in A/JCr mice SO CARCINOGENESIS LA English DT Article ID CHRONIC ACTIVE HEPATITIS; MOUSE-LIVER; PROTOONCOGENE ACTIVATION; LUNG-TUMORS; GASTRIC-CANCER; B6C3F1 MOUSE; GENES; FREQUENCY; SPECTRA; PYLORI AB Helicobacter hepaticus is a recently discovered bacterium that invades mouse liver causing chronic active hepatitis followed by development of preneoplastic hepatocellular foci, hepatocellular adenomas and carcinomas. This establishes a unique animal model for study of the mechanisms of cancer development due to a chronic bacterial infection. A possible mechanism of bacteria-associated tumorigenesis is mutation of oncogenes or tumor suppressor genes. Since mutations in ras oncogenes have been widely detected in a variety of chemically induced and spontaneous mouse liver tumors and specific mutations in the p53 tumor suppressor gene have been associated with human bladder cancers attributed to chronic schistosomal infection, we studied exons 1 and 2 of the N-, K- and H-ras genes and exons 5-8 of the p53 gene for the presence of point mutations in 25 liver tumors from 10 naturally infected A/JCr mice, ranging in age from 16 to 24 months. The 20 adenomas and five carcinomas varied in size from 0.1 to 2.3 cm and arose in livers characterized by a wide assortment of pathological profiles, including hepatitis, inflammation, hyperplasia, hypertrophy, leukocyte infiltration, necrosis and focal phenotypic alteration. DNA samples extracted from formalin-fixed paraffin-embedded tissues were screened by PCR/SSCP analysis and showed no mutations in the analyzed genes. Complete absence of mutations in ras genes in 25 mouse liver tumors is unusual. Other genes may be targeted or H.hepaticus infection causes liver cancer through other pathways than direct damage to DNA. C1 SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD. US FDA,OFF SPECIAL NUTR,CLIN RES & REVIEW STAFF,LAUREL,MD. RP Sipowicz, MA (reprint author), NCI,COMPARAT CARCINOGENESIS LAB,FCRDC,FREDERICK,MD 21702, USA. NR 32 TC 26 Z9 27 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 1997 VL 18 IS 1 BP 233 EP 236 DI 10.1093/carcin/18.1.233 PG 4 WC Oncology SC Oncology GA WJ978 UT WOS:A1997WJ97800031 PM 9054612 ER PT J AU Doerge, DR Divi, RL Deck, J Taurog, A AF Doerge, DR Divi, RL Deck, J Taurog, A TI Mechanism for the anti-thyroid action of minocycline SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID RADICAL MECHANISM; COVALENT BINDING; PEROXIDASE; IODINATION; THYROGLOBULIN; ACTIVATION AB Administration of minocycline (MN), a tetracycline antibiotic, produces a black pigment in the thyroids of humans and several species of experimental animals and antithyroid effects in rodents. We have previously shown that these effects appear to be related to interactions of MN with thyroid peroxidase (TPO), the key enzyme in thyroid hormone synthesis. In the present study, the mechanisms for inhibition of TPO-catalyzed iodination and coupling reactions by MN were investigated. MN was stable in the presence of TPO and H2O2, but adding iodide or a phenolic cosubstrate caused rapid conversion to several products. TPO-dependent product formation, characterized by on-line LC-APCI/MS and H-1-NMR, involved oxidative elimination to form the corresponding benzoquinone with subsequent dehydrogenation at the aliphatic 4-(dimethylamino) group. Addition of thiol-containing polymers (bovine serum albumin or thiol-agarose chromatographic beads) had a minimal effect on MN oxidation by TPO, but substantially reduced product formation and produced concomitant losses in free thiols. Covalent bonding through a thioether linkage of a reactive intermediate, the benzoquinone iminium ion, was inferred from these findings. Iodide- and phenolic cosubstrate-dependent oxidation of tetracycline to demethylated and dehydrogenated products was also observed, although at a slower rate than MN. The products and kinetics observed with MN were consistent with oxidation of MN by either the enzymatic iodinating species formed by reaction of TPO compound I with iodide or phenoxyl radicals/cations generated by TPO-mediated oxidation of a phenolic cosubstrate. The proposed reaction mechanism is consistent with alternate substrate inhibition of TPO-catalyzed iodination of tyrosyl residues in thyroglobulin (Tg) by MN, as previously reported. Furthermore, the observed phenoxyl radical-mediated oxidation of MN is consistent with its previously reported potent inhibition of the coupling of hormonogenic iodotyrosine residues in Tg in the reaction that forms thyroid hormones. The proposed reaction mechanism also implicates a reactive benzoquinone iminium ion intermediate that could be important in toxicity of MN. C1 UNIV TEXAS,SW MED CTR,DEPT PHARMACOL,DALLAS,TX 75235. RP Doerge, DR (reprint author), US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 37 TC 22 Z9 23 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN PY 1997 VL 10 IS 1 BP 49 EP 58 DI 10.1021/tx960150g PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA WD805 UT WOS:A1997WD80500007 PM 9074802 ER PT J AU Burkhart, GA Sevka, MJ Temple, R Honig, PK AF Burkhart, GA Sevka, MJ Temple, R Honig, PK TI Temporal decline in filling prescriptions for terfenadine closely in time with those for either ketoconazole or erythromycin SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article AB Temporal changes in the rates of filling terfenadine prescriptions within 2 days of those for either oral erythromycin or oral ketoconazole were described with use of paid pharmacy claims data from 1988 through 1994 in state Medicaid programs from Michigan and Ohio and in a large health maintenance organization. There were rapid and significant declines in the rates of filling prescriptions for either erythromycin or ketoconazole within 2 days of prescriptions for terfenadine in all three databases that coincided with 1992 publicity about the cardiovascular risk of terfenadine. These findings suggest that the use of terfenadine with contraindicated medications has declined in response to relabeling and publicity concerning the safe use of terfenadine. Further study is necessary to estimate the absolute level of concurrent use of terfenadine with contraindicated medications. RP Burkhart, GA (reprint author), US FDA,CTR DRUG EVALUAT & RES,HFD-120,1451 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 4 TC 26 Z9 26 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 1997 VL 61 IS 1 BP 93 EP 96 DI 10.1016/S0009-9236(97)90185-5 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WF291 UT WOS:A1997WF29100010 PM 9024177 ER PT J AU Blodgett, RJ AF Blodgett, RJ TI Adding functions to ensure regression converges SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE nonlinear regression; L-p-regression; exponential growth curves; probit curves; logistic curves ID EXISTENCE; MODELS AB Regression fits a curve to data by minimizing a function of the residuals. The process of fitting a family of functions may fail to converge because the family of candidate functions has no minimum. After investigating what functions to add to a family to ensure a minimum exists, four families are examined. The family of polynomials needs no additional functions. Additional functions are found for the families of exponential growth curves, probit curves, and logistic curves. A sufficient condition tells when the minimum is not in the original family. C1 US FDA,WASHINGTON,DC 20204. NR 10 TC 0 Z9 0 U1 1 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0361-0926 J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PY 1997 VL 26 IS 5 BP 1203 EP 1214 DI 10.1080/03610929708831976 PG 12 WC Statistics & Probability SC Mathematics GA WX125 UT WOS:A1997WX12500010 ER PT J AU Lee, CJ Wang, TR Tai, SS AF Lee, CJ Wang, TR Tai, SS TI Immunologic epitope, gene, and immunity involved in pneumococcal glycoconjugate SO CRITICAL REVIEWS IN MICROBIOLOGY LA English DT Review DE monoclonal antibody; pneumolysin gene; protective immunity; conjugate vaccine ID INFLUENZAE TYPE-B; MEMBRANE PROTEIN COMPLEX; THIOL-ACTIVATED TOXIN; STREPTOCOCCUS-PNEUMONIAE; CONJUGATE VACCINES; SURFACE PROTEIN; CAPSULAR POLYSACCHARIDE; NUCLEOTIDE-SEQUENCE; OTITIS-MEDIA; COMPARATIVE EFFICACY AB Pneumococcal infection persists as a major cause of pneumonia, otitis media, and meningitis in infants. Children less than 2 years of age show the highest incidence of pneumococcal diseases. Production of monoclonal antibody (MAb) to polysaccharide (PS) and binding characteristics to PS epitopes were studied. Removal of the O-acetyl group from 9V PS by alkali hydrolysis resulted in a decreased binding with rabbit 9V antiserum (AS). However, the binding reaction with 9V MAb was less affected by the loss of O-acetyl content. Type 9V IgG MAb provided passive protection and enhanced the opsonophagocytic activity of polymorphonuclear (PMN) leukocytes to kill type 9V pneumococci. The pathogenecity of pneumococci is attributed to various virulence factors distributed on the cell surface, including capsular polysaccharide and protein antigens, for example, pneumolysin, autolysin, pneumococcal surface protein A (PspA), pneumococcal surface adhesion (PsaA), and hemin binding protein. Some of these protein antigens may be used as a component to combine with pneumococcal PS vaccine or as a carrier of conjugate vaccine. Clinical trials of pneumococcal conjugate vaccines showed that covalent linkage of capsular PS to protein carriers improved the immunogenicity of the PS. Development of glycoconjugate vaccine for selected pneumococcal types will help solve the problem of poor immunogenecity of PS vaccine in young children used for prevention of pneumococcal infection. C1 HOWARD UNIV,COLL MED,DEPT MICROBIOL,WASHINGTON,DC 20059. RP Lee, CJ (reprint author), US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852, USA. NR 129 TC 10 Z9 10 U1 0 U2 1 PU CRC PRESS INC PI BOCA RATON PA 2000 CORPORATE BLVD NW, JOURNALS CUSTOMER SERVICE, BOCA RATON, FL 33431 SN 1040-841X J9 CRIT REV MICROBIOL JI Crit. Rev. Microbiol. PY 1997 VL 23 IS 2 BP 121 EP 142 DI 10.3109/10408419709115133 PG 22 WC Microbiology SC Microbiology GA XJ351 UT WOS:A1997XJ35100003 PM 9226111 ER PT S AU Murano, G AF Murano, G BE Brown, F Fernandez, J TI FDA perspective on specifications for biotechnology products - from IND to PLA SO DEVELOPMENT OF SPECIFICATIONS FOR BIOTECHNOLOGY PHARMACEUTICAL PRODUCTS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Symposium on Development of Specifications for Biotechnology Pharmaceutical Products CY MAY 02-03, 1996 CL SAN FRANCISCO, CA SP PDA W Coast Chapter, Int Assoc Biol Stand DE specifications; characterization; validation; identity purity; potency AB Quality standards are obligatory throughout development, approval and post-marketing phases of biotechnology-derived products, thus assuring product identity, purity, and potency/strength. The process of developing and setting specifications should be based on sound science and should represent a logical progression of actions based on the use of experiential data spanning manufacturing process validation, consistency in production, and characterization of relevant product properties/attributes, by multiple analytical means. This interactive process occurs in phases, varying in rigour. it is best described as encompassing a framework which starts with the implementation of realistic/practical operational quality limits, progressing to the establishment/adoption of more stringent specifications. The historical database is generated from preclinical, toxicology and early clinical lots. This supports the clinical development programme which, as it progresses, allows for further assay method validation/refinement, adoption/addition due to relevant or newly recognized product attributes or rejection due to irrelevance. In the next phase, (licensing/approval) specifications are set through extended experience and validation of both the preparative and analytical processes, to include availability of suitable reference standards and extensive product characterization throughout its proposed dating period. Subsequent to product approval, the incremental database of test results serves as a natural continuum for further evolving/refining specifications. While there is considerable latitude in the kinds of testing modalities finally adopted to establish product quality on a routine basis, for both drugs and drug products, it is important that the selection takes into consideration relevant (significant) product characteristics that appropriately reflect on identity, purity and potency. RP Murano, G (reprint author), US FDA,CTR BIOL EVALUAT & RES,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 0 TC 10 Z9 10 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6569-0 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1997 VL 91 BP 3 EP 13 PG 11 WC Biology; Biotechnology & Applied Microbiology SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology GA BK04H UT WOS:A1997BK04H00001 ER PT J AU Whiteley, M Mathers, PH Jamrich, M AF Whiteley, M Mathers, PH Jamrich, M TI Expression pattern of an axolotl floor plate-specific fork head gene reflects early developmental differences between frogs and salamanders SO DEVELOPMENTAL GENETICS LA English DT Article DE axolotl; Xenopus; fork head; gastrulation; floor plate; notochord ID DNA-BINDING MOTIF; XENOPUS-LAEVIS; AMBYSTOMA-MEXICANUM; TRANSCRIPTION FACTORS; NOTOCHORD FORMATION; MOUSE EMBRYO; GASTRULATION; PINTALLAVIS; MESODERM; FAMILY AB Gastrulation is one of the most important stages of animal development and, as such, tends io be remarkably conserved. Therefore ii is interesting to see that the two amphibian species, Xenopus laevis (frog) and Ambystoma mexicanum (axolotl), are different in the arrangement of cell types lust before and during gastrulation. in Xenopus, the cells that will form dorsal mesoderm are located deep in the dorsal marginal zone, while in the axolott, these are on the surface of the embryo. in this study we investigated whether homologous genes known io be involved in the formation of dorsal structures show a different pattern of expression in these two species. For this purpose, we isolated a fork head gene (AxFKHI) from the axolotl, which is likely io be the homologue of the Xenopus fork head gene, XFKH1 (Pintallavis, XFD-1). We find that AxFKH1 and XFKH1 have a similar pattern of expression, but there are some important differences. In early gastrulae, transcripts are detected in the organizer region of both species. In late gastrulae, the transcripts in Xenopus are located in both the superficial and deep layers, but they are only found in the superficial layer of axolotl embryos. During neurulation, XFKH1 is expressed in notochord and neural floor plate, whereas AxFKH1 is expressed in the neural floor plate only We propose that the differences in expression pattern of these two genes are due io a difference in formation of dorsal structures between these two species. Furthermore, the expression pattern of these two genes early in gastrulation is consistent with the idea that al least some of the neural floor plate cells are already determined at this time. (C) 1997 Wiley-Liss, Inc. RP Whiteley, M (reprint author), CTR BIOL EVALUAT & RES,FOOD & DRUG ADMIN,DIV CELLULAR & GENE THERAPIES,DEV BIOL LAB,ROCKVILLE,MD 20852, USA. NR 40 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0192-253X J9 DEV GENET JI Dev. Genet. PY 1997 VL 20 IS 2 BP 145 EP 151 DI 10.1002/(SICI)1520-6408(1997)20:2<145::AID-DVG7>3.0.CO;2-7 PG 7 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA WX470 UT WOS:A1997WX47000007 PM 9144925 ER PT S AU Prosky, L Lee, SC AF Prosky, L Lee, SC BE Kritchevsky, D Bonfield, C TI Classification of complex carbohydrates SO DIETARY FIBER IN HEALTH AND DISEASE SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 5th Washington Symposium on Dietary Fiber - The Vahouny Fiber Symposium CY MAR 26-29, 1996 CL WASHINGTON, D.C. RP Prosky, L (reprint author), US FDA, 10265 NOLAN DR, ROCKVILLE, MD 20850 USA. NR 24 TC 1 Z9 1 U1 1 U2 2 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45703-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 427 BP 55 EP 61 PG 7 WC Medicine, Research & Experimental; Nutrition & Dietetics SC Research & Experimental Medicine; Nutrition & Dietetics GA BJ94B UT WOS:A1997BJ94B00007 PM 9361831 ER PT J AU Rafii, F RuselerVanEmbden, JGH Asad, YF AF Rafii, F RuselerVanEmbden, JGH Asad, YF TI Azoreductase and nitroreductase activity of bacteria in feces from patients with an ileal reservoir SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE pouchitis; azoreductase; nitroreductase; ulcerative colitis; ileal reservoir ID POUCHITIS; REDUCTION; BOWEL AB Azoreductase and nitroreductase activities of bacteria in feces of five patients with ileal reservoirs were evaluated, both at the onset of symptoms of pouchitis and following recovery after treatment with drugs. All stool samples tested had bacteria with azoreductase and nitroreductase activities. Azoreductase and nitroreductase activities were higher after recovery than during attacks of pouchitis. During reestablishment of the normal microflora in the ileal reservoirs after pouchitis, the anaerobic bacteria increased and the aerobic bacteria decreased. C1 ERASMUS UNIV ROTTERDAM,DEPT IMMUNOL,NL-3000 DR ROTTERDAM,NETHERLANDS. RP Rafii, F (reprint author), US FDA,NATL CTR TOXICOL RES,DIV MICROBIOL,JEFFERSON,AR 72079, USA. NR 15 TC 8 Z9 9 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JAN PY 1997 VL 42 IS 1 BP 133 EP 136 DI 10.1023/A:1018801608744 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WE663 UT WOS:A1997WE66300021 PM 9009128 ER PT B AU Paule, MG AF Paule, MG BE Nahas, GG Burks, TF TI Behavioral consequences of chronic marijuana smoke exposure in primates SO DRUG ABUSE IN THE DECADE OF THE BRAIN LA English DT Proceedings Paper CT International Symposium on Drug Abuse in the Decade of the Brain CY SEP 22-23, 1995 CL HOUSTON, TX SP Univ Texas, Houston Hlth Sci Ctr, Houstons Drug Free Business Initiat AB Adolescent male rhesus monkeys were trained to perform behavioral tasks thought to allow measurement of aspects of motivation and color and position discrimination. Subjects were assigned to one of four treatment groups (n=7-8): SH = sham exposure 7 days/week; EX = smoke from one extracted marijuana cigarette/day, 7 days/week; LO = marijuana smoke on weekends, sham exposure Mon-Fri; and HI = smoke from one marijuana cigarette/day, 7 days/week For the motivation task, both LO and HI group subjects worked less for food than did both control groups during the last several months of exposure. These effects disappeared within 2-3 months of cessation of treatment. Performance of the color and position discrimination task was adversely affected in one of eight HI subjects throughout most of the chronic exposure. These data suggest that: 1) marijuana produces an 'amotivation'-like syndrome in rhesus monkeys during periods of chronic use; 2) this syndrome occurs whether exposure occurs daily or on weekends only; 3) this effect of chronic marijuana exposure disappears only several weeks to months after the last exposure; and 4) some subjects may be much more sensitive to the adverse effects of marijuana than are others. RP Paule, MG (reprint author), NATL CTR TOXICOL RES,DIV NEUROTOXICOL,BEHAV TOXICOL LAB,HFT-132,JEFFERSON,AR 72079, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA VAN DIEMENSTRAAT 94, 1013 CN AMSTERDAM, NETHERLANDS BN 90-5199-305-6 PY 1997 BP 153 EP 157 PG 5 WC Substance Abuse SC Substance Abuse GA BH38Z UT WOS:A1997BH38Z00019 ER PT J AU AbuLafi, S Turujman, SA AF AbuLafi, S Turujman, SA TI A chiral HPLC method for the simultaneous separation of configurational isomers of the predominant cis/trans forms of astaxanthin SO ENANTIOMER LA English DT Article; Proceedings Paper CT 7th International Symposium on Chiral Discrimination (ISCD 7) CY NOV 12-16, 1995 CL JERUSALEM, ISRAEL DE astaxanthin; chiral HPLC; chromatographic separation; Pirkle D-phenylglycine column; salmon; Sumichiral column ID MESO-ASTAXANTHIN; CAROTENOIDS; RESOLUTION; SALMON AB We report an HPLC method that allows the simultaneous separation of configurational isomers of the predominant cis/trans forms of astaxanthin. The configurational isomers of the all-trans-, and most of the configurational isomers of the 9-cis-, 13-cis- and 15-cis-astaxanthin were separated on a Sumichiral OA-2000 column, which is manufactured and packed in Japan with a Pirkle covalent D-phenylglycine chiral stationary phase (CSP). The large separation of the cis isomers from the all-trans isomers that we report here ensure the suitability of this method for the routine determination of the ratio of the configurational isomers of all-trans-astaxanthin. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,OFF COSMET & COLORS,WASHINGTON,DC 20204. NR 13 TC 8 Z9 8 U1 1 U2 3 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1024-2430 J9 ENANTIOMER JI Enantiomer PY 1997 VL 2 IS 1 BP 17 EP 25 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA XD743 UT WOS:A1997XD74300003 PM 9676271 ER PT J AU Montuenga, LM Martinez, A Miller, MJ Unsworth, EJ Cuttitta, F AF Montuenga, LM Martinez, A Miller, MJ Unsworth, EJ Cuttitta, F TI Expression of adrenomedullin and its receptor during embryogenesis suggests autocrine or paracrine modes of action SO ENDOCRINOLOGY LA English DT Article ID IMMUNOREACTIVE ADRENOMEDULLIN; HYPOTENSIVE PEPTIDE; PORCINE TISSUE; GROWTH-FACTORS; CELLS; RAT; PHEOCHROMOCYTOMA; IDENTIFICATION AB The present study reports the developmental patterns of expression of adrenomedullin (AM) in rat and mouse embryos. AM is a novel multifunctional peptide recently isolated from a human pheochromocytoma, which has been shown to promote growth in a variety of mammalian cell Lines. We have applied several techniques to investigate the localization of both tile AM peptide and its receptor throughout development. Immunocytochemical detection has been performed using different specific antibodies against AM and its gene-related peptide pro-AM N-terminal 20 peptide. In situ hybridization showed the localization of the messenger RNAs for AM and its receptor. Western blot analysis together with reverse transcription-PCR gave further support to the localization of AM and ita receptor in a variety of embryonic tissues. The localization of the receptor paralleled that of AM itself, suggesting an autocrine or paracrine mode of action. The spatio-temporal pattern of expression of AM in cardiovascular, neural, Rad skeletal-forming tissues as well as in the main embryonic internal organs is described. The primitive placenta, especially the giant trophoblastic dells, shows high levels of AM and AM receptor. The heart is the first organ that expresses AM during development. Tho kidney, lung, and developing tooth, in which epithelial-mesenchymal interactions are taking place, show specific patterns of AM expression. In several regions of the embryo, the patterns of AM expression correspond to the degree of differentiation. The possible involvement of AM in the control of embryonic invasion, proliferation and differentiation is discussed. C1 UNIV NAVARRA, DEPT HIST & PATHOL, E-31080 PAMPLONA, SPAIN. US FDA, CTR BIOL EVALUAT & RES, BETHESDA, MD 20892 USA. RP Montuenga, LM (reprint author), NATL CANC INST, BIOMARKERS & PREVENT RES BRANCH, 9610 MED CTR DR, ROCKVILLE, MD 20850 USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 33 TC 156 Z9 158 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 1997 VL 138 IS 1 BP 440 EP 451 DI 10.1210/en.138.1.440 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VZ824 UT WOS:A1997VZ82400059 PM 8977434 ER PT J AU Foran, JA Allaben, WT Ashby, J Bass, R Wharf, C Bucher, JR Burnam, W Bus, JS Butterworth, BE Carakostas, M Emerson, J Cardona, RA Cohen, SM DeGeorge, J FennerCrisp, P Gaylor, D Gee, JF Goodman, JI Grant, DL Hattan, DG Hayashi, Y Henderson, RF Herrman, JL Koeter, HBWM LeBoeuf, RA Lorentzen, RJ McConnell, EE Mitsumori, K Olin, SS Parker, JC Renwick, A Stevens, JT Swenberg, JA Taylor, AS VanGemert, M Vu, V Walker, R Watson, M Yielding, KL AF Foran, JA Allaben, WT Ashby, J Bass, R Wharf, C Bucher, JR Burnam, W Bus, JS Butterworth, BE Carakostas, M Emerson, J Cardona, RA Cohen, SM DeGeorge, J FennerCrisp, P Gaylor, D Gee, JF Goodman, JI Grant, DL Hattan, DG Hayashi, Y Henderson, RF Herrman, JL Koeter, HBWM LeBoeuf, RA Lorentzen, RJ McConnell, EE Mitsumori, K Olin, SS Parker, JC Renwick, A Stevens, JT Swenberg, JA Taylor, AS VanGemert, M Vu, V Walker, R Watson, M Yielding, KL TI Principles for the selection of doses in chronic rodent bioassays SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material ID CARCINOGENICITY AB Dose selection in chronic rodent bioassays has been one of the most debated issues in risk assessment. The Committee on Risk Assessment Methods of the National Research Council attempted but failed, in 1993 to reach consensus on how to select doses for chronic rodent bioassays. However, a more recent effort conducted by the ILSI Risk Science Institute has resulted in a consensus set of principles for dose selection, including selection of the highest dose for chronic rodent bioassays. The principles encourage a move away from sole reliance on a maximum tolerated dose (MTD), as it has been traditionally defined (primarily by body weight and histopathology), and toward the use of sound scientific and toxicologic principles for the selection of all doses in the chronic bioassay. Specifically, the principles recommend that dose selection for chronic studies must be based on sound toxicologic principles; dose selection should consider human exposure; dose selection should be based on a variety of endpoints and effects derived from prechronic studies; and dose selection should consider physicochemical and other factors. Implementation of the principles internationally will have two important benefits: improvement in the quality and consistency of the rodent bioassay and international harmonization of dose selection procedures. C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. ZENECA LTD,ALDERLEY PARK,CHESHIRE,ENGLAND. NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. US EPA,OFF PESTICIDE PROGRAMS,WASHINGTON,DC 20460. DOW CHEM CO USA,MIDLAND,MI 48674. CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. COCA COLA CO,ATLANTA,GA. UNIROYAL CHEM CO,BETHANY,CT. UNIV NEBRASKA,MED CTR,OMAHA,NE. US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. CALIF ENVIRONM PROTECT AGCY,DEPT PESTICIDE REGULAT,SACRAMENTO,CA. MICHIGAN STATE UNIV,DEPT PHARMACOL & TOXICOL,E LANSING,MI 48824. HLTH CANADA,PEST MANAGEMENT REGULATORY AGCY,OTTAWA,ON K1A 0L2,CANADA. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NATL INST HLTH SCI,DIV RISK ASSESSMENT,TOKYO,JAPAN. LOVELACE BIOMED & ENVIRONM RES INST,INHALAT TOXICOL RES INST,ALBUQUERQUE,NM 87185. WHO,INT PROGRAMME CHEM SAFETY,CH-1211 GENEVA,SWITZERLAND. ORG ECON COOPERAT & DEV,ENVIRONM DIRECTORATE,PARIS,FRANCE. PROCTER & GAMBLE CO,CINCINNATI,OH. US FDA,OFF PLANNING & STRATEG INITIAT,WASHINGTON,DC 20204. NATL INST HLTH SCI,BIOL SAFETY RES CTR,TOKYO 158,JAPAN. US EPA,OFF RES & DEV,WASHINGTON,DC 20460. UNIV SOUTHAMPTON,CLIN PHARMACOL GRP,SOUTHAMPTON,HANTS,ENGLAND. CIBA GEIGY LTD,BASEL,SWITZERLAND. UNIV N CAROLINA,CHAPEL HILL,NC. BRI INT,SAN DIEGO,CA. US EPA,OFF POLLUT PREVENT & TOX,WASHINGTON,DC 20460. UNIV SURREY,SCH BIOL SCI,GUILDFORD GU2 5XH,SURREY,ENGLAND. UNIV TEXAS,MED BRANCH,GALVESTON,TX 77550. CHARLES CONN & VAN GEMERT,CHARLOTTE HALL,MD. RP Foran, JA (reprint author), ILSI RISK SCI INST,1126 16TH ST NW,WASHINGTON,DC 20036, USA. NR 13 TC 12 Z9 13 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 1997 VL 105 IS 1 BP 18 EP 20 DI 10.2307/3433048 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA WM698 UT WOS:A1997WM69800008 PM 9074868 ER PT J AU Duffy, PH Leakey, JEA Pipkin, JL Turturro, A Hart, RW AF Duffy, PH Leakey, JEA Pipkin, JL Turturro, A Hart, RW TI The physiologic, neurologic, and behavioral effects of caloric restriction related to aging, disease, and environmental factors SO ENVIRONMENTAL RESEARCH LA English DT Article; Proceedings Paper CT 5th International Symposium on Neurobehavioral Methods and Effects in Occupational and Environmental Health CY DEC 03-07, 1994 CL CAIRO, EGYPT ID MYC PROTOONCOGENE EXPRESSION; SCHEDULE-INDUCED-POLYDIPSIA; MALE FISCHER-344 RAT; DIETARY RESTRICTION; MICE; HYPOTHALAMUS; STRESS; ACQUISITION; METABOLISM; VARIABLES AB Little is known about the mechanisms by which acute and chronic caloric restriction (CR) modulate disease, longevity, and toxicity. To study these endpoints, behavioral parameters such as food and water consumption and physiologic parameters such as motor activity, body temperature, metabolic output (oxygen use), and respiratory quotient (RQ) were continuously monitored in 26-month-old male B6C3F1 mice and Fischer 344 rats fed either ad libitum (AL) or a CR diet (60% of AL). Different dietary regimens were used: rodents were (1) chronically food-restricted using daily feeding starting at 14 months of age, (2) chronically food-restricted using alternate day feeding, or (3) abruptly switched from CR to AL (acute CR). The physiologic and behavioral changes seen with chronic and acute CR were consistent across strains and species. Average body temperature, the number of meals, and the ratio of food/water consumption were significantly lower in CR rodents than in AL rodents. Also, the daily range of body temperature, oxygen metabolism, RQ, average water consumption, and motor activity was significantly higher in CR rodents. CR caused the onset of altered neurobehavioral functions such as abnormal water consumption; increases in motor activity, serum corticosterone, and stress proteins (HSP); and decreases in the basal setpoint for body temperature and brain metabolism. These changes strongly suggest that many beneficial effects of CR are controlled by the hypothalamic-pituitary-adrenal axis via hormonal regulation. This study supports the assertion that nutritional status may be a primary factor of consideration in development of safety standards and assessment of risk. (C) 1997 Academic Press. RP Duffy, PH (reprint author), NATL CTR TOXICOL RES,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 25 TC 69 Z9 69 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PY 1997 VL 73 IS 1-2 BP 242 EP 248 DI 10.1006/enrs.1997.3714 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA XY135 UT WOS:A1997XY13500029 PM 9311553 ER PT S AU Ambrosone, CB Shields, PG AF Ambrosone, CB Shields, PG BE Aldaz, CM Gould, MN McLachlan, J Slaga, TJ TI Molecular epidemiology of breast cancer SO ETIOLOGY OF BREAST AND GYNECOLOGICAL CANCERS SE PROGRESS IN CLINICAL AND BIOLOGICAL RESEARCH LA English DT Article; Proceedings Paper CT 9th International Conference on Carcinogenesis and Risk Assessment CY NOV 29-DEC 02, 1995 CL AUSTIN, TEXAS ID MAMMARY EPITHELIAL-CELLS; NITROSO-N-METHYLUREA; DNA ADDUCT FORMATION; FRAGMENT-LENGTH-POLYMORPHISM; LUNG-CANCER; METABOLIC-ACTIVATION; GENETIC POLYMORPHISMS; CARCINOGEN-METABOLISM; HETEROCYCLIC AMINES; CIGARETTE-SMOKING C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Ambrosone, CB (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 109 TC 8 Z9 9 U1 0 U2 0 PU WILEY-LISS, INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0361-7742 BN 0-471-16901-3 J9 PROG CLIN BIOL RES JI Prog.Clin.Biol.Res. PY 1997 VL 396 BP 83 EP 99 PG 17 WC Biology; Oncology; Public, Environmental & Occupational Health; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Oncology; Public, Environmental & Occupational Health; Research & Experimental Medicine GA BK06D UT WOS:000071016800006 PM 9108591 ER PT B AU Barnett, J Staruszkiewicz, W AF Barnett, J Staruszkiewicz, W BE Martin, RE Collette, RL Salvin, JW TI Standards development and implementation SO FISH INSPECTION, QUALITY CONTROL AND HACCP: A GLOBAL FOCUS LA English DT Proceedings Paper CT 2nd International Conference on Fish Inspection and Quality Control CY MAY 19-24, 1996 CL ARLINGTON, VA SP Natl Fisheries Inst, US FDA, UN Food & Agr Org, US Natl Marine Fisheries Serv, Canadian Dept Fihseries & Oceans, Fisheries Council Canada, Joseph Slavin & Associates, GEM Biomed Inc AB Seafood is a commodity for which consumer consumption continues to increase each year. One of the reasons for this continued increase is that consumers are becoming aware of the quality characteristics of seafood and its nutritional value. But, when purchased, they expect to receive high quality because of the high price associated with the purchase of seafood items. C1 US FDA, Bothell, WA USA. RP Barnett, J (reprint author), US FDA, Bothell, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TECHNOMIC PUBL CO INC PI LANCASTER PA 851 NEW HOLLAND AVE, BOX 3535, LANCASTER, PA 17604 USA BN 1-56676-546-3 PY 1997 BP 206 EP 209 PG 2 WC Fisheries; Food Science & Technology SC Fisheries; Food Science & Technology GA BQ50E UT WOS:000088535800027 ER PT B AU Kraemer, DW AF Kraemer, DW BE Martin, RE Collette, RL Salvin, JW TI Sanitation issues in a HACCP program SO FISH INSPECTION, QUALITY CONTROL AND HACCP: A GLOBAL FOCUS LA English DT Proceedings Paper CT 2nd International Conference on Fish Inspection and Quality Control CY MAY 19-24, 1996 CL ARLINGTON, VA SP Natl Fisheries Inst, US FDA, UN Food & Agr Org, US Natl Marine Fisheries Serv, Canadian Dept Fihseries & Oceans, Fisheries Council Canada, Joseph Slavin & Associates, GEM Biomed Inc AB As you probably already know, FDA published a "Seafood HACCP Regulation" on December 18, 1995. It will become effective two years from that date, on December 18, 1997. Part of the regulation identifies eight critical areas of sanitation that must be controlled - either as part of the HACCP program or separately, as part of a sanitation program. C1 US FDA, CFSAN, Off Seafood, Washington, DC 20005 USA. RP Kraemer, DW (reprint author), US FDA, CFSAN, Off Seafood, 1110 Vermont Ave,Suite 1110, Washington, DC 20005 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU TECHNOMIC PUBL CO INC PI LANCASTER PA 851 NEW HOLLAND AVE, BOX 3535, LANCASTER, PA 17604 USA BN 1-56676-546-3 PY 1997 BP 461 EP 464 PG 4 WC Fisheries; Food Science & Technology SC Fisheries; Food Science & Technology GA BQ50E UT WOS:000088535800055 ER PT B AU Snyder, MI Randolph, SC AF Snyder, MI Randolph, SC BE Martin, RE Collette, RL Salvin, JW TI Application of FDA's regulatory fish encyclopedia SO FISH INSPECTION, QUALITY CONTROL AND HACCP: A GLOBAL FOCUS LA English DT Proceedings Paper CT 2nd International Conference on Fish Inspection and Quality Control CY MAY 19-24, 1996 CL ARLINGTON, VA SP Natl Fisheries Inst, US FDA, UN Food & Agr Org, US Natl Marine Fisheries Serv, Canadian Dept Fihseries & Oceans, Fisheries Council Canada, Joseph Slavin & Associates, GEM Biomed Inc AB Sampling procedures are in part dependent on knowledge of the product and the ability to have reliable analytical techniques. The regulatory fish encyclopedia can be useful as both an industry and a regulatory tool. The FDA, whose authority over seafood extends to economic fraud and species substitution, has developed numerous tools, such as species substitution, to assist in species identification. C1 US FDA, CFSAN, Off Seafood, Washington, DC 20005 USA. RP Snyder, MI (reprint author), US FDA, CFSAN, Off Seafood, 1110 Vermont Ave,Suite 1110, Washington, DC 20005 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU TECHNOMIC PUBL CO INC PI LANCASTER PA 851 NEW HOLLAND AVE, BOX 3535, LANCASTER, PA 17604 USA BN 1-56676-546-3 PY 1997 BP 525 EP 529 PG 3 WC Fisheries; Food Science & Technology SC Fisheries; Food Science & Technology GA BQ50E UT WOS:000088535800062 ER PT B AU Hungerford, J Manger, R Wekell, M Hollingworth, T AF Hungerford, J Manger, R Wekell, M Hollingworth, T BE Martin, RE Collette, RL Salvin, JW TI Rapid chemical tests: Laboratory and field screening methods for seafood analysis SO FISH INSPECTION, QUALITY CONTROL AND HACCP: A GLOBAL FOCUS LA English DT Proceedings Paper CT 2nd International Conference on Fish Inspection and Quality Control CY MAY 19-24, 1996 CL ARLINGTON, VA SP Natl Fisheries Inst, US FDA, UN Food & Agr Org, US Natl Marine Fisheries Serv, Canadian Dept Fihseries & Oceans, Fisheries Council Canada, Joseph Slavin & Associates, GEM Biomed Inc ID FLOW-INJECTION ANALYSIS; BREVETOXINS; CIGUATOXINS; SAXITOXINS; TOXINS; ASSAY AB To ensure the quality and safety of seafoods, the development of chemical screening methods is crucial. Screening methods can be broken down into two broad categories, laboratory screening methods and field screening methods. Both allow coverage of more samples and have applications in both quality assurance and regulatory efforts. Field screening methods provide these capabilities and in addition are portable and simple enough to be used on-site. The development of rapid chemical tests for seafoods demands a pragmatic approach. In either field or laboratory screening, detection must be rapid and sensitive. To simplify and expedite sample preparation, the detection step must also be very tolerant of sample matrix components. Not all chemical tests can meet these demanding requirements. In either case, one of the primary goals of field screening methods is to avoid the needless testing of acceptable samples. Examples of laboratory screening methods are flow injection analysis, most enzyme linked immunosorbent assays, and rapid chromatographic methods. Laboratory screening methods such as flow injection analysis are readily automated and have high throughput. Field screening methods require even simpler sample preparation and greater overall speed. Examples are optimized and simplified "dip stick" immunoassays, enzymatic assays, and chemical systems that use volatility to separate and detect analytes. This paper will describe the development and performance of sampling and screening procedures for seafood analysis developed at FDA's Seafood Products Research Center (SPRC). C1 US FDA, Bothell, WA 98041 USA. RP Hungerford, J (reprint author), US FDA, POB 3012, Bothell, WA 98041 USA. NR 9 TC 6 Z9 6 U1 0 U2 0 PU TECHNOMIC PUBL CO INC PI LANCASTER PA 851 NEW HOLLAND AVE, BOX 3535, LANCASTER, PA 17604 USA BN 1-56676-546-3 PY 1997 BP 538 EP 550 PG 3 WC Fisheries; Food Science & Technology SC Fisheries; Food Science & Technology GA BQ50E UT WOS:000088535800064 ER PT B AU Spiller, P AF Spiller, P BE Martin, RE Collette, RL Salvin, JW TI The new USFDA HACCP program SO FISH INSPECTION, QUALITY CONTROL AND HACCP: A GLOBAL FOCUS LA English DT Proceedings Paper CT 2nd International Conference on Fish Inspection and Quality Control CY MAY 19-24, 1996 CL ARLINGTON, VA SP Natl Fisheries Inst, US FDA, UN Food & Agr Org, US Natl Marine Fisheries Serv, Canadian Dept Fihseries & Oceans, Fisheries Council Canada, Joseph Slavin & Associates, GEM Biomed Inc AB At the Coder Fish and Fishery Products meeting in Bergen, Norway, where the chief topic was integrating HACCP into Coder Codes of Practice for various seafood commodities, I learned that HACCP has become an international common language for seafood. In December, 1995, the USFDA published a regulation that requires HACCP systems for seafood processed in the U.S. and for seafood imported into the U.S. As the U.S. regulatory authority for seafood, the USFDA has developed a comprehensive seafood program over the decades, many aspects of which have been based traditionally on the GMP approach to food regulation. We have a GMP regulation that provides principles for the production of all foods. Our HACCP program does not abandon these GMPs. The HACCP regulation states that the fundamental principles in our GMPs continue to apply, and HACCP builds upon these principles. The point being, that we agree with recent decisions at Coder that there are fundamental prerequisites to HACCP, such as good sanitation. In order to be successful, HACCP must be built upon a solid, preexisting base. C1 US FDA, CFSAN, Off Seafood, Washington, DC 20005 USA. RP Spiller, P (reprint author), US FDA, CFSAN, Off Seafood, 1110 Vermont Ave,Suite 1110, Washington, DC 20005 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU TECHNOMIC PUBL CO INC PI LANCASTER PA 851 NEW HOLLAND AVE, BOX 3535, LANCASTER, PA 17604 USA BN 1-56676-546-3 PY 1997 BP 589 EP 594 PG 4 WC Fisheries; Food Science & Technology SC Fisheries; Food Science & Technology GA BQ50E UT WOS:000088535800071 ER PT B AU Snyder, MI Spitzig, PA AF Snyder, MI Spitzig, PA BE Martin, RE Collette, RL Salvin, JW TI FDA's view on seafood inspection agreements SO FISH INSPECTION, QUALITY CONTROL AND HACCP: A GLOBAL FOCUS LA English DT Proceedings Paper CT 2nd International Conference on Fish Inspection and Quality Control CY MAY 19-24, 1996 CL ARLINGTON, VA SP Natl Fisheries Inst, US FDA, UN Food & Agr Org, US Natl Marine Fisheries Serv, Canadian Dept Fihseries & Oceans, Fisheries Council Canada, Joseph Slavin & Associates, GEM Biomed Inc AB The world of international trade policy has seen many new developments lately. This is as true in the area of seafood as other commodities. We see change due to GATT, the WTO and the NAFTA agreements. We are working with the EU and APEC to harmonize our systems. This effort to harmonize government systems often leads to agreements between countries. These agreements have many names depending on the country and the type of agreement. At the Food and Drug Administration (FDA), we usually refer to these agreements as Memoranda of Understanding or MOU's. FDA's overall policy on international agreements is based on the agency's published formal policy with regard to these international agreements and a standard protocol for handling both the negotiations and the flow of paperwork. It is the policy of FDA to pursue the development of MOU's that will further the agency's domestic public health mission. MOU's between FDA and an agency of a foreign government or an international organization should be designed to: enhance FDA's ability to ensure that regulated products are in compliance with U.S. regulations; allow FDA to use its resources more effectively and efficiently, without compromising its ability to carry out its responsibilities; and improve communications between FDA and foreign officials concerning FDA-regulated products. Further, before accepting the procedures, activities, and enforcement methods, of foreign governments as equivalent to its own, FDA will seek assurance that such activities provide the same level of consumer protection that is provided under our laws and regulations. FDA may find it necessary to confirm by on-site review or other appropriate means that the foreign government agency has the necessary authorities, product standards capabilities, and infrastructure to successfully achieve the proposed terms of the MOU and, therefore, that a determination of equivalence can be made. Where appropriate, FDA will publish proposed equivalence determinations for comment. Our statement of policy describes three general types of agreements as examples. They may be combined or changed as necessary to fit individual situations. C1 US FDA, Off Seaford, Washington, DC 20005 USA. RP Snyder, MI (reprint author), US FDA, Off Seaford, Washington, DC 20005 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU TECHNOMIC PUBL CO INC PI LANCASTER PA 851 NEW HOLLAND AVE, BOX 3535, LANCASTER, PA 17604 USA BN 1-56676-546-3 PY 1997 BP 772 EP 778 PG 5 WC Fisheries; Food Science & Technology SC Fisheries; Food Science & Technology GA BQ50E UT WOS:000088535800096 ER PT J AU Canas, BJ Diachenko, GW Nyman, PJ AF Canas, BJ Diachenko, GW Nyman, PJ TI Ethyl carbamate levels resulting from azodicarbonamide use in bread SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE ethyl carbamate; urethane; azodicarbonamide; bread ID ALCOHOLIC BEVERAGES; FERMENTED FOODS; GAS-CHROMATOGRAPHY AB Azodicarbonamide (ADA), a dough conditioner, is an additive approved in the US up to a maximum of 45 mg/kg in flour. The addition of 45 mg/kg of ADA was investigated and found to increase the ethyl carbamate (EC) content of commercially prepared bread; by 1-3 mu g/kg. A similar increase in EC was observed in breads baked in the laboratory with a bread machine. The increase in EC levels appears to depend on a variety of factors, most notably the concentration of ADA added and the time of fermentation. The addition of 20 mg/kg ADA caused only a slight increase, if any, in commercial products but a 2.3 mu g/kg increase of EC in breads baked with a bread machine. When 100 mg/kg of ascorbic acid was added along with ADA, smaller EC increases were observed. Addition of urea was also found to enhance the BC content of the bread. Toasting, which was previously shown to increase EC levels, caused even larger increases when ADA or urea had been added. RP Canas, BJ (reprint author), US FDA,DIV NAT PROD HFS347,200 C ST SW,WASHINGTON,DC 20204, USA. NR 21 TC 5 Z9 5 U1 2 U2 7 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD JAN PY 1997 VL 14 IS 1 BP 89 EP 94 PG 6 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA WE845 UT WOS:A1997WE84500012 PM 9059587 ER PT J AU Bradlaw, JA Wilcox, NL AF Bradlaw, JA Wilcox, NL TI Workshop on eye irritation testing: Practical applications of non-whole animal alternatives SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article AB In November 1993, over 200 people from 14 nations participated in an IRAG workshop on eye irritation testing. The goal of the workshop was to set a course for the scientific approval and acceptance of non-whole animal alternatives to the Draize eye test. Through a retrospective review of existing in vitro and in vivo data by expert working groups, the endeavour examined the current status of practical application of in vitro alternatives used to predict eye irritation. Over 74 data sets from 59 laboratories were reviewed for approximately 26 different test methods. The submissions were illustrative of varied approaches and broad applications of in vitro assays. It was concluded that: (1) data are insufficient to support the total replacement of in vivo ocular irritancy testing with in vitro methods; (2) alternative methods to the in vivo standard (Draize) are currently being used extensively by industry as screens in the risk assessment process for product development; and (3) based on current practices for ocular irritancy testing, it appears that some models exist that may have the potential to reduce the need for new animal testing, provided they are validated and conducted under well defined conditions. Several recommendations are proffered to facilitate scientific review of in vitro and in vivo data sets in parallel: for example, basic research is encouraged to further identify mechanistic endpoints targeting human ocular injury; a chemical test bank is necessary for testing standards; an international data bank should be established; test batteries need to be identified that adequately test novel substances for safety; a third party needs to take the lead to identify promising tests and to facilitate validation studies; and international harmonization of method development, validation and acceptance should be given high priority. Grateful appreciation is conveyed to the many contributors to this complex endeavour. C1 US FDA,OFF COMMISSIONER,OFF SCI,ROCKVILLE,MD 20857. RP Bradlaw, JA (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204, USA. NR 0 TC 13 Z9 14 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 JAN PY 1997 VL 35 IS 1 BP 1 EP 11 DI 10.1016/S0278-6915(97)83155-9 PG 11 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA WR560 UT WOS:A1997WR56000001 ER PT J AU Scala, RA Springer, J AF Scala, RA Springer, J TI IRAG working group 6 - Guidelines for the evaluation of eye irritation alternative tests: Criteria for data submission SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article C1 US FDA,WASHINGTON,DC 20204. NR 3 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JAN PY 1997 VL 35 IS 1 BP 13 EP 22 DI 10.1016/S0278-6915(96)00102-0 PG 10 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA WR560 UT WOS:A1997WR56000002 PM 9100812 ER PT J AU Feder, P Carr, G Holzhutter, HG Lovell, D Springer, J AF Feder, P Carr, G Holzhutter, HG Lovell, D Springer, J TI Appendix I - Statistical planning and analysis considerations in the evaluation of in vitro alternatives to whole animal use for eye irritation testing SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article AB Reports from the IRAG Working Groups assessing the current status of in vitro alternatives to whole animal eye irritation tests reflect some common approaches. Although each Working Group studied a particular class of assay, typically all Groups evaluated the in vitro alternatives on the basis of correlation with an in vivo test and the statistical significance of that correlation. However, the data furnished to them by the testing organizations had been obtained with little or no standardization of procedures for testing and evaluation of results. This paper presents issues of design and execution of such rest programs that are of statistical concern, including objectives of the evaluation process; limitations of correlation; sources of variation and distinction between actual replication and repeated measurements; evaluation of the predictive ability of in vitro tests; association criteria; and other approaches to such evaluation programs. The distinction between statistical significance and toxicological significance is pointed out. Suggestions are presented for standardization of test protocols, test materials and evaluation programs for both in vitro and in vivo tests. A central repository for such standardization, under the aegis of a government agency, professional standards organization, university or research institute, would be a valuable asset. An addendum is furnished to illustrate assertions about a number of factors influencing correlations and their statistical significance. Copyright (C) 1997 Elsevier Science Ltd. C1 PROCTER & GAMBLE CO,CINCINNATI,OH. HUMBOLDT UNIV BERLIN,BERLIN,GERMANY. US FDA,WASHINGTON,DC 20204. RP Feder, P (reprint author), BATTELLE MEM INST,505 KING AVE,COLUMBUS,OH 43201, USA. NR 6 TC 10 Z9 11 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 JAN PY 1997 VL 35 IS 1 BP 167 EP 174 DI 10.1016/S0278-6915(96)00108-1 PG 8 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA WR560 UT WOS:A1997WR56000010 PM 9100820 ER PT J AU Bradlaw, J Gupta, K Green, S Hill, R Wilcox, N AF Bradlaw, J Gupta, K Green, S Hill, R Wilcox, N TI Appendix II - Practical application of non-whole animal alternatives: Summary of IRAG workshop on eye irritation testing SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article AB In November 1993, the Interagency Regulatory Alternatives Group (IRAG) sponsored a workshop to examine the current scientific status of alternatives to the Draize eye irritation test by assessing the current practical application of methods used to predict in vivo eye irritation. Laboratories from around the world were invited to submit detailed in vitro and in vivo data in parallel according to a specific set of guidelines in a consistent formal. in vitro scores were compared with individual tissue scores. Over 60 data sets from 41 laboratories were received for 29 different test methods. Methods were grouped into five categories: organotypic models, chorioallantoic membrane-based assays, cell function-based assays, cytotoxicity assays and other systems. Data submissions and correlation analyses have been used to demonstrate the application of guidelines in method evaluations. Findings are summarized and future directions are indicated. A significant outcome of the workshop was the co-operation demonstrated among representatives of industry, academia and government in sharing test data on more than 2000 chemicals, products and product formulations for evaluation by their peers. Information obtained from this workshop will add to the weight of scientific evidence and scientific consensus about in vitro test methods and will establish credibility for regulatory acceptance of non-whole animal alternatives for ocular irritation. C1 US CONSUMER PROD SAFETY COMMISS,WASHINGTON,DC 20204. US EPA,WASHINGTON,DC 20204. RP Bradlaw, J (reprint author), US FDA,WASHINGTON,DC 20204, USA. NR 0 TC 23 Z9 23 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 JAN PY 1997 VL 35 IS 1 BP 175 EP 178 DI 10.1016/S0278-6915(96)00110-X PG 4 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA WR560 UT WOS:A1997WR56000011 PM 9100821 ER PT J AU Kessler, DA AF Kessler, DA TI Remarks by the Commissioner of Food and Drugs SO FOOD AND DRUG LAW JOURNAL LA English DT Editorial Material RP Kessler, DA (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 4 TC 4 Z9 4 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 J9 FOOD DRUG LAW J JI Food Drug Law J. PY 1997 VL 52 IS 1 BP 1 EP 5 PG 5 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA WQ866 UT WOS:A1997WQ86600001 PM 10346704 ER PT J AU Porter, MJ AF Porter, MJ TI The Lohr decision: FDA perspective and position SO FOOD AND DRUG LAW JOURNAL LA English DT Article RP Porter, MJ (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 3 TC 22 Z9 22 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 J9 FOOD DRUG LAW J JI Food Drug Law J. PY 1997 VL 52 IS 1 BP 7 EP 11 PG 5 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA WQ866 UT WOS:A1997WQ86600002 PM 10346705 ER PT J AU Boring, D Doninger, C AF Boring, D Doninger, C TI The need for balancing the regulation of pharmaceutical trademarks between the Food and Drug Administration and the Patent and Trademark Office SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 US FDA,CTR DRUG EVALUAT & RES,OFF PHARMACEUT SCI,OFF NEW DRUG CHEM 3,DIV ANTIVIRAL DRUG PROD,ROCKVILLE,MD 20857. RP Boring, D (reprint author), US FDA,LABELING & NOMENCLATURE COMM,ROCKVILLE,MD 20857, USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 J9 FOOD DRUG LAW J JI Food Drug Law J. PY 1997 VL 52 IS 1 BP 109 EP 116 PG 8 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA WQ866 UT WOS:A1997WQ86600011 PM 10346714 ER PT J AU Woodcock, J AF Woodcock, J TI An FDA perspective on the drug development process SO FOOD AND DRUG LAW JOURNAL LA English DT Article; Proceedings Paper CT Georgetown Conference on Drug Development - Who Knows Where the Time Goes CY JUN, 1996 CL GEORGETOWN UNIV, WASHINGTON, DC SP FDLI, US FDA. Ctr Drug Evaluat & Res, Georgetown Univ, Ctr Drug Dev Sci HO GEORGETOWN UNIV RP Woodcock, J (reprint author), US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857, USA. NR 1 TC 7 Z9 7 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 J9 FOOD DRUG LAW J JI Food Drug Law J. PY 1997 VL 52 IS 2 BP 145 EP 150 PG 6 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA XF350 UT WOS:A1997XF35000003 PM 10557550 ER PT J AU Holston, SS AF Holston, SS TI An overview of international cooperation SO FOOD AND DRUG LAW JOURNAL LA English DT Article; Proceedings Paper CT Georgetown Conference on Drug Development - Who Knows Where the Time Goes CY JUN, 1996 CL GEORGETOWN UNIV, WASHINGTON, DC SP FDLI, US FDA. Ctr Drug Evaluat & Res, Georgetown Univ, Ctr Drug Dev Sci HO GEORGETOWN UNIV RP Holston, SS (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 5 TC 4 Z9 4 U1 0 U2 1 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 J9 FOOD DRUG LAW J JI Food Drug Law J. PY 1997 VL 52 IS 2 BP 197 EP 201 PG 5 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA XF350 UT WOS:A1997XF35000013 PM 10557560 ER PT J AU Geyer, RE AF Geyer, RE TI Extralabel drug use and compounding in veterinary medicine SO FOOD AND DRUG LAW JOURNAL LA English DT Article; Proceedings Paper CT FDLI 40th Annual Education Conference CY DEC 10-11, 1996 CL WASHINGTON, DC SP FDLI RP Geyer, RE (reprint author), US FDA,OFF SURVEILLANCE & COMPLIANCE,CTR VET MED,ROCKVILLE,MD 20857, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 J9 FOOD DRUG LAW J JI Food Drug Law J. PY 1997 VL 52 IS 3 BP 291 EP 295 PG 5 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA XR452 UT WOS:A1997XR45200004 PM 10343027 ER PT J AU Spiller, PC AF Spiller, PC TI Status of seafood HACCP SO FOOD AND DRUG LAW JOURNAL LA English DT Article; Proceedings Paper CT FDLI 40th Annual Education Conference CY DEC 10-11, 1996 CL WASHINGTON, DC SP FDLI RP Spiller, PC (reprint author), US FDA,OFF SEAFOOD,CTR FOOD SAFETY & APPL NUTR,ROCKVILLE,MD 20857, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 J9 FOOD DRUG LAW J JI Food Drug Law J. PY 1997 VL 52 IS 3 BP 327 EP 330 PG 4 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA XR452 UT WOS:A1997XR45200010 PM 10343033 ER PT J AU Wells, MA AF Wells, MA TI Overview of FDA regulation of human cellular and tissue-based products SO FOOD AND DRUG LAW JOURNAL LA English DT Article; Proceedings Paper CT FDLI Pharmaceutical Update 97 Meeting CY MAY 20-21, 1997 CL WASHINGTON, D.C. SP FDLI C1 US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Human Tissue Program, Rockville, MD 20857 USA. RP Wells, MA (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Human Tissue Program, Rockville, MD 20857 USA. NR 22 TC 4 Z9 4 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA J9 FOOD DRUG LAW J JI Food Drug Law J. PY 1997 VL 52 IS 4 BP 401 EP 408 PG 8 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA YN516 UT WOS:000071176400004 PM 10346672 ER PT J AU Crumpler, ES Rudolph, H AF Crumpler, ES Rudolph, H TI FDA software policy and regulation of medical device software SO FOOD AND DRUG LAW JOURNAL LA English DT Article; Proceedings Paper CT FDLI 40th Annual Education Conference CY DEC 10-11, 1996 CL WASHINGTON, D.C. SP FDLI C1 US FDA, Ctr Devices & Radiol Hlth, Off Compliance, Rockville, MD 20857 USA. US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. RP Crumpler, ES (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Compliance, Rockville, MD 20857 USA. NR 13 TC 4 Z9 4 U1 0 U2 1 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA J9 FOOD DRUG LAW J JI Food Drug Law J. PY 1997 VL 52 IS 4 BP 511 EP 516 PG 6 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA YN516 UT WOS:000071176400008 PM 10346676 ER PT J AU Ali, LH Angyal, G Weaver, CM Rader, JI AF Ali, LH Angyal, G Weaver, CM Rader, JI TI Comparison of capillary column gas chromatographic and AOAC gravimetric procedures for total fat and distribution of fatty acids in foods SO FOOD CHEMISTRY LA English DT Article ID TRANS; HUMANS; CIS AB There is increasing interest in the fatty acid composition, including levels of trans fatty acids, of foods. The trans fatty acid content of American diets is increasingly studied because of reported adverse effects of trans fatty acids on risk of coronary heart disease. In this study, total fat content and fatty acid composition of 43 food products were determined after acid hydrolysis by gas chromatography using an SP-2560 flexible fused silica capillary column. Total fat content determined by the gas chromatographic method was compared with fat content determined by AOAC gravimetric method 922.06 for all food products. Total fat, saturated fat and unsaturated fat content of the foods determined by the gas chromatographic method ranged from 0.9 to 96.7, 0.2 to 16.8 and 0.5 to 89.3%, respectively. Trans fatty acids hexadecenoate (t-16:1), elaidic (t-18:1), and octadecadienoate (t,t-18:2) were identified by comparison of their retention times with those of known standards and quantitated. These fatty acids were present in foods at levels of 0.25 to 1.50 (t-16:1), 0.87 to 268.32 (t-18:1), and 0.23 to 7.92 (t,t-18:2) mg/g. Published by Elsevier Science Ltd RP Ali, LH (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,OFF FOOD LABELING,200 C ST SW,WASHINGTON,DC 20204, USA. NR 14 TC 16 Z9 17 U1 2 U2 5 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 JAN-FEB PY 1997 VL 58 IS 1-2 BP 149 EP 160 DI 10.1016/S0308-8146(96)00181-1 PG 12 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA WC899 UT WOS:A1997WC89900025 ER PT B AU Tortorello, ML AF Tortorello, ML BE Tortorello, ML Gendel, SM TI A new look at an old technique: Application of microscopy to food microbiological analysis SO FOOD MICROBIOLOGICAL ANALYSIS: NEW TECHNOLOGIES SE IFT BASIC SYMPOSIUM SERIES LA English DT Proceedings Paper CT 1996 Basic Symposium on Food Microbiological Analysis - New Technologies CY JUN 21-22, 1996 CL NEW ORLEANS, LA SP Inst Food Technologists RP Tortorello, ML (reprint author), US FDA,NATL CTR FOOD SAFETY & TECHNOL,SUMMIT ARGO,IL 60501, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MARCEL DEKKER PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 BN 0-8247-0087-2 J9 IFT BAS SYM PY 1997 VL 12 BP 45 EP 56 PG 12 WC Biotechnology & Applied Microbiology; Chemistry, Analytical; Food Science & Technology SC Biotechnology & Applied Microbiology; Chemistry; Food Science & Technology GA BJ42W UT WOS:A1997BJ42W00003 ER PT B AU Raybourne, RB AF Raybourne, RB BE Tortorello, ML Gendel, SM TI Flow cytometry in food microbiology: Detection of Escherichia coli O157:H7 SO FOOD MICROBIOLOGICAL ANALYSIS: NEW TECHNOLOGIES SE IFT BASIC SYMPOSIUM SERIES LA English DT Proceedings Paper CT 1996 Basic Symposium on Food Microbiological Analysis - New Technologies CY JUN 21-22, 1996 CL NEW ORLEANS, LA SP Inst Food Technologists RP Raybourne, RB (reprint author), US FDA,LAUREL,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 BN 0-8247-0087-2 J9 IFT BAS SYM PY 1997 VL 12 BP 57 EP 68 PG 12 WC Biotechnology & Applied Microbiology; Chemistry, Analytical; Food Science & Technology SC Biotechnology & Applied Microbiology; Chemistry; Food Science & Technology GA BJ42W UT WOS:A1997BJ42W00004 ER PT B AU Jinneman, KC Hill, WE AF Jinneman, KC Hill, WE BE Tortorello, ML Gendel, SM TI Applications of gene probes for the detection of foodborne pathogens SO FOOD MICROBIOLOGICAL ANALYSIS: NEW TECHNOLOGIES SE IFT BASIC SYMPOSIUM SERIES LA English DT Proceedings Paper CT 1996 Basic Symposium on Food Microbiological Analysis - New Technologies CY JUN 21-22, 1996 CL NEW ORLEANS, LA SP Inst Food Technologists RP Jinneman, KC (reprint author), US FDA,SEAFOOD PROD RES CTR,SEATTLE DIST OFF,OFF REGULATORY AFFAIRS,BOTHELL,WA, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MARCEL DEKKER PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 BN 0-8247-0087-2 J9 IFT BAS SYM PY 1997 VL 12 BP 115 EP 181 PG 67 WC Biotechnology & Applied Microbiology; Chemistry, Analytical; Food Science & Technology SC Biotechnology & Applied Microbiology; Chemistry; Food Science & Technology GA BJ42W UT WOS:A1997BJ42W00008 ER PT B AU Gendel, SM AF Gendel, SM BE Tortorello, ML Gendel, SM TI Gene sequence databases and food microbiology SO FOOD MICROBIOLOGICAL ANALYSIS: NEW TECHNOLOGIES SE IFT BASIC SYMPOSIUM SERIES LA English DT Proceedings Paper CT 1996 Basic Symposium on Food Microbiological Analysis - New Technologies CY JUN 21-22, 1996 CL NEW ORLEANS, LA SP Inst Food Technologists RP Gendel, SM (reprint author), US FDA,NATL CTR FOOD SAFETY & TECHNOL,SUMMIT ARGO,IL 60501, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 BN 0-8247-0087-2 J9 IFT BAS SYM PY 1997 VL 12 BP 229 EP 248 PG 20 WC Biotechnology & Applied Microbiology; Chemistry, Analytical; Food Science & Technology SC Biotechnology & Applied Microbiology; Chemistry; Food Science & Technology GA BJ42W UT WOS:A1997BJ42W00011 ER PT J AU Jackson, GJ Leclerc, JE Bier, JW Madden, JM AF Jackson, GJ Leclerc, JE Bier, JW Madden, JM TI Cyclospora - Still another new foodborne pathogen SO FOOD TECHNOLOGY LA English DT Editorial Material RP Jackson, GJ (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,200 C ST SW,WASHINGTON,DC 20204, USA. NR 0 TC 7 Z9 7 U1 1 U2 1 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA SUITE 300 221 N LASALLE ST, CHICAGO, IL 60601-1291 SN 0015-6639 J9 FOOD TECHNOL-CHICAGO JI Food Technol. PD JAN PY 1997 VL 51 IS 1 BP 120 EP 120 PG 1 WC Food Science & Technology SC Food Science & Technology GA WB992 UT WOS:A1997WB99200017 ER PT J AU Wamer, WG Yin, JJ Wei, RR AF Wamer, WG Yin, JJ Wei, RR TI Oxidative damage to nucleic acids photosensitized by titanium dioxide SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE DNA damage; free radicals; 8-oxodG; 8-oxo-7,8-dihydro-2'-deoxyguanosine; oxidative damage; photooxidation; phototoxicity; RNA damage; titanium dioxide ID POWDERED SEMICONDUCTOR TIO2; BASE DAMAGE; DEOXYRIBONUCLEIC-ACID; HYDROGEN-PEROXIDE; DNA; SUPEROXIDE; HYDROXYL; 8-HYDROXYGUANINE; PHOTOCATALYSIS; IRRADIATION AB The semiconductor TiO2 is known to have photobiological activity in prokaryotic and eukaryotic cells. Applications of this photobiological activity have been suggested including sterilization of waste water and phototherapy of malignant cells. Here, several model and cellular systems were used to study the mechanism of photocatalysis by TiO2. Treatment of TiO2 (anatase, 0.45 mu m), suspended in water containing a spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), with UV radiation (320 nm) resulted in an electron spin resonance (ESR) signal characteristic of the hydroxyl radical. Irradiation of solutions containing calf thymus DNA and TiO2 with UVA (320-400 nm) radiation resulted in hydroxylation of guanine bases. The degree of hydroxylation was dependent on both UVA fluence and amount of TiO2 in suspension. Human skin fibroblasts, preincubated 18 h with 10 mu g/cm(2) TiO2 and then UVA-irradiated (0-58 KJ/m(2)), showed dose dependent photocytoxicity. RNA, isolated from similarly treated fibroblasts, contained significant levels of photooxidation, measured as hydroxylation of guanine bases. However, no oxidative damage was detectable in cellular DNA. These results suggest that nucleic acids are a potential target for photooxidative damage sensitized by TiO2, and support the view that TiO2 photocatalyzes free radical formation. Published by Elsevier Science Inc. RP Wamer, WG (reprint author), US FDA,COSMET TOXICOL BRANCH HFS 128,CTR FOOD SAFETY & APPL NUTR,200 C ST SW,WASHINGTON,DC 20204, USA. RI Yin, Jun Jie /E-5619-2014 NR 36 TC 189 Z9 205 U1 3 U2 34 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1997 VL 23 IS 6 BP 851 EP 858 DI 10.1016/S0891-5849(97)00068-3 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA XW761 UT WOS:A1997XW76100007 PM 9378364 ER PT J AU Hahn, SM Mitchell, JB Shacter, E AF Hahn, SM Mitchell, JB Shacter, E TI Tempol inhibits neutrophil and hydrogen peroxide-mediated DNA damage SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE oxidative stress; nitroxides; DNA damage; inflammation; protection; anti-oxidant; inflammation; neutrophil; free radicals ID TUMOR PROMOTION; POLYMORPHONUCLEAR LEUKOCYTES; MAMMALIAN-CELLS; OXYGEN; RADICALS; PHAGOCYTES; INDUCTION; BASES; TRANSFORMATION; PLASMACYTOMAS AB Inflammatory conditions characterized by neutrophil activation are associated with a variety of chronic diseases, Reactive oxygen species are produced by activated neutrophils and produce DNA damage which may lead to tissue damage. Previous studies have shown that activated murine neutrophils induce DNA strand breaks in a target plasmacytoma cell, RIMPC 2394. We studied the effect of a water soluble nitroxide anti-oxidant, Tempol, on murine neutrophil induction of DNA strand breaks in this system. Murine neutrophils were isolated from the peritoneal cavity of BALB/cAn mice after an IP injection of pristane oil. Neutrophils were activated by the phorbol esther PMA and co-incubated with RIMPC 2394 cells. Control alkaline elution studies revealed progressive DNA strand breaks in RIMPC cells with time. The addition of Tempol to the incubation mixture prevented DNA damage in a dose dependent fashion. Five mM Tempol provided complete protection. Tempol protection against DNA strand breaks was similar for both stimulated neutrophils and exogenously added hydrogen peroxide. Measurement of hydrogen peroxide produced by stimulated neutrophils demonstrated that Tempol did not decrease hydrogen peroxide concentration. Oxidation of reduced metals, thereby interfering with the production of hydroxyl radical, is the most Likely mechanism of nitroxide protection, although superoxide dismutase (SOD)-like activity and scavenging of carbon-based free radicals may also account for a portion of the observed protection. The anti-oxidant activity of Tempol inhibited DNA damage by activated neutrophils. The nitroxides as a class of compounds may have a role in the investigation and modification of inflammatory conditions. Published by Elsevier Science Inc. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NCI,DIV CLIN SCI,RADIAT BIOL BRANCH,BETHESDA,MD 20892. NR 51 TC 37 Z9 37 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1997 VL 23 IS 6 BP 879 EP 884 DI 10.1016/S0891-5849(97)00079-8 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA XW761 UT WOS:A1997XW76100010 PM 9378367 ER PT J AU Mondoro, TH Shafer, BC Vostal, JG AF Mondoro, TH Shafer, BC Vostal, JG TI Peroxynitrite-induced tyrosine nitration and phosphorylation in human platelets SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE peroxynitrite; tyrosine nitration; tyrosine phosphorylation; platelets; thrombin; platelet aggregation ID NITRIC-OXIDE; SIGNAL-TRANSDUCTION; ENDOTHELIAL-CELLS; SUPEROXIDE; PROTEINS; CALCIUM; GLUTATHIONE; INHIBITION; THIMEROSAL; PRODUCT AB Peroxynitrite (ONOO-) induces nitration of tyrosine residues and inhibits tyrosine phosphorylation in cell free systems. We investigated the effect of peroxynitrite on protein tyrosine nitration and phosphorylation in resting or thrombin-activated platelets. Peroxynitrite (150 mu M) rapidly induced tyrosine nitration of 187, 164, 113, 89, and 61 kDa proteins in gel-filtered platelets which persisted up to 4.5 h. Repeated exposure of platelets to peroxynitrite produced increasing levels of nitration. Peroxynitrite also rapidly increased tyrosine phosphorylation of 120, 117, 95, 80-85, and 70 kDa platelet proteins, but this decreased by 5 min. The same pattern of tyrosine phosphorylation, but with higher intensity, was induced by thrombin in control platelets. Pretreatment of platelets with peroxynitrite decreased thrombin-induced tyrosine phosphorylation at 0.05 and 1 U/ml thrombin but not at 2 U/ml thrombin. Platelet activation responses such as P-selectin expression, serotonin secretion, and aggregation were also decreased by peroxynitrite treatment at low thrombin concentrations. Peroxynitrite exposure and tyrosine nitration decreased platelet sensitivity to thrombin but did not absolutely prevent tyrosine phosphorylation and other platelet responses. Copyright (C) 1997 Elsevier Science Inc. C1 US FDA,CTR BIOL EVALUAT & RES,LAB CELLULAR HEMATOL,BETHESDA,MD. NR 30 TC 73 Z9 76 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1997 VL 22 IS 6 BP 1055 EP 1063 DI 10.1016/S0891-5849(96)00510-2 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA WG659 UT WOS:A1997WG65900014 PM 9034245 ER PT B AU Stromberg, K AF Stromberg, K BE Ziegler, TR Pierce, GF Herndon, DN TI FDA regulatory concerns for wound healing biologics SO GROWTH FACTORS AND WOUND HEALING: BASIC SCIENCE AND POTENTIAL CLINICAL APPLICATIONS SE SERONO SYMPOSIA, USA LA English DT Proceedings Paper CT International Symposium on Growth Factors and Wound Healing - Basic Science and Potential Clinical Applications CY SEP 28-OCT 01, 1995 CL BOSTON, MA RP Stromberg, K (reprint author), US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20014, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 BN 0-387-94968-2 J9 SERONO SYMP PY 1997 BP 333 EP 343 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA BJ63T UT WOS:A1997BJ63T00020 ER PT B AU Bogner, MS AF Bogner, MS BE Mouloua, M Koonce, JM TI Human factors research in medical systems SO HUMAN-AUTOMATION INTERACTION: RESEARCH AND PRACTICE LA English DT Proceedings Paper CT 2nd Automation Technology and Human Performance Conference CY MAR 07-09, 1996 CL COCOA BEACH, FL SP Catholic Univ Amer, Cognit Sci Lab, Univ Cent Florida, Ctr Appl Human Factors Aviat, Univ Cent Florida, Coll Arts & Sci, USN, Off Naval Res, NASA, Langley Res Ctr RP Bogner, MS (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC PUBL PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430 BN 0-8058-2841-9 PY 1997 BP 212 EP 217 PG 6 WC Engineering, Aerospace; Computer Science, Cybernetics; Ergonomics SC Engineering; Computer Science GA BH32S UT WOS:A1997BH32S00029 ER PT B AU Dennis, JE AF Dennis, JE GP LASER INST AMER TI Amendments to the CDRH federal performance standard for laser products - A status report SO ILSC'97 - PROCEEDINGS OF THE INTERNATIONAL LASER SAFETY CONFERENCE, VOL 3 LA English DT Proceedings Paper CT 1997 International Laser Safety Conference (ILSC 97) CY MAR 17-20, 1997 CL ORLANDO, FL SP Laser Inst Amer AB Federal law requires that all laser products that are imported into or introduced into commerce in the United States comply with the performance standard published in the Code of Federal Regulations (CFR), Title 21, Parts 1040.10 and 1040.11, administered by the Center for Devices and Radiological Health, U.S. Food and Drug Administration. Although it contains somewhat different requirements for hazard classification, engineering controls and labeling, the ANSI Z136.1 standard defers to the CDRH standard. The CDRH standard first became effective in August, 1976 and has twice been amended, in 1978 and in 1985. In the early 1990s, U.S. experts met to formulate an approach to bring the requirements of the CDRH standard and those of the International Electrotechnical Commission (IEC) standard, IEC 825 into closer agreement in order to lower barriers to international trade and to remove any excessive compliance burdens on manufacturers. In 1993, the CDRH published, formally in the Federal Register and informally, a Notice of Intent to amend the CDRH standard. Responses to those notices have now been analyzed and informal draft amendments were distributed in 1996. This draft is now being prepared for formal issuance as a Notice of Proposed Rulemaking. Meanwhile, the IEC standard was amended in 1993 and republished as IEC 825-1; these amendments were met with considerable controversy since they resulted in over classification of the hazard of many products, especially light emitting diodes (LEDs) that have large divergence and increased source dimensions. Additional amendments are now being developed to correct this problem. The CDRH has carefully monitored developments in the IEC and actively participated in its proceedings as a guide in developing its own proposal. This paper describes the major changes that are being proposed for the CDRH standard and presents some rationale for the major changes. The more significant changes include expansion of applicability to include LEDs, reduced emission durations for classification, revised measurement procedures for hazard classification, reduced performance requirements for lower power visible radiation products, and revised requirements for medical products. RP Dennis, JE (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LASER INST AMERICA PI ORLANDO PA 12424 RESEARCH PKWY, STE 130, ORLANDO, FL 32826 BN 0-912035-13-7 PY 1997 BP 58 EP 67 PG 10 WC Public, Environmental & Occupational Health; Optics SC Public, Environmental & Occupational Health; Optics GA BJ29K UT WOS:A1997BJ29K00007 ER PT B AU Wagner, RF Chan, HP Sahiner, B Petrick, N Mossoba, JT AF Wagner, RF Chan, HP Sahiner, B Petrick, N Mossoba, JT BE Hansen, KM TI Finite-sample effects and resampling plans: Applications to linear classifiers in computer-aided diagnosis SO IMAGE PROCESSING - MEDICAL IMAGING 1997, PTS 1 AND 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 1997 Symposium - Image Processing CY FEB 25-28, 1997 CL NEWPORT BEACH, CA SP Soc Photo Opt Instrumentat Engineers, Amer Assoc Physicists Med, Amer Physiol Soc, US FDA, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Informat Syst Consortium, Radiol Soc N Amer, Soc Comp Applicat Radiol AB This work provides an application and extension of the analysis of the effect of finite-sample training and test sets on the bias and variance of the classical discriminants as given by Fukunaga. The extension includes new results for the area under the ROC curve, A(z). An upper bound on A(z) is provided by the so-called resubstitution method in which the classifier is trained and tested on the same patients; a lower bound is provided by the hold-out method in which the patient pool is partitioned into trainers and testers. Both methods exhibit a bias in A, with a linear dependence on the inverse of the number of patients Nt used to train the classifier; this leads to the possibility of obtaining an unbiased estimate of the infinite-population performance by a simple regression procedure. We examine the uncertainties in the resulting estimates. Whereas the bias of classifier performance is determined by the finite size of the training sample, the variance is dominated by the finite size of the test sample. This variance is approximately given by the simple result for an equivalent binomial process. A number of applications to the linear classifier are presented in this paper. More general applications, including the quadratic classifier and some elementary neural-network classifiers, are presented in a companion paper. RP Wagner, RF (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857, USA. NR 0 TC 25 Z9 25 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2445-5 J9 P SOC PHOTO-OPT INS PY 1997 VL 3034 BP 467 EP 477 DI 10.1117/12.274133 PN 1&2 PG 11 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BH84E UT WOS:A1997BH84E00046 ER PT S AU Appel, NM AF Appel, NM BE Lester, DS Felder, CC Lewis, EN TI Classical and contemporary histochemical approaches for evaluating central nervous system microanatomy SO IMAGING BRAIN STRUCTURE AND FUNCTION: EMERGING TECHNOLOGIES IN THE NEUROSCIENCES SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Current and Emerging Techniques in Monitoring Brain Structure and Function CY MAR 28-29, 1996 CL BETHESDA, MD SP US FDA, Ctr Drug Evaluat & Res, NIMH ID INTERMEDIOLATERAL CELL COLUMN; COEXISTING NEUROTRANSMITTERS; PREGANGLIONIC NEURONS; SPINAL-CORD; TRANSPORT; FIBERS; BRAIN; VIRUS C1 NIA, NEUROSCI LAB, NIH, BETHESDA, MD 20892 USA. RP Appel, NM (reprint author), US FDA, MOD 1 LAB FACIL, DIV APPL PHARMACOL RES, OFF TESTING & RES, CTR DRUG EVALUAT & RES, LAUREL, MD 20708 USA. NR 49 TC 3 Z9 3 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 1-57331-069-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 820 BP 14 EP 28 DI 10.1111/j.1749-6632.1997.tb46186.x PG 15 WC Multidisciplinary Sciences; Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Science & Technology - Other Topics; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BJ18E UT WOS:A1997BJ18E00002 PM 9237446 ER PT S AU Lewis, EN Kidder, LH Levin, IW Kalasinsky, VF Hanig, JP Lester, DS AF Lewis, EN Kidder, LH Levin, IW Kalasinsky, VF Hanig, JP Lester, DS BE Lester, DS Felder, CC Lewis, EN TI Applications of Fourier transform infrared imaging microscopy in neurotoxicity SO IMAGING BRAIN STRUCTURE AND FUNCTION: EMERGING TECHNOLOGIES IN THE NEUROSCIENCES SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Current and Emerging Techniques in Monitoring Brain Structure and Function CY MAR 28-29, 1996 CL BETHESDA, MD SP US FDA, Ctr Drug Evaluat & Res, NIMH C1 ARMED FORCES INST PATHOL, DEPT ENVIRONM & TOXICOL PATHOL, WASHINGTON, DC 20306 USA. US FDA, CTR DRUG EVALUAT & RES, LAUREL, MD 20708 USA. RP Lewis, EN (reprint author), NIDDKD, CHEM PHYS LAB, NIH, BLDG 2, BETHESDA, MD 20892 USA. NR 26 TC 14 Z9 14 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-069-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 820 BP 234 EP 247 DI 10.1111/j.1749-6632.1997.tb46199.x PG 14 WC Multidisciplinary Sciences; Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Science & Technology - Other Topics; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BJ18E UT WOS:A1997BJ18E00015 PM 9237459 ER PT S AU Hanig, JP Sobotka, T Contrera, J Rapoport, S Munzner, R Slikker, W Johannessen, J Wilcox, B Vocci, F OCallaghan, JP Lester, D AF Hanig, JP Sobotka, T Contrera, J Rapoport, S Munzner, R Slikker, W Johannessen, J Wilcox, B Vocci, F OCallaghan, JP Lester, D BE Lester, DS Felder, CC Lewis, EN TI Future directions for neurotoxicity testing: Towards a unified approach - Panel Discussion SO IMAGING BRAIN STRUCTURE AND FUNCTION: EMERGING TECHNOLOGIES IN THE NEUROSCIENCES SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Current and Emerging Techniques in Monitoring Brain Structure and Function CY MAR 28-29, 1996 CL BETHESDA, MD SP US FDA, Ctr Drug Evaluat & Res, NIMH C1 US FDA, CTR FOOD SAFETY & APPL NUTR, LAUREL, MD USA. NIA, NIH, BETHESDA, MD 20892 USA. US FDA, NATL CTR TOXICOL RES, JEFFERSON, AR 72079 USA. US FDA, CTR BIOL EVALUAT & RES, BETHESDA, MD 20014 USA. NIDA, NIH, ROCKVILLE, MD USA. US EPA, RES TRIANGLE PK, NC 27711 USA. RP Hanig, JP (reprint author), US FDA, CTR DRUG EVALUAT & RES, LAUREL, MD 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 1-57331-069-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 820 BP 300 EP 313 DI 10.1111/j.1749-6632.1997.tb46203.x PG 14 WC Multidisciplinary Sciences; Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Science & Technology - Other Topics; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BJ18E UT WOS:A1997BJ18E00019 ER PT S AU Sathe, P Tsong, Y Shah, VP AF Sathe, P Tsong, Y Shah, VP BE Young, D Devane, JG Butler, J TI In vitro dissolution profile comparison and IVIVR - Carbamazepine case SO IN VITRO-IN VIVO CORRELATIONS SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Workshop on In Vivo-In Vitro Relationships CY SEP 04-06, 1996 CL BALTIMORE, MD RP Sathe, P (reprint author), US FDA,OFF PHARMACEUT SCI,CTR DRUG EVALUAT & RES,METROPK N 2,7500 STANDISH PL,ROCKVILLE,MD 20855, USA. NR 15 TC 5 Z9 5 U1 0 U2 2 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45600-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 423 BP 31 EP 42 PG 12 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA BJ40H UT WOS:A1997BJ40H00003 PM 9269481 ER PT S AU Gillespie, WR AF Gillespie, WR BE Young, D Devane, JG Butler, J TI Convolution-based approaches for in vivo in vitro correlation modeling SO IN VITRO-IN VIVO CORRELATIONS SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Workshop on In Vivo-In Vitro Relationships CY SEP 04-06, 1996 CL BALTIMORE, MD ID INVITRO AB One approach to in vivo-in vitro correlation (IVIVC) for extended release (ER) oral dosage forms is to directly model the relationship between the time courses of in vitro release and plasma drug concentrations. For drugs that exhibit linear, time-invariant disposition this can be done using models based on the convolution integral. Advantages of this approach relative to deconvolution-based IVIVC approaches include the following: The relationship between measured quantities (in vitro release and plasma drug concentrations) is modeled directly in a single stage rather than via an indirect two stage approach. The model directly predicts the plasma concentration time course. As a result: The modeling focuses on the ability to predict measured quantities (not indirectly calculated quantities such as the cumulative amount absorbed). The results are more readily interpreted in terms of the effect of in vitro release on conventional bioequivalence metrics. It is easier to construct methods that do not require the administration of an IV, oral solution, or IR reference dose. A variety of convolution-based IVIVC models and modeling strategies are possible depending on the relationship between in vivo and in vitro release, the existence of nonlinear absorption or presystemic biotransformation, and the in vivo study design. The simplest approach is applicable to the case where the in vitro release rate equals the in vivo release (or absorption) rate and the study design includes the administration of an TV, oral solution, or IR dose. That basic convolution-based method can be extended to adjust for differences between the in vitro and in vivo release rates. This is accomplished by formally modeling those differences. Potential models include time-scaling and convolution. The extent of drug absorption may sometimes depend upon the release rate. This may be due to phenomena such as saturable presystemic biotransformation or truncated absorption due to intestinal transit past the sites of absorption. The relationship between the in vitro release rate and extent of absorption may be modeled empirically or mechanistically. Such models may be coupled with convolution to construct an overall IVIVC model for the relationship between in vitro release and plasma drug concentrations. It is also possible to apply convolution-based IVIVC models to study designs in which no IV, oral solution, or IR dose has been administered. Details of the various modeling approaches listed above are presented. Selected approaches are illustrated by examples of their application to real data. RP Gillespie, WR (reprint author), US FDA,CTR DRUG EVALUAT & RES,OFF CLIN PHARMACOL & BIOPHARMACEUT,5600 FISHERS LANE HFD-855,ROCKVILLE,MD 20857, USA. NR 5 TC 34 Z9 38 U1 0 U2 6 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45600-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 423 BP 53 EP 65 PG 13 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA BJ40H UT WOS:A1997BJ40H00005 PM 9269483 ER PT S AU Hussain, AS AF Hussain, AS BE Young, D Devane, JG Butler, J TI Artificial neural network based in vitro in vivo correlations SO IN VITRO-IN VIVO CORRELATIONS SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Workshop on In Vivo-In Vitro Relationships CY SEP 04-06, 1996 CL BALTIMORE, MD ID PHARMACEUTICAL PRODUCT DEVELOPMENT RP Hussain, AS (reprint author), US FDA,CTR DRUG EVALUAT & RES,OFF TESTING & RES,DIV PROD QUAL RES,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 18 TC 2 Z9 2 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45600-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 423 BP 149 EP 158 PG 10 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA BJ40H UT WOS:A1997BJ40H00012 PM 9269490 ER PT S AU Malinowski, HJ AF Malinowski, HJ BE Young, D Devane, JG Butler, J TI The role of in vitro in vivo correlations (IVIVC) to regulatory agencies SO IN VITRO-IN VIVO CORRELATIONS SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Workshop on In Vivo-In Vitro Relationships CY SEP 04-06, 1996 CL BALTIMORE, MD RP Malinowski, HJ (reprint author), US FDA,OFF CLIN PHARMACOL & BIOPHARMACEUT,DIV PHARMACEUT EVALUAT 1,ROCKVILLE,MD 20852, USA. NR 5 TC 7 Z9 7 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45600-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 423 BP 261 EP 268 PG 8 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA BJ40H UT WOS:A1997BJ40H00024 PM 9269502 ER PT S AU Mia, RS Loew, MH Wear, KA Wagner, RF AF Mia, RS Loew, MH Wear, KA Wagner, RF BE Duncan, J Gindi, G TI Quantitative estimation of scatterer spacing from backscattered ultrasound signals using the complex cepstrum SO INFORMATION PROCESSING IN MEDICAL IMAGING SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 15th International Conference on Information Processing in Medical Imaging CY JUN 09-13, 1997 CL GREEN MT COLL, POULTNEY, VERMONT HO GREEN MT COLL ID LIVER-DISEASE AB This paper presents a new method of estimating the distance between regularly-spaced coherent scatterers within soft tissue from backscattered radio-frequency (RF) signals. Periodic components in the RF signal manifest themselves as peaks in the quefrency (cepstral) domain. Using simulation data, we show that these peaks are easier to detect using the complex cepstrum rather than the commonly used power cepstrum. Similar improvements are seen using phantom and in vivo liver data. C1 George Washington Univ, Dept Elect Engn & Comp Sci, Inst Med Imaging & Image Anal, Washington, DC 20052 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Mia, RS (reprint author), George Washington Univ, Dept Elect Engn & Comp Sci, Inst Med Imaging & Image Anal, Washington, DC 20052 USA. NR 14 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0302-9743 BN 3-540-63046-5 J9 LECT NOTES COMPUT SC PY 1997 VL 1230 BP 513 EP 518 PG 6 WC Computer Science, Theory & Methods; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BK96M UT WOS:000073946600052 ER PT J AU Scheiner, O Aberer, W Ebner, C Ferreira, F HoffmannSommergruber, K Hsieh, LS Kraft, D Sowka, S VanekKrebitz, M Breiteneder, H AF Scheiner, O Aberer, W Ebner, C Ferreira, F HoffmannSommergruber, K Hsieh, LS Kraft, D Sowka, S VanekKrebitz, M Breiteneder, H TI Cross-reacting allergens in tree pollen and pollen-related food allergy: Implications for diagnosis of specific IgE SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Allergy-A Disease of Modern Society Meeting CY SEP 06-11, 1996 CL SALZBURG, AUSTRIA DE allergens; birch pollen; cDNA; conserved proteins; food allergy ID JAPANESE CEDAR POLLEN; 2ND MAJOR ALLERGEN; CRY-J-II; BIRCH POLLEN; CLONING; BET-V-1; AVOCADO; APPLE; LATEX AB Background: A number of recombinant allergens are by now constituents of devices that can be routinely used for the detection of specific IgE. Therefore, the results of diagnostic procedures using conventional allergen extracts can be compared with those employing selected recombinant allergens. Methods: Thirty-four sera from patients allergic to birch pollen were tested with the standard t3-CAP(TM) and rBet v 1a- and rBet v 2-CAP(TM). cDNA was prepared by RT-PCR using primers according to the N terminus of purified allergens. Expression cDNA libraries were screened with IgE from selected patients. Results: Twenty-four patients allergic to birch pollen showed the same RAST class with t3 as with rBet v la; 8 patients differed within 1 RAST class. In addition, 3 patients showed RAST class 3 with rBet v 2. Besides Bet vl and Bet v 2, 3 allergens from celery and avocado belonging to highly conserved protein families were cloned and sequenced. Conclusions: rBet via can be expected to represent an excellent tool for the diagnosis of patients allergic to birch pollen in Central, Northern, and Eastern Europe. Still, a much higher number of patients has to be tested. For their high degree of conservation, further protein families have to be identified to explain cross-reactivities of birch pollen allergens other than Bet v 1 and Bet v 2 with, e.g., allergens from vegetable food. C1 UNIV VIENNA,DEPT GEN & EXPT PATHOL,VIENNA,AUSTRIA. GRAZ UNIV,DEPT DERMATOL,GRAZ,AUSTRIA. US FDA,BETHESDA,MD 20014. RI Ferreira, Fatima/E-4889-2011 OI Ferreira, Fatima/0000-0003-0989-2335 NR 17 TC 19 Z9 20 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PY 1997 VL 113 IS 1-3 BP 105 EP 108 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA WV647 UT WOS:A1997WV64700025 PM 9130495 ER PT J AU Green, MD AF Green, MD TI Problems associated with the absence of activity in standard models of safety pharmacology used to assess biologic products SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the American-College-of-Toxicology CY NOV 12-15, 1995 CL VIENNA, VA SP Amer Coll Toxicol DE biotechnology drugs; predictive value; safety pharmacology ID BIOTECHNOLOGY PRODUCTS; HYPERTENSIVE RATS; ERYTHROPOIETIN; INTERFERON AB The absence of activity may represent either a true or false negative effect. If an assay is valid for the particular test article and fails to indicate activity, it is an appropriate indicator of future events. However if the assay is insensitive or incapable of response, the test represents a form of bias, albeit unconscious. Many biological products demonstrate a specificity of response that limits the utility of commonly employed safety studies. Specificity for many biologics arises from both their physicochemical properties and their similarity to endogenous substances which are regulated in a carefully controlled manner. To overcome the issue of a lack of predictive value, various approaches may be used. For example, a multiple testing strategy of mutually reinforcing studies may be employed or safety studies may be adaptively fit to the biological circumstance. RP Green, MD (reprint author), FDA,CBER,HFM 579,DIV CLIN TRIALS DESIGN & ANAL,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 12 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD JAN-FEB PY 1997 VL 16 IS 1 BP 33 EP 40 DI 10.1080/109158197227341 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA XB220 UT WOS:A1997XB22000007 ER PT J AU King, JW CygnarowiczProvost, M Favati, F AF King, JW CygnarowiczProvost, M Favati, F TI Supercritical fluid extraction of evening primrose oil kinetic and mass transfer effects SO ITALIAN JOURNAL OF FOOD SCIENCE LA English DT Article DE evening primrose; extraction; kinetics; mass transfer; oilseed; supercritical fluid ID CARBON-DIOXIDE; SOYBEAN OIL; CO2; SEED; SOLUBILITIES; LIQUID AB For processing utilization, supercritical fluid extraction requires a thorough understanding of the relevant phase equilibria, mass balance, and kinetic factors that impact on the successful recovery of extracts. In this study, we have determined the factors contributing to the kinetics and mass transfer of evening primrose oil (EPO) from its ground seed matrix, to supplement previously determined solubility data and chemical characterization of this oil moiety, The effect of ex-traction pressure, temperature, fluid density, and flow rate (over a threefold range) have been ascertained; the flow rate effect being correlated in terms of the extracted seed mass and similar data from the literature performed on a pilot and production plant scale, Using a dual mass transfer model, we have correlated the theory with extraction experiments conducted over a pressure range from 20-70 MPa, temperatures from 40 degrees-60 degrees C, and carbon dioxide now rates in the interval from 9-27 g/min. The agreement between the model calculations and experimental data is excellent allowing potential use of the data in process design. C1 US FDA,OFF DEVICE EVALUAT,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20850. UNIV BASILICATA,DIPARTIMENTO BIOL DBAF,I-85100 POTENZA,ITALY. RP King, JW (reprint author), ARS,FOOD QUAL & SAFETY RES UNIT,NATL CTR AGR UTILIZAT RES,USDA,1815 N UNIV ST,PEORIA,IL 61604, USA. RI Favati, Fabio/J-1601-2012 NR 44 TC 19 Z9 19 U1 1 U2 2 PU CHIRIOTTI EDITORI PI PINEROLO PA PO BOX 66, 10064 PINEROLO, ITALY SN 1120-1770 J9 ITAL J FOOD SCI JI Ital. J. Food Sci. PY 1997 VL 9 IS 3 BP 193 EP 204 PG 12 WC Food Science & Technology SC Food Science & Technology GA YA118 UT WOS:A1997YA11800003 ER PT J AU Nightingale, SL AF Nightingale, SL TI Donepezil approved for treatment of Alzheimer disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP Nightingale, SL (reprint author), US FDA, OFF HLTH AFFAIRS, PARKLAWN BLDG, 5600 FISHERS LN, ROCKVILLE, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 JAN 1 PY 1997 VL 277 IS 1 BP 10 EP 10 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VZ767 UT WOS:A1997VZ76700008 ER PT J AU Nightingale, SL AF Nightingale, SL TI Certified mammography facilities listed on Internet SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP Nightingale, SL (reprint author), US FDA, OFF HLTH AFFAIRS, PARKLAWN BLDG, 5600 FISHERS LN, ROCKVILLE, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 1 PY 1997 VL 277 IS 1 BP 10 EP 10 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VZ767 UT WOS:A1997VZ76700007 ER PT J AU Nightingale, SL AF Nightingale, SL TI Guidance for industry on dissemination of reprints and texts 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 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 1 PY 1997 VL 277 IS 1 BP 10 EP 10 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VZ767 UT WOS:A1997VZ76700006 ER PT J AU Allen, LB Siitonen, PH Thompson, HC AF Allen, LB Siitonen, PH Thompson, HC TI Methods for the determination of arsenic, cadmium, copper, lead, and tin in sucrose, corn syrups, and high-fructose corn syrups by inductively coupled plasma atomic emission spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE trace metal analysis; sweeteners; plasma atomic emission spectrometry ID ABSORPTION SPECTROMETRY; SUGARS AB This paper demonstrates the determination of arsenic, cadmium, copper, lead, and tin in sucrose, corn syrups, and high-fructose corn syrups by inductively coupled plasma atomic emission spectrometry (ICP-AES). Sample digestion by both open vessel/hot plate and closed vessel/microwave techniques is reported. Open vessel digestion was suitable for the simultaneous determination of cadmium, copper, and lead. Average recoveries (five different sample types) for the open vessel procedure were 98%, 88%, and 93% for cadmium, copper, and lead, respectively, at 0.10 mu g/g. In contrast, microwave digestion yielded average recoveries (five different sample types) of 92%, 83%, 89%, 85%, and 88%, respectively, for arsenic, cadmium, copper, lead, and tin at 1.0 mu g/g. Method detection limits were lower with open vessel digestion versus microwave digestion because of sample volume reduction. Sample introduction included microporous membrane desolvation, which assisted digestion and matrix normalization. RP Allen, LB (reprint author), US FDA,NATL CTR TOXICOL RES,DIV CHEM,HFT-230,JEFFERSON,AR 72079, USA. NR 18 TC 29 Z9 30 U1 0 U2 12 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 JAN PY 1997 VL 45 IS 1 BP 162 EP 165 DI 10.1021/jf960376p PG 4 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA WD696 UT WOS:A1997WD69600030 ER PT J AU Rosenthal, LA Yarboro, CH Finbloom, DS AF Rosenthal, LA Yarboro, CH Finbloom, DS TI Formation of atypical interferon-stimulated response element (ISRE) binding complexes in peripheral blood mononuclear cells (PBMC) from systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 81 EP 81 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200081 ER PT J AU Kutza, J Hayes, MP Clause, KA AF Kutza, J Hayes, MP Clause, KA TI The effect of IL-2 on M-CSF production and RT activity of HIV-1 infected human macrophages. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 197 EP 197 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200196 ER PT J AU Hayes, MP Burd, PR AF Hayes, MP Burd, PR TI Interferon-gamma-mediated inducible expression of the human interleukin-12 p35 gene in monocytes occurs from a TATA box located 3 to the constitutive promoter initiation sites active in EBV-transformed lymphoblastoid cells. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,CBER,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 219 EP 219 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200218 ER PT J AU Ito, S Ansari, P Larner, AC Finbloom, DS AF Ito, S Ansari, P Larner, AC Finbloom, DS TI IL-10 differentially inhibits the expression of interferon gamma (IFN) induced early response genes in human peripheral blood monocytes. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 228 EP 228 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200227 ER PT J AU GarciaOjeda, PA Krasnokutsky, MV Stein, KE AF GarciaOjeda, PA Krasnokutsky, MV Stein, KE TI VH and VK gene usage in response to Neisseria meningitidis group C polysaccharide. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 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 MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 237 EP 237 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200236 ER PT J AU Kondo, Y Hsieh, LS Lin, Y AF Kondo, Y Hsieh, LS Lin, Y TI Cross-reactive allergens in Japanese cedar, mountain cedar pollen, and tomato extracts. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 CBER,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 572 EP 572 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200570 ER PT J AU Akasawa, A Tanaka, K Shibata, A Shirakata, M Capulong, MCT Hsieh, L Lin, Y Iikura, Y Saito, H AF Akasawa, A Tanaka, K Shibata, A Shirakata, M Capulong, MCT Hsieh, L Lin, Y Iikura, Y Saito, H TI Extractable latex antigen in latex products. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NATL CHILDRENS HOSP,TOKYO 154,JAPAN. US FDA,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 647 EP 647 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200645 ER PT J AU Lightfoote, MM Bushar, G Greenfield, W Langone, JJ AF Lightfoote, MM Bushar, G Greenfield, W Langone, JJ TI Animal models for predicting autoimmune responses to biomaterials. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 787 EP 787 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200785 ER PT J AU Feldman, GM Wahl, SM Vachhani, B McCarthy, J AF Feldman, GM Wahl, SM Vachhani, B McCarthy, J TI Regulation of interferon signalling by the extracellular matrix. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20892. NIDR,IMMUNOL LAB,BETHESDA,MD 20892. UNIV MINNESOTA,DEPT LAB MED PATH,MINNEAPOLIS,MN 55455. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 1009 EP 1009 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14201006 ER PT J AU Segal, BM Klinman, DM Shevach, EM AF Segal, BM Klinman, DM Shevach, EM TI Activation of pathogenic Th1 T cells by microbial products is mediated by IL-12. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID,NIH,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 1232 EP 1232 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14201229 ER PT J AU Jiang, SP Vacchio, S AF Jiang, SP Vacchio, S TI Peripheral tolerance: The fate of fetal antigen-specific T cells during pregnancy. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 1274 EP 1274 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14201271 ER PT J AU Tomazic, VJ Merritt, K Umbreit, TH AF Tomazic, VJ Merritt, K Umbreit, TH TI Significance of the size and chemical composition of biomaterial particles on the deposition pattern and the host response in mice. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 1296 EP 1296 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14201292 ER PT J AU Liu, T Lin, Y AF Liu, T Lin, Y TI Use of monoclonal antibodies for the stability study of Der p and Der f in mite extracts. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 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 MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 1386 EP 1386 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14201385 ER PT J AU Hsieh, LS Martin, BM Doherty, AE Lin, Y AF Hsieh, LS Martin, BM Doherty, AE Lin, Y TI Determination of major IgE-binding epitopes of a latex acidic allergen, Hev b 5. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 CBER,BETHESDA,MD. NIMH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 1395 EP 1395 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14201394 ER PT J AU Oravecz, T Pall, M Wang, J Norcross, MA AF Oravecz, T Pall, M Wang, J Norcross, MA TI Cell surface heparan sulfate mediates anti-HIV-1 activity of CC cemokines. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 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 MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 1614 EP 1614 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14201610 ER PT J AU Sagawa, K Swaim, WD Zhang, J Unsworth, E Siraganian, RP AF Sagawa, K Swaim, WD Zhang, J Unsworth, E Siraganian, RP TI The surface adhesion protein PECAM-1 (CD31) is tyrosine phosphorylated after aggregation of the high affinity IgE receptor. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,NIH,BETHESDA,MD 20014. NIDR,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 1782 EP 1782 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14201776 ER PT J AU VanekKrebitz, M Sowka, S Hsieh, LS Scheiner, O Breiteneder, H AF VanekKrebitz, M Sowka, S Hsieh, LS Scheiner, O Breiteneder, H TI Molecular characterization and purification of conserved pollen and food allergens in avocado (Persea americana). SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 UNIV VIENNA,DEPT GEN & EXPT PATHOL,A-1010 VIENNA,AUSTRIA. US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 1943 EP 1943 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14201937 ER PT J AU Ang, CYW Luo, WH AF Ang, CYW Luo, WH TI Rapid determination of ampicillin in bovine milk by liquid chromatography with fluorescence detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ELECTROSPRAY MASS-SPECTROMETRY; BETA-LACTAM ANTIBIOTICS; PENICILLIN-G; CONFIRMATION; AMOXICILLIN AB A rapid and sensitive liquid chromatographic (LC) method was developed for the determination of ampicillin residues in raw bovine milk, processed skim milk, and pasteurized, homogenized whole milk with vitamin D. Milk samples were deproteinized with trichloroacetic acid (TCA) and acetonitrile. After centrifugation, the clear supernatant was reacted with formaldehyde and TCA under heat. The major fluorescent derivative of ampicillin was then determined by reversed-phase LC with fluorescence detection. Average recoveries of ampicillin fortified at 5, 10, and 20 ppb (ng/mL) were all >85% with coefficients of variation <10%. Limits of detection ranged from 0.31 to 0.51 ppb and limits of quantitation, from 0.66 to 1.2 ppb. After appropriate validation, this method should be suitable for rapid analysis of milk for ampicillin residues at the tolerance level of 10 ppb. RP Ang, CYW (reprint author), US FDA,NATL CTR TOXICOL RES,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 15 TC 12 Z9 15 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 JAN-FEB PY 1997 VL 80 IS 1 BP 25 EP 30 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WE486 UT WOS:A1997WE48600006 PM 9011055 ER PT J AU Turnipseed, SB Roybal, JE Plakas, SM Pfenning, AP Hurlbut, JA Long, AR AF Turnipseed, SB Roybal, JE Plakas, SM Pfenning, AP Hurlbut, JA Long, AR TI Determination of methylene blue in channel catfish (Ictalurus punctatus) tissue by liquid chromatography with visible detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MALACHITE GREEN; METABOLITES AB Methylene blue (MB) is a thiazine dye that, although not regulated for use with edible fish, may sometimes be used as a chemotherapeutic agent in the aquaculture industry, A liquid chromatographic (LC) method was developed for the determination of MB in fish muscle, MB was extracted from catfish tissue with an acetonitrile-acetate buffer solution containing hydroxylamine and toluene-sulfonic acid, partitioned into methylene chloride, and cleaned up on alumina and carboxylic acid solid-phase extraction cartridges, MB concentrations were determined by LC with visible detection at 660-665 nm, Recoveries of MB from catfish fortified at 10-50 ng/g were 75-90% (RSDs, 5-12%), Leucomethylene blue also can be recovered from catfish tissue as the MB colored form at low levels with similar recoveries, Analysis of catfish exposed to MB in a bath treatment at 5 ppm MB for 1 h recovered 10-20 ppb of the drug in the muscle tissue, The low tissue concentration suggests poor absorption of this drug compared with other antifungal dyes that tend to concentrate and remain in fish tissue at high levels. RP Turnipseed, SB (reprint author), US FDA,ANIM DRUGS RES CTR,POB 25087,DENVER,CO 80225, USA. NR 19 TC 19 Z9 24 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 JAN-FEB PY 1997 VL 80 IS 1 BP 31 EP 35 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WE486 UT WOS:A1997WE48600007 PM 9011056 ER PT J AU Bunch, EA AF Bunch, EA TI Drugs .1. SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article RP Bunch, EA (reprint author), US FDA,22201 23RD DR SE,BOTHELL,WA 98021, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1997 VL 80 IS 1 BP 111 EP 111 PG 1 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WE486 UT WOS:A1997WE48600022 ER PT J AU Long, AR AF Long, AR TI Color additives SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article RP Long, AR (reprint author), US FDA,ANIM DRUGS RES CTR,DENVER FED CTR,POB 25087,DENVER DIST,DENVER,CO 80225, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1997 VL 80 IS 1 BP 114 EP 114 PG 1 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WE486 UT WOS:A1997WE48600025 ER PT J AU Thompson, RD AF Thompson, RD TI Nonalcoholic beverages SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article RP Thompson, RD (reprint author), US FDA,240 HENNEPIN AVE,MINNEAPOLIS,MN 55401, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1997 VL 80 IS 1 BP 115 EP 116 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WE486 UT WOS:A1997WE48600028 ER PT J AU Warner, CR AF Warner, CR TI Food additives SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article RP Warner, CR (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,200 C ST SW,WASHINGTON,DC 20204, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 JAN-FEB PY 1997 VL 80 IS 1 BP 116 EP 118 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WE486 UT WOS:A1997WE48600030 ER PT J AU Trucksess, MW AF Trucksess, MW TI Mycotoxins SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MONILIFORME CULTURE MATERIAL; LIQUID-CHROMATOGRAPHIC DETERMINATION; IMMUNOAFFINITY COLUMN CLEANUP; FARMERS STOCK PEANUTS; FEEDING FUMONISIN B-1; FUSARIUM-MONILIFORME; OCHRATOXIN-A; ALTERNARIA MYCOTOXINS; ENZYME-IMMUNOASSAY; NATURAL OCCURRENCE RP Trucksess, MW (reprint author), US FDA,DIV NAT PROD,200 C ST SW,WASHINGTON,DC 20204, USA. NR 119 TC 17 Z9 17 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 JAN-FEB PY 1997 VL 80 IS 1 BP 119 EP 126 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WE486 UT WOS:A1997WE48600031 ER PT J AU Betz, JM AF Betz, JM TI Plant toxins SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PYRROLIZIDINE ALKALOIDS; INTOXICATION; IDENTIFICATION; CHROMATOGRAPHY; HYDROLYSIS; TOMATINE; HEMLOCK; CATTLE RP Betz, JM (reprint author), US FDA,DIV NAT PROD,200 C ST SW,WASHINGTON,DC 20204, USA. NR 59 TC 1 Z9 1 U1 2 U2 5 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1997 VL 80 IS 1 BP 126 EP 131 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WE486 UT WOS:A1997WE48600032 ER PT J AU Prosky, L AF Prosky, L TI Dietary fiber and complex carbohydrates SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article RP Prosky, L (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,OFF SPECIAL NUTR,DIV PROGRAMS & ENFORCEMENT POLICY,WASHINGTON,DC 20204, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1997 VL 80 IS 1 BP 138 EP 140 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WE486 UT WOS:A1997WE48600035 ER PT J AU Firestone, D AF Firestone, D TI Fats and oils SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; HYDROGENATED VEGETABLE-OILS; GAS-CHROMATOGRAPHY; FOODS RP Firestone, D (reprint author), US FDA,DIV PESTICIDES & IND CHEM,200 C ST SW,WASHINGTON,DC 20204, USA. NR 29 TC 0 Z9 0 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 JAN-FEB PY 1997 VL 80 IS 1 BP 140 EP 143 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WE486 UT WOS:A1997WE48600036 ER PT J AU Chase, GW AF Chase, GW TI Infant formula and medical diets SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article RP Chase, GW (reprint author), US FDA,ATLANTA CTR NUTRIENT ANAL,60 8TH ST,ATLANTA,GA 30309, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1997 VL 80 IS 1 BP 143 EP 143 PG 1 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WE486 UT WOS:A1997WE48600037 ER PT J AU Long, AR AF Long, AR TI Fat-soluble vitamins SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article RP Long, AR (reprint author), US FDA,ATLANTA CTR NUTRIENT ANAL,60 8TH ST NE,ATLANTA,GA 30309, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1997 VL 80 IS 1 BP 145 EP 145 PG 1 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WE486 UT WOS:A1997WE48600039 ER PT J AU Mulvaney, TR AF Mulvaney, TR TI Processed vegetable products SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article RP Mulvaney, TR (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,200 C ST SW,HFS 302,WASHINGTON,DC 20204, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1997 VL 80 IS 1 BP 162 EP 163 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WE486 UT WOS:A1997WE48600047 ER PT J AU McMahon, BM AF McMahon, BM TI Organohalogen residues and fumigants SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article RP McMahon, BM (reprint author), US FDA,DIV PESTICIDES & IND CHEM,WASHINGTON,DC 20204, USA. NR 3 TC 0 Z9 0 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 JAN-FEB PY 1997 VL 80 IS 1 BP 167 EP 168 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WE486 UT WOS:A1997WE48600049 ER PT J AU Parfitt, CH AF Parfitt, CH TI Multiresidue methods SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article RP Parfitt, CH (reprint author), US FDA,DIV PESTICIDES & IND CHEM,WASHINGTON,DC 20204, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1997 VL 80 IS 1 BP 169 EP 172 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WE486 UT WOS:A1997WE48600051 ER PT J AU Baratta, EJ AF Baratta, EJ TI Radioactivity SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article RP Baratta, EJ (reprint author), US FDA,WINCHESTER ENGN & ANALYT CTR,WINCHESTER,MA 01890, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1997 VL 80 IS 1 BP 172 EP 172 PG 1 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WE486 UT WOS:A1997WE48600052 ER PT J AU Singleton, ER AF Singleton, ER TI Disinfectants SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article RP Singleton, ER (reprint author), US FDA,DFC,BLDG 20,POB 25087,DENVER,CO 80225, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1997 VL 80 IS 1 BP 173 EP 174 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WE486 UT WOS:A1997WE48600053 ER PT J AU Placencia, AM AF Placencia, AM TI Drug- and device-related microbiology SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article RP Placencia, AM (reprint author), US FDA,240 HENNEPIN AVE,MINNEAPOLIS,MN 55401, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1997 VL 80 IS 1 BP 174 EP 175 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WE486 UT WOS:A1997WE48600054 ER PT J AU Hitchins, AD AF Hitchins, AD TI Cosmetic microbiology SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article RP Hitchins, AD (reprint author), US FDA,DIV MICROBIOL STUDIES,HFS-516,200 C ST,SW,WASHINGTON,DC 20204, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1997 VL 80 IS 1 BP 175 EP 176 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WE486 UT WOS:A1997WE48600055 ER PT J AU Ziobro, GC AF Ziobro, GC TI Filth and extraneous materials in foods and drugs SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article RP Ziobro, GC (reprint author), US FDA,DIV MICROANAL EVALUAT,200 C ST,SW,WASHINGTON,DC 20204, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1997 VL 80 IS 1 BP 176 EP 177 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WE486 UT WOS:A1997WE48600056 ER PT J AU Andrews, WH AF Andrews, WH TI Food microbiology - Nondairy SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article RP Andrews, WH (reprint author), US FDA,DIV MICROBIOL STUDIES,HFS-516,200 C ST,SW,WASHINGTON,DC 20204, USA. NR 0 TC 1 Z9 1 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 JAN-FEB PY 1997 VL 80 IS 1 BP 177 EP 183 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA WE486 UT WOS:A1997WE48600057 ER PT J AU Wolfarth, DL Han, DW Bushar, G Parks, NL AF Wolfarth, DL Han, DW Bushar, G Parks, NL TI Separation and characterization of polyethylene wear debris from synovial fluid and tissue samples of revised knee replacements SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article AB A study was made of in vivo-generated polyethylene wear particles as separated from synovial fluid samples and from tissue samples surrounding total knee arthroplasty. A comparison of particle size and morphology between the two particle groups was made to assess any effects of selective tissue capture, and macrophage encapsulation and digestion. In addition, a Raman spectroscopy technique was evaluated that enables positive identification of individual wear particles. The particles of the same size range found in the synovial fluid and tissue samples exhibited a comparable morphology. Notably, submicron-sized debris was present in both the synovial fluid and tissue samples surrounding knees with osteolysis. The novel micro-Raman analysis of individual particles was successful in the categorizing of wear debris as polyethylene or nonpolyethylene. (C) 1997 John Wiley & Sons, Inc. C1 SANDIA NATL LABS, LIVERMORE, CA 94551 USA. US FDA, CTR DEVICES & RADIOL HLTH, ROCKVILLE, MD 20857 USA. ANDERSON ORTHOPAED RES INST, ARLINGTON, VA 22206 USA. NR 17 TC 30 Z9 31 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD JAN PY 1997 VL 34 IS 1 BP 57 EP 61 DI 10.1002/(SICI)1097-4636(199701)34:1<57::AID-JBM8>3.0.CO;2-M PG 5 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA VY898 UT WOS:A1997VY89800008 PM 8978653 ER PT J AU Zhang, MJ Dayton, AI AF Zhang, MJ Dayton, AI TI Targeting to the HIV-1 RRE of the influenza virus NS1 protein effector domain as a potent, specific anti-HIV agent SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE HIV; antiviral agents; Rev; RNA ID HUMAN-IMMUNODEFICIENCY-VIRUS; NUCLEAR EXPORT; RETROVIRAL VECTORS; REV TRANSACTIVATOR; ACTIVATION DOMAIN; MESSENGER-RNA; T-CELLS; TYPE-1; REPLICATION; EXPRESSION AB The Rev axis of HIV autoregulation is one of two critical viral regulatory pathways required for expression of viral genomic and mRNA and for replication. Consequently it is an attractive therapeutic target. Previous studies have investigated the anti-HIV efficacy of targeting to the RRE (the viral RNA target sequence of the Rev axis) a trans-dominant negative inhibitor mutant Rev, M10. In this study we have fused a portion of the influenza virus NS1 protein (which normally inhibits polyA(+) mRNA transport and splicing) to the Rev M10 gene while deleting the NS1 poly(A) binding region. The resulting chimera demonstrates specific and enhanced inhibition of viral-RRE-containing RNA expression. C1 US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,MOL VIROL LAB,ROCKVILLE,MD 20857. NR 27 TC 6 Z9 7 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD JAN-FEB PY 1997 VL 4 IS 1 BP 35 EP 38 DI 10.1007/BF02255591 PG 4 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA YD086 UT WOS:A1997YD08600005 ER PT J AU Johnson, KA Beitz, J Justice, R Schmidt, W Andrews, P DeLap, R AF Johnson, KA Beitz, J Justice, R Schmidt, W Andrews, P DeLap, R TI Protocol design considerations that relate to demonstrating the safety and effectiveness of chemopreventive agents SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT International Cancer Chemoprevention Conference CY OCT 13-16, 1996 CL BEIJING, PEOPLES R CHINA DE cancer; chemoprevention; clinical trial; surrogate endpoint biomarker; protocol design; safety; efficacy; FDA ID CANCER; TRIAL AB As with other drugs, applications for marketing approval of new chemopreventive agents in the United States must include data from adequate and well-controlled clinical trials that demonstrate effectiveness and safety for the intended use. Knowledge of a drug's pharmacologic actions and metabolism may benefit protocol design, by identifying the patient populations and dosing schedules associated with a Favorable risk/benefit profile. With availability of appropriate preclinical data, including standard assessments of an agent's toxicology, effects on reproductive performance, and genotoxicity, initial Phase studies of 1-3 months may be performed in normal volunteers or an appropriate higher-risk population. For chronic dosing studies of longer duration, preclinical toxicology studies of longer duration are relevant. Enrollment in chemoprevention studies should be directed toward individuals at sufficient risk of developing cancer so that potential benefit may counterbalance the unpredictable and possibly serious adverse effects that may be observed with prolonged administration of a study drug. Phase I and II studies with clinical dosing lasting up to 12 months often afford opportunities to assess drug effect on surrogate endpoint biomarkers that may correlate with endpoints of clinical effectiveness. Phase III and late phase II chemopreventive investigations should routinely utilize a prospective, randomized study design (double-masked and placebo-controlled, when possible). To support marketing approval, there must be evidence that a chemopreventive agent significantly delays or prevents the occurrence of malignancy, with acceptable safety. In some circumstances, modulation of a surrogate marker may provide a basis for marketing approval, before more definitive endpoint data become available. However, the acceptability of a surrogate depends on the nature and quality of the data supporting its predictive value. Given the considerations of large study size, long duration, and high cost that may hamper development of potential agents, studies designed to examine the predictive value of surrogate endpoint biomarkers are of great importance to the future development of chemoprevention research. (C) 1998 Wiley-Liss, Inc.dagger C1 US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20852 USA. RP Johnson, KA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, 1451 Rockville Pike,Rm 2080, Rockville, MD 20852 USA. NR 16 TC 0 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1997 SU 27 BP 1 EP 6 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZM634 UT WOS:000073559800003 ER PT J AU Herrington, EE Ram, TG Salomon, DS Johnson, GR Gullick, WJ Kenney, N Hosick, HL AF Herrington, EE Ram, TG Salomon, DS Johnson, GR Gullick, WJ Kenney, N Hosick, HL TI Expression of epidermal growth factor-related proteins in the aged adult mouse mammary gland and their relationship to tumorigenesis SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID HUMAN-BREAST-CANCER; MESSENGER-RNA; FACTOR-ALPHA; TGF-ALPHA; EPITHELIAL-CELLS; TRANSGENIC MICE; FUNCTIONAL-PROPERTIES; INSITU HYBRIDIZATION; SECONDARY STRUCTURE; FACTOR RECEPTOR AB Mammary glands from female BALB/c mice of different ages and parity were screened for production of three epidermal growth factor (EGF) related transforming growth factors and their corresponding mRNAs. Glands were obtained from 2-26-month-old nulliparous, 4-26-month-old parous, and 2-8-month-old midpregnant mice. Reverse-transcribed polymerase chain reaction (RT-PCR) was used to screen for mRNA from the transforming growth factor alpha (TGF alpha), cripto-1 (CR-1), and amphiregulin (AR) genes in extracts of whole mammary glands. TGF alpha, CR-1, and AR transcripts were detected in all of the mammary glands assayed. in situ hybridization was then used to localize these mRNAs among various cell types in sections of glands. TGF alpha mRNA levels were low in the mammary epithelium from young nulliparous mice, high in the stroma of midpregnant mammary glands, and highest in luminal epithelium of the aged glands. AR mRNA levels were high and remained unchanged in all developmental stages. CR-1 mRNA level increased with age and was detected primarily in epithelium, with some scattered expression in adjacent stroma. Finally, TGF alpha CR-1, and AR proteins were immunolocalized in histological sections of mammary glands from the various developmental stages. TGF alpha was detected sporadically in midpregnant mice, with more conspicuous reactivity seen in 18-26-month-old mice (38% of mice). CR-1 immunoreactivity was detected in 100% of the 18-26-month-old glands but not in any other age groups. Strong AR immunoreactivity was observed in in all glands, including 100% of the 18-26-month-old glands. Staining for all three of these growth factors was observed primarily in the epithelium, with some reactivity detected in the periductal fibroblasts. No significant difference was discerned between glands from nulliparous and parous animals. We also found intense CR-1 and AR mRNA expression and strong immunoreactivity in seven different carcinogen-induced and eight spontaneous mammary tumors. Our results demonstrate that these growth factors accumulate in significant amounts in the old gland of both nulliparous and parous mice. The observations suggest that these growth factors are positioned to contribute to abnormal development in the older mammary gland, predisposing them to tumorigenesis. (C) 1997 Wiley-Liss, Inc. C1 WASHINGTON STATE UNIV,DEPT GENET & CELL BIOL,PULLMAN,WA 99164. NCI,TUMOR IMMUNOL & BIOL LAB,TUMOR GROWTH FACTOR SECT,NIH,BETHESDA,MD 20892. US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20892. HAMMERSMITH HOSP,IMPERIAL CANC RES FUND,MOL ONCOL UNIT,LONDON W12 0NN,ENGLAND. GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. FU NCI NIH HHS [CA 62039] NR 49 TC 30 Z9 30 U1 0 U2 1 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 JAN PY 1997 VL 170 IS 1 BP 47 EP 56 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA WA981 UT WOS:A1997WA98100006 PM 9012784 ER PT J AU Mesmer, MZ Satzger, RD AF Mesmer, MZ Satzger, RD TI Determination of anabolic steroids by HPLC with UV-vis-particle beam mass spectrometry SO JOURNAL OF CHROMATOGRAPHIC SCIENCE LA English DT Article; Proceedings Paper CT 43rd ASMS Conference on Mass Spectrometry and Allied Topics CY MAY 21-25, 1995 CL ATLANTA, GA SP ASMS RP Mesmer, MZ (reprint author), US FDA,FORENS CHEM CTR,1141 CENT PKWY,CINCINNATI,OH 45202, USA. NR 0 TC 8 Z9 8 U1 0 U2 8 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0021-9665 J9 J CHROMATOGR SCI JI J. Chromatogr. Sci. PD JAN PY 1997 VL 35 IS 1 BP 38 EP 42 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WC025 UT WOS:A1997WC02500006 PM 8989871 ER PT J AU Fernandes, G Venkatraman, JT Turturro, A Attwood, VG Hart, RW AF Fernandes, G Venkatraman, JT Turturro, A Attwood, VG Hart, RW TI Effect of food restriction on life span and immune functions in long-lived Fischer-344 X Brown Norway F-1 rats SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE aging; cytokines; food restriction; immune functions; lymphocyte subsets ID AGE-RELATED-CHANGES; CD4+ T-CELLS; MITOGEN-INDUCED PROLIFERATION; OLD MICE; CALORIC RESTRICTION; CONCANAVALIN-A; EXPRESSION; SUBSETS; INTERLEUKIN-2; LYMPHOCYTES AB Life-long food restriction is known to slow aging and reduce the rate of occurrence of age-associated disease processes, but the mechanism by which this is accomplished is unknown. In this study we have examined the effect of food restriction on the proliferative response of spleen cells to mitogens and lymphokine production in 6-, 18-, and 30-month-old AL and FR Fischer-344 X Brown Norway (F-344XBNF(1)) female rats whose average life span is 137 weeks on an ad libitum (AL) diet and 177 weeks on a food-restricted (FR) diet. In addition, the ability of food restriction to recall antigens was rested in 10-month-old rats by immunizing them with keyhole limper and hen's egg albumin and measuring proliferative response of draining lymph node cells to these antigens. Our results indicated that the spleen-cell proliferative response to phytohemagglutinin and concanavalin A (Con A) was equal in 6- and 18-month-old rats but declined significantly in 30-month-old AL rats compared to FR rats. Although flow cytometric analyses did not reveal differences for CD4, CD8, and Ig(+) cells with age, a significant rise in memory T cells (Ox-22(low)) in both CD4(+) and CD8(+) T-cell subset lineage was noted in AL-fed rats at 30 months of age. In FR rats, however, only a minimal shift of naive T cells (OX-22(high)) to memory cells was observed. In FR rats, the observed changes in the naive and memory T-cell subsets correlate well with the observed higher levels of the antiinflammatory interleukin-2 (IL-2) and lower levels of the proinflammatory cytokines such as IL-6 and tumor necrosis factor-alpha. The ability of food-restricted animals to recall antigens was lower compared to their age-matched controls, though the proliferative response to T-cell mitogen Con A and superantigen staphylococcal enterotoxin B was higher. These findings indicate that food restriction may selectively act to maintain a lower number of antigen-induced memory T cells with age, thereby maintaining the organism's ability to produce higher levels of IL-2 with age. In summary, the increased cell-mediated immune function noted in aged FR rats appears to be due to the presence of a higher number of naive T cells, which are known to produce elevated levels of the antiinflammatory cytokines, which may in part be responsible for reducing the observed age-related rise in disease. C1 UNIV TEXAS, HLTH SCI CTR, DEPT MED, SAN ANTONIO, TX 78284 USA. UNIV TEXAS, HLTH SCI CTR, DEPT MICROBIOL, SAN ANTONIO, TX 78284 USA. UNIV TEXAS, HLTH SCI CTR, DEPT PHYSIOL, SAN ANTONIO, TX 78284 USA. SUNY BUFFALO, NUTR PROGRAM, BUFFALO, NY 14260 USA. NATL CTR TOXICOL RES, JEFFERSON, AR 72079 USA. FU NIA NIH HHS [AG R01-10531]; NIDCR NIH HHS [DE-10863] NR 57 TC 70 Z9 71 U1 3 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD JAN PY 1997 VL 17 IS 1 BP 85 EP 95 DI 10.1023/A:1027344730553 PG 11 WC Immunology SC Immunology GA WJ841 UT WOS:A1997WJ84100010 PM 9049789 ER PT J AU Gannot, G Gannot, I Gandjbakhche, AH Bonner, RF Fox, PC AF Gannot, G Gannot, I Gandjbakhche, AH Bonner, RF Fox, PC TI Development of a non invasive method to diagnose Sjogren's syndrome. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,DCRT,NCRR,NIH,CDRH,FDA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1997 VL 76 SI SI BP 2088 EP 2088 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WB680 UT WOS:A1997WB68002084 ER PT J AU Rajaratnam, VS Webb, PJ Fishman, RB Streck, RD AF Rajaratnam, VS Webb, PJ Fishman, RB Streck, RD TI Maternal diabetes induces upregulation of hepatic Insulin-Like Growth Factor Binding Protein-1 mRNA expression, growth retardation and developmental delay at the same stage of rat fetal development SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID FACTOR-I; IGF-I; CONGENITAL-MALFORMATIONS; EARLY EMBRYOGENESIS; MESSENGER-RNAS; ORGANOGENESIS; PREGNANCY; THERAPY; MOUSE; SERUM AB Since maternal diabetes is associated with fetal growth abnormalities in humans and rats, effects of maternal diabetes on fetal expression of genes regulating growth are of interest. Increased expression of Insulin-like Growth Factor Binding Protein-1 (IGFBP-1) is associated with several examples of growth retardation and is upregulated in response to diabetes. As we have shown previously, IGFBP-1 expression is upregulated in gestational day(GD) 14 rat fetuses in response to maternal diabetes. Here we analyze the effect of streptozotocin-induced maternal diabetes on IGFBP-1 mRNA expression during GD12-16 of rat fetal development, using in situ hybridization. IGFBP-1 mRNA was more abundant in GD12-14 fetal livers from diabetic darns than in livers of age-matched controls. This upregulation is not due to the approximately 1-day fetal developmental delay associated with maternal diabetes, as there is no gross difference in the level of IGFBP-1 mRNA in GD13 vs GD12 or GD14 vs GD13 control fetal livers. At GD15-16, however, we detected little difference in IGFBP-1 expression between experimental and control fetuses. This transient period of maternal diabetes-stimulated IGFBP-1 mRNA. expression (GD12-14) is coincident with the sensitive period for maternal diabetes-induced defects in fetal growth and development, suggesting that IGFBP-1 is involved in the regulation of fetal growth and development in response to the maternal condition. RP Rajaratnam, VS (reprint author), US FDA, NATL CTR TOXICOL RES, DIV REPROD & DEV TOXICOL, DEPT HLTH & HUMAN SERV, 3900 NCTR RD, JEFFERSON, AR 72079 USA. NR 40 TC 9 Z9 9 U1 0 U2 0 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 EI 1479-6805 J9 J ENDOCRINOL JI J. Endocrinol. PD JAN PY 1997 VL 152 IS 1 BP R1 EP R6 DI 10.1677/joe.0.152R001 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WB692 UT WOS:A1997WB69200020 PM 9014852 ER PT J AU Hussain, S Rodgers, DA Duhart, HM Ali, SF AF Hussain, S Rodgers, DA Duhart, HM Ali, SF TI Mercuric chloride-induced reactive oxygen species and its effect on antioxidant enzymes in different regions of rat brain SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART B-PESTICIDES FOOD CONTAMINANTS AND AGRICULTURAL WASTES LA English DT Article DE mercury; oxidative stress; reactive oxygen species; antioxidant enzymes; superoxide dismutase; glutathione peroxidase ID LIPID-PEROXIDATION; INDUCED INCREASES; METHYL MERCURY; VITAMIN-E; TOXICITY; METHYLMERCURY; INVITRO; INVIVO; MECHANISMS; SELENIUM AB The present study was undertaken to determine if in vitro exposure to mercuric chloride produces reactive oxygen species (ROS) in the synaptosomes prepared from various regions of rat brain. The effects of in vivo exposure to mercury on antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in different regions of rat brain were also investigated. Adult male Sprague-Dawley (CD) rats were dosed with 0, 1, 2.0 or 4.0 mg HgCl2/kg body weight, for 7 days. One week after the last dose, animals were sacrificed by decapitation, their brains were removed and dissected and frozen in dry ice prior to measuring the activities of these enzymes. The results demonstrated that in vitro exposure to mercury produced a concentration-dependent increase of ROS in different regions of the rat brain. In vivo exposure to mercury produced a significant decrease of total SOD, Cu,Zn-SOD and Mn-SOD activities in the cerebellum of rats treated with different doses of mercury. SOD activity did not vary significantly in cerebral cortex and brain stem. GPx activity declined in a dose-dependent manner in the cerebellum with a significant reduction in animals receiving the 4 mg HgCl2/kg body weight. The activity of GPx increased in the brain stem while unchanged in the cerebral cortex. The results demonstrate that inorganic mercury decreased SOD activity significantly in the cerebellum while GPx activity was affected in both cerebellum and brain stem. Therefore, it can be concluded that oxidative stress may contribute to the development of neurodegenerative disorders caused by mercury intoxication. C1 FLORIDA A&M UNIV,COLL PHARM & PHARMACEUT SCI,TALLAHASSEE,FL 32307. UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM & MOL BIOL,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT NEUROL,LITTLE ROCK,AR 72205. RP Hussain, S (reprint author), US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,NEUROCHEM LAB,JEFFERSON,AR 72079, USA. NR 30 TC 58 Z9 60 U1 2 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0360-1234 J9 J ENVIRON SCI HEAL B JI J. Environ. Sci. Health Part B-Pestic. Contam. Agric. Wastes PY 1997 VL 32 IS 3 BP 395 EP 409 DI 10.1080/03601239709373094 PG 15 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA XB928 UT WOS:A1997XB92800005 PM 9177012 ER PT J AU Liu, F Ang, CYW Huang, YW Toledo, RT AF Liu, F Ang, CYW Huang, YW Toledo, RT TI Fat and water composition affects residual catalatic activity in chicken breast heated to specific end-point temperatures SO JOURNAL OF FOOD SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Institute-of-Food-Technologists CY JUN 03-07, 1995 CL ANAHEIM, CA SP Inst Food Technologists DE chicken meat; composition; enzymatic activity; catalatic activity AB Fat and water contents of meat tissues strongly influence their thermophysical properties. Seven groups of ground chicken breast meat containing varying amounts of fat and water were prepared for this investigation. Each group was heated to end-point temperatures (EPTs) of 69.0 to 71.0 degrees C at 0.5 degrees C intervals. Severity of heat treatments was evaluated by the total process lethality calculated using the General Method. The fat and water contents affected the heating time to reach specific EPTs and the residual catalatic activity at EPTs of 69.0, 69.5 and 70.0 degrees C, but did not affect total process lethality. The variation of the catalase method for determining EPT was related to the sample composition. C1 US FDA,NATL CTR TOXICOL RES,DHHS,DIV CHEM,JEFFERSON,AR 72079. UNIV GEORGIA,DEPT FOOD SCI & TECHNOL,ATHENS,GA 30602. NR 15 TC 5 Z9 5 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 JAN-FEB PY 1997 VL 62 IS 1 BP 66 EP 68 DI 10.1111/j.1365-2621.1997.tb04369.x PG 3 WC Food Science & Technology SC Food Science & Technology GA WG856 UT WOS:A1997WG85600014 ER PT J AU Walker, AE Pothuluri, JV Heinze, TM Volmer, D Cerniglia, CE AF Walker, AE Pothuluri, JV Heinze, TM Volmer, D Cerniglia, CE TI Biosynthetic production of C-13 and C-14 erythronolide labeled erythromycin A SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE erythromycin A; (1-C-13)-sodium propionate; [1-C-14]-sodium propionate; Saccharopolyspora erythraea; erythronolide AB (1,3,5,7,9,11,13-C-13)-Erythromycin A and [1,3,5,7,9,11,13-C-14]-erythromycin A were produced in liquid fermentation broths of Saccharopolyspora erythraea CA340 after the administration of (1-C-13)-sodium propionate and [1-C-14]-sodium propionate, respectively. Fermentations were carried out in shake flasks. Labeled erythromycin A products were isolated by ethyl acetate extraction of the fermentation broth, followed by chromatographic purification on silica gel and Sephadex LH-20. C-13 NMR verified (C-13) incorporation at the seven possible positions on the erythronolide nucleus. Mass spectral analysis of (C-13) labeled erythromycin A revealed a distribution of (C-13) label which could be rationalized based on the known biosynthetic pathway for production of the erythronolide nucleus. C1 NATL CTR TOXICOL RES,DIV MICROBIOL,JEFFERSON,AR 72079. BIONET CORP,JEFFERSON,AR 72079. RP Walker, AE (reprint author), NATL CTR TOXICOL RES,DIV CHEM,3900 NCTR RD,JEFFERSON,AR 72079, USA. RI Volmer, Dietrich/G-7900-2012 OI Volmer, Dietrich/0000-0003-2820-1480 NR 15 TC 2 Z9 2 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JAN PY 1997 VL 39 IS 1 BP 59 EP 67 DI 10.1002/(SICI)1099-1344(199701)39:1<59::AID-JLCR946>3.3.CO;2-F PG 9 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA WF389 UT WOS:A1997WF38900007 ER PT J AU Frick, C TomazicJezic, V Umbreit, T Merritt, K AF Frick, C TomazicJezic, V Umbreit, T Merritt, K TI In vivo effects of polymethylmethacrylate (PMMA) and polystyrene (PS) particles on splenic and peritoneal exudate cells (PEG). SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 MARQUETTE UNIV,DEPT BIOL,MILWAUKEE,WI 53233. US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 1997 SU S BP 17 EP 17 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA YG406 UT WOS:A1997YG40600017 ER PT J AU Kaplan, DS Picciolo, GL Moore, MA Kowolik, MJ AF Kaplan, DS Picciolo, GL Moore, MA Kowolik, MJ TI Evaluation of respiratory burst of human leukocytes to pyrolytic carbon used in biomedical applications SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 US FDA,CDRH,ROCKVILLE,MD 20852. INDIANA UNIV,SCH DENT,INDIANAPOLIS,IN 46202. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 1997 SU S BP 19 EP 19 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA YG406 UT WOS:A1997YG40600018 ER PT J AU Nasr, MM Tschappler, TJ AF Nasr, MM Tschappler, TJ TI High performance liquid chromatographic analysis of erythromycin and related impurities in pharmaceutical formulations SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID SOLID DOSAGE FORMS; ELECTROCHEMICAL DETECTION; SEPARATION; SUBSTANCES; ASSAY; SERUM AB In the last few years, several liquid chromatographic methods for the analysis of erythromycin have been published. Until recently, most of the published methods were either complex or lacked the selectivity needed for the assay of erythromycin in the presence of erythromycin derivatives and impurities. Recently, we developed a significantly improved C-18 liquid chromatographic method for the assay of erythromycin. In comparison, our method is simpler, more rugged, faster, and more sensitive and selective than other published methods. In this investigation, the developed method was successfully used for the assay of erythromycin in several pharmaceutical formulations. RP Nasr, MM (reprint author), US FDA,DIV DRUG ANAL,1114 MARKET ST,ST LOUIS,MO 63101, USA. NR 13 TC 8 Z9 8 U1 0 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 1997 VL 20 IS 4 BP 553 EP 565 DI 10.1080/10826079708010944 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WH642 UT WOS:A1997WH64200005 ER PT J AU Holak, W DiProssimo, V Malek, EG AF Holak, W DiProssimo, V Malek, EG TI Reductive voltammetric HPLC detection of aflatoxins: Determination of aflatoxin B-1 in foods SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article AB A reductive voltammetric detector, consisting of static mercury drop electrode was investigated for possible determination of aflatoxins B-1, B-2, G(1), and G(2) by HPLC. The HPLC system consisted of a C-18 ODS column and a mobile phase composed of 30% acetonitrile and 0.01M tetrabutylammonium bromide. The detector was operated in a differential pulse mode, set to the peak potential of -1.25 volts vs. Ag/AgCl. Under these conditions the sensitivity of the system was sufficient to determine aflatoxin B-1 present in several foods. Good agreement was obtained between this method and thin layer chromatography. RP Holak, W (reprint author), US FDA,NEW YORK REG LAB,850 3RD AVE,BROOKLYN,NY 11232, USA. NR 6 TC 4 Z9 4 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 1997 VL 20 IS 7 BP 1057 EP 1065 DI 10.1080/10826079708010958 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WR664 UT WOS:A1997WR66400006 ER PT J AU Cooney, CA Wise, CK Poirier, LA AF Cooney, CA Wise, CK Poirier, LA TI An improved sample preparation method for the quantitative HPLC determination of 5-methyldeoxycytidine in animal tissue DNA SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; 5-METHYLCYTOSINE CONTENT; XIST GENE; METHYLATION; DEFICIENT; RATS; AGE; HYPOMETHYLATION; EXPRESSION; SEQUENCES AB Techniques are presented for the purification of DNA from mammalian tissues, its enzymatic hydrolysis to deoxyribonucleosides and the separation and quantification of these by high pressure liquid chromatography (HPLC). The method is used to quantify 5-methyldeoxycytidine (5MdC) and deoxycytidine (dC) in DNA. From this data the molar %5MdC, i.e. 100 x 5MdC/(dC + 5MdC), is calculated for DNA. The precision of the method matches or exceeds that of other published HPLC methods for quantifying the %5MdC. The DNA obtained is extremely clean, and the enzymatic hydrolysis provides deoxyribonucleosides without contamination so there are no extraneous peaks in the region of interest, and peaks that are obtained have sufficient area to eliminate errors from variation in integration. The %5MdC is a quantitative and absolute measure of the genome wide DNA methylation. This method is suitable to quantify small changes in mammalian enzymatic DNA methylation due to age, diet, drugs or carcinogens. RP Cooney, CA (reprint author), NATL CTR TOXICOL RES,DIV NUTR TOXICOL,3900 NCTR RD,JEFFERSON,AR 72079, USA. OI Cooney, Craig/0000-0003-4279-557X NR 32 TC 14 Z9 14 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 1997 VL 20 IS 8 BP 1279 EP 1293 DI 10.1080/10826079708010976 PG 15 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WT517 UT WOS:A1997WT51700012 ER PT J AU Chase, GW Eitenmiller, RR Long, AR AF Chase, GW Eitenmiller, RR Long, AR TI Liquid chromatographic analysis of all-rac-alpha-tocopheryl acetate, tocopherols, and retinyl palmitate in SRM 1846 SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID VITAMIN-E; FLUOROMETRIC DETECTION; INFANT FORMULAS; FLUORESCENCE DETECTION; FOODS; HPLC; MILK; TOCOTRIENOLS AB A liquid chromatographic method is described for the analysis of all-rac-alpha-tocopheryl acetate, tocopherols, and retinyl palmitate in the infant formula standard reference material 1846. The vitamins are extracted in isopropanol and hexane/ethyl acetate without saponification and quantitated by normal phase chromatography with fluorescence detection. Retinyl palmitate, all-rac-alpha- tocopheryl acetate, and naturally occurring tocopherols are quantitated isocratically with a mobile phase of 0.5% isopropanol in hexane. The results were within the certified ranges for all-rac-alpha-tocopheryl. acetate and retinyl palmitate. Recoveries averaged 97.5% for retinyl palmitate and 101% for all-rac-alpha- tocopheryl acetate (n = 20). The method provides a rapid, specific, and easily controlled assay approach to the analysis of vitamin A and vitamin E in fortified infant formula. Additionally, the method eliminates the use of chlorinated solvents. C1 UNIV GEORGIA,DEPT FOOD SCI & TECHNOL,ATHENS,GA 30602. RP Chase, GW (reprint author), US FDA,60 8TH ST,ATLANTA,GA 30602, USA. NR 18 TC 20 Z9 20 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 1997 VL 20 IS 20 BP 3317 EP 3327 DI 10.1080/10826079708005833 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA YL125 UT WOS:A1997YL12500004 ER PT J AU Ali, SF Freyaldenhoven, TE Schmued, LC AF Ali, SF Freyaldenhoven, TE Schmued, LC TI Systemic administration of MPTP induces thalamic neuronal degeneration in mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,NEUROCHEM LAB,JEFFERSON,AR 72079. UNIV ARKANSAS MED SCI,DEPT NEUROL,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI,DEPT BIOCHEM & MOL BIOL,LITTLE ROCK,AR 72205. 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 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1997 VL 69 SU S BP S40 EP S40 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA XM285 UT WOS:A1997XM28500155 ER PT J AU Appel, NM Hayakawa, T Chang, M Bell, J Seemann, R Rapoport, SI AF Appel, NM Hayakawa, T Chang, M Bell, J Seemann, R Rapoport, SI TI Effect of D-2 dopamine receptor activation on [H-3]arachidonic acid incorporation in rats with unilateral 6-hydroxydopamine lesions SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA,LNS,NIH,BETHESDA,MD 20892. US FDA,CDER,OTR,DAPR,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 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1997 VL 69 SU S BP S71 EP S71 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA XM285 UT WOS:A1997XM28500275 ER PT J AU Winsky, L Nagula, S Lester, DS AF Winsky, L Nagula, S Lester, DS TI Calcium dependent association of calretinin with phospholipid vesicles SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIMH,CLIN SCI LAB,BETHESDA,MD. US FDA,CDER,DAPR,LAUREL,MD. 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 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1997 VL 69 SU S BP S182 EP S182 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA XM285 UT WOS:A1997XM28500717 ER PT J AU Hood, HL Kraeling, MEK Robl, MG Bronaugh, RL AF Hood, HL Kraeling, MEK Robl, MG Bronaugh, RL TI The effects of an alpha hydroxy acid (glycolic acid) on hairless guinea pig skin SO JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS LA English DT Article; Proceedings Paper CT 1997 Annual Scientific Seminar of the Society-of-Cosmetic-Chemists CY MAY 01-02, 1997 CL NASHVILLE, TN SP Soc Cosmet Chemists C1 US FDA,OFF BELTSVILLE TECH OPERAT,WASHINGTON,DC 20204. RP Hood, HL (reprint author), US FDA,OFF COSMET & COLORS,WASHINGTON,DC 20204, USA. NR 4 TC 1 Z9 1 U1 0 U2 1 PU SOC COSMETIC CHEMISTS PI NEW YORK PA 120 WALL STREET, SUITE 2400, NEW YORK, NY 10005-4088 SN 0037-9832 J9 J SOC COSMET CHEM JI J. Soc. Cosmet. Chem. PD JAN-FEB PY 1997 VL 48 IS 1 BP 53 EP 55 PG 3 WC Chemistry, Applied; Dermatology SC Chemistry; Dermatology GA XX686 UT WOS:A1997XX68600005 ER PT J AU May, JC DelGrosso, AV Wheeler, RM Etz, NM AF May, JC DelGrosso, AV Wheeler, RM Etz, NM TI TG/MS capillary interface - Applications to determination of residual moisture in BCG vaccine and other freeze-dried biological products SO JOURNAL OF THERMAL ANALYSIS LA English DT Article DE lyophilization; residual moisture; TG/MS interface AB A TA Instruments Thermal Analysis System (TG) has been interfaced to the Hewlett Packard 5972 quadrupole mass spectrometer. An OSS-2 variable outlet splitter was plumbed between the TG and the mass spectrometer. This interface allows continuous monitoring of the ion intensities of mass peaks m/e = 18 (water) and m/e = 44 (carbon dioxide) used to elucidate the TG transitions attributable to residual moisture in freeze-dried biological products. Moisture specifications must be met in order to insure product stability throughout the approved shelf life. TG/MS results are discussed for BCG Vaccine, BCG Live (Intravesical) and U.S. Standard Antihemophilic Factor. Karl Fischer and TG/MS moisture results are compared. RP May, JC (reprint author), US FDA,CTR BIOL EVALUAT & RES,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 9 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0368-4466 J9 J THERM ANAL JI J. Therm. Anal. PY 1997 VL 49 IS 2 BP 929 EP 936 DI 10.1007/BF01996778 PG 8 WC Thermodynamics; Chemistry, Analytical; Chemistry, Physical SC Thermodynamics; Chemistry GA XJ183 UT WOS:A1997XJ18300040 ER PT J AU Bushar, G Sagripanti, JL AF Bushar, G Sagripanti, JL TI Molecular characteristics of Junin virus SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE arenavirus; Argentine hemorrhagic fever; Junin virus ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; HEMORRHAGIC-FEVER; PROTEIN; ARENAVIRUSES; ASSAY AB Results suggest that protein, glycerophospolipid, galactoside, and sialyl glycoside residues are present in Junin virus (JV), are accessible to enzymatic digestion, and play an important role in infection. Four major protein bands with molecular masses (M(r)) 64+/-2: 56+/-2, 52+/-3 (mean+/-standard deviation, n=4) and approximately 12-18 kDa were consistently detected after denaturing gel electrophoresis analysis of purified attenuated JV. The 52 kDa protein showed a diffuse tail in the 52-56 kDa range and was considered to be the JV glycoprotein. By Western blotting, the 64 kDa protein bound a JV neutralizing antibody and was considered to be the viral nucleoprotein. Additional bands corresponding to larger proteins (approximately 200, 96, 86, and 78-80 kDa in size), as well as fainter and broader bands in the 23-44 kDa region were also present in purified JV preparations. The relative resistance of virus infectivity to RNase digestion demonstrates that the genome of JV is protected from enzymatic attack. Analysis of purified JV virions by electrophoresis resolved the viral small (S) RNA and large (L) RNA species, 3636+/-54 bases and 7667+/-154 bases long, respectively (average length+/-range, in four determinations). The (S) RNA of attenuated JV appeared slightly larger than that reported for a pathogenic strain, ruling out a large sequence deletion as a reason for attenuation. Copyright (C) 1997 Elsevier Science B.V. C1 US FDA,CTR DEVICES & RADIOL HLTH,MOL BIOL BRANCH HFZ113,ROCKVILLE,MD 20857. NR 31 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD JAN PY 1997 VL 63 IS 1-2 BP 27 EP 35 DI 10.1016/S0166-0934(96)02106-4 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA WF060 UT WOS:A1997WF06000004 PM 9015273 ER PT J AU TeruyaFeldstein, J Jaffe, ES Burd, PR Kingma, DW Tosato, G AF TeruyaFeldstein, J Jaffe, ES Burd, PR Kingma, DW Tosato, G TI Expression of interferon-gamma inducible protein 10 (IP-10) and macrophage interferon-gamma induced gene (Mig) in Hodgkin's disease (HD) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,PATHOL LAB,HEMATOPATHOL SECT,CTR BIOL EVALUAT & RES,FDA,BETHESDA,MD 20892. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1997 VL 76 IS 1 BP 787 EP 787 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA WD486 UT WOS:A1997WD48600802 ER PT J AU Ediger, MN Pettit, GH Matchette, LS AF Ediger, MN Pettit, GH Matchette, LS TI In vitro measurements of cytotoxic effects of 193 nm and 213 nm laser pulses at subablative fluences SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE cytotoxicity; free radicals; corneal ablation; photorefractive keratectomy ID SOLID-STATE LASER; PHOTOREFRACTIVE KERATECTOMY; CORNEA; ABLATION AB Background and Objective: The frequency-quintupled q-switched Nd:YAG laser is being studied as an alternative to the ArF excimer laser for photorefractive procedures. The present report describes two experiments comparing biologic effects of these laser devices. Study Design/Materials and Methods: Bovine corneas were irradiated with subablative laser pulses in Liquid nitrogen and analyzed by electron paramagnetic resonance spectroscopy to assess free radical production. Aqueous bacterial suspensions were irradiated with low-intensity laser pulses and assayed for cell survival. Results: Electron paramagnetic resonance spectra were very similar in both amplitude and shape for exposure at the two wavelengths. Bacterial survival was markedly less for 213 nn irradiation than 193 nn exposure and displayed a different dependence on cumulative exposure. Conclusion: Free radical production by 213 nn laser exposure is quite comparable to that seen previously for 193 nm irradiation. However, cell lethality appears to be significantly greater at the longer ultraviolet wavelength. This difference may contribute to complications observed after corneal photoablation with the 213 nn device. (C) 1997 Wiley-Liss, Inc. RP Ediger, MN (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,MAIL STOP HFZ-134,ROCKVILLE,MD 20857, USA. NR 18 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 1997 VL 21 IS 1 BP 88 EP 93 DI 10.1002/(SICI)1096-9101(1997)21:1<88::AID-LSM13>3.0.CO;2-5 PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA XH886 UT WOS:A1997XH88600013 PM 9228645 ER PT S AU Schwan, WR Kopecko, DJ AF Schwan, WR Kopecko, DJ BE Paul, PS Francis, DH Benfield, DA TI Serovar specific differences in Salmonella survival within macrophage cells SO MECHANISMS IN THE PATHOGENESIS OF ENTERIC DISEASES SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 1st International Rushmore Conference on Mechanisms in the Pathogenesis of Enteric Diseases CY SEP 28-30, 1995 CL RAPID CITY, SD SP USDA NRICGP, NAF EPSCoR S Dakota, Bayer, Agr Div, Shawnee Mission, Kansas, Pfizer, Cent Res Div, Lincoln, Solvay Anim Hlth, Mendota Heights, Boehringer Ingelheim Anim Hlth, St Joseph, Grand Labs Inc, Freeman, Ambico Inc, Dallas Ctr, Iowa, Eli Lilly & Co Fdn, Indianapolis, NOBL Labs Inc, Sioux Ctr, Iowa, Oxford Vet Labs Inc, Worthington, Rural Technol Inc, Brookings, Coll Agr & Biol Sci, Agr expt Stn, S Dakota State Univ, Dept Vet Sci ID GROWTH RP Schwan, WR (reprint author), US FDA, CBER, HFM440, 8800 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 4 TC 5 Z9 5 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45519-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 412 BP 277 EP 278 PG 2 WC Agriculture, Dairy & Animal Science; Medicine, Research & Experimental; Veterinary Sciences SC Agriculture; Research & Experimental Medicine; Veterinary Sciences GA BH98Z UT WOS:A1997BH98Z00046 PM 9192030 ER PT B AU Haffner, ME AF Haffner, ME BE Yamazaki, M TI Support for orphan drug development: legislation in the United States, Japan and Europe SO MEDICINAL CHEMISTRY: TODAY AND TOMORROW LA English DT Proceedings Paper CT AFMC International Medicinal Chemistry Symposium (AIMECS 95) CY SEP 03-08, 1995 CL TOKYO, JAPAN SP Asian Federat Med Chem, European Federat Med Chem, Amer Chem Soc, Div Med Chem, Pharm Soc Japan AB Between 10 and 20 million Americans suffer from one of the estimated 5,000 rare diseases. Most of these rare diseases are orphan diseases; they have no parent organization, investigator, or agency dedicated to research on the prevention, diagnosis, or treatment of their victims. Orphan Products are those to treat diseases or conditions characterized by low prevalence, or special subsegment patient populations that often lack economic viability. Congress enacted the U.S. Orphan Drug Act in 1983, after a long struggle by rare disease patient groups in the United States to attract attention to their hopeless plight. Incentives of the Act encourage pharmaceutical manufacturers to develop products that would otherwise provide little return on invested capital due to small patient populations. The Orphan Drug Act has brought hope to victims of rare, life-threatening diseases and has had a major impact on the discovery of ways to use already developed products to save lives and improve patient quality of life. The Orphan Drug Act amended the U.S. Federal Food, Drug, and Cosmetic Act, and has been amended several times to adjust to changing trends. RP Haffner, ME (reprint author), US FDA,OFF ORPHAN PROD DEV,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD, ENGLAND OX2 0EL BN 0-632-04272-9 PY 1997 BP 243 EP 250 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA BJ40J UT WOS:A1997BJ40J00037 ER PT J AU Bolger, M AF Bolger, M TI Commentary: Safety risk assessment of neurodevelopmental toxins in food SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS LA English DT Editorial Material DE safety; assessment; food; neurodevelopmental; additives; contaminants ID UNITED-STATES; DIETARY LEAD AB A number of substances of natural and anthropogenic origin that may exhibit neurodevelopmental potential have been associated with the food supply. In describing the safety assessment process and standards that are used to evaluate the public health significance of these types of substances in food, a clear understanding of the relationship between the requirements of the law and the scientific knowledge required to meet the statutorily mandated safety standards is necessary. The process by which the FDA considers dietary neuroeffective substances is dependent on the statutory mandate under which it operates, namely the federal Food, Drug, and Cosmetic (FD&C) Act of 1958. The FD&C Act specifically mandates 1) the types of food-related substances and associated adverse health effects; 2) the scientific standards of safety/risk; and 3) the assignment of burden of required to achieve compliance with these standards. The categories of food substances vary in their safety/ risk objectives from zero/negligible risk to significant probability of harm. In order to monitor dietary changes, the FDA develops data for estimating changes in dietary exposure of consumers to foodborne substances. The toxicological testing and assessment methodologies utilized to uncover the neurotoxic/developmental properties of food-borne substances can vary considerably. Various regulatory/control procedures are available to maximize public health protection by assuring that the public is either not exposed, or exposure is minimized, to levels that pose negligible risk of neurodevelopmental effects. In exercising its public health and regulatory responsibilities for food-borne substances, the FDA is committed to assessing all relevant toxicological end points, including those substances that have the potential to elicit neurodevelopmental effects. (C) 1997 Wiley-Liss, Inc.dagger RP Bolger, M (reprint author), US FDA,CONTAMINANTS BRANCH,CTR FOOD SAFETY & APPL NUTR,200 C ST SW,WASHINGTON,DC 20204, USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1080-4013 J9 MENT RETARD DEV D R JI Ment. Retard. Dev. Disabil. Res. Rev. PY 1997 VL 3 IS 3 BP 275 EP 278 PG 4 WC Clinical Neurology; Neurosciences; Pediatrics; Psychiatry SC Neurosciences & Neurology; Pediatrics; Psychiatry GA XV164 UT WOS:A1997XV16400008 ER PT J AU Hattori, T Zhang, XY Weiss, C Xu, YN Kubo, T Sato, Y Nishikawa, S Sakaida, H Uchiyama, T AF Hattori, T Zhang, XY Weiss, C Xu, YN Kubo, T Sato, Y Nishikawa, S Sakaida, H Uchiyama, T TI Triazine dyes inhibit HIV-1 entry by binding to envelope glycoproteins SO MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE HIV; gp120; gp41; triazine dye ID HUMAN-IMMUNODEFICIENCY-VIRUS; AFFINITY-CHROMATOGRAPHY; DEXTRAN SULFATE; T-CELLS; TYPE-1; AIDS; CD4; PURIFICATION; INFECTION; MECHANISM AB We have attempted to purify envelope (Env) glycoproteins of human immunodeficiency virus (HIV) from the culture supernatants of CHO-Sec cells that secreted truncated 140-kDa precursor and mature 120-kDa Env glycoproteins. The concentrated culture supernatants were applied to a column coupled with cibacron blue 3GA (CB3GA) to separate albumin from the Env proteins because CB3GA, a triazine dye, has been known to have a high affinity to albumin, Unexpectedly, Env proteins as well as albumin bound to the column, and the bound Env proteins were eluted by increasing the ionic strength using KCI, Gp120 was eluted at 0.5-0.9 M of KCl, while a higher concentration (0.9-1.5 M) was necessary for the elution of gp140. The agarose gel coupled with reactive red 120 (RR120), another triazine dye with similar characteristics, also retained both Env proteins, and the bound Env proteins could be eluted in a similar manner, In addition, these agents inhibited syncytium formation caused by HTLV-IIIB and HTLV-IIIMN. Inhibition was also seen when a virus-free fusion assay between Env protein expressed in CHO cells and fluorescent labeled SupT1 cells were used, These findings indicate that triazine dyes bind to the functional regions of Env proteins of HIV-1 that play important role(s) for HIV infection. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. WAKENYAKU CO,R&D,KYOTO 606,JAPAN. RP Hattori, T (reprint author), KYOTO UNIV,INST VIRUS RES,RES CTR HUMAN IMMUNODEFICIENCY,LAB AIDS IMMUNOL,SAKYO KU,KYOTO 606,JAPAN. NR 29 TC 11 Z9 11 U1 0 U2 1 PU CENTER ACADEMIC PUBL JAPAN PI TOKYO PA 4-16 YAYOI 2-CHOME, BUNKYO-KU, TOKYO 113, JAPAN SN 0385-5600 J9 MICROBIOL IMMUNOL JI Microbiol. Immunol. PY 1997 VL 41 IS 9 BP 717 EP 724 PG 8 WC Immunology; Microbiology SC Immunology; Microbiology GA XW160 UT WOS:A1997XW16000011 PM 9343823 ER PT J AU Farag, SA Wells, CE AF Farag, SA Wells, CE TI Capillary electrophoresis determination of diatrizoic acid and its impurities in diatrizoate radiopaque solutions SO MIKROCHIMICA ACTA LA English DT Article DE capillary electrophoresis; diatrizoate; separation; radiopaque; impurities; degradation ID CONTRAST-MEDIA; NEPHROPATHY; IOHEXOL; PROTEIN; ASSAY; RATS; HPLC AB A capillary electrophoresis method has been developed for the separation and determination of diatrizoic acid (DTZA) and its four mono- and diiodo degradation products (2-iodo,4-iodo, 2,4-diiodo, and 2,6-diiodo-3,5-diacetamidobenzoic acid) in radiopaque solution for injection (RSI). DTZA and its degradants were assayed in suitable dilutions without pretreatment. Optimum conditions included the use of low-pressure sample injection (6 s), sample and standard solutions with a molarity less than that of the separation buffer, and adjustment of the buffer molarity to obtain a current of 50 mu A at a constant 15 kV separation voltage. After each six runs or less, the inlet and outlet buffer were replaced with more buffer from the same batch. When the method was applied to a sample of SI levels of 5-10 mg/ml were found for each of the mono and diiodo impurities. The optimum method showed a precision (peak area measurement) in the range 1.7-7.2% RSD, depending on the concentration. A linear correlation coefficient of 0.997 was obtained over a DTZA concentration range of 5-60 mg/mL. RP Farag, SA (reprint author), US FDA,DIV DRUG ANAL,1114 MARKET ST,ROOM 1002,ST LOUIS,MO 63101, USA. NR 26 TC 7 Z9 7 U1 0 U2 2 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0026-3672 J9 MIKROCHIM ACTA JI Mikrochim. Acta PY 1997 VL 126 IS 1-2 BP 141 EP 145 DI 10.1007/BF01242676 PG 5 WC Chemistry, Analytical SC Chemistry GA WU287 UT WOS:A1997WU28700022 ER PT S AU Brown, SA Abera, A DOnofrio, M Flemming, C AF Brown, SA Abera, A DOnofrio, M Flemming, C BE Marlowe, DE Parr, JE Mayor, MB TI Effects of neck extension, coverage, and frequency on the fretting corrosion of modular THR bore and cone interface SO MODULARITY OF ORTHOPEDIC IMPLANTS SE AMERICAN SOCIETY FOR TESTING AND MATERIALS SPECIAL TECHNICAL PUBLICATION LA English DT Proceedings Paper CT Symposium on Modularity of Orthopedic Implants CY NOV 08, 1995 CL NORFOLK, VA SP Amer Soc Testing & Mat, Comm F4 Med & Surg Mat & Devices DE fretting corrosion; Ti 6A1 4V; CoCrMo alloy; mixed metal; modular total hips; frequency AB Examination of retrieved modular total hip replacements (THR's) has identified fretting corrosion as one of the principal mechanisms of implant corrosion at the bore and cone interface. Increased instability due to increased neck extension has been attributed to one of the design factors affecting corrosion rates. A series of experiments was conducted on THR's with cobalt chromium molybdenum alloy heads and Ti 6Al 4V stems, which demonstrated higher fretting corrosion currents with longer neck extensions. Shortening the skirt reduced corrosion rates. In a second series, the effects of wave form and cycling frequency demonstrated higher currents with a ramp versus a sine wave, and higher currents with higher frequencies. Examination of the frequency components of the Paul curve for loads on the hip during gait demonstrated that higher frequencies may be appropriate for device testing. RP Brown, SA (reprint author), US FDA,CDRH,DMMS,12200 WILKINS AVE,ROCKVILLE,MD 20852, USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU AMERICAN SOCIETY TESTING AND MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DRIVE, W CONSHOHOCKEN, PA 19428-2959 SN 1071-5827 BN 0-8031-2415-5 J9 AM SOC TEST MATER PY 1997 VL 1301 BP 189 EP 198 DI 10.1520/STP12032S PG 10 WC Materials Science, Biomaterials; Orthopedics SC Materials Science; Orthopedics GA BH43N UT WOS:A1997BH43N00016 ER EF